The Oxford Handbook of Evolutionary Psychology

and Behavioral Endocrinology

Oxford Library of Psychology

Area Editors:

Clinical Psychology
David H. Barlow

Cognitive Neuroscience
Kevin N. Ochsner and Stephen M. Kosslyn

Cognitive Psychology
Daniel Reisberg

Counseling Psychology
Elizabeth M. Altmaier and Jo-Ida C. Hansen

Developmental Psychology
Philip David Zelazo

Health Psychology
Howard S. Friedman

History of Psychology
David B. Baker

Methods and Measurement

Todd D. Little

Neuropsychology
Kenneth M. Adams

Organizational Psychology
Steve W. J. Kozlowski

Personality and Social Psychology

Kay Deaux and Mark Snyder
 OX F O R D L I B R A RY O F P S YC H O LO G Y

The Oxford Handbook

of Evolutionary
Psychology and
Behavioral
Endocrinology
Edited by
Lisa L. M. Welling
Todd K. Shackelford

1
2019
1
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Library of Congress Cataloging-in-Publication Data
Names: Welling, Lisa L. M., editor. | Shackelford, Todd K. (Todd Kennedy),
1971–editor.
Title: The Oxford handbook of evolutionary psychology and behavioral
endocrinology/edited by Lisa L. M. Welling, Todd K. Shackelford.
Other titles: Handbook of evolutionary psychology and behavioral endocrinology
Description: New York NY: Oxford University Press, [2018] |
Series: Oxford library of psychology | Includes bibliographical references and index.
Identifiers: LCCN 2018015650 | ISBN 9780190649739 (hardcover: alk. paper)
Subjects: LCSH: Evolutionary psychology. | Human behavior—Endocrine aspects.
Classification: LCC BF698.95 .O946 2018 | DDC 155.7—dc23
LC record available at https://lccn.loc.gov/2018015650

135798642
Printed by Sheridan Books, Inc., United States of America
S H O RT C O N T E N T S

About the Editors vii

Contributors ix

Table of Contents xiii

Chapters 1–442

Name Index 443

Subject Index 446

v
A B O U T T H E E D I TO R S

Lisa L. M. Welling is an Associate Professor of Psychology at Oakland University

in Rochester, Michigan. Dr. Welling received her PhD in 2008 from the University
of Aberdeen in the United Kingdom. She heads the Welling Research Laboratory,
where her and her students’ research focuses on behaviors related to sexual selection,
with a special focus on hormonal mediation.

Todd K. Shackelford is Distinguished Professor and Chair of the Department of

Psychology at Oakland University. He received his PhD in evolutionary psychology
in 1997 from the University of Texas at Austin. Much of Dr. Shackelford’s research
addresses sexual conflict between men and women, with a special focus on testing
hypotheses derived from sperm competition theory.

vii
 C O N T R I B U TO R S

Melissa K. Allen Frances S. Chen

McGovern Medical School University of British Columbia
Houston, TX, USA Vancouver, British Columbia, Canada
Christine Anderl Elena Choleris
University of British Columbia University of Guelph
Vancouver, British Columbia, Canada Guelph, Ontario, Canada
Karen L. Bales Yasmine-Marie Cissé
University of California—Davis The Ohio State University
Davis, CA, USA Columbus, OH, USA
Joyce F. Benenson Kelly D. Cobey
Emmanuel College Ottawa Hospital Research Institute
Boston, MA, USA Ottawa, Ontario, Canada;
Kristin Bernard University of Ottawa
Stony Brook University Ottawa, Ontario, Canada;
Stony Brook, NY, USA University of Stirling
Lynda G. Boothroyd Stirling, Scotland
Durham University LillyBelle K. Deer
Durham, England, UK University of California—Davis
Jeremy C. Borniger Davis, CA, USA
The Ohio State University Pieternel Dijkstra
Columbus, OH, USA The Netherlands
Adam H. Boyette Alexandra N. Duran
Duke University McGovern Medical School
Durham, NC, USA Houston, TX, USA
Robert P. Burriss Mark A. Ellenbogen
University of Basel Concordia University
Basel, Switzerland Montreal, Quebec, Canada
Abraham P. Buunk Kelsy S. J. Ervin
University of Groningen University of Guelph
Groningen, the Netherlands; Guelph, Ontario, Canada
Netherlands Interdisciplinary Demographic Ana Maria Fernandez
Institute University of Santiago, Chile
The Hague, The Netherlands Santiago, Chile
Justin M. Carré Steven W. Gangestad
Nipissing University University of New Mexico
North Bay, Ontario, Canada Albuquerque, NM, USA
Kathleen V. Casto Shawn N. Geniole
University of Oregon University of Vienna
Eugene, OR, USA Vienna, Austria

ix
Lee T. Gettler Randy J. Nelson
University of Notre Dame The Ohio State University
Notre Dame, IN, USA Columbus, OH, USA
Stefan M. M. Goetz Teresa A. Piggott
Wayne State University McGovern Medical School
Detroit, MI, USA Houston, TX, USA
Nicholas M. Grebe Simon D. Reeve
Duke University Oakland University
Durham, NC, USA Rochester, MI, USA
Amanda C. Hahn Francisco J. Sánchez
Humboldt State University University of Missouri—Columbia
Arcata, CA, USA Columbia, MO, USA
Elizabeth Hampson Shimon Saphire-Bernstein
University of Western Ontario University of California—Los Angeles
London, Ontario, Canada Los Angeles, CA, USA
Camelia E. Hostinar Laura A. Schoenle
University of California—Davis Virginia Tech
Davis, CA, USA Blacksburg, VA, USA
Isha Jalnapurkar Lisa Serravalle
University of Massachusetts Medical Concordia University
School Montreal, Quebec, Canada
Boston, MA, USA Todd K. Shackelford
Tyler Kimm Oakland University
McGovern Medical School Rochester, MI, USA
Houston, TX, USA Trenton C. Simmons
Stephanie Linscheid University of California—Davis
University of Michigan Medical Davis, CA, USA
School Alex J. Swanson
Ann Arbor, MI, USA University of Missouri—Columbia
Jenna Lunge Columbia, MO, USA
Oakland University Virginia Tsekova
Rochester, MI, USA Concordia University
Karlijn Massar Montreal, Quebec, Canada
Maastricht University Laura N. Vandenberg
Maastricht, the Netherlands University of Massachusetts—Amherst
Pranjal H. Mehta Amherst, MA, USA
University College London Maren N. Vitousek
London, England, UK Cornell University
Virginia E. Mitchell Ithaca, NY, USA;
Oakland University Virginia Tech
Rochester, MI, USA Blacksburg, VA, USA
Justin K. Mogilski Jovana Vukovic
Oakland University Broward College
Rochester, MI, USA Fort Lauderdale, FL, USA
Nicholas C. Neibergall Glenn Weisfeld
University of Missouri—Columbia Wayne State University
Columbia, MO, USA Detroit, MI, USA

x Contributors
Lisa L. M. Welling Anna Wysocki
Oakland University Oakland University
Rochester, MI, USA Rochester, MI, USA
Lynea R. Witczak Samuele Zilioli
University of California—Davis Wayne State University
Davis, CA, USA Detroit, MI, USA

Contributors xi
TA B L E O F C O N T E N T S

1. Integrating Mechanisms and Functions to Understand Behavior 1

Lisa L. M. Welling and Todd K. Shackelford

Part 1 • Development and Survival

2. Hormones and Behavior: A Life History Perspective 13
Maren N. Vitousek and Laura A. Schoenle
3. Sex Differences in Primate Social Relationships During Development 27
Joyce F. Benenson
4. Sex Differences in Cognition: Evidence for the Organizational–Activational
Hypothesis 43
Elizabeth Hampson
5. Involvement of the Sex Hormones in Learning and Memory 67
Kelsy S. J. Ervin and Elena Choleris
6. Endocrine Disruptors and Other Environmental Influences on
Hormone Action 87
Laura N. Vandenberg

Part 2 • Reproductive Behavior

7. Investigating the Ovulatory Cycle: An Overview of Research
and Methods 109
Lisa L. M. Welling and Robert P. Burriss
8. Reproductive Behavior in the Human Male 125
Stefan M. M. Goetz, Glenn Weisfeld, and Samuele Zilioli
9. Mate Preferences Across the Lifespan 143
Lynda G. Boothroyd and Jovana Vukovic
10. The Influence of Maternal Stress and Child Maltreatment
on Offspring 161
LillyBelle K. Deer, Kristin Bernard, and Camelia E. Hostinar
11. Evolution and Human Fatherhood 179
Adam H. Boyette and Lee T. Gettler
12. Hormones, Sexual Orientation, and Gender Identity 201
Nicholas C. Neibergall, Alex J. Swanson, and Francisco J. Sánchez
13. Intersexual and Intrasexual Competition and Their Relation
to Jealousy 215
Abraham P. Buunk, Karlijn Massar, Pieternel Dijkstra,
and Ana Maria Fernandez

xiii
14. Synthetic Hormones: The Influence of Hormonal Contraceptives
and Hormone Replacement Therapy on Aspects of Women’s
Mating Psychology 237
Amanda C. Hahn and Kelly D. Cobey

Part 3 • Social and Affective Behavior

15. The Endocrinology of Social Relationships and Affiliation 259
Christine Anderl, Shimon Saphire-Bernstein, and Frances S. Chen
16. Hierarchy and Testosterone: How Can Testosterone Promote Upward
Mobility in Status Hierarchies? 281
Shawn N. Geniole and Justin M. Carré
17. Competition, Dominance, and Social Hierarchy 295
Kathleen V. Casto and Pranjal H. Mehta
18. Oxytocin: An Evolutionary Framework 317
Nicholas M. Grebe and Steven W. Gangestad
19. Social Bond Paradoxes 335
Lynea R. Witczak, Trenton C. Simmons, and Karen L. Bales
20. Stress Hormones, Physiology, and Behavior 351
Justin K. Mogilski, Anna Wysocki, Simon D. Reeve, Virginia E. Mitchell,
Jenna Lunge, and Lisa L. M. Welling
21. Hormones, Circadian Rhythms, and Mental Health 367
Yasmine-Marie Cissé, Jeremy C. Borniger, and Randy J. Nelson
22. Hormones and Major Depressive Disorder 381
Mark A. Ellenbogen, Virginia Tsekova, and Lisa Serravalle
23. Sex Differences in Anxiety Disorders 405
Teresa A. Piggott, Alexandra N. Duran, Isha Jalnapurkar, Tyler Kimm,
Stephanie Linscheid, and Melissa K. Allen
24. Future Directions in Human Behavioral Endocrinology 433
Lisa L. M. Welling and Todd K. Shackelford

Name Index 443

Subject Index 446

xiv Table of Contents

 CH A PT E R
Integrating Mechanisms and Functions
1 to Understand Behavior

Lisa L. M. Welling and Todd K. Shackelford

Abstract

Evolutionary psychology and behavioral endocrinology provide complementary perspectives on

interpreting human behavior and psychology. Hormones can function as underlying mechanisms that
influence behavior in functional ways. Understanding these proximate mechanisms can inform ultimate
explanations of human psychology. This chapter introduces this edited volume by first discussing
evolutionary perspectives in behavioral endocrinology. It then briefly addresses three broad topic areas
of behavioral endocrinology: (1) development and survival, (2) reproductive behavior, and (3) social and
affective behavior. It provides examples of research within each of these areas and describes potential
adaptations. The chapter concludes with a discussion on the importance of integrating mechanisms
with function when investigating human behavior and psychology.
Key words: evolutionary psychology, behavioral endocrinology, mechanisms, function, behavior

Hormones are chemical messengers secreted into the of oxytocin receptors in the uterus during the third
bloodstream or tissue fluid system by specialized trimester (Gimpl & Fahrenholz, 2001), whereas ele-
cells. They travel from their source until they reach vated levels of insulin cause a down-regulation of
target cells with specialized receptors, to which they insulin receptors (Fröjdö, Vidal, & Pirola, 2009). In
bind to evoke a response. The three main classes addition to these biological functions, hormones
of hormones are steroids, peptide hormones, and may serve other evolved purposes under certain cir-
monoamines. Steroid hormones in humans include cumstances by influencing human behavior.
estrogens (e.g., estradiol), progestins (e.g., progester- Evolutionary psychology and behavioral endo-
one), androgens (e.g., testosterone), and corticoste- crinology have progressed as relatively i­ndependent
roids (e.g., cortisol). They are lipophilic and must fields over the last few decades. Evolutionary psychol-
bind to carrier proteins (e.g., sex hormone–binding ogists seek to explain human behavior and psy-
globulin) to circulate in the bloodstream. Peptides chology in terms of functional outcomes of natural
(e.g., oxytocin) and monoamines (e.g., melatonin) and sexual selection across our evolutionary past.
are made of one (monoamines) or more (peptides) Specifically, evolutionary psychology stands on the
amino acids. They are hydrophilic and travel freely supposition that selection pressures designed the
in the bloodstream. Hormones can change gene adaptations of the mind (as well as the body)
expression (e.g., Béchet, 1986), influence signaling and these adaptations produced behavior through
pathways (e.g., Goglia, Moreno, & Lanni, 1999), psychological, neurological, and physiological mech-
and/or change cell sensitivity by increasing (i.e., up- anisms (Tooby & Cosmides, 1992, 2005). Similar
regulating) or decreasing (i.e., down-regulating) the to physical adaptations, such as how the human foot
number of receptors for that or another hormone. For is designed to afford long-distance running (e.g.,
example, pregnancy hormones cause an up-regulation Bramble & Lieberman, 2004; Raichlen, Armstrong,

1
& Lieberman, 2011; Rolian, Lieberman, Hamill, biology, zoology, and other disciplines. The com-
Scott, & Werbel, 2009), evolutionary psychologists plementary nature of these areas is increasingly
maintain that behavior and psychological traits (e.g., recognized; annual conferences hosted by the Human
memory, learning, perception, personality, prefer- Behavior and Evolution Society and the Society for
ences) are the result of psychological mechanisms Behavioral Neuroendocrinology include a variety of
that evolved because they served an adaptive func- speakers who are investigating the hormonal basis
tion during our ancestral past (e.g., Buss, 2005; of behavior from an evolutionary perspective. In
Pinker, 2002). Hypotheses are generated accordingly other words, researchers are acknowledging that
and tested against alternative explanations using both integrating mechanisms in our understanding of
Western and cross-cultural samples (discussed in function provides additional insight that produces
Tooby & Cosmides, 2005). more complete theories and hypotheses.
Behavioral endocrinologists investigate the under- Focusing on underlying mechanisms moves
lying hormonal and neuroendocrine ­mechanisms that evolution-minded researchers from asking ultimate
influence or regulate behavior in humans and other (“Why?”) to proximate (“How?”) questions. Ultimate
animals. Behavioral endocrinology is the scientific explanations outline the function of a trait or
study of the bidirectional relationship between hor- ­behavior, whereas proximate explanations outline
mones and behavior, and of the interactions among how underlying mechanisms interact with the envi-
the brain, the endocrine system, hormones, and ronment to produce that trait or behavior (Tinbergen,
­behavior (Nelson, 2010). Although the field argua- 1963). For example, an ultimate explanation for
bly dates back to Berthold’s (1849) landmark exper- birds singing is that birds that sang over that species’
iment on castrated chicks, which provided the first ancestral past were more likely to attract a mate and
formal evidence that the testes produce substances pass on their genes (i.e., singing conferred a repro-
that influence both physiology and behavior, Frank ductive advantage), whereas a proximate explanation
Beach, who wrote the book Hormones and Behavior for birds singing is that seasonal fluctuations in tes-
(1948) and cofounded the journal of the same tosterone level cause singing behavior during the
name, first branded and defined the discipline more breeding season. Proximate explanations deal with
than a century later (Beach, 1975). Behavioral en- mechanisms, whereas ultimate explanations deal
docrinologists examine relationships with behaviors with evolved functions. Certainly, understanding
of interest using measured (e.g., Denson, Mehta, & how a m­ echanism works informs the understanding
Ho Tan, 2013; Hahn, DeBruine, Fisher, & Jones, of why a mechanism came to exist in the first
2015; Welling et al., 2007, 2008), estimated (e.g., place, and hypotheses about why mechanisms exist
Garver-Apgar, Gangestad, & Thornhill, 2008; inform research on how they function. Therefore,
Jones et al., 2005; Lukaszewski & Roney, 2009), or both proximate and ultimate explanations should
manipulated (e.g., Carré et al., 2015; Donaldson, be considered when investigating behavior.
Welling, & Reeve, 2017; Welling, Moreau, Bird,
Hansen, & Carré, 2016; Welling, Puts, Roberts, Broad Areas of Behavioral Endocrinology
Little, & Burriss, 2012) circulating hormone levels, The current chapter discusses evolutionary perspec-
or through investigating the associated biological tives in behavioral endocrinology by introducing
circuitry (e.g., receptor-binding sites, gene expres- and briefly reviewing the three broad topic areas that
sion) of these interactions (e.g., Arango et al., 1990; are the focus of this volume: (1) development and
Farfel, Kleven, Woolverton, Seiden, & Perry, 1992; survival, (2) reproductive behavior, and (3) social
Israel, 2016). Hormones influence gene expression and affective behavior. Within each of these topic
or cellular function, and increase the likelihood of areas, chapter authors discuss research and theory in
specific behaviors occurring under certain circum- important subareas. We conclude this chapter with a
stances by affecting sensory (i.e., input) systems, note on the importance of integrating mechanisms
central nervous system processing systems, and/or (proximate questions) with function (ultimate ques-
peripheral effectors (i.e., output systems such as stri- tions) to disentangle the how and why of behavior.
ated muscles; Nelson, 2010).
Scholars of both evolutionary psychology and Development and Survival
behavioral endocrinology often study interactions An organism’s investment in growth, reproduction,
using interdisciplinary methods. Both investigate and survival defines its life history strategy (e.g., Roff,
questions and/or borrow techniques from neuro­ 2002; reviewed in Vitousek & Schoenle, this volume),
science, anthropology, social psychology, genetics, and hormones govern multiple biological processes

2 Integrating Mechanisms and Functions to Understand Behavior

related to development from conception onward. deal of attention in recent years (reviewed in Ervin
Differential hormone exposure in utero affects sexual & Choleris, this volume; see also Duarte-Guterman,
behavior later in life in multiple species (reviewed in Yagi, Chow, & Galea, 2015), although most work
Clark & Galef, 1995). Behavioral sex differences are has been done with rodents (e.g., Kim, Szinte,
noticeable early on (reviewed in Benenson, this Boulware, & Frick, 2016; Luine, 2015).
volume) and likely stem, at least in part, from this Together, this work highlights how underlying
differential hormone exposure (see Collaer & Hines, hormonal mechanisms can evolve to influence mul-
1995). Across primate species, young males are more tiple domains. Sex differences in play behavior and
likely than females to engage in rough-and-tumble adult cognition appear to develop under the influ-
play and confrontations over status (e.g., Meaney, ence of sex steroids (e.g., Hampson & Rovet, 2015;
Stewart, & Beatty, 1985). Work with rhesus and Hines, 2003; Puts et al., 2008; Williams et al., 1990)
vervet monkeys documents sex-differentiated toy and likely reflect different selection pressures on
preferences similar to those documented in human males and females (see Cashdan & Gaulin, 2016).
children, with females preferring dolls and cooking For instance, travel over large ranges may have
pots more than males and males preferring cars and been more important for males due to different
balls more than females (Alexander & Hines, 2002; reproductive interests (Miner, Gurven, Kaplan, &
Hassett, Siebert, & Wallen, 2008). These prefer- Gaulin, 2014), which would lead to greater selec-
ences are unlikely to be about the objects them- tion for visuospatial abilities in males compared to
selves, given that monkeys have no use for cooking females (e.g., Halpern, 2013). Others have hypoth-
pots or cars, but rather are likely about movement, esized that the female advantage in object location
with males preferring toys that move actively through memory reflects a sex-linked division of labor in our
space more than females do. Correspondingly, human ancestral past, with females engaging in compara-
girls are more likely than boys to help their parents tively more gathering than males (e.g., Neave,
with child-rearing tasks for their siblings and take Hamilton, Hutton, Tildesley, & Pickering, 2005;
more pleasure in caring for infants (e.g., Edwards, Silverman, Choi, & Peters, 2007). Thus, differences
2002). These sorts of sex-conforming behaviors are in hormonal profile are related to evolved differences
weaker among girls exposed to testosterone prenatally, in behavior, although it is worth noting that evolved
such as those girls born with congenital adrenal hormonal mechanisms can be affected by modern
hyperplasia (reviewed in Bailey & Zucker, 1995). pollutants called endocrine-disrupting chemicals (re-
The Organizational-Activational Hypothesis posits viewed in Vandenberg, this volume), which may alter
that sex steroid hormones permanently organize important hormonal functions, including those as-
neural circuitry during early development (i.e., via sociated with reproductive behavior (e.g., Colborn,
exposure to specific steroids at critical ­developmental vom Saal, & Soto, 1993). These mechanisms work
periods) to give rise to sexually ­ differentiated between individuals (e.g., sex differences) but also
behaviors that are activated by steroid hormone
­ within individuals as levels of endogenous hor-
­exposure in adulthood (reviewed in Hampson, this mones fluctuate. Next, we review how changes in
volume). Most evidence for this hypothesis comes these hormones within an individual functionally
from animal work (e.g., Phoenix et al., 1959), but influence changes in behavior that promote repro-
evidence in humans is accumulating (e.g., Heil, duction and parenting.
Kavšek, Rolke, Beste, & Jansen, 2011; Vuoksimaa
et al., 2010). Indeed, several sex differences in cog- Reproductive Behavior
nition have been identified; for example, women tend Sexual selection involves members of one sex
to excel at object location memory tasks (Voyer, choosing members of the other sex to mate with
Postma, Brake, & Imperato-McGinley, 2007), whereas and competing with members of the same sex for
men tend to excel at mental rotation tasks (Voyer, access to potential mates. Over the last few de-
Voyer, & Bryden, 1995), among other sex differences cades, increasing evidence suggests that women’s
(see, e.g., Kimura, 2004). These sex differences often fertile status is not entirely concealed, as had
appear or increase around puberty when sex hormone been previously supposed (see, e.g., Gangestad &
levels increase (e.g., Hyde, Mezulis, & Abramson, Thornhill, 2008; Gilldersleeve, Haselton, & Fales,
2008), lending support to the proposed organizing 2014a, 2014b). Rather, hormonal fluctuations
(and later activating) role of sex steroids in behavior. ­associated with ovulation are related to shifts in
Similarly, the influence of estrogens in activating as- ­attractiveness (e.g., Miller & Maner, 2011; Pipitone
pects of learning and memory has r­eceived a great & Gallup, 2008; Puts et al., 2013; Roberts et al.,

Welling and Shackelford 3

2004), sexual motivation (e.g., Gangestad, Thornhill, Agustin, McDade, & Kuzawa, 2012). Given the
& Garver, 2002; Haselton & Gangestad, 2006; association between testosterone and aggression
­
Roney & Simmons, 2013), and preferences for (e.g., Archer, 2006), this research suggests that tes-
male traits putatively associated with underlying tosterone functionally decreases across a long-term
genetic quality (e.g., Gangestad, Simpson, Cousins, relationship and in response to fatherhood in order
Garver-Apgar, & Christensen, 2004; Havlíček, to decrease aggressive and mate-seeking behaviors
Roberts, & Flegr, 2005; Little & Jones, 2012; and, in turn, to increase resource allocation toward
Welling et al., 2007). Within-subject changes in parenting effort (i.e., investment in one’s mate and
measured or estimated sex hormones associated children; see also, e.g., Bribiescas, 2001).
with the fertile phase of the menstrual cycle may Mate preferences in both sexes likely evolved to
underlie physical, psychological, and behavioral facilitate reproduction with individuals possessing
changes that increase conception probability and “good” genes and other traits (e.g., kindness) in-
the likelihood of reproducing with high-quality dicative of fecundity and good parenting potential
mates (reviewed in Welling & Burriss, this volume). (reviewed in, e.g., Little, 2015). To be sure, stress
Relatedly, women report greater jealousy (Buunk during gestation and poor parenting can have a
& Van Brummen-Girigori, 2016; Cobey et al., ­severely negative impact on offspring well-being
2012) and engage in more intrasexual competition and survival (e.g., Gilbert et al., 2015; Pratchett &
(e.g., Fisher, 2004; Lucas, Koff, & Skeath, 2007; Yehuda, 2011; Taylor, Guterman, Lee, & Rathouz,
Piccoli, Foroni, & Carnaghi, 2013) when maximally 2009; for a review, see Deer, Bernard, & Hostinar,
fertile (for an in-depth review of the hormonal this volume), making mate choice an important
correlates of jealousy and intrasexual competition, component of reproductive outcomes. Preferences
see Buunk, Massar, Dijkstra, & Fernandez, this for these traits emerge very early; newborn infants
volume). Because jealousy and i­ntrasexual compe- spend longer looking at faces judged as attractive by
tition facilitate securing and ­retaining a mate (e.g., adults compared to faces judged as relatively unat-
Buss, 2005), these findings lend support to the tractive (Slater et al., 1998; Slater, Quinn, Hayes,
premise that within-woman variation in sex ste- & Brown, 2000), although childhood preferences
roid hormones influences mating psychology and do not become fully mature until around age 14 years
behavior. Moreover, synthetic hormones such as (e.g., Boothroyd, Meins, Vukovic, & Burt, 2014; for
those found in the hormonal contraceptive pill a review of mate preferences across the lifespan, see
may alter aspects of mate choice (e.g., Roberts et Boothroyd & Vukovic, this volume). The onset of
al., 2014) and behavior (e.g., Welling et al., 2012), adult mate preferences peripubertally implicates a hor­
indicating that exogenous hormones also impact monal component, such as dehydroepiandrosterone
behavior and may disrupt evolved functions of (e.g., Boothroyd et al., 2014; Saxton, DeBruine,
­endogenous hormones (reviewed in Hahn & Cobey, Jones, Little, & Roberts, 2009), and further evinces
this volume). the connection between hormones and reproductive
Sex steroids can serve similar functions in men behavior (e.g., Jones et al., 2005; Welling et al., 2008).
(reviewed in Goetz, Weisfeld, & Zilioli, this volume); Yet, sex steroids and other hormones serve a multi-
testosterone in men amplifies risk-taking behaviors tude of other social and affective functions. Next,
in the service of mating effort (Ronay & von Hippel, we briefly review some findings on the bidirectional
2010), increases mate-seeking behavior (van der relationships between hormones, affect, and social
Meij, Almela, Buunk, Fawcett, & Salvador, 2012), behavior.
and decreases interest in infants (Zilioli et al., 2016).
Likewise, men’s testosterone is negatively correlated Social and Affective Behavior
with relationship length (Gray et al., 2004), relation- The relationships between hormones and affect are
ship commitment (Edelstein, van Anders, Chopik, among the most well established of the many re-
Goldey, & Wardecker, 2014), marriage and father- search areas within behavioral endocrinology. For
hood (Gettler, McDade, Agustin, Feranil, & Kuzawa, example, when someone colloquially refers to a
2013; Gettler, McDade, Feranil, & Kuzawa, 2011; person as “hormonal,” they are often referencing
Gray, Ellison, & Campbell, 2007; Gray, Kahlenberg, sudden changes in mood or general negative affect.
Barrett, Lipson, & Ellison, 2002; see also Boyette & This pejorative use aside, hormones do influence
Gettler, this volume, for a review on fatherhood), and multiple aspects of affect and social behavior, both
involvement in parenting (e.g., Gettler, McDade, positive (e.g., affiliation; Brown et al., 2009) and
Agustin, Feranil, & Kuzawa, 2015; Gettler, McKenna, negative (e.g., aggression; Carré, Putnam, &

4 Integrating Mechanisms and Functions to Understand Behavior

McCormick, 2009). Affiliation, which consists of Schaefer, Weren, Hill, & Granger, 2016; reviewed
close interpersonal relationships (e.g., parent–child, in Casto & Mehta, this volume). Specifically, in
romantic partners) and the behaviors necessary to primate species in which hierarchical rank is main-
establish and maintain those relationships (e.g., tained with aggression, dominant individuals are
caregiving, trustworthiness; Feldman, 2012), is a under more stress and have higher cortisol levels
commonly studied element of social behavior (e.g., Muehlenbein & Watts, 2010), whereas in pri-
(­reviewed by Anderl, Saphire-Bernstein, & Chen, mate species in which the subordinates are suppressed
this volume). Social/affiliative behaviors are related with intimidation, the subordinates are under more
to steroid ­concentrations, such as cortisol level (e.g., stress and have higher cortisol levels (e.g., Sapolsky,
higher salivary cortisol levels are associated with 2005). Although acute stress can be functional in
less social networking; Koernienko, Clemans, Out, that it fuels survival-related behaviors and moti-
& Granger, 2014), but the majority of research has vates relationship reparation, chronic stress and
­focused on the mediating influence of the peptide the associated hormones can have detrimental
hormone oxytocin. Oxytocin increases in response long-term impacts on health and well-being, in-
to affectionate contact with infants (e.g., Apter-Levi, cluding decreased physical and mental health
Zagoory-Sharon, & Feldman, 2014) and romantic ­(reviewed in Mogilski et al., this volume). Indeed,
partner empathy (Schneiderman, Kanat-Maymon, hormonal changes may precede or accompany
Ebstein, & Feldman, 2014), and is positively cor- ­several mental health disorders, such as depressive
related with reports of relationship quality (e.g., disorders (reviewed in Ellenbogen, Tsekova, &
­
Holt-Lunstad, Birmingham, & Light, 2015). Some Serravalle, this volume) and anxiety disorders
findings are somewhat contradictory, however. For (­reviewed in Pigott et al., this volume). For example,
example, oxytocin has been found to both increase chronic dysregulation of the hypothalamic-pituitary-
(Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005) adrenal (HPA) axis resulting in abnormally high
and decrease (Bartz et al., 2011) trust during an cortisol concentrations is commonly found in
economic game. This contradictory evidence suggests ­individuals with depressive disorders (e.g., Carroll
that hormones can be co-opted across social con- et al., 2007). Dysregulation of diurnal hormone
texts to accomplish specific behavioral goals under levels can have a similar impact on mental health
specific conditions (e.g., nurturing behavior char- (reviewed in Cissé, Borniger, & Nelson, this
acterized by high oxytocin and low testosterone vs. volume). This research demonstrates that mental
sexual behavior characterized by high oxytocin and health issues can manifest physiologically as a down-
high testosterone; van Anders, Goldey, & Kuo, 2011; stream consequence of hormonal ­mechanisms being
see also Witczak, Simmons, & Bales, this volume, out of balance.
for a discussion of social bond paradoxes). Oxytocin
may function more broadly as a component of a Conclusion
threat management system, whereby it enhances Behavioral endocrinology and evolutionary psy-
the salience of social cues in response to perceived chology encompass the topics covered in this
threats to important social relationships and mo- chapter and many more. Evolutionary psychology,
tivates the individual to repair possible damage in particular, has at times been mischaracterized as
(see Grebe & Gangestad, this volume). In this supporting or justifying negative behaviors (e.g.,
way, oxytocin would serve a prosocial function, rape, aggression; discussed in Nicolas & Welling,
but may be expressed differently depending on the 2015). These critiques are often based in the natu-
circumstances. ralistic fallacy—the idea that what is ought to be
Other hormones, particularly testosterone and (i.e., what is natural is good; see Hagen, 2005).
cortisol, influence antisocial behaviors. Circulating Such criticisms are unfounded, however, because
testosterone influences status-seeking (e.g., studying or postulating why something exists does
Eisenegger, Haushofer, & Fehr, 2011), competitive not mean something ought to exist. Put another
(e.g., Carré et al., 2009), and aggressive (e.g., way, because a trait or behavior is natural does not
Klinesmith, Kasser, & McAndrew, 2006) behaviors make it morally defensible. Similarly, evolutionary
(reviewed in Geniole & Carré, this volume). These psychology and behavioral endocrinology have at
behaviors help define social hierarchies within times been mistakenly assumed to support genetic
­primates, and placement within these hierarchies determinism (i.e., the view that human behavior is
is reflected in an individual member’s circulating entirely controlled by genes/biology). For example,
testosterone and cortisol levels (e.g., Kornienko, the cross-cultural finding that men are, on average,

Welling and Shackelford 5

more aggressive than women and that testosterone Bartz, J., Simeon, D., Hamilton, H., Kim, S., Crystal, S., Braun,
is associated with aggression can be misinterpreted A., . . . Hollander, E. (2011). Oxytocin can hinder trust and
cooperation in borderline personality disorder. Social
as claiming that men are biologically incapable of Cognitive and Affective Neuroscience, 6(5), 556–563.
controlling their aggression (reviewed in Campbell, Beach, F. A. (1948). Hormones and behavior. New York, NY: Paul
2012). But genetically determined mechanisms do Hoeber.
not necessarily translate into specific behaviors (see Beach, F. A. (1975). Behavioral endocrinology: An emerging
Hagen, 2005); for instance, the extent to which discipline. American Scientist, 63, 178–187.
Béchet, D. (1986). Control of gene expression by steroid
men engage in intimate partner violence varies hormones. Reproduction, Nutrition, & Development, 26(5A),
greatly depending on the gender equality of their 1025–1055.
culture (Archer, 2006), showing that environment Berthold, A. A. (1849). Transplantation der Hoden [The
plays a role in shaping behavioral responses. By the transplantation of the testes]. Archiv für Anatomie, Physiologie
same token, although feelings of pathogen disgust und Wissenschaftliche Medicin, 16(1), 42–46.
Boothroyd, L. G., Meins, E., Vukovic, J., & Burt, D. M. (2014).
likely evolved to facilitate contagion avoidance Developmental changes in children’s facial preferences.
(Tybur, Lieberman, Kurzban, & DeScioli, 2013), Evolution and Human Behavior, 35(5), 376–383.
people (e.g., healthcare professionals, sanitation Bramble, D. M., & Lieberman, D. E. (2004). Endurance
workers) can and do purposefully come into contact running and the evolution of Homo. Nature, 432, 345–352.
with disease-causing agents. Thus, mechanisms Bribiescas, R. G. (2001). Reproductive ecology and life history of
the human male. American Journal of Physical Anthropology,
such as hormones may predispose individuals to 116, 148–176.
behave in certain ways given a particular environ- Brown, S. L., Fredrickson, B. L., Wirth, M. M., Poulin, M. J.,
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Buss, D. M. (2005). Handbook of evolutionary psychology.
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­ Newmann, C. S., & Goldfarb, B. (2015). Digit ratio
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and risk for maternal maltreatment of young children. Psychoneuroendocrinology, 64, 136–142.
American Journal of Public Health, 99(1), 175–183. Welling, L. L. M., Puts, D. A., Roberts, S. C., Little, A. C., &
Tinbergen, N. (1963). On the aims of methods of ethology. Burriss, R. P. (2012). Hormonal contraceptive use and mate
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Tooby, J., & Cosmides, L. (1992). The psychological foundations Hormones and Behavior, 61, 114–120.
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Tooby, J., & Cosmides, L. (2005). Conceptual foundations 104, 84–97.
of evolutionary psychology. In D. Buss (Ed.), Handbook of Zilioli, S., Ponzi, D., Henry, A., Kubicki, K., Nickels, N.,
evolutionary psychology (pp. 5–67). Hoboken, NJ: Wiley. Wilson, M. C., & Maestripieri, D. (2016). Interest in babies
Tybur, J. M., Lieberman, D., Kurzban, R., & DeScioli, P. (2013). negatively predicts testosterone responses to sexual visual
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Welling and Shackelford 9

 PA R T
1
Development and
Survival
 CH A PT E R

2 Hormones and Behavior

A Life History Perspective

Maren N. Vitousek and Laura A. Schoenle

Abstract

Hormones mediate the expression of life history traits—phenotypic traits that contribute to lifetime
fitness (i.e., reproductive timing, growth rate, number and size of offspring). The endocrine system
shapes phenotype by organizing tissues during developmental periods and by activating changes in
behavior, physiology, and morphology in response to varying physical and social environments.
Because hormones can simultaneously regulate many traits (hormonal pleiotropy), they are
important mediators of life history trade-offs among growth, reproduction, and survival. This
chapter reviews the role of hormones in shaping life histories with an emphasis on developmental
plasticity and reversible flexibility in endocrine and life history traits. It also discusses the advantages
of studying hormone–behavior interactions from an evolutionary perspective. Recent research in
evolutionary endocrinology has provided insight into the heritability of endocrine traits, how selection
on hormone systems may influence the evolution of life histories, and the role of hormonal pleiotropy
in driving or constraining evolution.

Keywords: life history, trade-offs, hormones, reproductive timing, growth, endocrine traits, fitness

What Is Life History? a­ ttempts, or species that migrate annually between

The life history of an organism is defined as the wintering and breeding grounds.
­pattern of investment it makes in growth, reproduc- Life history traits are specific behavioral, mor-
tion, and survival throughout its lifetime (Ricklefs, phological, or physiological traits that influence the
1977; Roff, 2002; Stearns, 1992). Life histories are rate or timing of life history stages, or the location
composed of different stages, which are characterized in which they occur. In birds, important life history
by differing patterns of investment. For example, traits include the timing of clutch initiation and the
during ontogeny, juvenile great apes devote most of number of eggs laid in a clutch. Because these traits
their energy to growth and survival. Once they reach influence organisms’ lifetime fitness in different
sexual maturity, investment in growth is replaced ways depending on the environment, life history
by investment in reproduction. All organisms have traits show distinct patterns across environments.
a life history, but the sequence of stages, and the For example, birds that inhabit more seasonal envi-
particular challenges that they entail, can differ ronments, where breeding seasons are shorter and
dramatically. Insects like the Monarch butterfly, each pair is likely to have only a single reproductive
which undergo complete metamorphosis, proceed ­attempt per season, invest more in each attempt by
through multiple stages of ontogeny (egg, larval, laying more eggs per clutch (Cardillo, 2002; Jetz,
and pupal) before reaching adulthood. The life Sekercioglu, & Bohning-Gaese, 2008).
­history of many species involves entering the same Because resources are finite, life histories are
life history stage repeatedly, for example, multiparous shaped by fundamental trade-offs among allocation
individuals e­ngaging in repeated reproductive to different key components (Roff, 2002; Stearns,

13
1992). Thus, organisms often differ in their “pace of challenges (e.g., psychological, physiological, or
life” (Ricklefs & Wikelski, 2002). Short-lived species, social stressors) and activate a suite of behaviors that
like many insects and rodents, often invest an enor- can help organisms respond effectively to challenges.
mous amount in one or a few reproductive a­ ttempts. In many species, moderate stressors increase foraging
In contrast, long-lived species, like African elephants behavior (Landys, Ramenofsky, & Wingfield, 2006);
and many primates, delay reproduction in favor of a in humans and rodents, elevated glucocorticoids
long period of growth, before investing heavily in promote the intake of specific food types, often those
the care of a small number of young, often over an with high fat or sugar content (Dallman, 2009;
extended period of time. Such trade-offs among in- Dallman et al., 2004; la Fleur, 2006). For most or-
vestment in different life history traits or stages also ganisms this “stress eating” phenomenon is likely to
operate within populations. For example, investment be ­adaptive, as it supports the acquisition of energy
in immune function (which can be crucial for sur- required to deal with a challenge. The stressors facing
vival) often impairs reproduction (Bonneaud et al., modern humans, however, are largely psychological
2003); conversely, when reproductive effort increases, in nature, and are rarely accompanied by food limi-
immune investment declines (Ardia, Schat, & Winkler, tation. Instead, this pattern of eating has been impli-
2003; Knowles, Nakagawa, & Sheldon, 2009). As a cated in generating a variety of health problems, from
result of these trade-offs, individuals within a popu- obesity to heart disease.
lation can differ—sometimes dramatically—in their Hormones mediate the expression of life history
life history. traits, and other phenotypic traits, by binding to
receptors on or inside cells. Thus, trait expression is
How Do Hormones Mediate Phenotypic affected not only by circulating hormone concen-
Expression? trations but also by other factors that influence
Hormones are key mediators of life history. They how effectively hormones reach receptors, and how
influence the expression of life history traits, initiate they change cellular function and gene expression
transitions among life history stages, and mediate following binding (e.g., carrier/transport protein
trade-offs among investment in different components ­expression, receptor affinity and location, and the
of life history. Mechanistically, hormones can presence of cofactors). Hormone concentrations
change the probability that a behavior will be per- and other regulatory factors produce multiple vari-
formed, or an individual’s physiological state, through ants of hormone–trait relationships. For example,
two main modes of action: organizational and activa- trait expression can be linear and dose dependent,
tional ­effects (see also Hampson, this volume). During remain constant across a range of hormone concen-
development, hormones organize phenotypes by
­ trations (step function), and/or peak at intermedi-
shaping tissue structure and function or by inducing ate concentrations (inverted-U function) (Adkins-
epigenetic changes (i.e., long-term alterations in the Regan, 2005).
transcriptional potential of a cell). Hormones’ organi- Hormones frequently influence the expression
zational effects, which are often irreversible, are a form of multiple traits simultaneously. Such pleiotropic
of developmental plasticity; a single g­ enotype could actions are an important mechanism, enabling
lead to different phenotypes depending on hormone ­hormones to coordinate the multitude of traits that
concentrations during development (Arnold, 2009). make up an individual’s life history strategy. Pleiotropic
For example, exposure to gonadal hormones during actions can all contribute to inducing the same
puberty contributes to the development of adult phenotypic state—for instance, when females of
­
sexual behavior in rodents. Males castrated during many mammal species give birth, oxytocin induces
adolescence attempt fewer matings than intact males uterine contractions, initiates the release of milk,
and can fail to successfully mate as adults, even when and primes females for postpartum maternal behav-
supplemented with testosterone (K. M. Schulz & ior (Gimpl & Fahrenholz, 2001). These actions of
Sisk, 2016; Sisk & Zehr, 2005). oxytocin all support reproduction. Pleiotropy can
Hormones play an activational role when they also result in the same hormone producing positive
reversibly influence the probability of trait expression. and negative effects on a life history trait. For exam-
Hormone-regulated phenotypic flexibility allows or- ple, estrogens support egg production in birds,
ganisms to respond rapidly to changes in the physical but at the same time can suppress red blood cell pro-
or social environment (Arnold, 2009). For ­instance, duction (Wagner, Prevolsek, Wynne-Edwards, &
glucocorticoid hormones increase in ­ response to Williams, 2008; Wagner, Stables, & Williams, 2008).

14 Hormones and Behavior

The ­resulting reduction in red blood cell counts, s­ignals, both through their direct effects and by
­hematocrit, and hemoglobin (Wagner, Stables, & ­altering the concentration or temporal dynamics of
Williams, 2008) can impair reproductive success other hormones. A particularly well-studied example
(Fronstin, Christians, & Williams, 2015). of this phenomenon is the complex learned songs
From embryonic development through senes- that songbirds use to advertise to conspecifics (e.g.,
cence, endocrine phenotype shapes the physiology Nowicki, Peters, & Podos, 1998). Males exposed to
and behaviors that underlie life history traits. Further­ developmental stress, or to experimentally elevated
more, hormones facilitate the developmental plas- glucocorticoids during development, show a reduced
ticity and trait flexibility that enable individuals to ability to learn the complex songs used in sexual
alter life history traits to match the environment. In ­interactions (Bell et al. 2018; Spencer, Buchanan,
the following section we present specific examples Goldsmith, & Catchpole, 2003). Females show a dis-
of the endocrine mediation of life history traits to tinct preference for the song of nondevelopmentally
illustrate the importance of endocrine physiology to stressed males (Spencer et al., 2005).
survival and reproduction. Hormones also activate the production and
­expression of dynamic signal traits—those whose
The Endocrine Mediation of Life History: expression levels change over time—in adulthood.
Examples Androgens are well-known mediators of a diversity
Reproductive Rate: Sexual Signals and of signal types, including bright or distinctively
Mate Choice colored feathers and skin, behavioral displays, court-
Life histories are intimately linked with reproductive ship vocalizations, and olfactory signals (Evans,
rate because of the inherent trade-off between Goldsmith, & Norris, 2000; Gosling & Roberts,
­investment in reproduction and survival. One of the 2001; Mougeot, Dawson, Redpath, & Leckie, 2005;
ways that hormones influence reproductive rate is Wikelski, Steiger, Gall, & Nelson, 2005). Androgens
by changing how much individuals invest in acquir- can also be involved in maintaining the honesty of
ing mates. Hormones play a central role in mediating sexual advertisements through pleiotropic effects
the development and expression of many diverse on immune function (Foo, Nakagawa, Rhodes, &
behaviors and morphological traits used to advertise Simmons, 2016) or other aspects of phenotype
to potential mates. They also influence how these (Wingfield, Lynn, & Soma, 2001). Yet androgens
signals are perceived and evaluated by competitors are by no means ubiquitous mediators of sexual sig-
and by members of the opposite sex—thus yielding nals; the expression of many signal types is ­mediated
their ultimate effect on reproductive success. by other hormones, or by the combined actions of
Organizational effects of exposure to sex steroids multiple hormones. For example, the vocal signals
during development have long been known to shape of midshipman fish are mediated by the opposing
the expression of secondary sexual traits. The pio- effects of steroids (11-ketotestosterone and cortisol)
neering work of Arnold Berthold in the 1840s and nonapeptides (arginine vasotocin and isotocin)
revealed that the male-typical plumage, colorful
­ (Bass, 2008; Goodson & Bass, 2000).
comb, and sexual behavior of roosters are absent in Hormones also influence mating success by alter-
individuals castrated as chicks, but can be restored by ing how sexual signals are perceived and evaluated.
reimplanting testes in the abdomen. More recent The hypothalamic-pituitary-gonadal (HPG) axis,
work has revealed that natural variation in the which regulates the production of gonadal hormones
amount or timing of exposure to androgens during (e.g., estrogens and androgens), plays a particularly
development can also impact sexual signal develop- important role in mediating mating preferences.
ment and expression. For example, male rodents that Female tungara frogs and zebra finches increase
develop in utero in between two other male embryos their response to the acoustic displays of males when
are ­exposed to higher testosterone levels than those they are dosed with gonadal hormones (Lynch,
that develop between two females. As adults, they Crews, Ryan, & Wilczynski, 2006; Vyas, Harding,
differ in their sexual, aggressive, and parental behav- Borg, & Bogdan, 2009). Gonadotropin-releasing
ior (­reviewed in Clark & Galef, 1995) and develop hormone (GnRH), which constitutes the first step
­olfactory signals that are perceived as more attractive of the HPG axis, can influence females’ willingness
to females (Clark & Galef, 1994). Exposure to ele- to mate (Sakuma & Pfaff, 1980), as well as changing
vated glucocorticoid levels during development also how prior experience influences mating decisions
can profoundly affect the development of sexual (Okuyama et al., 2014).

Vitousek and Schoenle 15

 Because organisms in stressful environments known about whether variation in endocrine system
often have a lower residual reproductive value (i.e., function drives individual variation in parental in-
a lower chance of reproducing successfully in the vestment, but clues are emerging in several systems.
future), they are more likely to benefit from invest- Stressor exposure during development has been
ing in a current reproductive attempt rather than linked to differences in parental investment in a
waiting for the uncertain possibility that they will number of species. A remarkable demonstration of
reproduce again. It is thus unsurprising that gluco- this effect can be seen in the children born in the
corticoid hormones also appear to influence how western Netherlands in 1945. During this period, a
accepting females are of potential mates. This can Nazi embargo cut off food transport into the region,
occur through both organizational and activational and its inhabitants suffered a several-month period
effects. For example, female European starlings that of acute starvation. Once the Netherlands were
are developmentally stressed show less of a prefer- ­liberated by the Allies, food was again plentiful.
ence for the song of conspecifics over heterospecifics Exposure to this prenatal stressor had lasting effects
and differ in their immediate early gene response to not only on the health and senescence rates of the
song in the auditory forebrain (Farrell, Neuert, Cui, individuals that were born from exposed mothers
& Macdougall-Shackleton, 2015). In rats and frogs, but also on their own patterns of parental investment
females with experimentally elevated circulating (L. C. Schulz, 2010). As adults, prenatally exposed
glucocorticoids are more accepting of males that women reproduced sooner and gave birth to babies
display nonpreferred signals (Davis & Leary, 2015; with more body fat; their offspring also suffered
Kavaliers & Ossenkopp, 2001). In some cases, from poor health in adulthood (Painter et al., 2008).
­investment in mate choice may be more closely Experimental work in other species has begun to
­related to the response to acute stressors than baseline pinpoint the mechanisms linking stressor exposure
hormone levels. Female Galapagos marine iguanas to transgenerational changes in parental investment
down-regulate glucocorticoid production during and other life history traits. In rats, the amount of
mate choice—an extraordinarily costly process in licking and grooming that young receive from their
which females can lose over 20 percent of their mothers shapes their own parental behavior as
body mass (Vitousek, Mitchell, Woakes, Niemack, adults (Francis, Diorio, Liu, & Meaney, 1999). Rats
& Wikelski, 2007; Vitousek, Mitchell, Romero, groomed at higher rates in their youth are also
Awerman, & Wikelski, 2010). Natural variation in more attentive mothers to their own young. Work
baseline glucocorticoid levels is unrelated to mate by Michael Meaney and colleagues has determined
selectivity, but females that mount a stronger gluco- that these changes occur through glucocorticoid-
corticoid response to acute stress invest less effort in mediated ­epigenetic programming (Weaver et al.,
mate choice (Vitousek & Romero, 2013). 2004). Grooming activates the serotonin systems of
offspring and increases glucocorticoid receptor gene
Parental Investment and Offspring Fitness transcription. As adults, offspring reared by high-
Following mating, individuals of one or both sexes grooming mothers have reduced methylation in the
face a series of decisions about how much to invest glucocorticoid receptor gene promoter region, which
in their developing offspring—decisions that can leads to greater glucocorticoid receptor expression
have major consequences for offspring survival, and in the brain and a more muted hormonal stress
for parents’ ability to engage and invest in future response (van Hasselt et al., 2012; Hellstrom, Dhir,
reproductive attempts. It is often clear from casual Diorio, & Meaney, 2012; Weaver et al., 2004).
observation that individuals differ enormously in Such effects are not limited to mammals; maternal
the extent to which they invest in their offspring. stressor exposure and maternal care have been caus-
These differences can include the extent to which ally linked with endocrine function, gene expression,
developing embryos are provisioned with nutrients behavior, and cognitive function in a wide variety of
and immune compounds, postnatal feeding rates, taxa (e.g., Andrewartha & Burggren, 2012; Boogert,
nest defense, and affiliation behaviors like grooming Zimmer, & Spencer, 2013; Nyman, Fischer, Aubin-
and licking offspring. The hormones that activate Horth, & Taborsky 2018; Marasco, Herzyk, Robinson,
and mediate parental investment differ across spe- & Spencer, 2016; Roche, McGhee, & Bell, 2012).
cies and between the sexes, but steroid hormones It has also recently been discovered that fathers’
(estrogens, progesterone, glucocorticoids, and tes- experiences can program aspects of offspring phe-
tosterone), prolactin, and nonapeptides are commonly notype through stress-induced changes in sperm
involved (Adkins-Regan, 2005; Lynn, 2016). Less is microRNA (Rodgers, Morgan, Leu, & Bale, 2015).

16 Hormones and Behavior

Understanding the extent to which hormones metamorphosis (Denver, 2009, 2013; Denver &
function as transgenerational mediators of phenotype Middlemis-Maher, 2010). However, accelerating
and life history trade-offs, and the situations under meta­morphosis involves life history trade-offs: Indi­
which such effects are evolutionarily advantageous, viduals that metamorphose at a smaller size also reach
are exciting and active areas of investigation. a smaller maximal body size (Denver, 2013, 2009).
Smaller individuals are less likely to survive to sexual
Hormones Mediate Life History Transitions maturity, and reproduce later (Berven, 1990;
Transitioning between life history stages involves Semlitsch, Scott, & Pechmann, 1988).
coordinated changes in the expression of morpho- In species that reproduce seasonally, appropriately
logical, physiological, and behavioral traits. This timing reproduction can be critical to success (Hahn
phenotypic flexibility enables an animal to cope & Macdougall-Shackleton, 2008; van Noordwijk,
with fluctuating environmental conditions (e.g., Mccleery, & Perrins, 1995; Perrins, 1970; Verhulst
seasons, drought) or perform different functions & Nilsson, 2008). As a result, many species rely on
(e.g., reproduction, growth). Hormones can regu- environmental cues to determine when to transition
late the onset of life history transitions in response into breeding condition (Wingfield, 2008). Hormonal
to environmental and internal cues, allowing indi- responses to changing day length are fundamental
viduals to time the transition to match current con- to reproductive readiness in many vertebrates, par-
ditions (Wingfield, 2008). ticularly those living at high latitudes (Dawson, King,
The morphological transformations that occur Bentley, & Ball, 2001; Gerlach & Aurich, 2000;
throughout metamorphosis might be the most Kriegsfeld, Ubuka, Bentley, & Tsutsui, 2015). In
­extreme example of phenotypic plasticity during a birds and mammals, patterns of melatonin release
life history transition. Metamorphosis has been change with day length. In spring and summer
widely studied in insects and amphibians, but also breeders, long duration and high levels of melatonin
occurs in other taxa including fish, invertebrates, secretion inhibit reproduction via suppression of
fungi, and plants (Bishop et al., 2006). In insects, the HPG axis that regulates production of the re-
metamorphosis is regulated primarily by antagonistic productive steroids (Falcon et al., 2009).
interactions between juvenile hormones and ecdys- Environmental conditions are not perfectly
teroids (Mitra, 2013; Truman & Riddiford, 2002). linked to cyclic cues, like photoperiod. If organisms
Ecdysteroids support growth and development (Di depend on a single predictable cue to time transitions,
Cara & King-Jones, 2013), whereas juvenile hor- they risk a mismatch between life history stage
mones typically restrict metamorphosis, resulting in and environmental conditions (Wingfield, 2008).
the maintenance of juvenile traits (Mitra, 2013). Hormonal flexibility allows individuals to fine-tune
The hormones’ release and, thus, the timing of met- life history transitions in alignment with a fluctuating
amorphosis depend on multiple factors, including environment (Wingfield, 2015). The hypothalamic-­
temperature, energy stores, and the often photo- pituitary-adrenal (HPA) axis, which leads to the
regulated circadian clock (Di Cara & King-Jones, production of glucocorticoids, regulates behavioral
2013). The endocrinology of amphibian metamor- and physiological responses to challenges (e.g., low
phosis parallels that of insects in that it involves food availability, high predation risk; Sapolsky,
­antagonistic interactions between endocrine signals Romero, & Munck, 2000). The HPA axis plays a
that promote development (thyroid hormones) and critical role in regulating the onset of reproduction
those that inhibit metamorphosis (prolactin) (Flatt, in arctic-breeding birds, which encounter unpre-
Moroz, Tatar, & Heyland, 2006; Galton, 1992; dictable weather and food availability at their breed-
Kikuyama, Kawamura, Tanaka, & Yamamoto,1993; ing grounds (Ramenofsky & Wingfield, 2017). If
but see Huang & Brown, 2000). The optimal timing conditions are poor (e.g., inclement weather, low
of transitioning between life history stages is likely food availability), elevated glucocorticoids suppress
to be influenced by the quality of the environment. reproductive behaviors. However, glucocorticoids’
In amphibians, environmental stressors affect the effects may be buffered by other components or
timing of metamorphosis through their effect on ­mediators of HPA axis activity, including the carrier
glucocorticoid hormones. For example, pond protein corticosteroid-binding globulin (Breuner &
­desiccation—which is typically more costly to larval Orchinik, 2002). By reducing the amount of free,
stage individuals than to adults—accelerates meta- circulating glucocorticoids, corticosteroid-binding
morphosis by increasing glucocorticoid levels, which globulin might limit the extent of reproductive
act in synergy with thyroid hormones to advance ­suppression, allowing birds to initiate or continue

Vitousek and Schoenle 17

breeding once conditions improve (Lynn, Breuner, breeds having shorter lifespans and higher concen-
& Wingfield, 2003; Ramenofsky & Wingfield, 2006; trations of IGF-1 than small breeds. An observa-
Wingfield et al., 2004). tional study of small and giant breeds demonstrated
Differences among species in the extent to that a single mutation in the IGF-1 gene of small
which they base life history transitions on flexible breeds is likely the source of the phenotypic varia-
(e.g., temperature, food availability) versus fixed tion in size and longevity (Sutter et al., 2007).
(e.g., photoperiod) cues could have significant con- Studies of humans have found that among older
sequences for patterns of resource availability, as women, those with lower IGF-1 concentrations
well as the ability of a given species to persist in (Milman et al., 2014) or reduced activity in the
changing environments. For example, larger mam- IGF-1 signaling pathway (van Heemst et al., 2005)
mals living in middle to high latitudes (e.g., caribou, live longer.
marmots) often initiate breeding based on photope- Responding effectively to substantial challenges
riod alone, but depend on resources that fluctuate can be crucial for survival. However, the increase in
according to environmental conditions. Because of glucocorticoids that supports adaptive responses to
this mismatch, large mammals are predicted to suffer challenges can also accelerate senescence (Garrido,
greater consequences from the changing climate 2011; Haussmann & Marchetto, 2010; Sapolsky,
than smaller ­rodents (e.g., voles, mice), which typ- Krey, & McEwen, 1986). The relationship between
ically utilize other environmental cues, like food glucocorticoids and senescence may be mediated by
availability, to time reproduction (Bronson, 2009). changes in telomere length (mechanisms discussed
in Haussmann & Marchetto, 2010). Telomeres are
Hormones and Senescence noncoding DNA sequences located at the ends of
Organisms cannot escape death, but life history chromosomes, and telomere shortening eventually
strategy influences their rates of aging, or senes- leads to cellular aging and death (Aubert & Lansdorp,
cence. Lifespan is inextricably linked to investment 2008; Haussmann & Marchetto, 2010). Among
patterns early in life: Organisms that invest heavily birds and mammals, species whose telomeres shorten
in rapid growth and reproduction tend to senesce more quickly have shorter lifespans (Haussmann
quickly and have short lifespans, whereas those that et al., 2003). In some cases, telomere length can
extend growth over a longer time and/or invest predict an individual’s likelihood of survival (e.g., in
more in self-maintenance typically live longer. humans [e.g., Bakaysa et al., 2007; Kimura et al.,
Across species, the timing of senescence, and thus 2008] and birds [e.g., Haussmann, Winkler, & Vleck,
lifespan, correlates with a suite of life history traits 2005; Heidinger et al., 2012; Pauliny, Wagner,
along the pace-of-life continuum, including growth Augustin, Szép, & Blomqvist, 2006]). For example,
rate, age at sexual maturity, and fecundity (Metcalfe women that self-identify as highly stressed have
& Monaghan, 2003; Stearns, 1992). Pleiotropic ef- significantly shorter telomeres than less stressed
­
fects of hormones may integrate life history pheno- women—in one study, the difference between groups
types along the pace-of-life continuum (Ketterson was equivalent to 9 to 17 years of telomere attrition
& Nolan, 1992; Ricklefs & Wikelski, 2002). due to aging (Epel et al., 2004).
Insulin-like growth factor-1 (IGF-1) mediates life Stressor exposure can also have transgenera-
history trade-offs among growth, fecundity, and tional effects on telomere length. Parents can pass
survival by promoting tissue growth and development shortened telomeres to their offspring directly (via
at a cost to longevity (Dantzer & Swanson, 2012; germ cells), or offspring telomere length and attri-
Stewart & Rotwein, 1996). The IGF-1-mediation tion rate can be influenced by exposure to parental
of trade-offs has been observed in mouse models glucocorticoids during development or stress-in-
(­reviewed in Bartke et al., 1998; Berryman, Sandahl duced reductions in parental care (Haussmann &
Christiansen, Johannsson, Thorner, & Kopchick, Heidinger, 2015). The multigenerational links
2008; Chistyakova, 2008); for example, Snell and among stress, telomere length, and lifespan could
Ames dwarf mice, which have lower levels of circu- have important implications for humans. In the
lating IGF-1 than control mice, are characterized by United States, stressor exposure (social, financial,
small size, reduced fertility, and an over 45 percent and environmental) is correlated with low socioec-
increase in longevity (Bartke et al., 1998). Similar onomic status, as well as with being a racial minor-
patterns have been observed in domestic animals ity. Likely as a result, individuals in these groups
and humans. The lifespan of domestic dogs covaries face poorer health (Senn, Walsh, & Carey, 2014;
with size and IGF-1 concentrations, with giant D. R. Williams, 1999) and a lower life expectancy

18 Hormones and Behavior

(Chetty et al., 2016; Meara, Richards, & Cutler, suggesting that environmental variation can generate
2008). It is not yet clear whether these results are selection on endocrine phenotypes.
driven by within-individual and/or transgenera- While the emerging picture suggests that endo-
tional effects of stressor exposure; however, experi- crine variation can be shaped by selection, deter-
mental work in animal systems suggests that the mining when and how selection operates on specific
physiological costs of socioeconomic status and traits remains a substantial challenge. One of the
race could be passed from parent to child (Baum reasons for this difficulty relates to the high level
et al., 1999; Cavigelli & Chaudhry, 2012). of phenotypic plasticity of many endocrine traits.
In addition to developmental plasticity, most
an evolutionary perspective on the ­endocrine traits show reversible flexibility, changing
endocrine mediation of life histories across seasons and environments (Clinchy, Sheriff,
Because hormone systems mediate many traits & Zanette, 2013; Romero, 2004), in response to
­important for survival and reproduction, selection social interactions (Fuxjager & Marler, 2009), and
operating on these traits could help to match the life intrinsic ­condition (e.g., body condition, immune
history of a population to its environment. But to activation; Cook, Connor, Mcconnachie, Gilmour,
what extent are endocrine traits shaped by selection? & Cooke, 2012; see Figure 2.1). Because of this, it
For selection to operate on any trait, it must be var- can be difficult, particularly in natural populations,
iable, heritable, and linked with fitness. Individual to determine whether individuals show consistent
variation in hormone concentrations and other or heritable variation in endocrine trait expression
­endocrine traits is widespread (Kempenaers, Peters, in a given set of contexts. Nevertheless, a growing
& Foerster, 2008; T. D. Williams, 2008). As discussed number of studies on free-living animals have found
earlier, hormones can have dose-dependent effects that circulating hormone levels are individually
on life history traits in ways that could influence repeatable within years—and even across years
­
lifetime fitness. (­reviewed in Taff, Schoenle & Vitousek 2018).
Less is known about the heritability of endo-
crine traits, but a growing number of studies are Developmental Current
investigating the heritability of hormone concen- Genes
Environment Environment
trations. Artificial selection experiments (Evans,
Roberts, Buchanan, & Goldsmith, 2006; Pottinger
& Carrick, 1999), twin studies (Ring et al., 2005;
Steptoe, Jaarsveld, Semmler, Plomin, & Wardle, Endocrine
2009), and estimates in free-living populations Phenotype
(Jenkins, Vitousek, Hubbard, & Safran, 2014; King,
Cline, & Hubbard, 2004) all indicate that steroid
hormone levels have low to moderate heritability Regulatory Hormone-Trait
Cross-Talk Relationships
(Cox, McGlothlin & Bonier 2016). These findings
are also consistent with large-scale phylogenetic
comparisons that have found links between circu- Life History Trait
Expression & Flexibility
lating hormone concentrations and life history
strategies across species. For example, higher circu-
Figure 2.1 The endocrine regulation of life history traits.
lating testosterone concentrations are correlated Genes and the developmental and current environments
with shorter breeding season length in amphibians influence life history trait expression via effects on endocrine
(Eikenaar et al., 2012), reptiles (Eikenaar et al., 2012), phenotype (neuroendocrine architecture and activation),
and birds (Goymann et al., 2004; Hau, Ricklefs, hormone–trait relationships, and regulatory cross-talk within
and among physiological networks. The developmental
Wikelski, Lee, & Brawn, 2010). Among birds, spe-
environment stimulates semipermanent organi­zational changes
cies with higher brood values (i.e., high value of the in tissue structure and cellular transcription potential that
current reproductive effort relative to future oppor- contribute to phenotypic expression throughout an organism’s
tunities) release lower concentrations of glucocorti- life. Current environmental conditions, which can shift rapidly,
coids in response to stressors (Bókony et al., 2009). induce corresponding changes in physiology that are often but
not always reversible. Within an organism, expression of an
In addition, both endocrine and life history traits
endocrine phenotype both influences and is affected by other
can covary with environmental characteristics includ- regulatory networks and the relationships among hormones and
ing net primary production and latitude (Jessop, traits. Together, this constellation of traits and interactions
Woodford, & Symonds, 2013; Scharf et al., 2015), mediates the expression and flexibility of life histories.

Vitousek and Schoenle 19

 As several recent conceptual papers have with which hormone systems respond to a change
­ ighlighted, individual differences in the capacity or
h in context; Taff & Vitousek, 2016). Furthermore,
propensity to shift endocrine expression across con- this approach helps to control for some of the
texts could be an important predictor of fitness ­confounds and misinterpretations associated with
(Bonier & Martin, 2016; Hau, Casagrande, Ouyang, ­correlating labile, condition-dependent traits with
& Baugh, 2016; Taff & Vitousek, 2016). However, fitness (Bonier & Martin, 2016). Once a reaction
most endocrine research examines circulating hor- norm approach has identified the elevation and flex-
mone levels in one or more discrete contexts but ibility of an endocrine response, these metrics can
does not determine the presence or functional sig- be evaluated for variation among individuals, herit-
nificance of variation in endocrine flexibility across ability, and correlations with fitness.
contexts. Individual differences in both the level of Several recent studies have used a reaction norm
endocrine trait expression and its flexibility can be approach to quantify individual variation in endo-
assessed using a modified reaction norm approach crine flexibility across environments or challenges
(Figure 2.2), which has been widely used for other (e.g., Furtbauer, Pond, Heistermann, & King, 2015;
flexible traits (e.g., behaviors; Brommer, Kontiainen, Lendvai et al., 2014). Variation in the scope of flex-
& Pietiäinen, 2012; Dingemanse, Kazem, Réale, & ibility of endocrine responses is also suggested by
Wright, 2010). In this approach an endocrine trait, studies that have used pharmacological compounds
like hormone concentration, is measured in the to measure individual differences in the potential to
same individual multiple times across an environ- mount an endocrine response (e.g., GnRH [Jawor
mental or social gradient, or across discrete contexts et al., 2006, Needham, Dochtermann, & Grieves,
(Taff & Vitousek, 2016). This approach enables the 2017], adrenocorticotropic hormone [ACTH; Sheriff,
separate quantification of the level of trait expres- Dantzer, Delehanty, Palme, & Boonstra, 2011]).
sion (or elevation of the reaction norm) and its flex- Even less is known about variation in the speed of
ibility (the slope of change over time; Figure 2.2). flexibility, but some evidence suggests that individu-
Research on behavioral flexibility shows that this als differ in the speed of the glucocorticoid and cat-
distinction is important, as the elevation and slope echolamine stress responses (Baugh, Oers, Naguib,
of behavioral reaction norms are in some cases & Hau, 2013; Koolhaas, Boer, Buwalda, & Reenen,
genetically distinct traits that can be differently
­ 2007). To date, no studies have addressed the herit-
shaped by selection (Han & Brooks, 2014; Nussey, ability of endocrine traits across environmental or
Wilson, & Brommer, 2007). Another benefit of the social gradients, but ongoing research in tree swal-
reaction norm approach is that it can be used to lows indicates that the scope of the glucocorticoid
decouple differences in distinct components of
­ response to restraint stress is heritable and predicts
­endocrine flexibility, including the scope (or magni- both survival and reproductive success (Stedman
tude) of a response and its speed (i.e., the rapidity et al., 2017; Vitousek et al., 2018). Future research

(A) (B) (C) (D)

Endocrine Expression

Environmental Gradient or Change in Context

Figure 2.2 Endocrine reaction norms. Each panel illustrates two hypothetical individuals (or genotypes) whose endocrine trait
expression (e.g., circulating hormone levels, receptor expression) is measured across a gradient of environmental conditions, or
changes in context. The mean level of trait expression across contexts is considered to be the elevation of the reaction norm. Endocrine
flexibility is defined as the slope of change over the gradient. (A) Individuals differ in endocrine expression but show no flexibility
across contexts. (B) Individuals differ in endocrine expression but show the same amount of flexibility across contexts. (C) Individuals
show similar endocrine expression in one context but differ in both mean trait expression and endocrine flexibility across contexts.
(D) Individuals have similar mean trait expression but differ in flexibility.
(Adapted from Taff, C. C., & Vitousek, M. N. [2016]. Endocrine flexibility: Optimizing phenotypes in a dynamic world? Trends in Ecology & Evolution,
6, 476–488.)

20 Hormones and Behavior

that addresses the reaction norms of endocrine flexibility—the extent to which their life history
­expression will be important for understanding how strategy changes over time. This flexibility could
hormones mediate life h ­ istories, and how distinct have important fitness consequences: When resources
components of these reaction norms are shaped by or social environments change, individuals that
selection. Although circulating hormones are the can alter the timing of life history stages, or their
easiest traits to measure repeatedly, they are only investment in a given stage, could have a significant
one of many traits that influence the ultimate effect advantage (Wingfield, 2015). Consistent between-
of endocrine activation. Thus, it is also vital to begin individual differences in plasticity have been found
to address the potential for selection to shape the in some life history traits. For example, like many
expression and flexibility of other endocrine traits, birds, the great tit adjusts the timing of breeding
including receptor and carrier protein expression. each year based on spring temperatures (Nussey,
Understanding how selection shapes endocrine Postma, Gienapp, & Visser, 2005). Birds that breed
systems will also require a more explicit focus on earlier in the year have access to more insect prey
context-dependence in hormone-fitness relationships but also face the risk that spring storms or cold
(Schoenle, Zimmer & Vitousek, 2018). While many fronts will destroy their nests. Long-term studies
conceptual models of endocrine regulation incorpo- in great tits have found that some individuals show
rate life history trade-offs (e.g., Ketterson & Nolan, consistently greater plasticity in the onset of breeding
1992; Wingfield & Sapolsky, 2003; Zera & Harshman, than others, advancing breeding more in warmer
2001), few quantitative analyses of hormone-fitness springs and delaying it in cooler years. At least in
relationships have explicitly incorporated life history. some populations, this flexibility is a heritable trait
Incorporating such context-dependence may help that can be shaped by selection (Husby, Visser, &
to clarify why hormone-­fitness relationships often Kruuk, 2011; Nussey et al., 2005). Thus, as springs
differ within and across populations. become warmer and more variable, selection could
operate not only on the mean timing of breeding
Conclusion and Future Directions but also on the flexibility of this important life history
From development through senescence, endocrine trait. Despite the potential importance of life history
traits organize and activate many of the behavioral plasticity, relatively few studies have explored whether
and physiological traits central to life history. life history traits show consistent, heritable plastic-
Hormonal regulation of life history is taxonomically ity (Brommer, 2013). Even fewer have addressed the
widespread; although we have focused here on ver- mechanistic basis of differences in plasticity (Taff &
tebrates and insects, hormones also mediate life Vitousek, 2016). Determining the extent to which
history traits in a diversity of taxa, from echino- variation in life history flexibility reflects ­underlying
derms to plants (e.g., Finch & Rose, 1995; Heyland differences in the endocrine ­mediators of life history
& Moroz, 2006). Both laboratory and field-based or in other mechanisms—including sensory percep-
research has provided fascinating insights into the tion or integration—is an important future direction.
mechanisms by which environmental and social Another major frontier in endocrine research lies
stimuli are transduced into endocrine signals, and in dissecting the intricate coregulatory networks that
the specific processes by which these signals regulate connect neuroendocrine systems with one another
transitions among life history stages and mediate in- and with other physiological elements (e.g., immune
vestment in different stages. Yet despite this progress, system, metabolism; Martin & Cohen, 2015).
much remains to be determined about how hor- Because of the extraordinary complexity of these
mone systems evolve, how they are shaped by the systems, they have been difficult to tackle with
environments and experiences of an individual, and ­traditional methods; the vast majority of endocrine
how they interact with other regulatory systems to research to date has focused on the role of one or a
influence life histories. small number of hormone systems in mediating a
One of the most fundamental gaps in our given trait. Yet the e­ xistence of these vast regulatory
­understanding of life histories concerns how and networks suggests that the activation of one hormo-
why individuals within a population differ in their nal cascade can create ripple effects that influence a
life history strategy. Within-population variations diversity of physiological systems. Physiological
in life history strategies are widespread, yet we still ­regulatory networks may be particularly important
lack a clear understanding of the mechanistic basis mediators of the suites of integrated traits whose
of this variation for many (T. D. Williams, 2008, expression levels must be coordinated—like the
­
2012). Likewise, individuals can differ in life history suites of traits that make up a life history strategy.

Vitousek and Schoenle 21

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26 Hormones and Behavior

 CH A PT E R
Sex Differences in Primate Social
3 Relationships During Development

Joyce F. Benenson

Abstract

The chapter focuses on the social development of immature primates across several species in the
Cercopithecidae and Hominidae families, in particular rhesus macaques, the great apes, and humans.
The chapter provides an overview of critical factors that characterize the rearing environments of
immature females and males, including social structure, residence patterns, and dominance relations.
Regardless of rearing environment, consistent sex differences in immatures occur in relationships with
mothers, adult males, same-sex peers, and infants. Additionally, sex differences regularly are found in
rates of development, quests for dominance, frequency of social play, and rate and intensity of direct
aggression across species.
Key words: Sex differences, primates, social relationships, development, social behavior, dominance,
aggression, social play

In Non-Human Primates the development of A major difficulty in investigating sex differences

­immature females’ and males’ social behavior has in immature animals’ social relationships is that the
­received relatively little attention. Instead, research- behaviors that have been investigated in one species
ers have focused on sex differences in adults’ social often are not examined in another. Nonetheless, the
structures or patterns of relationships (Kappeler & behavior of young members of our own species pro-
van Schaik, 2002). In humans, however, the reverse vides a valuable starting point because the majority
has occurred. Sex differences in myriad immature of research on sex differences in social structures has
social behaviors have been documented, but adult been conducted on human children (Homo sapiens).
social structure remains little studied. The adult social This permits comparisons with data that are availa-
structure of a primate species provides an explanatory ble for immatures of living members of the most
framework for understanding the behavior of the closely related species.
­individuals within the community. Moreover, it pro- Old World monkeys (Cercopithecidae), particularly
vides the context for socialization of immatures. At macaques and specifically rhesus monkeys, who share
the same time, sex differences in immature behaviors over 90 percent of their genes with humans, have
help ­illuminate both the phylogenetic adaptations been studied extensively, so they provide a rich source
and proximate constraints and opportunities pro- of data for comparisons with humans (Suomi, 1997).
vided by the community that contribute to adults’ Further, because the four great apes—orangutans
patterns of relationships. When consistent sex dif- (Pongiae), gorillas (Gorilla), bonobos (Pan paniscus),
ferences are found from early in life across closely and chimpanzees (Pan troglodytes)—human’s closest
­related species, this suggests strong adaptive pressures, living genetic relatives, share over 98 percent of
both phylogenetic and environmental, produce sex- humans’ genes (Prüfer et al., 2012), they also pro-
differentiated patterns of relationships. vide critical comparisons. The focus here will be

27
confined to reviewing regularities in sex differences bonobos (Kanō, 1992), and orangutans, where
in the social behavior of immatures across some subadults form a class in between adolescents and
­species of Cercopithecidae and Hominidae families, fully flanged adult males (Rijksen, 1978). Somewhat
particularly rhesus macaques and the great apes. paradoxically, although development of secondary
Sexual behavior, atypical behaviors, and development sexual characteristics often is separated from fertil-
in atypical environments will be excluded, and, to ity by a relatively longer interval for ­females than
the greatest extent possible, social behavior will be males (Hochberg, 2011), once females produce
included from wild as opposed to captive groups. their first offspring, their social behaviors change
Sex differences in social behavior in adulthood dramatically, whereas the same is not true for males.
are to be expected in mammals because females Thus, a corollary to the more rapid development
typically take more responsibility than males for of females is that males gain a prolonged time as
raising offspring, whereas males invest more in immatures.
mating (e.g., Emlen & Oring, 1977). Thus, adult
Community social structure, residence patterns, and
female primates must emphasize satisfying energy
mating systems. Critical to understanding the devel-
and safety needs to be able to produce offspring,
opment of an individual’s social behavior is the social
lactate, provide protection, and socialize offspring,
environment into which it is born and socialized.
possibly for a number of years. In contrast, adult
For infants, social interactions are limited to one
males compete to attain access to fertile females.
other individual at a time, most often the mother
Whether sex differences arise in immatures that
holding, touching, caressing, carrying, sniffing, and
reflect these basic sex-differentiated goals provides
inspecting it (Fairbanks, 2002). As an infant matures,
insight into both potential biological and socializa-
however, the social organization or numbers of indi-
tion influences that cannot easily be disentangled.
viduals who are present, sex ratio, and spatiotempo-
At the same time, these fundamental sex differences
ral organization of a primate society, as well as the
in social behavior must be understood within the
relationships between adults in the community or
context of stage of development, social structure of
social structure (Kappeler & van Schaik, 2002), in-
the species, mating systems, and dominance rela-
fluence the environment in which it is raised. The
tions (Kappeler & van Schaik, 2002; Ostner &
social structure of a species is defined by proximity
Schülke, 2014; Sterck, Watts, & van Schaik, 1997).
between individuals, association patterns, grooming,
support in agonistic coalitions, and food sharing
Stages of development. Immature primates undergo
(Dunbar, 1988/2013). It is determined by relation-
three stages of development: infancy (before
ships that depend on a partner’s kinship, sex, sta­tus,
weaning), the juvenile period (before puberty), and
friendship, and age (Bissonnette et al., 2015).
­adolescence (after puberty commences; Bogin, 1999).
Although most primates live in large multimale, mul-
There are species differences, however, with humans’
tifemale groups, orangutans are semisolitary, and
juvenile period seeming to be divided into early
gorillas live in harems.
(before feeding independence) and middle (before
puberty) childhood. Likewise, orangutan males enter In many species, social structure differs for ­females
into a period of delayed adolescence, which can last and males (Kappeler & van Schaik, 2002). Relation­
from 10 to 20 years, although they are fertile during ships between females depend on the degree of
this period (Rijksen, 1978). Humans and apes have ­ompetition over food or protection from predators.
more prolonged periods of development compared When food is clumped, females usually form coali-
to other primate species. tions, primarily with female kin, to defend food
patches. When food is scattered or the threat of
One principle that appears to apply across primate predation is small, females may be solitary. Females’
species is that females develop more rapidly than relationships within a species are determined by
males, with females attaining puberty a full two years their residence patterns (philopatry), preference for
earlier in the great apes and humans (Bogin, 1999). kin (nepotism), and tolerance or despotism in
Therefore, studies of sex differences in immatures dominance relationships (Sterck et al., 1997). When
that compare females and males of the same age females continue to reside in a community through-
must be interpreted with caution as age cannot out their lives, they form long-term, ­differentiated
be disentangled from sex. However, adolescence bonds, primarily with kin, but also with female friends,
often lasts longer for males than females in humans and these can last a lifetime and enhance reproduc-
(Hochberg, 2011), chimpanzees (Goodall, 1986), tive success (Silk, Alberts, & Altmann, 2003).

28 Sex Differences in Primate Social Rel ationships

 In contrast, relationships between males often females (Chapais & Berman, 2004). Infants are
depend on access to fertile females. The extent to born into a community composed of female kin
which one male can gain access to all reproductive who have strongly differentiated bonds. This com-
females appears to play a large role in determining munity occupies a territory, although the community
whether males are solitary, form differentiated may travel to other territories over time. In contrast,
relationships, or interact in groups (Ostner &
­ males disperse at adolescence and face an increased
Schülke, 2014). Because matings cannot be shared, threat of mortality, as high as 50 percent, when they
males’ relationships are almost always more directly attempt to enter a new troop. Orangutans appear to
and immediately competitive than females’ rela- be female philopatric, with males dispersing farther
tionships. When several females reside together, from mothers at adolescence (Arora et al., 2012).
males may benefit from forming coalitions to aid Nonetheless, orangutans are semisolitary and female
one another in rank changing or leveling coalitions adults meet with their mature daughters only in
vis-à-vis other males within the community or in large fruiting trees. An adult female’s territory
repelling takeovers by other male coalitions from ­unusually overlaps with those of other adult females,
outside the community. In larger communities, so that as a juvenile develops, he or she comes into
when hostile intergroup interactions occur, males contact with the offspring of other nearby mothers,
benefit from widespread cooperation against external some of whom are older sisters. Although imma-
communities. Whether males form opportunistic ture males too will meet the adult females and
and temporary associations or long-term differenti- their offspring of nearby territories, by adolescence
ated bonds depends on a number of factors includ- they will move farther away from this familiar
ing reproductive skew within the community. ­environment.
Residence patterns play an important role in In marked contrast, gorillas form harems with
social structure, and they too are highly sex differ- one dominant silverback male and several (usually
entiated. When only one sex disperses, which is unrelated) females who do not get along easily,
often the case, each sex will differ markedly in how unless they are sisters (Robbins et al., 2004). In
much its development will be influenced by the mountain gorillas, sometimes more than one male
patterns of relationships it has established during is present (Harcourt & Stewart, 2007). Both female
childhood. Where females remain in their natal and male infants grow up physically close to their
communities throughout their lives, they are sur- father, the silverback, and their own mothers and will
rounded by kin and hence more likely than males to travel together as a harem or small group. Neither
form long-term bonds with same-sex kin and friendly sex forms relationships with unrelated ­ females
nonkin. At adolescence, males must disperse, and before puberty. At adolescence, both males and
the developmental processes that prepare a male ­females emigrate, though in some mountain gorillas
and/or produce this permanent separation from a the silverback will allow one or two males to remain.
male’s kin and familiar conspecifics remain little Bonobos and chimpanzees reside in multimale,
understood. Likewise, where males are philopatric, multifemale communities with prescribed territo-
females must disperse at adolescence. The prepara- ries, similar to humans. Infants and juveniles there-
tion for this major transition to an unfamiliar com- fore grow up surrounded by many adults of both
munity apart from kin and familiar conspecifics has sexes. In both bonobo and chimpanzee communities,
not been explored. It is highly likely that residence males remain in their natal communities through-
patterns exert a powerful influence on the develop- out their lives, so that some of the adolescent
ment of immatures, as one sex derives the safety and adult males are related. In contrast, adolescent
and familiarity of spending its entire life in the com- ­females disperse. Female bonobos transfer to ­another
munity in which it was born, and the other sex must community between 6 and 10 years of age, even
join a new community as an individual with all the before adolescence (Furuichi et al., 2012), whereas
stress that such a transition entails. Understanding female chimpanzees transfer after estrus commences.
the proximate factors that lead one sex to disperse at However, in a few communities or cases, females
adolescence is an area that is ripe for further investi- will spend their entire lives in their natal communi-
gation of developmental processes. ties (Pusey, 1990).
In most Cercopithecine species, a number of In bonobo communities, females and their
matrilines consisting of several generations of adolescent and adult sons form the core of the
­

­females will structure the infant and juvenile lives community. Females cooperate to share food
of both sexes, and the adolescent and adult lives of and occasionally dominate males, but a female’s

Benenson 29
c­ losest ally is her son, though adult females form Sex Differences in Quests for Dominance
differentiated bonds (Moscovice et al., 2017). A and Status
young adolescent female who emigrates to a new Despite the vast species differences in social envi-
community, however, often finds an older resident ronments in which immatures are raised, dominance
female with whom she develops a bond, which determines access to physical and social ­resources
helps her become integrated into the community across species and sexes. In most species, adult
(Tokuyama & Furuichi, 2016). Offspring of female dominance rank exerts a strong effect on survival of
bonobos spend time in mixed-sex parties with offspring and subsequent reproductive success,
their mothers and older brothers and with unrelated because rank increases either access to higher qual-
females and their sons. Male bonobos do not form ity foods and safer territories for females or more
bonds with anyone but their mothers until their mating opportunities for males (Clutton-Brock &
mothers die, after which they may bond. All mem- Huchard, 2013).
bers of the community spend time together in large One principle that applies across species is that,
mixed-sex groups, though members of the groups even as immatures, males are more likely than
frequently change (Hohmann & Fruth, 2002). ­females to engage in direct one-on-one confronta-
In contrast, unrelated and related males form the tions over status beginning in late infancy or the
core of chimpanzee communities. Adult females are early juvenile period and continuing through ado-
subordinate to both adolescent and adult males. In lescence (Meaney, Stewart, & Beatty, 1985). The
many, but not all, chimpanzee communities, adult reason that females do not engage in as many direct
females live in core territories, whereas males travel contests for status is likely related to the greater
across the entire community (Boesch & Boesch- costs that potential physical injuries could inflict
Achermann, 2000). An adolescent female who emi- on females—who produce and raise offspring over
grates to a new community often is protected by many years—relative to males, who can attain
resident adult males because adult resident f­emales equivalent reproductive success in a briefer period
may attack her when she attempts to emigrate. (Campbell, 1999). It is also possible that females are
Infants grow up in close proximity to their mothers more likely than males to attain status in differing
and older siblings but do not spend much time with ways, such as by relying more on alliances, especially
other adults. It is only when their mothers join par- with kin, or by competing indirectly over time for
ties, which happens increasingly as weaning ap- resources, territory, and allies, thereby obviating the
proaches and the mothers come into estrus, that need for direct one-on-one contests (Clutton-Brock
they join other members of the community. It is & Huchard, 2013).
then that they meet the adolescent and adult males In female philopatric Old World monkeys, such
and unrelated adult females, though in smaller par- as macaques, vervets, and baboon species, both
ties than in bonobo communities. female and male infants rapidly learn about their
Human societies are often considered male phil- mothers’ dominance status within the community
opatric as well, though it is clear that there is much through observing the outcomes over her contests
more flexibility in dispersal patterns than in most with other mothers, her aggressive reactions toward
other primate species. Unrelated and related men other mothers’ infants and older offspring, and
often form the core of the wider community other mothers’ aggressive reactions toward them.
(Rodseth, Wrangham, Harrigan, & Smuts, 1991). Female dominance ranks are stable within and
Unlike other species, however, human mothers do ­between matrilines in a community over many
not take sole responsibility for raising their children. generations. Thus, a daughter enters a rigid, lifelong
Older infants, children and adolescents almost dominance hierarchy in which her position is pre-
always are cared for by other kin and affines, but determined under most circumstances. An infant
particularly by fathers, grandmothers, and older female can expect to rank where her mother does
siblings (Konner, 2010; Sear & Mace, 2008). and often slightly above her older sisters. The mech-
Frequently, a mother will move close to her own anism that allows the intergenerational transmission
mother after she gives birth, so the infant is cared of status is that daughters are aided in coalitions
for by a grandmother and her kin. When a mother by their mothers and other female kin (Chapais &
divorces, she also endeavors to move closer to her Berman, 2004; Silk, 2009). As infant females ­develop
own mother, so that she can obtain assistance in into juveniles, coalitions form between mothers
raising her children (Alvarez, 2004). and daughters, and those who are higher ranked

30 Sex Differences in Primate Social Rel ationships

have greater access to food, space, and other limited ­ ominance hierarchy and depends on an older
d
resources (Chapais & Gauthier, 2002). Nevertheless, resident female’s support to integrate her into the
an individual immature male can dominate a female, community (Tokuyama & Furuichi, 2016). With
unless she can form a coalition. increasing age and length of residence, adolescent
Another principle that appears to apply across females attain higher status, so that relative rank
these species is that many intrinsic assets and skills, remains constant as older residents die and younger
including age, size, strength, intelligence, motivation, ones move up the hierarchy.
and ability to form new alliances with a range of In chimpanzees, as adolescence approaches,
individuals, determine males’ more than females’ every male learns to dominate every female in the
status (Bercovitch, 1997; Goodall, 1986). These community, including female adults. Older juvenile
assets and skills will develop for males as they grow and adolescent male chimpanzees begin to compete
and learn, and form differing coalitions. A corollary for status, which is based on the same intrinsic factors,
therefore is that a male’s status fluctuates more than including age, size, strength, intelligence, motiva-
a female’s status does. For many females in female tion, and social alliances, as in the female philopat-
philopatric species, relative status is stable through- ric old world monkeys (Goodall, 1986). Again, as
out their lives, beginning even before they are born with Old World monkeys, chimpanzee males’ rank
in terms of the food and safety their pregnant moth- depends on intrinsic factors, acquired skills, devel-
ers can access. opmental changes, and alliances. Dominance status
In the great apes, the same principles apply: As peaks at age 21 when chimpanzee males are at the
immatures, males engage in more direct confronta- height of their physical prowess, but there are con-
tions over status. Further, a number of assets and tinual rank shifts as a male joins differing coalitions
skills that fluctuate with both an individual’s devel- in his quest to defeat higher ranked individuals.
opmental stage and which individuals are present Female chimpanzees usually emigrate at adoles-
appear to influence males’ more than females’ status. cence, though in some communities they remain in
Little is known about status quests in immature residence throughout their lives. Because adult fe-
orangutans, most likely because of their relatively males form hierarchies (Pusey, Williams, & Goodall,
solitary nature, although adolescent males and 1997), a female who remains with her mother in her
unflanged males are subordinate to flanged adult natal community likely obtains the same advantages
males (Rijksen, 1978). In gorillas, by adolescence, as daughters in female philopatric Old World mon-
all male adolescent gorillas will dominate all females keys. Mothers and adolescent daughters can form
(Watts & Pusey, 2002), but they all are subordinate coalitions to ensure that daughters gain access to
to the silverback. Adolescent female gorillas will territories richer in food (Foerster et al., 2016). In
submit to adolescent males and the silverback, but most communities, however, ­females emigrate to a
they may not submit to unrelated female adults. new community at adolescence, and status occurs
In male bonobos, competition for dominance through queueing. Increasing age or length of resi-
begins in adolescence, when adolescent males a­ ttempt dence determines status, so that newcomer female
to enter the linear adult male dominance hierarchy. adolescents begin with the poorest quality territo-
Unusually, what partially determines rank in adoles- ries and must queue for richer territories by await-
cent and adult male bonobos is their mothers’ rank, ing the deaths of older resident females. Thus, in
similar to the situation for immature females in both male philopatric bonobos and chimpanzees,
female philopatric Old World monkeys. Mothers just as in female philopatric Old World monkeys,
maintain close proximity to their adolescent sons relative rank remains stable for females, so that,
and support them in conflicts. The rank of an ado- unlike males, continual direct contests over rank do
lescent male therefore is highly correlated with his not occur.
mother’s rank until she dies, after which he drops in In humans, in hunter-gather societies that con-
rank (Kanō, 1992). Little is known about whether sist of small bands that frequently change in compo-
daughters benefit from their mothers’ dominance sition, relations between adults are relatively egali-
status before they emigrate, though this seems tarian (Boehm, 1999). When communities become
likely as adult females form coalitions against males larger and more stable, however, clear hierarchies
during food competition. What is clear, however, emerge. Differences in socioeconomic status strongly
is that after an adolescent female emigrates to a new influence infant mortality, health, and longevity
community, she is at the bottom of the female (Marmot & Wilkinson, 2006; Sapolsky, 2004). In

Benenson 31
modern humans, before the end of infancy, human sons than daughters compared to low-ranked families
males dominate females, who withdraw during (Dickemann, 1979), few empirical studies exist.
mixed-sex dyadic contests (Jacklin & Maccoby,
1978). Thus, although it has not been directly Physical and Verbal Contact With Mothers
­reported in most species, in both female philopatric Mothers take primary responsibility for keeping
macaque species (Cords & Aureli, 2002) and humans their offspring alive, and humans are one of the few
(Charlesworth & La Freniere, 1983), an individual primate species in which they receive assistance
male dominates an individual female, even as imma­ from others. Across species, mothers invest to a sim-
tures of roughly the same size and strength. ilar extent in daughters and sons. At the same time,
Limited evidence suggests that across species, another principle that guides development is that
high-ranked mothers invest more in immatures of immature females spend more time than males in
the sex that is philopatric. In a few studies in female close proximity to mothers. This is because imma-
philopatric species, high-ranked mothers invest ture males are more likely than females to reduce
more than low-ranked mothers in daughters rather physical proximity to mothers.
than in sons, presumably because the daughters In female philopatric rhesus macaques, infants of
serve as current and future allies (Silk, Altmann, & both sexes maintain physical contact with their
Alberts, 2006). High-ranked adult females may also mothers about 70 percent of the time for the first two
form a coalition to attack a low-ranked female’s months (Kulik, Amici, Langos, & Widdig, 2015).
infant, but only a female infant (Silk & Boyd, 1983). By the second year of life, however, daughters spend
Nonetheless, in female philopatric species in more time than sons in close proximity to their
which males emigrate at adolescence, high-status mothers. Beginning in the early juvenile period and
mothers can also invest in sons by forming coali- continuing into adolescence, females increase their
tions with them against other community mem- grooming of mothers and other female kin, and in
bers. Consequently, it appears that sons of higher some species, even males in the troop. In contrast,
status mothers often remain longer than sons of from infancy through adolescence, males spend
lower status mothers in their natal communities more time grooming male kin and nonkin (Roney
before undergoing the stress of emigration (Lee & & Maestripieri, 2003). After they emigrate, adoles-
Johnson, 1992). cent males who survive the transition then begin
A few studies likewise show that in male philo- grooming females in their new troops.
patric species, high-ranked females invest more in In orangutans, who spend the longest time alone
sons than in daughters as predicted by the Trivers- with their mothers, mothers and daughters appear
Willard hypothesis (Trivers & Willard, 1973). For to have more positive interactions compared with
example, in one community, dominant chimpanzee mothers and sons. Further, in this female philopatric
mothers invested up to two years longer in sons species, daughters remain closer than sons to their
than daughters compared to nondominant mothers mothers throughout life (Galdikas, 1995). It is infant
(Boesch & Boesch-Achermann, 2000). Because and juveniles, however, who take responsibility for
almost all females in this community emigrated at maintaining close proximity to mothers. Juvenile
adolescence, mothers can aid only their adult sons female orangutans are less submissive to mothers as
in conflicts. However, in chimpanzee communi- they approach adulthood than before, and their
ties where daughters often remain for life, mothers mothers seem to be more tolerant of their daugh-
do not invest differentially in either sex. In these ters than their sons (van Adrichem, Utami, Wich,
communities, a mother’s status can positively van Hooff, & Sterck, 2006). In gorillas, j­uvenile
­influence both her son’s and her daughter’s status females spend more time closer to their mothers
(Goodall, 1986). Whether this influences a daugh- than juvenile males do (Watts & Pusey, 2002). As
ter’s decision to emigrate remains unknown. adolescents, males spend much of their time alone
In humans, in many cultures, mothers invest more as they leave their harems (Harcourt & Stewart,
in sons than daughters, perhaps because humans are 2007). An important question is whether imma-
male philopatric (Rodseth et al., 1991). Regardless ture female bonobos maintain closer proximity
of the reason, evidence that boys are the preferred sex than males to mothers, given the unusual nature of
comes from cross-cultural findings that daughters the community in which unrelated adult females
are more likely than sons to be n­ eglected or killed in bond more than unrelated males, but mothers
childhood (Sen, 1990). Although there is some form close lifetime bonds with sons. No evidence
evidence that high-ranked families invest more in exists yet to answer this question.

32 Sex Differences in Primate Social Rel ationships

 Immature chimpanzee females maintain closer not wish an adolescent male to usurp their positions
proximity than sons to their mothers beginning in the dominance hierarchy, so adolescent males
early in life. Chimpanzee male infants begin to travel become targets of adult males’ brutal attacks. At the
independently from their mothers earlier than same time, adolescent males are highly motivated to
­females do, and by age 3 years distance themselves assume their place in the adult community and
more than females from their mothers (Lonsdorf must therefore compete for a position. Adult males
et al., 2014). However, during the juvenile years, benefit however from increasing the size of the male
­females spend 100 percent of their time and males community because of their participation in inter-
spend almost 90 percent of their time in close community aggression in which victory depends on
proximity to their mothers (Pusey, 1990). Juvenile strength in numbers (Ostner & Schülke, 2014).
females groom their mothers and siblings almost In humans, there is some evidence that even by
exclusively and the grooming is more reciprocal, the end of the first year of life, girls spend more
whereas males groom their mothers about 67 percent time than boys close to their mothers (Goldberg &
of the time while also grooming other members of Lewis, 1969). By early childhood, this sex difference
the community, including any adult males who may becomes marked and continues into adolescence
be present. Adolescent female chimpanzees who do (Schlegel & Barry, 1991; Whiting et al., 1988; Lancy,
not emigrate remain in close proximity to their 2015). Across cultures, daughters more than sons
mothers. In contrast, males increasingly spend time cooperate with mothers by caring for their younger
away from their mothers and with other female siblings and completing household tasks. In con-
adults and males (Watts & Pusey, 2002). Young trast, boys are found farther away from mothers and
chimpanzee females also learn to fish for termites homes. Even when fathers are present, boys are found
using sticks by observing their mothers and learn- on the periphery of men’s groups. Nonetheless, ad-
ing their mothers’ method, whereas males do not olescents of both sexes increase their distance from
learn this technique from their mothers (Lonsdorf, mothers, although sons distance themselves more
Eberly, & Pusey, 2004). than daughters. Sons also are more likely than
Beginning in early adolescence, however, a chim- daughters to dominate mothers (Conger, Patterson,
panzee mother is less likely to reciprocate her daugh- & Ge, 1995). Moreover, across diverse societies,
ter’s than her son’s grooming (Goodall, 1986). This even when daughters move to another community,
likely pushes her daughter to emigrate. Nevertheless, they are more likely than sons to maintain their
time spent in close proximity to mothers remains emotional closeness to mothers (Troll, 1987).
high for females until they emigrate, whereas Greater communication between mothers and
­adolescent males spent about one-third of their time daughters versus sons is another potential principle.
alone, and the remainder with adolescent or adult Beginning in infancy, macaque females and males
males or unrelated females in estrus (Goodall, 1986; differ in their frequencies and intensities of calls
Pusey, 1990). Just before emigrating, adolescent (Wallen, 2005). Females exhibit vocalizations ear-
­females often spend most of their time alone or with lier and, after separation from or rejection by their
males. Those adolescent females who remain in their mothers, call more frequently and for longer inter-
natal communities vary between spending time with vals than males do. Further, their vocalizations are
their mothers, alone, and when they are in estrus, more pleasant and softer and hence probably more
with males. attractive to mothers. Whether this sex difference
Adolescent male chimpanzees who remain in appears in ape species is unknown. Like rhesus
their natal communities suddenly leave their mothers’ ­macaques, however, beginning in infancy human
sides and begin to integrate themselves into the females are more advanced in their verbal skills than
adolescent male peer group, which maintains
­ males (Bouchard, Trudeau, Sutton, Boudreault, &
proximity to the adult males of the community. Deneault, 2009), and this continues throughout
Grooming rates toward mothers diminish and childhood (Kimura, 2000). Accordingly, beginning
grooming of other adolescent males and adult males in early childhood, human mothers converse with
suddenly increases (Pusey, 1990). Individual adoles- their daughters more than with their sons (Leaper,
cent males often obtain support from an adult Anderson, & Sanders, 1998).
male who wishes to forge a future alliance, who may
be (but is not always) a brother (Goodall, 1986). Interaction With Same-Sex Peers
Adolescent males confront an approach–avoidance Sex segregation and asymmetry in preference for same-
dilemma regarding adult males. Adult males do sex peers. Across most primate species, immature

Benenson 33
individuals of each sex prefer to interact with same- Adolescent females do not form all-female groups
sex peers. Sex segregation begins early as immatures either before emigrating or after having emigrated
begin to interact with peers, usually by the end of to a new community.
infancy (Meredith, 2013). This same-sex preference In humans, beginning at the end of infancy, chil-
likely occurs due to differing behavioral preferences dren universally segregate themselves by sex. By the
of each sex that emerge early in life. An important end of early childhood, males do this more strongly
corollary, however, is that immature males exhibit a than females do (Maccoby, 1998), which produces
greater preference than females for interaction with an asymmetry whereby boys prefer to interact
same-sex peers (Meaney et al., 1985). By definition, with same-sex peers more than girls do (Fouts,
this partially results from the fact that immature Hallam, & Purandare, 2013; Lancy, 2015; Munroe
­females spend more time than males with mothers & Romney, 2006). The asymmetry is so strong that
and other female kin and friends. However, it is not beginning in early childhood boys are less accepting
simply a reflection of less time available for interac- than girls of boys who engage in feminine activities,
tion with same-sex peers because there are many such as doll play or domestic activities, or play
other classes of individuals with whom an immature with girls (Ruble, Martin, & Berenbaum, 2006).
could affiliate. This continues cross-culturally in adolescents when
In rhesus monkeys, who leave their mothers’ males who do not fit gender stereotyped norms
bodies after a few months, both sexes interact most ­experience more difficulties in peer relations than
frequently with those of the same sex and age, but their female counterparts (de Vries, Steensma,
female infants spend more time than male infants Cohen-Kettenis, VanderLaan, & Zucker, 2016).
with female kin of all ages (Brown & Dixson, 2000; Whether nonhuman primates make this type of
Mitchell, 1979). In contrast, males spend more time gender distinction based on behavior or other types
interacting with same-sex peers (Bernstein, Judge, of stimuli has not been investigated.
& Ruehlmann, 1993). Ape species exhibit similar
Size of same-sex peer networks. Another principle is
patterns. Orangutans meet one another as they
that when males interact with same-sex peers, both
become juveniles and explore the periphery of their
juvenile and adolescent males form larger same-sex
mothers’ territory. Adolescent and subadult males
social networks than their female counterparts do
have been reported to spend time together, whereas
(Lancy, 2015; Mitchell, 1979). In particular, males
groupings of adolescent females have not been
interact with more peers simultaneously, whereas
­reported unless male adolescents or subadults are
females are more likely to interact with only one
also present (Rijksen, 1978). Even in infancy, infant
­individual or a small clique. In female philopatric
gorilla males prefer to play with same-sex peers
species, adolescent males form temporary bachelor
more than females do (Maestripieri & Ross, 2004).
groups and may enter new communities together.
Bachelor groups of unrelated juvenile and adoles-
Their alliances, along with their physical strength,
cent gorilla males who leave their natal groups also
can increase their chances of successful assimilation
occur, but there are no female bachelorette counter-
into their new communities (Schülke, Bhagavatula,
parts (Watts, 2000).
Vigilant, & Ostner, 2010).
No evidence exists at present for groups of
same-sex males or females in immature bonobos. In Old World monkeys, by 6 months of age,
Only males whose mothers have died interact in j­uveniles spend most of their time with same-sex
­all-male groups, and in most cases, these are adult peers. Males however, spend time in larger peer
males (Kanō, 1992). Nonetheless, an adolescent groups than females, with both central and periph-
male whose mother had died would join the all-male eral males (Roney & Maestripieri, 2003). Further,
group. Although it would be expected that imma- after they emigrate, adolescent males often tempo-
ture female bonobos would interact with same-sex rarily join adolescent male peer groups until they
peers given the dominance and coalitionary power singly or jointly join a new community (Suomi,
of females in bonobo communities, this has not yet 1997). In contrast, females spend more time with
been examined. Adolescent chimpanzee males, how- female kin and friends of differing generations and
ever, form groups after they permanently leave their interact with fewer same-sex peers at a time.
mothers’ sides. These all-male adolescent groups Although little evidence is available, what does
compete for dominance and form a way station exist suggests that even in semisolitary orangutans,
as each male begins to integrate himself into the juvenile and adolescent males interact with slightly
adult male dominance hierarchy (Goodall, 1986). larger same-sex peer groups than females, whereas

34 Sex Differences in Primate Social Rel ationships

females interact in mixed-sex groups or with one fighting in particular appears to assist in rehearsing
other female at a time (Rijksen, 1978). In gorillas, motoric and cognitive skills required for establish-
adolescent males occasionally form same-sex groups ing status based on physical assets and social skills,
(Watts, 2000). Chimpanzee males, but not females, which in adulthood will influence reproductive
regularly form single-sex adolescent peer groups success (Meaney et al., 1985). In macaque species,
(Goodall, 1986). With increasing age, juvenile infants and juveniles begin by engaging in recipro-
chimpanzees of both sexes spend less time with their cal interactions involving active play with same-age,
mothers, but only adolescent males join an adoles- same-sex unrelated individuals. Eventually, this leads
cent peer group until they enter the adult male to dominance contests where only one individual
community. wins, but only for males (Meaney et al., 1985).
In humans, by the end of infancy, males cluster Sex differences in social play in the great apes are
in larger groups than females (Fabes, Martin, & less consistent, but, when they are found, infant and
Hanish, 2003). Beginning in middle childhood and juvenile males play more than females. Greater in-
continuing through adolescence across diverse cul- volvement in social play has been reported in imma-
tures, the size of same-sex peer groups is larger for ture orangutans (Rijksen, 1978), gorillas (Maestripieri
males than females (Fine, 1980; Lancy, 2015; Savin- & Ross, 2004), and chimpanzees (Lonsdorf et al.,
Williams, 1980; Schlegel & Barry, 1991). In con- 2014). In chimpanzees, male i­nfants and juveniles
trast, immature females are more likely to interact initiate play using tactile gestures more than females
with one close same-sex friend at a time or in a small do (Fröhlich, Wittig, & Pika, 2016). In humans too,
clique of females. beginning in early childhood across diverse cultures,
males play more than females who are more engaged
Social play. Most primates play, particularly during than males in providing assistance with household
the late infancy and juvenile stages, after which its responsibilities (Lancy, 2015; Whiting et al., 1988).
frequency declines (Fagen, 1993). Play likely pro- Further, beginning at the end of infancy, males con-
vides rehearsal for competing, reconciling conflicts, sistently engage in more rough-and-tumble play than
and cooperating with same-sex peers, skills that will females do (Fry, 2005), whereas females engage in
be valuable throughout life. There are many forms more parallel play than males do (Barbu et al., 2011).
of social play, including play fighting, chasing, and
Direct aggression. In most primate species, males
initiating and receiving bids to play. Solitary play
engage in more frequent and more intense direct
and play with infants are not included here in the
verbal and physical aggression than females across
definition of social play.
the lifespan. Further, as the intensity of the aggres-
Infant and juvenile males play more than fe-
sion and concomitant potential for harm increases,
males across primate species, and the sex difference
the magnitude of the sex difference also increases. In
continues through adolescence (Mitchell, 1979;
­
macaque species, for example, aggression increases
Roney & Maestripieri, 2003). This may result
from infancy through adolescence for males, but
simply from the fact that immature males who in-
levels off during the juvenile period for females.
teract with peers play, so that peer interaction and
Beginning in infancy, males are more aggressive
social play may be synonymous (Meaney et
than females, and this sex difference becomes par-
al., 1985). Nonetheless, it is possible that peer inter-
ticularly pronounced in adolescence (Lonsdorf &
action and social play are more likely to overlap
Ross, 2012). Adolescent males are the most aggres-
completely for males than females. Thus, female
sive class of individual in the troop, and they form
peers might interact in other ways, such as by exam-
coalitions to defeat individual males. They also are
ining objects or spending time with one another’s
the biggest recipients of aggression. Although males
mothers, without engaging in play.
are dominant over all females by adolescence, sup-
In rhesus monkeys, males compared to females
port from maternal kin allows females to counter an
engage in more stationary and chasing play, give
individual male’s aggression.
and receive more invitations to play, and engage in
more rough-and-tumble play or play fighting (Brown Little is known about aggression in immature
& Dixson, 2000). Rough-and-tumble play requires orangutans, though the limited evidence suggests that
high energy, involves grasping and wrestling, and male juveniles are more aggressive than females in
universally occurs more frequently in juvenile males captivity (Nadler & Braggio, 1974). In mountain
than females across macaque species, regardless of gorillas, the severity of aggression increases with age
rearing environment (Wallen, 1996, 2005). Play in both sexes, but immature males are more aggressive

Benenson 35
than females (Watts & Pusey, 2002). Bonobo males Paternity certainty likely increases male invest-
increase their aggression markedly in adolescence, ment in immatures. For example, in gorillas, the
as they compete for status in the male hierarchy, silverback (who is virtually always the father of the
with the support of their mothers (Kanō, 1992). In offspring in his harem) can provide extended care to
marked contrast, adolescent female bonobos who his offspring (Harcourt & Stewart, 2007). In many
have just emigrated almost never engage in aggressive species, however, adult males provide important
behavior. As n ­ ewcomers, they are quiet and rarely sources of protection from infanticide to any infant
even counterattack. Whether individual adolescent in the community, although they also are most
females are as aggressive as individual males in their likely to commit infanticide (Boesch & Boesch-
natal communities before they emigrate has not Achermann, 2000). Further, in males of species that
been examined. However, it is likely that aggression compete against other communities, adult males
is a matter of physical strength, and as happens with protect all immatures in the community (Ostner &
adult bonobos, only through coalitions can females Schülke, 2014).
dominate a male. Adult males often exhibit a preference for male
In chimpanzees, frequency of aggressive play immatures over female immatures. This likely has to
peaks between 2 and 4 years and males are more do with their mutual enjoyment of play. In most
aggressive than females (Goodall, 1986). Intensity macaque species, adult males exhibit greater interest
of aggression peaks in late adolescence and early in male than female infants (Meaney et al., 1985).
adulthood when males are most likely to become Adult males spend more time and play more with
the highest ranked member of their communities. sons than daughters. Concomitantly, beginning in
Adolescent males become aggressive toward adult the juvenile period, young males groom adult males
females as they begin to work their way up the male more than females do (Roney & Maestripieri, 2003).
dominance hierarchy. Adolescent females joining a However, as immatures reach adolescence, adult
new community often confront severe aggression males become much less tolerant as adolescent males
from high-ranked female residents. In response, they become competitors for status and mating opportu-
appear to associate with adult males who provide nities. Lack of tolerance for adolescent males occurs
protection (Boesch & Boesch-Achermann, 2000). both in male and female philopatric societies.
Similar to chimpanzees, across diverse cultures In orangutans, adult males are solitary, but they
in humans, frequency of aggression peaks between will tolerate adolescent and unflanged males during
2 and 4 years of age (Coie & Dodge, 1998; Konner, feeding (Rijksen, 1978). In gorilla harems, in con-
2010), and intensity of aggression peaks in adoles- trast, with age infants and juveniles of both sexes
cence and early adulthood (Daly & Wilson, 2001). spend increasing amounts of time near the silverback
At all ages, males are more directly aggressive than male, who most likely is their father, and away from
females (Archer, 2004). The magnitude of the sex their mothers. By adolescence, however, most females
difference increases in direct proportion to the spend more time than males near the silverback.
­intensity of the aggression (Moffitt, Caspi, Rutter, When immature males reach adolescence, the sil-
& Silva, 2001). Other forms of aggression may be as verback begins to attack them more than females
high or higher in females, particularly in adoles- (Watts & Pusey, 2002).
cence (Archer, 2006), but direct aggression is invar- In bonobos, some evidence suggests that only
iably higher in males beginning in infancy. adult males and not adult females are allowed
by mothers to carry their infants on their backs
Interaction With Adult Males (Kanō, 1992). Further, adult male bonobos will
Paternal care is relatively rare in primates (Cabrera & play with adolescent males in bouts of wrestling
Tamis-LeMonda, 2013). Therefore, immatures in (Kanō, 1992). As the adolescent male approaches
most primate species have less contact with adult adulthood, however, he is attacked by the adult
males than adult females. This does not mean, males. Consequently, older adolescent males remain
however, that adult males never assist mothers with on the periphery of the community except when
carrying, grooming, supporting, and protecting their mothers can provide coalitional support.
­infants and juveniles. Nevertheless, they engage in Adult male chimpanzees will play with infants
these activities much less frequently than mothers and sometimes even attempt to adopt orphaned
do, and there is large variance across species with ­juveniles (Goodall, 1986). Furthermore, chimpanzee
respect to the degree of investment by adult males infant males spend more time than infant f­emales
in immatures. with adult males, as their mothers are more likely

36 Sex Differences in Primate Social Rel ationships

than mothers of females to maintain close proxim- infant care increases a mother’s chances of keeping
ity to males in the community (Murray et al., 2014). her infant alive. A mother learns the appropriate
Whether this occurs because of male infants’ greater ­motoric repertoire for handling a vulnerable infant
attraction to adult males, mothers’ greater desire and rehearses her future role as a mother (Meaney
to integrate their sons than daughters into the et al., 1985). For female philopatric species, young
­community, or adult males’ greater interest in infant ­females attempt to babysit higher ranked females’
males is unknown. Juvenile chimpanzee males, how- infants. This provides parenting rehearsal and also
ever, spend increasing amounts of time near the males enhances the probability that the higher ranked
of the community by actively persuading their adult female will provide reciprocal support to her
mothers to spend more time with adult males. By babysitter (Smith, 2005). The exceptions to greater
­adolescence, males’ time in the presence of adult interest in infants by females than males occur in
males and away from their mothers increases further; the few species in which males provide as much care
adolescent chimpanzee males groom adult males as or more care than mothers, such as in some New
more than adolescent females do (Nishida, 1988). World monkeys.
As stated, the adult male community becomes less Studies of rhesus macaques in the first three years
welcoming to adolescent males than it was to juve- of life show large sex differences in interest in
nile males, who could not challenge them for dom- ­infants, with females more likely to touch, groom,
inance (Pusey, 1990). However, it is often the case initiate proximity, embrace, hold, play with, chase,
that an adult male will form a bond with an adoles- harass, and kidnap infants, and the sex differences
cent male and help integrate him into the community. increase in magnitude after the first year (Herman,
Often, the adult male is the adolescent male’s Measday, & Wallen, 2003). In some macaque species,
brother, but not always (Goodall, 1986). Older mothers are careful to permit only older siblings to
­adolescents eventually join the adult male community handle infants, and almost all of these are daughters.
and engage in shared activities. In contrast, ­juvenile Female immature gorillas also exhibit greater interest
and adolescent chimpanzee females avoid adult than males in infants (Meder, 1990). Likewise, in
males until they emigrate to a new community chimpanzees, female juveniles and young adoles-
(Watts & Pusey, 2002). cents are more likely than their male counterparts to
Even in humans, who are one of the rare pair- care for infants, especially their siblings (Watts &
bonded primate species (which increases paternity Pusey, 2002). In chimpanzees, females even engage
certainty), fathers are estimated to invest in off- in maternal pretend play- cradling and making nests
spring at medium or high levels only 40 percent of for sticks as if they were infants (Kahlenberg &
the time (Barry & Paxson, 1971). Again, fathers Wrangham, 2010).
spend more time with sons than daughters and are Across cultures, in humans too, beginning
less likely to divorce their wives when they have ­between 2 and 6 years of age, girls spend more
sons (Lundberg, 2005). Moreover, fathers engage in time than boys caring for their infant siblings. Girls
more gross motor play with infant sons than daugh- also work harder than boys helping their mothers
ters and initiate more physical contact with sons than with child care and other household responsibilities
daughters (Lamb, 2004; Parke, 1996). Beginning in especially when their mothers require more help,
early childhood, fathers will also spend more time such as in poorer households (Lancy, 2015). Further,
and play more with sons than daughters. Adolescent the evidence suggests that between 3 and 11 years,
sons are more likely than daughters to join their girls enjoy caring for infants more than boys do
fathers, other male relatives, and unrelated adult (Edwards, 2002; Lancy, 2015; Whiting et al., 1988).
males in the community in common activities Thus, it appears that girls are not simply being more
(Schlegel & Barry, 1991). In many cultures, how- compliant with commands to look after infants, but
ever, adolescent males must first undergo initiation actually take pleasure in the activity.
rites that often involve injury before they are allowed
to join the adult male community (Sosis, Kress, & Conclusion and Future Directions
Boster, 2007). This review outlines several principles that apply
across multiple primate species from the Cerco­
Interaction With Infants pithecidae and Hominidae families. The first princi-
Across primate species, immature females demon- ples concern rate of development. Immature ­females
strate greater interest in infants than males do. develop more rapidly than males and maintain
This almost certainly occurs because practice with closer proximity to mothers than males. Males also

Benenson 37
experience a prolonged adolescence compared with c­ ooperation between unrelated immature same-sex
females. Another set of principles apply to the estab- peers, examining the role that competition may
lishment of dominance ranks. Immature males more play in relations between immature female same-sex
than ­females compete in one-on-one contests over peers, and uncovering the proximate processes that
status. Outcomes appear to be based on a number of lead adolescents to emigrate to a new community.
developing physical characteristics, including age,
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parental ability to vary the sex ratio of offspring. Science, of different worlds: The formation of social behavior. Cambridge,
179(4068), 90–91. MA: Harvard University Press.

Benenson 41
 CH A PT E R

4 Sex Differences in Cognition

Evidence for the Organizational–Activational Hypothesis

Elizabeth Hampson

Abstract

Organizational and activational effects of sex steroids were first discovered in laboratory animals, but
these concepts extend to hormonal actions in the human central nervous system. This chapter begins
with a brief overview of how sex steroids act in the brain and how the organizational-activational
hypothesis originated in the field of endocrinology. It then reviews common methods used to study
these effects in humans. Interestingly, certain cognitive functions appear to be subject to modification
by sex steroids, and these endocrine influences may help explain the sex differences often seen in
these functions. The chapter considers spatial cognition as a representative example because the spatial
family of functions has received the most study by researchers interested in the biological roots of sex
differences in cognition. The chapter reviews evidence that supports an influence of both androgens and
estrogens on spatial functions, and concludes with a glimpse of where the field is headed.

Keywords: cognitive function, spatial, estrogen, androgen, estradiol, mental rotation

Over the past few decades, evidence from laboratory How Do Hormones Act in the Brain?—A
animals has amply demonstrated that sex steroids, Brief Overview
through their actions at various points in the lifespan, Steroid hormones are small lipid-based molecules
affect the morphology and function of the central that have a characteristic four-ring (“sterane”) struc-
nervous system (CNS). These effects are exerted in a ture and are derived from cholesterol. They can easily
region-specific manner in the CNS and underlie diffuse across cell membranes, including neurons,
many sexual dimorphisms that have been identified in but are able to exert physiological effects only where
other species, including differences that are expressed cells express receptors for a particular steroid. Most
at a behavioral level. Although these so-called organ- of the major hormones produced by the gonads are
izational and activational effects of steroids are steroids, including testosterone (T) and its more
widespread in the CNS of laboratory animals, their potent offspring, dihydrotestosterone (DHT). Both
application to the human brain is less well mapped. T and DHT act largely by binding to the androgen
This chapter will survey the principles of sex steroid receptor. The estrogen 17β-estradiol (which we will
action that have been derived from animal research simply call “estradiol”) is a steroid too, and is the
and then discuss their translation to understanding dominant form of estrogen produced by the ovaries
certain sex differences found in humans. Nowhere in women of reproductive age. It acts by binding to
has this translation been more controversial than in estrogen receptors (ERs), of which there are at least
understanding whether these fundamental principles three types (Galea, Frick, Hampson, Sohrabji, &
can be applied to higher order cortical functions, Choleris, 2017). Progesterone is another gonadal
including processes related to cognition. steroid, but we will have less to say about it in the

43
present chapter because it has not been prominently (1959) was a major turning point in the study of sex
implicated in cognition (for a review of its known differences and provided the conceptual framework
effects in the CNS, see Schumacher et al., 2014). for two major distinct classes of steroid effects.
The classic “genomic” mechanism of steroid hor- Briefly, Phoenix and colleagues found that treating
mone action is one whereby a particular steroid female guinea pigs with T prenatally masculinized
(such as DHT, for example) crosses from the blood- the pattern of reproductive behaviors they showed
stream where it is carried, into cells, then binds with as adults—when primed in adulthood with a stimulus
intracellular receptors if present (in our example the dose of hormone to elicit sexual responding, females
type of receptor that would need to be present is the exposed to T prenatally displayed less lordosis and
androgen receptor). The steroid–receptor complex greater mounting than female controls. In other
is then translocated to the cell’s nucleus, where it words, the treated females showed both defeminiza-
binds to acceptor sites on the DNA and initiates an tion and masculinization of their sexual behavior as
increase or decrease in local gene transcription. The a consequence of exposure to T during the develop-
ability to regulate gene transcription is an enormously mental period when the brain was organizing. The
powerful mechanism, allowing steroids to control a effects that resulted were permanent and could not
vast array of gene products made by cells. If the cell be duplicated by treatment with T postnatally or in
is a neuron, a steroid might influence structural pro- adulthood. Phoenix and his colleagues suggested that
teins made by the cell or the production of particular T’s effects were “organizational” in that they influ-
enzymes (such as those involved in neurotransmitter enced the differentiation of sites within the CNS:
synthesis or metabolism). In recent years, it has been “testosterone or some metabolite acts on those central
discovered that certain steroids (e.g., estradiol) act not nervous tissues in which patterns of sexual behaviour
only through classic genomic mechanisms but also by are organized” (Phoenix et al., 1959, p. 381).
binding to membrane receptors associated with the Thus, the concept of “organizational effects” was
plasma membrane (see Galea et al., 2017; Schumacher born. It gave rise to the modern concept that certain
et al., 2014). Membrane receptors are believed to regions of the brain are developmentally modified
mediate the rapid effects of steroids that are some- by specific sex steroids if those steroids are available
times seen, which occur too rapidly to be mediated during a particular temporal window in early devel-
by a genomic mechanism. Thus, steroid hormones opment. Once induced, the effects are long-lasting
can act via both genomic and sometimes nongenomic (usually permanent). Although we do not always
mechanisms to influence cellular activity. know where to look in the brain to see the molecular
Importantly, a number of different steroids can or cellular changes that are the substrate for organiza-
exert effects within the CNS. This is possible because tional effects apparent at the behavioral level, some
particular regions of the brain seem to be programmed type of permanent neural change is caused by the
to express steroid receptors. Animal studies have steroid exposure and is a basis for the surface sex
demonstrated that receptors are not expressed difference we see expressed. The organizational hy-
equivalently across all parts of the brain, nor are pothesis has evolved over time to add a number of
they necessarily expressed at all points in an animal’s refinements (see Arnold, 2009), such as the fact that
lifespan, but when present they allow for effects to T may exert its organizing effects via conversion to
occur under the guidance of particular steroids that a metabolite (estradiol or DHT), the fact that mas-
can either permanently or temporarily produce altera- culinization and defeminization are orthogonal
tions in brain structure and function (Breedlove & processes, and the new and fascinating prospect that
Hampson, 2002). These are called the organizational puberty might be another period in development
and activational effects of sex steroids, and we will when the CNS becomes sensitive to the organizing
now describe the historical origins of this highly effects of steroids. However, the basic idea of
influential concept in further detail. long-lasting effects on neuronal differentiation that
take place under steroid guidance during prenatal or
Origins of the Organizational–Activational early postnatal development remains at the core
Hypothesis of the organizational concept. Processes such as
The organizational hypothesis traces its roots to sev- neurite outgrowth, the amount of programmed cell
eral important landmark studies published from death (apoptosis), the numbers and types of syn-
around 1960 to the early 1980s. A publication on apses formed, synaptic pruning, and possibly cell
the guinea pig by Phoenix, Goy, Gerall, and Young migration and specification of cell type or epigenetic

44 Sex Differences in Cognition

changes are among the developmental processes critical window, are reversible, are temporally linked
subject to the organizational effects of sex steroids to the presence of steroid in the bloodstream, and
(Arnold, 2009). involve the modulation of neuronal activity in pre-
Phoenix did not identify a particular brain region existing target pathways via genomic regulation of
that might underlie the effects he observed, but neurotransmitter function (McEwen & Alves, 1999),
other landmark studies soon followed. Sex differ- or via dynamic changes in the synaptic contacts
ences in neural structure were discovered in the between neurons, or via rapid nongenomic signaling
1970s. One of the earliest studies was an electron mechanisms (McEwen, Akama, Spencer-Segal,
microscopy study by Raisman and Field (1973), Milner, & Waters, 2012).
who discovered that female rats had more of a par- Although the exact details of the physiological
ticular synapse type in the preoptic area (POA) of processes have been refined and elaborated since
the hypothalamus than male rats did. In accordance Phoenix’s era, the conceptual distinction he pro-
with the organizational hypothesis, manipulations posed between two broad classes of steroid effects in
of early androgen exposure were able to reverse the the brain has withstood the test of time. It is a theo-
sex difference. Sexual dimorphisms in the brain retical framework that has been found to explain a
were also discovered to exist at a macroscopic level, large majority of the phenotypic sex differences seen
such as the sexually dimorphic nucleus of the pre- in brain and behavior across many mammalian
optic area (SDN-POA) of the rat, a prominent di- species. Because of their wide applicability, we
morphism first identified by Roger Gorski’s group might expect the same principles to apply to the
at UCLA (Gorski, Gordon, Shryne, & Southam, human brain.
1978). The SDN-POA is now considered a classic
model of how organizational effects of steroids can Do Organizational and Activational Effects
regulate hypothalamic differentiation in the peri- Apply to Extra-Hypothalamic Brain Areas?
natal period (see Breedlove & Hampson, 2002, for The earliest tests of the organizational–activational
a review). The discovery of the spinal nucleus of hypothesis were limited to investigating the effects
the bulbocavernosus (Breedlove & Arnold, 1980) of various endocrine manipulations on behaviors
showed that sexual dimorphism resulting from closely related to reproduction and mating, and to
­steroid exposure was not limited to the hypothal- the sexual differentiation of the hypothalamus. An
amus, and revealed further new insights into the important question, therefore, was whether such
vagaries of organizational processes (Breedlove & effects extended to nonreproductive functions and
Hampson, 2002). to brain regions outside the hypothalamus.
Although less explored in the early days of the An early clue that organizational and activational
field than organizational effects, activational effects effects would not be limited to the hypothalamus
of steroid hormones were also described by Phoenix came from songbirds such as zebra finches who
et al. (1959). Notably, for sexual behavior to be trig- use learned songs as part of their courtship rituals.
gered in adult guinea pigs, it was necessary to treat In these species, song production is sexually di-
the adult animals acutely with estradiol benzoate morphic, with males using song to attract female
(followed by progesterone) or with testosterone mates. Correspondingly, the volumes of several
­propionate to stimulate the expression of mating ­regions involved in birdsong display substantial sex
behavior. Phoenix et al. (1959) recognized that they differences and contain more neurons in males than
were looking at a second type of steroid effect, females (Nottebohm & Arnold, 1976). Studies of
where adult treatment elicited effects that were tran- the zebra finch showed that sexual dimorphism in
sient, reversible, with no lasting residues, and whose the size of these nuclei arises from exposure to hor-
end result was to “activate” specific neural pathways mones (estradiol) early in development, and that
in order for a particular behavior to be expressed: adult singing is then activated by androgens acting
“Adulthood, when gonadal hormones are being se- upon a male-typical neural substrate that was laid
creted, is a period of activation; neural tissues are down during the ­organizational period (Gurney &
the target organs and mating behaviour is brought Konishi, 1980). However, studying organizational
to expression” (Phoenix et al., 1959, pp. 379–380). effects in songbirds has proven to be complex, with
Phoenix accordingly dichotomized hormonal effects some endocrine manipulations inexplicably having
as either organizational or activational. We now un- little or no effect, leading to suggestions that ele-
derstand that activational effects do not require a ments of sexual differentiation in birds may proceed

Hampson 45
under the direct guidance of genes (“cell autonomous work has begun to explore the effects of estrogens in
effects”; Arnold, 2009). Although the learning and adult animals on increasingly sophisticated tasks,
production of birdsong can be construed as “cogni- including measures of social cognition, and has im-
tive” and clearly involves nonhypothalamic brain plicated the rapid effects of estrogens and not merely
regions, the prospect of direct gene effects compli- their classic genomic mode of action in generating
cates its interpretation as a straightforward model of these effects (see Galea et al., 2017, for an over-
organizational effects on cognition. view). For instance, infusion of 17β-estradiol or the
Both organizational and especially activational ERα agonist PPT into the dorsal hippocampus of
effects in extra-hypothalamic brain regions have the mouse rapidly improves performance in social
now been confirmed by experimental and observa- recognition, object recognition, and object placement
tional studies using rodents or nonhuman primates tasks, whereas the ERβ agonist DPN is ineffective
as subjects. Examples of androgen- and estrogen- (Phan et al., 2015). In recent work, increasing at-
driven effects on brain physiology are so numerous tention is being paid to moderator variables such as
that a 40-page review can now be written on the the form of estrogen studied; dose dependency of the
effects of a single hormone (e.g., estradiol) in a single effects; distinctions between working and reference
neurotransmitter system (e.g., s­erotonin; Bethea, memory; defining whether hormonal manipulations
Lu, Gundlah, & Streicher, 2002). Reversible effects act at the encoding, consolidation, or retrieval stages
of estradiol have been found to extend beyond the of memory processing; and identifying which form of
neurochemical level to include features of brain the estrogen receptor mediates any effects observed.
microanatomy, such as the regional densities of Older studies, however, which led to these modern
dendritic spines (Woolley & McEwen, 1992) or advances, initially focused only generically on spa-
rates of neurogenesis in the hippocampus of the tial memory. Spatial memory became a focal point
adult rat (Galea et al., 2013; Tanapat, Hastings, of early work primarily because several types of
Reeves, & Gould, 1999). However, it is not always spatial tasks (i.e., tasks that emphasize knowledge
clear from basic studies exactly how the effects re- of object positions, accurate movement through
ported translate to the functional level (i.e., cognitive space, or navigation to reach a distant target) com-
or behavioral counterparts). monly used to evaluate learning and memory in
Progress in documenting organizational effects rodents elicit robust sex differences (making them
outside of the hypothalamus has been slower, because candidates for organizational or activational influ-
of the practical challenges of studying ­organizational ences or both).
effects and of knowing where to look. Presumably, The radial-arm maze (RAM) and Morris water
functions subject to the effects of steroids would be maze (see Figure 4.1) were commonly used in this
those that show sex differences, but cognitive sex early body of work to assess spatial learning. These
differences are less well characterized in nonhuman two tasks involve, respectively, learning over a series
species than in humans, and cognition (especially in of trials which arms of a maze are baited with food
rodents) is often conceptualized in a less finely frac- rewards and learning where a hidden platform (which
tionated way. Still, early suggestions of an effect of serves as a refuge) is located within a circular enclo-
neonatal gonadectomy on cortical thickness in the sure that is filled with opaque water in which a rat is
rat (Stewart & Kolb, 1988), discovery of high levels initially placed. Both tasks depend on hippocampal
of aromatase activity in the association cortex of the function and both are acquired more rapidly by
developing rhesus monkey (MacLusky, Naftolin, & male than female rats ( Jonasson, 2005). (In c­ ontrast,
Goldman-Rakic, 1986), and observations of sexual the reverse pattern, more rapid acquisition by
dimorphism in the dentate gyrus of the mouse ­females, is seen for certain other forms of learning,
(Roof & Havens, 1992; Wimer & Wimer, 1989) all such as active avoidance or classical trace eye-blink
indicated that organizational effects might poten- conditioning; Dalla & Shors, 2009). Thus, the pres-
tially extend to the differentiation of cortical and ence and direction of a sex difference on a cognitive
limbic regions, implying that effects of steroids on task is dependent on the particular cognitive pro-
higher order functions, including cognitive func- cesses required and the set of brain regions brought
tions, might be found. to bear.
Numerous studies in rats and mice have now Consistent with the idea that activational effects
demonstrated a wide range of effects on learning of estrogens can exert a modulatory influence on
and memory. Hippocampally mediated forms of hippocampal function, the performance of female
memory have been an especially active focus. Recent rats on tests of hippocampally d ­ ependent spatial

46 Sex Differences in Cognition

 progesterone were administered exogenously to
ovariectomized female rats (Chesler & Juraska, 2000;
Frye, 1995; Snihur, Hampson, & Cain, 2008) to
simulate the hormonal conditions found naturally at
proestrus. Some experiments have further suggested
that progesterone and not just estradiol might con-
tribute (e.g., Chesler & Juraska, 2000; Johansson,
Birzniece, Lindblad, Olsson, & Bäckström, 2002).
Some of estrogen’s effects are age dependent (i.e.,
different in young vs. old rats) or dosage depend-
ent (e.g., Markham, Pych, & Juraska, 2002; Foster,
Sharrow, Kumar, & Masse, 2003).
The standard Morris water maze procedure
Figure 4.1 An illustration of the radial-arm maze (top) and emphasizes reference memory, but if the procedure
Morris water maze (bottom), commonly used to assess spatial is modified to emphasize the “unlearning” of previ-
learning and memory in laboratory animals. In the radial maze, ously learned platform positions by relocating the
food rewards are placed at the ends of the arms. All of the arms
hidden platform each test day, then the performance
may be baited or only a fixed subset, allowing the experimenter to
differentiate between working memory errors and reference of female rats is better if they are tested at high
memory errors. Entries into never-rewarded arms are reference ­instead of low levels of gonadal steroids (Dohanich,
memory errors; re-entering an arm already visited within a Korol, & Shors, 2009). This modification might in-
particular trial is a working memory error. In the water maze task, crease the recruitment of the frontal cortex during
the animal is released from different vantage points around the
task performance (Sinopoli, Floresco, & Galea, 2006),
circular periphery of the pool and over a series of spatial training
trials learns to navigate directly to the location of the hidden which could explain the differing results. Higher
escape platform (dashed line) submerged below the surface of the estradiol also facilitates working memory in the
­
water, by using visual cues present in the environment to orient RAM (Bimonte & Denenberg, 1999; Fader et al.,
toward the platform location (which is fixed). Dependent 1999; Pompili et al., 2010). Either way, a systematic
variables typically measured in the water maze include latency to
change in performance under different hormonal
find the hidden platform and path length. An optional probe trial
may be used to evaluate memory, where the refuge is removed conditions implies that an activational effect is
following the spatial training. Time spent searching in the present. A recent review concluded that hippocam-
(now-empty) platform quadrant is then monitored. pal function is sensitive to changes in estrogens that
occur over the estrous cycle, and with pregnancy,
memory appears to be influenced by estradiol con- motherhood, or aging in the rat (Duarte-Guterman,
centrations over a rat’s estrous cycle. Some studies, Yagi, Chow, & Galea, 2015).
primarily in mice, report improved spatial memory These behavioral effects are thought to be medi-
in the standard water maze paradigm under higher ated by effects of estrogens on hippocampal morphol-
estrogen conditions,1 but most rat studies report ogy and physiology. Consistent with this prospect, the
lower performance in female rats when tested at rodent hippocampus expresses estrogen receptors,
proestrus (when endogenous production of ovarian especially in the cornu ammonis (CA) subfield CA1,
hormones is highest) compared with estrus or diestrus but also in CA3 and the dentate gyrus. Both types
(when hormones are low; Frye, 1995; Korol et al., of classic ERs (ERα and ERβ) and the G-protein-
1994; Pompili, Tomaz, Arnone, Tavares, & Gasbarri, coupled membrane estrogen receptor (GPER) are
2010; Warren & Juraska, 1997). Poorer water maze expressed in the hippocampus, making it an impor-
acquisition in high estrogen states is also seen in tant target for estrogens. The hippocampus shows
meadow voles and deer mice (Galea, Kavaliers, dynamic neuroplastic changes in dendritic spine
Ossenkopp, & Hampson, 1995; Galea, Kavaliers, densities in CA1 as a function of the estrous cycle
Ossenkopp, Innes, & Hargreaves, 1994). Plasma­ (the number of spine synapses in CA1 is increased
­estradiol correlated positively with latency to locate about 30 percent during proestrus in the rat;
the hidden platform (Galea et al., 1995), indicating Woolley & McEwen, 1992), and the dentate is a
poorer spatial performance. These effects have been site of estrogen-dependent rates of neurogenesis in
confirmed by experiments where estradiol and adult brains (Duarte-Guterman et al., 2015). Some
of estradiol’s effects on spines are initiated within
1
It should be noted that a small female, not male, advantage is minutes of estradiol application. These and other
evident in mice performing the water maze task (Jonasson, 2005). observations confirm that activational effects of

Hampson 47
estrogens take place in the hippocampus at a cellular aromatization of T to e­ stradiol (Williams et al., 1990;
level. Modulatory effects of estradiol on hippocampal but see Isgor & Sengelaub, 1998), although species
neurochemistry during place learning also contrib- differences exist and it is not clear that aromatiza-
ute to spatial memory, and formal models have been tion to estrogens is necessary for T to organize the
proposed (Dohanich et al., 2009). primate brain.
Activational effects of androgens with respect to Compared with rodents, the effects of gonadal
spatial learning have received less study. Early research steroids on cognition in nonhuman primates are far
on learning and memory suggested that removal of less studied. There is preliminary support for an
the testes in male rats (at age 20, 50, 90, 130, or 170 activational influence of estrogens on learning and
days) did not affect maze acquisition (Commins, memory (Lacreuse, Mong, & Hara, 2015), at least
1932). This suggested that T is inert with respect to in aging female animals, but the research base is not
spatial memory in an activational sense. However, extensive. In the first study of its kind, Lacreuse,
recent work on androgens has thrown this overly Chiavetta, Shirai, Meyer, and Grow (2009) found
strong conclusion into doubt (Goudsmit, Van De that administration of testosterone enanthate to
Poll, & Swaab, 1990; Sandstrom, Kim, & Wasserman, young male monkeys following gonadal suppression
2006; Spritzer, Gill, Weinberg, & Galea, 2008) and with a gonadotropin-releasing hormone (GnRH)
suggests that effects may be especially prominent for agonist reduced their performance on a delayed
working memory. Castration also causes a decline nonmatching-to-sample task of recognition memory.
in dendritic spine density in hippocampal CA1, This finding might suggest that androgens, not just
which can be reversed by the acute administration estrogens, can exert activational effects within the
of T or DHT in male rats (Leranth, Petnehazy, & medial temporal lobe.
MacLusky, 2003). Even fewer studies of organizational effects are
Whether or not adult T concentrations have available from nonhuman primates. Early work sug-
an influence, perinatal exposure to T appears to be gested a possible role for T in the developing frontal
important for sexual differentiation of neural struc- cortex of the rhesus monkey (Clark & Goldman-
tures that support spatial learning in the rat. Early Rakic, 1989; see also MacLusky et al., 1986). Female
work involving neonatal hormone manipulations monkeys treated with T propionate on postnatal
indicated a possible role for sex steroids (Dawson, days 1 to 46 showed male-like performance on an
Cheung, & Lau, 1975; Joseph, Hess, & Birecree, object reversal task dependent upon the orbitofron-
1978; Stewart, Skvarenina, & Pottier, 1975), but tal cortex when tested at 75 days of age (Clark &
was not followed up until 1990. Organizational ef- Goldman-Rakic, 1989). A temporary male a­ dvantage
fects on learning in the RAM were then elegantly in object reversal can be seen in young monkeys
demonstrated by Williams, Barnett, and Meck (1990), (Clark & Goldman-Rakic, 1989) and young chil-
who showed that neonatal manipulations of sex ste- dren (Overman, Bachevalier, Schuhmann, & Ryan,
roids could systematically alter and even ­sex-reverse 1996). Although Clark and colleagues believed the
the adult levels of accuracy displayed by male and sex difference to be only transient, a sex difference
female rats in the RAM. Adult female rats exposed on a probabilistic reversal task has recently been ob-
to estradiol during the first few days of life showed a served in human adults (Evans & Hampson, 2015).
level of acquisition in the RAM that resembled male Clearly, much work remains to be done, but, based
controls, whereas male rats castrated on postnatal on the limited data presently available, effects of re-
day 1 resembled female controls. Furthermore, the productive steroids on learning and memory do
same manipulations altered rats’ reliance on geome- appear to generalize to the primate brain.
try versus landmark cues when navigating in the
RAM (Williams et al., 1990). (Differences in utiliz- Translating the Organizational–Activational
ing the two classes of visual cues is another, related, Hypothesis to Humans
sexually dimorphic facet of spatial performance in A number of reliable sex differences in cognition
the rat). Roof and Havens (1992) showed that rats and behavior are found in humans (for reviews see
exposed to T neonatally displayed visible changes in Halpern, 2012; Maccoby & Jacklin, 1974). Unlike
the hippocampal dentate gyrus. The width of the laboratory animals, however, who are raised under
granule cell layer predicted the efficiency of acquisi- standardized controlled conditions, human behav-
tion in the reference memory version of the water ior is more prominently influenced by variation in
maze in adulthood. In the rodent brain, some of the social environment (e.g., differences in family
these early organizational effects depend upon the upbringing or the experiences typical of girls vs.

48 Sex Differences in Cognition

boys in a given society). Therefore, even though CAH is an autosomal recessive condition
a body of data suggests that the organizational–­ where the adrenal cortex is deficient in the enzyme
activational hypothesis applies to humans too, social 21-hydroxylase. One consequence is elevated pro-
variables must always be considered. In principle, a duction of androgens by the adrenal glands,
sex difference in cognitive performance could be beginning in the third month of fetal gestation.
caused by an activational effect of sex steroids on Although d ­ifficult to detect in males, excess
brain function, an organizational effect of steroids ­production in f­emales causes masculinization of
exerted during early brain development, relevant ex- the external genitalia, which varies in severity. The
periential differences that exist between females and genital ambiguity is usually detected at birth or soon
males due to cultural expectations, direct sex-linked after, at which point the androgen overproduction
gene effects, or any combination of these variables. can be normalized by introducing appropriate
The challenge of dissociating the influence of culture hormone replacement therapy. Most females with
is most acute for researchers who study ­organizational CAH begin treatment by about 2 weeks of postna-
effects. On the other hand, if a difference is system- tal age. Females with CAH usually undergo surgical
atically accentuated, is reduced, or disappears alto- correction of the genital ambiguity in infancy and
gether when it is evaluated under various hormonal are raised as females despite the increased androgen
conditions in adults, then an activational effect of exposure before birth. Because psychosocial up-
sex steroids may be implicated. bringing tends to be female typical (and often even
Although sex differences have been reported in a more gender stereotypical than control females;
number of human cognitive functions, only a few Pasterski et al., 2005), CAH affords a unique op-
have been studied with respect to the ­organizational– portunity to dissociate the effects of upbringing
activational hypothesis. In the following sections, and biology.
we concentrate on spatial cognition as a core e­ xample, Studies of CAH have been supplemented recently
because in its various forms it has received the most by studies that involve other methodologies. One is
study to date. One might at first think the emphasis the study of opposite-sex twins in which diffusion
on spatial cognition grew out of the animal studies of androgens from the male co-twin is thought to
of learning and memory discussed previously. In expose the developing female fetus to higher than
fact, though, in the human literature it grew out of a usual concentrations of androgens prenatally (i.e.,
separate tradition, and its origins preceded all but higher than a female fetus would normally experi-
the earliest animal studies. It might seem narrow to ence before birth). The source of T is the gonads of
use spatial cognition as a key example, but the term the male co-twin, which undergo activation from
spatial cognition encompasses a number of separable about weeks 8 to 24 of gestation (Forest, de Peretti,
processes and brain regions, not all of which respond & Bertrand, 1976), a period when genital differen-
to sex steroids in the same way. Although we might tiation occurs in the normally developing male
wish that a wider range of cognitive processes had fetus. Although significantly lower than the levels of
been studied, even a single example of a particular androgen exposure seen in CAH, the availability
domain of human cognition where organizational or of small amounts of testicular-derived T is thought
activational effects can be demonstrated is “proof of to potentially have an impact on the development
concept” that may encourage researchers to begin of the female’s CNS. It should be noted that this
inquiring into other areas of the cognitive panorama. mechanism is still somewhat speculative in humans,
but there is a precedent in other species for the mas-
Common Paradigms Used to Study the culinization or defeminization of females’ behavior
Organizational Hypothesis in Humans via a similar ­mechanism, when male and female
In humans, it would be unethical to experimentally ­fetuses develop in close proximity in utero (Ryan &
manipulate hormones prenatally to study the Vandenbergh, 2002).
­resulting effects on brain development. Accordingly, In the past 20 years, it has been suggested that
researchers interested in characterizing the effects of a particular sexually dimorphic feature of digit
androgens on cognitive differentiation have studied (finger) differentiation, visible postnatally, can serve
clinical conditions in which androgen production as a retrospective biological marker of the relative
is increased or decreased outside the normal range degree of T exposure that a normally developing
(i.e., “experiments of nature”). Foremost among these fetus experienced prenatally (Manning, 2002). The
is the classical form of congenital adrenal hyperplasia so-called 2D:4D digit ratio is defined as the ratio
(CAH; Merke & Bornstein, 2005). of the lengths of the second to fourth digits of the

Hampson 49
hand. When studied in adults using standardized A
measurement procedures, the 2D:4D ratio is said to
reflect, in a graded fashion, the level of androgen
activity during a particular period in utero that is
important for differentiation of the hands. The va-
lidity of the 2D:4D ratio as an indicator of prenatal B
T level is controversial. Evidence for an impact of
androgen levels on the ratio is based on data from
CAH (Hönekopp & Watson, 2010), data from
­individuals with an inherited insensitivity of the
androgen receptor (Berenbaum, Bryk, Nowak,
­
C
Quigley, & Moffat, 2009), and a few experiments in
birds or mammals suggesting that the ratio is per-
ceptibly influenced by differences in T availability
during early development. However, counterevi-
dence to the androgen theory also exists (e.g.,
Hampson & Sankar, 2012), and the issue of validity Figure 4.2 The original Shepard-Metzler stimuli, shown here,
is not settled. Over the past 20 years, the 2D:4D are used in several standard mental rotation tasks, including
the Vandenberg and Kuse Mental Rotations Test (1978).
ratio has been used in a significant number of studies (A) A “same” pair that differ by an 80-degree angular rotation
as a gauge of prenatal T concentrations, but it must in the picture plane. (B) A “same” pair that differ by an
be taken under advisement until its validity (or lack 80-degree rotation in the depth plane. (C) A “different” pair
thereof ) can be more conclusively established. that cannot be aligned by any rotation. The Vandenberg and
Although it is an infrequently used paradigm, a Kuse rotations employ similar figures, but the test uses a
multiple-choice format.
few researchers have directly measured fetal T and/ (From Shepard, R. N., & Metzler, J. [1971]. Mental rotation of
or estradiol in amniotic fluid collected from expect- three-dimensional objects. Science, 171, 701–703. Reprinted
ant mothers, or have measured neonatal T from with permission from AAAS.)
infant saliva collected after birth. A great advantage
of these methods is the ability to measure hormones the last of these carries a significant memory load,
directly. However, for amniotic fluid the timing of because the visual stimuli in the first two types of
sample collection is dictated by when amniocentesis tasks normally remain in view throughout each ex-
is performed and typically only a single measure- perimental trial. Meta-analysis shows that mental
ment (sample of fluid) is available for a given preg- rotation and spatial navigation tasks tend to elicit
nancy. Nevertheless, direct sampling of hormone the largest sex differences, with tasks requiring
concentrations provides an important opportunity three-dimensional mental rotation or navigating in
to assess whether or not hormone levels encoun- a three-dimensional virtual environment exhibiting a
tered at these time points are predictive of later mean sex difference on the order of d = 0.80 or
cognitive abilities. above (Voyer, Voyer, & Bryden, 1995).
Whereas learning to navigate in a new environ-
Evidence for an Organizational Effect ment is a “spatial memory” task and elicits activity in
of Androgens on Spatial Cognition the hippocampus (e.g., Pintzka, Evensmoen, Lehn,
Many studies have used measures of mental rotation & Håberg, 2016), often accompanied by activation
(i.e., the ability to dynamically manipulate an object in the retrosplenial cortex (Goodrich-Hunsaker,
in one’s mind, viewing it from different angles or Livingstone, Skelton, & Hopkins, 2010), mental
points of view; see Figure 4.2) or other spatial tasks rotation typically recruits sites in the parietal cortex,
requiring visualization (e.g., transforming in one’s not the hippocampus (Zacks, 2008). Therefore, the
mind the three-dimensional shape of an object) to tasks used in human studies are not always hippo-
assess spatial performance, or have used either virtual campally dependent and do not necessarily parallel
or real-world tasks that require learning to navigate spatial findings obtained from other species. To
in an unfamiliar spatial environment. These types of ­interpret the varying effects of steroids across d
­ ifferent
tasks typically exhibit sex differences. On average, studies, we must take into account the differing brain
adult males as a group show superior performance regions recruited by different sorts of spatial tasks.
relative to adult females, although there are very Resnick, Berenbaum, Gottesman, and Bouchard
large individual differences within both sexes. Only (1986) were the first to demonstrate superior

50 Sex Differences in Cognition

­ erformance on mental rotation tasks in females
p of healthy girls (offspring of the sampled pregnancies)
with the classical form of CAH (who are exposed to who were tested on a children’s mental rotation test
elevated androgens prenatally) compared to unaf- at age 7 (Grimshaw, Sitarenios, & Finegan, 1995).
fected female controls. The effect was not seen in This important study has yet to be replicated.
males with CAH, who did not differ from male However, Auyeung et al. (2012) found a significant
controls. Spatial superiority in females with CAH correlation between T concentration in second-­
has been replicated by several studies using mental trimester amniotic fluid and another type of spatial
rotation or other visualization tasks (Berenbaum, test (but not mental rotation) in children who were
Korman Bryk, & Beltz, 2012; Hampson, Rovet, & tested at age 7 to 10 years. Ideally mental rotation
Altmann, 1998), but the observation remains con- would be assessed at older ages, as not all children
troversial because not all studies have observed these are yet capable of doing the rotations by age 7.
effects (e.g., Hines et al., 2003). Given the twin findings, it seems likely that the
A possible resolution is suggested by recent critical period for T to act in the CNS is prenatal.
work from our lab (Hampson & Rovet, 2015); we Yet studies employing the 2D:4D ratio as an indica-
discovered that superior spatial performance is tor of the level of prenatal androgen exposure have
not as evident in females with the simple-virilizing largely failed to support any association between the
form of CAH as in patients who have the salt-­ digit ratio and mental rotation, in either women or
wasting form, where the severity of androgen excess men (e.g., Hampson, Ellis, & Tenk, 2008; see Puts,
is usually much greater. (These are two phenotypic McDaniel, Jordan, & Breedlove, 2008, for a meta-
forms of classical CAH). Most studies do not analysis). The lack of association with 2D:4D in
permit separate analysis by subtype because of the females conceivably could reflect the smaller range
limited sample sizes usually available (classical of prenatal T found in normally developing female
CAH affects 1 in 30,000 female births; Merke & fetuses (consistent with the lack of distinct spatial
Bornstein, 2005). Because the proportion of salt- effects in females who have simple-virilizing CAH,
wasters varies considerably from one study to an- where androgen production is raised but only mod-
other, it might explain the variable findings across estly) or could reflect inaccuracies associated with
studies. In favor of this hypothesis, superior per- the digit ratio as a measurement technique, or ques-
formance was also observed in females with salt- tions surrounding its validity.
wasting but not simple-virilizing CAH in a study Males ordinarily produce a high enough level of
that used a virtual Morris water maze to assess spa- T during prenatal development to organize brain
tial learning (Mueller et al., 2008). Although the pathways that underlie mental rotation. However,
cognitive demands of the water maze differ from correlations between 2D:4D and mental rotation
mental rotation and it recruits the hippocampus to are largely lacking in male samples (see Puts et al.,
a greater degree, both sets of findings support the 2008), except where sample sizes are enormous (e.g.,
hypothesis of an organizational effect of androgens Peters, Manning, & Reimers, 2007, n > 134,000). An
on spatial functions. association between behavioral markers of androgen
If an organizational effect does occur prenatally, exposure and mental rotation competency has been
then evidence for an androgen influence ought to be reported in samples of men where prenatal exposure
seen using other research methodologies. Although is expected to have a larger range than usual (e.g.,
the effect size is much smaller than for CAH, twin Rahman & Wilson, 2003). Where found, associa-
studies have found better mental rotation capa- tions tend to be positive (i.e., higher mental rotation
bilities in female twins who gestated in utero with scores are associated with indicators of higher pre-
a male co-twin compared with those who had a natal androgen levels). Paradoxically, reduced spatial
female co-twin (Heil, Kavšek, Rolke, Beste, & function in boys with CAH has been reported by
Jansen, 2011; Vuoksimaa et al., 2010). It is unlikely several labs, including our own (Hampson et al.,
that the improved spatial performance is due to psy- 1998; Hines et al., 2003), but this phenomenon is
chosocial or experiential effects of having a brother not well understood. Potentially it may be explained
because the effect was not seen in other, nontwin, by the dynamics of adrenal androgen production
girls who had brothers of a similar age (Heil et al., in CAH and its feedback effects on the testicular
2011). It is seldom possible to quantify prenatal T production of T by the male fetus (Hampson et al.,
directly, but a significant correlation between the 1998; but see Grimshaw et al., 1995 for a simi-
level of T in second-trimester amniotic fluid and lar association observed in a nonclinical sample
efficiency of mental rotation was found in a sample of boys).

Hampson 51
 If there are organizational effects of androgens 2001; Reber & Tranel, 2017; van den Bos, Homberg,
on cognitive function, how widely do they apply? & de Visser, 2013). Thus, human research is begin-
Few other cognitive functions have been studied. ning to move beyond the conventional boundaries
At present, candidates include, among others, verbal of verbal and spatial functions to the study of
fluency and phonological processes (e.g., Hampson more sophisticated and abstract domains of cog-
& Rovet, 2015; Rahman, Abrahams, & Wilson, nition where new sex differences are only now
2003), but if anything the direction of the associa- being revealed.
tions is reversed, with a greater level of androgen As studies begin to venture beyond mental rota-
exposure predicting reduced scores (e.g., Helleday, tion, we must be open to the possibility that not all
Bartfai, Ritzén, & Forsman, 1994). This agrees cognitive functions are organized during the same
with the fact that small sex differences in these temporal window in early development. We and
functions are found in the general population, but others have long pointed to the possible impor-
the differences are in favor of females, not males. tance of the postnatal infant period (e.g., Collaer
Accordingly, it may not be surprising to see a reversed & Hines, 1995; Hampson, 1995). Many critical
association with prenatal androgens. Language-related neuro­developmental processes, including migration
functions are of special interest in light of an ele- and cellular pruning, occur in the first few months
vated incidence of speech or language problems after birth and are important candidates for inter-
and developmental dyslexia reported among girls vention by sex steroids given that, in human male
with CAH (Inozemtseva, Matute, & Juárez, 2008; infants (and monkeys), there is a second rise in
Nass & Baker, 1991), although these issues remain T production by the testes that takes place in the
poorly documented in the clinical literature. Effects first few months of postnatal life. Following a brief
of prenatal androgens on language processes, if period of activity, the testes are then quiescent
eventually confirmed, would be in keeping with until puberty.
morphological sex differences in the language zones Hines et al. (2003) speculated that the critical
of the left hemisphere reported in a few studies (“sensitive”) period when androgens modify neural
in normally developing male and female brains processes that support mental rotation might in fact
(e.g., Harasty, Double, Halliday, Kril, & McRitchie, be postnatal (during the first six months of infancy),
1997; Witelson, Glezer, & Kigar, 1995) and the not prenatal. In retrospect, this is unlikely because
modest cognitive differences reported in these same the best data currently available from studies of
processes (Hawke, Olson, Willcutt, Wadsworth, & CAH and opposite-sex twins now implicate an ear-
DeFries, 2009; Heister, 1982). Unfortunately, func- lier time point for sexual differentiation of mental
tions other than mental rotation are inadequately rotation, but it is still possible that the postnatal
studied, and there are simply too few data to permit peak in T production could coincide with the differ-
any conclusions. entiation of other cognitive or behavioral functions,
Far from being exceptional, organizational effects affording an opportunity for androgens to exert
of androgens may in fact turn out to be widespread ­organizational effects. Such a possibility would be
in the human cortex: anatomical imaging shows compatible with Goldman-Rakic’s finding in
that sexual dimorphism is present in numerous cor- monkeys (Clark & Goldman-Rakic, 1989) and
tical regions of the human brain, many of them with a handful of reports that imply that T exposure
known to express sex steroid receptors during early during infancy may be important for the develop-
brain development in other species (Goldstein et al., ment of certain lateralized functions (Drea, Wallen,
2001). For most of these regional differences, we Akinbami, & Mann, 1995; Hampson, 2016). The
know little about whether or not there are any cor- possibility that there may be cognitively relevant
relates at the functional level. As one example, Clark processes that undergo a postnatal period of sen­
and Goldman-Rakic (1989) reported a possible sitivity to androgens is territory that is virtually
organizational effect of neonatal androgens in the uncharted.
orbitofrontal cortex of the rhesus monkey, and In humans and other primates, it is typically
­reports exist of volumetric sex differences in this ­believed that the aromatization of T to estradiol is
region in humans (Welborn et al., 2009), but it is not essential for sexual differentiation of the CNS to
only recently that human researchers have begun to occur. However, this assumption is questionable be-
describe behavioral differences between adult men cause it has rarely been tested. In a rare exception,
and women on tasks that rely on the orbitofrontal Hines and colleagues studied females exposed in
cortex (Evans & Hampson, 2015; Reavis & Overman, utero to the synthetic estrogen diethylstilbestrol

52 Sex Differences in Cognition

(DES), used to prevent miscarriage. This compound length of the cycle must be carefully taken into ac-
has masculinizing effects on the behavior of guinea count along with other subject variables that affect
pigs. Among women who were exposed to DES in the pattern, timing, or magnitude of endocrine
utero, Hines and Sandberg (1996) found no differ- changes (Hampson & Young, 2008). Serum or
ences in mental rotation or verbal fluency between saliva assays are typically used to confirm that the
the DES-exposed women and their unexposed sisters. expected endocrine profile was in fact present when
However, because aromatization is an important the cognitive testing was performed and, because
avenue to sexual differentiation in the rodent brain, concentrations vary across women within each
we should not be too hasty to dismiss it as a poten- phase of the cycle, assays can be used to search for
tial route to masculinization of the CNS in humans graded correlations between cognitive performance
too, including, potentially, cognitive functions. and the levels of a particular hormone. Menstrual
Unfortunately, opportunities to experimentally test cycle paradigms allow for statistically powerful
the aromatization hypothesis in humans are exceed- within-subject designs to be used and have the
ingly limited. virtue of being naturalistic—the identity of the hor-
mones studied, the timing of their changes in the
Activational Effects of Sex Steroids bloodstream, and the concentration ranges seen
on Cognition are all completely physiological.
In other species, sex differences can be caused by sex Although activational effects are easier to study
steroids acting on the differentiation of the CNS than organizational effects, there are still ethical
during an early window in fetal or neonatal devel- constraints on the types of research designs that may
opment (i.e., organizational effects of sex steroids). be used. Randomized placebo-controlled designs
However, another class of steroid effect that can bring are not normally feasible except as part of a medical
about sex differences is activational effects, which trial where a hormonal treatment is being tested
are exerted in the adult brain. Activational effects to alleviate a pre-existing medical condition (e.g.,
modify activity within existing neural pathways, but hypogonadism). Randomized designs have been
the effects are impermanent and reversible. They used fruitfully in the context of menopause, for ex-
wax and wane as a function of the concentration of ample. It is the adult reproductive years, however,
the active steroid that is available in the bloodstream where we would expect activational effects of sex
and dissipate when the steroid milieu changes. Sex steroids to be maximally evident, and fewer oppor-
differences can be generated by either class of effect tunities exist to exogenously deplete or else deplete
acting on its own (earlier termed Type II [activational then restore sex steroid levels in young adults. Risks
only] and Type III [­organizational only] behaviors; that must be navigated in studies involving hormonal
Goy & McEwen, 1980), but also by activational interventions include the potential for manipu­
effects that occur within brain regions previously lations to disrupt the menstrual cycle and thus
subject to organization by steroids in early develop- ­increase the risk of an unplanned pregnancy or, for
ment (Type I). Mental rotation is an example of a androgens, the potential to cause lasting virilization
cognitive function that may be subject to both the (i.e., development of male physical characteristics,
­organizational and activational effects of steroids. such as deepening of the voice) if not managed care-
fully. Rarely, a placebo-controlled design may be
Paradigms Used to Study the Activational permitted for purposes that are purely experimental
Hypothesis in Humans if only a single administration of active steroid is
During the past two decades, many cognitive inves- to be given. Synthetic hormones are typically used
tigations have focused on the activational roles of medically and are often given at arbitrary doses on
estrogens in cognitive function. One of the most a temporal schedule that does not replicate the
common paradigms used to explore the effects of ­endogenous conditions under which the natural
ovarian hormones is the menstrual cycle. Typically, form of the hormone is secreted. For these reasons,
cognitive testing is prospectively timed to coincide cognitive studies that employ a true experimental
with target phases of a woman’s cycle that differ design, especially in young adults, are fairly infre-
significantly in the levels of circulating estradiol quent and not always straightforward to interpret.
(and/or progesterone) that are present, allowing a
researcher to test for small differences in performance Mental Rotation and the Menstrual Cycle
that are evident under high vs. low hormone condi- Our own early studies suggested an effect of
tions. Individual differences in the characteristic the menstrual cycle on certain elements of spatial

Hampson 53
function (e.g., the perception of true vertical, are selective; they are not observed for control tasks
Hampson & Kimura, 1988), but mental rotation that do not exhibit any sex differences and, if any-
per se was not evaluated in our earliest work thing, the direction of the correlation is reversed for
(Hampson, 1990a, 1990c; Hampson & Kimura, tasks that exhibit a female superiority instead of a
1988). We did observe a significant correlation be- male superiority in performance (although less evi-
tween serum estradiol concentrations and women’s dence is available for such functions; see, e.g., Maki
performance on a spatial visualization test (which re- et al., 2002).
quired mental rotation but included other spatial Of course, there are also studies that have failed
elements too; Hampson, 1990a). A correlation was to find a significant menstrual cycle effect, but most
found at the preovulatory phase of the ovarian cycle can be explained by methodological issues. In a
where estradiol peaks but progesterone is low. This recent study from our lab, we found that the men-
implicated estradiol rather than progesterone, but it strual cycle effect is evident only for large angles of
did not conclusively demonstrate an effect on the rotation, but not when an overly simple, minimal
rotational process per se. Although controversial at angular rotation is required to bring two visually
the time, this work was considered seminal because presented stimuli into alignment (Hampson et al.,
it was the first indication that circulating estradiol 2014). This suggests that some failures to detect the
levels may affect cognitive function in women, sug- effect might be explained by the use of insensitive
gesting that ovarian hormones affect brain function mental rotation tasks. We also confirmed that a
beyond the hypothalamic-­pituitary region. correlation was present for estradiol, but not for
Follow-up studies employed standard psycho- progesterone levels, which also varied across women
metric mental rotation tasks, such as the Shepard- in our recent study (Hampson et al., 2014). Data
Metzler figures (1971) or the Vandenberg and Kuse presently available suggest that for mental rotation
mental rotations test (1978), and confirmed that at least, progesterone has weak if any effects on per-
performance varied with phase of the menstrual formance (see also Maki et al., 2002).
cycle. Consistent with the phase-related differences Collectively, the existing menstrual cycle find-
we had observed in our own studies (e.g., Hampson, ings suggest that estradiol has an activational effect
1990c), accuracy on rotation tests was found to be in one or more brain regions required for mental
best at menses (when estradiol is lowest) and slightly rotation. However, a recent review concluded that
diminished when women were tested during the further confirmatory research is needed (Sundström
midluteal phase of the cycle (when estradiol is Poromaa & Gingnell, 2014). Correlational evidence
elevated; Hausmann, Slabbekoorn, Van Goozen,
­ is not evidence for causation, so it is important to
Cohen-Kettenis, & Güntürkün, 2000; Maki, Rich, note that several studies using research designs
& Rosenbaum, 2002; Mäntylä, 2013; McCormick where estradiol (ethinyl estradiol) was administered
& Teillon, 2001; Moody, 1997; Phillips & exogenously have also found a weak effect on mental
Silverman, 1997; Silverman & Phillips, 1993; Šimić rotation scores (e.g., Slabbekoorn, Van Goozen,
& Santini, 2012). In a study featuring multiple Megen, Gooren, & Cohen-Kettenis, 1999; Van
­repeated a­ ssessments of the same women, Courvoisier Goozen, Cohen-Kettenis, Gooren, Frijda, & Van de
et al. (2013) showed that mental rotation perfor- Poll, 1995; but see Haraldsen, Egeland, Haug, Finset,
mance was reliably slightly better during menses. & Opjordsmoen, 2005). These studies, however, are
These studies reported predictable phase-of-cycle complex to interpret for several reasons, including
differences. Fewer studies tested for a direct corre- the fact that estrogens were given to biological males,
lation with measured estradiol levels, but studies not females, whose brains therefore differ in organi-
by Maki et al. (2002) and Hausmann et al. (2000), zational history. Confounds introduced by multiple
as well as from our own lab (Hampson, Levy- repeated test administrations and incompletely
Cooperman, & Korman, 2014), ­ independently counterbalanced designs (Schmidt et al., 2013) have
tested and verified a significant inverse correlation posed a significant problem for many studies in-
between estradiol and mental rotation using serum volving exogenous hormone administration.
or salivary quantification of concomitant estradiol Recently, support for an activational effect of
concentrations. Saliva has an advantage over serum ­estrogens on mental rotation processes has begun
in that it directly reflects the bioavailable fraction to arise from a new source: brain imaging studies
of the circulating hormone (i.e., the fraction that investigating functional activation of the cortex
is free to interact with the brain and diffuse into during mental rotation. Studies using functional
neurons). Importantly, the observed correlations magnetic resonance imaging (fMRI), a technique

54 Sex Differences in Cognition

that enables the direct visualization of changes in ences in estradiol (but not progesterone) correlated
brain activation under contrasting conditions, have significantly with the level of BOLD activation in
reported visible alterations over the menstrual cycle the superior parietal lobe bilaterally and inferior
in brain regions involved in mental rotation. Women parietal lobe on the right. Because fMRI affords a
were scanned twice, at contrasting phases of the direct way to visualize the physiological effects of
menstrual cycle, while they performed mental rota- estrogens on task-related neuronal activation, it is a
tion (or control tasks). Dietrich et al. (2001), for unique and powerful tool to investigate steroid-driven
example, scanned women during menses (low estra- effects on brain function.
diol) and at the preovulatory peak in estradiol and
found that the number of activated voxels in the Mental Rotation and Oral
parietal cortex (BOLD activation, the blood oxygen Contraceptive Use
level–­dependent signal) was markedly greater under Coincident with our menstrual cycle studies in the
high than low estradiol conditions (798 vs. 36 acti- 1980s and early 1990s, we collected data on spatial
vated voxels; see Figure 4.3). A phase-of-cycle effect function in women using combination oral con-
was not evident in a control task. In women who traceptives (COCs). COCs consist of an estrogen
performed mental rotation at the midluteal phase, (ethinyl estradiol) combined with 1 of 19 synthetic
Schöning et al. (2007) found that individual differ- progestins and are most often used to prevent

number of voxels (p = 0.0001)

Control 37

Menses 36
798
Ovulation

Figure 4.3 Regions of significant brain activation during mental rotation in a functional magnetic resonance imaging (fMRI) study
(Dietrich et al., 2001). Areas of significant activation (BA 39/37 and BA 7) in the grouped data are depicted in black on a normalized
brain viewed from above. Activation in men (upper right) and women tested during menses (low estradiol; lower right) did not differ.
When the same women were tested during the late follicular phase (high estradiol; lower left), a large increase was seen in the number
of activated voxels during the peak estradiol condition. The number of activated voxels is shown in the upper left.
(Reprinted from Dietrich, T., Krings, T., Neulen, J., Willmes, K., Erberich, S., Thron, A., & Sturm, W. [2001]. Effects of blood estrogen level
on cortical activation patterns during cognitive activation as measured by functional MRI. NeuroImage, 13, 425–432. Copyright [2001], with
permission from Elsevier.)

Hampson 55
c­onception, especially when prescribed in healthy the cycle (higher estradiol). The effect appeared to
young women. Based on the effects of estradiol seen be dependent upon ethinyl estradiol dosage in the
during the natural menstrual cycle, one might pills, because we found that women using higher
expect ethinyl estradiol to affect mental rotation in dose COCs (50 to 80 µg/day of ethinyl estradiol)
COC users, particularly as it has an affinity for the showed lower performance on the same spatial tests
estrogen receptor (ERα) at least equal to, if not compared with women taking low-dose formula-
slightly greater than, that of endogenous 17β-estradiol tions (Hampson & Moffat, 2004).
(Escande et al., 2006). As pointed out earlier, our spatial tests did not
However, using the COC paradigm to test for include a dedicated measure of mental rotation, but
an activational effect is more complex than it first our findings were soon followed by work from other
appears. Because they are combined into a single labs using the Vandenberg and Kuse mental rotations
tablet, there is no point in the contraceptive cycle test (Vandenberg & Kuse, 1978). Those studies
where ethinyl estradiol can be varied by a researcher ­appeared to confirm an effect of COCs on mental
independently of the progestin it is combined with. rotation scores (McCormick & Teillon, 2001; Moody,
Although progesterone produced by the corpus 1997; Silverman & Phillips, 1993). They included
luteum over the natural menstrual cycle typically repeated-measures designs (Moody, 1997; Silverman
is uncorrelated with scores on mental rotation & Phillips, 1993), in which spatial performance
tests, the progestins used in COCs often derive during active COC use was contrasted with perfor-
from 19-nortestosterone and biologically they exert mance by the same women during the COC wash-
androgenic and not simply progestogenic ­effects out phase (the seven-day interval each month when
in tissue. This is problematic in light of ­increasing COCs are not taken and the uterine lining is shed).
evidence that circulating levels of androgens, not Further evidence that the effect is related to ethinyl
just estrogens, may influence mental rotation in estradiol was obtained in a recent study where ethi-
young adults (see later). If the impact of andro- nyl estradiol dosage was discovered to be a signifi-
gens is to improve mental rotation, as some studies cant predictor of scores on the Vandenberg and
­suggest, then the simultaneous presence of andro- Kuse rotations test in a group of 148 women taking
genic progestins might counteract any effect of the a wide range of commercially available brands of
ethinyl estradiol component of COCs on mental COCs (Beltz, Hampson, & Berenbaum, 2015).
rotation ability. Increased ethinyl estradiol dose was associated with
At the time our first COC data were collected in decreased mental rotation scores. Where dosage is

COCs ranged from 30 to 50 μg/day. Many present-­

the 1980s, dosages of ethinyl estradiol contained in not explicitly taken into account, several recent

day COCs are substantially lower (15 to 30 μg/day).

studies have failed to find significant effects of COC
use on mental rotation (e.g., Mordecai, Rubin, &
Dosage reduction during the last few decades adds a Maki, 2008).
further layer of complexity because, over the naturally Some reports suggest that the use of COCs also
occurring menstrual cycle, diminished mental rota- reduces mental rotation performance in male-to-­
tion performance is only visible at phases of the female transgender patients being treated with high
cycle characterized by the highest levels of estradiol doses of COCs in the context of sex reassignment
production. Thus, the change in COC formulations (Van Goozen et al., 1995). Such data are hard to
leaves open the question of whether current dosages interpret because antiandrogens are typically ad-
are high enough to support an activational effect. ministered simultaneously as an adjunct part of the
Despite these considerations, COC use is one treatment regimen. However, in favor of an inhibitory
of the few opportunities to test for an effect on effect exerted by estradiol, Kozaki and Yasukouchi
cognition in young women receiving sex steroids (2008) found that estradiol levels in ordinary men
exogenously. Note that when COCs are used, the were systematically related to the slope of the reac-
endogenous production of steroids by the ovaries is tion time function on a mental rotation test. Based
suppressed, including testosterone. In our earliest on ordinary women, the findings from studies of oral
report (Hampson, 1990b), we found that the spatial contraceptive use are consistent with an activational
ability of women taking low-dose COCs (defined as effect of contraceptive steroids on spatial cognition,
30 to 35 µg/day of ethinyl estradiol) fell interme- but the quality of many existing studies is low, and
diate between naturally cycling women tested at it is hard to attribute the effects unambiguously to
menses (lowest estradiol) and matched naturally ethinyl estradiol given the complications of the
cycling women tested at the midluteal phase of COC paradigm.

56 Sex Differences in Cognition

Spatial Cognition in Postmenopausal the midluteal peak, giving rise to the typical finding
Women from menstrual cycle studies that spatial performance
Postmenopausal women have been widely used to is diminished under high estradiol. The possibility
study the effects of estrogens on cognitive function. of a nonlinear association over a broadened range
However, episodic memory has been the main focus, of concentrations is largely untested, but it would
not mental rotation as in younger adults. The litera- be consistent with several existing observations,
ture on menopause is rich, complex, and extensive including improved mental rotation in postmeno-
(Hogervorst & Bandelow, 2010). Long-term estrogen pausal women treated with only low amounts of
deprivation of the CNS as a result of undergoing estrogens, the menstrual cycle findings of reduced
surgical or natural menopause, and the effects of performance at the highest estradiol levels, and our
various hormone replacement therapies have been own early findings of an inverted U-shaped func-
studied. Observational designs and randomized tion covering a wider physiological range of serum
controlled trials have been used. The menopause lit- estradiol levels in young women who were tested
erature does speak to the possibility of activational on a visualization task that had a prominent mental
effects of estrogens on memory, but mental rotation rotation requirement (Hampson, 1990a).
is seldom studied because it is a cognitive function
that is markedly impaired by aging. Floor effects on Do Androgens Have Activational Effects
mental rotation tests are commonly seen by the age on Spatial Cognition?
of menopause (e.g., Jansen & Heil, 2010), and the Whether or not circulating levels of androgens influ-
decline in mental rotation competency begins even ence mental rotation is a controversial and unresolved
earlier, in young to middle adulthood (Wilson & issue. Androgens have received less study in this
Vandenberg, 1978). When studying older adults, it context than estrogens (the reverse of the situation
is common for researchers to select simpler rotation that presently prevails for the study of ­organizational
tests, precede the tests with extended practice, or effects). The earliest studies dedicated to this ques-
give them without time limits, making it difficult to tion were mostly correlational, but clinical studies
compare the results obtained with studies based on based on patient populations receiving T (or other
young adults. androgens) therapeutically, and more recently stud-
Studies of postmenopausal women have produced ies in which circulating levels of androgens are
mixed findings; in a large sample of women random- manipulated experimentally in healthy people,
ized to receive estradiol valerate, performance on a allow for a few causal inferences to be made.
conventional test of mental rotation was negatively Beginning in the mid-1980s, several labs inde-
correlated with the absolute levels of estradiol pendently reported finding significant correlations
posttreatment (measured in serum) and with the between endogenous T concentrations in young
magnitude of the increase in estradiol from pre- to men and accuracy on spatial tests (e.g., Christiansen
posttreatment (Kocoska-Maras et al., 2013). However, & Knussman, 1987; Shute, Pellegrino, Hubert, &
some studies have found no effects on mental rotation Reynolds, 1983), including tests of mental rotation
or even positive effects of treatment with transder- (Hausmann, Schoofs, Rosenthal, & Jordan, 2009;
mal estradiol (Duka, Tasker, & McGowan, 2000) or Moffat & Hampson, 1996; Neave, Menaged, &
conjugated equine estrogens (Kimura, 1995). The Weightman, 1999; Silverman, Kastuk, Choi, &
variable findings might reflect the types of estrogens Phillips, 1999; Yang, Hooven, Boynes, Gray, & Pope,
used, age of the participants, adaptations of the tests 2007). Correlations were also reported in aging
for older people, or other variables. men, including men followed longitudinally over
A more interesting (but theoretical) possibility is time (Moffat et al., 2002; Yonker, Eriksson, Nilsson,
that the effects of estradiol on mental rotation might & Herlitz, 2006), although simpler spatial tests
be nonlinear (see later for a discussion of androgen were used. Circulating T levels have also been found
effects, where such a phenomenon has been reported). in a few studies to predict performance on mental
Small increases in estradiol from a hypogonadal rotation tasks in women (e.g., Hausmann et al., 2000;
state may improve performance, whereas large in- Moffat & Hampson, 1996; but see van Anders &
creases, beyond some optimum point, may dimin- Hampson, 2005), with higher concurrent T pre-
ish it. Over the ordinary menstrual cycle, estradiol is dicting superior performance. However, studies of
produced in small amounts even at menses where it male samples have been complex to interpret, as a
is lowest, and studies often compare this time point number have indicated that a nonlinear relationship
with points of high estradiol production, such as may be present in which the correlation reverses and

Hampson 57
is negative at the very highest levels of T in men Ortiz, & Sutherland, 1998; Moffat, Hampson, &
(Moffat & Hampson, 1996; Neave et al., 1999; Hatzipantelis, 1998), allowing potential scope for an
Shute et al., 1983). If this observation is correct, it activational influence of T to be observed. However,
makes it less likely that simple associations will be these studies too have been inconsistent in supporting
identified in studies of men, especially when statis- the possibility of an association ­between concurrent
tics are used that assume linearity. T concentrations and spatial performance, whether
Studies where T is given exogenously support the defined by rate of acquisition, path integration,
possibility of a dose-dependent effect, in that the spatial memory for the location of an escape platform
administration of T to healthy women has been (in the virtual Morris maze), or other variables.
­reported to temporarily improve performance on Using virtual adaptations of the Morris water maze,
mental rotation tasks (Aleman, Bronk, Kessels, T was associated with adeptness at finding the
Koppeschaar, & van Honk, 2004; Pintzka et al., hidden platform in women only (Burkitt, Widman,
2016), whereas the administration of T to healthy & Saucier, 2007), or in men only (Driscoll, Hamilton,
young men (who already have high T) impairs it Yeo, Brooks, & Sutherland, 2005), or was inversely
(O’Connor, Archer, Hair, & Wu, 2001). In aged related to men’s performance in accord with the
men, evaluated with simpler mental rotation tests, theory positing an o­ptimal level of T (Nowak,
performance was improved after treatment with Diamond, Land, & Moffat, 2014).
T compared with placebo (Cherrier et al., 2001; When a single dose of T was given to women in
Janowsky, Oviatt, & Orwoll, 1994), consistent with a double-blind placebo-controlled design, Pintzka
their hypogonadal status before the treatment was et al. (2016) found improved knowledge of the
initiated. However, a perceptible change in mental directions among target objects in a novel virtual
rotation performance is not always found in aged environment among women who received T com-
samples (Resnick et al., 2017; Wolf et al., 2000). Wolf pared with placebo prior to entering the environ-
et al. (2000) brought T into the supra-physiological ment. The women treated with T also achieved
range, which may interfere with seeing any effect. significantly higher accuracy scores on a mental ro-
Cherrier, Aubin, and Higano (2009) found a deteri- tation test. Correlations between T concentrations
oration in mental rotation in men with prostate and proficiency in virtual spatial environments have
cancer when they underwent treatment-related an- been harder to identify in men, and again, structural
drogen blockade, relative to their pretreatment level variation in the androgen receptor might conceivably
of performance. Not all studies have found associa- moderate the correlations seen (Nowak et al., 2014).
tions between T and mental rotation, however. This The possible impact of individual variation at the
may potentially reflect methodological factors, but receptor level requires further study in the cognitive
the failure to detect any association includes several context, especially given its purported impact on
seemingly well-done studies with large sample sizes other androgen-dependent traits (Zitzmann, 2009).
(e.g., Puts et al., 2010; Resnick et al., 2017). For Besides studies formally designed to address the
these and other reasons, the question of whether question, indirect support for an activational effect
adult T levels presently in the circulation exert acti- comes from studies where another variable (not T)
vational effects on spatial cognition remains open. was the primary focus of investigation, but where T
Notably, there is substantial genetically based varia- happened to be measured too. A few menstrual cycle
tion across individual men in the responsiveness of studies, for example, have ­measured T in ­addition
the androgen receptor to T binding (Chamberlain, to estradiol concentrations and have ­reported a neg-
Driver, & Miesfeld, 1994). Receptor polymorphism ative correlation between estradiol levels and mental
is rarely taken into account in cognitive research, rotation, but a positive correlation with current T
but because T must act via its receptors to trigger a levels ­measured simultaneously in the same women
tissue response, it could be one factor that contrib- (e.g., Hausmann et al., 2000). This further empha-
utes to variability in study outcomes. sizes the independence of the two effects. In women
A few researchers have ventured beyond mental with polycystic ovarian disease (a gynecological con-
rotation to explore the effects of T on spatial learn- dition in which androgen production by the ovaries
ing, spatial orientation, or navigational efficiency or adrenals is raised and ovulation becomes less fre-
when exploring new environments in either real- quent), increased mental rotation scores were lim-
world surroundings or virtual simulations. A male ited to a hyperandrogenic subgroup of women, and
advantage in acquiring the layout of an unfamiliar a positive correlation was observed between serum
virtual environment is often reported (Astur, T and the Vandenberg and Kuse mental rotation

58 Sex Differences in Cognition

test score (Barry, Parekh, & Hardiman, 2013; but spatial positions), the sex difference is in favor of
see Schattmann & Sherwin, 2007). females, not males.
Data from women using COCs also support an An increasing body of data supports the hypoth-
activational influence—based on the hormonal for- esis of an activational influence of estrogens on work-
mulations of standard COCs, one analysis revealed ing memory, including spatial working memory,
that brands containing progestins with more highly and brain regions that support it. Sources of evi-
androgenic properties were statistically associated dence include postmenopausal women tested on
with higher scores on a mental rotation test (Wharton working memory tasks, with or without estrogen
et al., 2008), whereas women using brands of COCs treatment in the form of ­ standard replacement
containing progestins with anti-androgenic proper- ­therapy (Duff & Hampson, 2000; Keenan, Ezzat,
ties performed significantly more poorly (Griksiene, Ginsburg, & Moore, 2001), or after a short-term
Monciunskaite, Arnatkeviciute, & Ruksenas, 2018). experimental treatment with estradiol versus pla-
Although this evidence suggests an effect of andro- cebo (three days of estradiol treatment; Krug, Born,
gens, it does not implicate the hormone T specifi- & Rasch, 2006). fMRI reveals increased activation
cally, as the findings were based on the androgen in regions of the prefrontal cortex during working
potencies of specific synthetic progestins contained memory tasks if aging women are tested under
in the COCs (defined as their level of activity at the ­estradiol versus placebo (e.g., Smith et al., 2006).
androgen receptor). Of course, an improvement in Ovariectomized female rhesus monkeys treated
mental rotation was observed directly by Aleman with estradiol cypionate showed superior per­formance
et al. (2004) in healthy women who were treated on the delayed response task (a classic behavioral task
with a single acute dose of T on an experimental used to evaluate working memory in nonhuman
basis, in a double-blind placebo-controlled crosso- primates) compared with monkeys treated with vehi-
ver design. Mental rotation improved significantly cle only (Rapp, Morrison, & Roberts, 2003). Data
within four to five hours after treatment with T from young women are rare, but our lab found that
compared with placebo. This is a rare example of estradiol levels over the menstrual cycle correlated
T being administered directly in healthy young inversely with the numbers of working memory
adults, albeit on a one-time basis. Because it was errors committed on a test of spatial working memory
a single administration, and because a repeated-­ (Hampson & Morley, 2013). Figure 4.4 shows data
measures design was used, it constitutes strong on the same test collected from a group of young
support for the activational hypothesis. women using COCs, who were tested either while
they were taking their COCs or during the monthly
Not All Spatial Functions Are Equal pill-free interval (Hampson, unpublished data). As
Mental rotation was used as an example in this shown in Figure 4.4, fewer working memory errors
chapter because of the large amount of research de- were ­observed during the active use of COCs than
voted to this cognitive process. However, not every during the one-week washout period when the
spatial function exhibits a sex difference. Of those women a­ bstained from estrogen use.
that do, the direction of the difference does not In all of these studies the direction of the estra-
­invariably favor males. For example, our lab discov- diol effect is reversed, compared with the effects that
ered a sex difference in favor of women (not men) have been reported for mental rotation. These two
that is seen on certain tests of spatial working memory spatial processes rely on differing networks or path-
(Duff & Hampson, 2001). The sex difference was ways in the brain, with regions of special importance
replicated by other labs using memory tests pos- being the parietal cortex (vicinity of the intraparietal
sessing similar features (e.g., Lejbak, Vrbancic, & sulcus) for the rotational process and the dorsolateral
Crossley, 2009). A recent meta-analysis concluded prefrontal cortex for the executive components of
that the female superiority in spatial working memory spatial working memory (Owen, Evans, & Petrides,
is seen reliably on this particular family of tasks and 1996; Zacks, 2008). The differences in cortical repre-
certain other working memory tasks that emphasize sentation and in the direction of the sex difference
the spatial positions of object identifiers, under con- observed emphasize the importance of conceptual
ditions where active short-term maintenance and/or precision when making predictions about any partic-
repeated updating of the spatial positional informa- ular cognitive process and its hormonal control by
tion held in short-term store is required (Voyer, sex steroids. It is a mistake to think that a hormone
Voyer, & Saint-Aubin, 2017). Thus, despite the fact such as estradiol has one ­singular effect that applies
that the material to be remembered is spatial (i.e., across-the-board to all spatial functions.

Hampson 59
 SPWM
50

40
WM Errors

30

20

10

0
0 1 2 3 4
Trial
OC_On OC_Off Males

Figure 4.4 The Spatial Working Memory task (SPWM; shown in top image) involves participants being asked to find the spatial
locations of matching pairs of colored dots hidden beneath the doors of a 4 × 5 array. A working memory error (WM error) is
defined as revisiting an already-visited pair of locations (for full description see Duff & Hampson, 2001). Bottom image shows the
numbers of WM errors committed on three consecutive trials of the SPWM task by female combination oral contraceptive (COC)
users (n = 60) and demographically matched male controls (n = 96). SPWM data from women with naturally occurring menstrual
cycles (non-COC users) collected in the same study have been reported elsewhere (Hampson & Morley, 2013). All women were
tested blind then retrospectively classified into subgroups based on health information supplied at the end of the test session, after
cognitive testing was completed. Bottom figure shows the numbers of WM errors committed by women taking a COC on the day
they were tested (OC_On, n = 40) and numbers of WM errors committed by equivalent COC users tested during the monthly
COC washout phase when no active pills are ingested (OC_Off, n = 20). Women actively taking a COC (higher levels of ethinyl
estradiol) displayed superior working memory compared to OC_Off or male controls. All COC users took COCs containing 20 to
35 µg/day of ethinyl estradiol. Thus, women tested at higher estradiol levels made significantly fewer spatial working memory errors,
among both COC users (shown here) and nonusers (Hampson & Morley, 2013).
(Reprinted from Hampson, E. [2018]. Regulation of cognitive function by androgens and estrogens. Current Opinion in Behavioral Sciences, 23, 49–57.
Copyright [2018], with permission from Elsevier.)

The Organizational–Activational a­ ttention has begun to shift to cognitive processes

Hypothesis Today—Current Status mediated by the frontal cortex and its input and
Mental rotation is the cognitive process that has output pathways to the amygdala and striatum
­received the most attention to date from human re- (e.g., Hampson & Morley, 2013; Hermans et al.,
searchers exploring the organizational–activational 2010; Peper, Koolschijn, & Crone, 2013; Stanton,
hypothesis. In contrast, clinical work on menopause Liening, & Schultheiss, 2011). In parallel, increas-
has focused heavily on verbal episodic memory (see, ing effort is being devoted to investigating whether
e.g., Hogervorst & Bandelow, 2010). A growing va- frontal functions might exhibit sex differences (e.g.,
riety of data support the existence of organizational Duff & Hampson, 2001; Evans & Hampson, 2015).
or activational effects that operate on cognitive It is important for researchers to get beyond the tra-
functions, but the details of these relationships remain ditional boundaries of looking only at mental rota-
to be discovered. Over the past decade, ­research tion and episodic memory, as we are only scratching

60 Sex Differences in Cognition

the surface of the many cognitive and affective virtual Morris water task: A large and reliable sex difference.
­domains where hormonal regulation of the CNS Behavioural Brain Research, 93, 185–190.
Auyeung, B., Knickmeyer, R., Ashwin, E., Taylor, K., Hackett,
by sex steroids might exist. G., & Baron-Cohen, S. (2012). Effects of fetal testosterone
Although modern-day neuroscience has begun on visuospatial ability. Archives of Sexual Behavior, 41,
to acknowledge sex differences in the CNS, the dy- 571–581.
namic regulatory effects of sex steroids in the adult Barry, J. A., Parekh, H. S. K., & Hardiman, P. J. (2013). Visual-
limbic system and cerebral cortex are still under- spatial cognition in women with polycystic ovarian syndrome:
The role of androgens. Human Reproduction, 38, 2832–2837.
appreciated, even though they have wide-ranging Beltz, A. M., Hampson, E., & Berenbaum, S. A. (2015). Oral
implications for understanding brain function that contraceptives and cognition: A role for ethinyl estradiol.
go beyond cognition per se. Establishing these Hormones and Behavior, 74, 209–217.
­effects on firmer ground will lead to new theoretical Berenbaum, S. A., Bryk, K. K., Nowak, N., Quigley, C. A., &
and applied advances. Already, growing evidence Moffat, S. (2009). Fingers as a marker of prenatal androgen
exposure. Endocrinology, 150, 5119–5124.
for steroid effects on cognitive function supports Berenbaum, S. A., Korman Bryk, K. L., & Beltz, A. M. (2012).
theoretical conceptualizations in which cognitive Early androgen effects on spatial and mechanical abilities:
sex differences are discussed as evolved adaptations Evidence from congenital adrenal hyperplasia. Behavioral
(e.g., Anderson & Rutherford, 2012; Sherry & Neuroscience, 126, 86–96.
Hampson, 1997), not solely the products of social Bethea, C. L., Lu, N. Z., Gundlah, C., & Streicher, J. M. (2002).
Diverse actions of ovarian steroids in the serotonin neural
learning as formerly thought. Greater appreciation by system. Frontiers in Neuroendocrinology, 23, 41–100.
clinicians of the important regulatory roles played Bimonte, H. A., & Denenberg, V. H. (1999). Estradiol facil­
by sex steroids in extra-hypothalamic regions might itates performance as working memory load increases.
inform new insights into the sex differences in prev- Psychoneuroendocrinology, 24, 161–173.
alence or symptom severity observed in a number of Breedlove, S. M., & Arnold, A. P. (1980). Hormone accumulation
in a sexually dimorphic motor nucleus of the rat spinal cord.
psychiatric or neurological conditions that afflict Science, 201, 564–566.
humans. For basic scientists, awareness might also Breedlove, S. M., & Hampson, E. (2002). Sexual differentiation
transform the way that functional imaging is cur- of the brain and behavior. In J. B. Becker, S. M. Breedlove,
rently done by highlighting the need to control for D. Crews, & M. M. McCarthy (Eds.), Behavioral
relevant endocrine variables when studying human endocrinology (pp. 75–114). Cambridge, MA: MIT Press.
Burkitt, J., Widman, D., & Saucier, D. M. (2007). Evidence for
brain function using f MRI. Understanding which the influence of testosterone in the performance of spatial
regions of the CNS are influenced by steroids, at navigation in a virtual water maze in women but not in men.
which stages of the lifespan, and why, is an important Hormones and Behavior, 51, 649–654.
future goal for cognitive neuroscience. Chamberlain, N. L., Driver, E. D., & Miesfeld, R. L. (1994). The
length and location of CAG trinucleotide repeats in the
androgen receptor N-terminal domain affect transactivation
Acknowledgments function. Nucleic Acids Research, 22, 3181–3186.
I would like to thank the following funding sources who
Cherrier, M. M., Asthana, S., Plymate, S., Baker, L., Matsumoto,
financially supported work from my laboratory described in this
A. M., Peskind, E., . . . Craft, S. (2001). Testosterone
chapter: the Natural Sciences and Engineering Research Council
supplementation improves spatial and verbal memory in
of Canada (NSERC) and the Ontario Mental Health Foundation.
healthy older men. Neurology, 57, 80–88.
I also gratefully acknowledge the following former students for
Cherrier, M. M., Aubin, S., & Higano, C. S. (2009). Cognitive
their contributions to data collection on the cognitive associations
and mood changes in men undergoing intermittent
of oral contraceptive use: S. Duff and E. Morley.
combined androgen blockade for non-metastatic prostate
cancer. Psychooncology, 18, 237–247.
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66 Sex Differences in Cognition

 CH A PT E R
Involvement of the Sex Hormones
5 in Learning and Memory

Kelsy S. J. Ervin and Elena Choleris

Abstract

Learning and memory can be defined as the processes by which we acquire information about our
environment and experiences, to be used later in similar situations. These cognitive processes are
important for behaviors crucial to survival, such as finding food and shelter, assessing risk, and behaving
appropriately in social contexts. Research provides insights into how hormones influence animal and
human cognition. Here, we focus on the sex hormones, which influence both learning or acquisition
and memory consolidation through two mechanisms: (i) the genomic pathways, acting longer-term
to modulate gene transcription, protein expression, and structural changes implicated in establishing
memory traces; and (ii) rapid pathways in which receptor activation initiates cell signaling cascades and
more immediate neural responses. Investigating the roles of sex hormones in learning and memory
enhances our understanding of neural networks involved in different types of learning, in ways that may
be applied to human health and cognition.

Keywords: Learning, memory, sex steroids, encoding, retrieval, acquisition

The sex hormones are steroid molecules synthesized cortisol, and corticosterone (Compagnone & Mellon,
via multiple steroidogenic pathways from cholesterol 2000). Androgens, such as testosterone (T), act
(see Nelson, 2017, for an introduction to sex on the androgen receptor (AR). Testosterone can be
­hormones). Steroidogenesis has been described in converted to the potent androgen dihydrotestoster-
the gonads and other organs, including the brain. All one (DHT), GABAA active metabolites, and the
three classes of sex hormones (i.e., androgens, estro- three estrogens 17β-estradiol, estrone, and estriol.
gens, and progestogens) are produced in both biolog- The conversion of testosterone to estrogens is cata-
ical sexes and act on multiple physiological functions, lyzed by the aromatase enzyme and is very relevant
including behavior and cognition. Progesterone is to our understanding of testosterone effects on
the most abundant of the progestogens; it binds to brain and cognition (reviewed in Atwi, McMahon,
the progesterone receptor (PR), and it can be con- Scharfman, & MacLusky, 2016) because testos-
verted to a number of metabolites that act on other terone affects behavior via both androgenic
neurochemical systems (reviewed in Compagnone (AR-mediated) and estrogenic (estrogen receptor–
& Mellon, 2000). For example, allopregnanolone mediated after aromatization) mechanisms (reviewed
(5α-tetrahydroprogesterone) is an allosteric modu- in Atwi et al., 2016). In humans, 17β-estradiol,
lator of the GABAA receptor. Thus, progestogens can also referred to simply as estradiol, is the most bio-
affect biological systems and behavior either directly, logically active of the estrogens and it is also the most
via the PR, or indirectly, through their metabolites. abundant estrogen during the reproductive years.
With a few synthesizing steps, progesterone is also a Postmenopausally, 17β-estradiol levels greatly decline
precursor to the other two classes of sex steroids and estrone ­becomes the most abundant estrogen
and other steroid hormones, including aldosterone, (Rannevik, Carlström, Jeppsson, Bjerre, & Svanberg,

67
1986; reviewed in Galea, Frick, Hampson, Sohrabji, Learning, the acquisition of novel information,
& Choleris, 2017). Estrogens act via the estrogen involves the formation of new memories through
receptors (ERs), the better described being ERα, various stages including acquisition (initial encoding
ERβ, and the G protein–coupled ER 1 (GPER1). of the memory), consolidation, and recall (retrieval
Other ERs have also been described, including ER-X of the consolidated memory). In more recent years,
and the Gq-coupled membrane ER (Gq-mER), but a fourth stage has been added: reconsolidation,
their functions are less characterized (reviewed in which is triggered by the reactivation of consolidated
Galea et al., 2017; Srivastava & Evans, 2013). memories at recall (Nader & Hardt, 2009). During
The steroid hormones have long been known for consolidation and reconsolidation, memories are
their genomic actions. PR, AR, ERα, and ERβ are labile to both interfering and enhancing effects
all intracellular ligand-regulated transcription fac- (reviewed in Kandel, Dudai, & Mayford, 2014). Two
tors (reviewed in Gustafsson, 2016; although some types of memory consolidation have been described:
ligand-independent activity also exists, reviewed in cellular and system consolidation. Cellular consoli-
Heldring et al., 2007) that, in combination with dation occurs within the first one to two hours
multiple coactivators, can drive the activity of thou- postacquisition and requires DNA transcription and
sands of genes (Carroll et al., 2006). These genomic protein synthesis. Following the initial cellular consol-
effects are delayed in their onset and are long-lasting idation, there is evidence that system consolidation
(hours to days). Much more rapid (minutes) effects occurs over multiple days/weeks and involves the
of the steroid hormones have also been described reorganization of brain structures and the transfer
and recently have been receiving much research of the new memories to long-term storage (Clark,
attention, especially in investigations on estrogen Broadbent, Zola, & Squire, 2002; Dudai, 2004;
effects. The rapid effects of estrogens are being Frankland & Bontempi, 2005). Consolidated memo-
found to be mediated by the classical transcription ries are characterized by slow decay and resistance to
factor receptors and the membrane-bound GPER1 disruption (reviewed in Kandel et al., 2014).
and Gq-mER, and depend on membrane-associated Experimental manipulations can target the various
actions of intracellular ERs and/or membrane- phases of memory to elucidate their underlying
bound ERs triggering intracellular signaling cascades mechanisms and to determine the influence of spe-
(reviewed in Galea et al., 2017; Srivastava, Woolfrey, cific chemicals. For example, effects of a treatment
& Penzes, 2013). Three main cellular pathways have that was administered before the acquisition phase
been identified that are rapidly triggered by estro- can be attributed to effects on the initial encoding
gens and affect cell function: (1) rapid activation of and/or consolidation (depending on how long that
actin signaling cascades (e.g., Rap, RhoA); (2) rapid treatment lingers in the system) phases of memory
initiation of second messenger systems (i.e., signaling formation. Instead, effects observed shortly after
molecules released by the cell to trigger physio­ acquisition can elucidate action on the consolidation
logical changes) such as protein kinase C (PKC), phase. When treatments are administered after a
protein kinase A (PKA), the Akt signaling pathway, certain retention delay after acquisition and consol-
extracellular signal-regulated kinase (ERK) 1 and 3, idation, any effects can be attributed to mechanisms
and the c-Jun N-terminal kinase (JNK) pathway; underlying the retrieval or reconsolidation of a
and (3) rapid modulation of local protein synthesis memory. Finally, treatment effects postretrieval can
mechanisms such as 4E-BP1 (for recent reviews, identify the processes underlying memory recon-
see Frick, Kim, Tuscher, & Fortress, 2015; solidation (e.g., Winters, Tucci, & DaCosta-Furtado,
Srivastava et al., 2013). 2009). Researchers have been using this approach to
Sex hormones act in the brain to regulate or mod- determine the effects of sex steroids on learning and
ulate multiple functions, including learning and memory.
memory, and dysfunctions of these actions have been Long-term potentiation (LTP) and long-term
linked to a number of psychiatric disorders such as depression (LTD) are key cellular processes of syn-
anxiety, depression, and various types of cognitive aptic plasticity that are believed to be critical for
impairments including autism spectrum disorder memory acquisition/encoding and cellular consoli-
and Alzheimer’s disease (reviewed in Gobinath, dation (reviewed in Kandel et al., 2014). LTP is the
Choleris, & Galea, 2017). This chapter focuses on enhanced responsiveness of a synapse following
the involvement of the sex hormones in learning intense stimulation and was initially described in
and memory and describes effects that are mediated the dentate gyrus region of the hippocampus (Bliss
via delayed long-term and rapid mechanisms. & Lømo, 1973) and subsequently found in the CA1

68 Involvement of the Sex Hormones in Learning and Memory

and CA3 hippocampal regions and other brain areas, role on the effects of estrogens in the female
with similar and different characteristics (reviewed ­hippocampus (reviewed in Mahmoud et al., 2016).
in Kandel et al., 2014). In addition to synaptic plas- In adult males, long-term exposure to androgens
ticity, structural plasticity—changes in dendritic spine enhances the survival of new neurons in the hippo-
and spine synapse density, patterns of dendritic campus, whereas estrogens seem to enhance cell
arborization, and neuronal survival—in the hippo- survival only with short-term exposure during axon
campus and other regions have been implicated in growth (reviewed in Atwi et al., 2016; Mahmoud et
memory. Dendritic spines are the site of most excit- al., 2016). In summary, estrogens have been shown
atory synapses, and an increase in their number and to enhance LTP, dendritic spines, dendritic arbori-
changes in their structural and molecular character- zation, and neurogenesis. The effects of progesterone
istics are associated with LTP and the formation and and testosterone are less investigated (especially pro-
consolidation of new memories (reviewed in Bailey, gesterone effects) but are often similar to those of
Kandel, & Harris, 2015). Neurogenesis (i.e., the estrogens, even though results tend to be more mixed.
proliferation, survival, migration, and functional Collectively, these effects of sex hormones on brain
integration of new neurons) in the hippocampal cir- plasticity may explain why these hormones also
cuit has also been linked to new and consolidated have profound effects on learning and memory, as
memories in humans and other animals (reviewed in reviewed next.
Gonçalves, Schafer, & Gage, 2016; Ihunwo, Tembo,
& Dzamalala, 2016). Sex Hormones and Spatial Memory
All three classes of sex hormones affect synaptic Spatial memory involves memory for spatial position-
and structural plasticity in the brain. LTP and syn- ing and/or for environmental or contextual cues. In
aptic plasticity are enhanced by estrogens (reviewed tests of spatial memory, spatial cues or context may
in Srivastava et al., 2013) and inhibited by testoster- be learned passively or as the result of predicting an
one (Skucas et al., 2013). Progesterone was found to outcome such as a reward or an aversive experience
enhance, inhibit, or not affect LTP (reviewed in (in the laboratory the latter is often a mild electric
Hansberg-Pastor, González-Arenas, Piña-Medina, shock). In both humans and animals, the hippocam-
& Camacho-Arroyo, 2015). Dendritic spines are also pus is necessary for encoding of spatial cues. Spatial
regulated by sex hormones. In females, dendritic spine memory can be tested in animals using mazes (e.g.,
density peaks when endogenous estrogen levels are Morris water maze, radial arm maze), memory for
high and is increased with both chronic and within context (e.g., contextual fear conditioning), or spatial
20-40 minutes of acute estrogen treatments (reviewed recognition tasks (e.g., object placement tasks; Luine
in Frankfurt & Luine, 2015; Phan, Lancaster, & Frankfurt, 2012; Tuscher, Fortress, Kim, &
Armstrong, MacLusky, & Choleris, 2011; Phan et al., Frick, 2015; Figure 5.1). Similar tasks are performed
2015; Srivastava et al., 2013). Progesterone also in humans with the advantage that humans can
enhances dendritic spines after chronic treatments report what they remember (Squire, 1992).
(reviewed in Hansberg-Pastor e­ t al., 2015). In males,
dendritic spines fluctuate with androgen levels, and The Study of Spatial Memory in
this appears to be an androgen- and not estrogen- Laboratory Rodents
mediated effect. Conversely, in females, testosterone- In spatial versions of the radial arm maze and Morris
enhancing effects on dendritic spines are mediated water maze, animals are provided with extra-maze
by estrogenic mechanisms (reviewed in Atwi et al., cues with which they can learn and locate the posi-
2016). Sex hormones also affect various aspects of tion of an escape platform (Morris water maze) or
neurogenesis. In adult females, endogenous hormonal in which arm they receive a food reward (radial arm
fluctuations are correlated with hippocampal neu- maze). Another test of spatial memory in rodents is
rogenesis in a manner consistent with enhancing the object placement task, a spatial recognition task
effects of ovarian hormones (reviewed in Mahmoud, in which an animal is habituated to objects in a
Wainwright, & Galea, 2016). Several investigations testing area (e.g., open field, home cage) and, at
have highlighted a role for estrogens in cell prolifer- test, one object is moved to a new location
ation and survival even though these effects seem to (Figure 5.1A). Rodents naturally investigate novel
be modulated by age and hormonal environment at environmental stimuli; therefore, preferential
the time of treatment (reviewed in Mahmoud et al., investigation of the displaced object indicates that
2016). Limited investigations into the effects of the animal identifies the object’s position as new
progesterone on neurogenesis point at a modulatory and/or recognizes that the other object has not been

Ervin and Choleris 69

moved from the old position (Ervin, Phan, Gabor, Frick, 2017). Sex differences in mental rotation tasks
& Choleris, 2013; Koss & Frick, 2017; Luine, 2015; are often cited as differences in spatial abilities; how-
Tuscher et al., 2015). Less common in the literature ever, there is evidence that mental rotation depends
on sex hormones and behavior are hippocampus- on object working memory, rather than spatial work-
dependent contextual fear conditioning and inhibi- ing memory (Hyun & Luck, 2007; Kaufman, 2007).
tory avoidance tasks. In inhibitory avoidance, the In this section on spatial memory, we will focus on
animal learns to avoid a location it normally prefers hippocampus-dependent spatial memory.
(e.g., a nonelevated location or a dark chamber) Sex differences in the spatial memory abilities
when it is associated with footshock, and instead to of laboratory rodents further support a role for the
inhibit leaving a nonpreferred location (e.g., an ele- gonadal hormones in learning and memory for
vated platform or a brightly lit area; Ervin et spatial environmental cues. For example, male rats
al., 2013; Luine, 2014; Luine & Frankfurt, 2012; typically outperform females on the radial arm maze
Figure 5.1B). (Luine, 2014, 2015). Studies of female rodents
across the stages of the estrous cycle and during
Endogenous Hormones and Spatial Memory pregnancy further implicate the sex hormones in
In humans, only subtle sex differences exist in spatial regulation of spatial memory. Female rats and mice
memory abilities. No consistent sex differences in the proestrus phase (high circulating hormones)
emerge in tests using a human version of a radial arm of the estrous cycle tend to perform better than
maze, and men only outperform women on an those in diestrus (low circulating hormones) on object
adapted Morris water maze with no landmarks avail- placement, inhibitory avoidance, and the Morris
able, suggesting that even though performance is water maze (Frick, 2009; Luine & Frankfurt, 2012;
comparable in the sexes, men and women use differ- Tuscher et al., 2015). Similarly, pregnant, postpar-
ent strategies to encode spatial information (Koss & tum, and lactating rats also outperform rats that are

(A) (B)

Figure 5.1 Spatial memory tasks. Both object placement (A) and inhibitory avoidance (B) are frequently used to test hippocampal-
dependent spatial memory in rodents. In object placement (A), an animal is presented with and allowed to investigate one or more
objects either in an open field or in the home cage. At test, one object is moved to a new location and the animal shows intact spatial
memory if it preferentially investigates the object in the new location (e.g., the cylinder in the diagram). In the inhibitory avoidance
task (B), an animal is placed in a nonpreferred location such as a brightly lit chamber or elevated platform. When the animal steps
down off the platform or through to a darkened chamber, a normally preferred location, it receives a mild foot shock. If the animal
remembers the context in which it receives the foot shock, it will inhibit or delay entering the darkened chamber or stepping down off
the platform. Other spatial memory tasks include the Morris water maze and radial-arm mazes, in which animals navigate the maze to
find an escape platform or food reward, respectively, using extra-maze visual cues.

70 Involvement of the Sex Hormones in Learning and Memory

not pregnant or are in early pregnancy, analogous to acquisition. Similar treatment enhanced memory in
the first trimester in humans. Although estrogens and object placement, the Morris water maze, and
progesterone are low during lactation, it is possible inhibitory avoidance in ovariectomized female rats,
that effects on hippocampal plasticity by steroid hor- and in the Morris water maze in castrated male rats
mones are sustained by the effects of elevated prenatal (Luine, 2015; Luine & Frankfurt, 2012; Tuscher
hormones and/or that other hormones are involved et al., 2015). Estradiol treatment is only effective at
in enhancing spatial memory (Tuscher et al., 2015). enhancing object recognition memory if it is given
Multiparous rats perform better on object placement immediately postacquisition; if given after a delay of
than primiparous rats, suggesting that these sex hor- even one hour, it is ineffective (Ervin et al., 2013;
mones have a sustained effect on memory (Tuscher Frick et al., 2015; Luine, 2015; Luine & Frankfurt,
et al., 2015). Complementary to these findings, ovar- 2012; Tuscher et al., 2015). Animals in these studies
iectomy impairs spatial memory, and as female rats were tested at least four hours after training, at a
and mice age, circulating sex hormones decrease and time when memory is consolidated via DNA tran-
reproductive function declines, and spatial memory scription-dependent processes (Bourtchuladze et al.,
on object placement and in the Y- and T-maze, radial 1994; Da Silva et al., 2008; Nguyen, Abel, & Kandel,
arm maze, and Morris water maze is impaired 1994). However, there is an accumulating literature
(Frick, 2009; Luine & Frankfurt, 2012; Tuscher supporting the idea that estradiol’s action through
et al., 2015). Collectively, these results point at a rapid nonnuclear cell signaling pathways is necessary
role for gonadal hormones in spatial learning. for the memory-enhancing effects on object recog-
nition (Fortress & Frick, 2014; Luine, 2014; Tuscher
Estrogenic Enhancement of Spatial Memory et al., 2015). Thus, estrogens enhance spatial mem-
in Female Rodents ories, likely through both genomic and nongenomic
While aged and ovariectomized female rodents are mechanisms, the latter likely via cell signaling pro-
impaired in spatial memory, chronic treatment with cesses that are also involved in nonspatial memory.
estrogens typically restores or ameliorates perfor-
mance. Chronic 17β-estradiol or estradiol benzoate Estrogen Action in the Hippocampus
treatment ameliorates performance on object place- There is growing evidence identifying the hippo-
ment, delayed matching to sample, the T-maze, the campus as a site of estrogenic improvements in spatial
radial arm maze, and the Morris water maze in ovari- memory, as well as in other types of learning and
ectomized rats and mice (Fortress & Frick, 2014; memory. Recently, it has become clear that estro-
Luine & Frankfurt, 2012; Tuscher et al., 2015). gens are synthesized de novo in the hippocampus.
Similarly, spatial memory can be improved in aged Although estrogens in the hippocampus correlate
rats and mice with estradiol treatments, although with fluctuating levels of circulating hormones over
effectiveness varies depending on the timing and the estrous cycle, hippocampal levels of estradiol
dose (Frick, 2009; Luine & Frankfurt, 2012). are about 40 times higher than circulating levels in
Studies using acute treatments of estrogens pro- female and male rats (Luine, 2014; Srivastava &
vide further evidence for specific estrogenic regulation Penzes, 2011). Furthermore, induced hippocampal
of spatial memory. Preacquisition treatment with neural activity increases local estradiol synthesis in
17β-estradiol improved object placement in ovariec- rats and songbirds, and aromatase has been detected
tomized rats when given in two doses over two days in the human brain (Luine, 2014). This suggests
(Jacome et al., 2010) or in ovariectomized mice when that effects of hippocampal estrogens in these model
tested within 40 minutes of one acute treatment species may generalize to humans.
(Phan et al., 2012). In the latter study, the short dura- Estradiol treatment also affects dendritic mor-
tion of the test likely rules out classical genomic phology in the hippocampus. Estradiol administered
effects of estradiol, and the learning improvement systemically or to hippocampal slices ex vivo
was likely due to rapid mechanisms of action through increases the density of dendritic spines, the postsyn-
activation of intracellular signaling cascades (Ervin aptic sites of excitatory neural transmission, and
et al., 2013; Luine & Frankfurt, 2012; Phan et al., ovariectomy reduces hippocampal dendritic spine
2012; Tuscher et al., 2015). Postacquisition treat- density (Fortress & Frick, 2014; Koss & Frick, 2017;
ments with estradiol show a similar pattern of effects. Luine, 2014; Phan et al., 2015). Increases in spine
Estradiol administered immediately postacquisition density occur as early as 30 minutes after systemic
to ovariectomized female mice improved object treatment with estradiol; this and further manipula-
placement memory when tested 24 hours after tions of downstream cell signaling targets of estradiol

Ervin and Choleris 71

indicate that estradiol likely acts through rapid Mauk, Ninaci, Nelson, & Gibbs, 2009). Thus, ERα
mechanisms to influence hippocampal dendritic activation may facilitate spatial memory but is not
morphology (Srivastava et al., 2013). These actions necessary for estrogenic enhancement of performance
of estrogens are thought to enhance memory by pro- on these tasks. Alternatively, chronic treatment may
viding the substrate upon which new memories may lead to a loss of selectivity of the agonist for the
be formed (Ervin et al., 2013; Fortress & Frick, 2014; receptor (Luine & Frankfurt, 2012).
Koss & Frick, 2017; Luine, 2014; Phan et al., 2015). ER-specific agonists also allow the investigation of
With regard to spatial memory specifically, the contributions of rapid estrogenic effects on spatial
17β-estradiol infused into the dorsal hippocampus memory. Preacquisition and postacquisition treat-
immediately postacquisition enhanced object place- ments with PPT, both systemically and in the hippo-
ment memory in ovariectomized rats and mice campus, enhanced object placement in female mice
(Kim, Szinte, Boulware, & Frick, 2016; Luine, 2015; (Frye, Duffy, & Walf, 2007; Phan et al., 2011, 2015).
Luine & Frankfurt, 2012; Tuscher et al., 2015) and However, postacquisition PPT in female rats had
improved Morris water maze performance in both no effect on object placement or Morris water
ovariectomized female and castrated male rats maze performance (Jacome et al., 2010; Rhodes
(Packard, 1998). Preacquisition infusion of estra- & Frye, 2006). Differences in PPT effects on spatial
diol similarly facilitated object placement in ovari- memory could be due to differences in ER expression
ectomized mice tested within 40 minutes of treatment in rats and mice, or to dosage and timing of treat-
(Phan et al., 2015). While the specific intracellular ments with respect to the phases of memory, acqui-
mechanisms of the estrogenic effects on spatial sition, or consolidation (Ervin et al., 2013; Luine &
memory are unclear, studies of their effects on Frankfurt, 2012; Tuscher et al., 2015). Consistent
object memory suggest involvement of the estrogen-­ with ERKO studies, preacquisition treatment with
mediated activation of ERK, phosphatidylinositol the ERβ agonist DPN enhanced object placement
3-kinase (PI3K), mammalian target of rapamycin in female mice, and postacquisition DPN enhanced
(mTOR) pathways, and/or epigenetic changes to object placement and Morris water maze perfor-
histone acetylation or DNA methylation (Fortress mance in female rats (Ervin et al., 2013; Luine &
& Frick, 2014; Kim et al., 2016; Luine, 2014; Frankfurt, 2012), confirming a prominent role for
Tuscher et al., 2015). ERβ in spatial memory. Less is known about the
role of the GPER1, but chronic treatment with the
Roles of Estrogen Receptors in Estrogenic agonist G1 enhanced spatial delayed matching
Enhancement of Spatial Memory to position in ovariectomized female rats, and
Research has investigated whether ERα, ERβ, or acute systemic and intrahippocampal preacquisi-
GPER1 plays a role in estrogenic enhancement of spa- tion treatment rapidly facilitated object placement
tial memory. Long-term manipulations of the recep- in ovariectomized female mice (Ervin et al., 2013;
tors suggest that ERβ plays a prominent role. Mice Gabor, Lymer, Phan, & Choleris, 2015; Hammond,
with ERβ gene knockout (ERβKO) exhibit impaired Nelson, Kline, & Gibbs, 2012; Hawley et al., 2013;
Morris water maze performance, and estradiol was Kim et al., 2016; Lymer, Robinson, Winters, &
only effective in improving performance on object Choleris, 2017). GPER1-mediated enhancements
placement and in a spatial Y-maze task in ERαKO of spatial memory are dependent on the JNK path-
and wild-type control mice (with intact ERβ expres- way, as inhibition of c-Jun phosphorylation blocks
sion), but not in ERβKO mice (Luine & Frankfurt, the enhancing effects of the agonist G1, but ERK
2012; Tuscher et al., 2015). Treatment with the ERβ inhibition has no effect (reviewed in Frick, 2015).
agonist diarylpropionitrile (DPN) also improved This suggests a mechanism of GPER1’s role in spatial
object placement in wild-type but not ERβKO mice memory that is distinct from ERα and ERβ.
and performance on delayed matching to sample
and the radial arm maze in female rats (Luine, 2014; Progesterone Effects on Spatial Memory
Luine & Frankfurt, 2012; Tuscher et al., 2015). The Less research has focused on the role of progester-
ERα agonist propyl pyrazole triol (PPT) was inef- one in spatial learning and memory. In young
fective at improving spatial memory via delayed, adult rats and mice, postacquisition progesterone
long-term mechanisms, in which animals received enhanced object placement memory (Frye et al.,
PPT treatments 48 hours or more prior to testing, 2007; Frye, Koonce, & Walf, 2013; but see Frye &
except in one study in which chronic PPT treatment Walf, 2008). Similarly, chronic and acute postac-
enhanced delayed matching to sample (Hammond, quisition progesterone improved performance in

72 Involvement of the Sex Hormones in Learning and Memory

the object placement task in aged mice (Frye & with regard to spatial information processing, and
Walf, 2008, 2010). When administered chroni- there are sex differences in the structure and function
cally, progesterone impaired inhibitory avoidance, of the rodent hippocampus. In addition to, or poten-
but acute treatment given immediately posttraining tially because of, these differences, male and female
improved performance (Farr et al., 1995; Frye & rodent hippocampal circuits are affected differently
Lacey, 2000). These findings suggest either that pro- by gonadectomy. Notably, gonadectomy generally
gesterone impairs memory only through genomic decreases CA1 dendritic spine density in females,
mechanisms or that rather than impairing memory, but not in males. Castrated males also have enhanced
chronic treatment with progesterone may have LTP, neuronal excitability, and synaptic transmission
affected inhibitory avoidance performance through in the hippocampus, while the opposite is true for
the analgesic and anxiolytic effects of its metabolites, ovariectomized females. Castrated male rats also have
such as allopregnanolone (Bitran, Hilvers, & Kellogg, longer, more branching dendrites in the CA3 than
1991; Frye & Duncan, 1994). Intrahippocampal intact controls, and have more mossy fiber projec-
progesterone treatment had no effect on Morris water tions to the CA3, both important for establishing
maze performance (Tuscher et al., 2015). Overall, LTP (Atwi et al., 2016; Mendell et al., 2017). Rather
these findings suggest that the role of ­progesterone in than being mediated through estrogenic pathways
spatial learning may be less robust than that of estro- from testosterone aromatized to estradiol, it seems
gens, but further investigation is warranted. these effects in males are mediated by androgenic
interaction with brain-derived neurotrophic factor
Androgen-Mediated Effects on Spatial (BDNF) and/or by other metabolites such as dihy-
Memory drotestosterone and 5α-androstane-3α17β-diol (Atwi
Although some androgen effects on spatial memory et al., 2016; Mendell et al., 2017). These structural
are attributable to testosterone conversion to estro- and functional sex differences in the hippocampus
gens via the aromatase enzyme, there is likely a suggest organizational as well as activational effects
nonestrogenic mechanism that also influences per- of neurosteroids and highlight a need to understand
formance. In castrated male rats that are impaired their effects through development.
in spatial memory tasks, chronic testosterone pro- Spatial memory is important in animals for a
pionate e­nhances object placement memory and variety of essential processes, such as finding food,
performance on Y-maze, T-maze, and radial arm identifying a dangerous environment, and estab-
maze tasks (Gibbs, 2005; Spritzer et al., 2011; lishing a territory (Fagan et al., 2013; Sherry, 1998).
Hawley et al., 2014). In the test of object placement, Territoriality in particular is important for both
similar improvements in memory could not be male and female mate selection, and this could
replicated with chronic treatment with estradiol be one reason that sex hormones influence cogni-
benzoate, suggesting that in males, androgen tive aspects of territorial behaviors. The benefits of
receptor–­mediated mechanisms contribute to spatial sex hormones, notably estrogens, on hippocampal-
memory (Luine, 2015). dependent memory could be specific to spatial
memory. However, estrogens’ effects on hippocampal
Conclusions dendritic plasticity, neurogenesis, and epigenetic
Sex differences in spatial memory capabilities seem changes could support learning and memory more
to involve the action of gonadal steroid hormones in generally.
the brain. Estrogens play a major role in the acqui-
sition and consolidation of spatial information, Sex Hormones and Declarative
likely through their action in the hippocampus. In Object Memory
females, the ERβ seems to mediate these effects, Object memory is a type of declarative memory well
both rapidly and longterm, though ERα and GPER1 characterized in humans and other animals. Humans
also influence spatial memory through rapid effects can be asked to recall whether they recognize an
(Ervin, Lymer, et al., 2015; Tuscher et al., 2015). In object or image. Object memory in rats and mice is
males, testosterone has similar enhancing effects on typically tested using an object recognition task.
spatial learning and memory, some of which occur Similar to object placement, animals are presented
through aromatization to estradiol and action on the with one, two, or more objects to freely explore
ERs. However, androgen-specific effects on spatial during a training or acquisition phase (Figure 5.2A).
memory have been found (Luine, 2015). The hippo- After one or more training exposures, the animal is
campus is a prominent site of neurosteroid action tested for recognition by swapping one now-familiar

Ervin and Choleris 73

 (A) seen with spatial memory, female rats and mice in
the proestrus phase (high circulating hormones) of
the estrous cycle tend to perform better than those
in diestrus (low circulating hormones), pregnant
rats perform better than rats that are not pregnant,
and aged female rats with reduced reproductive
function are impaired on object recognition (Luine
& Frankfurt, 2012; Tuscher et al., 2015). These
findings suggest an important role for the sex hor-
mones in object recognition.

Estradiol Effects on Object Recognition

Memory
(B)
Although estrogens, progesterone, and androgens
have all been implicated in modulating object recog-
nition, most of the research has focused on estrogens.
Chronic 17β-estradiol or estradiol benzoate preserved
object recognition abilities in ovariectomized female
rats and mice (Luine, 2015; Luine & Frankfurt, 2012;
Tuscher et al., 2015). Similarly, acute treatments with
17β-estradiol, estradiol benzoate, or 17α-estradiol
administered before the acquisition phase enhanced
object recognition (Luine & Frankfurt, 2012; Tuscher
et al., 2015). Treatments in these studies were admin-
istered at least four hours before the test or recogni-
tion phase, therefore the memory-enhancing effects
may be mediated by either delayed long-term or
Figure 5.2 Object memory task. Object memory in rodents is rapid effects of estrogens, or both. Acute, preacqui-
commonly tested using the object recognition task. The animal
is first presented with one or more objects in an open field or in
sition treatments in which the animal was tested
the home cage (A). After one or more of these habituation within 40 minutes provide evidence that rapid effects
sessions, the animal is given a test in which one object is of estrogens play a critical role in object recognition
swapped for a novel object (B). If the animal preferentially (Phan et al., 2012, 2015).
investigates the novel object (e.g., the pyramid in the diagram), In many other studies, estradiol treatment was
it is interpreted as having recognized or shown intact object
memory for the object it investigated during the previous
administered immediately postacquisition, ruling
habituation sessions (e.g., the cube). out estradiol’s effects on acquisition, or learning about
the objects, which allows for assessment of its effects
on memory consolidation specifically. As with
object for a new object. If the animal recognizes the spatial memory tasks, estradiol only enhances object
previously encountered object, it will spend more recognition memory if administered immediately
time exploring the new object and less time with the after the acquisition phase (Ervin et al., 2013;
familiar objects from the training phases (e.g., Frick et al., 2015; Luine, 2015; Luine & Frankfurt,
Ervin et al., 2013; Luine, 2015; Tuscher et al., 2015; 2012; Tuscher et al., 2015). These changes depend
Winters, Saksida, & Bussey, 2008; Figure 5.2B). on ERK signaling, as inhibition of ERK phospho-
Object memory uses the ventral visual stream, and rylation and its downstream targets prevents estra-
the perirhinal cortex has been shown to be particu- diol-mediated improvements of object recognition
larly important (Winters et al., 2008). (Fernandez et al., 2008; Fortress, Fan, Orr, Zhao,
& Frick, 2013; Lewis, Kerr, Orr, & Frick, 2008).
Endogenous Hormones and Rodent Other research also implicates the PI3K, mTOR,
Object Recognition and PKA pathways; inhibition of any of these
Male and female animals with high levels of circu- pathways abolishes the improving effects of estra-
lating sex hormones display enhanced object recog- diol on object recognition memory. Estradiol inter-
nition, whereas gonadectomy impairs it in both sexes actions with the N-methyl-D-aspartate (NMDA)
(Frick et al., 2015; Luine, 2015). Similar to patterns and metabotropic glutamate receptors are also

74 Involvement of the Sex Hormones in Learning and Memory

necessary for its improvements of object memory In several studies, the ERβ agonist DPN enhanced
(Fortress & Frick, 2014; Luine, 2014). memory when given pre- and postacquisition in
Longer term actions of estrogens on object mice and rats, and estradiol was effective at
­recognition may be mediated through epigenetic enhancing object recognition in ERα (but not in
mechanisms, likely both through classical genomic ERβ) knockout mice (Luine & Frankfurt, 2012;
mechanisms involving estrogen response elements Tuscher et al., 2015). However, the results are
on DNA and by downstream effects of rapid initia- mixed and some studies find no enhancing effect
tion of cellular signaling cascades (Fortress & Frick, of DPN on object recognition when administered
2014; Galea et al., 2017; Gustafsson, 2016). systemically or intrahippocampally (Pereira, Bastos,
Estrogens likely influence DNA histone wrapping de Souza, Ribeiro, & Pereira, 2014; Phan et al.,
through acetylation of the H3 domain, dependent 2011, 2015). Although the gene knockout study
on estrogenic activation of the ERK pathway. suggests that ERα may not be necessary for object
However, estradiol also reduces expression of his- recognition, the agonist PPT enhanced perfor-
tone deacetylase 2 (HDAC2) and HDAC3 in the mance in rats and mice when administered system-
dorsal hippocampus, thus reducing the impairing ically or in the dorsal hippocampus (Ervin et al.,
effects of HDAC2 and HDAC3 on hippocampal- 2013; Luine & Frankfurt, 2012; Phan et al.,
dependent memory (Fortress & Frick, 2014). Less 2011, 2015; Tuscher et al., 2015; but see Jacome et
is known about specific estrogenic actions influencing al., 2010). In addition, studies investigating the
DNA methylation; however, methylation does play role of GPER1 have found that it too rapidly
a role in estrogen-mediated object memory consoli- enhanced object recognition in mice when given
dation, as DNA methyltransferase (DNMT) inhibi- systemically or intrahippocampally preacquisition
tors block the enhancing effects of estradiol on or immediately postacquisition (Gabor et al.,
object recognition. Estradiol seems to specifically 2015; Kim et al., 2016; Lymer et al., 2017). In
increase de novo methylation of DNA by increasing conclusion, there is no one estrogen receptor that
expression of DNA methyltransferases DNMT3a is solely responsible for the estrogenic effects on
and DNMT3b, suggesting a possible mechanism object recognition, and it is possible that the three
for estrogenic enhancement of long-term memory main receptors for estrogens act synergistically to
consolidation (Fortress & Frick, 2014). enhance object memory.

Estrogenic Action in the Hippocampus Progesterone and Object Recognition

for Object Recognition Memory Progesterone’s effects on object recognition have been
Despite the well-known role of the hippocampus in far less studied, but a few investigations suggest it also
spatial memory, this brain region is also a site of estro- plays a role. When administered postacquisition,
genic improvements of object recognition memory. progesterone or combined estradiol and progesterone
Preacquisition infusion of 17β-estradiol into the hip- treatment improved object recognition memory in
pocampus improved object recognition memory ovariectomized female mice and rats. Similar to effects
within 40 minutes of treatment, as did postacquisi- of estrogenic manipulations, these treatments were
tion treatment, suggesting enhancement of memory only effective if given immediately postacquisition
consolidation and likely also acquisition or learning (Tuscher et al., 2015). Although estrogens adminis-
mechanisms (Phan et al., 2015; Tuscher et al., 2015). tered to aged female animals do not always enhance
Learning enhancements with preacquisition treat- object recognition, acute and chronic progesterone
ment with estradiol seem to occur concurrently with treatments improved performance in middle-aged
estrogen-induced rapid changes in dendritic spine and aged mice (Tuscher et al., 2015). It is unclear

spines” with low α-amino-3-hydroxy-5-methyl-4-

density, specifically an increase in immature “silent whether these memory enhancements are due to
progesterone’s action at progesterone receptors or to
isoxazolepropionic acid (AMPA) receptor sensitivity its metabolites such as androgens, estrogens, and/or
(Luine & Frankfurt, 2012; Phan et al., 2015). allopregnanolone. The effects of acute postacquisition
treatments suggest that, like estrogens, progesterone
Roles of Estrogen Receptors in Object acts through rapid cell signaling mechanisms to
Recognition enhance memory. While the mechanisms are cur-
Much evidence on specific estrogen receptors rently unclear, one study has shown that when pro-
points to a role for ERβ in mediating the memory- gesterone was infused into the dorsal hippocampus
enhancing effects of estradiol on object recognition. of mice, levels of phosphorylated ERK increased

Ervin and Choleris 75

five minutes after treatment, and blockade of the or of a specific role for encoding information about
ERK and mTOR pathways prevented progesterone’s stimuli in the environment.
enhancing effects on object recognition memory
(Orr, Rubin, Fan, Kent, & Frick, 2012). Thus, pro- Sex Hormones and Memories Within
gesterone, like estradiol, seems to rapidly activate the Social Context
cell signaling cascades that support object memory Social memory seems to involve neural pathways
consolidation (Tuscher et al., 2015). that can both overlap and be distinct from those
underlying memory for objects or emotional stimuli
Conclusions (e.g., fear). Social memory involves social recognition,
Object memory, like spatial memory, is affected by or recognizing others within a social group based on
the hormonal status of the animal. In general, either the unique identity of specific individuals or
gonadectomy impairs object memory, and hormone features shared by a class of individuals (e.g., kin-
replacement with either estrogens or progesterone ship, position in a dominance hierarchy, familiarity)
tends to improve or restore it, though the effects of (Choleris, Clipperton-Allen, Phan, & Kavaliers,
estrogens have received more research attention. 2009; Ervin, Lymer, et al., 2015). In most tests of
Estrogens seem to influence object memory through social recognition, the animal is tested for familiarity
a variety of mechanisms including intracellular sig- recognition using a similar test to object recognition.
naling cascades (e.g., PI3K, mTOR, and PKA), by An animal is presented with, and habituates to, one
interacting with ionotropic and metabotropic gluta- or more conspecific stimulus animals (Figure 5.3A).
mate receptors, through changes in dendritic spine At test, one stimulus animal is swapped for an unfa-
plasticity, and through changes to the epigenome, miliar animal. As in tests of object recognition, if the
primarily through histone acetylation, though there animal recognizes the animal it encountered during
is evidence for estrogens’ effects on DNA methyl- habituation sessions, it will preferentially investigate
transferases (Fernandez et al., 2008; Fortress & Frick, the novel conspecific (Ervin, Lymer, et al., 2015;
2014; Lewis et al., 2008; Luine, 2014; Luine & Ervin et al., 2013; Figure 5.3B).
Frankfurt, 2012; Phan et al., 2015). There is no one Social learning is a distinct process from social
ER that is clearly responsible for estrogens’ effects recognition, in which an animal acquires new
on object memory, as ERβ, ERα, and GPER1 all information about its environment from another
seem to play a role, and may act synergistically individual, rather than learning about that individual.
(Gabor et al., 2015; Jacome et al., 2010; Kim et al., Humans and other animals use social learning for
2016; Luine & Frankfurt, 2012; Lymer et al., 2017; many types of adaptively relevant information, such
Pereira et al., 2014; Phan et al., 2011; 2015; Tuscher as how and/or where to find food, how to avoid
et al., 2015). Many of the effects of estrogens on predators, and with whom to mate (Ervin, Lymer,
object memory have been observed in the hippo- et al., 2015). The neurobiology of social learning
campus, though it is unclear if estrogens in the has been most thoroughly studied in birdsong and
hippocampus are required for object memory rodents. In passerine bird species, males must learn
encoding itself or for encoding other relevant con- species-specific songs by listening to an adult tutor
textual information. (Bolhuis & Moorman, 2015). In rodents, social
Object memory has adaptive relevance for a few learning is often investigated using the social trans-
different reasons. It can be involved in processes mission of food preferences phenomenon, in which
such as recognizing predators or food sources, risk an “observer” animal given a choice of novel fla-
appraisal, and/or associating objects in the environ- vored foods preferentially eats a food it previously
ment with contingent fearful or rewarding stimuli smelled on the breath of another “demonstrator”
and situations (Dere, Kart-Teke, Huston, & De Souza animal (Ervin, Lymer, et al., 2015; Figure 5.4).
Silva, 2006; Morris, 2001). Object memory in more In humans, women tend to perform better when
general terms can be classified as a type of declar- evaluating emotional faces, and seem to attend more
ative memory. If object memory is generalizable to to social stimuli than men (reviewed in Little, 2013;
declarative memory, it has clear adaptive advantages Sherwin, 2012). Physiological measurements support
for identifying relevant stimuli in the environment these findings: when presented with social stimuli,
or even for remembering specific events (Dere et al., women show higher activity (measured with electro-
2006; Morris, 2001). Enhancement of object memory encephalography or functional magnetic resonance
by estrogens and other neurosteroids may be indic- imaging) in cortical areas of the brain associated
ative of their general role in memory enhancement with facial recognition (e.g., fusiform face area)

76 Involvement of the Sex Hormones in Learning and Memory

 (A) Endogenous Hormones in Rodent Social
Recognition and Social Learning
In tests of social recognition, female mice in proes-
trus during acquisition had enhanced memory for a
familiar conspecific. Similarly, memory for a socially
acquired food preference was facilitated among
proestrus or postpartum mice (compared to diestrus
mice) that interacted with a “demonstrator” conspe-
cific that was previously fed a novel food. Postpartum
rats and pregnant gerbils also showed an enhanced
memory for a socially acquired food preference.
Together, these studies suggest a prominent role for
(B) sex hormones in the acquisition of and/or memory
for social information (reviewed in Choleris et al.,
2009; Ervin, Lymer, et al., 2015).

Estrogens and Social Recognition

As with other tests of recognition memory, estrogens
administered exogenously to ovariectomized animals
tend to enhance memory for a familiar conspecific.
These effects occurred when estradiol benzoate or
estradiol dipropionate was administered days before
acquisition and when 17β-estradiol was administered
within 40 minutes of acquisition and testing, suggest-
ing that estrogens can enhance social recognition
Figure 5.3 Memory for familiar conspecifics. Social recognition
through both rapid and long-term mechanisms
is commonly tested using a familiarity recognition test similar
to that of object recognition tasks. The animal is first presented (Ervin, Lymer, et al., 2015).
with one or more conspecifics (A). At test, one conspecific is The ERα seems to play a major role in the long-
swapped for a novel conspecific (B). If the animal recognizes the term and rapid estrogenic modulation of social recog-
conspecific it encountered previously in habituation sessions nition, unlike other recognition tasks in which ERβ
(e.g., the gray mouse in the diagram), it will preferentially
may play a more significant role, at least in studies
investigate the novel conspecific (e.g., the black mouse).
that do not focus on rapid effects (e.g., Ervin, Lymer,
et al., 2015). ERα gene knockout abolished social
and with mirror neuron systems (in which brain recognition abilities in female mice and reduced
areas associated with a movement are activated while memory retention for a familiar conspecific in
watching another person perform the movement; male mice. Correspondingly, the ERα agonist PPT
Luine, 2014; Proverbio, 2017). While these findings improved social recognition when administered
suggest neurobiological underpinnings of a sex dif- 48 hours before acquisition in both ovariectomized
ference in social information processing, it is difficult and gonadally intact mice. Treatment with the ERβ
in humans to disentangle biological from cultural agonist DPN 48 hours prior to acquisition also
influences on the ability to attend to and use social enhanced social recognition in female mice. However,
information by men and women. Girls may show social recognition was impaired, but not blocked, in
an early preference for social interactions and emo- female ERβKO mice. These findings suggest that
tional stimuli, and then develop an enhanced com- ERα is required for social recognition in female
petency at interpreting these stimuli by virtue of mice, whereas ERβ helps modulate but is not neces-
increased exposure and “practice.” Furthermore, little sary for social recognition (reviewed in Ervin,
is known about how changes in hormone levels over Lymer, et al., 2015; Gabor, Phan, Clipperton-Allen,
the menstrual cycle and/or with use of hormonal Kavaliers, & Choleris, 2012).
contraceptives affect performance on these tasks Investigation of the rapid effects of estrogens
(Proverbio, 2017). Animal studies may therefore through specific ERs confirms a prominent role for
provide useful insight into possible mechanisms of ERα in the control of social recognition. Acute, sys-
social cognition that could generalize to aspects of temic treatment with the agonist PPT, but not the
human social behavior. ERβ agonist DPN, improved social recognition in

Ervin and Choleris 77

 (A) (B)

(C)

Figure 5.4 Memory for socially acquired information. Social learning in rodents can be assessed using the social transmission of food
preferences. First, a “demonstrator” animal eats a novel-flavored food (A). In a subsequent social interaction, an “observer” animal,
naïve to that flavor, can smell the food the demonstrator ate on its breath (B). When the observer is later tested for a food preference
and offered two or more novel-flavored foods, it prefers to eat the food it smelled on the demonstrator’s breath (C). Social learning is
observed when the observer eats more of the demonstrated food than the other novel food(s). Social learning is impaired when the
observer prefers neither food and eats roughly equal quantities of each.

ovariectomized mice when it was administered just (Ervin, Lymer, et al., 2015; Lymer et al., 2017;
15 minutes before acquisition and mice were tested Phan et al., 2015). However, these experiments
within 40 minutes of treatment. This time scale rules involved testing social recognition in the home cage.
out most classical genomic effects and provides evi- When tested in a Y-maze designed to limit spatial
dence for rapid estrogenic enhancements of social rec- cues, 17β-estradiol administered systemically still
ognition specifically through ERα (Phan, Lancaster, enhanced social recognition, but not when infused
Armstrong, MacLusky, & Choleris, 2011). There has into the dorsal hippocampus. Estrogens in the
been less research on the involvement of the GPER, hippocampus may therefore facilitate social recog-
but one study showed a rapid facilitation of social nition indirectly by encoding spatial cues associated
recognition when administered within 40 minutes with the stimulus mice. The fact that ­systemic estra-
of testing (Gabor et al., 2015). Whether the ERα diol still enhanced social recognition in the Y-maze
and GPER1 act independently or synergistically to suggests that other brain regions are involved in
improve social recognition is yet to be determined, the rapid effects of estrogens on social recognition
and further research is also required to clarify the (Ervin et al., 2013).
role of the different ERs in male mice. The medial amygdala seems to play a major role
in the rapid and long-term effects of estrogens on
Brain Regions Involved in Estrogenic social recognition. ERα gene silencing with short
Facilitation of Social Recognition hairpin RNA in the medial amygdala prevented
Both the hippocampus and medial amygdala have enhancement of social recognition with estradiol
been implicated in the estrogenic control of social and progesterone treatment in ovariectomized rats
recognition. Infusion of 17β-estradiol, the ERα (Spiteri et al., 2010). Furthermore, infusions of
agonist PPT, or the GPER1 agonist G1 into the 17β-estradiol or the GPER1 agonist G1 directly into
dorsal hippocampus of ovariectomized female mice the medial amygdala improved social recognition in
enhanced social recognition within 40 minutes, ovariectomized mice within the rapid 40-minute
suggesting that estrogens in the hippocampus act timeframe. In contrast to findings with systemic
through ERα to rapidly facilitate social recognition and intrahippocampal investigations, the ERβ agonist

78 Involvement of the Sex Hormones in Learning and Memory

DPN also rapidly enhanced social recognition when impaired social recognition, and it is yet unknown
infused into the medial amygdala, whereas a much how rapid mechanisms of progesterone action or how
higher dose of the ERα agonist was required (Lymer postacquisition treatment affect social recognition
et al., 2018). Estrogens likely influence social recog- in either males or females.
nition both through genomic action in the medial
amygdala through the control of oxytocin synthesis Androgens and Social Recognition in Male
and receptor expression (Choleris et al., 2003), and Rodents
through rapid, cell signaling mechanisms (Ervin, Compared with tests of spatial and object memory,
Lymer, et al., 2015). Overall, both the medial amyg- social recognition in male mice and rats seems to
dala and the hippocampus seem to be involved in depend more heavily on testosterone conversion
estrogenic effects on social recognition, with the to estrogens via aromatase, and less on androgen
hippocampus playing a lesser role, possibly by associ- receptor–mediated mechanisms. The effect of gonad-
ating the conspecific with environmental cues when ectomy on social recognition in males is less clear
they are available. than in females. Some studies show that castrated
male rats show prolonged habituation to a previously
Progesterone and Social Recognition encountered individual compared with gonadally
Little research has investigated the influence of pro- intact males, suggesting prolonged social recogni-
gesterone in social recognition. Overall, it seems tion memory (Bluthé, Gheusi, & Dantzer, 1993;
that progesterone may impair social recognition in Thor, 1980). In contrast, another study found that
male rats via long-term mechanisms, whereas it could castrated male rats habituated only to repeated
facilitate social recognition in female animals. As exposures to a live conspecific, whereas gonadally
previously noted, female mice in proestrus perform intact males habituated to exposures to a conspecific
better than mice in diestrus on social recognition, a or exposures to odor cues from the conspecific animal,
stage during which both estradiol and progesterone suggesting an impairment of social recognition
levels are elevated (Choleris et al., 2009; Ervin, (Sawyer, Hengehold, & Perez, 1984). Other studies
Lymer, et al., 2015). In one study, ovariectomized found similarly mixed effects in which the social
rats that received a combined treatment of estradiol recognition abilities of castrated male rats seemed to
and progesterone also had enhanced social recogni- depend on the timing of exposures to the social
tion compared to vehicle-treated control rats (Spiteri stimuli (reviewed in Choleris et al., 2009).
& Ågmo, 2009). Conversely, male rats that received Studies using prenatal manipulations of androgen
three progesterone treatments over three days prior receptors or gene knockout models support a primary
to social recognition acquisition and testing showed role for estrogens in social recognition. Prenatal
impaired recognition (Bychowski & Augur, 2012). treatment with an androgen receptor antagonist did
This impairment was reversed by postacquisition not affect social recognition in male rats (Axelson,
infusion of vasopressin into the lateral septum, sug- Smith, & Duarte, 1999). Male aromatase knockout
gesting that progesterone likely acts through long- (ArKO) mice are impaired in social recognition.
term genomic mechanisms to disrupt vasopressin Because aromatase is necessary to convert testosterone
signaling required for social recognition in the male into estrogens, ArKO mice have negligible levels
rats (Bychowski, Mena, & Augur, 2013). In agree- of estrogens and higher levels of testosterone. Thus,
ment with these findings, male rats that received disruptions in social recognition in ArKO mice
prenatal exposure to alcohol had impaired social could be due to lack of estrogens and/or impairing
recognition in adulthood, as well as elevated circulat- effects of testosterone (Fisher, Graves, Parlow, &
ing progesterone, and higher levels of its precursor Simpson, 1998; Pierman et al., 2008). Treatment
pregnenolone and the metabolite allopregnanolone in with the testosterone metabolites estradiol and dihy-
the cortex and hippocampus (Barbaccia et al., 2007). drotestosterone restored social recognition in ArKO
These findings are in contrast with the improving mice (Pierman et al., 2008). Together, these studies
effects found in female mice and rats when given suggest that androgens do not have major develop-
postacquisition, possibly due to rapid mechanisms mental effects on mechanisms involved in social rec-
of action (reviewed in Tuscher et al., 2015). These ognition, but rather that estrogens are critical
differences could indicate a sex difference in the role (Choleris et al., 2009). The effects of castration and
of progesterone in social recognition. It could also ArKO in male rats and mice on social recognition
be that chronic elevation or repeated treatments of are likely mediated by estrogenic mechanisms and
progesterone activated long-term mechanisms that downstream regulation of arginine v­asopressin.

Ervin and Choleris 79

Castrated male rats and male ArKO rats have reduced 72 hours, respectively, prior to testing, found that
vasopressin levels in limbic structures associated activation of ERβ prolonged the duration for which
with social recognition, including the medial amyg- observers preferred the demonstrated food, whereas
dala. In castrated rats, these effects were reversed with ERα activation blocked the socially acquired food
testosterone or estradiol treatment, but not dihy- preference (Clipperton, Spinato, Chernets, Pfaff, &
drotestosterone, a nonaromatizable androgen (Brot, Choleris, 2008). On a shorter time scale, in which
De Vries, & Dorsa, 1993; De Vries, Wang, Bullock, mice were treated with ER agonists and tested for a
& Numan, 1994). Although arginine vasopressin food preference within 45 minutes, only the GPER1
synthesis requires both androgenic and estrogenic agonist G1 facilitated social learning in a way similar
mechanisms, it seems that estrogenic mechanisms to 17β-estradiol. ERα and ERβ agonists instead
play a predominant role in social recognition, even shortened the duration of the socially acquired
in male animals (Choleris et al., 2009). food preference, suggesting that activation of these
ERs may inhibit social learning (Ervin, Lymer, et al.,
Neurohormonal Control of Social Learning 2015; Ervin, Mulvale, Gallagher, Roussel, & Choleris,
Compared with social recognition, little is known 2015). In conclusion, it seems that ERβ may play a
about the influence of gonadal hormones on social role in enhancing social learning, but only through
learning. However, studies with ovariectomized long-term mechanisms, having no effect or perhaps
mice suggest a prominent role for estrogens in the impairing social learning through rapid mechanisms.
modulation of social learning in rodents. Similarly, Similarly, ERα has no effect, or a slight impairing
a broader range of research in birdsong learning effect, on social learning through rapid mechanisms
also supports a role for estrogens and androgens in and impairs it through long-term mechanisms. These
social learning. Social learning in rodents is com- findings are in contrast with the roles of these
monly tested using the social transmission of food ERs on social recognition, and other recognition
preference. This test, like spontaneous recognition learning tasks, and perhaps set social learning apart as
tasks, takes advantage of a natural behavior in a ­distinct learning system. The GPER1, however,
rodents. In brief, an “observer” animal investigates facilitated social learning, consistent with its rapid
the nose and mouth of a “demonstrator” animal facilitatory effects on social recognition and other
that previously ate a novel food (Figure 5.4A, B). types of memory.
When the observer subsequently encounters this The long-term enhancing effect of the ERβ ago-
food, smelled on the breath of the demonstrator, nist on social learning co-occurred with an increase in
and another novel food, it will typically prefer, submissive behaviors displayed by the observer mouse
or consume more of, the demonstrated food to the demonstrator, which may have facilitated
(Figure 5.4C). The social transmission of food pref- acquisition of the socially acquired food preference.
erence is thought to be a strategy by which rodents This would be in agreement with other studies
can overcome neophobia and expand their diet to involving socially learned avoidance of biting flies in
novel foods that are likely to be safe (Ervin, Lymer, which observers learned better from a more dominant
et al., 2015; Ervin et al., 2013). than a subordinate demonstrator (Kavaliers, Colwell,
As mentioned previously, mice in the proestrus & Choleris, 2005). Thus, ERβ activation may indi-
phase tend to show an enhanced preference for the rectly facilitate social learning by changing the
demonstrated food (Choleris, Clipperton-Allen, Gray, nature of the social interaction (i.e., when observers
Diaz-Gonzalez, & Welsman, 2011). Ovariectomized acquire information), rather than acting directly on
female mice administered estrogens exogenously social learning mechanisms (Choleris et al., 2009;
days before or within 45 minutes of testing similarly Ervin, Lymer, et al., 2015; Ervin et al., 2013).
show enhanced social learning, suggesting that However, further research is required to determine
estrogens may facilitate this learning strategy through the specific mechanisms by which the different ERs
both long-term and rapid mechanisms (Ervin, influence social learning. Social learning in the
Lymer, et al., 2015). Unlike social recognition, which social transmission of food preference is well known
seems to strongly involve the ERα, social learning to involve acetylcholine and dopamine, and a recent
seems to be more influenced by estrogenic action study showed a sex difference in manipulations of
through ERβ and the GPER1. A study of the long- the hippocampal dopaminergic system, in which
term effects of estrogens on social learning, in female mice were less sensitive to a dopamine D1-type
which the ERα agonist PPT and the ERβ agonist receptor blockade in the hippocampus (Matta,
WAY-200070 were administered 48 hours and Tiessen, & Choleris, 2017). Estrogens’ interactions

80 Involvement of the Sex Hormones in Learning and Memory

with dopamine and/or their aforementioned effects learning such as object recognition and object
on cell signaling cascades and epigenetic mechanisms placement (Ervin, Lymer, et al., 2015; Gabor et al.,
could potentially underlie the estrogenic effects on 2015; Lymer et al., 2017). Thus, GPER1 may have a
social learning. general facilitatory effect on learning. Conversely,
Research on hormonal modulation of birdsong ERα and ERβ may have more specific roles depend-
learning can provide additional insight on the role ing on the type of social or nonsocial information.
of the sex hormones on social learning. There is a ERα-mediated enhancements of social recogni-
high density of androgen receptors throughout the tion may play a larger role in a suite of sexual and
neural pathways involved in song learning and territorial behaviors. ERα also plays a prominent
production, and testosterone has been found to
­ role in the estrogenic control of aggression and
drive development of a mature, crystallized song in sexual behaviors; social recognition is crucial in
young male songbirds (Bolhuis & Moorman, 2015; both of these contexts for recognizing intruders versus
Brainard & Doupe, 2002). These effects seem to familiar individuals, and for recognizing potential
arise through downstream effects on the vasotocin mates. Combined with the fact that ERα also medi-
system (evolutionarily homologous to vasopressin ates anorexic effects of estradiol, it could be that
in mammals) and likely contribute to the control of ERα-activated mechanisms prioritize reproduc-
a suite of t­erritorial behaviors (Goodson & Bass, tively motivated behaviors over foraging and/or
2001). In addition to testosterone action through behaviors related to social learning (reviewed in
androgen receptors, there is also evidence of its Ervin, Lymer, et al., 2015).
influence through estrogenic mechanisms after aro- While estrogens clearly play a role in social learn-
matization to estradiol. Song learning is disrupted by ing in rodents, the mechanisms and ERs involved are
aromatase inhibition or blockade of ERs. Estradiol unclear. The involvement of estrogens and androgens
also modulates song preferences of female songbirds and their downstream effect on ­vasopressin in another
for male songs (Bailey & Saldanha, 2015). Whether form of social learning, birdsong learning, may pro-
the evidence from birdsong learning suggesting vide some clues about the neurohormonal under-
involvement of androgens and v­ asopressin translates pinnings of social learning in rodents (Goodson &
to rodent social learning about food requires further Bass, 2001; Bailey & Saldanha, 2015). However,
investigation. one major difference between the role of sex hor-
mones in birdsong learning and the social transmis-
Conclusions sion of food preference is the probable motivational
Estrogens play a stronger role in the modulation of differences in these two types of behaviors. As testos-
social recognition learning than other types of terone promotes aggression and territorial behaviors
learning in both male and female animals (Choleris and sexual behavior, it may be no surprise that it
et al., 2009; Ervin, Lymer, et al., 2015). ERα plays also supports song learning and production in male
a prominent role in social recognition through both songbirds for whom songs serve to attract mates
rapid and long-term mechanisms, while ERβ can and/or establish territories. This is in contrast to the
support social recognition but is not necessary social transmission of food preference in rodents, in
(Ervin, Lymer, et al., 2015). Progesterone also seems which aggression can impede acquisition of a socially
to facilitate social recognition in female animals but learned food preference (Choleris et al., 1998; Ervin,
disrupts it in male rodents, likely through down- Lymer, et al., 2015). Nonetheless, the convergence
stream inhibition of vasopressin signaling (Choleris of the songbird and rodent literature supporting a
et al., 2009; Bychowski & Augur, 2012; Bychowski role for estrogens provides strong evidence for their
et al., 2013; Tuscher et al., 2015). In contrast with role in social learning and other social behaviors.
the findings from social recognition, ERα impairs
social learning as observed with the social transmis- General Conclusion
sion of food preferences. ERβ is involved to some We have summarized the literature on the results of
extent through long-term mechanisms, either by laboratory studies examining the involvement of sex
direct enhancement of learning or indirectly by steroids in learning and memory. The results of these
changing the dominance relationship between the investigations paint a complex picture—the type of
observer and demonstrator (Clipperton et al., 2008; learning examined, hormone, receptor, brain region,
Ervin, Lymer, et al., 2015). Unlike the classical ERs, timing of administration, and sex can all affect learn-
GPER1 has been found to enhance not only social ing and memory. Unsurprisingly, then, the results of
recognition and social learning but also nonsocial these investigations are mixed. Some hormones,

Ervin and Choleris 81

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ergistically or competitively affect survival and repro- us about learning. Nature, 417, 351–358.
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Ervin and Choleris 85

 CH A PT E R
Endocrine Disruptors and Other
6 Environmental Influences on
Hormone Action
Laura N. Vandenberg

Abstract

Endocrine-disrupting chemicals (EDCs) interfere with hormone action by altering hormone synthesis,
secretion, transport in the blood, binding to receptors, metabolism, or excretion. This chapter reviews
the history of EDCs and other environmental chemicals, methods used to identify EDCs, and common
uses for these chemicals in consumer products. It also describes major principles of endocrinology and
how these features influence the actions of EDCs. This chapter will also evaluate controversies in the
study and regulation of EDCs, including the concept of “low dose effects,” the question of whether
humans are exposed to EDCs at levels that can cause harm, and the determination of “safe” doses of
exposure. Finally, this chapter reviews other environmental factors that can influence the health of
laboratory animals and interfere with the study of EDCs.

Keywords: endocrine disruptor, adverse effect, potency, low-dose effect, threshold, nonmonotonic

The endocrine system plays an important role in endocrine machinery that is required to maintain the
mediating the interaction of individuals with their health of the individual but also the developmental
environments. Hormones are responsible for the processes and epigenetic regulation of gene expres-
maintenance of body temperature and body fat; sion, inducing effects that can persist for ­generations.
they allow creatures to utilize sugars and store energy This chapter will discuss the effects of EDCs on
in the body; they regulate fertility and the response the function of the endocrine system with a specific
of mothers to their young; they mediate social and focus on hormone action. Knowledge from several
sexual behaviors; and they regulate water intake and scientific fields including environmental health,
blood pressure. Hormones also regulate develop- toxicology, endocrinology, and epidemiology will
ment of many of the body’s organs and play an be combined to describe why EDCs have emerged
­important role in cell differentiation and organo- as an important public health concern. Finally, this
genesis. Moreover, hormones allow the organs, chapter will describe other environmental factors
­tissues, and cells of the body to respond to environ- that, like EDCs, can interfere with normal biologi-
mental changes. Only recently has it begun to be cal processes. We will specifically focus on variables
understood that some environmental influences can that are present in laboratory animal studies but are
interfere with these responses. One aspect of the often ignored; these environmental factors could
­environment that has received significant attention influence developmental and homeostatic processes,
over the last decade is the discovery and under- inducing variability in experiments and making it
standing of endocrine-disrupting chemicals (EDCs). difficult to replicate prior research collected under
These compounds affect not only the homeostatic different environmental conditions.

87
Environmental Chemicals: A Brief was sprayed per acre across more than 1 million
Historical Review acres in Montana; this led to measurable levels of
Chemicals have been used throughout known human DDT in every fish that was examined (reviewed
history for the benefit of individuals or groups. in Carson, 1987). Carson noted that the fish were
Chemicals added to animal hides allowed for the not usually killed by DDT, but rather that they
preservation of these materials for use in clothing experienced higher mortality due to loss of other
and other fabrics; chemicals added to food (e.g., salt, food sources. Birds of prey, eating these fish, had
sugar) allowed these items to be preserved for later significantly higher levels of DDT in their bodies,
consumption. In the 18th and 19th centuries, chem- illustrating the bioaccumulation of DDT in body
ical manufacturing reached a much larger scale, tissues, as well as the biomagnification of this chem-
­allowing chemicals to be produced by the ton to ical in the food chain (see Figure 6.1). The adverse
alter fabrics, foods, and other goods. By the early ­effects that were observed in birds of prey included
20th century, a number of large chemical companies egg shell thinning (which contributed to decreased
had formed, focused on the production of chemicals ­fecundity, as eggs would often crack when parents sat
for use in detergents, plastics, inorganics, fertilizers, on their nests to keep them warm), neuromuscular
pharmaceuticals, and pesticides. Modern warfare diseases, wasting, and death. Importantly, Carson
was changed due to the availability of chemicals to documented that the effects of DDT and other pesti-
protect soldiers from insects—which often were cides were most profound on embryos and hatchlings
more than a nuisance due to their transmittal of rather than the exposed adult birds. Further, although
­infectious diseases—as well as chemicals to be used observational studies of wild birds were a central
as weapons. Following World War II, the number of focus of her work, Carson also reviewed dozens of
synthetic pesticides soared, allowing humans to studies detailing the effects of controlled experi-
“tame” environments that had previously been diffi- mental studies with a range of species.
cult to farm or inhabit due to insects. Yet, this same Although Carson was not alone in her research
use of pesticides that improved the use of lands and examining the effects of environmental agents on
the health of many populations at risk from infec- wildlife populations, Silent Spring is widely credited
tious diseases caught the attention of environmental with raising awareness of multiple scientific issues
health scientists due to their u ­ nintended effects on that have continued to be examined in the field of
nontarget species, including ­exposed humans. environmental health. These include (1) acknowl-
Perhaps the most famous example of concern over edgment that even low doses of chemicals can have
the widespread and indiscriminate use of pesticides profound effects on exposed creatures, many of
arose from the 1962 publication of Silent Spring, which were not the intended target of the chemical;
an environmental science book written by Rachel
Carson. Carson explored the unintended conse-
(A)
quences of exposures to pesticides, including
dichlorodiphenyltrichloroethane (DDT), diel-
­
drin, endrin, and methoxychlor. With the publica-
tion of Silent Spring, experts from a growing number TIME
of disciplines, as well as the public at large, became
aware that exposures to chemicals in the environ- (B)
ment could affect the health of wild animals, with
potentially devastating effects that were docu-
mented and widely acknowledged. Carson suggested
that similar effects could happen to exposed humans,
and she documented human exposures to insecti- FOOD CHAIN
cides like DDT, which was found in foods ranging
from fruits to breads (Carson, 1987). Figure 6.1 Bioaccumulation and biomagnification of
Lay audiences that recall the work of Carson environmental contaminants. (A) Bioaccumulation refers to
often point to her “discovery” that DDT affected the increased level of a compound that is stored in the body,
the health of birds of prey, including American bald typically in fat, after exposures. Bioaccumulation is typically
attributed to the physio­chemical properties of a compound
eagles. In fact, many researchers were working to (e.g., features of a chemical that increase its lipophilic tendencies).
understand the effects of DDT on nontarget spe- (B) Biomagnification refers to the increased level of exposure
cies. In the 1950s, approximately 1 pound (0.45 kg) observed at higher levels of the food chain.

88 Endocrine Disruptors and Other Influences on Hormone Action

(2) understanding that chemical mixtures can reproductive function, neurobehavioral development,
have compounded effects, inducing more extreme and autoimmune diseases. At the conclusion of the
outcomes than are observed after exposures to single meeting, the scientists collectively wrote a consen-
chemicals; and (3) the realization that the timing sus statement that summarized the state of the sci-
of chemical exposures is critical, indicating that some ence on these environmental chemicals. They wrote,
populations—often developing creatures—are more “We are certain of the following: A large number of
vulnerable to exposures than others. man-made chemicals that have been released into
The chemical industry’s reaction to Carson’s the environment, as well as a few natural ones, have
book was extremely negative; although it might be the potential to disrupt the endocrine system of
understandable that companies have an interest in ­animals, including humans” (Colborn et al., 1993
protecting their products, the personal vilification [emphasis added]).
of Carson was unprecedented. In spite of this nega- The Wingspread meeting marked the first time
tive attention, Carson’s understanding that many that the term endocrine disruptor was widely used.
chemicals used as pesticides could alter metabolism Although the meeting participants did not expressly
and function of the nervous systems of exposed ani- define this term, it stuck; this term continues to be
mals continued to draw attention from scientists used today. Furthermore, the study of EDCs has
working in a range of fields. Since the 1960s, many moved from a fairly small field with only a few
dedicated conservationists and wildlife biologists dozen laboratories committed to their study to a
have described the effects of environmental com- field that is acknowledged and addressed by scien-
pounds on wildlife. In the 1980s and 1990s, one tists with a wide range of expertise. At the time of
­researcher, Theo Colborn, began to document the Wingspread, the contributions from experts in
effects of chemicals on the health of wildlife in the fields, including ecology, endocrinology, medicine,
Great Lakes area in the United States. Collecting law, reproductive physiology, toxicology, wildlife
papers published by her fellow scientists, Colborn management, and cancer biology, came together to
found that adverse health outcomes were often advance the study of EDCs. Today, the dogma from
­reported in birds and fish, with effects seen in a wide each of these fields has significantly affected how
range of species. Like Carson, Colborn observed public health agencies approach the study and regu-
that effects were often seen in animals at the top of lation of these compounds.
the food chain. She also noted, similar to what
Carson had documented in Silent Spring, that the Defining and Identifying
worst effects of chemical exposures were often Endocrine-Disrupting Chemicals
­measured in the offspring of exposed animals, and Following the Wingspread Conference and publi-
not the exposed adults themselves (see Colborn, cations from its attendees (Colborn et al., 1993),
vom Saal, & Soto, 1993). regulatory agencies around the world began to pay
To try to identify patterns in the data, Colborn much closer attention to the issue of EDCs. The
created a spreadsheet to tally the effects observed first step taken by many of these agencies was to
across dozens of species (Krimsky, 2003). With this develop a working definition that could be used
analysis, she noted that the most common effects for the study, identification, and future regulation
were diminished reproduction, thyroid problems, of these c­ ompounds. The first agency to define an
altered behavior, and metabolic changes. For the EDC was the U.S. Environmental Protection Agency
first time, she noted that the underlying commonal- (EPA), which offered this definition in 1996: “An
ity in these effects is the central role of the endocrine exogenous agent that interferes with the production,
system. These findings led Colborn to organize a ­release, transport, metabolism, binding, action, or
meeting at the Wingspread Conference Center in elimination of natural hormones in the body
Wisconsin. This meeting, held in 1991, brought ­responsible for the maintenance of homeostasis and
­together scientists from a wide range of backgrounds the regulation of developmental processes” (Kavlock
to describe the data each one had collected from their et al., 1996: 716). In 2012, scientists affiliated with
own studies of hormonally active pharmaceuticals the Endocrine Society, a 100-year-old international
and environmental chemicals. The group noted society composed of basic scientists and physicians
­effects of these chemicals on cultured cells, labora- dedicated to the study and treatment of conditions
tory animals, and human populations and p ­ atients. and diseases related to hormones, worked to sim-
The Wingspread participants further discussed the plify the EPA’s definition. They defined an EDC as
effects of these chemicals on sexual ­differentiation, “an exogenous chemical, or mixture of chemicals,

Vandenberg 89
that interferes with any aspect of hormone action” EPA’s ­definition, argues that any alteration to the
(Zoeller et al., 2012: 4097). action of hormones in the body will induce adverse
EDCs are a global health issue, and thus outcomes, at least in some populations (Zoeller
other groups, including international agencies, have et al., 2012, 2014). Thus, they argue, any compound
weighed in on their definition and identification. that is an EDC is also expected to cause harm.
In 2002, the World Health Organization (WHO) Identifying EDCs is, of course, dependent on
and International Programme on Chemical Safety how these compounds are defined. One definition
(IPCS) defined these chemicals as that was proposed for use in the European Union
(and has since been rejected) required that a
an exogenous substance or mixture that alters
­compound be “known to cause harm to humans”
function(s) of the endocrine system and
before it could be labeled an EDC. This definition
consequently causes adverse effects in an intact
would thus require a relatively large body of epi-
organism, or its progeny, or (sub)populations.
demiological studies before a compound could be
A potential endocrine disruptor is an exogenous
identified as an EDC. From the public health per-
substance or mixture that possesses properties
spective, such a requirement is unacceptable; even
that might be expected to lead to endocrine
in relatively lax regulatory environments, requir-
disruption in an intact organism, or its progeny,
ing that a compound be known to harm humans
or (sub)populations.
before it can be regulated is not scientifically or
(IPCS, 2002: 1)
ethically defensible.
There are several reasons that different countries, Starting in the 1990s, the EPA worked with
and different agencies within single countries, have ­scientific experts to develop methods to screen
selected different definitions for EDCs. In 2016, a ­environmental chemicals for endocrine-disrupting
debate within the European Commission over the properties. As a part of the Endocrine Disruptor
definition for an EDC highlighted some of these Screening Program (EDSP), the EPA developed a
reasons (Bourguignon et al., 2016; Kortenkamp two-tiered testing system to characterize compounds
et al., 2016). Much of this debate has focused on the as EDCs (Borgert et al., 2011). The first tier is com-
political and economic consequences for the word- posed of 11 assays that allow for the identification of
ing used within each definition (Solecki et al., 2016): chemicals that have the potential to interact with
some definitions require that “proof ” of a link the endocrine system (Table 6.1). These assays are
­between a chemical and an adverse effect be estab- focused on three hormones (estrogens, androgens,
lished before a compound can be labeled an EDC; and thyroid hormone) and steroidogenesis pathways.
this is a high burden to reach, and even determining Chemicals that are identified as “positive” in Tier 1
which endpoints are “adverse” is a complex and assays are then tested in Tier 2 assays, which exam-
controversial issue (Zoeller et al., 2014). Others ine specific adverse outcomes associated with dis-
have required that data be available to demonstrate ruption of the endocrine system (e.g., endpoints
the mechanism by which a chemical causes harm that demonstrate developmental and reproductive
prior to the labeling of a compound as an EDC toxicity). Members of the Endocrine Society and
(Slama et al., 2016); again, this is a high burden other scientific experts have raised serious con-
of proof, depending on the level of mechanistic cerns about the use of the EDSP assays, suggesting
­information that is required. that they are not comprehensive enough to evalu-
The use of different definitions by different ate all aspects of hormone biology; it has been
agencies has caused controversy, and likely will ­suggested—and demonstrated empirically—that
cause further political and economic issues, because the assays will not detect all compounds that inter-
a chemical could be labeled an EDC according to fere with hormone action (Myers, Zoeller, & vom
one definition (in one jurisdiction) but be considered Saal, 2009; Zoeller et al., 2012, 2014). Concerns
“safe” from this label in another country, or by have also been raised about how the data from the
­another agency. The EPA’s definition, for example, EDSP assays are combined and collectively analyzed
­requires only that a compound be demonstrated to (Myers et al., 2009, 2015; L. H. Vandenberg &
affect the action of hormones in the body for it Bowler, 2014; L. H. Vandenberg, Colborn, et al.,
to be considered an EDC, whereas the WHO/IPCS 2013). For this reason, alternative testing programs
definition requires that such actions be linked to a have been proposed (Schug et al., 2013) and have
downstream adverse effect (Beronius & Vandenberg, begun to be used (Soto, Schaeberle, Maier,
2016). The Endocrine Society, having adapted the Sonnenschein, & Maffini, 2017).

90 Endocrine Disruptors and Other Influences on Hormone Action

Table 6.1. Summary of Endocrine Disruptor Screening Program (EDSP) Tier 1 Assays

Type of Assay Assay Hormone System Evaluated

Cell fraction assay Aromatase Enzyme converting testosterone to estradiol

ER binding assay Estrogen receptor agonists and antagonists
AR binding assay Androgen receptor agonists and antagonists
In vitro assays ER transcriptional activation assay Estrogen receptor agonists and antagonists
Steroidogenesis assay Hormone synthesis
In vivo assays Uterotrophic assay Estrogen receptor agonists (rodent)
Hershberger assay Androgen receptor antagonists (rodent)
Pubertal female assay Estrogen receptor agonists and antagonists, thyroid
hormone receptor antagonists (rodent)
Pubertal male assay Androgen receptor agonists and antagonists, thyroid
hormone receptor antagonists (rodent)
Fish short-term reproductive assay Estrogen receptor agonists and antagonists (fish)
Amphibian metamorphosis assay Thyroid hormone receptor agonists and antagonists (frog)

For the remainder of this chapter, discussions of electronics, upholstery and other furnishings,
EDCs will rely on the Endocrine Society’s defini- ­medical and sports equipment, and building mate-
tion of an EDC (Zoeller et al., 2012), which is a rials (Bergman, Heindel, Jobling et al., 2013a; Gore
simplification of the definition originally proposed et al., 2015). Chemicals used in a wide range of
by the EPA (Kavlock et al., 1996). ­industrial processes, and compounds that are the
byproducts of industrial reactions, have also been
Sources of Endocrine-Disrupting identified as EDCs. Some EDCs are chemicals that
Chemicals have been developed specifically to be biologically
Estimates from government agencies suggest active. Many chemicals used as pesticides (herbi-
there are now more than 80,000 chemicals in cides, insecticides, fungicides, etc.) were designed to
­commerce (Bergman, Heindel, Kasten, et al., 2013). interfere with biological processes and have endo-
Unfortunately, few of these chemicals have been crine-disrupting properties as unintended features.
well evaluated for toxicity, and even fewer tests for Furthermore, some pharmaceuticals have been
endocrine-disrupting activity have been completed. ­developed that were designed to mimic or block
For this reason, it is difficult to determine exactly the actions of hormones (e.g., to treat hormone-
how many EDCs are in the environment, or to dependent cancers or as birth control agents). These
estimate how many EDCs are produced in high vol- compounds are used by patients to purposely
umes. Different groups that have used various crite- ­“disrupt” the endocrine system (e.g., by blocking
ria to evaluate chemical toxicity data have identified ovulation or preventing the conversion of andro-
between 800 and 1,200 compounds as EDCs. For gens to estrogens in the case of estrogen-sensitive
example, the Endocrine Disruption Knowledgebase tumors). However, because these pharmaceuticals
developed by the US Food and Drug Administration are typically administered at high doses, they are
(FDA) includes more than 1,000 chemicals based ­excreted by patients into the environment, where
on their ability to bind to just a handful of nuclear they disrupt hormone action in wildlife (Bhandari
hormone receptors in either in vitro or in vivo assays et al., 2015; Christen, Hickmann, Rechenberg, &
(FDA, 2010; The Endocrine Disruption Exchange Fent, 2010; Orlando & Ellestad, 2014). Many phar-
[TEDX], 2015). Because most of these chemicals maceuticals, including contraceptives, have been
have not been evaluated with Tier 2 assays, the FDA detected in public drinking water, suggesting that
argues that they cannot yet be considered EDCs. low-level environmental exposures to human popu-
Others have argued that Tier 1 assays are sufficient lations are also likely. Finally, there are some natu-
to conclude that a compound is an EDC according rally occurring EDCs, including phytoestrogens (i.e.,
to the EPA definition. plant-derived estrogens) and mycoestrogens (i.e.,
Compounds that have been identified as EDCs fungal-derived estrogens) and some heavy metals
are used in a variety of consumer products, including including lead, cadmium, nickel, copper, and
­
personal care products, food and beverage p ­ ackaging, ­chromium that have been shown to display hor-
detergents, toys and other children’s items, fragrances, monal activities.

Vandenberg 91
Defining “Hormone Action” are transported in blood and travel to target cells.
As described previously, the vast majority of com- Within target cells, they bind to receptors located
pounds identified as actual or putative EDCs by on the cell membrane or within the cell (in the
the FDA were discovered to bind to three hormone ­cytoplasm or the nucleus). Hormones are metabo-
receptors: estrogen, androgen, and thyroid hor- lized and excreted, allowing serum concentrations to
mone (FDA, 2010). Because the endocrine system is be tightly controlled. By definition, EDCs can inter-
much more complex than these three nuclear recep- fere with any of these steps, altering hormone action.
tors, it is likely that many more compounds with
endocrine-disrupting properties have not yet been Endocrine-Disrupting Chemicals
identified. For example, few chemicals that mimic and Endocrine Principles
or block the actions of glucocorticoid or mineralo- The endocrine system is complex, with involvement
corticoid hormones have been identified; this is in virtually all aspects of life from conception until
likely due to the absence of high-throughput meth- death (Diamanti-Kandarakis et al., 2009). Thus,
ods to evaluate compounds that disrupt these endo- although most screening tools and studies of EDCs
crine pathways. have focused on the hormones involved in repro-
Although receptor binding (agonism and antag- duction, dozens of signaling molecules work together
onism) is the most common feature of identified to coordinate the organs and systems of the body
EDCs, hormones have a number of actions; each (Gore, Heindel, & Zoeller, 2006; Myers et al.,
step in the pathway is subject to possible disruption. 2009). Furthermore, the narrow view of ­hormones
In addition to their interactions with receptors, hor- in the context of “homeostasis” is an inappropriate
mones are understood to be synthesized, secreted, understanding of signaling molecules that have
transported in blood, metabolized, and eliminated important—and vastly different—roles at ­different
(Diamanti-Kandarakis et al., 2009). Hormones are stages of development (Bergman, Heindel, Jobling,
also known to induce downstream actions, includ- et al., 2013b; Diamanti-Kandarakis et al., 2009;
ing alterations to gene expression and subsequent Heindel & Vandenberg, 2015).
changes to tissue morphology and function. EDCs A number of prominent endocrinologists have
can block any—or all—of these steps; disruption suggested that studies evaluating compounds that
could involve up-regulation or down-regulation of interfere with one or more aspect of hormone
any of these steps as well (see Figure 6.2). action would be better informed if they under-
Hormones are synthesized and secreted from stood the principles of endocrinology (Beausoleil
­endocrine organs into the bloodstream, where they et al., 2013; Gore et al., 2006; Myers et al., 2009;

target cells
1

4a
an
org
ine
ocr

3
end

4b

1 - synthesis bloo
d ve
2 - secretion ssel
3 - transport
4 - binding 5
(a) membrane 4c
(b) cytoplasm
(c) nucleus
5 - metabolism target cells
6 - excretion

Figure 6.2 Hormone actions and disruption by endocrine-disrupting chemicals (EDCs).

92 Endocrine Disruptors and Other Influences on Hormone Action

L. H. Vandenberg, Colborn, et al., 2013; Zoeller (Norman & Henry, 2015). Only cells that express
et al., 2012). Five major principles dictate the study a hormone’s receptor will be responsive to that
of hormones: ­molecule. Altering the responses of cells, tissues, and
Principle 1. Hormones are responsible for coordi- organs to hormones can be mediated by changing
nating the tissues of the body from conception until the number of receptors or by altering the concen-
death (Diamanti-Kandarakis et al., 2009). Hormones tration of the hormone itself, either in circulation or
have essential roles at all life stages including embry- in the target tissue.
ogenesis, fetal development, birth, puberty, preg- There are a number of additional features about
nancy, parturition, and aging. Because hormones the interactions between hormones and their recep-
integrate the tissues of the body at all stages of life, tors that guide how hormones, and EDCs, are often
disrupting the endocrine system will produce dis- evaluated. One is the concept of binding affinity,
eases and other types of dysfunction that are specific which is a way to characterize the relationship be-
to the period of disruption, even if the diseases take tween the concentration of the ligand that is re-
years or decades to manifest (Heindel, 2005, 2008). quired to maximally occupy the ligand-binding site

one receptor (estrogens bind to estrogen receptor α

For example, exposure to synthetic estrogens such as of the receptor. Some hormones have more than

and β, for example), and some hormone receptors

the potent pharmaceutical estrogen diethylstilbestrol
(DES) while in the womb induces clear cell adeno-
carcinoma of the vagina that begins to manifest in have multiple isoforms (e.g., progesterone receptor).
puberty and breast cancer that begins to manifest If a hormone has a different binding affinity for the
in the fourth decade of life (Soto, Vandenberg, receptors or isoforms, it will influence the likeli-
Maffini, & Sonnenschein, 2008; Trichopoulos, hood of binding to each receptor, and thus influ-
1990). Mothers exposed to DES during pregnancy ence subsequent downstream effects, including
had modest increases in their own breast cancer gene expression. Binding affinity is a constant—
risk, but no increase in vaginal cancer (McLachlan, hormones have a specific binding affinity for each
Newbold, Burow, & Li, 2001). receptor.
Although most EDCs that have been identified With regard to EDCs, there is an expectation
and well studied disrupt the estrogen, androgen that binding affinity can be used to determine
(testosterone), and thyroid hormone signaling which compounds are “weak” or “strong” agonists.
­pathways, the number of hormones operating in the Using this approach, a binding affinity similar to
bodies of vertebrates, including humans, is much the natural hormone is interpreted to be a “strong”
greater. Thus, the signaling pathways controlled agonist. Unfortunately, this approach conflates
by these hormones are similarly large in number. binding affinity with potency, defined as the concen-
There is no reason to expect that EDCs will not tration of a compound that is required to produce
affect these different pathways as well, with likely a biological effect at a given intensity (Bergman
implications on the reproductive tract, brain, cardi- et al., 2015; Zoeller et al., 2014). Potency is thus
ovascular system, bone, immune system, metabolic endpoint specific, and may not necessarily be pre-
machinery, and others (Heindel, 2008; Schug, dicted by binding affinities. In fact, there are
Janesick, Blumberg, & Heindel, 2011). In fact, high- ­numerous examples where compounds could have
throughput screening assays for some of these “novel” binding affinities that are quite divergent but poten-
pathways are beginning to reveal novel endocrine- cies that are similar, at least for some endpoints. In
disrupting properties (Janesick et al., 2016). The these cases, compounds that bind to the receptor
concept of “obesogens” and metabolism-disrupting with much lower affinity compared to the endoge-
chemicals emerged, in fact, because of compounds nous hormone can have surprisingly “strong”
that could increase adipocyte number and size, ­effects—which closely mimic the actions of the nat-
alter function of the liver and pancreas, and induce ural hormone. For this reason, broad-stroke labeling
diseases, including type 2 diabetes and nonalcoholic of EDCs as “weak” estrogens, for example, should
fatty liver disease (Grun & Blumberg, 2009; be avoided. Furthermore, such labels often fail to
Heindel, Blumberg, et al., 2017; Heindel, vom Saal, consider life stage, another important feature of
et al., 2015). hormones (see Principle 4).
Principle 2. Hormones act via highly specific Principle 3. Hormones act at exceptionally low
binding to receptors. The activity of hormones is doses. Most hormones circulate in the blood at
­mediated by receptors, and hormones have highly ­part-per-billion (ppb) or part-per-trillion (ppt) con-
specific interactions with one or more receptors centrations (L. N. Vandenberg, 2014; Vandenberg

Vandenberg 93
et al., 2012). Specifically, circulating concentrations (A) 10
of hormones are typically in the ppt range for estra-

% receptors bound
8
diol, testosterone (in adult females), and thyroid
hormone; other hormones that circulate in the ppb 6
range include progesterone, testosterone (in adult 4
males), growth hormone, and prolactin (Jones, 1996).
2
These concentrations change depending on age and
physiological status (e.g., puberty, pregnancy). For 0
1 2 3 4 5 6 7
example, testosterone levels in human male neo- Hormone concentration (arbitrary units)
nates are typically in the range of 0.2 to 0.5 ng/ml.
(B)
These levels increase to 4 to 6 ng/ml in most adult 10
men, which is about a 10-fold increase. Similarly, 8
estradiol concentrations are typically in the range of

biological effect
50 to 100 pg/ml in women during the early follicu- 6
lar phase of the menstrual cycle, but raise to 600 pg/ 4
ml during the luteal phase, which is again about a
2
10-fold increase.
The specific interactions (described in Principle 0
2 4 6 8 10
2) between a hormone and its receptor(s) are re- % receptors bound
sponsible for the ability of hormones to have potent
effects at such low concentrations. There are several Figure 6.3 Nonlinear relationships between hormone
concentration, bound receptors, and biological effects.
specific factors responsible for these low-dose effects:
(A) A nonlinear relationship is observed between hormone
the ligand’s binding affinity for the receptor, the concentration and the percentage of receptors that is bound by
number of receptors, the concentration of the hor- the hormone. This means that the greatest increase in percent
mone, and the developmental stage when exposures bound receptors is seen in the low-dose range. (B) A nonlinear
occur (Barouki, Gluckman, Grandjean, Hanson, & relationship is observed between percent bound receptors and
biological effects. This means that the greatest change in
Heindel, 2012; Charlton, 2009; Lees, Cunningham,
biological effect is seen when relatively few receptors are bound.
& Elliott, 2004; Welshons et al., 2003). There is a
nonlinear relationship between the concentration
of the hormone and the number of bound recep- range, which is not “low” compared to hormone
tors, and a nonlinear relationship between the concentrations.
number of bound receptors and the induced bio- Another important feature that distinguishes
logical effect (Vandenberg et al., 2012). What this some hormones from EDCs is their transport in
means is that, at low concentrations, even small the blood. When steroid hormones are found in the
increases in hormone concentration will have large blood, they are distributed into three phases: (1)
biological effects; in contrast, at high concentra- free, representing the unconjugated, unbound form;
tions, the same increase in hormone level will have (2) bioavailable, representing hormones bound to
little biological effect (see Figure 6.3). Most hor- low-affinity carrier proteins such as albumin; and
mone receptors are actually unbound—a situation (3) inactive, representing the form that is bound to
previously termed “the spare receptor hypothesis” high-affinity binding proteins such as sex hormone–
(May, Moran, Kimelberg, & Triggle, 1967; Zhu, 1996); binding globulin (SHBG) or α-fetoprotein (Welshons
less than 10 percent of hormone receptors are typi- et al., 2003). For a hormone to be physiologically
cally bound at any time. Thus, small changes in active and thus capable of inducing biological ef-
hormone concentration translate to relatively large fects, it must be found in either the free or bioavail-
changes in the total number of bound receptors able phases. In contrast, many EDCs do not bind
(Welshons et al., 2003). In essence, the system is to these same circulating proteins; therefore, the
“primed” to respond to low doses of ­hormone and entire concentration of EDC found in the blood is
to small changes in hormone concentration. In the ­available and capable of inducing biological effects
context of EDCs, many of these c­ ompounds circu- (Dechaud, Ravard, Claustrat, de la Perriere, & Pugeat,
late in the ppb and ppt concentration range. Thus, 1999; Milligan, Khan, & Nash, 1998; Nagel, vom
it is not surprising that they can have biological Saal, & Welshons, 1999; Sheehan & Young, 1979).
­effects at these low doses. Some EDCs are found Although there is sufficient understanding
in tissues in the part-per-million concentration from multiple disciplines that hormones and other

94 Endocrine Disruptors and Other Influences on Hormone Action

s­ignaling molecules can have potent effects at low In humans, DES, the pharmaceutical estrogen
doses, there remains significant controversy about that was administered to pregnant women in the
“low-dose effects” in the study of EDCs. This is 1940s to 1970s, provides another example of the or-
­discussed in detail later in this chapter. ganizational versus activational effects of exposure
Principle 4. The effects of hormones depend on life (Bern, 1992). Mothers exposed to DES during preg-
stage (Heindel & Vandenberg, 2015; Wallen, 2009). nancy did not develop reproductive cancers or mal-
In over 50 years of study, endocrinologists have come formations, whereas their daughters, exposed during
to understand how the same hormone can have differ- gestation, had a significantly increased risk of clear
ent effects depending on the period of exposure. cell adenocarcinoma of the vagina and other repro-
Typically, exposures have been broken down into two ductive malformations. Further study revealed that
categories: exposures occurring during adulthood there were specific times during gestation when
and those occurring during development. Exposures DES induced the most harm in exposed daughters;
occurring in adulthood induce “activational” re- those that were exposed to the pharmaceutical
sponses because the individual will be activated to during the first 15 weeks of gestation had the high-
respond only as long as the hormone is present. est incidence of clear cell adenocarcinomas of the
An example of this is the use of pharmaceutical vagina and other vaginal and cervical pathologies
contraceptives, where women do not ­ovulate when (Mittendorf, 1995). These results indicate not only
exposed to synthetic estrogens like 17α-ethinyl estra- that prenatal development is uniquely sensitive to
diol (or estrogen plus progesterone combinations), estrogenic compounds like DES but also that for
but regain their fertility once they cease using these some health endpoints, the critical window of expo-
pharmaceuticals. In contrast, exposures occurring sure is even smaller.
during development (often characterized as embry- Principle 5. Hormones display nonlinear and even
onic or fetal exposures) induce “organizational” nonmonotonic relationships between dose and effect.
responses because they promote changes to the differ- As described earlier, the relationship between the
entiation of cells and organization of tissues. These dose/concentration of a hormone and the percent-
organizational effects of hormones can permanently age of receptors that are bound is nonlinear, such
alter the development of cells, tissues, and organs. that greater increases in bound receptors are ob-
Only recently have endocrinologists and devel- served in the low-dose range (Welshons et al., 2003).
opmental biologists realized that organizational A similar nonlinear relationship has been demon-
effects of hormones can extend beyond embryonic strated between the percentage of bound receptors
and fetal development to other periods of life. For and the biological effect that is induced, with a
some organs such as the brain, it is well established greater relative increase in biological effects observed
that development can continue for decades after in the low-dose range. For this reason, linear rela-
birth (Heindel, Balbus, et al., 2015). Other studies tionships between hormone dose/concentration
have revealed that some organs (e.g., the breast) and any biological outcome are unexpected if a
have critical windows of development at several dis- receptor mediates the effect that is being observed
­

tinct phases of life (embryonic, pubertal, pregnancy, (see Figure 6.3).

lactation), and thus organizational effects of hor- Many dose–response relationships that are ob-
mones occur during these critical periods (Macon served are nonlinear but are still monotonic; this
& Fenton, 2013). means that with increasing dose, the effect is always
EDCs have shown similar time-dependent ­effects. either increasing (see Figure 6.4A) or decreasing
For example, studies in rodents have shown that rela- (see Figure 6.4B), and although the slope of the line
tively large (mg/kg) doses of bisphenol A (BPA), an may change, the sign of the slope (either positive
estrogenic EDC, are needed to induce a uterotrophic or negative) does not. Yet, there are also many
response (an increase in the wet weight of the uterus) ­examples from the literature where the relationship
when exposures occur in adults (Kanno et al., 2003). between dose and effect are nonmonotonic, defined
Further, when exposures cease, the uterotrophic re- as a dose–response curve where the slope of the
sponse is similarly lost. Yet, much lower doses of line ­representing the dose–response curve changes
BPA during early d ­ evelopment (ng/kg) will shift the sign from negative to positive (or vice versa; see
phenotype of uterine cells, altering tissue organiza- Figure 6.4C; Kohn & Melnick, 2002). These kinds
tion permanently (Markey, Luque, Munoz De Toro, of curves are often referred to as biphasic, U-shaped,
Sonnenschein, & Soto, 2001; Markey, Michaelson, or inverted U-shaped. Nonmonotonic curves defy
Veson, Sonnenschein, & Soto, 2001). traditional ways of thinking of toxicants, where

Vandenberg 95
 (A) (B)
10 10

8 8

6 6
Effect

Effect
4 4

2 2

0 0
1 2 3 4 5 6 7 1 2 3 4 5 6 7
Dose Dose
(C) (D)
10 10
inhibitor of
8 cell proliferation
8 inverted
U-shaped
6 6

Effect
Effect

4 4
cell proliferation
2 2
U-shaped (promoter)
0 0
1 2 3 4 5 6 7 1 2 3 4 5 6 7
Dose Dose

Figure 6.4 Nonmonotonic relationships are common for hormones and endocrine-disrupting chemicals (EDCs). (A) Nonlinear,
monotonic relationship between dose and effect with a positive slope. (B) Nonlinear, monotonic relationship between dose and effect
with a negative slope. (C) Examples of nonmonotonic relationships between dose and effect. (D) Nonmonotonic dose responses can
manifest due to two overlapping monotonic effects that act on a common endpoint.

more of an exposure is anticipated to lead to more at higher doses, and desensitization of receptors
of an effect; consider the expected relationship be- (Vandenberg et al., 2012; Zoeller & Vandenberg,
tween poison and death, or consumption of sweets 2015). In the case of EDCs, nonmonotonic dose
and body weight. Yet, the literature contains many responses can also be observed when a compound
examples that illustrate nonmonotonic relation- binds to more than one hormone receptor and
ships; these are observed for essential nutrients and ­induces competing effects; some EDCs bind to one
vitamins, where both too much and too little of receptor at low doses and a second receptor at higher
these substances lead to dysfunction or death, and doses (Watson, Bulayeva, Wozniak, & Alyea, 2007;
optimal levels of exposure are in the moderate range. Watson, Jeng, & Guptarak, 2011).
Similarly, the relationship between water consump- There are hundreds of examples of nonmono-
tion and health is nonmonotonic; both too much tonic dose responses that have been observed for
and too little can lead to death. both hormones and EDCs (Vandenberg et al., 2012).
With regard to hormones and EDCs, the These nonmonotonic effects occur in cultured cells
­mechanisms by which nonmonotonic dose responses and in laboratory animals following controlled ad-
can be produced are now well understood. One ministration of compounds. Importantly, they have
mechanism is similar to what has been observed for also been observed in human epidemiology studies
vitamins and other essential nutrients: when levels examining environmentally exposed groups.
are too low, cellular function is disrupted, but high
levels (often achieved via exogenous hormone expo-
sures) can be overtly toxic. Other mechanisms that Controversies in the Study of
generate nonmonotonic dose responses include the Endocrine-Disrupting Chemicals
activation of negative- and positive-feedback loops A number of scientific statements and position
within the endocrine system, the overlapping effects papers from endocrinologists have been published,
of hormones acting on two monotonic responses that indicating that (1) a number of chemicals are known
influence the same endpoint (e.g., estrogens stimulate to disrupt the action of hormones; (2) humans and
both cell proliferation and inhibit cell proliferation; wildlife populations are exposed to these compounds;
see Figure 6.4D), the down-regulation of receptors (3) controlled exposures to these compounds induce

96 Endocrine Disruptors and Other Influences on Hormone Action

a range of effects, including effects associated with e­valuating the consequences of natural variability
disease, in laboratory animals; and (4) observational in hormone concentrations comes from the study
studies from wildlife and humans also demon- of intrauterine position in animals with litters,
strate associations between chemical exposures and ­including mice and rats. In mice and rats, male
adverse health outcomes (Diamanti-Kandarakis fetuses produce testosterone in midgestation (starting
et al., 2009; Gore et al., 2015; Zoeller et al., 2012). around gestational day 13/14 in mice), and some
Similar conclusions were drawn by other experts. of this hormone is transferred passively to neigh-
One report was published in February 2013 by the boring fetuses via the maternal blood supply
United Nations Environment Programme (UNEP) (J. G. Vandenbergh, 2004). Thus, pups (both male
and World Health Organization (WHO), entitled and female) positioned between two males are
“State of the Science of Endocrine Disrupting ­exposed to higher concentrations of testosterone
Chemicals – 2012” (WHO, 2013). Similar to the compared to pups positioned between two females.
scientific statements written by members of the Differences as low as 1 ng/ml testosterone in females
Endocrine Society, the 2013 UNEP/WHO report and 25 pg/ml estradiol in males have serious effects
concluded the following: (1) Data from controlled on a large number of phenotypes, including
laboratory studies confirm that chemicals can ­prostate development, mammary gland morphol-
­contribute to endocrine disorders. Many of these ogy, responsiveness to testosterone, aggressive be-
diseases have been observed in humans and wildlife haviors, steroid metabolism, age of pubertal onset,
populations. (2) Wildlife populations are affected by and ­estrous cycle length, among others (Ryan &
EDC exposures, with negative effects specifically Vandenbergh, 2002). Studies from human twins
observed on growth and reproductive endpoints. have also revealed that exceptionally low differences
(3) The methods that are widely used to identify and in hormone exposures during fetal development can
evaluate the safety of EDCs examine only limited influence health endpoints including reproductive
endpoints, missing a large fraction of the known success and risk of adult diseases like breast cancer
spectrum of endocrine-disrupting effects. As a result, (Vandenberg et al., 2012). Thus, intrauterine posi-
the methods used by decision makers, including risk tion and intrauterine exposures to endogenous hor-
assessors, to draw conclusions about chemical safety mones provide robust examples of low-dose effects
are likely underestimating the harmful effects of for natural hormones.
EDCs. Finally, (4) the increased risk of diseases due The low-dose hypothesis, originally articulated
to EDC exposures may be underestimated by regu- in the 1990s, postulated that EDCs have effects on
latory agencies around the world. exposed animals at doses that are thought to be safe
Other groups, including many researchers and for humans, and that humans are also affected by
advocates associated with the chemical industry, these same environmentally relevant doses (Davis
have denied these conclusions (Lamb et al., 2014, et al., 1993; Sharpe & Skakkebaek, 1993). With
2015; Nohynek, Borgert, Dietrich, & Rozman, 2013; regard to EDCs and other environmental chemicals,
Rhomberg, Goodman, Foster, Borgert, & Van Der the term low dose actually has a number of meanings
Kraak, 2012). Importantly, these individuals and (Melnick et al., 2002): (1) doses below those used in
the groups they represent often have financial in- traditional toxicology studies (i.e., doses below
terests in delaying action on EDCs (Bergman et al., those that induce overt signs of toxicity); (2) doses
2015; Zoeller et al., 2014). However, the debate over in the range of what humans are typically exposed
public health concerns about EDCs continues in to (e.g., environmental, not occupational, exposures);
scientific communities and among government and (3) doses that produce blood levels in experi-
decision makers. Next, we will discuss some of the mental animals that mimic the levels m ­ easured in
controversies that have arisen in the identification, humans, accounting for differences in how species
study, and regulation of EDCs. metabolize chemicals. Many studies use the term
low dose without specifically defining which of the
Can Endocrine-Disrupting Chemicals cutoffs detailed previously was used to determine
Have Effects at Low Doses? that the dose is low.
Studies evaluating the role of hormones in fetal These differing definitions for what constitutes a
development have confirmed how even small
­ “low dose” produce quite different cutoffs for the
­differences in hormone concentrations can influ- same environmental chemical. For example, the
ence physiological, morphological, and behavioral ­estrogenic chemical BPA has three different cutoff
endpoints. Perhaps the best studied system for doses based on these three definitions. For doses

Vandenberg 97
below those tested in traditional toxicology studies, f­actors are discussed further in the last section of
the cutoff dose would be set by the no observed this chapter.
adverse effect level (NOAEL) of 50 mg/kg/day
­ In 2012 and 2013, a group of 12 experts from a
(Welshons et al., 2003). For human exposure levels, range of scientific disciplines re-examined the low-
consumer product assessments estimate that expo- dose literature, concluding that low-dose effects
sures are in the range of ng/kg or low µg/kg daily have been demonstrated for a larger number of
(Lakind & Naiman, 2008). Finally, for doses that ­environmental chemicals (Vandenberg et al., 2012;
produce blood concentrations found in the general Vandenberg, Colborn, et al., 2013). Four com-
population, doses of 100 to 400 µg/kg/day would be pounds were evaluated in depth: (1) low doses of
set as the cutoff dose, although there is also contro- BPA on prostate weight and development, mam-
versy about whether this compound can be accu- mary gland development, and the response of the
rately measured in blood (Vandenberg, Hunt, mammary gland to secondary environmental chal-
Myers, & Vom Saal, 2013). Importantly, exposure lenges including stimulation with carcinogens; (2)
levels, urine/blood concentrations, and studies that atrazine and sexual development and differentiation
carefully determine how compounds are metabo- in amphibians; (3) dioxin and spermatogenesis in
lized are not available for the vast majority of chem- exposed rodents and humans; and (4) perchlorate
icals on the market. For this reason, establishing and thyroid function in humans. Approximately
evidence-based cutoffs to distinguish “low dose” two dozen additional compounds were found to
studies will be difficult and will require commit- have consistent low-dose effects on at least one end-
ments to produce these data by either chemical point (Vandenberg, Colborn, et al., 2013).
manufacturers or regulatory bodies. In 2017, the National Academy of Sciences con-
Considering these limitations, there are several ducted a systematic review of two chemical families
EDCs that have been well studied at low doses. In characterized as EDCs, phthalates and brominated
2002, the National Toxicology Program assembled flame retardants, and concluded that there was suf-
an expert panel to evaluate the published ­literature ficient evidence from the literature for low-dose
and found evidence for low-dose effects for four ­effects (National Academies of Sciences & Medicine,
compounds (Melnick et al., 2002): (1) DES, the 2017). Specifically, phthalates were shown to alter
pharmaceutical estrogen, induced effects on pros- anogenital distance and male hormone levels at low
tate weight after gestational exposures to low doses; doses, and brominated flame retardants were shown
(2) genistein, a phytoestrogen found in soy, pro- to affect learning, memory, and IQ at low doses.
duced effects on the volume of sexually dimorphic The National Academy selected just two case studies
brain nuclei in male rats, the morphology of the to evaluate the use of systematic review protocols
mammary gland in male rats, and the proliferation (discussed briefly later in this chapter) and as a
of immune cells after exposures to low doses; (3) proof of principle to demonstrate that low-dose
nonylphenol, a surfactant and industrial chemical ­effects are reproducible for these compounds.
with estrogenic properties, altered sexually dimorphic In looking at the kinds of conditions that have
nuclei in the brain, thymus weight, estrus cyclicity, been observed to be associated with low-dose ef-
and proliferation of immune cells in rats exposed fects, the endpoints include alterations in the size of
to low doses during perinatal development; and nuclei in the brain, alterations to the weight of
(4) methoxychlor, an insecticide with estrogenic ­endocrine organs (i.e., the prostate, uterus, and
properties, altered the immune system of rats ex- ovaries), metabolic disruptions (i.e., increased body
posed to low doses during perinatal development. weights, alterations to adipose differentiation, and
At that time, the expert panel also noted that both nonalcoholic fatty liver disease), reduced sperm
biological features and factors related to study count and abnormal sperm quality, altered mor-
design may impact the ability to detect low-dose phology of the mammary gland and increased sus-
­effects. For example, differences in animal species ceptibility to carcinogen challenges, expression of
and strains can influence responses to hormones and atypical behaviors (i.e., anxiety-like behaviors,
EDCs. Furthermore, the use of varying diets with hyperactivity, and disruptions to learning and
­
different concentrations of phytoestrogens, and memory), altered release or circulating concentra-
leaching of hormonally active compounds from tions of hormones (i.e., testosterone, corticosterone,
caging, water bottles, bedding material, and other and thyroid-stimulating hormone), abnormal tissue
environmental media, could interfere with the organization in hormone-sensitive organs (e.g., the
detection of effects from low-dose EDCs. These
­
prostate, thyroid, mammary gland, and uterus), and

98 Endocrine Disruptors and Other Influences on Hormone Action

others (reviewed in Vandenberg et al., 2012). These exposures are affecting human health. Hundreds of
endpoints are considered adverse to endocrinolo- environmental epidemiology studies suggest associ-
gists, developmental biologists, and physicians, and ations between EDCs and a range of health out-
therefore there is concern about low-dose exposures comes including obesity, infertility, attention deficit
to these compounds. hyperactivity disorder, cancers, anxiety disorders,
Based on the number of examples that have now thyroid dysfunction, IQ, and others (reviewed in
been evaluated by different groups, some scientists Gore et al., 2015; Vandenberg et al., 2012; Zoeller
(see Vandenberg et al., 2012) have argued that the et al., 2012). Importantly, these studies do not in-
low-dose hypothesis should not be considered a volve controlled or randomized exposures, and thus
hypothesis any longer. A significant body of evidence it can be challenging to draw conclusions about the
indicates that EDCs can induce adverse effects, causal relationships between exposures and effects.
including diseases that are relevant to human popu- Furthermore, many environmental epidemiology
lations, at doses in the range of human exposures. studies use cross-sectional study designs, where
­exposures and health outcomes are evaluated at the
Are Humans Exposed to Endocrine- same time, making it impossible to determine the
Disrupting Chemicals at Doses That temporal relationship between the two (e.g., does
Have Effects on Health? exposure cause the disease, or does having the dis-
Hundreds of compounds have been measured in ease influence exposure?). In the last decade, epide-
human blood or urine, with concentrations that are miologists have focused on building prospective
typically in the ppb or ppt range, although some cohorts, allowing exposures to be measured (often
are measured in the ppm range (e.g., Braun et al., during vulnerable periods of development) and indi-
2014; Kato, Wong, Jia, Kuklenyik, & Calafat, 2011; viduals to be followed over time to determine if they
Woodruff, Zota, & Schwartz, 2011; Ye, Zhou, Wong, develop diseases. These longitudinal studies, although
& Calafat, 2012). Many of these compounds are limited in number, have provided stronger evidence
characterized as EDCs. Examination specifically of for causal relationships between EDCs and disease
pregnant women shows that these individuals have outcomes (Bergman, Heindel, Kasten, et al., 2013;
dozens of chemicals, and specifically EDCs, in their Heindel, Skalla, Joubert, Dilworth, & Gray, 2017).
bodies at any one time. These findings are particu-
larly concerning because they provide unequivocal Are There Safe Doses of Endocrine-
evidence that the fetus is exposed to large numbers Disrupting Chemicals?
of chemicals during gestation (Arbuckle, 2010). But The traditional approach to the evaluation of toxic
the mere presence of these compounds in human compounds is to determine which (high) doses
tissues and fluids is not sufficient to conclude that induce morbidity and mortality, and then find
they are also causing harm. a (lower) dose where no such effects exist (see
Certainly, controlled studies of EDCs in labora- Figure 6.5). This point, below which adverse out-
tory animals provide evidence that effects on humans comes are not expected following exposures, is often
are anticipated. Yet, human epidemiology studies referred to as a “threshold” (Bergman, Andersson,
also provide support for the conclusion that EDC et al., 2013; Bergman et al., 2015). The absence of

10

6 no-threshold
biological effect

threshold
4

0
1 2 3 4 5 6 7
–2

–4
dose

Figure 6.5 No-threshold and threshold models for environmental chemicals.

Vandenberg 99
biological effects below this threshold dose is rarely Androgens produced by the fetal testis are responsible
demonstrated. This approach, where high-dose for development of the male reproductive tract and
­toxicity is extrapolated to low-dose safety, does not increase the size of the tissue between the anus and
appear to apply to hormonally active substances. the genitals (typically measured by either the base
This is because the endocrine system is already func- of the scrotum or the penis). For centuries, farmers
tioning within organisms, and therefore substances have used anogenital distance as a simple way to dis-
that alter receptor binding (by mimicking or block- tinguish male and female animals at birth because it
ing the actions of endogenous hormones) or other is a reliable and visible way to determine the sex of
aspects of hormone action (synthesis, secretion, me- animals, even at an age where other sexually dimor-
tabolism, etc.) are either adding or subtracting from phic features (e.g., the presence/absence of testes)
processes that are already ongoing; rather than a are difficult to discern. Antiandrogenic compounds
substance activating a system that is dormant (and decrease anogenital distance in males, even to the
might be considered to have a biological threshold point of making it problematic to distinguish the
for activation), the endocrine system is active and sexes (Gray et al., 2001). This effect is i­mportant
can readily be disrupted by small amounts of chem- not just because it makes it difficult to distinguish
icals that activate or antagonize it. male and female animals, but because in humans
In the threshold model, there is a dose below anogenital distance is predictive of a number of
which effects are not observed. Thresholds are as- health outcomes in men, including fertility, semen
sumed to exist for many environmental chemicals, parameters, and serum reproductive hormone con-
although they are rarely evaluated empirically. On centrations, among others (Mendiola, Stahlhut,
this graph, a threshold model is represented by a Jorgensen, Liu, & Swan, 2011).
dotted line, and the threshold is indicated by a black If there are no “thresholds” for EDCs, the logical
circle. For EDCs, thresholds are difficult if not impos- conclusion is that there are no doses that would not
sible to demonstrate because these compounds alter have at least some effect. The question is whether the
active biological processes. Thus, the no-threshold tools that are being used to evaluate those effects are
model can be used, where even minute quantities sensitive enough, and whether the sample size or
of EDCs are anticipated to have biological effects, population being examined is large enough to pro-
even if they cannot be measured experimentally. vide sufficient power to detect these effects. Rodent
The no-threshold model is represented by a solid studies evaluating carcinogens have found that
black line. thousands of mice are needed per treatment group
Some examples from endocrinology illustrate to determine which dose increases cancer incidence
the concept of an active endocrine system and how by just 1 percent (Littlefield, Farmer, Gaylor, &
it can be disrupted by EDCs that either “add” to Sheldon, 1980). These so-called mega-mouse stud-
or “subtract” from those active processes. The first ies suggest that even low doses of compounds could
­example comes from a relatively large literature dem- have effects with significant implications for public
onstrating that gestational exposures to estrogens— health, but the likelihood of detecting these effects
endogenous and exogenous—can contribute to in- in traditional studies (with sample sizes of 20 to 50
creased breast cancer risk (Soto et al., 2008). The per treatment group) is low.
embryonic mammary tissue expresses estrogen re- Another issue to consider when determining the
ceptors, yet the fetal ovaries produce little if any safety of EDCs is the types of tests and the end-
estrogen (depending on the species; Soto et al., points included in those tests that are used during
2008). Pharmaceutical estrogens like DES and es- hazard and risk assessment. As described earlier in
trogenic environmental chemicals like BPA can this chapter, standardized tests such as those used in
disrupt development of the fetal mammary gland, the EDSP Tier 1 and Tier 2 evaluate endpoints that
altering gene expression in the epithelium and
­ are globally recognized as toxicologically relevant.
composition of the stroma. These changes increase Tier 2 assays and other tests that follow prescribed
the sensitivity of the gland to hormones and car- methodologies (described as test guidelines) exam-
cinogens, contributing to increased risk of precan- ine endpoints that are described as “apical,” includ-
cerous lesions and carcinomas in adulthood. ing body weight and food consumption in the dam,
A second example is illustrated by the effect of time to pregnancy and length of gestation, number
antiandrogenic compounds like many phthalates on of pups and uterine implantation sites, sex ratios,
anogenital distance in both rodents and humans. gross morphology of exposed pups, weight of organs

100 Endocrine Disruptors and Other Influences on Hormone Action

in the exposed pups, and histopathology of repro- research setting. Shipping of animals, or movement
ductive organs in exposed pups. Are these the best within or between animal facilities, is stressful to
endpoints to evaluate EDCs, and low-dose effects animals and should be avoided during critical win-
more specifically? Although these endpoints are dows of development or periods of time relevant to
likely appropriate for assessing toxicity, they are not the exposure or evaluation. Handling of animals is
sufficient to evaluate the broad range of endocrine also stress inducing, even when care is given to pro-
diseases and dysfunctions that affect human popula- vide pain-free handling. Furthermore, differences in
tions. Suggestions have been made that traditional how experimenters handle animals can influence
methods for evaluating chemical safety should incor- the induction of stress. A recent study revealed that
porate more sensitive endpoints relevant to endocrine male experimenters induce greater stress responses
diseases, such as mammary gland morphology in in rodents compared to female experimenters,
whole mount preparations, sensitive behavioral assays and these heightened stress reactions can diminish
that test for sexually dimorphic behaviors, assays that the animals’ responses to painful stimulants (Sorge
evaluate cardiovascular and immune function, met- et al., 2014).
abolic assays that evaluate pancreatic function, tests In the context of EDCs, attention has been given
that examine endpoints relevant to thyroid hor- to how animals are exposed to environmental com-
mone action rather than simple measurements of pounds. In many cases, experimenters attempt to
serum hormones, and others (Gore et al., 2006; recapitulate human-relevant routes of exposure,
Myers et al., 2009). but the common means of oral exposure involves
gavage, a method where a needle is inserted into the
Beyond Endocrine-Disrupting Chemicals: animal’s mouth and passed through the esophagus
Other Environmental Influences into the stomach, where the test compound is re-
The environment plays an important role in disease leased. The process of gavage is stressful, does not
risk, severity, latency, and other features of high rel- truly replicate human oral exposures because it by-
evance to human and wildlife health. Understanding passes the oral mucosa, and can confound the
how much the environment, and which specific ­evaluation of environmental chemicals (Vandenberg,
­aspects of the environment, influences disease is an Welshons, Vom Saal, Toutain, & Myers, 2014).
important part of modern medicine and public
health. Many additional environmental factors can Food and Water
influence human health, including alcohol con- Researchers often do not pay attention to the type
sumption, use of pharmaceuticals, exposure to other of feed that is provided to their animals. Yet, numer-
pollutants, UV and other radiation exposures, ous studies have shown that rodent chow can have
­vibrations, and noise, among others. Acknowledging varying concentrations of chemical contaminants,
how environmental influences can affect controlled including pesticides and heavy metals that can in-
laboratory studies is also important, and deserves terfere with evaluations of EDCs, or can themselves
­attention from scientists working in a broad range induce biological effects (Mesnage, Defarge, Rocque,
of fields. Differences in environmental factors in Spiroux de Vendomois, & Seralini, 2015). Similarly,
animal facilities and other laboratory environments the composition of the feed, including the amount
may contribute to the “replication crisis” that has of phytoestrogens, the fat content, and the presence/
recently received attention in the scientific commu- absence of other essential nutrients, is an important
nity; many studies cannot be replicated, either in consideration for laboratory animal studies (Ruhlen
other labs or in the original labs that conducted the et al., 2011).
initial studies (Iqbal, Wallach, Khoury, Schully, & Most animal researchers provide water ad libi-
Ioannidis, 2016). Changes to environmental condi- tum, and otherwise do not think about how this
tions in laboratories cannot be discounted (Kolla, resource will affect their experiments. Not only
Pokharel, & Vandenberg, 2017). Next, other envi- should the vessel used to deliver water be consid-
ronmental features that can interfere with labora- ered (e.g., glass bottles, plastic bottles, unseen
tory studies are briefly described. ­plastic piping delivering water directly to cages),
but also the source of water is important. Pollutants
Stress and natural variation in minerals in water can in-
Laboratory animals experience stress from numer- terfere with experiments, leading some researchers
ous sources, many of which can be controlled in the to go to what may be seen as extremes (e.g., the use

Vandenberg 101
of reverse-osmosis purification systems) to treat understand and characterize not only the effects of
their water. EDCs but also their impact on societies. The first
is the use of systematic review methodologies to
Housing better synthesize data derived from in vitro, labo-
Other features of housing can contribute to stress ratory animal, wildlife, and epidemiology studies
and/or interfere with laboratory experiments. Caging (Vandenberg et al., 2016). Systematic reviews are
is clearly an important aspect of housing (Koehler common in the medical field and are important
et al., 2003), as is the material used for bedding and for drawing broader conclusions from multiple
any enrichment activities provided to animals (e.g., studies with approaches arising from disparate
cotton nestlets, wooden dowels, running wheels). fields. Systematic review methods allow research-
Researchers often provide enrichment materials ers to evaluate the quality of published studies and
only to animals that appear stressed, but this can determine the strength of the evidence for spe-
lead to uneven chemical exposures if the enrich- cific, directed questions (e.g., does chemical X
ment activity includes an unknown chemical con- cause disease Y?). Methods are being developed to
taminant. use systematic review methods to address much
Crowding is often controlled by institutional larger questions that are relevant to the study of
guidelines for animal housing, but solitary housing EDCs (Beronius & Vandenberg, 2016), such as
can also be stressful for animals that are social. For “What is the strength of the evidence that EDCs
rodents, long periods of isolation from other con- affect male fertility?”
specifics should be avoided, although this can be A final approach that has received attention uses
challenging when treatments (or age, or reproduc- tools from health economics to measure the cost of
tive status) induce aggression; this is common in EDC exposures to human populations and society.
adult male rodents. Using conservative estimates of the contribution
of EDCs to specific diseases, and examining only
Culling and Fostering a small number of chemicals, researchers have
Many researchers cull litters to maintain feasible ­assessed the annual health care cost of EDCs in the
experimental protocols and decrease animal care
­ European Union at more than €150B (Trasande
costs. Yet, culling can introduce (or remove) biolog- et al., 2015) and in the United States at more than
ical variability, depending on the outcome to be $200B (Attina et al., 2016). Thus, ignoring EDCs
evaluated. Culling has been shown to lead to catch- and their effects on endocrine diseases is a costly
up growth due to the restrictive nutrients experi- choice, both to human health and to the health
enced in utero with large litters and the sudden care economy.
availability of nutrients available via nursing when
the litter is smaller, altering body weight and met-
Conclusion
abolic endpoints (Suvorov & Vandenberg, 2016).
In humans, evidence is mounting that secular trends
Culling litters to change the overall sex ratio can
for many endocrine-related diseases and disorders are
also influence behavioral outcomes in pups, as can
increasing in prevalence (Bergman, Heindel, Jobling
rearing in single-sex litters, which occasionally is
et al., 2013a). Some of these conditions include
observed without the interference of culling.
­
infertility (male, female, and idiopathic); neu-
Researchers also often foster or cross-foster pups
robehavioral disorders including anxiety disorders,
­between litters to equalize litter size, optimize the
attention deficit hyperactivity disorder, and autism;
use of lactating females, or evaluate specific hypoth-
asthma and autoimmune disorders; birth defects in-
eses. Although most strains of mice and rats will
volving the male genital tract; endocrine-related
accept and care for fostered pups, this care does de-
cancers of the breast, ovary, prostate, thyroid, testes,
viate somewhat from the care that is provided to a
and uterus; early puberty in females; and metabolic
dam’s own pups (Francis, Diorio, Liu, & Meaney,
syndrome including obesity, type 2 diabetes, and
1999; Maccari et al., 1995).
nonalcoholic fatty liver disease, among others.
Although improved detection and changes in diag-
Emerging Issues for Endocrine-Disrupting nostic criteria may account for some of these in-
Chemicals in Public Health creases, evidence suggests that the absolute risk
A number of relatively new steps have been taken in for many of these conditions is increasing. These
the field of environmental health sciences to better changes are occurring not only in the developed

102 Endocrine Disruptors and Other Influences on Hormone Action

world but also in developing countries where toxicology journal editors. Environmental Health, 12, 69.
­noncommunicable diseases recently became more doi:10.1186/1476-069X-12-69
Bergman, A., Becher, G., Blumberg, B., Bjerregaard, P., Bornman,
common causes of death than communicable R., Brandt, I., . . . Zoeller, R. T. (2015). Manufacturing doubt
­diseases (Balbus et al., 2013). about endocrine disrupter science—A rebuttal of industry-
Because many of these changes in disease inci- sponsored critical comments on the UNEP/WHO report
dence have been observed over short periods of “State of the Science of Endocrine Disrupting Chemicals
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106 Endocrine Disruptors and Other Influences on Hormone Action

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Reproductive Behavior
 CH A PT E R

7 Investigating the Ovulatory Cycle

An Overview of Research and Methods

Lisa L. M. Welling and Robert P. Burriss

Abstract

An abundant amount of research into the human ovulatory cycle and related adaptive shifts in
preferences and behaviors has been published in recent decades. Evidence suggests that fertility in
women is accompanied by increased preferences for male traits that putatively signal underlying genetic
quality, adaptive increases in sexual motivation, and changes in attractiveness. Yet, these supposed
adaptive shifts remain controversial and disputed, while methods across studies have been inconsistent.
In this chapter, we review the research on phenotypic variation across the human menstrual cycle,
focusing on the related areas of preferences for male traits, sexual behavior and motivation, and cues
to ovulation. Next, we consider the various methods currently used by researchers to ascertain
conception risk and review recently published recommendations intended to guide future research and
facilitate comparison across studies.

Keywords: menstrual cycle, fertility, conception risk, mate preferences, mating behavior, attractiveness

Since the 1990s, the study of phenotypic variation Preferences for Male Traits
across the human ovulatory cycle has expanded The ovulatory shift hypothesis predicts systematic
greatly. Researchers have investigated cyclical effects variation in androphilic women’s behavior, specifically
on women’s sexual desires, preferences, mate choice, behaviors related to mating and mate preferences,
intrasexual competitiveness, physical appearance, over the course of the ovulatory cycle (e.g., Gangestad
and partner mate retention behavior, among other & Thornhill, 1998; Grammer, 1993; Thornhill &
constructs (reviewed by Gangestad & Thornhill, Gangestad, 1999). The likelihood of a woman con-
2008; Gangestad et al., 2016). However, as recently ceiving after a single act of intercourse (termed her
noted by Gangestad et al. (2016), the methods conception risk) varies over her ovulatory cycle, reach-
used by researchers to assess women’s fertility are ing a peak in the days preceding ovulation. As a
inconsistent, which hinders comparison across woman’s conception risk peaks, her preferences for
studies and led critics to question the validity and male traits that indicate good genes should likewise
robustness of findings. In this chapter, we review increase (Gangestad & Thornhill, 1998). Preferences
the evidence for phenotypic variation across the are not expected to remain constant because men who
human ovulatory cycle in three interconnected areas: possess good genes do not necessarily offer other
preferences for male traits, sexual behavior and potential benefits, such as resources and investment
motivation, and cues to ovulation. We then consider (Perrett et al., 1998). In fact, men who putatively
the various methods currently used by researchers to possess these good genes may be less attractive as
ascertain fertility status and review recently pub- long-term mates because they invest fewer resources
lished recommendations. in their partners (e.g., Penton-Voak & Perrett, 2001;

109
Perrett et al., 1998). Preference shifts are especially greatest at peak fertility (Macrae, Alnwick, Milne,
pronounced when women judge men for short- & Schloerscheidt, 2002), particularly when those
term, sexual relationships, as opposed to long-term, faces are masculine (L. Johnston, Miles, & Macrae,
committed relationships (e.g., Gangestad, Simpson, 2008). That said, the sexual relevance of the target face
Cousins, Garver-Apgar, & Christensen, 2004; Little is important, with lesbian women categorizing female
& Jones, 2012; Penton-Voak et al., 1999; Puts, 2005), faces more accurately at peak fertility (Brinsmead-
which is consistent with the hypothesis that these Stockham, Johnston, Miles, & Macrae, 2008).
patterns reflect evolved strategies for obtaining good Nevertheless, the validity of cyclic shifts in wom-
genes for offspring (Gangestad & Thornhill, 1998). en’s preferences, particularly relating to masculinity
Alternative functions, such as securing physical pro- preferences, has been questioned. A recent meta-
tection (Thornhill & Gangestad, 2008) or increasing analysis by Gildersleeve, Haselton, and Fales (2014a)
the probability of conception by copulating with a found evidence for robust cyclic shifts specific to
fertile mate (Puts, 2006), are also consistent with women’s preferences for hypothesized cues of male
these findings. genetic quality, at least when men were evaluated
Many studies have demonstrated fertile phase for a short-term (i.e., purely sexual) relationship.
increases in women’s preferences for men’s traits, However, the high number of studies included
including facial masculinity (V. S. Johnston, Hagel, in that meta-analysis that produced null findings
Franklin, Fink, & Grammer, 2001; Jones, Little, (60 percent) led others to argue that the few signifi-
et al., 2005; Little & Jones, 2012; Little, Jones, & cant findings are research artifacts (i.e., publication
DeBruine, 2008; Penton-Voak & Perrett, 2000; bias; Wood, Kressel, Joshi, & Louie, 2014) or the
Penton-Voak et al., 1999; Roney, Simmons, & Gray, result of “p-hacking,” whereby researchers adjust the
2011; Welling et al., 2007; but see Jones et al., parameters of their analysis to produce a desired
2018; Marcinkowska et al., 2016; Marcinkowska, result (Harris, Pashler, & Mickes, 2014). To address
Galbarczyk, & Jasienska, 2018), facial symmetry these concerns, Gildersleeve, Haselton, and Fales
(Little & Jones, 2012; Little, Jones, Burt, & Perrett, (2014b) constructed p curves of significant findings
2007; but see Cárdenas & Harris, 2007; Koehler, from their original meta-analytic data, finding that,
Rhodes, Simmons, & Zebrowitz, 2006; Mar­ consistent with their original report of robust cyclic
cinkowska, Galbarczyk, & Jasienska, 2018), the faces shifts, the p curves were right-skewed and had a
of bodily symmetrical men (Thornhill & Gangestad, large number of highly significant p values (p < .01),
2003), darker facial skin color (Frost, 1994), mascu- which is characteristic of a nonzero true effect
line body shape (Little, Jones, & Burriss, 2007; but (Simonsohn, Nelson, & Simmons, 2014). More
see Peters, Simmons, & Rhodes, 2009; Jünger, recently, in the largest study to date (n = 584) of
Kordsmeyer, Gerlach, & Penke, 2018; Marcinkowska, cyclic shifts in women’s preferences for masculine
Galbarczyk, & Jasienska, 2018), voices with mascu- male faces, Jones et al. (2018) used a within-subjects
line characteristics (lower fundamental frequency and design and found no evidence that preferences for
formant dispersion; Feinberg et al., 2006; Puts, 2005; facial masculinity are related to cyclic variation in
but see Jünger, Motta-Mena, et al., 2018), greater women’s steroid hormone levels. This suggests that
height (Pawłowski & Jasienska, 2005), and the odor menstrual cycle shifts, at least in terms of masculinity
of men who are more dominant, symmetrical, and preference, are not as robust as previously supposed,
heterozygous at major histocompatibility complex but future work of this scale (i.e., large within-subject
(MHC) loci (Gangestad & Thornhill, 1998; Havlíček, designs) should be conducted to assess preferences
Roberts, & Flegr, 2005; Rikowski & Grammer, for other physical traits.
1999; Thornhill & Gangestad, 1999; Thornhill Preferences for nonphysical traits, such as
et al., 2003). Although the ovulatory shift hypothe- dominant and intrasexually competitive behavior
sis predicts that women should be choosier at peak (Gangestad, Garver-Apgar, Simpson, & Cousins,
conception risk, some studies have documented that 2007; Gangestad, Simpson, Cousins, Garver-Apgar,
at periovulation women’s ratings of male attractive- & Christensen, 2004; Lukaszewski & Roney, 2009),
ness generally increase, including ratings of the courtship language (Rosen & López, 2009), and
face (Danel & Pawłowski, 2006), body (Jünger, creativity/intelligence (Haselton & Miller, 2006; but
Kordsmeyer, et al., 2018), and voice (Jünger, Motta- see Gangestad, Garver-Apgar, Simpson, & Cousins,
Mena, et al., 2018). Furthermore, women pay more 2007; Prokosch, Coss, Scheib, & Blozis, 2009), are
attention to attractive men (Anderson et al., 2010), also higher at peak fertility than at times when
and their accuracy at classifying faces as male is ­conception risk is lower. Guéguen (2009a, 2009b)

110 Investigating the Ovul atory Cycle

showed in two field studies that women may be more Larson, Pillsworth, & Haselton, 2012; Pillsworth &
receptive to courtship behavior at peak fertility. In Haselton, 2006; see also Meltzer, 2017, for findings
these two studies, women were more likely to agree related to masculinity and marital satisfaction), are
to a man’s request to dance or to share phone num- less symmetrical (Gangestad, Thornhill, & Garver-
bers if they were in the late follicular (fertile) phase Apgar, 2005), and have MHC alleles that do not
of their cycle (the phase directly preceding ovula- complement their own (Garver-Apgar, Gangestad,
tion), compared with the luteal phase (the phase Thornhill, Miller, & Olp, 2006). Although there is
following ovulation, when fertility is lower) and some evidence that women’s interest in their part-
menses. Other cyclic shifts have also been detected ners (as indicated by pupil dilation) is greatest at
at other points in the cycle. During the luteal phase, ovulation, a similar pattern is observed for responses
preferences increase for traits such as apparent to attractive opposite-sex celebrities (Laeng &
health (Jones, Little, et al., 2005; Jones, Perrett, et al., Falkenberg, 2007). Furthermore, sexual interest and
2005) and self-resemblance (DeBruine, Jones, & number of sexual encounters also peak during the
Perrett, 2005; Holzleitner et al., 2017), suggesting late follicular phase in lesbians (Burleson, Trevathan,
a motivation to promote affiliation with healthy & Gregory, 2002), suggesting that cyclical effects on
and related individuals prior to and during preg- motivation and behavior may not be related to fear
nancy. Corre­spondingly, increases in progesterone of pregnancy, proximity to men, or a reaction to
across the cycle are associated with increased sensi- male sexual advances.
tivity to social information (Maner & Miller, 2014) Women may be more competitive at peak fertility
and the salience of emotional displays indicating (e.g., Pearson & Schipper, 2013). Financially, women
danger (Conway et al., 2007). However, preferences are more likely to discount the future by preferring
for putative signals of investment have not been smaller rewards in the present over larger rewards later
shown to increase during this phase (Gangestad (Lucas & Koff, 2017), suggesting increased impulsiv-
et al., 2007), suggesting that these traits remain ity, although they do so less after viewing images
consistently attractive. of attractive males (Kaighobadi & Stevens, 2013).
Women are less cooperative and more likely to punish
Sexual Behavior and Motivation other women when playing an ultimatum game
Various cyclical effects are nullified when women during peak fertility (Eisenbruch & Roney, 2016;
judge men for a long-term rather than a short-term Lucas, Koff, & Skeath, 2007), especially if their
relationship (Gangestad et al., 2007; Haselton & opponent is attractive (Lucas & Koff, 2013). Perhaps
Miller, 2006; V. S. Johnston et al., 2001; Jones, relatedly, competition with same-sex rivals for access
Perrett, et al., 2005; Little, Jones, & Burriss, 2007; to desirable men also seems to increase with concep-
Pawłowski & Jasienska, 2005; Penton-Voak et al., tion risk, with women exhibiting two main strate-
1999; Puts, 2005; Rosen & López, 2009). This may gies for competing with same-sex rivals for male
be because women trade off good genes against attention: derogation of female competitors and
material benefits by securing as long-term partners appearance enhancement (Buss & Schmitt, 1996; al-
men who provision, while engaging men whose though it should be noted that men also use these
traits signify good genes as short-term or extra-pair intrasexually competitive strategies, see Fisher & Cox,
copulation partners (Gangestad & Simpson, 2000). 2010). Despite rating their own attractiveness more
In support of this hypothesis is evidence that women highly (Röder, Brewer, & Fink, 2009; Schwarz &
at high conception risk report greater sexual desire Hassebrauck, 2008), women derogate competitors
(Roney & Simmons, 2013), are more interested by judging their facial attractiveness more harshly
in extra-pair men (Gangestad, Thornhill, & Garver, (Fisher, 2004; see also Piccoli, Foroni, & Carnaghi,
2002), are less motivated toward sex for the pur- 2013; Vukovic et al., 2009; Welling et al., 2007) when
poses of intimacy (Sheldon, Cooper, Geary, Hoard, maximally fertile. Exposure to this derogation in turn
& DeSoto, 2006), are more sexually opportunistic causes men to lower their attractiveness judgments
(Gangestad, Thornhill, & Garver-Apgar, 2010), se- of the derogating females’ rivals (Fisher & Cox,
lectively flirt more with men who possess markers of 2009), demonstrating the effectiveness of this tactic.
genetic fitness (Cantú et al., 2014), are more likely Spending patterns also appear to reflect intrasexual
to visit a singles nightclub without their primary competitiveness: women at peak fertility are more
partner (Grammer, Jutte, & Fischmann, 1997), and willing to spend money on and choose products that
show greater interest in extra-pair men if their part- enhance appearance (Durante, Griskevicius, Hill,
ners are less attractive (Haselton & Gangestad, 2006; Perilloux, & Li, 2011; Hill & Durante, 2009),

Welling and Burriss 111

a­lthough the total amount of money they spend Cues to Ovulation
­remains the same (Röder et al., 2009). The long-held assumption that human females have
Additionally, women’s aversion to behaviors that lost estrus has been challenged by suggestions that
may be sexually maladaptive or dangerous is greater there may be physical and behavioral cues to a
at peak fertility, with increases in ratings of disgust woman’s cycle phase (for reviews, see Haselton &
toward incest (Fessler & Navarrete, 2003) and de- Gildersleeve, 2011; Thornhill & Gangestad, 2008).
creases in behaviors that may increase the risk of At peak fertility, women are more attractive in terms
rape (Bröder & Hohmann, 2003; but see Fessler, of facial appearance (Puts et al., 2013; Roberts et al.,
2003). Attention from unwanted suitors around 2004), odor (Gildersleeve, Haselton, Larson, &
peak conception risk could be tremendously detri- Pillsworth, 2012; Havlíček, Dvořáková, Bartoš, &
mental because rape at this time would be more Flegr, 2006; Kuukasjärvi et al., 2004; S. L. Miller
likely to lead to conception (i.e., would be more & Maner, 2011; Singh & Bronstad, 2001), and voice
reproductively costly), and so ancestral women (Bryant & Haselton, 2009; Pipitone & Gallup, 2008;
may have evolved “rape avoidance” strategies that but see Fischer et al., 2011). In fact, the scent of
they use more often during peak fertility than at an ovulating woman has a direct endocrinological
other times. Indeed, fewer women are raped near influence on men: men who smell T-shirts worn by
ovulation than would be expected by chance and women near ovulation, but not worn by women at
women engage in fewer behaviors that may put other cycle phases or T-shirts not worn by anyone,
them at risk of sexual assault (e.g., walking alone in experience an increase in their circulating testos-
a dimly lit area, going on a first date, going out to a terone levels (S. L. Miller & Maner, 2010), which
bar) when they are near ovulation, despite being is a response associated with sexual arousal (e.g.,
more physically active in general (see Chavanne & Stoleru, Ennaji, Cournot, & Spira, 1993). Women
Gallup, 1998). Women are more assertive during also have greater breast symmetry (Manning, Scutt,
times characterized by high estradiol and low pro- Whitehouse, Leinster, & Walton, 1996; Scutt &
gesterone (i.e., the late follicular phase; Blake, Manning, 1996), are perceived as more attractive
Bastian, O’Dean, & Denson, 2017) and perform by their romantic partners (Cobey, Buunk, Pollet,
better on a measure of physical strength after reading Kippling, & Roberts, 2013), and modulate their
a sexual assault scenario near ovulation (Petralia & appearance and clothing to enhance attractiveness
Gallup, 2002), which could reflect adaptive shifts (Durante, Li, & Haselton, 2008; Haselton, Mortezaie,
designed to thwart an attacker when conception is Pillsworth, Bleske-Rechek, & Frederick, 2007; Hill
most likely. Furthermore, women show greater bias & Durante, 2009; Röder, Brewer, & Fink, 2009;
against out-group men near ovulation (Navarrete, Schwarz & Hassebrauck, 2008; see also Meltzer,
Fessler, Fleischman, & Geyer, 2009), and this bias McNulty, Miller, & Baker, 2015, for findings re-
may depend on the extent to which women associ- lated to women’s weight loss goals) when they are
ate out-group men with physical formidability (i.e., most fertile. G. Miller, Tyber, and Jordan (2007)
they report a greater preference for familiar men investigated earnings through tips among female lap
when fertility is high, particularly if they perceive dancers as a function of menstrual cycle and contra-
unfamiliar men as being more physically intimidat- ceptive status. They found that lap dancers receive
ing; McDonald, Asher, Kerr, & Navarrete, 2011). larger tips at peak fertility compared to when they
Correspondingly, female gait has been shown to be were in nonfertile phases (menstruation and the luteal
more attractive during the luteal phase than during phase) of their cycle, whereas contraceptive pill users
the follicular phase (Provost, Quinsey, & Troje, 2008), showed no such variation. It is not clear which trait(s)
which the authors argue may serve to prevent fertil- drive this pattern. One possibility is that men are
ity from being widely advertised, as changes in gait responding to dynamic cues, such as change in a
are likely to be easier to detect at a distance than are woman’s scent (Thornhill et al., 2003), flirtation
changes in face shape or odor. If gait were to be (Cantú et al., 2014), or increased sexual opportunism
more attractive at peak fertility, male attention may be (Gangestad et al., 2010), which are known to vary
drawn indiscriminately, which may bring unwanted over the cycle (discussed earlier).
male attention. These inhibitory effects on motivation Further support for the existence of perceivable
may help to ensure that women less frequently per- cues to ovulation comes from studies of the effects
form behaviors that can lead to disadvantageous of a woman’s cycle phase on other persons. If selection
pairings or ill-timed/unwanted pregnancies. has acted on women to promote late-follicular-phase

112 Investigating the Ovul atory Cycle

copulations with high-quality and compatible men, Researchers might then determine whether the
one may also expect it to have acted on their long- ­dependent variables of interest vary as a function of
term partners to decrease the likelihood of infidelity cycle phase (e.g., Penton-Voak et al., 1999) or assess
and/or poaching. Three studies have suggested that the correlation between these dependent variables and
women at peak conception risk perceive their part- assigned conception risk probabilities (e.g., Gangestad
ners to be more proprietary and attentive (Gangestad & Thornhill, 1998), or both (e.g., Haselton & Miller,
et al., 2002; Haselton & Gangestad, 2006; Pillsworth 2006). However, although the various methods
& Haselton, 2006), and one has shown that men’s used to produce estimates of conception risk may
ratings of the dominant appearance of other men differ considerably in accuracy, to suggest that one
increase when their partners are fertile (Burriss & method is inherently “better” than any other is to
Little, 2006). Moreover, men whose proprietary overlook the fact that not all are applicable to every
behaviors increase most during their partners’ fertile situation. For example, it would not be practical to
phase have partners whose interest in extra-pair cop- draw blood for hormonal assay or use transvaginal
ulation increases most during peak fertility (Gangestad ultrasonography to check follicle growth at every
et al., 2002; Haselton & Gangestad, 2006). This sug- testing session for diary-, field-, or internet-based
gests that women’s attention to extra-pair men during studies. Thus, our discussion focuses on practical
estrus (and perhaps their tendency toward ornamen- techniques for maximizing accuracy in conception
tation, see Haselton et al., 2007) may drive their risk estimation for a variety of methods. We begin
partner’s increased attention to them. by outlining the less commonly used methods of
In sum, the variety and volume of studies inves- transvaginal ultrasonography, basal body tempera-
tigating human sexual behavior as a function of cycle ture, and cervical mucus qualities, and then review the
status are substantial, and the importance of collect- more popular self-report and hormonal assay meth-
ing accurate, comparable ovulatory cycle informa- ods. Lastly, we discuss conception risk values, which
tion is becoming increasingly evident (Ganges­tad can be used in conjunction with other techniques
et al., 2016). Next, we review the various methods (e.g., self-report).
of ascertaining conception risk, including recently
published recommendations for future research Transvaginal Ultrasonography, Basal Body
(Gangestad et al., 2016; Gonzales & Ferrer, 2016; Temperature, and Cervical Mucus Qualities
Jones et al., 2018). The most accurate method of identifying the timing
of ovulation is daily transvaginal ultrasonography.
Ascertaining Conception Risk This method involves the insertion of an ultrasound
Studies of ovulatory effects differ substantially in their probe into the vaginal canal to examine the ovaries
methods, which may explain some of the disparities and other reproductive organs. Transvaginal ultra-
between studies’ results (e.g., Little, Jones, Burt, & sonography can be used to precisely track follicu-
Perrett, 2007, vs. Cárdenas & Harris, 2007). Similar lar growth and release, and to correlate phenotypic
results might suggest that methodological differences changes to these underlying biological events (Cobey
between studies are not important, but differences et al., 2012, 2013). Although accurate, this method
impede comparison of results and some methods may is invasive and requires medical training and expen-
be more reliable than others (Gangestad et al., 2016). sive equipment. Therefore, transvaginal ultrasonog-
At a minimum, studies investigating ovulatory effects raphy is unlikely to be considered appropriate for all
must measure an aspect of the phenotype of a woman researchers when the focus is on cyclic shifts in mate
(or man, e.g., the woman’s primary partner) and preference or behavior.
relate it to estimates of the woman’s conception risk A simpler method of estimating the timing of
or hormonal profile. Estimating conception risk re- ovulation involves tracking a woman’s basal body
quires determining a woman’s position in her cycle temperature (BBT), which exhibits a periovulatory
(usually the day of her cycle when she participates increase and remains elevated throughout the luteal
in a study, with the day of the onset of menstrual phase (Marshall, 1968). The day of ovulation can be
bleeding classed as day one, or in relation to the approximated using the “three over six rule,” mean-
number of days before/after ovulation), or assessing ing that ovulation typically occurs on the first day of
her hormonal profile (by assaying samples of saliva, the first time in the cycle when BBT is higher for
blood, or urine) and assigning conception risk values three consecutive days than the mean of the preced-
or categorical phases according to actuarial data. ing six days (Marshall, 1968). Exceptions to this rule

Welling and Burriss 113

may be permitted if there is a spike in temperature on methods offer good overall accuracy (with neither
only a single day among six lower temperature days, high rates of false positives nor high rates of false
or if a rise in BBT can be accounted for by illness or ­negatives), are less invasive, and rely less on (poten-
other disturbances (Colombo & Masarotto, 2000). tially inaccurate) reports by participants. Importantly,
Participants may be given a chart on which to record although the more valid methods of estimating
­
their daily temperature readings (and menstruation cycle day involve monitoring physiological variables
days), or a commercially available temperature com- that change cyclically, including hormone levels,
puter may be used (e.g., the OvuTherm “Sophia,” BBT, and the appearance or consistency of salivary
Craig Medical Distribution). Temperature computer and cervical mucus, these methods are often imprac-
devices measure and record daily BBT readings and tical when predicting ovulatory status for scheduling
calculate the probable fertile days of the cycle testing sessions. For these purposes, researchers often
(Freundl et al., 2003). rely on self-report data.
The consistency of cervical mucus can also indicate
conception risk. Cervical mucus is typically thin, Self-Report
clear, and ductile during the follicular phase. After Location in the cycle can be quickly estimated via
ovulation, the mucus becomes more viscous and self-report, although women are often inaccurate
opaque (Colombo & Masarotto, 2000). In addition, when asked to estimate their cycle length (Jukic et al.,
follicular phase mucus crystallizes in a “ferning” 2008; Small, Manatunga, & Marcus, 2007) or last
pattern, which can be seen under a microscope menstrual onset (Waller, Spears, Gu, & Cunningham,
when a drop of mucus is placed on a glass slide and 2000; Wegienka & Baird, 2005). Self-report ques-
allowed to dry (Freundl et al., 2003). Mucus col- tions often target the date of the onset of menstrual
lected from the vulva can be palpated and examined bleeding for the previous or current menses. Providing
with the naked eye for opacity and consistency. a calendar or asking participants in advance to track
Because salivary mucus shows similar cyclic changes their menstruation using one of the several available
in ferning patterns, commercial kits may allow for mobile phone applications may help participants
examination of either cervical or salivary mucus report more accurately their cycle onset date, which
(Freundl et al., 2003). Ovulation generally occurs can then be used to establish the cycle day on which
on the last day of the cycle during which cervical the task is administered. The date of the onset of
mucus is thin, clear, and ductile and exhibits a fern- menses is usually classed as day one (i.e., a woman
ing pattern (Colombo & Masarotto, 2000). whose period began 10 days ago would currently
To compare the accuracy of various approaches be at day 11). Conception risk values or categorical
for detecting ovulation, Freundl et al. (2003) tested phases can then be assigned according to cycle day.
eight different methods of cycle monitoring, each on This method, usually called the “forward counting”
a sample of 14 to 16 women. The methods included method, is the easiest to use because it requires the
hormonal measures, BBT, mucus characteristics, or participant to provide only one date, usually at the
a combination of these methods. The true day of time the task is administered. No further contact
ovulation was determined by daily urinary luteiniz- with the participant is required and so it is frequently
ing hormone (LH) measurements and transvaginal employed in between-subject internet-based studies
ultrasonography. Temperature computer devices or when using a between-subject design in general
exhibited the lowest false-negative rate but high (e.g., Little, Jones, & Burriss, 2007; Little, Jones, &
rates of false positives, whereas the reverse was true DeBruine, 2008). The “backward counting” method
of examining mucus ferning patterns under a (sometimes called “reverse cycle day” or “backward”
­microscope. A hormone computer device based on method; see Gangestad et al., 2016), which predicts
LH and an estrogen metabolite showed intermediate the day of ovulation by counting back from the
false-negative and false-positive rates. The symp- onset of the menses phase subsequent to testing, is
tothermal method of natural family planning, in considered more reliable because the follicular phase
which women chart both daily body temperature and tends to be more variable in duration than the luteal
mucus characteristics, produced the greatest overall phase (Baird et al., 1995). The cycle day of interest
predictive accuracy. Thus, without transvaginal ul- in relation to ovulation is calculated by assuming that
trasonography, the most reliable approach is probably ovulation occurs 14 (Beckmann et al., 1998; Knaus,
to use two methods: one with a low rate of false 1929; Ogino, 1930) or 15 (Dixon, Schlesselman,
positives (mucus characteristics), the other with a low Ory, & Blye, 1980) days prior to the first day of the
rate of false negatives (BBT). However, hormonal next menstruation. Trussell, Rodriguez, and Ellertson

114 Investigating the Ovul atory Cycle

(1998) suggest that subtracting 13 days from a (Gangestad, Simpson, Cousins, Garver-Apgar, &
woman’s usual cycle length (i.e., 14 days before the Christensen, 2004), or fewer than 21 days (Bryant
next menses begins) provides a less biased estimate. & Haselton, 2009; Frost, 1994; Gangestad &
Women vary in the duration of their cycles, so a Thornhill, 1998), or omitting those who are more
further optional stage in this process is to transform than two standard deviations from a mean of 29 days
women’s estimated cycle days into their expected (Puts, 2005).
equivalents in a 28-day cycle, such that the cycle Although counting methods, and self-report
begins on day 1 and ends on day 28, and the actual methods in general, are less accurate than other
or estimated day on which ovulation occurs is day methods (e.g., transvaginal ultrasonography; Cobey
15 (Burriss et al., 2015; Puts, 2006). et al., 2012, 2013), their relative ­convenience for
There are two general methods of obtaining both researchers and participants makes their use
data that permit the backward-counting method. popular. To address which counting techniques are
The first method involves establishing probable most accurate, Gangestad et al. (2016) created
cycle duration (by soliciting reports of average more than 58,000 simulated cycles using published
­duration or having participants specify the dates distributions of the lengths of follicular and luteal
for more than one previous menstrual onset and phases. Using these data, they assessed the validity of
calculating the interval). It is then assumed that various counting methods and provided suggestions
the next menses will begin one expected cycle length for fu­ture research. Their analyses showed modest
after the previous known date of onset. This method validity (d range: 0.40 to 0.55) for most counting
is sometimes referred to as the “forward-backward meth­ods, and that backward-counting with a con-
counting” method and days can be classed relative firmed next menstrual onset (d = .70) and daily LH
to estimated ovulation (i.e., number of days before/ testing (d = .85) is most accurate. These authors
after). The second method involves having par- recommended the use of within-subject designs to
ticipants report back to the researcher the date of ensure sufficient power for analyses, as between-
onset of their first menses after testing has ended. subject designs require substantially larger sample
This method has the advantage of greater accuracy sizes for equivalent power (see Gangestad et al.,
and of providing data specific to the cycle during 2016, for power analyses). Moreover, researchers
which the participant has been tested. However, should use the backward-counting method with
this method cannot be used to schedule testing confirmed next menstrual onset and kits to detect
during the cycle of interest, and some participants the LH surge and/or assay reproductive hormones
may fail to provide further information after test- (Gangestad et al., 2016). In line with these sugges-
ing has finished, so it is prudent to use both meth- tions, Jones et al. (2018) outlined four common
ods in conjunction (e.g., Fales, Gildersleeve, & issues with cycle work: insufficient power, overuse
Haselton, 2014). of biased self-report methods, overuse of between-
Self-report methods have been employed success- subject designs, and testing hormones only twice in
fully in many studies but are not precise. Ovula­ the cycle (at estimated high and low fertility phases).
tion does not follow every menstruation (Wilcox, Taking the aforementioned suggestions and ad-
Weinberg, & Baird, 1995), and the opposite is also dressing these criticisms of menstrual cycle work
true (Check et al., 1989). Moreover, there is evidence may yield important insights into the relationships
that the duration of the luteal phase is not fixed and, among conception risk, hormones, and women’s
as with the duration of the menses and follicular behavior.
phases, can be highly variable (Stern & McClintock,
1998). Wilcox, Dunson, and Baird (2000) found Hormonal Assessment
that only 10 percent of women with 28-day cycles To measure hormone levels across the cycle,
ovulated precisely 14 days before menstruation. The ­researchers can have participants visit the laboratory
accuracy of self-report methods can be improved multiple times to provide several samples (i.e.,
by omitting women who report irregular cycles or saliva, blood, or urine) for hormonal assay across
abnormal cycle lengths. Cutoff points for abnormal one or more menstrual cycles (e.g., Jones et al., 2018),
cycle length vary across studies, with some authors or they can use counting methods to estimate the
omitting participants with cycle lengths in excess date of ovulation and test participants during the
of 28 days (Guéguen, 2009a, 2009b), in excess of fertile window and other points in the menstrual
40 days (DeBruine et al., 2005; Garver-Apgar, cycle when fertility is likely to be lower (e.g., Haselton,
Gangestad, & Thornhill, 2008), in excess of 50 days Mortezaie, Pillsworth, Bleske-Rechek, & Frederick,

Welling and Burriss 115

2007). Ovulation test kits provide a relatively inex- with the menstrual cycle. Menstrual cycle effects may
pensive and effective means of monitoring cycling be driven by estradiol (Feinberg et al., 2006; Garver-
hormones. Most over-the-counter ovulation test Apgar et al., 2008; Roney & Simmons, 2008; Roney
kits respond to levels of LH in urine or to both LH et al., 2011; Rosen & López, 2009; Rupp et al.,
and metabolites of estradiol, both of which peak at 2009), progesterone (Garver-Apgar et al., 2008;
midcycle. LH levels spike about one or two days Jones, Perrett, et al., 2005; Puts, 2006; Rupp et al.,
before ovulation (Garcia, Jones, & Wright, 1981; 2009), prolactin (Puts, 2006), cortisol (López, Hay,
World Health Organization, 1980). Urinary tests & Conklin, 2009), testosterone (Welling et al., 2007),
for the LH surge agree with results from ultraso- or a combination of these hormones (e.g., Puts
nography 97 to 100 percent of the time, making this et al., 2013). Also, different hormonal fluctuations
one of the most accurate tests available (Guermandi can be associated with different phenotypic changes,
et al., 2001). When researchers use ovulation test and it is unlikely that one hormone is singularly
kits, it is typically in conjunction with counting responsible for all noted cyclic shifts. Therefore,
methods; participants are generally scheduled for measuring change in multiple hormones over time—
study sessions according to self-report data and then not necessarily in conjunction with high versus low
take LH tests on several consecutive days around the fertility (e.g., across the day)—can yield important
time the surge is expected (e.g., Burriss et al., 2015; information about underlying mechanisms.
Haselton et al., 2007). Once researchers have con-
firmed an LH surge, they can be reasonably confident Conception Risk Values
that their participant is within the fertile window A woman’s daily conception risk is an estimate of
of their cycle. A further advantage of this method the average likelihood of her conceiving with a
is that the results of LH tests are available immedi- single unprotected copulation. After estimating
ately, which makes it possible for researchers to reac- the day of the cycle on which a participant has
tively schedule testing sessions. been tested, a researcher may determine that the
The preovulation rise in LH is also highly cor- day is inside or outside of the cycle’s fertile window
related with an increase in the ratio of estrogen or assign the day a conception risk value taken
to progesterone levels (Baird, Weinberg, Wilcox, from one of several studies. Daily conception risk
McConnaughey, & Musey, 1991; Baird, Weinberg, values may be reported by cycle day relative to the
Wilcox, McConnaughey, Musey, & Collins, 1991). onset of the previous menses (e.g., Jochle, 1973;
Consequently, the ratio of the levels of these hor- Wilcox, Dunson, Weinberg, Trussell, & Baird, 2001)
mones can also provide a fairly accurate measure of or relative to the day of ovulation (e.g., Wilcox
a woman’s proximity to ovulation (Wilcox et al., et al., 1995). Conception risk is strongly deter-
1995), even without the use of ovulation test kits to mined by the timing of copulation in relation to
confirm ovulation. Therefore, the experimenter can ovulation (Wilcox et al., 1995), and the number of
collect biological samples from participants, usually days since the onset of the previous menstruation
saliva (e.g., Welling et al., 2007) or urine (e.g., may be a poor estimate of a woman’s proximity to
Venners et al., 2006), at the time(s) of their partici- ovulation. For example, the 14th day after the
pation and then store the samples in a noncycling onset of menstruation may be very near ovulation
freezer before conducting hormonal assays. for a woman with a 28-day cycle, but probably sev-
In studies of cyclical phenotypic variation in which eral days away from ovulation for a woman with a
users and nonusers of hormonal contraceptives have 32-day cycle. Thus, greater precision in estimating
been separately tested, cyclical effects present in the fertile window facilitates detection of significant
nonusers have consistently not been present in users relationships between estimated conception risk
(e.g., Burriss & Little, 2006; Frost, 1994; Gangestad and preferences, behaviors, or attitudes. However,
& Thornhill, 1998; Guéguen, 2009b; Laeng & this is not to say that a narrower fertile window
Falkenberg, 2007; Little et al., 2007; Penton-Voak (e.g., six days) is necessarily preferable to a broader
et al., 1999; Puts, 2005). This suggests that these window (e.g., nine days): When a woman’s actual
effects are controlled by fluctuations in hormone date of ovulation is unknown, it is advisable to
levels and are not connected to changes due to assign a broader fertile window so as to increase
menstruation independent of ovulation (Gangestad the likelihood of including genuinely high fertility
& Thornhill, 1998). In other words, the underlying days (Gildersleeve, Haselton, & Fales, 2014b).
hormonal mechanisms, and not fertility per se, are Gangestad et al. (2016) assessed the optimal window
likely responsible for changes in behavior associated size and found that broader windows (eight to nine

116 Investigating the Ovul atory Cycle

days) are more likely to be valid, except when the Stirnemann et al. (2013) defined conception risk
backward-counting method is used and the date differently (i.e., probability of conception on a given
of ovulation is known (in which case the chances day vs. probability of being in the five-day fertile
of classifying a fertile day as a nonfertile day are window), validities of estimates using either method
reduced). Nevertheless, methods that rely on are roughly equivalent (Gangestad et al., 2016).
­continuous measures of conception risk rather than
discrete cycle windows are consistently more valid Conclusion
(Gangestad et al., 2016). The method researchers use depends largely on their
Estimates of daily conception risk values relative available resources and on their quasi-independent
to the day of ovulation are available from several variable of interest. If conception risk is the variable
sources (Barrett & Marshall, 1969; Bremme, 1991; of interest, it makes sense to exclude participants
Colombo & Masarotto, 2000; Schwartz, MacDonald, when there is evidence that their cycles are anovu-
& Heuchel, 1980; Schwartz, Mayaux, Martin-Boyce, latory. However, if a researcher is interested in un-
Czyglik, & David, 1979; Stirnemann, Samson, derlying hormonal mechanisms, then anovulation
Bernard, & Thalabard, 2013; Weinberg, Wilcox, matters less because there are still (albeit smaller)
Baird, & Gladen, 1998; Wilcox et al., 1995, 2001; hormone fluctuations across anovulatory cycles
Wilcox, Weinberg, & Baird, 1998), although some (e.g., Ellison, Lager, & Caffee, 1987). If a researcher
of these studies report reanalyses of the same data is interested in conception probability or the fertile
set. The appropriate values for use in menstrual effect window in general, it is preferable to estimate the
studies will depend on the quality of the methods day of a woman’s cycle on which she is tested rela-
and the sample size used in each conception risk tive to the day on which she ovulates rather than
study. The reliability of conception risk values in relative to the day on which her previous menses
these studies depends on both the precision in detect- began. The day of ovulation can most accurately be
ing ovulation and the proper attribution of preg- predicted via ovulation test kits or a combination
nancies to coital acts on the days on which concep- of BBT and mucus methods, with Gangestad et al.
tion occurred. As Colombo and Masarotto (2000) (2016) recommending the backward-counting
point out, attributing pregnancies to the coital method with participants’ confirmation of next
day closest to the presumed day of ovulation (e.g., menstrual onset and use of LH test strips to confirm
Bremme, 1991) produces a bias that artificially in- ovulation. Because underlying hormonal mecha-
creases conception risks nearer the day of ovulation. nisms, rather than fertility per se, likely drive men-
The model of Schwartz et al. (1980) produces the strual shifts in phenotype (e.g., Gangestad et al.,
best estimate of the day of conception for cycles in 2016; Roney & Simmons, 2013), multiple hormonal
which more than one coital act occurred (Colombo assays using within-subject designs with sufficiently
& Masarotto, 2000). Other researchers have used the large samples are preferred (Gangestad et al., 2016;
Schwartz et al. (1980) model and have sufficiently Jones et al., 2018). Furthermore, researchers relying
reliable methods for detecting ovulation—using BBT on counting methods are recommended to exclude
(Schwartz et al., 1980), BBT plus mucus ferning participants with irregular cycles or abnormal cycle
(Colombo & Masarotto, 2000), or the ratio of lengths at the recruitment stage (e.g., using a pre-
­estrogen to progesterone levels (e.g., Wilcox et al., screening questionnaire), rather than after data are
1998)—that we may consider their daily concep- collected, to avoid the appearance of p-hacking.
tion risk estimates reliable. Wilcox et al. (2001) Finally, none of the suggestions outlined in
provide conception risk values for each day of the this chapter necessarily invalidate findings of pre-
cycle (i.e., the probability of conception following vious studies whose methods differ from those
unprotected sex for each day of the cycle) using ­recommended here. However, the suggestions do
data from 696 cycles (213 women), and these values underline the need for replication of underpowered
are commonly used by researchers (e.g., Roney & studies and those studies using less than ideal
Simmons, 2008). More recently, Stirnemann et al. methods, as well as for preregistering methods to
(2013) calculated the probability of being within limit the opportunity for post hoc flexibility (Harris
a five-day fertile window for each day of the cycle et al., 2014). Our recommendations, like those
based on ultrasound measurements from 5,830 early outlined by Gangestad et al. (2016) and Jones et al.
pregnancies and determined that day 12 (using the (2018), are intended to serve as guidelines for future
forward-counting method) had the highest concep- research on menstrual effects and on the evolution
tion probability. Although Wilcox et al. (2001) and of human behavior in general.

Welling and Burriss 117

 As reviewed in this chapter, many menstrual Relations with menstrual cycle phase and partner availability.
cycle effects have been documented in the literature. Psychoneuroendocrinology, 27(4), 489–503. doi:10.1016/
S0306-4530(01)00066-X
These shifts in behavior, preferences, and appearance Burriss, R. P., & Little, A. C. (2006). Effects of partner conception
serve putatively adaptive functions that likely increase risk phase on male perception of dominance in faces.
the chances of reproducing, especially with optimal Evolution and Human Behavior, 27(4), 297–305. doi:10.1016/
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lying mechanisms can inform ultimate explanations Burriss, R. P., Troscianko, J., Lovell, P. G., Fulford, A. J. C.,
Stevens, M., Quigley, R., . . . Rowland, H. M. (2015). Changes
for human behavior. Despite recent controversies in women’s facial skin color over the ovulatory cycle are not
(e.g., Gildersleeve et al., 2014a, 2014b; Harris et al., detectable by the human visual system. PLoS One. 10(7),
2014; Wood et al., 2014) and inconsistencies (see e0130093. doi:10.1371/journal.pone.0130093
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fruitful area for further investigation. competition derogation: Sex and conflict effects on perceived
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 CH A PT E R

8 Reproductive Behavior in the Human Male

Stefan M. M. Goetz, Glenn Weisfeld, and Samuele Zilioli

Abstract

Given the pivotal role of differential reproduction to the evolutionary success of ancestral men,
evolution has produced a plethora of reproductive strategies aimed at solving the complexities of
intramale competition and satisfying and/or thwarting the reproductive desires of women. Life history
theory recognizes that an organism has limited resources and must invest energy appropriately.
Broadly, reproductive strategies can be dichotomized into short-term (emphasizing mating over
parental effort) versus long-term (emphasizing parenting over mating effort) strategies. Increasingly, the
neuroendocrine system—especially testosterone—has been recognized as the proximate mechanism
orchestrating adoption of one strategy over the other. This chapter reviews behaviors geared toward
solving problems associated with both long-term and short-term reproductive strategies and discusses
the neuroendocrine correlates. The adoption of one strategy over another is conceptualized as
conditional or facultative adaptations in which strategic switching points are tuned over evolutionary
time to produce optimal fitness responses to men’s social and physical conditions.
Keywords: reproduction, reproductive behavior, mating, parenting, male strategies, short term, long
term, testosterone

Differential reproduction is the driving force behind societies become less egalitarian, the men–women
evolution, altering the relative proportion of alleles difference only intensifies, with men vying for and
in the population. Men, and male mammals in gen- leveraging status and resources to monopolize a
eral, exhibit greater variance in reproduction relative greater proportion of fertile women (Betzig, 1986).
to women (i.e., asymmetric reproductive skew; Geary, Clearly, men in different socioecological and physi-
1998; Jokela, Rotkirch, Rickard, Pettay, & Lummaa, cal conditions face different reproductive challenges
2010), so much so that men such as Ismail ibn and opportunities with significant fitness implica-
Sharif (the warrior king) is estimated to have sired tions. These challenges drive the evolution of men’s
upward of 888 children, overshadowing the count- mating strategies.
less childless bachelors. In contrast, the most children Traditionally, evolutionary psychologists have
any one woman has ever birthed is 69, in a total of anchored the study of men’s reproductive strategies
27 births (Bateman & Bennett, 2006). Although along a single continuum ranging from short-term to
these are extreme examples, they are illustrative of
the general pattern. Among modern-day hunter-
However, there is some debate as to whether modern-day
gatherers, men’s reproductive variance is about twice hunter-gatherers provide a valid model to form inferences about
that of women’s1 (Betzig, 2012). Furthermore, as our ancestral past given that modern-day hunter-gatherers
primarily inhabit geographically marginal habitats, face pressure
from neighboring agricultural societies, and are not free from
1
This ratio was calculated based on data from Betzig (2012, acculturational influences of state-level societies (Walker, Hill,
Table 1), which included five hunter and gatherer societies. Flinn, & Ellsworth, 2011).

125
long-term mating strategies, designating short-term provisioning—the further division of reproductive
strategies with the moniker “cad” (polygynous and effort into mating and parental effort is particularly
uninvolved with childcare) and long-term strategists relevant to men’s life history strategies. For instance,
with the moniker “dad” (monogamous and involved in socioecological contexts in which paternal invest-
with childcare; e.g., Buss & Schmitt, 1993). ment is decoupled from offspring reproductive suc-
Although Western societies do not permit polyga- cess, men may gain greater fitness returns by divest-
mous marriages,2 approximately 20 to 40 percent ing from parental effort in favor of mating effort.
of men engage in an extramarital affair in their Indeed, given that parental effort is not an obligate
lifetimes (Greeley, 1994). Furthermore, the reproduc- adaptation in men, under some circumstances men
tive consequences of serial monogamy—in which can follow mating strategies that require no more
men and women can have several consecutive than the investment of producing sperm and gain-
partners—­resemble those found in polygynous so- ing sexual access to fertile women. However, when
cieties. Indeed, in the United States, men who had paternal investment and offspring reproductive suc-
married and remarried three or more times had 19 cess are closely related, men gain by investing more
percent more children than monogamously married heavily in parenting effort (Sear & Mace, 2008).
men ( Jokela et al., 2010). By utilizing more than These strategies can be viewed as “alternative mating
one woman’s reproductive lifespan, a man can en- strategies.”
hance his reproductive success ( Jokela et al., 2010).
Following an exclusively monogamous or polygy-
nous mating strategy represents extremes in men’s Alternative Mating Strategies
life history strategies,3 with varying fitness conse- Where life history strategies are discussed in terms
quences conditioned upon the socioecological and of reproduction, evolutionary biologists view them
sociocultural environment (Laland & Brown, 2011). as alternative mating strategies. Parsing the compara-
tive data, three broad categories of alternative mating
Life History Theory strategies have been identified: pure alternative,
Life history theory is a branch of evolutionary biology mixed, and conditional strategies (see Gross, 1996).
focused on the issue of energy allocation “choices” Pure alternative strategies are produced by genetic
an organism makes over its lifespan to maximize polymorphic differences in the population. That is,
biological fitness4 (Ellis, Figueredo, Brumbach, allelic differences underpin static phenotypes that
& Schlomer, 2009; Hill, 1993; McNamara & emerge in populations through frequency-dependent
Houston, 1996; Roff, 2002). These choices reflect selection. For example, negative frequency-­dependent
evolved resource allocation strategies, determining selection occurs when the relative fitness of a trait
the timing, rate, and extent of somatic growth and (e.g., psychopathy) depends on its rarity in the pop-
investment (e.g., immune function); reproductive ulation. Theoretically, frequency-dependent selection
maturity; fecundity; mating effort; parental effort; can maintain genetic polymorphisms in a population5
and senescence. All organisms have limited resources (Maynard-Smith, 1982). Mixed strategies, in contrast,
in the currency of both time and energy; how they are not underpinned by allelic polymorphisms,
are allocated is balanced as a function of historical but rather by organisms enacting each alternative
selection pressures that optimize the cost–benefit phenotype in some fixed proportion that is invari-
ratio of investing in each (e.g., Hill, 1993). ant at the population level. Phenotypic heterogeneity
Broadly, energy is allocated into various forms of is the product of each organism following a proba-
somatic investment and reproductive investment. bilistic allocation strategy. Finally, the third form
Due to the altricial nature of our species—offspring is that of conditional strategies. In contrast to pure
are born immature and require a long period of strategies, conditional strategies are underpinned by
a common genetic architecture but differ from mixed
2
A survey of world cultures indicates that 80 percent of the strategies, whereby each alternative is not determined
139 societies recorded in the standard cross-cultural sample probabilistically, but rather as a consistent response
permit polygynous marriages (Murdock & White, 1980).
3
In evolutionary biology, the term strategy denotes an
organism’s phenotype—behavioral, morphological, physiological,
and psychological—produced in response to both environmental 5
Under normal circumstances, the relative fitness conferred
input and genetic factors. The term does not imply conscious by an allele causes that allele to become “fixed” (i.e., all other
choice. versions are selected against) within a population. The variance
4
Biological fitness refers to an organism’s reproductive success around an optimal trait is due to genetic noise (i.e., random
in passing on genes through the production of offspring or kin. mutations and/or developmental insults).

126 Reproductive Behavior in the Human Male

mechanism6 to the conditions faced by an organism—­ ment (see Bass, 1996). Each male has the genetic
both external and internal—at several key develop- program to produce either morph, with the determin-
mental stages (e.g., Del Giudice, 2009). ing factor activating each morph being the degree of
Across the animal kingdom, few instances of reproductive competition (i.e., frequency of morphs).
pure genetic polymorphic strategies have been iden- Looking across nonhuman primate societies, this
tified.7 Rather, within-species differences in strategies clearly is the rule. Males in different positions within
are best explained by conditional and/or facultative the hierarchy adopt alternative reproductive strategies
adaptions to local conditions. Much like sexual dif- (e.g., sneaking copulations or forming temporary
ferentiation, within-sex phenotypic variation relies consortships away from the group rather than facing
on differential expression of genetic programs; that reproductive oblivion at the hands of a dominant
is, the basis for the strategies is instantiated in a ge- male). For instance, the sexual strategies observed in
netic architecture that is conditionally expressed by a population of chimpanzees from Tanzania were
the varying socioecological challenges faced by an flexible and consisted of three distinct strategies
organism (Gross, 1996). (Tutin, 1979). Males either followed an opportunis-
Conditional strategies do not necessarily require tic, possessive, or consortship mating strategy, with
equal fitness to be maintained within the population; the latter producing the greatest fitness dividends,
however, fitness is equal across options in contexts save for if the male was the alpha, in which case fol-
where a switching point exists. Stated differently, at lowing the possessive strategy was optimal. Indeed,
a given switch point, one strategy will lead to equal the strategy adopted was clearly linked to character-
fitness as adopting another strategy (see Gross, 1996). istics of the individual (e.g., age, physical condition,
For example, theoretically, there should exist a point and dominance position) and by social factors
at which the socioecological conditions facing, say, (e.g., stability of dominance relationships).
a subordinate male chimpanzee provide equal fit- The discussion of men’s mating strategies that
ness outcomes whether he adopts a possessive mating follows takes the perspective that men’s reproductive
strategy or a sneaky mating strategy. Beyond that life history strategies are conditional adaptions, in-
point, however, following one strategy over the other duced by neuroendocrine responses to the environ-
will produce different fitness outcomes. A subordi- ment. Indeed, because these adaptations require that
nate male who continues to try to pursue a possessive whole sets of mechanisms (both psychological and
strategy will leave fewer offspring than a subordi- behavioral) work in concert, the neuroendocrine
nate male who adopts a sneaky mating strategy, system represents a viable m ­ echanism for orches-
ceteris paribus. trating these changes. Not only does the endocrine
One oft-cited example can be seen in the various system respond to environmental stimuli, but also
reproductive strategies expressed by male bluegill its effects are systemic, thus enabling gene expres-
(Lepomis macrochirus; Gross, 1991). Large males sion across diverse neural and somatic tissues (Cox,
establish and defend a nest, enticing females to lay McGlothlin, & Bonier, 2016; Xu et al., 2012).
their eggs where they are then fertilized and defended
by the male. However, when the proportion of males Life History Strategies
following this strategy is high, it creates a niche for Traditionally, life history theory focused on
smaller males to develop a pseudo-female morph, ­cross-species comparisons, organizing species and
allowing them to sneak past a larger male’s defense taxa along an r-selected (rapid reproduction) to
and fertilize the eggs in his nest. Biologists have ­K-selected (slow reproduction) continuum, with scant
determined that these morphs are likely not pro- consideration given to within-species differences
duced through genetic differences between morphs (e.g., Pianka, 1970). What attention that was given
(e.g., in the case of pure alternative strategy), but to within-species differences was viewed as genetic
rather are the result of differential gene expression and developmental noise. More recent work has begun
induced by perception of the male’s social environ- to consider the possibility that within-species varia-
tion represents adaptive responses—adaptive plas-
6
But there are polymorphic alleles underpinning different ticity (West-Eberhard, 2003)—to the environment,
“reaction norm” profiles (see Manuck, 2010). particularly the early developmental environment
7
For example, the marine isopod Paracerceis sculptta has three (e.g., Del Giudice, 2009; Del Giudice, Ellis, &
mating phenotypes: larger fighter males, medium-sized males
Shirtcliff, 2011). Taking this latter approach, a hand-
that mimic females, and small sneaker males. These three morphs
are due to three alleles at a single autosomal locus (Shuster & ful of evolutionarily minded researchers have begun
Wade, 1991). using a fast–slow life history strategy distinction to

Goetz, Weisfeld, and Zilioli 127

explain individual differences from an evolution- history strategies (Del Giudice, 2009). For instance,
ary perspective (e.g., Belsky, Steinberg, & Draper, father absence, indicative of low parental invest-
1991; Del Giudice, 2009; Griskevicius, Tybur, ment, may lead to the development of a fast life his-
Delton, & Robertson, 2011). tory strategy (Draper & Harpending, 1982). Current
Slow strategies are characterized by slower rates reproduction is favored over later reproduction,
of development and later onset adrenarche, puberty, which is achieved by setting sexual maturation
and senescence. Behaviorally, slow life history earlier and lowering one’s own parental investment
strategies entail later sexual debut, fewer sexual part- (i.e., a quantity-over-quality approach to reproduc-
ners, stable reproductive relationships, later ages of tion; Chisholm, 1993).
reproduction, fewer offspring, and greater parental in- The experience of an unpredictable environment
vestment in offspring. Patterns of risk taking also during development in males engenders what
differ, with slow strategists tending to have longer Wilson and Daly (1985) termed the young male
time horizons, lower impulsivity, and greater aversion syndrome—a pattern of increased competitiveness,
to risk in general. Essentially, slow strategies involve risk taking, and violence that represents heavy in-
greater investment in somatic and parental effort. In vestment in mating effort at the expense of later re-
contrast, fast life history strategies entail less invest- production. For instance, sons from father-absent
ment in somatic and parental effort, instead favoring households—which may be indicative of mating
investment in mating effort (Griskevicius et al., 2013). low commitment and/or high mortality risk—are
Although these differences are in part driven by more aggressive and display hypermasculine behav-
genetic polymorphisms within human populations ior, consistent with heighted male–male competition
(Day et al., 2016; Plomin, DeFries, Knopik, & associated with a fast life history strategy (Draper &
Neiderheiser, 2013), much of the current spate of Harpending, 1982). Similarly, attachment relation-
research has focused on adaptive plasticity compo- ships in infancy and early childhood may serve as a
nents (e.g., Del Giudice et al., 2011). Furthermore, “Socioassay” (Chisholm, 1993), whereby the child
behaviors indicative of fast and slow life history gathers information about the danger and predicta-
strategies can be acutely induced, indicating that bility of the environment, thus (eventually) balanc-
life history strategies are not wholly genetically or ing trade-offs between current and future reproduc-
developmentally determined (Arnocky, Woodruff, & tive investment and mating and parenting effort
Schmitt, 2016; Griskevicius et al., 2013). Nevertheless, (Del Giudice, 2009). Intriguingly, sex differences in
adaptive plasticity of life history strategies stands to attachment emerge during middle childhood (and
explain many key individual differences observed by persist into adulthood) such that boys raised in risky
developmental psychologists and offers a framework environments tend to develop avoidant attachment
for bringing the study of individual differences under styles, whereas girls raised in risky environments tend
the auspices of evolutionary theory. to develop anxious attachment styles (Corby, 2006;
Del Giudice, 2008; Finnegan, Hodges, & Perry, 1996;
Adaptive Plasticity in Life History Strategies Granot & Mayseless, 2001; Karavasilis, Doyle, &
Examining the environmental antecedents of these Markiewicz, 2003; Toth, Szollosi, Danis, Green, &
strategies can elucidate the evolutionary pressures Gervai, 2006). Del Giudice (2009) proposed that
that these strategies evolved to address. The factors an avoidant attachment style may be a compo­nent
that appear to be the primary driver of variance in mechanism of the psychological architecture un-
life history strategies are cues to extrinsic risks—that derpinning short-term mating strategies, promoting
is, risks that are independent of an organism’s behav- a plurality of reproductive relationships.
ior, such as mortality due to war (Quinlan, 2007).
The translation of parental effort to offspring fitness Manifestations of Mating Effort
reaches a saturation point, at which additional effort Short-term mating can be construed as a zero-sum
does not increase offspring fitness. Importantly, the contest given that, ultimately, fertilization cannot
position of this point along the parental effort contin- be shared. Furthermore, sexual access to women
uum varies as a function of environmental risk and quickly becomes a limiting resource, especially when
is lower in high-risk environments (Quinlan, 2007) considering sex differences in desires for uncommit-
and in contexts in which paternity certainty is low ted mating (Buss & Schmitt, 1993; Symons, 1979).
(Geary, 2005). Thus, parental effort itself can be used Thus, these factors set the stage for heightened
as a developmental cue about the predictability of ­intramale contest, particularly in short-term mating
the environment, guiding the development of life domains (Ainsworth & Maner, 2012).

128 Reproductive Behavior in the Human Male

 One natural consequence of zero-sum contests traits and behaviors (e.g., risk taking and aggression)
over limited resources is the emergence of dominance that facilitate short-term mating may be favored
hierarchies, which are a ubiquitous feature of pri- (Ellis et al., 2012).
mate societies (e.g., Cummins, 2000). As described Testosterone likely functions to balance these risks
by the priority-of-access model, through dominance by allocating resources toward reproductive effort.
relations, access to mates is regulated such that more Specifically, testosterone may increase manifestations
dominant individuals generally are granted greater of mating effort—intrasexual competitive motivation
access to fertile mates (Altmann, 1962; Dubuc, (Carré & Olmstead, 2015), risk taking (Apicella,
Muniz, Heistermann, Engelhardt, & Widdig, 2011). Dreber, & Mollerstrom, 2014), and mate-seeking
Given the relationship between reproductive success behavior (van der Meij, Almela, Buunk, Fawcett, &
and dominance position (Betzig, 1986; Turke & Salvador, 2012)—and divert resources away from
Betzig, 1985), evolution has produced adaptations somatic effort (for review, see Bribiescas, 2001). It
that bias men toward gaining/defending status and should be noted, however, that other androgens
navigating dominance hierarchies (e.g., Griskevicius have also been implicated in mediating these trade-
et al., 2009). Indeed, this is reflected in our emo- offs; for instance, levels of dehydroepiandroste-
tional motivation system, in which status itself is a rone (DHEA) and dehydroepiandrosterone sulfate
powerful motivational goal (Huberman, Loch, & (DHEAS) during adolescence may impact later
Önçüler, 2004). Infants as young as 10 months old adult attachment styles, putatively in the service of
can extract dominance relationships between two supporting differential life history strategies (Del
novel “actors” (Thomsen, Frankenhuis, Ingold-Smith, Giudice, 2009).
& Carey, 2011), and judgments of other people’s One stark demonstration of testosterone’s poten-
dominance are made within milliseconds and are tial role in mediating the trade-off between somatic
fundamental to how they are evaluated (Carré, effort and mating effort is provided by the recent
McCormick, & Mondloch, 2009). Furthermore, practice of male castration in Korea. Removing the
dominance hierarchies form quickly among unac- primary source of androgen production in these
quainted men8 (Cheng, Tracy, Foulsham, Kingstone, men appears to result in increased longevity com-
& Henrich, 2013; Rosa & Mazur, 1979). pared to intact controls, potentially indicating that
In many social contexts, competition for domi- normal levels of testosterone actually lead to short-
nance position is therefore often integral for men to ened lifespans by facilitating traits associated with
achieve reproductive success (Ainsworth & Maner, reproductive effort (e.g., aggression and risk taking;
2012; Griskevicius et al., 2009). However, competing Min, Lee, & Park, 2012). Furthermore, testosterone
for dominance can entail heavy costs. Therefore, the and immune function (which represents somatic
cost–benefit trade-offs of pursing dominance status effort) are known to have negative bidirectional
over, say, somatic effort must be balanced (Wingfield, effects on each other. For instance, men who received
Lynn, & Soma, 2001). Importantly, under conditions an immune challenge (flu vaccination) show lower
in which these costs are reduced or the benefits testosterone levels than control men (Simmons &
increased, mating effort is expected to increase. Roney, 2009), and conversely, hypogonadal men
For instance, when the sex ratio is female biased undergoing testosterone replacement therapy decline
(i.e., more females than males), male mating effort in circulating antibodies and cytokines (e.g., Kocar
is expected to be increased because the likelihood of et al., 2000).
successfully pursuing a short-term mating strategy Given the costs associated with maintaining high
is greater (Arnkocky, Woodruff, & Schmitt, 2016). levels of testosterone, the endocrine system evolved
Indeed, this is reflected in violent crime rates, an to adaptively respond to the social environment
indicator of heightened male mating effort, which (Carré, McCormick, & Hariri, 2011; Eisenegger,
tracks sex ratios (Schacht, Tharp, & Smith, 2016). Haushofer, & Fehr, 2011). The “challenge hypoth-
Likewise, under conditions of heightened extrinsic esis” was proposed to explain fluctuations in testos-
risk (e.g., mortality that cannot be avoided through terone as a facultative adjustment to mating effort
altering one’s behavior), the benefits of developing (Wingfield, Hegner, Dufty, & Ball, 1990). Although
the hypothesis was originally developed to explain
testosterone dynamics in birds, it has since found
8
In support of the greater importance of dominance among
support across numerous taxa, including insects
men, women too form dominance hierarchies when first meeting,
although dominance hierarchies emerge on longer timescales (Tibbetts & Crocker, 2014), fish (Oliveira, 2009),
than they do in men (Anderson, John, Keltner, & Kring, 2001). nonhuman primates (Muller & Wrangham, 2004;

Goetz, Weisfeld, and Zilioli 129

Sobolewski, Brown, & Mitani, 2013; for a review, early experience of risk induces the development of
see Muller, 2016), and humans (Archer, 2006). fast life history strategies. Facultative adjustment to
For example, chimpanzees form stable linear dom- risk taking has also been observed in mating contexts.
inance hierarchies, which reduces aggression and In one study, men exposed to pictures of attractive
testosterone secretion (Muehlenbein, Watts, & women were less risk averse in a card game and risk
Whitten, 2004; Muller & Wrangham, 2004); how- taking was positively correlated with their mating
ever, when a group contains an estrous female— motivations, suggesting that risk taking may serve
which is advertised by sexual swellings, testosterone mating effort (Baker & Maner, 2008). Testosterone
levels, along with aggression, have been observed appears to mediate these effects on behavior, likely
to rise (Muller & Wrangham, 2004; Sobolewski, by altering the balance between reward and punish-
Brown, & Mitani, 2013). Nulliparous estrous females ment sensitivity (van Honk et al., 2004).
did not promote testosterone secretion, likely due Testosterone has been shown to alter the balance
to the fact that nulliparous females are by definition between sensitivity for punishment and reward in
inexperienced mothers and are thus less attractive both animals and humans by reducing punishment
to male chimpanzees despite similar copulatory sensitivity and increasing reward sensitivity (Boissy &
rates to parous females (which indicates that sexual Bouissou, 1994; van Honk et al., 2004). In humans,
behavior, per se, is not the cause of the observed van Honk and colleagues (2004) demonstrated that
increase in testosterone). administering testosterone to healthy young women
shifted their punishment–reward contingencies in
Risk Taking as a Function of Life History the Iowa gambling task toward a risk-prone pattern.
Strategy Similarly, men with high levels of endogenous tes-
As stated previously, the development of a fast life tosterone are less risk averse in this task than men
history is partially dependent on cues to environ- with lower levels of endogenous testosterone (Stanton,
mental risk (see Ellis et al., 2009). Indeed, if the Liening, & Schultheiss, 2011), suggesting a mech-
future is uncertain, investing in the present is likely anism by which testosterone amplifies risk taking in
on average to produce better fitness outcomes than the service of mating effort. For instance, Ronay and
delaying for a future that may never arrive (Ellis von Hippel (2010) observed that in the presence of
et al., 2009). One stark illustration of this principle is an attractive female, male skateboarders performed
the possibility that wartime rape, rather than (solely) more physically risky maneuvers, and this relation-
an expression of power over the powerless, is a fac- ship was shown to be partially mediated by increases
ultative adaptation to the real possibility of immi- in testosterone. Likewise, in the domain of financial
nent death (Henry, Ward, & Hirshberg, 2004). risk taking, endogenous baseline and responsive tes-
Experimentally priming mortality has been found tosterone are positively associated with increased
to increase men’s willingness to engage in risky sexual risk preferences (Apicella et al., 2008, 2014).
behaviors, as well as engendering a desire for offspring Further­ more, facial masculinity—an indicator of
(Taubman-Ben-Ari, 2004; Wisman & Goldenberg, pubertal-testosterone organizational effects (e.g.,
2005, respectively). Likewise, cues to life expectancy Hodges-­Simeon, Sobraske, Samore, Gurven, &
alter preferences for short-term and long-term Gaulin, 2016)—was also found to be positively asso-
mating, such that shorter life expectancy is associated ciated with risk taking (Apicella et al., 2008), and in
with a preference for short-term mating (Dunkel, a more recent study was shown, along with testoster-
Mathes, & Decker, 2010). Risk sensitivity theory one, to be related to proneness to boredom and sen-
frames risk sensitivity in terms of average outcomes, sation seeking (Campbell et al., 2010). With regard
variances around the average, and current need to punishment sensitivity, psychopathy—which
level. If relative reproductive success is in jeopardy, it entails insensitivity to punishment—is positively as-
is to the organism’s advantage to follow a more risky sociated with testosterone in men when under stress
strategy if a lower risk strategy is unlikely to meet an (as indicated by heightened cortisol; Welker, Lozoya,
organism’s needs (Mishra & Lalumière, 2010). Campbell, Neumann, & Carré, 2014). Thus, by
Recently, Griskevicius and colleagues (2011) amplifying rewards and tamping down sensitivity to
showed experimentally that childhood experience of punishment, testosterone may serve to enhance
resource scarcity (indexed by socioeconomic status) short-term mating success by increasing the likeli-
interacted with mortality cues to induce increased hood of enacting courtship displays and aggressive
risk taking, consistent with the interpretation that behaviors, both of which entail some degree of risk.

130 Reproductive Behavior in the Human Male

Aggression as a Manifestation Aggression, although detrimental to society
of Mating Effort and potentially harmful to the individual, never-
Male mating effort is marked by heighted violence theless serves an adaptive function (Archer, 2006;
and aggression (Ainsworth & Maner, 2012; Archer, Griskevicius et al., 2009). Men who successfully used
2006; Griskevicius et al., 2009), particularly in aggression in the context of intramale competition
mating markets in which long-term nurturant to gain sexual access to women and the means toward
­romantic relationships are not pursued (Wilson & achieving access (e.g., status) left more descendants
Daly, 1985). Young, unmarried men commit the than men without these traits. Indeed, in one survey
lion’s share of violence (Daly & Wilson, 1988; Wilson study, when asked to recall the motivating reasons
& Daly, 1985). Regions with more men have more behind their last act of aggression, nearly half of
violent crime (an indicator of increased male–male the participants cited status/reputation concerns as
competition) than regions in which the operational the underlying reason (Griskevicius et al., 2009).
sex ratio9 is female biased (Schacht, Tharp, & Moreover, priming mating motives has been shown
Smith, 2016). Marriage has been shown to decrease to increase aggression directed at male competitors
recidivism (e.g., Horney, Osgood, & Marshall, 1995) (Ainsworth & Maner, 2012; Griskevicius et al.,
and, in turn, marriage is associated with lower tes- 2009). For instance, men primed with either a
tosterone (e.g., Mazur & Michalek, 1998). Finally, courtship or competition motive report a greater will-
the development of men’s sexually dimorphic mor- ingness to use direct aggression in response to prov-
phological features (e.g., upper body strength) are ocation when the target is another man (Griskevicius
mediated by androgens (Hodges-Simeon et al., 2016; et al., 2009), and these results generalize beyond
Puts, Jones, & DeBruine, 2012) and enhance self-report aggression (Ainsworth & Maner, 2012).
men’s physical dominance (Puts, 2010; see Table 1 Thus, contexts involving competition for status and
in Sell, Hone, & Pound, 2012, for a list of putative mates are often characterized by heightened aggres-
adaptations for combat in men). Taken together, sion and testosterone (e.g., Wilson & Daly, 1985).
these data strongly support the notion that aggres- In addition to the challenge hypothesis, Mazur’s
sion is an adaptive expression of heightened male “biosocial model of status” provides a functional
mating effort (i.e., an adaptive product of intramale explanation for the observed effect of competitive
sexual selection). outcomes on changes in testosterone (Mazur, 1976,
Aggression, viewed in this context, comports well 1985; Mazur & Booth, 1998). The so-called winner/
with the challenge hypothesis (discussed earlier; loser effect, whereby winning a competition tends
Wingfield et al., 1990). Heightened mating effort is to increase testosterone whereas losing a competi-
supported by a facultative adjustment to testoster- tion tends to decrease testosterone, under Mazur’s
one levels, enhancing men’s competitive abilities and model is purposed to a­ daptively guide subsequent
motivations (Archer, 2004). Under this view, men dominance/deference behaviors; increases in testos-
following a fast life history strategy are expected to terone function to induce behavioral prerogatives of
show heightened androgen activity (both baseline dominance (e.g., aggression directed down the hier-
levels and responsivity to reproductive cues and archy and approaching potential mates), whereas
contexts). Indeed, in a recent study, Zilioli and col- decreases serve to dissuade subsequent attempts at
leagues (2016) found that men’s testosterone response gaining dominance over the current competitor.
to erotica was conditioned upon their interest in Androgen responses to winning and losing compe-
babies (an indicator of parental effort), such that men titions have been observed across numerous taxa.
who reported less interested in babies secreted more
testosterone than men who reported more interest. et al., 2010; McDonald, Donnellan, & Navarrete, 2012; Patch &
Furthermore, interest in babies was related to scores Figueredo, 2016; Strouts, Brase, & Dillon, 2016); in turn, some
on the Mini-K (a self-report measure of life history studies have found that short-term mating orientation is linked
with heightened testosterone levels (Edelstein, Chopik, & Kean,
strategy; Figueredo et al., 2005); however, testoster- 2011; McIntyre et al., 2006; Puts et al., 2015), although several
one reactivity was not related to life history strategy.10 others have failed to find this association (Charles & Alexander,
2011; Farrelly, Owens, Elliott, Walden, & Wetherell, 2015; van
Anders et al., 2007). More research directly evaluating the potential
9
Operational sex ratio is the ratio of potentially receptive relationship between life history strategies and testosterone are
males to receptive females (Emlen & Oring, 1977). warranted. In particular, research into the context in which
10
Despite this lack of association, the mini-K has been found testosterone responses are induced (e.g., male–male competition)
to be associated with a short-term mating orientation (Dunkel is needed.

Goetz, Weisfeld, and Zilioli 131

In humans, the winner/loser effect has been observed with the challenge hypothesis, unstable hierarchies
in athletes and their fans, chess players, voters, and (i.e., pairs of men in which each experienced both
the laboratory (for a review of field studies, see victory and defeat) induced the largest increase in
Carré & Olmstead, 2015). testosterone on the second day, in contrast to men
In the lab, changes in testosterone in response to who lost on both days, indicating that unstable hi-
a competitive outcome have been associated with an erarchies represent a challenge to men’s reproductive
increased motivation for future competition, com- success and would hence benefit from increased com-
petitive ability, and aggressive behavior, supporting petitive motivation. Indeed, unstable hierarchies
the second half of Mazur’s model (Carré, Campbell, consistently produce heightened aggression and
Lozoya, Goetz, & Welker, 2013; Carré & McCormick, testosterone in nonhuman primates (Holekamp &
2008; Mehta & Josephs, 2006; Zilioli & Watson, Strauss, 2016).
2014). Mehta and Josephs (2006), using a rigged In sum, aggression and mating effort in men are
competition, found that those that lost a competi- clearly linked and play a functional role in men’s
tion but still evinced an increase in testosterone were reproductive lives. Although increased mating effort
more willing to compete again compared to those at the expense of parental and somatic effort has been
that decreased in testosterone. Similarly, Carré and viewed as indicative of following a fast life history
McCormick (2008) showed that men who increased strategy, direct evidence relating individual differ-
in testosterone in response to behaving aggressively ences in testosterone and aggression to individual
were more likely to choose a competitive task rela- differences in life history strategy is lacking. Future
tive to men who did not show an increase in testos- research in this field that incorporates life history
terone. In a later study, Carré and colleagues (2013) measures is warranted.
found that the positive relationship between win-
ning a task and subsequent aggressive behavior was Mate Seeking, Testosterone, and Life
mediated by changes in testosterone, such that in- History Strategy
creases in testosterone predicted heightened aggres- Testosterone and mating success have been observed
sion. Subsequent work indicates that these changes to be positively associated in humans12 (Peters,
may function to increase men’s perceptions of their Simmons, & Rhodes, 2008; Pollet, van der Meij,
own dominance (Welling, Moreau, Bird, Hansen, Cobey, & Buunk, 2011), indicating that testosterone
& Carré, 2016). Specifically, in a double-blind, may function to orient men’s efforts toward court-
placebo-controlled study, exogenous testosterone ship behaviors. Indeed, even brief exposures of men
was shown to enhance men’s ratings of their own to attractive women induce testosterone release
dominance, particularly in men in whom the exog- (Roney, Mahler, & Maestripieri, 2003), and men’s
enous testosterone administration produced a large changes in testosterone during such interactions are
percent increase in testosterone (i.e., those with lower associated with women’s ratings of his extraversion
baseline endogenous testosterone levels). and degree of self-disclosure (Roney, Lukaszewski,
Although these studies all involved single-­ & Simmons, 2007). Field studies, which achieve
interaction episodes, in the environment of evolu- greater ecological validity, also find this exposure
tionary adaptiveness,11 relationships would involve effect (e.g., Flinn, Ponzi, & Muehlenbein, 2012).
encountering rivals over multiple episodes. Zilioli and Moreover, testosterone appears to facilitate entry
Watson (2014) sought to address this gap by into committed romantic relationships. In one study,
­designing a study in which men competed across two men with high testosterone at age 21 were more
consecutive days. The usual winner/loser effect was likely to be partnered fathers by age 26 compared
observed, but, importantly, changes in testosterone to men with low testosterone at age 21 (Gettler,
on the first day were positively associated with McDade, Feranil, & Kuzawa, 2011).
competitive task performance on the second day, Changes in testosterone in response to the pres-
replicating past murine models (e.g., Fuxjager, ence of an attractive woman are hypothesized to
Montgomery, & Marler, 2011). Also, consistent
12
There may exist a negative feedback loop in which satisfying
11
The environment of evolutionary adaptiveness denotes the one’s sexual desire decreases testosterone. When controlling for
series of ancestral environments in which selection pressures sociosexual interest, number of sexual partners negatively predicted
sculpted an adaptation. It is not a specific time or place, but baseline testosterone levels (Puts et al., 2015), and sexual activity
rather a statistical composite of selection pressures that shaped has been found to be associated with lower testosterone levels
the adaptive design of an organism over generations (Cosmides (Sakaguchi et al., 2007, but see Gettler, McDade, Agustin, Feranil,
& Tooby, 1997). & Kuzawa, 2013).

132 Reproductive Behavior in the Human Male

index a positive decision to pursue mating (Roney & interaction with a young woman than men with
Gettler, 2015). Contexts in which mating is precluded more CAG repeats and high basal cortisol. Variations
or unwanted (e.g., due to sexual satiety) do not induce in CAG repeat length predict variables associated
a rise in testosterone. For instance, subordinate mon- with intrasexual competitiveness such as upper body
keys in the presence of both a receptive female and strength and dominance but were not associated with
a dominant male do not produce an increase in tes- mating strategy, although mating strategy was only
tosterone, likely because the dominant male would assessed via self-reported sociosexuality (Simmons
thwart any attempt at mating (Glick, 1984). Similarly, & Roney, 2011).
in mating contexts, the perceived presence of a domi-
nant man can suppress creative displays (e.g., telling Coercive Mating Strategies
funny jokes) of subordinate men (Gambacorta & Sexually coercive mating tactics have been observed
Ketelaar, 2013). Social context also modulates testos- across a variety of species and taxa (McKibbin,
terone responses to potential mates. Flinn and col- Shackelford, Goetz, & Starratt, 2008) and are more
leagues (2012) documented that men in a Dominican common in species in which males are more aggres-
village evinced a testosterone increase when exposed sive, eager to mate, sexually assertive, and less discrim-
to women, but only if those women were women inating in mating decisions (Thornhill & Palmer,
from another village and not in relationships with 2000). Although there is clear evidence of adapta-
kinsmen or friends. tions for rape in some species (e.g., scorpionflies have
Testosterone’s role in promoting mating has been a notal organ designed to restrain females; Thornhill,
summarized in Roney and Gettler’s (2015) testos- 1980), evolutionary psychologists have long debated
terone-relationship cycle model. The testosterone-­ whether sexual coercion in humans represents an
relationship cycle model proposes that testosterone adaptation or whether it is a byproduct of other
functions to promote mate pursuit, increasing the adaptations (i.e., heightened aggression and desire
likelihood of entering into a romantic relationship. for sexual variety).
However, once in a relationship, mate pursuit may The adaptationist perspective posits that sexual
interfere with bond stability and effective parenting. coercion was selected over evolutionary history as
Thus, nurturant relationships are suggested to impose a facultative male reproductive tactic that increased
negative feedback on testosterone production and, reproductive success by increasing the number of
consequently, mating effort (Roney & Gettler, 2015). sexual partners (e.g., Thornhill & Thornhill, 1983).
For instance, administering testosterone to male Also, when comparing per-incident pregnancy rates
house sparrows after pairing prolongs courtship between consensual and nonconsensual vaginal sex,
behaviors but reduces offspring survival (Hegner & nonconsensual pregnancy rates are twice as high
Wingfield, 1987). In human couples, high testos- (6.42 percent vs. 3.1 percent), and climb to two
terone is associated with relationship dissatisfaction and a half times higher when adjusted for contra-
and partners of high-testosterone individuals are less ception use (Gottschall & Gottschall, 2003). In
satisfied and committed to the relationship (Edelstein, addition to increasing partner number and con-
van Anders, Chopik, Goldey, & Wardecker, 2014). ception rates, sexual coercion within an existing
Indeed, men’s testosterone positively predicts future relationship may function as a sperm competition
divorce (Booth & Dabbs, 1993). This negative feed- mechanism, an adaptation to the adaptive problems
back will be the focus of the upcoming section on associated with social monogamy, primarily the
parenting effort. problem of paternity uncertainty (e.g., Goetz &
In addition to social constraints, genetic poly- Shackelford, 2006). In many bird species forming
morphisms and hypothalamic-pituitary-adrenal socially monogamous pairs, forced in-pair copula-
axis (HPA) hormones also modulate testosterone tion frequently occurs after extra-pair copulations
responses to mating opportunities. Roney, Simmons, or situations in which extra-pair copulation may
and Lukaszewski (2010) showed that androgen re- have occurred, paralleling findings in humans and
ceptor (AR) gene variants, along with cortisol, mod- consistent with the interpretation that forced in-pair
erated the effect of exposure to a potential mate on copulation functions as an anticuckoldry tactic
men’s testosterone responses. Specifically, men with (Goetz & Shackelford, 2006). On the other hand,
fewer CAG repeats (which is associated with greater sexual coercion may be a byproduct of male adaptive
AR expression; Choong, Kemppainen, Zhou, & desire for sexual variety and male adaptation for
Wilson, 1996) and low basal cortisol demonstrated heightened aggression (Palmer, 1991; Thornhill &
a larger increase in testosterone following a brief Palmer, 2000).

Goetz, Weisfeld, and Zilioli 133

Long-Term Strategies Conversely, under female-based ratios, uncommitted
Marriage is a human universal (Walker, Hill, Flinn, strategies are more common (Mattingly et al., 2011;
& Ellsworth, 2011). However, ceteris paribus, the Schmitt, 2005). This may seem counterintuitive from
fitness benefits of men pursuing short-term mating a resource scarcity perspective (if sexually accessible
strategies outweigh the benefits of pursuing long- women are construed as a resource) in which men
term mating strategies, which begs the question as to are limited in their mating opportunities and are
why, then, so many men commit significant portions thus expected to compete more vigorously for sexual
of their adult lives to a single sexual union (Henrich, access to women. However, it appears that the way
Boyd, & Richerson, 2012). The long history and in which men in industrialized societies compete for
high frequency of monogamous marriage practices women when they are rare is not to increase direct
suggest that under some conditions, long-term pair- intramale competition, but rather to appear attrac-
bonding proved evolutionarily advantageous (Walker tive to women by conforming to women’s sexual
et al., 2011; van Anders, Goldey, & Kuo, 2011). desires (e.g., Schacht, Tharp, & Smith, 2016).
Evolutionary psychologists have proposed several Furthermore, research on the effects of pair-bonding
reasons that men might pursue a committed rela- and testosterone—a putative facilitatory mechanism
tionship. First, men may pursue a long-term mating to mating effort—generally indicates that committed
strategy because it is imposed on them by women. partnering decreases testosterone (reviewed in Gray,
That is, to gain sexual access to some women, men McHale, & Carré, 2016). However, a recent study
might have to signal their commitment to the union, a using longitudinal data also indicates that lower
critical evolutionary concern to ancestral women testosterone levels predict pairing (Dibble, Goldey, &
given the cost of bearing offspring (e.g., Schact, van Anders, 2016). To the extent that lower testoster-
Tharp, & Smith, 2016). Second, by conceding to a one indicates a less masculinized pattern of behavior
long-term strategy, men might gain access to more (Manuck et al., 2010)—in this case, attenuated
desirable women, provided that what men find de- short-term mating orientation (Buss & Schmitt,
sirable reflects women’s fecundity. If women desire 1993; Schmitt, 2005; Schmitt et al., 2012; Symons,
a committed mate, a more desirable woman is in 1979)—this result could indicate that entry (in the
a better position to find a man willing to accept the near term14) into a long-term mating strategy is facili-
costs of abandoning short-term mating strategies tated by matching women’s preferences. Alternatively,
(Perilloux, Cloud, & Buss, 2013). Third, men choos- sexual activity may be heightened around the time
ing to pursue a long-term strategy increase pater- of relationship initiation and thus could be pro-
nity certainty. Forming a longer union entails greater ducing negative feedback on testosterone levels
sexual access to one mate, which reduces the oppor- (Puts et al., 2015; Sakaguchi, Oki, Honma, Uehara,
tunity for the woman to mate with a different man, & Hasegawa, 2007).
and if the woman does engage in sexual intercourse Several studies have found that women’s physical
with another man, greater sexual access granted by attractiveness correlates with fertility (Hill &
the long-term pair-bond reduces the likelihood that Hurtado, 1996; Jokela, 2009; Pflüger, Oberzaucher,
the interloper will father her offspring (Bethmann & Katina, Holzleitner, & Grammer, 2012). In the Ache
Kvasnicka, 2011). Finally, forming a stable union of Paraguay, women with high facial attractiveness
with a woman provides the father with greater were found to have 1.16 times higher fertility than
­opportunity to directly invest in offspring through less attractive women (Hill & Hurtado, 1996,
parenting and provisioning of resources, both phys-
ical and social (reviewed in Geary, 2000).
Women’s imposition of commitment is reflected immediate material gains or genetic benefits to offspring, short-
term mating can be used as a strategy for defraying the costs of
in mating market dynamics. Indeed, when the adult leaving a relationship (e.g., costs of physical threat from a former
sex ratio (ASR; i.e., ratio of sexually mature men to partner; Buss, Goetz, Duntley, Asao, & Conroy-Beam, 2017).
women present in a population) is male biased 14
A longitudinal study of marriage and testosterone in the
Philippines found the opposite effect; higher testosterone
(i.e., more men than women), the dynamics of the
among unmarried men was associated with being married five
mating market ostensibly push men to cater more years later (Gettler et al., 2011). This result has been interpreted
to women’s preferred mating desires (i.e., committed as indicating that testosterone benefits men on the mating market,
relationships;13 e.g., Schacht, Tharp, & Smith, 2016). granting them greater success at procuring a mate. However, on
shorter intervals (months rather than years), perhaps once
intramale competition for a particular woman has been quelled,
13
This is not to say that women do not often desire short- lower testosterone facilitates signals of commitment (e.g.,
term mating. For instance, apart from the benefit of possible nurturant behaviors).

134 Reproductive Behavior in the Human Male

­ . 312). Likewise, in a sample of U.S. women, attrac-
p Campbell, 2007; Sakaguchi et al., 2007; van Anders
tive women had 16 percent more children than less & Watson, 2006, 2007; van Anders, Hamilton, &
attractive women ( Jokela, 2009). Finally, in a small Watson, 2007; van Anders & Goldey, 2010).
rural community of Austrians, both the total number Being in a relationship, however, is not always
of pregnancies and the total number of children associated with lower testosterone. Relationship
predicted ratings of facial attractiveness (Pflüger status, per se, does not appear to be the primary
et al., 2012). Thus, attractive women may be able to cause; rather, how men approach the relationship
more easily parlay their heightened mate value into (relationship orientation) appears to be the key
pressuring men to follow their preferred reproduc- variable along which testosterone varies (e.g.,
tive strategy (i.e., committed relationship). Indeed, Edelstein et al., 2011; van Anders & Goldey, 2010).
more attractive women are better able to actualize For instance, sociosexuality plays a moderating role
their current mating goals (Perilloux, Cloud, & (Edelstein et al., 2011; van Anders & Goldey, 2010,
Buss, 2013), which often center on commitment but see van Anders et al., 2007). Men reporting a
(Buss & Schmitt, 1993; Schmitt et al., 2012). desire for uncommitted sexual activity had similar
As an altricial species, offspring survival is en- levels of testosterone as single men, indicating that
hanced by provisioning from the father (Bribiescas, attitudes toward commitment play a key role in
Ellison, & Gray, 2012). However, paternity uncer- whether being in a relationship decreases mating
tainty poses an inherent challenge to men providing effort (as indicated by testosterone). Indeed, socio-
paternal investment. Before the advent of paternity sexual desire for uncommitted mating prospectively
testing, a man could not be 100 percent certain that predicts relationship dissolution (Penke & Asendorpf,
his children were in fact his and not the product of 2008), and testosterone increases around the time
an affair. Indeed, some estimates of nonpaternity of divorce but decreases with remarriage (Mazur &
rates are as high as 20 percent in low-socioeconomic Michalek, 1998). Additionally, the transition from
settings, whereas in other cultural contexts they are a committed to a noncommitted relationship co-
as low as 1 percent (see Geary, 2005, for a review). occurs with an increase in testosterone (Dibble ­et al.,
Research from cultural anthropology indicates that 2016), and testosterone is negatively associated with
in cultures in which paternity uncertainty is high, commitment to and satisfaction with a romantic
male investment in offspring tends to follow an relationship (Edelstein et al., 2014). Taken together,
“avuncular” investment strategy in which men invest these data indicate that high testosterone may be
not in their own offspring, but rather in their sisters’ detrimental to the maintenance of nurturant rela-
offspring (Flinn, 1981; Flinn & Low, 1986). One tionships.
of the functions of marriage, then, might be an Much of the ethnographic data indicates that
increase in men’s paternity certainty by simultane- norms associated with marriage and childcare mod-
ously conferring greater sexual access to the husband erate the relationship between testosterone and
while reducing extra-dyadic mating opportunities pairing. For instance, in a sample of high-socioeco-
for the wife (Bethmann & Kvasnicka, 2011). nomic men (university sample) from Beijing, married
and unmarried men did not differ in testosterone.
Parenting Effort However, married men with children did have sig-
As discussed in the mating effort section, testoster- nificantly lower testosterone than unmarried and
one has been linked with increased mating effort childless married men, indicating that norms of
(Gray et al., 2016). Indeed, one longitudinal study commitment to a union may be relaxed until a child
of men in the Philippines found that higher testos- has been produced. Indeed, among the married non-
terone positively predicted the likelihood of being fathers, many reported having had more than one sex
married 4.5 years later, suggesting that testoster- partner during the past year or anticipated having
one enhances mating effort (Gettler et al., 2011). more than one sexual partner in the next five years
Conversely, lower testosterone has been shown to be (Gray, Yang, & Pope, 2006). Also, similar to Western
associated with parenting effort. Studies of partnering samples (e.g., Edelstein et al., 2014), testosterone
status (single vs. partnered) have repeatedly found was negatively, albeit not significantly, correlated
that testosterone is lower among men in monoam- with relationship satisfaction (Gray et al., 2006).
orous relationships (Booth & Dabbs, 1993; Burnham Similarly, in the Philippines, the relationship be-
et al., 2003; Dibble et al., 2016; Edelstein, Chopik, tween testosterone and marriage was found to be
& Kean, 2011; Gray, Kahlenberg, Barrett, Lipson, & completely mediated by fatherhood, indicating that
Ellison, 2002; Gray et al., 2004; Gray, Ellison, & norms of direct parental care are a driving force

Goetz, Weisfeld, and Zilioli 135

mediating the trade-off between mating and par- c­ onsistently associated with lower levels of testos-
enting effort (Kuzawa, Gettler, Muller, McDade, & terone, supporting the notion that testosterone
Feranil, 2009). In a subsequent study on this pop- ­mediates the trade-off in reproductive effort between
ulation, childcare was shown to further reduce tes- mating and parenting effort (Gray et al., 2016).
tosterone levels (Gettler et al., 2011).
Other cross-cultural research indicates that Conclusion
direct paternal care is associated with decreased Life history theory provides a useful theoretical lens
testosterone (Alvergne, Faurie, & Raymond, 2009; through which to investigate individual differences in
Gray, 2003; Muller, Marlowe, Bugumba, & Ellison, many prosocial and antisocial behaviors. Furthermore,
2009). Among Senegalese men, a polygynous popu- the adoption of an adaptive plasticity perspective
lation but with a high degree of paternal care, fathers has provided consilience with a variety of develop-
had lower testosterone levels than nonfathers. mental fields that hitherto lacked theoretical depth.
Furthermore, paternal investment in the family (as By recognizing the trade-offs inherent in allocating
rated by the mother) was negatively associated with resources into any one life history trait, researchers
testosterone (Alvergne et al., 2009). Similarly, among are gaining a deeper understanding of the evolu-
a sample of Swahili men, men with younger children tionary pressures that have shaped individual dif-
had lower testosterone than men with older children, ferences, particularly in the domain of reproductive
but this relationship was not significant (Gray, 2003). strategies. Because the cost–benefit ratios associated
Among the Hadza, a foraging tribe in which fathers with these trade-offs are not constant across develop-
invest heavily in direct paternal care, fathers had mental contexts, differences in allocation schemes,
lower testosterone than nonfathers, and the magni- constituting conditional adaptations, maximize re-
tude of the testosterone decrement was negatively productive success across conditions. For instance,
associated with the age of the father’s youngest child. in socioecological contexts in which paternal in-
By contrast, fathers and nonfathers among the vestment is closely associated with offspring repro-
Datoga pastoralists, who invest little direct paternal ductive success, monogamous mating strategies
care, did not differ in testosterone levels (Muller emerge. A large body of research indicates that the
et al., 2009). conditional expression of these alternative reproduc-
Apart from direct investment in offspring, an- tive strategies is mediated by the neuroendocrine
other indicator of commitment that has been found system. In particular, testosterone has been impli-
to be associated with testosterone across cultures is cated in mediating the trade-off between mating
whether marriages are monogamous or polygynous; and parental investment. Further incorporation of
however, the direction of findings has been mixed. a life history perspective into the study of social
For instance, both Swahili and Senegalese men in neuroendocrinology will likely prove fruitful in
polygynous marriages were found to have higher understanding individual differences in neuroen-
testosterone than monogamously married men docrine profiles.
(Senegalese: Alvergne et al., 2009; Swahili: Gray,
2003). However, in two separate populations of
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 CH A PT E R

9 Mate Preferences Across the Lifespan

Lynda G. Boothroyd and Jovana Vukovic

Abstract

Humans show preferential responses to “attractive” individuals from the first hours of life onward.
However, these early preferences are subject to later development in terms of increasing agreement on
general attractiveness and preferences for specific dimensions of attractiveness. This chapter outlines
aspects of mate choice and considers evidence for their hormonal mediation in adults. It then examines
preferences for these traits across infancy, puberty, and menopause and considers potential hormonal
mediation arguments for the mate choice changes observed during these periods. The chapter finds
overall that expression of specific preferences is ambiguous in infancy, but there is clear evidence that
preferences become stronger in late childhood and adolescence (albeit subject to disruption around
puberty). There is also evidence suggesting a decline in some preferences at menopause in women.
Across the developmental and lifespan literature, there is a critical lack of studies directly assessing
hormones. The chapter closes with recommendations for future research.
Key words: facial attraction, voices, sexual dimorphism, symmetry, averageness, health, sex steroids,
infancy, puberty, menopause

Mate choice lies at the core of evolutionary age groups “agreed” in their overall preferences for
understandings of human behavior. Given that
­ some faces over others, in the last 10 years, research-
­selection of a mate, versus random mating, can yield ers have built a body of data that considers devel-
increased reproductive success even in Drosophila opmental change in preferences for specific traits.
(Edward & Chapman, 2012), it is unsurprising that Theories around the traits that humans tend to find
a long-lived species with high levels of parental in- attractive in potential reproductive partners focus
vestment, such as humans, demonstrates high levels on the immediate benefits to the chooser, the longer
of choosiness with regard to sexual partners. Further­ term indirect benefits to offspring, or both. In the
more, although males may on average invest less than next section, we outline the principal understand-
females, high rates of pair-bonding, (serial) monog- ings of the benefits derived from those traits that have
amy, and male provisioning of offspring lead to the been investigated in developmental/lifespan contexts
prediction that humans should display mutual mate thus far, and the methods used to assess preferences
choice (Brown, Laland & Mulder, 2009; Kokko & for these traits. Then, we go on to consider critical
Johnstone, 2002; Stewart-Williams & Thomas, 2013), developmental windows in which hormonal changes
with males and females both seeking to detect and may impact preferences: namely, infancy, puberty,
select partners on the basis of traits that will maximize and menopause.
immediate reproductive success and/or long-term
inclusive fitness. Traits Typically Preferred by Adults
Although initially most developmental research Direct indices of current health in a potential partner
into attraction assessed the extent to which different may include elements of vocal quality (e.g., Orlikoff,

143
1990), levels of carotenoid-linked yellow coloration or mating outcomes do control for systematic
in the skin (e.g., Stephen, Coetzee, & Perrett, 2011), asymmetry (e.g., the body landmarks chosen by
and the overall visible health of the face and skin Gangestad et al., 1994, are not typically subject to
quality (e.g., Fink & Matts, 2008; Jones et al., 2001). directional asymmetries), most studies of attraction
Selection of a more currently healthy mate yields simply look at preferences for stimuli varying in
potential reproductive benefits in terms of increased naturally occurring asymmetries without isolating
individual fitness via contagion avoidance, and in- fluctuating asymmetry specifically. For instance, the
creased inclusive fitness via (potentially) elevated developmental studies of symmetry preference dis-
offspring health (although see Adamo & Spiteri, cussed here all presented pairs of stimuli in which
2009, for discussion of this point). To date, although the natural asymmetries of an individual had been
the adult literature is increasingly interested in the reduced/eliminated, left intact, or even exaggerated.
specific skin and voice properties associated with Averageness is considered almost exclusively in
health, the developmental literature has investigated reference to faces (indeed, we are unaware of any
only global facial health as determined by third-party studies looking at other forms of averageness) and
observers; Boothroyd, Meins, Vukovic, and Burt refers to the degree to which the proportions of an
(2014) constructed pairs of stimuli varying in skin individual face resemble the population mean for
color, texture, and face shape based on composites those proportions. Preferences for averageness can
of individuals rated as appearing very healthy or very be determined by correlating attractiveness ratings
unhealthy and found that children preferred the of individual faces with composite averageness scores
“healthier” faces from 6 to 8 years onward. Relatedly, for those faces. The majority of research in develop-
Kościński (2011, 2013) had child participants rate mental contexts, however, tends to manipulate the
the attractiveness of individual faces already rated by proportions of individual facial identities to make
others for a healthy appearance and found a positive them closer to population average (usually based on
correlation between child-perceived attractiveness the proportions of 25+ individuals drawn from the
and adult-perceived health. same recruitment pool) and to exaggerate the dif-
Symmetry and averageness are often considered ferences between the faces and the average (i.e., to
to be indices of underlying quality with significant make them more distinctive; see, e.g., Boothroyd
implications for health (reviewed in, e.g., Stephen et al., 2014; Griffey & Little, 2014).
& Wei, 2015). Although the literature regarding Sexual dimorphism, in the context of attraction
symmetry presents an overall only modest link to research, refers to the degree to which an individual
health (Van Dongen & Gangestad, 2011), individ- demonstrates sexually dimorphic features—that is,
uals may yet benefit by selecting more symmetrical how strongly they show sex-typical shape, color, or
partners if the factors that lead to their elevated levels size. In terms of body size and shape, there has been
of symmetry result in more viable offspring. Similarly, a great deal of research into preferences for female
there is evidence that men with more diverse major waist–hip ratio, which is lower (i.e., more curvy) in
histocompatibility complex (MHC) alleles, who may women than in men, and for dimensions relating to
be resistant to more pathogens, have more “average” shoulder or chest width in men (e.g., waist–shoulder
faces than men with less diverse genetic profiles (Lie, and waist–chest ratio, respectively; reviewed in Reeve,
Rhodes, & Simmons, 2008). Thus, averageness may Kelly, & Welling, 2016). Facial shape is also sexually
offer comparable potential benefits to offspring as dimorphic and is the focus of a vast research litera-
symmetrical traits do. ture considering preferences for femininity in female
Symmetry can be quantified based on the devia- faces and women’s ambiguous attitudes toward
tions away from perfect bilateral symmetry (e.g., masculinity in male faces (reviewed in Little, 2015).
bodies: Gangestad, Thornhill, & Yeo, 1994; faces: Finally, voice pitch is also sexually dimorphic, being
Penton-Voak et al., 2001); it is important, however, deeper in men. Various researchers have linked sexual
to exclude systematic asymmetries, where all indi- dimorphism in the female direction (i.e., femininity)
viduals tend to show asymmetry in one direction with estrogen (e.g., Law Smith et al., 2006; although
(directional asymmetries, e.g., the heart is situated cf Jones et al., 2018), whereas dimorphism in the
asymmetrically to the left of midline) or in either male direction (i.e., masculinity) has been both
direction (antisymmetry, e.g., handedness). The correlationally (e.g., Pound, Penton-Voak, & Surridge,
­remaining “random” asymmetries are known as 2009) and pseudo-experimentally linked (e.g.,
fluctuating asymmetry. Although some studies of Verdonck, Gaethofs, Carels, & de Zegher, 1999) to
associations between body asymmetries and health testosterone. Femininity is hypothesized to confer

144 Mate Preferences Across the Lifespan

advantages in terms of fertility, such that males Pisanski et al., 2014; although cf Dixson et al., 2018,
­selecting more feminine female partners may be more and Jones et al., 2018) and testosterone (Bobst,
likely to sire offspring during a given sexual encounter. Sauter, Foppa, & Lobmaier, 2014; Thornhill,
Masculinity in men is more controversial and has Chapman, & Gangestad, 2013; Welling et al., 2007;
been hypothesized to indicate underlying quality although see Roney et al., 2011), with a potential
and to yield health benefits to offspring (e.g., effect of progesterone in suppressing masculinity
Thornhill & Gangestad, 2006; although see Scott, preferences (Jones et al., 2005b; Limoncin et al.,
Clark, Boothroyd, & Penton-Voak, 2013, for a 2015; Little, Burriss, Petrie, Jones, & Roberts, 2013;
counterargument, and Boothroyd et al., 2017, for but see Cobey, Little, & Roberts, 2015; see also
recent counterevidence). Alternatively, masculinity Welling & Burriss, this volume). Similarly, within-
may be primarily a signal of intrasexual competi- subject variation in men’s preferences for female
tiveness (Boothroyd, Jones, Burt, & Perrett, 2007; femininity is associated with testosterone (Welling
Puts, 2010). In either case, men who have more et al., 2008; see also Bird et al., 2016).
feminine faces are thought to be warmer, more co- On the other hand, female preference for male
operative, and more suitable long-term partners healthiness may be driven by progesterone insofar
(Boothroyd et al., 2007; Perrett et al., 1998), while as women prefer healthiness more in a potential
higher pitched (i.e., more feminine) voices are partner during the luteal phase of the cycle than
likewise perceived as less dominant (Puts, Hodges, the follicular phase, when taking hormonal con-
Cardenas, & Gaulin, 2007). The bulk of the develop- traceptives (which contain artificial progestins) than
mental literature into facial preferences has tended when naturally cycling, and when pregnant than
to utilize stimuli in which femininity is the preferred when not pregnant (Jones, Little, et al., 2005; Jones,
direction among the oldest participants, for both Perrett, et al., 2005). There is also a hint that hor-
male and female images (e.g., Boothroyd et al., mones may play a role in symmetry preference;
2014; Saxton, DeBruine, Jones, Little, & Roberts, although variation in symmetry preferences across
2009; Saxton et al., 2010). As such, in this context, the cycle is subject to limited and conflicting evi-
the question is primarily the extent to which children dence (Gangestad & Thornhill, 2008; Gildersleeve,
demonstrate adult-like preferences for femininity. Haselton, & Fales, 2014), Hadza women prefer more
Similarly, where we report on voice preferences, we symmetric male faces when pregnant or lactating than
will focus on whether the preferences exhibited are when naturally cycling (Little, Apicella, & Marlowe,
“adult-like” or not, regardless of direction. The only 2007). Pregnancy and lactation are hormonally
research to investigate body preferences from a devel- distinct periods, however, and the authors do not
opmental angle focused on children’s emerging give their data separately. Furthermore, Cobey et al.
preferences for differentiated waist–hip ratio between (2015) found that women’s masculinity preferences
male and female silhouettes (Connolly, Slaughter, differed between pregnant and postnatal participants,
& Mealey, 2004). suggesting these periods may also show differences
in other trait preferences. As such, it is not clear
Evidence for Hormonal Associations whether any particular hormone is driving this pat-
in Adults tern. Finally, an elevation in symmetry preferences
To our knowledge, the traits mentioned previously would be surprising during a period in which normal
are the only widely recognized specific preferences female sex hormones are suppressed, as they are in
that have been investigated from a developmental lactation in particular.
perspective, although Kościński (2010, 2011, 2013) Overall, therefore, there is strong reason to
has also considered the extent to which children ­believe that hormonal factors may drive the expres-
prefer faces that adults have rated on other nonphy- sion of mate preferences in adulthood, particularly
sical characteristics (e.g., friendliness, sexy appear- for masculinity/femininity and health, and may thus
ance). Preferences for the facial, vocal, and body have a role to play in developmental change in mate
traits discussed previously have also been the focus of preferences.
research into endocrine influences on mate choice
among adults of reproductive age. Expression of Facial Preferences in Infancy
female preferences for multiple forms of male mas- The first step in understanding the development of
culinity across the menstrual cycle may be driven mate preferences is to consider how early the prefer-
by both estrogen (Feinberg et al., 2006; Roney & ences described previously can be observed. Within
Simmons, 2008; Roney, Simmons, & Gray, 2011; the first few hours of life, infants show preferences

Boothroyd and Vukovic 145

(as indexed by looking times) for some faces over preferred a composite (i.e., average) face composed
others, in a manner that is consistent with adult of 32 individual faces to an unattractive face in a
judgments of overall attractiveness. For instance, paired visual preference test, this is difficult to inter-
Slater et al. (1998, 2000) have shown that neonates pret as we know that composite faces are of at least
spend longer looking at female faces that adults have average attractiveness, and often (but not always)
rated as attractive compared to female faces rated more attractive than the individual faces used (see
as unattractive. Furthermore, reanalyzing all the Perrett, May, & Yoshikawa, 1994, for early evidence
infant-level data presented by Slater et al. across both regarding attractiveness beyond simple averaging).
papers shows that age in hours (which ranges from A more appropriate test of this hypothesis is to
7 to 174 hours) does not relate to the strength of in- compare stimuli in which individual faces have been
fants’ preferences for the “attractive” faces (r50= 0.195, manipulated to be closer to population average in
p = 0.18), which suggests that either the preference facial structure (i.e., more average) or further from it
is formed within the first six hours of life and remains (i.e., more distinctive). Using this method, Rhodes,
stable thereafter or that infants are born with a basic Geddes, Jeffery, Dziurawiec, and Clark (2002) found
representation of attractiveness. that 6-month-old infants had a potential preference
Some authors, such as Langlois, Roggman, and (indexed by length of “longest look” in each trial, as
Musselman (1994), have argued that averageness is coded by human observers; there was no difference
the core feature underlying general attractiveness in in overall looking times) for less average/more dis-
adult faces, and Rubenstein, Kalakanis, and Langlois tinctive faces. Similarly, Griffey and Little (2014)
(1999) have suggested that since neonates may see used computer-mounted eye tracking and found that
16+ faces within hours of birth, we might expect an sixty-four 12- to 24-month-olds likewise had a sig-
early facial preference for averageness. Specifically, nificant visual preference for more distinctive, over
they argued that infants may rapidly construct a pro- more average, faces in terms of overall looking time.
totype of faces within the local population and utilize Both Rhodes et al. (2002) and Griffey and Little
this prototype in coding individual faces, with faces (2014) also investigated preferences for symmetry
closer to the prototype (i.e., more average) being in faces, and found contrasting results; Griffey and
easier to p­ rocess and thus favored. There is evidence Little’s toddlers showed a significant visual prefer-
for norm-based coding of facial identity and attrac- ence for symmetric over asymmetric faces, whereas
tiveness in adults’ preferences (e.g., Rhodes, Jeffery, infants in the Rhodes et al. study showed a longest
Watson, Clifford, & Nakayama, 2003), and there is look fixation that tended toward asymmetric faces.
also evidence that stimuli that are easier to process Other research found no evidence for symmetry pref-
trigger more positive affect than those that are harder erences in infants (Samuels, Butterworth, Roberts,
to process (Winkielman, Halberstadt, Fazendeiro, & Graupner, & Hole, 1994), although the stimuli used
Catty, 2006). Indeed, this is one hypothesis behind in this research failed to show a symmetry prefer-
why infants prefer female faces in general: that they ence in adults either, which is highly unusual in the
have greater experience with female faces and find wider literature (reviewed in Little, 2015) and likely
them easier to process (for discussion see, e.g., reflects a deliberate decision by the authors to present
Ramsey-Rennels & Langlois, 2006). However, cru- naturally varying more and less symmetric faces from
cially, de Haan, Johnson, Maurer, and Perrett (2001) different individuals in pairs matched to be overall
found that the ability to form facial prototypes begins equally attractive.
at approximately 2 months of age and that early There are two key caveats to be addressed in terms
preference must instead have an alternative basis. of infant preferences for symmetry and averageness;
Although 3-month-old infants treated a composite of first, although averageness may be attractive beyond
previously seen faces as “familiar” (e.g., by attending any elements of symmetry (as discussed by, e.g.,
more to a completely novel face), 1-month-old in- Rubenstein et al., 1999), it is not clear whether pre-
fants did not show this pattern. These data therefore vious research into infant preferences has controlled
support the suggestion by Slater et al. that although for the fact that average faces are also more symmet-
later experience may revise our internal prototypes, rical than individual/less average faces. Second, most
humans must have an innate, simple face representa- research thus far appears to have concentrated on
tion against which neonates may code novel faces. female faces. Although infants undoubtedly process
Research into the specific components of facial female faces more efficiently and at a younger age
attractiveness that infants favor is relatively sparse. than male faces (see, e.g., Ramsey-Rennels & Langlois,
Although Rubenstein et al. (1999) found infants 2006), it is nevertheless important to consider infants’

146 Mate Preferences Across the Lifespan

preferences for these traits among male faces, not for neoteny/femininity, for female faces over male
least because approximately half of infants will go faces, and for distinctive rather than average faces.
on to use male facial features as the basis for choos- Preferences for symmetry remain less clear, although
ing a mate. the strongest study to date (Griffey & Little, 2014)
Research into preferences for sex typicality (i.e., found a preference for symmetry in late infancy. These
masculinity and femininity) is likewise sparse. Early data are challenging to integrate. Sex hormones are
data suggested that infants show preferences for high in early infancy, but a simple model of hormone
larger eyes (Geldart, Maurer, & Carney, 1999) and levels driving more strongly expressed preferences,
more “baby-like” adult features (Kramer, Zebrowitz, as per the adult literature, is clearly inadequate here.
San Giovanni, & Sherak, 1995), which are both Preferences for neoteny/femininity and even symme-
contributors to a feminine appearance (Boothroyd try (if such a preference exists) can potentially be
et al., 2005). Only two studies have specifically explained by visual experience, although preferences
investigated sexual dimorphism. Rennels, Kayl, for distinctive over average faces defy that explana-
Langlois, Davis, and Orlewicz (2016) found no visual tion. Early sex hormones, however, are often described
preference for either high or low masculinity in as “organizational” and thus, once the limitations in
naturally varying male faces among forty 6- and infant visual perception are taken into account,
12-month-olds. Contrastingly, Griffey and Little may not direct attention to adult-preferred traits.
(2014) found a significant visual preference among Furthermore, visual preference itself is problematic
their 12- to 24-month-olds for manipulated femi- as a direct proxy for affective preference; visual at-
ninity in both male and female faces. The advantage tention during early development may serve multiple
to Griffey and Little’s data is again the use of eye learning purposes without necessarily indicating
tracking rather than human coding of looking times, social preference. All of these early tendencies are
although the Rennels et al. coders showed high also subject to change across childhood and it is
­interrater reliability. Another difference between the in this latter window (and puberty especially) that
studies is the use of stimuli in which faces were fully activational hormonal effects may be more pertinent
masked (i.e., hair and clothing covered; Griffey & (the organizational–activational hypothesis is further
Little, 2014) versus covering clothing only (Rennels discussed in Hampson, this volume).
et al., 2016). Adult data may suggest that preferences
for femininity should be stronger in the masked Activation of Preferences Across Childhood
stimuli (DeBruine, Jones, Smith, & Little, 2010), and Puberty
although in pilot data with children, Boothroyd Although there is evidence that children continue to
et al. (2014) found a nonsignificant trend whereby broadly agree with adults regarding the faces they
facial preferences were stronger using unmasked consider attractive once they are able to verbally
stimuli. Perhaps most crucially, Rennels et al. (2016) report preferences for naturally varying stimuli (e.g.,
used pairs of faces that varied in masculinity but Boothroyd et al., 2014; Cavior & Lombardi, 1973;
that were matched in attractiveness (as rated by adult Cross & Cross, 1971; Kissler & Bauml, 2000; Saxton,
observers), which means direct comparison with Caryl, & Roberts, 2006), data on specific trait pref-
objectively manipulated masculinity (as per Griffey erences remains sparse for the prepubertal period.
& Little, 2014, and a large portion of the adult To our knowledge, four studies have examined a
literature) is challenging. One key finding in the cross-section of children on specific aspects of
Rennels et al. study, however, is that infants may traits that contribute to mate preferences in adults.
find highly masculine male faces more challenging Connolly et al. (2004) found that although there
to process (as indexed by categorization performance) was a general trend for children aged 6 to 15 years
unless those faces are also high in attractiveness; these to increasingly view male and female body shapes
findings are ­consistent with the idea that female faces as distinct with age, they only began to significantly
may predominate in infants’ facial experience and distinguish between male and female waist–hip ratios
should therefore predict a tendency to favor femi- around 10 to 12 years of age. Similarly, Boothroyd
ninity in male faces, which perceptually makes them et al. (2014) showed children aged 4 to 17 years
more similar to the female average (although it does pairs of faces manipulated in averageness, symme-
not explain why infants would prefer exaggerated try, femininity, and healthiness; facial healthiness
femininity in female faces). was significantly preferred over unhealthiness from
Overall, studies of face preferences in infants sug- age 6 to 8 onward, and symmetry and averageness
gest that there are demonstrable early preferences were significantly preferred from 9 years onward.

Boothroyd and Vukovic 147

Femininity was not preferred until 17 years (although Furthermore, Saxton et al. (2010) found no evidence
some authors have found femininity preferences in of 12- to 14-year-old participants showing prefer-
peripubertal groups; see later in this section). Vingilis- ences for masculinized or feminized voice pitch.
Jaremko and Maurer compared 5-year-olds, 9-year- Documenting and explaining the actual changes
olds, and adults on preferences for symmetry and that occur during puberty, however, is a more chal-
averageness; like Boothroyd et al., they did not find lenging question. The first study to attempt com-
evidence for symmetry preferences until 9 years of parison of different peripubertal groups found that
age (Vingilis-Jaremko & Maurer, 2013a); they did, 13- to 14-year-olds had stronger facial preferences than
however, find averageness preferences from 5 years 11-year-olds (Saxton et al., 2009), a finding that was
of age onward (Vingilis-Jaremko & Maurer, 2013b). replicated in a study comparing 11- to 13- and 14- to
In both cases, preferences became stronger between 15-year-olds (although there were fewer age differ-
5 and 9 years, and between 9 years and adulthood. ences in preferences for female than male faces;
It is useful to note that Boothroyd et al. used adult Saxton et al., 2011). However, another study from
stimuli, whereas Vingilis-Jaremko and Maurer used the same authors suggested that these group differ-
stimuli drawn from each of their three participant ences may have been the result of using different,
age groups and found corresponding patterns of age-matched stimuli for each age group. When
preference in each. two age groups were tested with matching stimuli,
The pattern of results observed in infants by no main effect of age on face preferences was found
Rhodes et al. (2002), and particularly Griffey and (Saxton et al., 2010). In fact, although overall means
Little (2014), strongly suggests that the lack of for femininity and symmetry preferences increased
preferences seen in the 4- to 5-year-olds for all traits with age, preferences for averageness decreased.
in Boothroyd et al., and in the 5-year-olds for Correspondingly, Kościński (2010, 2011, 2013)
symmetry in Vingilis-Jaremko and Maurer’s (2013a), found a similar pattern of means in strength of pref-
is not due to an inability to perceive the differences erence for skin health in girls and boys aged between
between manipulated stimuli. Rather, it seems 11 and 14 years. In the only longitudinal data on
that from infancy onward, differences between sym- facial preferences we are aware of, Saxton et al. (2011)
metric and asymmetric, and average and distinctive were unable to document any clear changes in ado-
versions of the same faces can be visually distin- lescents’ facial preferences over a one-year period,
guished, but preferences for specific characteristics although in a later study on voices it was observed
such as these may only emerge (or re-emerge) in that 11- and 13-year-olds showed a drop in voice pitch
later childhood. This point further highlights the fact preference over a 9- to 12-month period (Saxton,
that maturation of the visual system alone is unlikely DeBruine, Jones, Little, & Roberts, 2013; see also
to explain the onset of preferences for specific Saxton et al., 2009, for similar cross-sectional patterns
facial characteristics. in voice pitch preference). These results are con-
A larger literature exists examining preferences cordant with the cross-sectional data of Boothroyd
during puberty. Multiple studies have found evidence et al. (2014) shown in Figure 9.1. Preferences for
for symmetry, averageness, health, and femininity health, symmetry, and averageness all emerged in
preferences existing from 11 or 12 years onward midchildhood but showed a plateau or dip sometime
(Boothroyd et al., 2014; Kościński, 2011, 2013; between 10 and 14 years of age before increasing to
Saxton et al., 2009, 2010; Saxton, DeBruine, Jones, adult levels by age 17. Likewise, although directional
Little, & Roberts, 2011), although Little et al. (2010) preferences for femininity never exceeded chance
found a significant preference for masculinized male levels until age 17, the same pattern of a drop in
faces in 11- to 14-year-old girls. Where these studies preferences occurred at 13 to 14 years.
have utilized adult comparison samples, results have There are therefore two issues that need resolving
tended to show that although specific preferences when considering preferences across childhood and
have been activated by puberty, they are still not adolescence: (1) What causes these preferences to
expressed at adult levels until some point after age emerge in the first place? (2) Why, when we would
14 (e.g., Boothroyd et al., 2014; Vingilis-Jaremko expect an explosion in mate-choice-relevant behav-
& Maurer, 2013a, 2013b). Similarly, Saxton et al. ior at puberty, do we instead see this emergence
(2006) have found that the nature of adolescents’ disrupted? In explaining the emergence of specific
voice and face preferences show more agreement than preferences across childhood, one hormone has
those of younger groups, but still do not show full come under repeated speculation. The earliest stage
agreement with adults’ ratings of the same stimuli. of puberty is adrenarche, when the adrenal gland

148 Mate Preferences Across the Lifespan

 0.8

0.7

Proportion of high trait faces chosen

0.6

0.5

0.4

4–5yo 6–8yo 9yo 10–12yo 13–14yo 17yo

Age Group
Error bars: 95% Cl
Averageness Femininity Health Symmetry

Figure 9.1 Summary of the trajectories of specific face preferences with age (data from Boothroyd et al., 2014). Most traits show stronger
preferences across mid-childhood, with a dip or plateau around puberty, before increasing to adult levels by 17 years. Children were
grouped by putative dehydroepiandrosterone (DHEA) levels/puberty stage; 4–5 DHEA at floor, 6–8 early adrenarche, 9 later adrenarche,
10–12 late adrenarche/early gonadarche, 13–14 late gonadarche, 17 years adult-like hormones.

600

500

400

300

200

100

0
–1 1 3 5 7 9 11 13 15
Girls Boys

Figure 9.2 DHEA levels (ng/100 ml) across 0–15 years, re-drawn from de Perretti & Forest (1976).

primes the body for full puberty by releasing sexual attraction in boys and girls (McClintock &
­dehydroepiandrosterone (DHEA), a hormone that Herdt, 1996). Furthermore, levels of DHEA are
mainly acts as a precursor to other sex hormones. also high during the postnatal period but drop to
DHEA release begins around 6 years of age and in- floor by age 2. If DHEA plays a role in the develop-
creases dramatically around 9 to 11 years (de Peretti ment of specific mate preferences, this may explain
& Forest, 1976; see Figure 9.2). This surge in the apparent U-shaped curve in certain facial prefer-
DHEA may trigger the first conscious feelings of ences across infancy and early childhood; as such,

Boothroyd and Vukovic 149

DHEA is an obvious candidate hormone for dip in face processing. Indeed, Scherf et al. explicitly
activation of adult-like preferences for specific
­ suggest that attraction may be subject to the same
facial traits, as has been suggested by multiple disruption as other aspects of face processing and
­authors (e.g., Boothroyd et al., 2014; Connolly comment on the current paucity of data assessing
et al., 2004; Saxton et al., 2009). this possibility. This suggests that, whereas changes
With respect to facial preferences in particular, it in DHEA may activate the initial onset of adult-like
is useful to consider the wider literature on the facial preferences, cognitive processing factors may
­development of face processing. A cognitive approach subsequently constrain the expression of preferences
to facial preferences assumes that preferences at least until puberty is completed.
partially reflect the manner in which faces are pro- Attempts to explicitly link pubertal development
cessed and stored in the brain. Thus, children’s judg- to changes in mate preferences and facial recognition
ments of attractiveness may become more similar alike, however, have yielded mixed results. Typically,
to those of adults as they get older because of in- researchers use standardized self- or parent report
creasing expertise in the perceptual and processing measures of puberty to assign puberty stages to
skills required to evaluate aspects of attractiveness. participants and assess whether stage or raw scores
Research has not yet investigated links between on pubertal development predict preferences/­
children’s facial preferences and their processing performance (e.g., Boothroyd et al., 2014; Saxton
of other visual stimuli; furthermore, it has been et al., 2010). These puberty measures typically utilize
argued that face processing is essentially mature by the Tanner classification images or verbal descrip-
midchildhood (McKone, Crookes, Jeffery, & Dilks, tions of physical development that align with the
2012; McKone, Crookes, & Kanwisher, 2009; but Tanner drawings. Although phenotypic cues to pu-
see Susilo, Germine, & Duchaine, 2013). However, berty are associated with changes in sex hormones,
much like the pattern of face preferences plateauing they remain a blunt instrument in assessing those
during later puberty, a “developmental dip” in other underlying hormones and are subject to report biases
forms of facial processing occurs around the same from children and parents alike (see, e.g., Carskadon
age. Multiple studies have documented a period & Acebo, 1993, for discussion). It is therefore not
between 10 and 14 years of age in which performance entirely surprising that Boothroyd et al. (2014)
on face recognition either dips or plateaus before found no link at all between mate preferences and
increasing to adult levels later on (Carey, Diamond, & puberty stage, whereas Saxton et al. (2010) found
Woods, 1980; Chung & Thomson, 1995; Lawrence that more advanced puberty was associated with
et al., 2008). Recent evidence has shown that the stronger preferences for symmetry, but not for aver-
dip is specific to ­processing faces; Johnston et al. ageness or voice pitch, and that pubertal develop-
(2011) found that both facial identity recognition ment had inverse effects on femininity preferences
and facial emotion recognition showed a dip, but at 12 versus 13 to 14 years. Kościński found little
that recognition of other complex stimuli, namely, evidence for breast development as a marker of
butterflies, did not. These data rule out alternative puberty being linked to girls’ preferences for skin
explanations such as task demands affecting perfor- health (Kościński, 2011, 2013) and indeed limited
mance and suggest that the “dip” is specific to facial evidence for it predicting any other aspects of girls’
(and perhaps particularly social) stimuli. preferences (e.g., for “sexy looking” or “friendly”
This developmental dip in face processing has faces). Only Kościński’s (2010) data on 11- and
been hypothesized to be part of a broader pubertal 12-year-old boys showed a strong link between
reorganization in which the brain is realigned to the current development and maturity of preferences.
social and cognitive challenges of mating. Scherf, To our knowledge, no researchers have assessed
Behrmann, and Dahl (2012) suggest that the ap- pubertal hormones directly when seeking to test links
parently sex-linked or directly sex-hormone-linked to mate choice. In a pilot study, Boothroyd and col-
anatomical and functional changes in cortical face leagues investigated whether salivary DHEAS levels
processing regions and subcortical bodies (e.g., to (a diurnally stable metabolite of DHEA) were associ-
the amygdala) during adolescence may demonstrate ated with face preferences in a group of 10-year-old
a period of increasing specialization for adult sexual children. The resulting data were largely nonsignifi-
behavior. They argue that this realignment may result cant; however, in part this may be due to 10 years of
in temporary disruption of social functions and age being an inappropriate window for assessing
may underlie phenomena such as the developmental these impacts (Boothroyd et al., in preparation). The

150 Mate Preferences Across the Lifespan

combined weight of the Boothroyd et al. (2014) coitus (e.g., Downing & Bellis, 2009; Udry, 1979),
cross-sectional data and the Scherf et al. (2012) and given the sex difference in age of puberty, those
review, regarding activatory and inhibitory periods of early relationships are likely to be with older males.
change in mate preferences, would suggest that any Related to this, Kościński (2010) found that boys’
activational effects of DHEA may best be observed in sexual experience predicted similar patterns of face
the 6-to-9-year window, whereas any inhibitory preferences as their pubertal development, high-
impact of gonadal hormones may best be observed in lighting the impact experience may have.
the 11-to-14-year window. Future research seeking to One key problem with the data on pubertal de-
test the hypothesis that adrenal and gonadal hor- velopment and mate choice during puberty may thus
mones may alternatively activate mate preferences be that pubertal hormones may have differing effects
and then inhibit face and other social ­processing within and between individuals. Indeed, although
must also concurrently test both mate preferences breast development was a weak predictor of prefer-
and facial processing alongside hormone assays to ences among Kościński’s (2013) female participants
fully explore the interactions between the three. within 12- and 13-year-old cohorts, girls with earlier
An additional qualification to the mixed results menarche had more adult-like preferences for health,
on puberty, however, is that cross-sectional samples facial “sexiness,” and facial cues considered by adults
may not offer the best determinants of this question. as indicating a good partner. Although Kościński
Individual differences in age of puberty are associated viewed time since menarche as an index of relative
with preferences for both faces and voices. Women pubertal development, the fact that breast develop-
who experienced first menses at an earlier age prefer ment showed no strong patterns suggests these data
more masculinized faces (Cornwell et al., 2006) were picking up on timing of previous developments
and deeper voices (Jones, Boothroyd, Feinberg, & rather than current hormonal status per se. As such,
DeBruine, 2010) in adulthood. When shown natu- research into hormonal drivers of pubertal develop-
rally varying male facial stimuli, Hoier’s (2003) par- ment in mate choice must include longitudinal,
ticipants showed a tendency for earlier first menses within-individual analyses. Indeed, many of the stud-
to predict rating all faces as more attractive than ies that have found hormonal influences on mate
women with later first menses. These differences preferences in adults have relied on within-individual
may reflect the impacts of early stressors on pubertal comparison. For instance, Welling et al. (2008) found
development (see Deer, Bernard, & Hostinar, this no difference between men with overall higher and
volume, for further discussion) and mate preferences lower testosterone in terms of their preferences for
alike or alternatively reflect differences in sexual and female femininity; there was, however, a significant
romantic experience, arising from earlier versus later difference in mate preferences when comparing
menarche, shaping future preferences. For instance, between the two sessions in which each man had
earlier first menses is associated with earlier first higher versus lower levels of testosterone.

Box 9.1. Facial Preferences and Parental Features

Despite any potential role of innate representations in early preference as per the neonates in Slater et al. (1998, 2000),
later infant preferences are undoubtedly influenced by experience with the faces of conspecifics. For instance, while
most studies show a preference among infants for female faces over male faces (see, e.g., Ramsey-Rennels & Langlois.,
2006, for a discussion), infants whose primary carer is male show a preference for male faces over female faces
(Quinn, Yahr, Kuhn, Slater, & Pascalis, 2002). This strongly suggests that in early life, at least, the primary carer is the
major influence on facial prototyping and facial preferences (although see, e.g., Cooper, Geldart, Mondloch, & Maurer,
2006, for evidence on the potential importance of peers in childhood preferences).
Parental features are also important in attraction in adulthood. The phenomenon of sexual imprinting (whereby
an organism bases its choice of adult sexual partner on the features of its parents) is well documented in some animal
species (e.g., Zebra finches: Vos, 1995) and has been shown to operate among humans, with adults showing preferences
for parental features in terms of race (Jedlicka, 1980), coloring (Little, Penton-Voak, Burt, & Perrett, 2003), hairiness
(Rantala, Pölkki, & Rantala, 2010), age (Perrett et al., 2002), and even personality (Gyuris, Jarai, & Bereczkei, 2010).
The ontogeny of this phenomenon, however, remains obscure.

(continued )

Boothroyd and Vukovic 151

 Box 9.1. Continued

It may be that our facial prototypes are based on the faces we are exposed to, and that although this process is
continuous throughout life (e.g., Anzures, Mondloch, & Lackner, 2009; Rhodes et al., 2003; Webster & MacLeod,
2011), extensive exposure to our parents in early life heavily biases our prototypes, and ergo our preferences,
toward parental features. However, evidence suggests that a degree of associative learning may also take place, with
positive parent–child relationships predicting greater imprinting. For instance, Bereczkei and colleagues (Bereczkei,
Gyuris, Koves, & Bernath, 2002; Bereczkei, Gyuris, & Weisfeld, 2004) used a photograph-matching task to show
that similarity between an individual’s opposite-sex parent and spouse was significantly greater if the individual
reported a warmer relationship with that parent (although see Marcinkowska & Rantala, 2012). Furthermore,
Bereczkei et al. (2004) controlled for self-similarity effects and used adoptive fathers and daughters so that genetic
explanations can be ruled out. Wiszewska, Pawlowski, and Boothroyd (2007) found that the objective facial
proportions of women’s fathers significantly correlated with the proportions of faces they found most attractive
out of an array, although only if the daughters reported a positive relationship with their father. Similarly, Kocsor,
Saxton, Láng, and Bereczkei (2016) found that participants who reported less rejecting opposite-sex parents had
stronger preferences for faces manipulated to resemble that parent.
Developmental research into imprinting-like phenomena is particularly rare. Two studies have demonstrated that
children may show a preference for parental features prior to puberty. Kocsor, Gyuris, and Bereczkei (2013) used a
story completion task with 3- to 6-year-olds and found that boys who completed a story about a young bird in a
storm with the bird flying to one of its parents preferred father-like faces more than boys who completed the story
with a different ending. There was no such pattern for maternal features or in girls. Using more standardized measures
of attachment, Vukovic, Boothroyd, Meins, and Burt (2015) looked at preference for parent-like faces in 9-year-olds
drawn from a longitudinal cohort and found that although infant attachment as measured in the strange situation
paradigm at 15 months did not predict preferences for parental features in either sex of face, children who reported
a currently more accepting relationship with their parents (on the Parental Acceptance and Rejection Questionnaire:
Rohner & Khaleque, 2005) favored more parent-like faces. This pattern held for girls looking at both sexes of face,
and for boys looking at female faces. For boys looking at male faces, visual exposure predicted preference for paternal
features but current relationship did not.
Interestingly, although Vukovic et al. (2015) interpreted their data as indicating that parental imprinting may
reflect a transient associative impact of positive parent–child relationships on attitudes to parental features, with
current experience superseding past experience, Saxton (2016) found that retrospective reports of parent–child
relationships had different impacts in different time periods. Specifically, the similarity of women’s ideal/actual
partner’s eye color and their father’s eye color was positively predicted by closeness to father in midchildhood and
negatively predicted by closeness to father after puberty. This would suggest that puberty may act as a watershed for
typical imprinting effects and that incest avoidance mechanisms may come more to the fore once individuals are
reproductively mature (although incest avoidance mechanisms regarding siblings typically have a much earlier critical
window; reviewed in Rantala & Marcinkowska, 2011).

Facial Preferences and Menopause greater variation in their preferences and had a lower
Further evidence that hormonal changes across intraclass correlation than perimenopausal women
the lifespan are associated with variation in mate of the same age. Studies into specific preferences
preferences comes from studies that tested pre- and and menopause have operated on the assumption
postmenopausal women. As women approach men- that the decline in fertility around menopause may
opause, estrogens, progesterone, and testosterone trigger a shift away from a mate-oriented mindset
decrease and fertility declines (Burger, Dudley, toward a community-oriented psychology (Hawkes,
Robertson, & Dennersten, 2002; Burger, Hale, O’Connell, Jones, Alvarez, & Charnov, 1998). Thus,
Dennerstein, & Robertson, 2008). Just as preferences postmenopausal women should be less attracted to
for overall attractiveness become more c­onsistent indices of mate quality. Furthermore, the decline in
within groups as children age (Saxton et al., 2009), sex hormones ought to be associated with a decline
so they may become less so across menopause. in face preferences that are strongly modulated by
Kościński (2011) asked peri- and postmenopausal these hormones.
Polish women aged 40 to 62 years to judge the Considering that previous research has established
­attractiveness of stimuli of male facial photographs. a small but robust link between women’s fertility
The postmenopausal women showed significantly across the menstrual cycle and heightened preferences

152 Mate Preferences Across the Lifespan

for masculinity in particular (Jones, Little, et al., It is also worth noting that although Vukovic
2005; Little, Jones, & DeBruine, 2008; Welling et al. (2009) and Jones et al. (2011) found an over-
et al., 2007), research around menopause has also all preference for femininity, the Little et al. (2010)
tended to focus on this trait. Vukovic et al. (2009) participants showed a general preference for mas-
first investigated the association between fertility culine men’s faces. These results are not surprising
across the lifespan and women’s masculinity prefer- considering that other studies have found no con-
ences. The authors tested 97 women’s masculinity sensus as to whether women overall prefer mascu-
preferences, 45 of whom were no longer experienc- line or feminine male faces (see Scott et al., 2014;
ing menstrual cycles due to menopause and all of Fink & Penton-Voak, 2002). It is therefore impor-
whom reported that they were not using any hor- tant for further studies to recruit participants of
mone replacement therapies or hormonal contra- various backgrounds and ages and from different
ceptives. Participants gave forced-choice preferences cultures. Also, although masculine men are per-
for pairs of masculinized and feminized versions of ceived to look older (Boothroyd et al., 2005) and
both male and female faces. Postmenopausal women older women have been found to prefer older faces
had weaker masculinity preferences than premeno- (Kościński, 2011), the studies on circum-menopausal
pausal women, but the difference between the pre- women’s masculinity preferences emphasize that
and postmenopausal groups was not significant. masculinity and perceived age are separate, com-
One possible reason for this null result may have pound facial traits. As such, manipulations of these
been the small sample. Little et al. (2010) investigated independently may differentially influence women’s
pre- and postmenopausal women’s preferences for preferences. Moreover, both Vukovic et al. (2009)
facial masculinity in two samples with nearly 200 and and Jones et al. (2011) considered both male and
nearly 2,000 participants, respectively. In Study 1, female faces. Postmenopausal (i.e., infertile) women
participants between the ages of 40 and 65 years preferred more feminine female faces than did
judged the attractiveness of 10 trials containing ­premenopausal (i.e., fertile) women. The authors
masculinized and feminized versions of men’s faces. controlled for age, suggesting that these results
In Study 2, women aged 36 to 45 years were com- were due to the differences in hormonal profiles
pared to women over 45 years (among other groups). between pre- and postmenopausal women. In line
In both cases, postmenopausal participants and/or with theories of heightened intrasexual competi-
those aged over 45 years preferred less masculine tion during periods of high fertility (see Fisher,
men than did premenopausal/younger women. These 2004; Jones, Little, et al., 2005; Welling et al.,
­results suggest that postmenopausal women are more 2007), this research implies that same-sex compe-
attracted to the direct prosocial benefits signaled by tition for potential mates decreases as women’s
relatively feminine men (see also Fink & Penton- fertility declines, and that women may become
Voak, 2002; Gangestad & Simpson, 2000; Jones more honest about the attractiveness of other women
et al., 2008; Little, Jones, Penton-Voak, Burt, & as they age (i.e., may be less likely to derogate their
Perrett, 2002; Rhodes, Simmons, & Peters, 2005). competitors).
Another factor contributing to the weak results Another testosterone-dependent masculine trait
in Vukovic et al. (2009) may be that the stimuli used in men’s faces, other than male-typical face shape,
in the study were of young adults. Therefore, it is and which has been studied in relation to menopause
possible that circum-menopausal women did not is facial hair. To test out women’s preferences for
view the young male faces used in the study as faces facial hair, Dixson, Tam, and Awasthy (2012) col-
of potential mates. Accordingly, Jones, Vukovic, Little, lected stimuli of men at various stages of beard
Roberts, and DeBruine (2011) replicated the study growth: clean shaven, light stubble, heavy stubble,
using face stimuli of individuals closer to the age of and full beard. Participants were women in New
a new sample of circum-menopausal participants. Zealand of various reproductive statuses who were
Results yielded a significant difference between pre- asked to choose the most attractive of the stimuli
and postmenopausal women’s preferences for men’s presented. Interestingly, postmenopausal women
faces, whereby postmenopausal women preferred the found all the stimuli more attractive than did pre-
feminized versions of the men’s faces. Collectively, menopausal women, although cohort effects are pos-
these results provide evidence for hormonally driven sible, suggesting a general shift in baseline thresholds
variation in women’s masculinity preferences and for attractiveness in (young) faces. There was no
highlight the importance of testing face preferences interaction between menopause and preferences for
using a wide range of stimuli. degree of facial hair in the stimuli, indicating no

Boothroyd and Vukovic 153

specific change in attitudes to beards in these groups. mate preferences, and how these preferences influence
Much like in Vukovic et al. (2009), the authors social interactions within this age cohort. For in-
suggested that images of older men should be used stance, menopause may not proceed in the same
in future studies and may yield different results. It is manner for all women (indeed, any study relying
also worth noting that Dixson et al. (2012, 2018) on proxies of hormones such as cycle phase is sub-
found minimal evidence for differences in fertility ject to this caveat) and, as in the pubertal period,
status in younger women affecting attitudes to there is a dearth of direct assessments of hormones
beardedness in the same and a more recent study. As in menopausal women. As such, suggestions that
discussed by Dixson et al. (2012), male mate quality these changes are directly the result of circulating
is signaled partly by shape-based traits like chins hormones rather than, for instance, byproducts of
and jaw lines, which are masked by facial hair. As changing self-rated attractiveness with age, or ex-
such, beardedness may not show a straightforward plicit knowledge of changing fertility and thus
relationship with typical predictors of mate prefer- changing attitudes toward relationships, remain
ences, being both a display and a mask of mate untested. These findings point to a need for more
quality. Indeed, Dixson, Sulikowski, Gouda-Vossos, studies using diverse participants, larger sample
Rantala, and Brooks (2016) showed evidence for an sizes, and more diverse stimuli of faces of various
interaction between masculinity and beardedness; phenotypes. Additionally, future studies should
extremely feminine and masculine men looked more employ more hormonal assay techniques to more
attractive when bearded, but not men in between. accurately assess participants’ hormonal profiles.
Given the evidence that women typically prefer men Finally, there is also a need to consider age-related
closer to “average” levels of masculinity (e.g., Scott, hormonal changes in men and the impacts of these
Pound, Stephen, Clark, & Penton-Voak, 2010), changes on preferences. To our knowledge, only one
this suggests beards may operate more as a mask study has examined trajectories in heterosexual male
than as a signal. preferences for females in later life. Marcinkowska,
Finally, Kościński (2011) also assessed circum- Dixson, Kozlov, and Rantala (2015) found a fairly
menopausal women’s preferences for mate-relevant linear decline in men’s preferences for facial femininity
aspects of facial appearance, such as health. As in in women between 30 and 70 years of age (although
the aforementioned studies, preferences for facial even the oldest participants still preferred feminized
health declined with menopause, as did preferences stimuli more than chance). This is a period in which
for faces rated by other women as “sexy” or “mar- testosterone may decline initially through lifestyle
riageable,” although preferences for “friendliness” factors (e.g., marriage and fatherhood; for review
remained constant. Although health preferences are see Gray & Campbell, 2009) and later through
a reasonably objective feature, it should be noted aging processes (Harman, Metter, Tobin, Pearson,
that “sexiness” and “marriageability” are inherently & Blackman, 2001), and thus may lead to decreased
subjective constructs shaped in part by the prefer- interest in indices of female mate quality. However,
ences of the perceiver, and as such these declines again, the study was unable to directly assess hormone
may simply reflect changing definitions of what levels and utilized young female stimuli. Given that
constitutes sexiness, for instance, in older women. feminine faces look younger, it is possible that this
The results are, however, consistent with those pre- decline in part merely reflects an interest in more
sented earlier for objectively manipulated masculinity age-appropriate partners.
and contribute to the overall suggestion that men-
opause does indeed lead to a decline in those mate Conclusion
preferences commonly ascribed to hormonal factors. There are several key themes that arise when consid-
Collectively, the aforementioned research suggests ering these lifespan approaches to mate preferences.
that women’s preferences for cues of mate quality First, although there are some aspects of faces about
in men change across the lifespan. Specifically, which individuals of all ages from birth through
these studies show hormonally driven variation in menopause consider attractive, preferences for spe-
women’s attraction to masculinity, health, and sex- cific aspects of faces, voices, and bodies that have
iness, whereby postmenopausal women tend to been linked to mate quality in adults are subject to
prefer more feminine, less healthy, and less sexy (as change over time. When we consider patterns across
rated by younger women) individuals than do fer- midchildhood and menopause, it seems likely that
tile women. More research is needed, however, to pubertal hormones may activate specific mate pref-
better understand the link between fertility and erences, whereas menopause and the corresponding

154 Mate Preferences Across the Lifespan

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Boothroyd and Vukovic 159

 CH A PT E R
The Influence of Maternal Stress
10 and Child Maltreatment on Offspring

LillyBelle K. Deer, Kristin Bernard, and Camelia E. Hostinar

Abstract

Child maltreatment has significant impacts on developmental trajectories and is one of the most
preventable early-life adversities. It shapes the development of many biological systems, with
most research concentrating on its influence on stress response systems like the hypothalamic-
pituitary-adrenal (HPA) axis. This chapter reviews associations between child maltreatment and HPA
axis activity across development. One emerging pattern is that of flattened diurnal cortisol slopes in
children, adolescents, and adults with childhood maltreatment histories. This effect was moderated
by psychiatric diagnosis, maltreatment subtype, and genetic vulnerability in some studies. Effects on
cortisol reactivity are more mixed, including reports of higher reactivity, lower reactivity, or no
differences compared to nonmaltreated samples. Interventions that focus on enhancing the quality of
parent–child relationships early in life may reverse some of the effects of maltreatment. This chapter
discusses implications of maltreatment-related alterations in HPA axis function for mental and physical
health and concludes with suggested future research directions.

Keywords: maltreatment, HPA axis, cortisol, early-life adversity, maternal stress, intervention

Child maltreatment can have a profound impact on axis (Burke, Finn, McGuire, & Roche, 2016;
developmental trajectories and is one of the most Chrousos, 2009; Lee, 2010; Pratchett & Yehuda,
preventable early-life adversities that children face 2011). The goal of the present review is to examine
(Bruce, Gunnar, Pears, & Fisher, 2013; Cicchetti, the evidence that child maltreatment shapes the
2016). Maltreatment during childhood is associated ­development of the HPA axis and reveal the nature
with increased risk of later psychopathology, espe- of the associations between maltreatment and several
cially posttraumatic stress disorder (PTSD) and aspects of HPA functioning: basal activity, reactivity
depression (Kaufman & Charney, 2001; Pratchett & to stressors, and responses to pharmacological chal-
Yehuda, 2011; Teicher & Samson, 2013). It also lenges. We describe the existing human literature on
­forecasts poorer adult physical health, including associations between child maltreatment and indi-
greater odds of developing cardiovascular disease ces of HPA activity in childhood, adolescence, and
and diabetes (Ehrlich, Miller, & Chen, 2016; Gilbert adulthood. We begin by discussing the influence of
et al., 2015), obesity (Danese & Tan, 2014), fibro- maternal stress and other risk factors for maltreat-
myalgia, and chronic fatigue syndrome (Borsini, ment. This is followed by brief overviews of the
Hepgul, Mondelli, Chalder, & Pariante, 2014; Lee, HPA axis and animal models of maltreatment
2010). It is theorized that one common pathway and its effects on the HPA axis. Then, we summa-
leading to the development of these diverse mental rize the existing human literature on maltreatment
and physical health problems involves the dysregu- and the HPA axis. We conclude by discussing some of
lation of the hypothalamic-pituitary-adrenal (HPA) the implications of maltreatment-related alterations

161
in HPA functioning for mental and physical health abuse (U.S. Department of Health & Human
and p­ roviding some suggested future directions for Services, Administration on Children, Youth and
this area of research. Families, Children’s Bureau, 2016). However, statis-
tics based on officially documented cases likely un-
Child Maltreatment: Definition, derestimate the overall prevalence of maltreatment,
Prevalence, and Risk Factors which is 10 times higher according to victim and
Although definitions of maltreatment vary based parent reports (Gilbert et al., 2009). Official records
on factors such as culture or purpose (e.g., legal vs. in the United States show that rates of child
research), maltreatment can be broadly defined as ­maltreatment have declined since the early 1990s
aberrant caregiving behaviors that threaten a child’s (Jud, Fegert, & Finkelhor, 2016). However, it is
well-being and capacity for psychobiological adap- unclear whether these statistics represent real change
tation (Cicchetti, 2016). Maltreatment can be divided or differences in how these incidents are reported or
into behaviors that reflect abuse (i.e., physical abuse, investigated. For obvious reasons, much less is known
sexual abuse, emotional abuse) or neglect (i.e., physi- about the rate of change over the past two decades
cal neglect, emotional neglect; Barnett, Manly, & among unreported cases. Despite the encouraging
Cicchetti, 1993). Physical abuse involves the nonac- indication of improvement over time, child maltreat-
cidental infliction of physical injury on a child and ment remains all too prevalent and is a significant
can range from a temporary injury to a permanent societal concern.
disfigurement. Sexual abuse involves an attempted Maltreatment is thought to be caused by a
or actual sexual act between a child and a family ­complex interplay of factors and systems (Garbarino,
member or caretaker for purposes of that person’s 1977; Howze & Kotch, 1984; Thompson, 2015).
sexual enjoyment or financial benefit. Emotional Studies have focused on maternal factors because
abuse involves threatening behavior that thwarts many of the families where child maltreatment is
a child’s basic emotional needs for psychological observed tend to be single-parent families where the
safety and security, acceptance and self-­esteem, and mother is the parent, and mothers tend to spend the
age-appropriate autonomy; emotional neglect simi- most time with their children (Taylor, Guterman,
larly conveys to a child that he or she is unloved, Lee, & Rathouz, 2009). The most commonly stud-
unwanted, or unworthy but involves the lack of ied risk factor is maternal stress, which can stem
­appropriate emotional responsiveness, rather than from multiple sources, including intimate partner
threatening emotional input. Physical neglect can violence (Antai et al., 2016; Taylor et al., 2009);
be divided into two different subtypes: failure to having an insecure attachment with their own par-
provide, which involves the failure to meet the child’s ents or being maltreated as a child (Cicchetti,
nutritional, medical, or hygiene needs, and lack of Rogosch, & Toth, 2006; De Bellis et al., 2001;
supervision, which includes either leaving a child Widom, Czaja, & DuMont, 2015); having many
unattended or with an inadequate caregiver. Severity, children (Cicchetti et al., 2006; Kotch et al., 1995);
frequency, and chronicity, as well as the develop­ being a single parent or having unstable relation-
mental period in which the abuse occurred, are also ships (Cicchetti et al., 2006; Taylor et al., 2009);
essential parameters to take into account when as- receiving low levels of family support (Cicchetti
sessing child maltreatment (Barnett et al., 1993). et al., 2006; Cowen, 2001); suffering from psycho-
The majority of research on the sequelae of child pathology such as substance abuse, depression, and
maltreatment has been conducted on samples from PTSD (De Bellis et al., 2001; Kotch et al., 1995;
the United States and Europe, with comparatively Taylor et al., 2009); having a child with conduct
fewer studies reporting results from other regions of disorder, which can create a vicious cycle of escalat-
the world (Stoltenborgh, Bakermans-Kranenburg, ing maltreatment and worsening conduct problems
Alink, & van IJzendoorn, 2015). More recent research (Cowen, 2001; Dodge, Bates, & Pettit, 1990); and
has begun examining the prevalence and risk factors certain maternal personality attributes, such as
for child maltreatment in developing countries poor impulse control (Cowen, 2001; De Bellis
(Antai, Braithwaite, & Clerk, 2016; Singhi, Saini, & et al., 2001). Low socioeconomic status and being
Malhi, 2013). The official prevalence estimate in from an area where there is large income inequality
the United States was of 702,000 abused or ne- are other risk factors (Cicchetti et al., 2006; Cowen,
glected children in 2014, or 9.4 victims per 1,000 2001; De Bellis et al., 2001; Eckenrode, Smith,
children, with rates of abuse decreasing with age McCarthy, & Dineen, 2014; Kotch et al., 1995).
and neglect being the most common subtype of Residence with a stepparent has also been noted as a

162 Influence of Maternal Stress and Child Maltreatment

significant epidemiologic risk factor for child abuse, anterior pituitary gland (Joëls & Baram, 2009; Levy
neglect, and murder (Daly & Wilson, 1988, 2005), & Tasker, 2012). The pituitary responds by releasing
which predicts outcomes i­ndependently of the adrenocorticotropic hormone (ACTH) into circula-
other risk factors mentioned previously. Naturalistic tion, which binds to its receptors in the cortex of the
studies also note that children living with steppar- adrenal gland. This stimulates the production of
ents exhibit elevated levels of basal cortisol com- the steroid hormone cortisol by the adrenal (Gunnar
pared to biological children living in the same et al., 2015; Smith & Vale, 2006).
families, perhaps suggesting greater exposure of
­ Cortisol has pervasive effects across the body
stepchildren to adverse events in the home (Flinn, (Sapolsky et al., 2000). Acutely, cortisol facilitates the
Ward, & Noone, 2005). Evolutionary explanations mobilization of energy to the muscles, increases car-
for these phenomena highlight the reproductive fit- diovascular output, sharpens cognition and alertness,
ness benefits of suppressing violent or conflictual and stimulates immune function, while inhibiting
tendencies toward genetically related offspring other bodily functions that are not as immediately
(Daly & Wilson, 1988). These are some of the pre- necessary, such as reproductive physiology and appe-
dictors that have been linked to higher likelihood of tite (Sapolsky et al., 2000). When cortisol is released
child maltreatment. For the remainder of the chap- into the circulation, it acts upon its receptors through-
ter we focus on the outcomes of child maltreatment, out the body, of which there are two main types:
with a primary emphasis on alterations in the func- mineralocorticoid receptors (MRs) and glucocorti-
tioning of stress response physiology and possible coid receptors (GRs; Gunnar et al., 2015; Joëls &
consequences for mental and physical health. Before Baram, 2009). MRs have higher binding affinity for
proceeding, a brief introduction to the activity of cortisol than GRs and regulate the basal activity of
the HPA axis is necessary. the HPA across the day (Herman et al., 2016). The
lower affinity GRs become activated at higher levels
Overview of the Hypothalamic-Pituitary- of cortisol, including at the peak of the diurnal cycle
Adrenal Axis and during stressors, mediating the effects of these
When confronted with physical or psychological stressors on many organs and systems including
challenges that overwhelm the individual’s capacity the brain (Herman et al., 2016).
to cope, the body initiates a number of physiologi- In the past two decades there has been burgeon-
cal and behavioral responses through the endocrine, ing interest in characterizing how early-life experi-
nervous, and immune systems (Gunnar, Doom, & ences shape both the basal activity and the reactivity
Esposito, 2015). The hypothalamic-pituitary-­adrenal of the HPA axis to stressors or under pharmacologi-
(HPA) axis plays an integral role in these processes cal challenge. Dysregulation of the HPA axis is fre-
by mobilizing energy for coping with stressors and quently noted in children and adolescents experi-
modifying the individual’s responses to similar encing psychosocial adversity (Ehlert, 2013; Fisher
stressors in the future (Gunnar et al., 2015; Sapolsky, et al., 2016; Tarullo & Gunnar, 2006) and has
Romero, & Munck, 2000; Smith & Vale, 2006). been increasingly linked to deleterious physical and
The activity of the HPA axis can be studied along mental health outcomes (Bruce et al., 2013; De
two basic dimensions: basal functioning and reac- Bellis, Spratt, & Hooper, 2011; Ehlert, 2013; Gunnar
tivity to stressors (Joëls & Baram, 2009). Basal HPA et al., 2015), as we discuss in more depth in subse-
functioning follows a diurnal rhythm whereby cor- quent sections.
tisol, the end product of the HPA axis, is secreted in
a pulsatile fashion across the day, reaching peak Animal Models of Early-Life Maltreatment
levels in the morning approximately 30 minutes Animal models have been critical in substantiating
after awakening, and declining gradually across the the causal role of maltreatment on neurodevelop-
day to reach minimum levels at night (Joëls & mental trajectories (Drury, Sanchez, & Gonzalez,
Baram, 2009). Superimposed on this basal rhythm 2016; Sanchez, 2006; Parker & Maestripieri, 2011).
is the reactivity of the HPA axis to physical or psy- Rodent models provided some of the earliest mech-
chological threats to well-being (i.e., stressors). anistic data on the effects of low- versus high-quality
Stress-induced cortisol production begins when maternal care on the HPA axis (Meaney & Szyf,
corticolimbic regions relay threat signals to the 2005; Plotsky & Meaney, 1993). Nonhuman primate
paraventricular nucleus (PVN) of the hypothala- models have greatly added to these insights, partic-
mus, which releases corticotropin-releasing hor- ularly since there are several important s­ imilarities
mone (CRH) and arginine vasopressin onto the between them and humans (e.g., the importance

Deer, Bernard, and Hostinar 163

of maternal care for primate development, the Despite these average trends, there is variability in
prolonged period of postnatal maturation and outcomes, such that some animals are more vulner-
growth; Sanchez, 2006). As nonhuman primate able than others to this experimental disruption
models are the most similar to human development, (Coplan et al., 2001). More research is needed to
we focus on them in this section. uncover the genetic and experiential bases for these
Research on early-life adversity in nonhuman individual differences in reactions to VFD condi-
primates has primarily focused on maternal stress tions in mothers and their offspring.
and its effects on the mother’s HPA system, the off- Other studies have focused on the effect of natu-
spring’s HPA system, and the dyad’s relationship rally occurring maltreatment on the offspring’s HPA
(Sanchez, 2006; Sanchez, McCormack, & Howell, axis. As in humans, the quality of maternal care
2015). Maltreatment tends to occur in 5 to 10 per- alters infants’ HPA axis and their reaction to stress
cent of rhesus macaques and other related primate (Drury et al., 2016), as well as their mothers’ ability
species and occurs primarily in infancy, similar to to buffer their stress response (Sanchez et al., 2015).
humans (Maestripieri & Carroll, 1998; Sanchez Maltreated primates exhibit heightened basal corti-
et al., 2010). Additionally, primates who abuse their sol levels in infancy, which appear to normalize at
offspring tend to have been abused themselves by later ages (Howell et al., 2013; Koch, McCormack,
their mothers, even if they were cross-fostered (i.e., Sanchez, & Maestripieri, 2014). Despite this appar-
not genetically related to their abusive mothers; ent normalization of basal levels, abnormalities in
Maestripieri, 2005). They also tend to abuse all of cortisol reactivity persist, including heightened cor-
their subsequent offspring, irrespective of whether tisol reactivity to stressors and CRH challenge, and
they are adoptive or biological offspring (Maestripieri, decreased ACTH response to CRH challenge
Megna, & Jovanovic, 2000). This suggests that the (Drury et al., 2016; Sanchez et al., 2010). In studies
abuse has little to do with the infant and is environ- of repeated maternal separation, animals similarly
mentally transmitted (Maestripieri, Lindell, Ayala, show an initial pattern of increased basal cortisol,
Gold, & Higley, 2005). which is followed by a flattened diurnal cortisol
The variable foraging demand (VFD) model has rhythm during the juvenile period, consistent with
been used as an ecologically valid way to study the many studies in humans (Drury et al., 2016). The
effects of maternal stress on the mother–infant dyad mechanisms underlying this transition from hyper-
(Andrews & Rosenblum, 1991; Rosenblum & cortisolism early in life to hypocortisolism later in
Paully, 1984; Sanchez, 2006). This experimental development have yet to be revealed, but down-
paradigm disrupts the mothers’ feeding pattern and regulation of CRH receptors and epigenetic altera-
makes the usual pattern of foraging for food unpre- tions are thought to be at play (Drury et al., 2016).
dictable. This results in elevated levels of corticotro-
pin-releasing factor (CRF) in the cerebrospinal fluid Maltreatment and Hypothalamic-Pituitary-
of the mothers (Coplan et al., 2005) and in more Adrenal Functioning in Children and
rejecting maternal behavior (e.g., mothers break Adolescents
contact with the infants more often; Rosenblum & The human literature on associations between early-
Andrews, 1994), compared to mothers maintained life maltreatment and indices of HPA axis activity in
under normal feeding conditions. The effects of youth is quite heterogeneous (Tarullo & Gunnar,
being randomly assigned to live in a VFD environ- 2006). As we review in more depth in this section,
ment are profound on the offspring as well, with some studies reveal that maltreated youth exhibit
infants showing hyperresponsiveness to stressful heightened cortisol levels, while others show lower
stimuli and elevated levels of CRF in cerebrospinal cortisol levels or no differences compared to non-
fluid (Coplan et al., 2001, 2005). Dysregulation of maltreated groups. There are several reasons for
the HPA system has also been found to persist these varying effects. First, these effects depend on
through the juvenile period, into young adulthood, the HPA axis indices used (basal levels vs. cortisol
and in the offspring of the infants raised in VFD reactivity vs. pharmacological challenge). Second,
conditions (Coplan et al., 2001, 2011; Kinnally the evidence suggests that effects vary based on fea-
et al., 2013; Rosenblum, Forger, Noland, Trost, & tures of the maltreatment experience, such as sub-
Coplan, 2001). These experimental studies indicate type (physical, emotional, or sexual abuse; physical
that induced maternal stress can not only affect the or emotional neglect) or developmental timing.
way that dyads interact but also shape the long-term Lastly, there are individual differences based on
neurobiological development of the offspring. gender, genetics, and the type of psychopathology

164 Influence of Maternal Stress and Child Maltreatment

that individuals develop (e.g., internalizing or were specific to children with two copies of the
­externalizing, posttraumatic stress disorder [PTSD], TAT haplotype of the CRH receptor 1 (CRHR1)
depression). We discuss findings regarding the
­ gene, a gene encoding a receptor that binds CRH,
­association between maltreatment and HPA activity a major player in the activation of the HPA axis
in children and adolescents next and highlight (Cicchetti, Rogosch, & Oshri, 2011). In conclusion,
how the overall pattern of results differs in light of the basal cortisol literature suggests that maltreated
these factors. children and adolescents are more likely to evince
Most of the prior studies in youth have exam- flatter cortisol slopes across the day compared to
ined diurnal cortisol production (e.g., diurnal slope, nonaffected groups, with some studies finding a
the typically steep decline in basal cortisol from main effect of maltreatment and others reporting
morning to evening) or cortisol levels at one point this effect only in subgroups with psychopathology,
during the day. Based on our review of these studies, greater severity, earlier onset of maltreatment, or a
the emerging pattern was that maltreated children genetic vulnerability.
tended to exhibit flattened diurnal cortisol slopes A few studies reported results that at least par-
compared to nonmaltreated comparison groups— tially contradict this overall pattern. A recent report
that is, lower morning cortisol levels and a less steep showed that girls who had been sexually abused
decline across the day (Bernard, Butzin-Dozier, exhibited heightened morning cortisol levels com-
Rittenhouse, & Dozier, 2010; Bernard, Zwerling, & pared to those without a trauma history (Simsek,
Dozier, 2015; Dozier et al., 2006; Fisher, Van Ryzin, Yuksel, Kaplan, Uysal, & Alaca, 2015). However,
& Gunnar, 2011). Consistent with this pattern of there was a negative correlation between morning
flatter slopes, some studies found that girls who had cortisol and time since abuse, suggesting decreasing
experienced sexual abuse had lower levels of morn- levels of morning cortisol as the time interval from
ing cortisol than nonmaltreated girls (King, the abuse increased. Furthermore, in this study chil-
Mandansky, King, Fletcher, & Brewer, 2001), and dren who had experienced multiple sexual assaults
this effect appears particularly pronounced for girls exhibited lower cortisol levels than the nonmal-
with PTSD (Keeshin, Strawn, Out, Granger, & treated group. A study with preschool-aged children
Putnam, 2014). Two other studies found that mal- found that even though children who experienced
treated children were more likely to exhibit flatter neglect exhibited the common lowering of morning
cortisol slopes, but in these studies the flatter slopes cortisol compared to a nonmaltreated sample, chil-
were more characteristic of maltreated children if dren who experienced emotional abuse exhibited
they were also depressed (Hart, Gunnar, & Cicchetti, heightened levels of morning cortisol (Bruce, Fisher,
1996; Kaufman, 1991). Another study found that Pears, & Levine, 2009). In a study of school-aged
lower morning cortisol levels and flatter diurnal children, those experiencing multiple types of abuse
slopes were more likely among maltreated children (physical and sexual abuse) showed elevated morn-
exhibiting both internalizing and externalizing ing cortisol levels compared to the nonmaltreated
symptoms, with a particularly prominent effect in group, though children exposed only to physical
maltreated boys with elevated levels of externalizing abuse showed lower levels of morning cortisol than
symptoms (Cicchetti & Rogosch, 2001b). Both the nonmaltreated group (Cicchetti & Rogosch,
maltreatment subtype and developmental timing 2001a). Finally, a longitudinal study of sexually
appear to matter, as one study found flatter diurnal abused females reported higher morning cortisol in
cortisol slopes among those experiencing early phys- 6- to 16-year-olds recruited within six months of
ical or sexual abuse (before age 5), but not for those disclosure of the abuse, but this pattern changed
exposed to abuse later in development or those across development such that the abused females
experiencing other types of maltreatment (Cicchetti, showed decreasing morning cortisol levels over time
Rogosch, Gunnar, & Toth, 2010). In another study and exhibited lower morning cortisol in young
suggesting a role for maltreatment subtype, Bick adulthood (ages 20 to 32 years) compared to the
et al. (2015) reported that adolescents with moderate nonabused control group (Trickett, Noll, Susman,
to severe neglect showed higher levels of afternoon Shenk, & Putnam, 2010). The conclusion emerging
cortisol than adolescents with little to no experience from some of these studies (Simsek et al., 2015;
of physical neglect, with no effects of other mal- Trickett et al., 2010) is that morning cortisol levels
treatment types. Finally, one investigation focusing can be elevated in some instances in the aftermath
on the role of genes regulating HPA function among of the maltreatment experience, but may lower
maltreated children reported that flatter slopes below normative levels over time. This pattern is

Deer, Bernard, and Hostinar 165

consistent with meta-analytic findings suggesting adolescents showed a blunted cortisol response to
that the HPA axis may hypersecrete cortisol soon the TSST when compared with nonmaltreated
after an adverse event, but may down-regulate and ­females (MacMillan et al., 2009). In another analysis
switch to a pattern of hyposecretion if the stressor of adolescents using the TSST, adolescents with a
becomes chronic or is distant in time (Miller, Chen, history of child maltreatment showed a blunted cor-
& Zhou, 2007). Indeed, naturalistic studies of tisol response to the TSST, and this effect was more
children in their home environments suggest that pronounced for adolescents who were carriers of
cortisol levels are elevated immediately after being one or two G alleles for the rs110402 polymorphism
reprimanded or punished by a caregiver, then de- of the CRHR1 gene (Sumner, McLaughlin, Walsh,
crease below normal levels in subsequent days and Sheridan, & Koenen, 2014). As already discussed,
appear below normal in children chronically exposed the CRHR1 gene plays important roles in regulating
to stressful situations (for a review, see Flinn et al., HPA function, and this study suggests that varia-
2005). Finally, two studies found no difference in tion in the CRHR1 gene may shape the effect
cortisol levels between maltreated children and non- of maltreatment on cortisol reactivity (Sumner
maltreated comparison groups (Doom, Cicchetti, et al., 2014). In one of only a few longitudinal stud-
& Rogosch, 2014; Fisher, Gunnar, Chamberlain, & ies in this area of research, maltreated adolescents
Reid, 2000). This may be due to small sample sizes were more likely to have a blunted cortisol response
(Fisher et al., 2000) or because of greater variability to the TSST than the nonmaltreated comparison
in cortisol levels among the maltreated youth, which group when they were 12 and 13 years old, but no
can make it difficult to capture group-level mean differences emerged at age 18 (Peckins et al., 2015).
differences (Doom et al., 2014). This was interpreted as a form of adaptive calibra-
In the literature examining cortisol reactivity to a tion to the environment over time, meaning that
stressor, findings were mixed. Some studies reported the stress response may adapt to meet the changing
that maltreated children and adolescents showed a demands of the environment across development.
blunted cortisol response to the stressor compared Adaptation is presumed to be a lengthy process, and
to nonmaltreated youth (Fisher, Kim, Bruce, & thus HPA functioning at any point in time likely
Pears, 2012; Gordis, Granger, Susman, & Trickett, reflects longer periods of cumulative life experiences
2008; Hart, Gunnar, & Cicchetti, 1995; MacMillan (Peckins et al., 2015).
et al., 2009; Peckins, Susman, Negriff, Noll, & Some studies reported mixed results within the
Trickett, 2015; Sumner, McLaughlin, Walsh, Sheridan, same sample based on maltreatment subtype or psy-
& Koenen, 2014). Others reported a heightened chiatric diagnosis. For instance, adolescents who
­response (Bugental, Martorell, & Barraza, 2003; had experienced physical and/or sexual abuse exhib-
Harkness, Stewart, & Wynne-Edwards, 2011) or no ited a blunted cortisol response to the TSST in
differences in cortisol reactivity by maltreatment comparison to nonmaltreated adolescents, whereas
status (Cook, Chaplin, Sinha, Tebes, & Mayes, 2012; adolescents who had experienced neglect or emo-
Eisen, Goodman, Qin, Davis, & Crayton, 2007). tional abuse did not differ from the nonaffected
To illustrate some of these findings, one of the comparison group (Trickett, Gordis, Peckins, &
earliest studies of cortisol reactivity was on reactions Susman, 2014). Moreover, adolescents who have a
to social conflict in the classroom in preschool boys history of maltreatment along with mild to moder-
who had been maltreated, who showed a blunted ate levels of depression show a heightened and pro-
response to this social stressor (Hart et al., 1995). longed cortisol response to the TSST (Harkness
Another widely used paradigm for eliciting a stress et al., 2011), whereas those with moderate or severe
response is the Trier Social Stress Test (TSST), a so- depression evince a blunted cortisol response whether
cial-evaluative stressor involving public speaking they were maltreated or not.
and mental arithmetic components (Kirschbaum, Another approach to understanding the effect of
Pirke, & Hellhammer, 1993). In one experiment maltreatment on the HPA axis is to use pharmaco-
using the TSST, foster children who had endured logical challenges. In these studies, exogenous CRH,
physical abuse, and children exposed to physical ACTH, or dexamethasone (Dex, a synthetic gluco-
abuse along with prenatal substance exposure, dis- corticoid) is administered. These studies are quite
played a blunted cortisol response over time when rare in pediatric populations, and sample sizes are
compared to children who had endured other small, which may explain why findings are quite
abuse subtypes and nonmaltreated children (Fisher mixed. For instance, one study reported lower ACTH
et al., 2012). In another study, maltreated female response to CRH challenge in sexually abused youth

166 Influence of Maternal Stress and Child Maltreatment

(De Bellis et al., 1994), whereas another reported challenge: Bremner et al., 2003; conflict role-play:
higher ACTH response to CRH challenge in de- Hagan, Roubinov, Mistler, & Luecken, 2014). In
pressed abused children currently living in adverse one study on cortisol reactivity using the TSST,
situations (Kaufman et al., 1997). Both investiga- adults who retrospectively reported childhood mal-
tions reported no difference in CRH-stimulated treatment showed a blunted cortisol response to
cortisol levels. These findings suggest different abnor- the stressor compared to adults without childhood
malities in pituitary responses to CRH (perhaps due maltreatment exposure (Carpenter et al., 2007).
­
to depressed versus nondepressed status), and possi- Another study found that women who experienced
ble compensatory mechanisms at the adrenal level childhood physical abuse exhibited a blunted corti-
allowing similar cortisol levels compared to controls sol response to the TSST when compared to women
despite differing ACTH levels. Two Dex challenge who had experienced other subtypes of abuse and
studies have also reported no differences in post- nonmaltreated women (Carpenter, Shattuck, Tyrka,
Dex cortisol levels, but lower ACTH responses Geracioti, & Price, 2011). A third study (Buchmann
(Bicanic et al., 2013; Duval et al., 2004). In con- et al., 2014) used the TSST as a stress elicitor to look
trast, one study reported that children who scored at the interaction between child maltreatment and
higher on the Child Trauma Questionnaire exhib- the FKBP5 rs1360780 genotype in explaining cor-
ited lower cortisol levels after Dex challenge than tisol reactivity in emerging adults (mean age 19).
children who had lower scores (Lipschitz et al., FKBP5 is a glucocorticoid receptor–regulating co-
2003), suggesting a more robust negative feedback chaperone (i.e., proteins that assist in protein folding
mechanism among these children. More research and other functions) that has been implicated in
is needed to examine the role of psychiatric symp- the negative feedback inhibition of the HPA axis.
toms and duration and severity of maltreatment Analyses revealed that adults who reported high
in explaining these somewhat inconsistent find- levels of maltreatment in childhood and were carri-
ings, as well as the extent to which these presumed ers of the rs1360780 CC genotype exhibited a lower
alterations in pituitary and adrenal function are cortisol response to the TSST when compared to
long-lasting. nonmaltreated adults, whereas carriers of the T
allele did not show this difference (Buchmann et al.,
Child Maltreatment and 2014). In contrast to these reports of lower reactiv-
Hypothalamic-Pituitary-Adrenal ity, one study found higher cortisol responses to the
Functioning in Adulthood TSST in women who had experienced child mal-
There have been few studies examining diurnal cor- treatment if they were also depressed compared to
tisol slopes in adults with maltreatment histories. three groups: nondepressed maltreated, depressed
However, the few extant studies reveal some evi- nonmaltreated, and nondepressed nonmaltreated
dence consistent with the presence of flatter diurnal women (Heim et al., 2000, 2002). These findings
slopes, similar to the literature on youth. For instance, suggest that genetic differences and concurrent
participants who had been adopted in childhood ­psychopathology moderate the effect of childhood
after experiencing neglect or abuse were more likely maltreatment on adult cortisol reactivity.
to exhibit flatter cortisol slopes in adulthood, espe- Among the studies using psychosocial stress tests
cially if they suffered from anxiety and had a history other than the TSST, null results predominated.
of severe neglect (vs. abuse; van der Vegt, van der For instance, a study of adults meeting criteria for
Ende, Huizink, Verhulst, & Tiemeier, 2010; van PTSD related to child abuse showed no group
der Vegt, van der Ende, Kirschbaum, Verhulst, & differences in reaction to a series of cognitive chal-
Tiemeier, 2009). Consistent with the possibility of lenges (Bremner et al., 2003), though the study re-
flatter slopes, adults who were maltreated as chil- ported higher anticipatory cortisol levels pretask in
dren also tended to show lower morning cortisol the PTSD group. Another study with young adults
levels (Power, Thomas, Li, & Hertzman, 2012) and (aged 18 to 22) found a null effect of maltreatment
higher afternoon levels (Bremner et al., 2003). on cortisol reactivity (Hagan et al., 2014). This
Most empirical investigations with adults mal- ­experiment used a conflict role-play challenge with
treated as children have focused on cortisol reactivity, a confederate in the lab acting as a peer and found
but the findings in these studies using experimental that there was no difference in cortisol reactivity
reactivity paradigms are mixed. The most widely between the maltreated and nonmaltreated group of
used paradigm was the TSST, but a few studies emerging adults (Hagan et al., 2014). It is difficult
employed other psychosocial stressors (e.g., cognitive to interpret these null results with any confidence.

Deer, Bernard, and Hostinar 167

They may be due to the fact that these protocols did that HPA alterations observed in maltreatment can
not elicit robust enough cortisol responses to reveal be causal and also reversible. We summarize these
individual differences in the samples. Alternatively, studies here.
lack of main effects at the group level may be the A number of interventions have been developed
result of averaging across subgroups with opposite to improve parent–child relationships in high-risk
profiles (i.e., blunted and heightened reactivity). families (e.g., families referred to Child Protective
Indeed, when Hagan et al. (2014) probed their Services). We review some of the most commonly
results further, maltreatment was associated with used interventions in studies that specifically assessed
lower reactivity in those with high levels of external- effects on children’s cortisol regulation.
izing symptoms, and higher reactivity in those with The Attachment and Biobehavioral Catch-up
internalizing symptoms. (ABC) intervention is a parent-coaching program
Pharmacological challenge tests have been con- that aims to enhance the quality of attachment
ducted much more frequently in adults compared ­between the caregiver and the child and support
to children or adolescents. Two Dex suppression children’s self-regulatory capabilities. Parent coaches
studies revealed enhanced negative feedback (or provide in-the-moment feedback in response to
“super suppression” of the HPA axis) as indicated by parent–child interactions as they occur to promote
lower ACTH or lower cortisol responses in adults nurturing, responsive, and nonfrightening care. In
with abuse or neglect histories compared to controls, randomized controlled trials, ABC has been com-
especially if they had a diagnosis of depression or pared with an active control condition that is meant
PTSD (Newport, Heim, Bonsall, Miller, & Nemeroff, to enhance motor, cognitive, and language skills
2004; Stein, Yehuda, Koverola, & Hanna, 1997; (Bernard, Dozier, Bick, & Gordon, 2015; Bernard,
Watson et al., 2007). Clinical studies using a CRH Hostinar, & Dozier, 2015; Dozier, Peloso, Lewis,
or Dex/CRH challenge have predominantly reported Laurenceau, & Levine, 2008). In a study of infants
hyporesponsiveness of the HPA axis (lower ACTH and toddlers who had been involved with Child
and/or lower cortisol) following these challenges in Protective Services, infants who received ABC
abused patients, especially if they were also suffering showed more typical diurnal cortisol production
from depression or PTSD (Carpenter et al., 2009; than the infants who received the control interven-
Heim, Newport, Bonsall, Miller, & Nemeroff, 2001; tion at a follow-up assessment within several months
Klaassens et al., 2009; Rinne et al., 2002; Stein of the intervention (Bernard, Dozier, et al., 2015).
et al., 1997). In contrast, chronically abused women At a preschool follow-up assessment of the same
with borderline personality disorder (BPD) exhib- children, at approximately three years postinterven-
ited a heightened ACTH and cortisol response to a tion, young children who had received the ABC
Dex/CRH test (Rinne et al., 2002), and adults with intervention still showed a more normalized diurnal
the GG genotype for two single-nucleotide poly- rhythm than the control group, who showed a flat-
morphisms (SNPs) in the CRHR1 gene (rs110402 tened diurnal rhythm (Bernard, Hostinar, & Dozier,
and rs242924) also exhibited higher cortisol responses 2015). In a study of infants in foster care, children
to the Dex/CRH challenge than never-maltreated randomly assigned to receive ABC showed a lower
adults and maltreated adults with the other alleles cortisol response during the Strange Situation, an
(Tyrka et al., 2009). The pharmacological findings assessment of attachment that involves brief separa-
add to the mixed patterns emerging from reactivity tions from caregivers, than children in the control
studies to underscore the importance of considering intervention (Dozier et al., 2008). Taken together,
psychiatric diagnosis and variations in genes regulat- these studies suggest that the ABC intervention was
ing the HPA axis in future studies, given that these effective in helping children to regulate both diurnal
two factors may explain the widespread heterogeneity production and stress reactivity responses of the
in the associations between maltreatment and the HPA system.
activity of the HPA axis. The Multidimensional Treatment Foster Care for
Preschoolers (MTFC-P) is a caregiver-based preven-
Intervention Studies tative intervention that aims to address the develop-
Most of the human literature on maltreatment and mental and socioemotional needs of preschool-aged
the HPA axis has been correlational, making it foster children by providing additional support to
­difficult to infer whether the effects described previ- foster parents, such as parenting skills that promote
ously are causal in nature. A growing number of in- responsiveness and consistency (Fisher & Stoolmiller,
tervention studies have provided important ­evidence 2008; Fisher, Stoolmiller, Gunnar, & Burraston,

168 Influence of Maternal Stress and Child Maltreatment

2007; Fisher et al., 2011; Graham et al., 2012). In showed decreasing cortisol levels over time (Cicchetti,
one study, children who received MTFC-P did not Rogosch, Toth, & Sturge-Apple, 2011).
show the increasingly flattened diurnal rhythm Collectively, these results indicate that the effects
over time, whereas foster children in regular foster of child maltreatment on the HPA axis can be
care did (Fisher et al., 2007). Following foster care prevented or reversed with interventions that
­
placement changes, which were found to be associ- focus on enhancing parenting and parent–child
ated with dysregulation in cortisol rhythms among relationships, which can inform future intervention
children in regular foster care, children who received strategies and policymaking (Slopen, McLaughlin,
MTFC-P continued to show the typical cortisol & Shonkoff, 2014).
decline from morning to evening (Fisher et al.,
2011). In a study aimed to identify potential mech- Child Maltreatment and Mental Health
anisms leading to changes in cortisol reactivity, Child maltreatment is associated with increased
Fisher and Stoolmiller (2008) examined changes in vulnerability to mental health disorders across the
foster parent stress as a result of MTFC-P. Indeed, lifespan. This includes higher risk of developing
foster parents who received MTFC-P demonstrated depression, PTSD, anxiety disorders, conduct dis-
lower stress than foster parents in the comparison order, substance abuse, and personality disorders
group. Further, in the regular foster care compari- (Edwards, Holden, Felitti, & Anda, 2003; Scott,
son group, higher foster parent stress was associated McLaughlin, Smith, & Ellis, 2012; Teicher & Samson,
with a more blunted diurnal rhythm and lower 2013). However, not everyone who experiences mal-
morning cortisol levels (Fisher & Stoolmiller, 2008). treatment suffers from mental health issues later in
Finally, in a study examining the potentially chal- life (Cicchetti, 2016). It has been proposed that altera-
lenging transition to school, foster children who tions in the HPA axis following early trauma may
received the MTFC-P showed a similar response to have an effect on whether psychopathology develops,
a community sample of children, whereas children and what form it takes (Heim, Newport, Mletzko,
in regular foster care showed elevated morning Miller, & Nemeroff, 2008; Susman, 2006).
­cortisol levels on the fifth day of the transition PTSD is one of the most prevalent mental health
(Graham et al., 2012). outcomes linked to child maltreatment. There is a
A study that investigated the effects of Promoting high rate of PTSD among adults who were exposed
First Relationships (PFR), an intervention aimed at to maltreatment during childhood (estimated to be
improving attachment quality in children who had as high as 72 to 100 percent in some studies), and
a recent caregiver change, found no effects on basal there are higher rates of child maltreatment among
morning cortisol levels after the intervention. adult patients diagnosed with PTSD than among
However, older children who received the interven- those without PTSD (Pratchett & Yehuda, 2011).
tion exhibited higher cortisol reactivity postinter- The current literature on links between childhood
vention compared to children who did not receive maltreatment and adult PTSD offers the hypothesis
the intervention and younger children receiving the that one of the mediating pathways for this vulner-
intervention (Nelson & Spieker, 2013). This finding ability may involve the sensitization of the HPA axis
was interpreted as a restoration of typical physiolog- by early maltreatment, which may be a particularly
ical stress reactivity as a result of the intervention, potent risk factor for those exposed to revictimiza-
given that most of these at-risk children showed a tion in adulthood (Brewin, Andrews, & Valentine,
flat cortisol production pattern during a challenging 2000; Pratchett & Yehuda, 2011). PTSD that devel-
situation at baseline. ops after various types of adult trauma has tended
Child–Parent Psychotherapy (CPP) is a dyadic to be associated with lower basal cortisol levels
intervention that aims to enhance the quality of the and enhanced negative feedback of the HPA axis
relationship between a parent and child by increas- (Pratchett & Yehuda, 2011). There are only a few
ing parents’ reflective capacity and sensitivity to examinations of adults with PTSD secondary to
child cues; the approach is supportive and nondirec- childhood maltreatment, and results are somewhat
tive. Over time, maltreated children whose parents inconsistent. For instance, one study assessed 24-hour
received CPP, as well as maltreated children whose plasma cortisol samples in adult women with a
parents received a psychoeducational parenting in- history of child abuse and concurrent PTSD and
tervention, displayed morning cortisol levels that were revealed lower basal cortisol levels in the afternoon
similar to nonmaltreated children; in contrast, mal- in these women compared to abused women with-
treated children who did not receive an intervention out PTSD and women without abuse or PTSD

Deer, Bernard, and Hostinar 169

(Bremner, Vermetten, & Kelley, 2007). Another Sheridan, 2016). Some have proposed that the
study reported higher levels of 24-hour urinary ­effects of early-life trauma on later conduct prob-
­cortisol in women with PTSD related to childhood lems may be, at least in part, mediated by attenu-
sexual abuse (Lemieux & Coe, 1995). This latter ated HPA responses (Susman, 2006), though a
sample also exhibited a tendency toward obesity, ­subgroup of those who exhibit antisocial behavior
which may explain the elevated cortisol output. and HPA axis hypoactivity show these behaviors
Although childhood abuse appears to create a ­independently of environmental adversity (Hawes,
vulnerability for later PTSD especially in those
­ Brennan, & Dadds, 2009). Furthermore, some
who are re-exposed to trauma in adulthood (Brewin children show disruptive behavior in the context
et al., 2000), more research is clearly needed to test of HPA hyperreactivity (Hawes et al., 2009). More
the hypothesis that this vulnerability is mediated by research is needed to test whether HPA activity
dysregulation of the HPA axis. plays a causal role in the development of aggressive
Depression is another prevalent condition in and antisocial behavior in general and for those
those exposed to childhood maltreatment (Batten, exposed to maltreatment in particular.
Aslan, Maciejewski, & Mazure, 2004; Heim et al., In sum, heterogeneity seems to be the norm
2008). Two recent reviews of more than four de- rather than the exception when examining patterns
cades of research on depression and the HPA axis of HPA activity linked to psychopathology in those
have reported a predominant pattern of hyperactiv- exposed to maltreatment. Several types of psychopa-
ity of the HPA axis in depression (Pariante & thology appear to be associated with hypercorti-
Lightman, 2008; Stetler & Miller, 2011), with the solism in some studies and hypocortisolism in others.
strongest effects being noted in older inpatients These complex patterns may be, at least in part,
with melancholic or psychotic depressive features explained by a recent meta-analysis of studies on
(Stetler & Miller, 2011). Early-life stress is thought chronic stress and HPA activity (Miller et al., 2007),
to affect the functioning of glucocorticoid receptors which revealed that HPA activity increases acutely
in the brain and the periphery, which results in after stressor onset but reduces over time as stressors
impaired negative feedback mechanisms and elevated become more chronic. Incorporating detailed as-
levels of basal or reactive cortisol in many depressed sessments of recent stressful life events and lifetime
patients (Pariante & Lightman, 2008). Results patterns of acute and chronic stress exposure in
become less consistent when considering HPA future studies may add clarity to this literature.
functioning in the context of child maltreatment
and concurrent depression, which can manifest Child Maltreatment and Physical Health
with hypo- or hyperreactivity of the HPA axis Child maltreatment has also been connected to an
­depending on comorbidity with PTSD, duration increased number of hospital visits in adulthood
of early-life stress exposure, and ongoing stress in and greater morbidity due to multiple causes, in-
adulthood (Penza, Heim, & Nemeroff, 2003). cluding cardiovascular disease and diabetes (Ehrlich
Conduct disorder, callous-unemotional behav- et al., 2016; Gilbert et al., 2015), obesity (Danese &
ior, aggression, and externalizing symptoms are also Tan, 2014), fibromyalgia, and chronic fatigue syn-
more prevalent among individuals who experience drome (Borsini et al., 2014; Lee, 2010). As with the
child maltreatment than in the general population effects of child maltreatment on the development
(Dackis, Rogosch, & Cicchetti, 2015; Gowin et al., of psychopathology, maltreatment does not always
2013; Maniglio, 2015). A growing literature has re- ensure physical health problems, but these condi-
ported physiological hypoarousal (e.g., low basal tions are more common in maltreated individuals.
cortisol levels and low sympathetic reactivity) in Importantly, most theoretical accounts of how mal-
those with antisocial behavior (Alink et al., 2008; treatment instantiates these health risks have hy-
Susman, 2006), though effect sizes are smaller than pothesized that the activity of the HPA axis plays
once thought. Hypoarousal of stress systems is a central role (Chrousos, 2009). Cortisol has wide-
thought to be linked to fearlessness, lack of empa- spread effects throughout the body, including effects
thy, and seeking stimulation from the environment on metabolism, immunity, and brain development
through disruptive or aggressive behavior. There is (Sapolsky et al., 2000). Thus, it is biologically plau-
increasing evidence that among children exposed to sible that chronic activation of the HPA axis during
interpersonal violence, blunted cortisol patterns are abuse or neglect might foster the development of
associated with externalizing behavior (Bernard, numerous physical health problems. However, few
Zwerling, & Dozier, 2015; Busso, McLaughlin, & studies have directly tested mediational models

170 Influence of Maternal Stress and Child Maltreatment

linking child maltreatment to altered HPA func- The few existing longitudinal investigations suggest
tioning and, in turn, physical health symptoms. a potential switch from cortisol hypersecretion in
Accumulating evidence suggests that links the aftermath of trauma to a pattern of hyposecre-
­between HPA activity and inflammation may play tion later in development (e.g., Trickett et al.,
a key role in this mediational pathway. Childhood 2010), but more studies are needed to corroborate
maltreatment is associated with elevated inflamma- this pattern.
tory biomarkers (Coelho, Viola, Walss-Bass, Brietzke, Intervention studies that follow participants over
& Grassi-Oliveira, 2014), which have been impli- time are especially needed to examine the p ­ ersistence
cated in the development of many conditions of intervention effects, and to compare interven-
with inflammatory underpinnings, such as coro- tions to each other (Fisher et al., 2011, 2016; Slopen
nary heart disease, diabetes, and obesity (Hotamisligil, et al., 2014). There is also a dearth of intervention
2006). Cortisol is known to play an important role studies attempting to ameliorate or normalize HPA
in countering the proinflammatory activity of functioning in adults with childhood trauma expo-
monocytes and macrophages (Irwin & Cole, 2011), sure. As summarized previously, interventions with
and there is evidence that dysregulated cortisol children have shown that there is some plasticity in
levels (either abnormally low or chronically high) children’s HPA activity, but it is unclear whether
can impair the control of inflammatory responses this plasticity extends into adulthood.
(Raison & Miller, 2003; Sapolsky et al., 2000). There is also a lack of cortisol reactivity studies in
Thus, dysregulation of the HPA axis may be one younger maltreated children. The majority of the
pathway through which maltreatment may lead to existing research with these younger participants
excessive inflammation and chronic diseases of has focused on diurnal cortisol, whereas studies that
aging precipitated by inflammation (Glaser & incorporated paradigms to test cortisol reactivity
Kiecolt-Glaser, 2005). Despite the important role have mostly been conducted with preteenagers,
likely played by the HPA axis and inflammation, teenagers, and adults. This makes it difficult to draw
we must recognize other pathways through which conclusions about developmental changes that may
maltreatment might impair health, such as the occur across the lifespan, and provides an incom-
adoption of health-compromising behaviors that plete characterization of HPA functioning within
are occasioned or exacerbated by stress, such as each life stage.
smoking, overeating, or sedentary lifestyles (Kiecolt- There is some emerging evidence supporting the
Glaser & Glaser, 1988; Raposa, Bower, Hammen, role of maltreatment subtypes and varying levels of
Najman, & Brennan, 2014). chronicity in shaping HPA outcomes, but this evi-
In conclusion, there is accumulating evidence to dence base needs to be expanded (McCrory, De
provide piecemeal support for associations between Brito, & Viding, 2010). Furthermore, the role of
maltreatment and HPA dysregulation, HPA activity interactions between genetic variation and maltreat-
and inflammation, and inflammation and multiple ment experiences in influencing psychiatric out-
disease endpoints. However, testing these full, comes is only beginning to be explored. Current
multistep pathways within the same participants results in these areas are relatively mixed, and the
followed longitudinally will be necessary to explicitly number of studies conducted is quite limited. This
examine the mediating role of the HPA axis in the research could lead to more targeted intervention
development of many of these health conditions. programs and a greater understanding of the devel-
opment of individual differences in HPA and
Future Directions mental health outcomes following child maltreat-
Recent literature has brought a greater understand- ment. More evidence is also needed to test the
ing of the range of possible effects of child maltreat- mediating role of HPA alterations in the relation
ment on the HPA system and its implications for between child maltreatment and mental or physical
mental and physical health, but many questions health. This research has only recently begun to gain
remain unanswered. One such question is whether traction (e.g., Bernard, Zwerling, & Dozier, 2015;
the effects of maltreatment on the HPA axis are Hagan et al., 2014), but it is critical for testing many
transient or persistent across the lifespan, and how contemporary theories of how early-life stress leads
they may change with development. A frequently to later psychopathology and chronic disease.
noted gap in the literature has been the scarcity of There are also a few methodological limitations
longitudinal studies to address this question (Bernard that have been noted in this literature (McCrory
et al., 2015; Cicchetti et al., 2011; Heim et al., 2008). et al., 2010; Pollak, 2015). These limitations include

Deer, Bernard, and Hostinar 171

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ment are assessed across studies, the widespread use in monkey infants raised in variable- and low-demand
environments. Child Development, 62(4), 686–693.
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sample sizes. Cortisol sampling occurs in multiple determinants of child abuse: Evidence of factors associated
settings (e.g., laboratory, home, clinic), and there is with maternal abuse from the Egypt demographic and health
little consistency in the timing of sample collection. survey. Journal of Injury and Violence Research, 8(1), 25–34.
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11 Evolution and Human Fatherhood

Adam H. Boyette and Lee T. Gettler

Abstract

This chapter reviews research on the evolution of paternal care in humans. It examines human
fatherhood within the phylogenetic distribution of paternal care in vertebrates, especially mammals.
Phylogenetic comparisons draw out several correlates of paternal care across species, with the most
important being social monogamy. Research on the evolution of paternal care in humans has also
focused on the relationship between social monogamy and the evolution of paternal care. The chapter
reviews this research and major debates around whether male provisioning was a key adaptation in
the evolution of pair-bonds and human life history. It discusses evidence for direct male care and
summarizes a possible evolutionary sequence of its evolution in humans. It considers studies on the
neuroendocrinology of male care in humans, drawing from comparative studies where appropriate.
Lastly, this chapter outlines several major biocultural frameworks for understanding population-level
patterns of paternal care as integrated, developmental responses to specific socioecological factors.
Keywords: fatherhood, paternal care, testosterone, male care, social monogamy, pair-bonds

Why Do Males Care? shape human fatherhood. In this regard, we will

Among mammals, humans are relatively rare in the highlight how recent advances in the study of the
extent to which fathers commonly cooperate with neuroendrocrinology of paternal care have been criti-
mothers to raise children. Although the roles of cal to unpacking how environmental factors are
fathers and the range of their investment vary across internalized and embodied, serving to moderate care
and within cultures, the unique breadth of ways behavior, and how plasticity in response to socioe-
human males contribute to their offspring’s survival cology has been crucial to human evolution.
and reproduction opens many questions into the We should begin with a brief review of taxonomy.
origins of human fatherhood. Evolutionary perspec- Workers in different fields use different terms to refer
tives are imperative to modeling why humans devi- to ways that males may contribute to their offspring,
ate from the general mammalian pattern of singular such that we can speak of paternal involvement,
maternal care, as well as to explaining the range of paternal investment, paternal care, and so on (Gray &
existing variation in fathering. In this chapter, we Anderson, 2010). We will use the specific terms used
review what we know of the evolution of human by those researchers we discuss whenever appropriate.
paternal care from both ultimate (i.e., phylogeny However, for the most part our review will focus
and ­adaptive value) and proximate (i.e., hormonal on the evolution of paternal care. Paternal care is
and neurobiological mechanisms) perspectives typically defined as the set of behaviors performed
(Tinbergen, 1963). We will finish with a review of by an adult male postfertilization that benefit the
approaches that integrate ultimate and proximate young and that the male would not perform in the
perspectives, and discuss multilayered factors that absence of the young (Fernandez-Duque, Valeggia,

179
& Mendoza, 2009; Kleiman & Malcolm, 1981; & Jennions, 2008). As a result, male care has not
Woodroffe & Vincent, 1994). For example, defense commonly evolved in mammals. This situation can
against conspecifics or predators may benefit the be contrasted with that in birds, where 90 percent
young because they are among the guarded females, of all species exhibit paternal care. Male birds can sit
but this would not be care. Similarly, as we will on eggs to aid in incubation, and studies across a
discuss more later (see Life History Theory and variety of species have shown that removing the
Human Fatherhood), human hunter-gatherer male has a negative effect on brood size and growth
men’s targeting of large game may contribute to (Clutton-Brock, 1991). As a result, egg guarding is
their offspring’s fitness, but because it also benefits the most common form of paternal care in animals—
potential mates (Hawkes & Bliege Bird, 2002), it and one unavailable to mammal fathers (Kleiman &
cannot be exclusively considered paternal care. Malcolm, 1981).
Both of these examples, however, are considered In both birds and mammals, male care is evolu-
paternal investment. Behaviors that are considered tionarily associated with and likely a result of (at
paternal care may include feeding, carrying, hud- least in most cases) social monogamy (Burley &
dling for thermoregulation, protection of the Johnson, 2002; Lukas & Clutton-Brock, 2013). In
young (“babysitting”), grooming, teaching, or mammals but not in birds, however, socially monog-
paying for college expenses (Anderson, Kaplan, & amous species also tend to be genetically monoga-
Lancaster, 1999; Woodroffe & Vincent, 1994). mous (Clutton-Brock & Isvaran, 2006). This suggests
These are all types of direct investment, whereas that in mammals, paternal care evolved in a context
sharing food with a pregnant or nursing mate where a stable bond between a breeding pair already
would be indirect investment. benefited males, likely because the benefits of a stable
partnership outweighed the costs of finding addi-
Phylogenetic Distribution of Paternal Care tional mates (Lukas & Clutton-Brock, 2013). For
Examining the place of human fathers among verte- example, social monogamy is found more commonly
brates more generally, especially others within the in mammalian orders where females live in low den-
class Mammalia, informs our understanding of the sities and rely on food resources of high quality but
social-ecological conditions that tend to select for low abundance. Territoriality and adult–adult intol-
paternal care and the evolutionary pathways through erance are also common in these groups, as breeding
which it emerges. Critically, the phylogenetic distri- pairs guard resource patches. Subsequent to the ev-
bution of paternal care reveals that it is a derived olution of social monogamy, male care evolved across
trait among various mammalian lineages. Thus, mammalian orders in a variety of ways, resulting in
human fatherhood can be seen as a unique adaptation greater fecundity in species with male care (West &
to specific selective factors faced by our ancestors— Capellini, 2016). According to phylogenetic recon-
although, as we will show later, a similar neuroen- struction, some monogamous species who gave birth
docrine biology likely underpins male parenting (or to litters and lived in particularly unpredictable
its absence) in all mammals. environments went through further evolution toward
In general, male care would be expected when cooperative breeding (Lukas & Clutton-Brock,
the benefits of helping a mate raise offspring outweigh 2012, 2013). In cooperative breeding social systems,
the costs. Costs to a male may be direct, as in the a group of nonbreeding helpers assist a breeding
energetic costs of carrying the young (e.g., Achenbach pair in raising their offspring, and fathers are one
& Snowdon, 2002), or suffered as opportunity costs of the possible alternative caretakers. Hrdy (1999)
from the loss of time spent finding additional mates has argued that humans are cooperative breeders.
(Clutton-Brock, 1991). Paternal care is relatively rare Although humans do not give birth to litters, her
in mammals, being present in about 3 to 5 percent argument hinges on the fact that human newborns
of species (Clutton-Brock, 1991; Lukas & Clutton- are unusually altricial and require more intensive
Brock, 2013), suggesting the costs of care for the care for longer than those of our closest genetic rela-
male typically outweigh the fitness benefits of tives, chimpanzees and gorillas. Alloparental/allo-
­deserting his mate. In mammals, because females in- maternal care—or care by those other than the
ternally gestate the young until parturition and mother (Hrdy 1999)—is all but absent among the
feed them postpartum for various durations through great apes.
lactation, males are essentially free of obligations after In mammals, genera exhibiting paternal care tend
ejaculation and can pursue further mating, although to cluster in three groups: social carnivores, rodents,
they are limited by the Fisher condition (see Kokko and New World monkeys (Kleiman & Malcolm,

180 Evolution and Human Fatherhood

1981). Males in the social carnivore group, such as of fewer, larger offspring, whereas in the larger,
wolves, coyotes, foxes, and mongooses, play a part slower growing social carnivores, indirect paternal
in feeding pups and will share food with their mates. investment increases maternal health and facilitates
In the case of these species, selection has favored a higher reproductive rate. However, it does seem
paternal investment as a component of risk pooling that female territoriality and female–female intoler-
within cooperative breeding packs. Such species ance, which would result in relatively lower female
have energetically costly reproduction where females densities, are associated with paternal care in mice,
cannot raise litters alone. This situation favors both suggesting this factor is still important in initiating
males forgoing alternative mating opportunities to the evolution of social monogamy and subsequent
provide paternal care and reproductive suppression male care in this group (Ribble, 2003). It may also
in subordinate females who will forgo breeding to be that, for example, in the case of Peromyscus califor-
act as helpers to the breeding female. Female repro- nicus, the larger offspring body size in monogamous
ductive suppression also decreases the available female species may also be a causal factor in the evolution
breeding population, further decreasing a male’s of paternal care, as male body heat is more crucial to
chances of finding alternative mating opportunities keeping the young warm when litters are smaller
(Woodroffe & Vincent, 1994). In addition, game is (Ribble, 2003).
an unpredictable, high-quality resource that is easily Paternal care in primates is highly diverse, occur-
divisible such that it pays for mated pairs to divide ring in some form in about 40 percent of all genera
the cost of hunting and share captured prey with (Kleiman & Malcolm, 1981). As is the case for
the young and other nonbreeding pack members paternal care in mammals in general, its presence is
(Clutton-Brock, 1991). Male care in social carni- more common in species whose diet is based on foods
vore groups does pay fitness dividends. Phylogenetic of low density but high nutritional value, especially
analysis has revealed that litters are larger and the fruit (Lukas & Clutton-Brock, 2013). However,
duration of lactation is shorter in carnivore groups nowhere is it more pronounced than among several
where males provision the breeding female (West & species of New World monkeys. For example, South
Capellini, 2016). Shorter lactation times lead to American titi monkeys (Callicebus) and owl mon-
greater reproductive potential for the breeding pair. keys (Aotus) exhibit the most extensive and obligate
Several species of rodents also demonstrate pater- paternal care among primates, where fathers assume
nal care behaviors, particularly grooming, huddling the role of primary carrier for infants soon after
to keep the young warm, and retrieving stray pups birth. Females give birth to a single offspring each
(Ribble, 2003; Woodroffe & Vincent, 1994), but year, and dependent infants may be carried by their
the evolutionary context is different than in social fathers as much as 90 percent of the time, only
carnivore groups. For example, a comparative study transferring to their mother for nursing bouts
of several closely related mice species (Peromyscus spp.) (Fernandez-Duque et al., 2009). In one field study,
exhibiting the full spectrum of mammalian breeding Spence-Aizenber, Di Fiore, and Fernandez-Duque
patterns found that paternal care is associated with (2016) observed red titi monkey (Callicebus discolor)
delayed reproduction in females, longer reproductive fathers to be more involved than mothers in all social
lifespans, smaller litter sizes, and larger offspring interactions with infants except nursing, including
(Jašarević et al., 2013). This suggests that paternal grooming, food sharing, inspecting, aggression, and
care in mice is associated with an overall shift in play. Mendoza and Mason (1986) demonstrated in
female life history strategy from investment in off- a series of experiments that titi monkey offspring
spring quantity to investment in offspring quality preferentially seek their father over their mother when
(see more in Life History Theory and Human given the choice, a preference established during the
Fatherhood later; see also Vitousek & Schoenle, this first months of life through frequent rejection by
volume), and that this shift is related to the greater mothers and acceptance by fathers.
offspring survivability facilitated by paternal behavior The role of fathers is also critical among the coop-
(Jašarević et al., 2013). Such a pathway to father- eratively breeding callitrichids. In these monkeys,
hood contrasts with that of the social carnivores, the marmosets (Callithrix) and tamarins (Saguinus),
where larger litters are made possible by males pro- females frequently give birth to twins whose weight
visioning their mates during shorter lactation periods. combined might make up as much as 20 percent of
These cases represent species-specific advantages of a female’s body weight at birth (Digby, Ferrari, &
paternal care and clues to its evolution: for mice, Saltzman 2007). They also have short interbirth
direct paternal investment increases the survivability intervals as they can conceive during a postpartum

Boyet te and Get tler 181

ovulation (Achenbach & Snowdon, 2002). In this and the potential for paternal care in our lineage.
reproductive system, contributions from other group Some argue that populations of Homo erectus showed
members are vital to infant survival, with care in- relatively modern human-like reduced sexual dimor-
volving constant carrying, food sharing, vigilance, phism by 2 million years ago (McHenry, 1994;
defense against predators, and huddling for thermo- O’Connell, Hawkes, & Blurton Jones, 1999), al-
regulation. The importance of paternal care to male though more recent finds have called that conclusion
fitness is underscored by the energetic costs of care. into question, demonstrating potentially significant
For example, Achenback and Snowdon (2002) found variation in size dimorphism across H. erectus’
that, in a sample of 10 captive adult male cotton-top range (Lordkipanidze et al., 2007; Ruff, 2010;
tamarins (Saguinus oedipus), adult males lost as much S. W. Simpson et al., 2008). Regardless, it remains
as 10 percent of their prebirth body weight during doubtful that there was substantial paternal care in
the first 12 months after birth. The weight loss was ancestral hominins, perhaps even before the appear-
less the more additional helpers were available in ance of Homo sapiens between 150,000 and 200,000
the group. years ago (Gray & Anderson, 2010). Given this
Of the apes besides humans, only among Southeast phylogenetic background, we now turn to the major
Asian siamangs (Symphalangus syndactylus), one of discussion of why paternal care became part of the
the hylobatids, or “lesser apes,” do we see any pater- human evolutionary package.
nal care. This instance is curious because the other
hylobatid group, the gibbons, does not exhibit pa- Life History Theory and Human
ternal care, although they share with the siamangs all Fatherhood
the other correlates of paternal care—social monog- Life history theory is a rich resource for under-
amy, territoriality, and reduced sexual dimorphism standing both the variability and universal potential
(van Schaik & Kappeler, 2003). The great apes, on for human paternal investment. According to life
the other hand, maintain more or less polygynous history theory, all organisms are faced with decisions
mating systems with one (gorillas, orangutans) or as to how to allocate their limited somatic resources
more (chimpanzees, bonobos) males living with a throughout their lifespan to optimize their inclusive
group of females, who tolerate each other’s presence fitness. The nature of these decisions requires that
but raise their own offspring individually. Sexual individuals make fundamental trade-offs, between
dimorphism is pronounced in each species. The dif- allocating energy to growth versus reproduction,
ference is at its most pronounced among the goril- for example (Roff, 2002; Stearns, 1976). Parental
las, where dominant males can be twice as large as Investment Theory (Trivers, 1972), a branch of life
the females in their harem. Males use their added history theory, focuses on the trade-offs inherent to
bulk and larger canine teeth to both compete with the allocation of reproductive effort. Once an organ-
each other and coerce females to mate. Given this ism has reproduced, it faces the decision of whether
pattern among the other great apes and our own to direct its resources toward its current offspring
phylogenetic tree, the evolution of paternal care in (parenting effort) or toward the production of future
humans may have been relatively recent and related to offspring (mating effort). As noted earlier, males of
other major changes in socioecology and life history. most mammals, including the great apes, our clos-
Our lineage separated from the ancestors of the est ­genetic relatives, direct their reproductive effort
chimpanzees around 7 million years ago, although exclusively toward mating. Hence, paternal care is
estimates vary. The clearest evidence in the fossil evolutionarily linked to social monogamy in most
record that hints at paternal care comes from the species where it occurs, as this entails a reduction in
level of sexual dimorphism apparent in skeletal re- mating effort. As a consequence, debates around the
mains. As in the other apes, males were larger than evolution of paternal care as an aspect of human life
females among the earliest bipedal hominins, the history have tended to focus on the origin of human
australopithecines, who appeared around 4 million pair-bonds (Gray & Crittenden, 2014) and whether
years ago. Geary and Flinn (2001) have suggested or not male contributions helped facilitate the evolu-
that australopithecine family groups may have re- tion of other unique aspects of the human family
sembled the single-male, multiple-female social and life history (Gettler, 2010; Gurven & Hill, 2009).
structure of gorillas. It remains unclear when the As is the case with birds, males may be enticed to
contemporary human pattern of reduced sexual stay with a current mate if his presence signifi-
dimorphism evolved, although consensus is that it cantly enhances the survivability of the offspring.
is an indicator of the evolution of social monogamy We wean our offspring before they are nutritionally

182 Evolution and Human Fatherhood

independent, which allows relatively short interbirth that men’s big-game hunting does not represent
intervals for our body size (Kaplan, Hill, Lancaster, parental effort but serves to advertise men’s quality
& Hurtado, 2000). Although potentially increasing to women who could become additional wives or
our reproductive success by giving birth to multiple extra-pair sexual partners. Data from Hadza hunter-­
dependent offspring in close succession, it dramati- gatherer big-game hunting and meat distributions
cally increases the energetic burden on mothers, was used to support this hypothesis. Hawkes and
who must support costly offspring during their long her colleagues found that, after meat was shared,
period of development. The lengthy human juvenile a Hadza man’s family did not receive more meat,
period, and the behavioral and nutritional invest- irrespective of his success or how much time he
ment required, has been argued to have shaped human spent hunting (Hawkes, O’Connell, & Blurton
cooperation and the family, as mothers required Jones, 2001b), nor did successful hunters’ families
help from others (Hrdy, 1999; Kaplan et al., 2000). receive more meat from others as return payment
In this evolutionary scenario, fathers were one of for their contributions (Hawkes, O’Connell, &
the individuals who could have subsidized maternal Blurton Jones, 2001a). One critique of their inter-
energy budgets by either direct or indirect invest- pretation of these data is that if better hunters simply
ment, leading to the evolution of paternal care. keep supplying the group with meat, what would
The influential “man the hunter” or “man the motivate any one woman to provide mating oppor-
provisioner” hypothesis of human pair-bonds devel- tunities to keep the meat coming—temptation to
oped from this line of evidence. The argument is “free ride” on good hunters would disfavor the evo-
that males formed relationships with females as a lution of such a system (Bliege Bird, Smith, &
result of the benefits to females and their young of Bird, 2001). Bliege Bird and colleagues (2001) pro-
male provisioning. Males would acquire high-quality posed that men’s hunting must serve as an honest
food resources, especially meat, which they would signal of their more general advantageous qualities—
share in the context of a division of labor. The ben- that he has “good genes”—such that it pays for any
efits of this relationship to males were reproductive individual woman to mate and produce offspring
access to a mate and increased offspring survival with him. In general, it does seem that better hunters
(Kaplan et al., 2000; Lancaster & Lancaster, 1983; have greater reproductive success, although it is not
Lovejoy, 1981). Some lines of evidence support this clear whether they are better providers (Gurven &
hypothesis; hunting was clearly one critical early Hill, 2009).
human adaptation (Plummer, 2004). There is paleo- Although Hawkes and colleagues’ proposition that
archeological evidence for increasingly complex stone hunting constitutes showing off, or a “costly signal”,
tool industries used for hunting by early Homo spe- has forced reconsideration of the long-standing
cies beginning as early as 2.6 million years ago. With notion of men’s care having evolved as provisioning,
the subsequent appearance of the large and wide-­ many are not convinced the empirical evidence sup-
ranging H. erectus, it is argued that females would ports the position that men’s hunting only reflects
have required assistance from others to raise multiple, mating effort. For example, Marlowe (1999) has
concurrent dependent children; that meat was likely shown that, among Hadza hunter-gatherer men, male
shared; and that it was consumed alongside nutri- care is at least partially parenting effort. He found
tionally dense plant foods. Early fieldwork among that men with the best hunting reputations are no
contemporary hunter-gatherers also supports the less likely to provide direct care (carrying, holding,
idea that there was a sexual division of labor in which feeding, cleaning, soothing) to their children. Indeed,
men typically did most of the hunting and women men who provided more direct care also brought in
a majority of the gathering (Lee & De Vore, 1968). more food, suggesting they are not trading off direct
This vision of male provisioning—a model based care for opportunities to show off. Additionally, those
on male parenting effort—was questioned by Kristen men with more biological children versus stepchil-
Hawkes (1991). She argued that, if the goal of men’s dren brought in more food, a finding contrary to
provisioning was to feed their families, they would the expectations of the show-off hypothesis, since
be better off targeting resources other than the big relatedness to the young should not matter if provi-
game typically hunted by hunter-gatherer men. Big sioning is mating effort. Furthermore, most calories
game is unpredictable and it is typically shared more men brought in were not from big-game meat, but
widely than other resources among contemporary rather from other food sources.
hunter-gatherers, meaning less is likely to come In another study, Marlowe (2003) found that
back to a man’s nuclear family. Rather, she proposed men increased their productivity during the period

Boyet te and Get tler 183

when their wives were nursing and had lower foraging sensitive, nurturant care (Bribiescas, Ellison, & Gray,
return rates. During this time, men also targeted less 2012; Gettler, 2010). For example, Gettler (2010)
widely shared but valuable resources, like honey. argues that male carrying of offspring would have
As lactation is the most energetically expensive com- significantly reduced energetic burden on mothers,
ponent of reproduction for females, this evidence facilitating the evolution of shorter interbirth inter-
supports the position that there are fitness advan- vals and higher fertility. Direct investment through
tages to male provisioning within a division of labor socialization behaviors, such as teaching, may also
and that there was a role for indirect paternal care in have been critical, and possibly more so after early
the evolution of pair-bonds. The association between childhood when carrying and provisioning are most
male care and lactation has been further substantiated important (Gray & Anderson, 2010). For instance,
in a cross-cultural study by Quinlan and Quinlan Kaplan and colleagues (2000) argue that the extraor-
(2008), who found a strong relationship between the dinarily long human childhood evolved to allow for
stability of pair-bonds in a culture and the mean learning necessary foraging skills. Men’s teaching
duration of lactation. may have been important in facilitating this critical
Gurven and Hill (2009) also develop several learning, likely during middle childhood and ado-
counterarguments to some assumptions of the show-­ lescence (Dira & Hewlett, 2016; Hill, Barton, &
off hypothesis. For example, the idea that if men’s Hurtado, 2009; Hrdy, 2009). Scelza (2010) argues
goal was to provide for their family they should target that men are especially likely to provide direct in-
more reliable resources is i­nconsistent with their vestment when it is not easily substitutable, as when
calculations that Ache, Hadza, and Hiwi hunter-­ they have specific cultural knowledge or status. In
gatherer men’s average hunting returns are equal to support of her argument, she found that, among
or greater than the returns from gathering more reli- Martu Aborigines of Australia’s Western Desert,
able starchy foods. Variability, whether seasonal or young men whose father was present had their initi-
daily, they argue, is inherent to foraging and some- ation ritual—a gateway to marriage—significantly
thing people adapt to. They also point out that the earlier than those without, and age at initiation pre-
added nutrient diversity of meat is a valuable com- dicted the young man’s chance of having a current
ponent of the division of labor. Furthermore, small child and the total number of his current children. In
game has been a part of human diets throughout our this case, we see direct paternal investment in young
history as a species and, in contrast to widely shared adult offspring directly impacting inclusive fitness.
large game, tends to be preferentially shared within Bribiescas, Ellison, and Gray (2012) emphasize
families. Moreover, contrary to the assumption that that what is truly distinctive about human paternal
a good hunter’s family would not receive enough of care is its variability. They note that the diversity
his kill for his hunting to be considered parental of observed male behavior toward offspring varies
effort, they point out that most studies of meat from carrying, teaching, and provisioning at one
sharing among contemporary hunter-gatherers show extreme to infanticide at the other, depending
the reverse trend, with hunters’ families receiving on the socioecological context. For instance, Aka
more. They conclude that it is more reasonable to hunter-gatherers of the Central African Republic are
assume that signaling benefits from hunting would known for their intimate, high-investing fathering
only motivate men to hunt more but are not suffi- (Hewlett, 1991). However, Hewlett found that the
cient to explain why men hunt. Many factors are level of direct investment depended on how many
likely to influence the opportunity costs men might brothers a man lived with. Men with more brothers
suffer by choosing to provision their families; thus, spent more time with other men and less time
it is more reasonable to see provisioning as a mix of holding their infants because, Hewlett believes,
mating effort and parenting effort that can shift their investment of time with their social network
depending on the context. has indirect payoffs for their children, who will receive
We can conclude that provisioning remains one shares of the resources the brothers cooperatively
likely important factor in the evolution of pair-bonds ­acquire. Similarly, among the same group, Meehan
and paternal care. However, an exclusive focus on (2005) found that men spent less time in direct care
provisioning is limiting with respect to the potential when the couple was living matrilocally (i.e., with
pathways for men to make significant impacts on the wife’s family). In this case, other women in the
their own and their mates’ reproductive success. For wife’s family assumed more of the childcare burden.
one, it ignores the possible evolutionary significance When men were living with their own families, patri-
of men’s direct investment in offspring through locally, they performed more direct care.

184 Evolution and Human Fatherhood

 Thus, levels of paternal care vary between and ­rimate species as well (Palombit, Seyfarth, &
p
within societies. Moreover, men may divide their Cheney, 1997). One solution to the problem of
resources between direct or indirect parental effort infanticidal males in baboon society is for females
and mating effort differentially across a lifetime or to court “friendships” with one or more specific
at times both simultaneously. Men’s behavior toward males (Palombit et al., 1997). Females grant these
stepchildren illustrates this well. A major factor in males sexual access and, subsequently, their “friends”
predicting male investment is paternity certainty. have been observed to come to their aid more read-
Thus, all types of male investment are expected to ily than “nonfriend” males to threats from aggres-
be greater for putatively biological than nonbio- sive or infanticidal males in the group. Thus, these
logical children. Evidence tends to support this comparative cases suggest that another potential
claim. In addition to Hadza fathers cited previously factor in the evolution of pair-bonds in hominins
(Marlowe, 1999), American men in Albuquerque, could have been protection from other males. For
New Mexico (Anderson, Kaplan, & Lancaster, 1999), example, in a scenario favored by Gray and Anderson
and Xhosa men in Cape Town, South Africa, spent (2010), mate guarding by groups of low-ranking
more on their biological children’s education expenses males would have been an early step in moving from
(Anderson, Kaplan, Lam, & Lancaster, 1999), and a polygynous social system with a single alpha male
men in rural Trinidad, where men are typically low monopolizing a group of females to a monogamous
investing, spent more time with their genetic chil- social system based on pair-bonds.
dren (Flinn, 1988). Most striking is work by Daly To conclude this section, the fact that paternal
and Wilson (1988b) demonstrating that infant and care in humans may at times be mating effort and at
child morbidity and mortality in the United States times parenting effort suggests that plasticity is cen-
and in Canada are far greater when the victim lives tral to the evolution of men’s parenting. Male pro-
with one or more stepparents than with both genetic tection and provisioning of females in exchange for
parents. For example, in the United States in 1976, sexual access may have been key to the early formation
fatal child abuse was 100 times more likely among of pair-bonds, a change that could have precipitated
children living with a stepparent than those living many more (Gray & Anderson, 2010). Likely, females
with biological parents (Daly & Wilson, 1988a). At had an important role in ensuring (or manipulating)
the same time, stepfathers do regularly invest in their men’s paternity certainty to keep males invested.
current mate’s children. As demonstrated in baboon Continued association with their mates may have
societies, the evolutionary basis for male investment facilitated bonding with their offspring, and men
in this context may be increased chances of mating may have taken to carrying their young, further in-
with their mothers, irrespective of genetic ties to creasing their own and their mates’ reproductive
the young (Smuts & Gubernick, 1992). Anderson, success by shortening the interbirth interval. As lives
Kaplan, and colleagues (1999), for example, found extended, extractive foraging technology became
that resident Xhosa stepfathers invested far more more efficient, networks expanded, and cultures
time with their stepchildren than did nonresident elaborated, men’s teaching and other socialization
biological fathers. One interpretation is that such behaviors would have become more valuable. We
investment in stepchildren can be described as must not forget that this scenario most likely occurred
mating effort. within the context of multimale, multifemale groups
The evidence for infanticide by stepfathers high- in which many others had overlapping fitness inter-
lights another potential evolutionary benefit to the ests in any single child, and alloparental care was
formation of pair-bonds—the prerequisite to pater- common (Hill et al., 2009; Hrdy, 1999). Thus,
nal care. Although relatively rare in contemporary men’s care would have oftentimes been substitutable
humans, primate models suggest the threat of infan- (Sear, Steele, McGregor, & Mace, 2002)—but at
ticide for ancestral hominin females may have been other times perhaps not (Scelza, 2010; Shenk &
much greater. Sexual dimorphism was greater, sug- Scelza, 2012).
gesting more competition between males over sexual Next, we review what we know about the evolu-
access to females. Since fertility is lower when females tion of the proximate mechanisms responsible for
have nursing infants, infanticide would have been the diverse array of paternal care we have discussed
one potential male strategy to increase female fertility here. What we know is that underlying the great
and lay claim to her future offspring. This strategy variation we see in paternal care in humans is
was famously first observed in use by Hrdy (1977) ­biology as complex and sensitive to the context of
among Hanuman langurs, but is seen in other care as is that of mothers. Later, we return to life

Boyet te and Get tler 185

history when considering approaches to the evolu- toward their vulnerable offspring and cooperative
tion of paternal care that integrate the multiple behavioral dynamics and away from aggression and
layers of explanation. competition (Wingfield et al., 1990). Building from
this framework, research on other vertebrates has
Evolution of Hormonal and found that committed fathers commonly show
Neurobiological Mechanisms Related similar physiological profiles, including some com-
to Human Fathering and Promoting bination of reduced T, elevated prolactin (PRL),
Paternal Care and heightened oxytocin (OT) production (Gettler,
As one of us (Gettler) has often jokingly remarked 2010, 2014; Gray & Anderson, 2010; Storey &
during professional talks on this subject, we do not Ziegler, 2016; Trumble, Jaeggi, & Gurven, 2015; van
find evidence for H. erectus or early human baby Björn Anders, 2013; van Anders, Goldey, & Kuo, 2011).
carriers in the archaeological record. Examining Because any similarities in paternal investment
contemporary fathers’ neurobiological and hormonal among birds and mammals is the result of conver-
profiles can prove insightful in this regard, however, gent evolution (rather than shared ancestry), one
by helping to fill in some of the potential evidential can infer that overlapping patterns in fathers’ phys-
gaps. The basis for this perspective is grounded in iology across taxonomic lines represents natural
cross-species comparisons. In terms of modeling selection (or other evolutionary processes) repeatedly
human paternal neuroendocrinology, cross-species co-opting similar neurobiological and hormonal
and evolutionary perspectives are salient because the pathways, however diverse the ecological settings are
physiological systems that underlie cognition, emo- in which paternal investment evolves (Gettler, 2014,
tion, and behavior are subject to selective pressure as 2016a; Gray & Anderson, 2010; Storey & Ziegler,
new demands and strategies arise (such as invested 2016). This process is sometimes referred to as
fatherhood in the course of hominin evolution), “opportunism in evolution” (G. G. Simpson, 1967).
and, as foreshadowed in the section on “Phylogenetic Here, it would reflect evolutionary changes emerg-
Distribution of Paternal Care,” those selective pres- ing through effects on existing physiological sub-
sures and the ecological and social contexts in which strates that are shared across vertebrates, such as the
paternal care arises and is potentially adaptive may hypothalamic-pituitary-gonadal axis that produces
be similar across taxa. Such perspectives and com- T and the hypothalamic-pituitary-­ dopaminergic
parisons provide the background to understand signaling pathways that regulate PRL. Such “oppor-
what selective factors might have shaped human tunistic,” convergent evolutionary processes are
fathers’ capacity to respond to parenthood physi- generally thought to be a path of less resistance for
ologically and under what circumstances those selection, compared to (in this case) the physiolog-
social neuroendocrine circuits might be engaged ical changes required for de novo fatherhood neuro-
(Gettler, 2010, 2014; Gray & Anderson, 2010; endocrine adaptations via random mutations in
Storey & Ziegler, 2016). diverse vertebrate taxa (Gettler, 2014). Those evolved
Much of the behavioral physiological research foundational neuroendocrine pathways provide the
that has been conducted on vertebrate fathers was scaffolding through which biosocial or biocultural
specifically grounded in Wingfield, Hegner, Ball, interfaces emerge in contemporary fathers today.
and Duffy’s (1990) Challenge Hypothesis. Drawing Indeed, our understanding of human fathers’ neu-
on extensive endocrine research on bird species, roendocrinology has expanded over the past decade
this model provided a framework to explain how as this evolutionary foundation has been integrated
mating- and parenting-related demands across the with biocultural approaches and concepts related to
reproductive cycle interrelated with male birds’ tes- parent–child biobehavioral synchrony (Feldman,
tosterone (T; Wingfield et al., 1990). For example, in 2012; Feldman, Monakhov, Pratt, & Ebstein, 2016;
species in which male–male competition was high Gettler, 2010, 2014; Gray & Anderson, 2010;
and paternal care was absent, males were predicted Trumble et al., 2015; van Anders, 2013; van Anders
to maintain consistently elevated T, which would et al., 2011).
help maintain somatic investment in musculature and As we will discuss in subsequent sections, the
ornamentation while also facilitating competitive, results of these studies cumulatively link specific
aggressive, and courtship behaviors. In contrast, paternal T, PRL, and OT profiles to overall in-
among species with biparental care, fathers’ T was volvement in direct care and specific forms of
expected to decline when they cooperated with ­nurturant, sensitive parenting behaviors in those
mothers to raise young, focusing their attention contexts (Feldman, 2012; Gettler, 2014; Gray &

186 Evolution and Human Fatherhood

Anderson, 2010; van Anders, 2013; van Anders data collected over a decade, Mazur and Michalek
et al., 2011). Consequently, in light of cross-species (1998) showed that U.S. veterans who became
comparisons, these patterns are broadly (albeit in- newly married during the study period experienced
directly) consistent with the notion that nurturant, a significant decline in T. They also found that
direct caregiving was sufficiently common and married men who had elevated T were more likely
­beneficial to male reproductive fitness during our to become divorced at future time points in the
evolutionary past that human male neurobiological study. Thus, these results hinted at a bidirectional
and endocrine systems have undergone selective or transactional relationship between men’s hor-
pressure to specifically help elicit and respond to mones and the social dynamics and outcomes they
sensitive, high-quality father–child social interactions experienced in their marriages. Building from this
(Gettler, 2014; Gray & Anderson, 2010; Storey & work and in a series of foundational cross-cultural
Ziegler, 2016). studies, others began testing whether T varied by
both fatherhood and marital status and how that
Connections Between Men’s Hormones variation might be influenced by cultural and eco-
and Fathering logical dynamics in settings around the world
testosterone (Gray & Campbell, 2009).
Drawing influence from the challenge hypothesis, In those studies and those by other teams, it has
as well as research on behavioral physiology among since been shown that men who are partnered (e.g.,
nonhuman mammalian species in which fathers are married or cohabitating) men, especially those who
involved with care, a large body of literature has are fathers, have lower T than single nonfathers in
explored the variation of human males’ T by life many global contexts, such as the United States,
history status (i.e., marriage/partnering and parent- Senegal, Tanzania, the Philippines, China, and
hood; Gettler, 2014; Gray, McHale, & Carré, Japan (Alvergne, Faurie, & Raymond, 2009; Gray,
2016; Storey & Ziegler, 2016; van Anders, 2013; Kahlenberg, Barrett, Lipson, & Ellison, 2002; Gray,
van Anders et al., 2011). Although the links be- Yang, & Pope, 2006; Kuzawa, Gettler, Muller,
tween elevated T and greater aggressive behavior McDade, & Feranil, 2009; Muller, Marlowe,
tend to be either weaker or mixed among humans, Bugumba, & Ellison, 2009). In contrast, this specific
compared to what has been observed in many other pattern did not hold among men in a Kenyan cultural
nonhuman species, a number of observational and group in which polygyny was common (Gray, 2003;
experimental studies are consistent with the notion see also Gray, Ellison, & Campbell, 2007), and in a
that men with elevated T might be prone to com- large, recent study of fathers in Jamaica, where it is
petitive behavior, anger, and reduced empathy culturally common for fathers’ relationship statuses
(Archer, 2006; Carré & Olmstead, 2015; Gettler and residence with their children to shift relatively
& Oka, 2016; Gettler, 2016b; Gray et al., 2016; frequently, patterns likewise varied (Gray et al.,
van Anders, 2013; van Anders et al., 2011). 2017). In total, these latter findings suggest a mod-
Neuroimaging studies also indicate that elevated erating effect of societal mating systems and cultural
T alters the neural communication and connectivity patterning of marriage and partnering on how and
between executive-functioning frontal areas and whether men’s T varies by life history status. U.S.
emotion-facilitating limbic areas, such as the amyg- based studies have also found that men in commit-
dala, when humans are confronted with status ted relationships do not have reduced T when they
challenges and threat. It is thought that such neural maintain interest in extra-pair sexual (McIntyre
profiles may increase the likelihood of reactive et al., 2006) or romantic (van Anders & Goldey,
­aggression. In contrast, lower T males generally show 2010) opportunities, which point to the interrela-
greater tendencies toward prosocial, empathetic tionships between T and dimensions of sociosexu-
behavior, and it is thought that reduced T may be ality in some contexts (Puts et al., 2015). Recent,
beneficial toward romantic and parent–child rela- complementary U.S.-based research has also shown
tionships grounded in warmth and nurturance cross-partner correlations between T and relation-
(Archer, 2006; Carré & Olmstead, 2015; Gettler & ship dynamics, as men and women with higher T
Oka, 2016; Gettler, 2016b; Gray et al., 2016; van reported lower relationship satisfaction and com-
Anders, 2013; van Anders et al., 2011). mitment and so did their partners (i.e., those part-
Some of the earliest and most influential insights nered to someone with high T also reported reduced
in this domain emerged from a long-term study of satisfaction and commitment; Edelstein et al., 2014).
U.S. military personnel. Drawing on longitudinal In a 2017 study, Jamaican fathers were similarly

Boyet te and Get tler 187

shown to have lower relationship quality if their T responses to different care contexts are also sensitive
was elevated (Gray et al., 2017). to the cultural context and should be interpreted
Multiple studies from various cultural settings in regards to factors such as marriage patterns (e.g.,
have also explored the associations between fathers’ polygyny vs. monogamy) and cultural values around
T and their involvement with childcare (Gettler, men’s roles as fathers.
2014, 2016a; Gray et al., 2016). In the only study Although most prior research in this area has
to date to explicitly compare these dynamics cross- been cross-sectional, a small number of studies have
culturally, Muller and colleagues (2009) showed used longitudinal data to model changes in men’s T
that fathers had lower T than nonfathers among a across the parenting transition and how shifts in
sample of Hadza hunter-gatherers in Tanzania, behavior, family dynamics, and T interrelate with
whereas among a neighboring group of Datoga one another. Drawing on a large longitudinal study
pastoralists fathers’ and nonfathers’ T did not differ. in the Philippines, Gettler and colleagues (Gettler,
These two groups have different models of fathers’ McDade, Agustin, Feranil, & Kuzawa, 2015;
involvement with children, as Datoga fathers have Gettler, McDade, Feranil, & Kuzawa, 2011; Gettler,
little involvement with young children and Hadza McKenna, Agustin, McDade, & Kuzawa, 2012)
fathers are routinely involved with childcare. These have made many critical contributions in this area.
differences might help account for the cross-cultural They showed that men transitioning from being
variability in T’s relationship to fatherhood status single nonfathers to partnered fathers experienced
(Muller et al., 2009). Supporting this notion, a large declines in T (e.g., a median of –34 percent for
number of other subsequent studies have shown evening T) across a 4.5-year period. Their declines
that fathers’ T tends to be lower when they are more in T were much larger than men who remained
involved with hands-on childcare (Alvergne et al., single nonfathers (Gettler et al., 2011). At this same
2009; Mascaro, Hackett, & Rilling, 2013; Weisman, site, fathers’ T and caregiving were shown to change
Zagoory-Sharon, & Feldman, 2014), a­ lthough that in tandem, with fathers’ T declining if they increased
pattern is not ubiquitous (Gray et al., 2017; Gray their involvement in care over the 4.5-year follow-up
et al., 2002). period (Gettler et al., 2015), and new fathers’ T
Adding complexity to our understanding of the re- decreased more steeply if they slept in close prox-
lationship between cultural models of fatherhood, T, imity to their children rather than separately from
and paternal care, recent research suggests men with them (Gettler, McKenna, et al., 2012). In addition,
T functioning that is too low are prone to lower Gettler, McDade, Agustin, Feranil, and Kuzawa
participation in childcare (Gettler et al., 2017). In (2013) showed that the greater men’s decline in T as
addition, high T might also facilitate paternal indirect they became newly partnered new fathers, the less
care when competitive or risk-taking behaviors, frequently they reported having sexual intercourse
which are promoted by T (e.g., hunting, predator with their partners. Finally, expanding this research
defense), benefit his offspring (van Anders, 2013). on male psychobiology, Gettler et al. (2017) recently
For example, our recent research has shown that, integrated data on an androgen receptor genetic
among Bondongo fisher-farmers in the Republic of polymorphism that contributes to the physiological
the Congo, men who were rated has better providers effects of T after binding (see review in Ryan &
of resources (i.e., more indirect care) had higher T. Crespi, 2012). Men who had particularly high levels
However, men rated as more likely to provide direct of androgenicity (i.e., androgen functionality) or low
care (e.g., socialization and care of sick children) levels of androgenicity were more likely to experi-
had middle-range levels of T—neither too high or ence relationship instability. Young men’s androgen-
too low— for their community (Boyette, Lew-Levy, icity before they were parents also predicted whether
Sarma, and Gettler, 2019). Furthermore, we found they were later involved as direct caregivers, with
that those children whose fathers had middle-range moderately androgenic men being more involved,
T were in better energetic condition. These findings on average, compared to low- or high-androgenic
indicate that father’s provisioning is highly valued males (Gettler et al., 2017).
in this cultural context and is linked to higher T, Elsewhere, a small, intensive study of pregnant
although it appears that there are potential costs to women and their partners in the United States has
having relatively higher levels of T, perhaps because found complementary results, showing that men’s
high T fathers direct their effort toward mating. T declines, on average, from the late prepartum
Our findings, along with those of Muller and col- to the early postpartum period. Fathers’ whose T
leagues (2009) noted earlier, indicate men’s biological decreased more from the pre- to postpartum period

188 Evolution and Human Fatherhood

reported higher relationship satisfaction and invest- (common marmosets; Storey & Ziegler, 2016).
ment, as did their partners. Men with more substan- Either suppressing PRL or artificially elevating it
tial declines in T were also rated as more supportive well beyond typical levels reduces common marmo-
by their partners after the baby arrived (Edelstein set fathers’ responsiveness to infant stimuli and also
et al., 2015; Edelstein et al., 2017; Saxbe et al., 2016). adjusted PRL’s relationship with T (with the norma-
In a similar study that tracked men at two time tive pattern being elevated PRL and reduced T),
points before and after their infants were born, which may be a potential joint-hormone pathway
fathers showed declines in T but only if they had related to care expression (cf. Almond, Brown, &
scored lower on an index of sensation-seeking during Keverne, 2006; Ziegler, Prudom, Zahed, Parlow,
the prepartum period. This suggests that personality & Wegner, 2009). Marmoset fathers with sup-
or disposition and/or their neurobiological or en- pressed PRL also lost substantial weight in this study,
docrine underpinnings help shape T responses to which parallels the prior observation that PRL
parenthood (Perini, Ditzen, Hengartner, & Ehlert, ­increases in expectant fathers contribute to weight
2012). In this study, fathers who reported more of a gain that helps buffer males from energetic stress
decline in T across the peripartum also reported ­related to metabolically costly transport of their litters
decreased tenderness in their relationship with the of twins and triplets (Storey & Ziegler, 2016).
mother postpartum, which the authors note could Among humans, some of the earliest hints that
reflect a shift in both parents’ focus to the infant PRL might be related to dimensions of human father-
(Perini, Ditzen, Fischbacher, & Ehlert, 2012). ing emerged from research on Canadian fathers.
Cross-sectional research targeting expectant and
prolactin new fathers at different stages across the peripartum
Compared to the extensive research that has been period indicated that fathers’ PRL was elevated in
done on T’s implications for human social relation- the weeks just before their babies were born. In that
ships and behaviors, far fewer studies have examined same study, men were exposed to recorded infant
PRL in these areas. PRL is a protein hormone that cries, and those who reported feeling the most con-
is produced in the pituitary gland and is regulated cerned had higher PRL than less responsive men
by hypothalamic release of dopamine (Freeman, (Storey, Walsh, Quinton, & Wynne-Edwards, 2000).
Kanyicska, Lerant, & Nagy, 2000). Among bird Similar results were found in a subsequent study of
species expressing biparental care, PRL has been Canadian fathers, as those with higher PRL were
shown to be elevated among males cooperating more alert and tended to be more positive in response
with females to raise young, and it is correlated to a to audio recordings of infant cries. In that study,
diverse array of parenting behaviors, including fathers with more experience caring for infants also
direct care, such as incubation and feeding, and had elevated PRL compared to less experienced
indirect care, such as provisioning of mothers and men (Fleming, Corter, Stallings, & Steiner, 2002).
offspring (Angelier, Wingfield, Tartu, & Chastel, Elsewhere, research conducted in Israel found that
2016; Gettler, McDade, Feranil, & Kuzawa, 2012). fathers’ PRL was generally stable across the first six
PRL is similarly commonly elevated among mam- months postpartum and that fathers with greater
malian males when they serve in caregiving roles PRL tended to play with their infants in a coordi-
(Gettler, 2014). For example, longitudinal research nated, exploratory manner, which is beneficial
on African striped mice, a species in which males to child development (Gordon, Zagoory-Sharon,
can alternate between multiple reproductive tactics, Leckman, & Feldman, 2010). In the Philippines,
has shown that males’ PRL goes up when they shift young adult fathers were found to have higher PRL
from being isolated roamers or group-living non- than nonfathers, and PRL was most elevated among
breeders to dominant breeders (i.e., becoming fa- fathers with infants (1-year-old or less). However,
thers; Schradin & Yuen, 2011). Among meerkats, fathers’ PRL was not correlated to their level of
PRL is elevated among males immediately before caregiving (Gettler, McDade, et al., 2012; Gettler
they opt to serve in “babysitting” roles over foraging et al., 2015). In contrast to these findings, in a com-
(Carlson et al., 2006). paratively smaller study in Jamaica, men’s PRL did
Among certain New World primates with inten- not vary based on whether they were nonfathers,
sive paternal care, PRL is elevated in experienced coresidential fathers, or nonresidential visiting fathers
fathers, relative to nonfathers (cotton-top tamarins), (Gray et al., 2007b).
or is particularly high during the postpartum period There are so few studies on human PRL and
when fathers play critical roles in carrying young social behavior, including fathering, that it would

Boyet te and Get tler 189

be premature to make definitive statements about these studies have methodological limitations,
PRL’s influence or responsiveness to paternal care. which are often variably addressed (Churchland
Some of the existing observations suggest that PRL & Winkielman, 2012; McCullough, Churchland, &
might mechanistically help elicit positive paternal Mendez, 2013). Human-based studies of OT, includ-
behaviors, such as beneficial forms of play or responses ing those we will review later in this section, virtually
to infant distress (Fleming et al., 2002; Gordon et al., uniformly measure OT from blood, saliva, or urine,
2010; Storey et al., 2000). In that sense, they show which provide measures of “peripheral” OT, mean-
broad similarities with patterns from other verte- ing that which is released into circulation outside of
brata taxa, including among nonhuman primates. the brain. Animal models demonstrate that OT that
Findings that fail to demonstrate similar patterns, is released peripherally and that which is released
such as Gettler and colleagues’ findings from the centrally (i.e., in the brain) are sometimes correlated
Philippines, are potentially indicative that PRL’s but also disassociated at times (Landgraf & Neumann,
interrelationships with parenting vary across cultures 2004). Unlike T and PRL, OT cannot cross from
in a similar manner to T (Gettler, McDade, et al., the peripheral circulation across the blood–brain
2012; Gettler et al., 2015). We would collectively barrier to reach central neuronal pathways. Conse­
be able to formulate more rigorous hypotheses quently, the effect of OT on behavior, emotion, and
about the implications of PRL within family systems cognition is thought to be primarily caused by its
and across various cultural and ecological contexts if central release into the brain, rather than through
we better understood its effects on other (nonpar- peripheral pathways, which constrains the insights
enting) types of social behaviors and cognitive that can be gained through the latter, although most
processes, as we do for T and OT. prominently for null associations between behavior
and OT (Churchland & Winkielman, 2012;
oxytocin Gettler, 2014; McCullough et al., 2013). In addi-
OT has been extensively studied for its promotion tion, many studies of OT’s effects on behavior rely
of certain mammalian social bonds, particularly on exogenous doses of OT through intranasal ad-
between mothers and their infants. In that vein, it ministration. Although triangulation across multi-
also has a critical role in lactation physiology, ple types of studies and data suggest such exogenous
stimulating milk letdown from the mammary gland. OT likely reaches the brain, questions do remain
In addition to its implications for mammalian about the mechanics and pathways involved to
mother–infant bonding, OT was shown to con- affect neural function and (ultimately) behavior
tribute to the formation of pair-bonds among (Churchland & Winkielman, 2012; Gettler, 2014).
(frequently) monogamous vole species, particularly Finally, some scholars have suggested that the assay
among females, and these monogamous species of procedure used to measure OT is often not con-
voles had more higher densities of OT receptors in ducted properly, whereas others have raised ques-
dopaminergic pathways related to reward and social tions as to how OT migrates to saliva, through
motivations and preferences (Carter, 1998; Young, which it is frequently measured, and why blood and
Lim, Gingrich, & Insel, 2001). Building largely salivary OT levels are only modestly correlated (see
from this body of research, early studies on the review in McCullough et al., 2013).
function of oxytocin in human social behavior and Much of the research that has been conducted
bonding focused extensively on its potential to fa- on fathering and OT has emerged from extensive
cilitate and respond to prosocial or nurturing social studies of Israeli families (Feldman, 2012). These
interactions, such as warm contact between roman- studies have shown that fathers and mothers gen-
tic partners or trust and generosity during low-stakes erally have comparable circulating levels of OT,
economic games (Bartz, Zaki, Bolger, & Ochsner, when maternal OT is not measured during breast-
2011). This body of literature continued to grow, feeding episodes, and fathers who served in pri-
with many studies confirming OT’s prosociality and mary caregiving roles had higher OT than those
bonding-promoting effects, until researchers began who were more secondary (Abraham et al., 2014;
testing whether OT might also facilitate agonistic Feldman, Gordon, & Zagoory-Sharon, 2011).
behaviors, depending on social context, which we Moreover, maternal and paternal OT tends to be
return to later in this section (Bartz et al., 2011; positively correlated within families, so if one
Feldman, 2012). ­parent’s OT is elevated, the other’s tends to be as
Before exploring the existing research regarding well. These within-family OT correlations also
OT and fathering, it is important to point out that extend to young children (i.e., higher OT mothers

190 Evolution and Human Fatherhood

and fathers have children with higher OT; stimuli, OT was not correlated to men’s responses
Feldman et al., 2011; Feldman, Gordon, Influs, to infant cries (compared to control stimuli; Mascaro,
Gutbir, & Ebstein, 2013). This research has yielded Hackett, Gouzoules, Lori, & Rilling, 2013). Similarly,
many notable insights regarding fathering and OT, a separate study examining men’s neural responses
including that fathers with higher OT exhibit to child faces along with images of adult men and
more positive engagement, communication, and women, including sexually provocative images of
affect synchrony with their children during interac- the latter, found limited results, with higher OT
tions and they also engage in more affectionate being related to greater hippocampus activity
touch. Overall, parents with greater OT report during child viewing tasks (Mascaro, Hackett, &
stronger bonding to their infants (Feldman et al., Rilling, 2014; Mascaro, Hackett, Gouzoules, &
2011). Feldman and colleagues have provided in- Rilling, 2013).
creasing evidence for the cross-generational trans- Finally, there is increasingly nuanced research
mission of OT profiles, prosocial behavior, and on OT demonstrating that its prosocial-promoting
­parental involvement. For example, fathers with effects are context dependent and that it can pro-
higher OT reported receiving more care from their mote antisocial, agonistic tendencies in specific
own parents (Feldman et al., 2012). In a study fo- situations. A review of this literature is beyond the
cusing on social behavior of toddlers, they observed scope of this chapter, particularly since the studies
that if mothers had elevated OT, their toddlers also in question have not focused on fathering (see reviews
had elevated OT, which was related to how proso- in Bartz et al., 2011; Ma, Shamay-Tsoory, Han, &
cially the t­oddlers behaved with their friends Zink, 2016). However, evidence suggests artificially
(Feldman et al., 2013). Finally, in both observa- elevating OT can increase gloating and envy, mob
tional studies of parent–infant OT and experi- mentality, ethnocentrism, and out-group hostility,
mental work in which fathers were administered as well as reaction to provocation (see reviews in
intranasal OT, it was found that when parental Bartz et al., 2011; Ma et al., 2016). Exogenous
OT was elevated and they engaged with the infant OT also contributes to reduced tension among
through affectionate and synchronous interac- nulliparous women in response to infant cries, but
tions, the infants’ OT also spiked significantly only if they had not received harsh parenting
(Feldman, Gordon, Schneiderman, Weisman, & during their own childhoods. Exogenous OT had
Zagoory-Sharon, 2010; Weisman, Zagoory-Sharon, no such tension-reducing effect for women who had
& Feldman, 2012). Although heritable genetic negative experiences with their own parents
polymorphisms related to OT function likely (Bakermans-Kranenburg, van Ijzendoorn, Riem,
have implications for parent–child correlations Tops, & Alink, 2012). Citing this work, Gettler
in OT function (Feldman et al., 2016), these (2014) argued that there are many circumstances
studies provide evidence for the ways in which during familial interactions, particularly across the
OT–social behavior profiles can be transferred span of child development from infancy to adoles-
across generations. cence, in which elevated OT would likely not elicit
Outside of this extensive work on Israeli fathers, positive interactions from parents or children and
there have been relatively few other studies specif- might even predispose certain parents to harsh,
ically focusing on OT and fathering. A small study reactive, or abusive behaviors. The importance of
of Jamaican fathers, mentioned earlier, did not find cultural models of family systems, gender norms,
differences in urinary OT between single men, resi- and parenting roles in shaping the contexts in which
dential fathers, and visiting fathers (Gray, Parkin, & OT’s effects find expression are also largely absent
Samms-Vaugh, 2007). Two studies of Dutch fathers from this literature.
in which men received intranasal OT and were
observed during in-home interactions with their tod- brief summary
dlers showed that elevated OT was related to great The existing literature on human paternal psychobi-
stimulation of exploratory and sensitive play and lower ology is consistent with the idea that males have
paternal hostility (Naber, Poslawsky, van IJzendoorn, the neurobiological and neuroendocrine capacity to
Van Engeland, & Bakermans-Kranenburg, 2013; respond to invested fatherhood with shifts in hor-
Naber, van Ijzendoorn, Deschamps, van Engeland, mones that likely help elicit nurturant behavior.
& Bakermans-Kranenburg, 2010). Finally, in func- The expression of these hormonal profiles also­
tional magnetic resonance imaging (fMRI) studies ­appears to be highly flexible and plastic and not
of paternal neural activity in response to infant canalized as a result of the transition to parenthood.

Boyet te and Get tler 191

Nonadaptationist explanations for these paternal discussed in this section, early-life contexts of stress
psychobiological profiles are plausible and should are emphasized such that psychological, cultural,
be considered. For example, based on behavioral and neuroendocrine foundations for parenting
physiological research across the Primate order, style are canalized—at least to some degree—during
Gettler (2014) has suggested that the capacity of development as a response to features of the envi-
human males to respond to fatherhood with neuro- ronment before a man is a father.
endocrine shifts might reflect broader primate psy- Knowledge of paternity certainty, ease of food
chobiological flexibility, reflecting our evolutionary acquisition and divisibility of shares, relationship
history as highly social, often tolerant and prosocial, with a child’s mother, and the number of other
group-living mammals. However, the similarities potential alloparents to aid in care may all influence
between the hormonal profiles associated with any individual male’s investment decisions, which
nurturant, committed partnering and parenting in are in turn moderated by his neuroendocrine systems.
humans and that of other taxa with evolved bipa- How, then, do we explain large-scale trends in male
rental care are consistent with the idea that humans investment across social groups or whole cultures?
have evolved these psychobiological capacities, Draper and Harpending (1982) proposed that
through direct selection or other evolutionary pro- developmental plasticity in relation to early-life
­
cesses (Gettler, 2014; Gray & Anderson, 2010; psychosocial stress may be key to the unfolding of
Storey & Ziegler, 2016). The common associations life history strategy. Their theory stems from the
between fathers’ lower T and their engagement in observation that father absence during childhood
childcare, observed across cultures, and the comple- seemed to be associated with “unfavorable” out-
mentary findings from PRL and OT from certain comes—early sexual activity, teenage pregnancy,
societal settings provide a line of evidence suggest- unstable partnerships, and risky behavior in men.
ing that such roles may have been evolutionarily From a life history perspective, there is a funda-
important to males’ reproductive fitness and to mental trade-off between reproducing now and
child outcomes (Gettler, 2014). These patterns are accumulating resources to invest in offspring later.
notable because human fathers in contemporary They reasoned that from a child’s perspective,
societies engage in relatively little direct care, on father a­bsence indicates that success is not de-
average, especially compared to mothers, but they pendent on parental investment (i.e., there are
do align with research on child development, largely risks in the e­nvironment that parental effort
from Western societies, suggesting that high-quality, cannot reduce or avoid; Quinlan, 2007), such
sensitive, nurturant parenting from fathers has pos- that the most successful strategy would be to
itive impacts on child well-being (Pleck, 2012). The mature quickly and invest in reproduction
notion that some fathers might have been involved (mating strategy). On the other hand, father pres-
caregivers during our evolutionary past is compati- ence indicates local resource stability, such that
ble with, and does not negate the notion that, they stable pair-bond and ­paternal investment will lead
cooperated with mothers in terms of foraging and to greater long-term fitness.
providing children with resources, which is more Draper and Harpending’s (1982) central claim
commonly emphasized in terms of paternal roles was that humans evolved a psychological ­mechanism
during hominin evolution (Gettler, 2010). that cued the early adoption of one or the other
strategy. Such a mechanism would be ­adaptive as
Multilayered Explanations for the Diversity long as the environment does not change substan-
of Male Caregiving tially between generations. Belsky, Steinberg, and
Given what is known about the ultimate and proxi- Draper (1991) and Chisholm (1993) extend this
mate basis for paternal care in humans, what theories theory, suggesting that parent–child attachment
have been proposed that explain the wide variation security is the mechanism that mediates between
observed in men’s care at both the population and paternal investment and adult behavior. Securely
individual level? Life history theory has again been attached individuals would be more likely to delay
useful in modeling how different features of the reproduction and invest more in building a stable
socioecological context might inform variation in partnership, as they tend to have an internal working
investment strategy (e.g., emphasis on parenting vs. model, or stable cognitive representation, of social
mating effort) of a group of men such that popula- relationships as stable and worthy of trust (Bowlby,
tion-level patterns emerge from the shared contexts 1969; Hewlett, Lamb, Leyendecker, & Schölmerich,
of individual men. In the theoretical treatments 2000). In contrast, the absence of reliable and

192 Evolution and Human Fatherhood

nurturant caregiving is associated with the develop- a­ ttributed to early-life parenting behavior (Quinlan
ment of an internal working model of relationships & Quinlan, 2007), consistent with the predictions
as unstable and based in mistrust and, accordingly, of Draper and Harpending (1982) and Belsky and
would prompt the adoption of a mating strategy colleagues (1991).
and early reproductive development. There is con- Building from these conceptual models and the
siderable evidence that father absence and parental demographic, reproductive, and behavioral empiri-
conflict without divorce are associated with earlier cal data that have emerged from them, del Guidice
age at menarche for females (e.g., Bogaert, 2005; and colleagues (2011) proposed a framework that
Chisholm, Quinlivan, Petersen, & Coall, 2005; they termed The Adaptive Calibration Model. This
Ellis, McFadyen-Ketchum, Dodge, Pettit, & Bates, framework rigorously incorporates life history the-
1999; Moffitt, Caspi, Belsky, & Silva, 1992; Quinlan, oretical, developmental biological, and psychobio-
2003). Only one study has shown a similar associa- logical perspectives to outline how our bodies’ stress
tion for males (Bogaert 2005). However, for both physiology systems filter and internalize relevant
sexes, there is evidence that mating strategy behav- ecological and developmental information to shape
iors are associated with insecure attachment (Belsky behavioral trajectories, in feedback loops across the
et al., 1991). life course, with a particular focus on critical devel-
Quinlan (2007) and Quinlan and Quinlan opmental windows and early-life exposures, prior to
(2007) apply Belsky and colleagues’ (1991) theory maturation. Relevant to our focus here, they outline
to the level of cultural variation. Significantly, their a predictive framework for modeling the ways in
“risk-response model” relates community-level par- which social neuroendocrine systems are plastically
enting practices to the degree of extrinsic risk faced shaped across development in domains relevant to
by a population. Children experience extrinsic risk fitness, including competition and risk taking, social
independent of parenting practices. If local extrinsic affiliation and bonding, and parenting. When con-
risk is high, then parental effort might be wasted, sidered alongside the other lines of evidence and
since increases in effort do not increase children’s comparative perspectives we have described in this
chances of survival. Parents maximize their long- chapter, the adaptive calibration model provides a
term fitness through high fertility and low parental conceptual basis for new studies aiming to model
investment. If local extrinsic risk is low, then sensi- variation in paternal psychobiology within and
tive-nurturant parenting may afford children the across cultures. It likewise informs our understanding
best chance of success, and would be associated of how social and ecological environmental varia-
with relatively low fertility. Thus, “cultures of risk” bility may have shaped the expression of fathers’
emerge where populations sharing in high extrinsic biology in our evolutionary past.
risk develop similar psychological tendencies, which Complementing this approach, two recent
support similar cultural models—shared cognitive reviews and conceptual frameworks have more
­
representations of appropriate behavior—of social ­explicitly tackled perspectives on the intergenera-
relationships, including marriage (i.e., pair-bonds). tional transmission of parenting behavior and
They found compelling evidence for their integrative the neurobiological and endocrine pathways that
model. Using a representative sample of cultures underlie it. Grounded in comparative, evolutionary,
(the Standard Cross-Cultural Sample), Quinlan and biocultural anthropological approaches, Gettler’s
(2007) showed that cultures exposed to a high (2016a) DADS model focuses on the role of early-
pathogen load shared reduced paternal and mater- life social experiences in shaping the function of
nal involvement, and earlier ages of weaning. social neuroendocrine pathways related to fathering.
Additionally, Quinlan and Quinlan (2007) found The acronym “DADS” stands for duration, attitude,
that father involvement (measured as father sleeping dedication, and salience, which reflect cognitive and
proximity to infants) and parental responsiveness to behavioral aspects of fathering that are shaped by
infant crying were associated with less acceptance of the cultural and ecological context in which they
extramarital affairs (unstable pair-bonds) and reduced find expression. Gettler argues that these dimen-
prevalence of witchcraft (mistrusting social relation- sions of fatherhood and family life interrelate with
ships). Furthermore, father involvement and later broader aspects of cultural systems, such as social-
weaning ages were prevalent in societies with lower ization into gender roles, to provide early-life
levels of aggression and theft. Socialization pressures ­experiences that alter the function and development
later in childhood were controlled for, and thus of evolved social neuroendocrine pathways related
the established statistical relationships can be to fathering.

Boyet te and Get tler 193

 Finally, in a recent extensive review of human of the young, freeing men to pursue other activities.
neuroscience and psychobiology research, Bos (2017) These quite remarkable shifts from a gorilla-like
conceptualized parenting-related neuroendocrine social system to the uniquely human group of mul-
pathways along a gradient of “tending and caring” tiple mated pairs living together may have been
versus “defending and explore.” In terms of inter- facilitated by the already present neurobiological
generational transfers of neuroendocrine profiles and neuroendocrine foundation that appears to
related to parenting, this model begins from herita- represent a feature of primate psychobiological
ble genetic polymorphisms that affect the function flexibility—a flexibility that can claim humanity as
of these systems (e.g., see Feldman et al., 2016; its poster child, as attested to by the several theoreti-
Gettler et al., 2017), to maternal–fetal physiological cal and empirical linkages between environmental
interactions during pregnancy, to the endocrine risk and degree of paternal investment or proclivities
experiences of birth and the early postpartum toward direct care.
period, and to childhood and adolescence, leading
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 CH A PT E R
Hormones, Sexual Orientation,
12 and Gender Identity

Nicholas C. Neibergall, Alex J. Swanson, and Francisco J. Sánchez

Abstract

Gender identity and sexual orientation are two characteristics that play a significant role in human
development. This chapter focuses on the potential role that hormones play in their development.
First, a review of the direct effects of hormones and endocrine-disrupting chemicals is provided with a
focus on animal models and persons born with disorders of sex development. Second, some evidence
from association studies linking characteristics that are known or suspected of being influenced by
hormones is provided. Although biological research has yielded some intriguing findings—especially
from neuroimaging studies—scientists have yet to conclude what specific factors contribute to their
development.
Keywords: homosexuality, gender dysphoria, human sexuality, sexual behavior, neuroendocrinology,
transgender, intersex, diethylstilbestrol (DES), phthalates, bisphenol A (BPA)

Which restroom should transgender people use, Unlike other characteristics for which people
and should they be allowed to serve in the military have been historically marginalized (e.g., disabilities),
(Steinmetz, 2017; Stewart & Chiacu, 2017)? Does many place great emphasis on the biological bases of
the ban on sex discrimination in the Civil Rights sexual orientation and gender identity. Some legal
Act of 1964 protect workers on the basis of their decisions have relied on biological research when
sexual orientation (Shear & Savage, 2017)? At what deliberating cases (see “Opinion of the Court” in
age should clinicians provide services to transgender Obergefell v. Hodges, 2015, p. 8, for an example).
youth who request medical treatment to help align Furthermore, public opinion related to civil rights
their bodies with their gender identity (Fishman, seems to be influenced by whether there is a biological
2017)? Such questions have been the focus of recent basis for these traits (e.g., Wood & Bartkowski, 2004).
articles in the public domain, and this focus has Although science has advanced our understanding
partly been stoked given recent decisions by the cur- of these complex issues, much remains unknown. In
rent administration in the United States. Although this chapter, we provide a brief overview of research
transgender issues are currently dominating the public related to hormones. Before reviewing this literature,
conversation related to sexual and gender minori- we present some key terms and brief background
ties, the questions being asked of this community information.
are ones that previously and primarily focused on
nonheterosexual people. When people encounter Key Terms and Background Information
others who seem to “deviate” from the “norm,” they A variety of terms are associated with the lesbian,
may assume that there is something “wrong.” Of gay, bisexual, and transgender (LGBT) community.
course, such simple generalizations overlook the fact Complicating the issue is that the transgender and
that when it comes to most complex human traits, gender-nonconforming community (henceforth
there is great variability between people. transgender, for simplicity) is diverse, and the needs

201
of any subset of the transgender community do not persons assigned a female birth sex but who
necessarily represent the needs of all (e.g., the needs identify as male (often referred to as female-to-
of someone seeking to transition from one gender male or FTM transsexuals in the literature).
to the other are more complex than the needs of
someone who “cross-dresses” for entertainment or Although there are a variety of psychological
personal enjoyment). An extensive list of terms can components that may factor into sexual orientation
be found in Bockting (2008). Here we provide some (e.g., emotional connection and fantasy vs. actual
key definitions as used in this chapter: behavior), most life science research has focused on
the behavior and/or self-identity components. The
• Birth sex refers to the sex assigned to a baby at most common way to assess this has been to ask
birth, which is typically based on the external participants to self-identify or with the use of specific
genitalia (Vilain, 2000). items from the Kinsey Scale (Kinsey, Pomeroy, &
• Cisgender refers to a person who identifies Martin, 1948). Even though Kinsey’s estimates for
with his or her birth sex (Schilt & the prevalence of nonheterosexual identities is often
Westbrook, 2009). cited—that 10 percent of men and 5 percent of
• Gender identity is the psychological sense of women are bisexual or gay/lesbian—more recent
maleness or femaleness (Stoller, 1968). population estimates suggest that about 5 to 6
• Homosexual will be used when describing ­percent of men and 3 to 4 percent of women are
nonheterosexual sexual behavior. Given that LGBT nonheterosexual (Laumann, Gagnon, Michael, &
and associated terms are identity terms that not all Michaels, 1994; Sell, Wells, & Wypij, 1995).
people adopt (e.g., many men who only have sex Estimating the prevalence of a transgender iden-
with men do not identify as gay), we will tity is challenging, in part because of the various
selectively use homosexual in reference to human aforementioned identity labels. The majority of
behavior when identity is not a key variable. It research on the transgender community, however, has
should be noted, however, that the term focused on those diagnosed with gender dysphoria
homosexual may be offensive to some people, and (formerly gender identity disorder). Thus, we will
one should remain sensitive to the terms used focus on this subset of the transgender community.
when referring to and working with people The American Psychiatric Association (2013) sug-
(American Psychological Association, 2009). gested that 1:10,000 to 1:20,000 persons in the United
• Intersex refers to conditions characterized by States will identify as a transwoman and that 1:30,000
atypical sexual development resulting from genetic, to 1:50,000 will identify as a transman. Estimates in
chromosomal, or hormonal anomalies Asia have suggested that these rates are as high as
(Vilain, 2000). Although we will use the term, the 1:2,900 for transwomen and 1:8,300 for transmen
current classification for these types of conditions (Tsoi, 1988).
is disorders of sex development (Hughes et al., 2006). Many hypotheses have been proposed in relation
• Transgender refers to people whose gender to what contributes to the development of these
identity and/or gender expression differ in identities. For both sexual orientation and gender
important ways from their birth sex (Davidson, identity, similar hypotheses have been proposed and
2007). A transgendered person may identify in a falsified, including the idea that they develop due
variety of ways, including transsexual, cross-dresser, to traumatic past experiences (e.g., childhood sexual
drag king/queen, gender queer, and intersex (see abuse), problematic parenting, and the absence
Bockting, 2008, for discussion of various of a specific parent (e.g., Bullough, Bullough, &
descriptors). Smith, 1983; Stevens, Golombok, Beveridge, & the
• Transsexual refers to a person who lives or ALSPAC Study Team, 2002). Just as the social sci-
desires to live full time as a person opposite to his ences have helped dispel some misunderstandings
or her birth sex; often the person takes steps to regarding these traits, the life sciences have made
alter his or her anatomy and physiology so that it is some advances in explaining how biological factors
congruent with his or her identity (APA Task contribute to sexual orientation and gender identity.
Force, 2008). We will use the term transwoman to Before proceeding, we offer an important caveat
refer to persons assigned a male birth sex but who related to the peer-reviewed literature in this area of
identify as female (often referred to as male-to- research: The research on sexual orientation is pri-
female or MTF transsexuals in the literature). marily based on gay men, and the research on gender
Similarly, we will use the term transman to refer to identity is primarily based on transwomen. Thus, it

202 Hormones, Sexual Orientation, and Gender Identit y

is less certain to what degree the results generalize to to engage in sexual relations with women instead of
lesbian women and transmen. In addition, those who men. The opposite, however, was found to occur:
identify as bisexual and asexual are usually com- Instances of homosexual behavior increased in the
bined into samples of gay men and lesbian women. majority of the men who were administered testos-
To some degree this may merely reflect the fact that terone (Glass & Johnson, 1944).
gay men and transwomen are more prevalent in the
Subsequently, limited research has found differ-
general population and because they are chromosom-
ences between heterosexual and nonheterosexual
ally less complex than those born female (i.e., they
adults. The few published reports primarily came
only possess one X chromosome). Nevertheless, this
from Robert Kolodny and colleagues (1971, 1972),
skewed representation in research limits how much
in which they showed that homosexual men had
we can generalize beyond gay men and transwomen.
lower levels of testosterone and impaired spermato-
Hormonal Influence genesis compared to controls. Conversely, the ma-
Sex hormones—specifically androgens and estro- jority of studies have shown that homosexual men
gens—play a key role in human development. Both do not differ in testosterone levels when compared
their organizational and activational effects have to heterosexual men (Barlow, Abel, Blanchard, &
been extensively studied (see, e.g., Arnold, 2009; see Mevissakalian, 1974; Meyer-Bahlburg, 1984; Pillard,
also Hampson, this volume). Even though it is no Rose, & Sherwood, 1974; Tourney & Hatfield, 1973),
longer believed that sex hormones are the sole reason and testosterone levels among homosexual women
for the observed differences between males and fe- were found to be comparable to heterosexual women
males (e.g., Dewing, Shi, Horvath, & Vilain, 2003), (Dancey, 1990; Downey, Ehrhardt, Schiffman,
they do play a critical role in sexual development. Dyrenfurth, & Becker, 1987; Gartrell, Loriaux, &
Consequently, the first area of research we focus on Chase, 1977). There is some evidence, however, that
addresses the role that hormones play in influencing among lesbians there may be an association between
the development of sexual orientation and gender androgen levels and their self-reported role within a
identity in three key ways: the activational effects of romantic relationship (Singh, Vidaurri, Zambarano,
circulating (i.e., endogenous) hormones, the organi- & Dabbs, 1999). That is, there was a paired differ-
zational effects of prenatal exposure to hormones, ence within each dyad, whereby the partner who
and the influence of exogenous hormones. endorsed more stereotypically masculine traits had
higher testosterone levels compared to the partner
Circulating Hormones who endorsed more stereotypically feminine traits
Most hormones are circulating hormones. They are (Pearcey, Docherty, & Dabbs, 1996).
produced and released by an endocrine cell in one
Gender identity. As with sexual orientation, early hy-
part of the body; they travel through the bloodstream
potheses for explaining transsexual identity related
to another part of the body; and they bind to specific
to atypical hormonal ranges. Two early studies re-
receptors within target cells, which signal or activate
ported lower plasma testosterone in transwomen
the cell to behave in predetermined ways. Given the
compared to heterosexual men (Starká, Spiová, &
role that sex hormones play in sexual d ­ evelopment
Hynie, 1975) and higher testosterone levels in trans-
and given sex differences in hormone levels observed
men compared to heterosexual women (Spiová &
among mammalian species, the first area of research
Starká, 1977). Yet, later studies did not find differ-
we highlight focuses on the role of circulating
ences in gonadotropin and sex steroid secretions
hormones in sexual orientation and gender identity.
when comparing transwomen to control males (e.g.,
Sexual orientation. Early theories regarding sexual Spijkstra, Spinder, & Gooren, 1988). Subsequent
orientation centered on the hypothesis that homo- clinical trials found that prior to hormonal treat-
sexual men and homosexual women had abnormal ment, transwomen are in the normal range for cisgen-
levels of sex hormones (Meyer-Bahlburg, 1977, 1979). der males (e.g., Dittrich et al., 2005).
For instance, it was believed that homosexual men
had lower levels of testosterone than their heterosex- Prenatal Exposure to Endogenous Hormones
ual counterparts, and it was hypothesized that this Most remaining hypotheses linking hormones with
“deficiency” contributed to an “immature” sexuality sexual orientation and gender identity focus on the
(Lurie, 1944). As a result, some early researchers prenatal environment. Specifically, there are critical
tested whether the administration of exogenous periods of development during which it is essential
testosterone to homosexual men would lead them that sex hormones be present at sufficient levels

Neibergall, Swanson, and Sánche z 203

to facilitate the differentiation and organization of time. Nevertheless, it is possible that, given the role
the developing embryo—especially the reproductive that hormones play in sex development, they also
system and sexually dimorphic brain regions. influence personality traits related to gender identity.
Otherwise, there can be long-term, irreversible Perhaps the closest naturally occurring “experi-
­effects if the exposure to these hormones occurs ment” with humans would be studying people who
too late or at atypical levels. Consequently, several have been diagnosed with a disorder of sex develop-
hypotheses suggest that extreme variations in ment. Two specific groups have been researched.
­prenatal exposure to hormones during this critical The first group includes women diagnosed with con-
period may contribute to the development of genital adrenal hyperplasia (CAH), in which females
nonheterosexual orientations and non-cisgender are prenatally exposed to high levels of androgens
identities. produced by their adrenal glands; such women
These hypotheses were primarily derived from report greater interest in stereotypically masculine
animal models. For instance, Phoenix, Goy, Gerall, interests and behaviors compared to women with-
and Young (1959) found that prenatally manipulat- out CAH (Zucker et al., 1996). Numerous studies
ing hormone levels in developing guinea pigs resulted examining the sexual orientation of women with
in adult animals that displayed sexual behavior CAH have mostly found that fewer such women
common of the opposite sex (e.g., females attempt- identify as exclusively or almost exclusively hetero-
ing to mount vs. assuming a receptive position). sexual compared to control women (e.g., Dittmann,
Similar results were found in rats that had their hor- Kappes, & Kappes, 1992; Frisén et al., 2009). This
mones manipulated either prenatally or perinatally outcome seems to be mediated by severity of the
(Davidson, 1969; Larsson & Sodersten, 1971; Paup, condition, whereby women with the more severe
Mennin, & Gorski, 1975; Quadagno, Shryne, form of CAH (with life-threatening sodium defi-
Anderson, & Gorski, 1972). Although intriguing, ciency symptoms) report a higher incidence of same-
using animal models to study these characteristics sex attraction compared to women with milder
makes it difficult to draw firm conclusions for two forms of CAH (Meyer-Bahlburg, Dolezal, Baker, &
main reasons: First, in most of these animal studies, New, 2008). It should be noted, however, that the
hormone levels were manipulated significantly physical consequences among women with CAH
beyond the naturally occurring range for a given can adversely affect their body image, such that they
sex. Second, the observed animal behavior does not view themselves as sexually undesirable and are
compare well to humans, at least in regard to sexual highly self-conscious (Frisén et al., 2009; Zucker
orientation and gender identity. From a behavioral et al., 1996). Consequently, the effects of this condi-
perspective, all that can be concluded is that hor- tion on sexual orientation are complex.
monally manipulated animals exhibited opposite- The second group includes persons diagnosed
sex sexual behaviors in response to sexual stimuli; with androgen insensitivity syndrome—a condition
nothing can be concluded regarding the animals’ resulting from a genetic mutation that impairs the
cognitions, affect, or “identity.” cell receptors for androgen. Persons with this condi-
A definitive way to test these hypotheses would tion inherited an XY sex chromosome complement
be to conduct such studies in humans. Of course, (which normally leads to the development of a male),
stricter ethical and moral parameters that exist for yet during the critical period of sexual development
human subjects compared to animal subjects prohibit in utero, their bodies were unable to utilize andro-
this type of experimental manipulation. Yet, many gens, thus impairing the “masculinization” of their
people have been exposed to atypical hormone bodies. Depending on the severity of the condition,
levels in the womb for a variety of reasons. Here we the degree of impairment ranges from mild to com-
report what this limited research has found related plete across all androgen-dependent features (e.g.,
to sexuality. reproductive organs and specific brain regions). In
Limited research has been published related to the extreme, a person with complete androgen insen-
prenatal exposure and gender identity. Classifying sitivity would develop as a female, and the condi-
this requires participants’ self-report, which cannot tion may not be discovered until the adolescent fails
be done with animal models. The low co-occurrence to experience menarche.
of a transgender identity within families (Green, Studies examining sexual orientation in these
2000)—a common method for studying the groups have yielded mixed results. Early reports found
­inheritance of traits—makes it difficult to conduct that participants identified as heterosexual relative
common methods (e.g., linkage analysis) at this to the gender of rearing versus their chromosomal

204 Hormones, Sexual Orientation, and Gender Identit y

composition—those raised as girls were attracted menopause) compared to unexposed females (Hoover
to males and those raised as boys were attracted to et al., 2011).
females (Lev-Ran, 1974; Money, Devore, & Norman, Psychosocial studies report that, on average, those
1986; Money & Dalery, 1976; Money & Ogunro, exposed to DES report interests and behaviors ster-
1974). Since then, studies found higher levels of eotypically associated with their sex (Lish, Meyer-
homosexual or bisexual behavior among these
­ Bahlburg, Ehrhardt, Travis, & Veridiano, 1992). In
groups when compared to the general population terms of sexual orientation, there does not seem to
(Hines, Brook, & Conway, 2004; Johannsen, Ripa, be an association between DES exposure and sexual
Mortensen, & Main, 2006; Zucker et al., 1996). orientation in men. The results for women exposed
A deeper analysis by Meyer-Bahlburg et al. (2008) to DES, however, are mixed. Based on three com-
suggested that the observed variation in sexual bined samples of women exposed to DES (n = 97),
orientation may have been an artifact of the severity Meyer-Bahlburg and colleagues (1995) found that 76
of the disorder of sex development. Specifically, percent reported exclusive heterosexual interests and
women with CAH exposed to extremely high levels experiences compared to 94 percent of women not
of testosterone were more likely to be classified as exposed to DES. Yet, based on a larger sample of
homosexual or bisexual (31 percent) compared to women exposed to DES (n = 3,946), Titus-Ernstoff
women with CAH who had been exposed to less and colleagues (2003) found no difference between
testosterone in utero. Although this seems to impli- these women and controls, and reports of exclusively
cate androgens in human sexual orientation, such heterosexual behavior were consistent with estimates
an interpretation must be made with caution: Most from the general population. The marked difference
people with CAH were exposed to levels of andro- between the two studies, however, may have been
gens far above the average exposure that developing influenced by the questions used, whereby the former
male fetuses, including many of those who identify team assessed multiple dimensions of sexuality (e.g.,
as homosexual, experience. fantasies, sexual attraction, and sexual arousal) and
Pharmaceuticals and Endocrine-Disrupting the latter team simply asked about actual sexual
Chemicals contact with others.
A different approach to estimate how hormonal Lutocyclin. Recently, Reinisch, Mortensen, and
anomalies may affect developing embryos has been Sanders (2017) examined if prenatal exposure to
to focus on the offspring of mothers given hormonal exogenous progesterone—a hormone naturally re-
treatments during pregnancy. Here we offer informa- leased to support fertilization and pregnancy—was
tion on a few chemicals that have been studied, but associated with sexual orientation. Based on medi-
there are others that may also affect sexual charac- cal records at University Hospital in Copenhagen,
teristics (e.g., synthetic thyroid medication, certain Denmark, the researchers identified and recruited
pesticides, and chlorinated hydrocarbons). 17 men and 17 women who had been prenatally ex-
Diethylstilbestrol (DES). DES is a synthetic form of posed to lutocyclin, a bioidentical form of proges-
estrogen. From the 1940s to 1970s, DES was pre- terone. Lutocyclin had been administered to their
scribed to pregnant women because it was believed mothers while they were pregnant with the partici-
to curtail complications, including miscarriage and pants to minimize the chance of miscarriage. When
premature labor (Rubin, 2007). In 1971, the FDA compared to a matched group of control men and
discontinued use of DES with pregnant women control women, Reinisch et al. found a higher inci-
­because, rather than preventing complications, it dence of identifying as nonheterosexual, increased
was found to increase the odds of having lifelong likelihood of being attracted to the same sex, and
problems of the reproductive system for those pre- increased likelihood of having engaged in same-sex
natally exposed (“Selected Item fFrom the FDA sexual behavior among the exposed group. These ini-
Drug Bulletin—November 1971: Diethylstilbestrol tial findings support the possibility that exogenous
Contraindicated in Pregnancy,” 1972). Although progesterone exposure during critical periods of in
DES-exposed males do experience more health prob- utero development may alter embryonic development
lems (e.g., testicular cancer) and structural differences in ways that influence later behavior.
of the genitals (e.g., misplaced urethral opening) Plastic compounds. Since the invention of the first
compared to unexposed males, DES-exposed females synthetic polymer in the mid-1800s, plastic prod-
experience proportionately greater problems (e.g., ucts have become an integral part of everyday life.
various types of cancer, fertility problems, and early From children’s toys to components within military

Neibergall, Swanson, and Sánche z 205

weapons, plastics can be found just about anywhere. animals had shown; yet, the translation of animal
Although there are many advantages to plastics (e.g., findings to humans has been complex and conten-
they are inexpensive and easy to produce), their tious, with some arguing that there is no harm
disadvantages may go beyond their massive envi- so long as doses are kept “low” (Habert, Livera, &
ronmental impact due to not being biodegradable. Rouiller-Fabre, 2014; Waring & Harris, 2011).
Specifically, compounds used to produce plastics may Nevertheless, it has been shown that these compounds
behave as endocrine disruptors—or chemicals that can cross the placenta into human fetuses (Silva
interfere with the endocrine system—if they enter et al., 2004), and several correlational studies have
the human body. Two compounds have been the found an association between plastic compounds
focus of concern: phthalates and bisphenol A (BPA). and numerous sexual traits among humans, includ-
Phthalates help make plastic flexible yet strong ing underdevelopment of the external genitalia
(e.g., soda bottles, medical tubing, and pacifiers). and incomplete testicular descent (Toppari, Virtanen,
However, concerns over the potential hazard that Skakkebaek, & Main, 2006; Swan et al., 2005).
phthalates could have on human health began to Whether or not these chemicals can influence sexual
mount in the 1960s because of reports that transfused orientation and gender identity remains unknown,
blood from plastic storage bags contained phthalates but it is certainly possible given the aforementioned
and because of reports of occupational illnesses among disruption of sex development seen in animals models
workers subjected to prolonged exposure to phthal- (e.g., Gray et al., 2000; Maamar et al., 2015) and
ates (Jaeger & Rubin, 1970; Marx, 1972; Milkov given the associations found in sex-related traits in
et al., 1973; Perspectives on PAEs, 1973). Subsequently, humans (e.g., Percy et al., 2016; Swan et al., 2005).
research demonstrated that phthalates adversely Future research should further investigate these
affected numerous mammalian species—especially potential associations.
among male organisms—including disrupting
metabolism (Bell, 1982), causing abnormal develop- Prenatal Stress
ment of the reproductive system (Howdeshell, Rider, Another area that we will briefly mention is maternal
Wilson, & Gray, 2008), inducing testicular atrophy stress during pregnancy (for a more in-depth account,
(Oishi & Hiraga, 1980), and impairing spermato- see Deer, Bernard, & Hostinar, this volume). Animal
genesis (Parmar, Srivastava, & Seth, 1986). studies have found that stressing pregnant animals,
Similarly, BPA is commonly used to make clear especially during critical periods of development,
plastics hard and shatter resistant (e.g., eyeglasses, had significant consequences on the offspring (Allen
food storage containers, and baby bottles). Laboratory & Haggett, 1977). For instance, Ward (1972) found
scientists unexpectedly discovered that BPA was that the male offspring of female rats repetitively
seeping out of plastic flasks and contaminating the subjected to an extremely stressful scenario during
results of experiments (Krishnan, Stathis, Permuth, pregnancy were less likely to engage in mounting
Tokes, & Feldman, 1993), which led to the discovery behavior and more likely to assume a receptive
that BPA was seeping out of many types of plastics position to sexual stimuli when compared to the male
(Feldman & Krishnan, 1995). Soon after, researchers offspring of rats that had not been stressed during
began to study the effects of BPA exposure on animal pregnancy. Similarly, Sachser and Kaiser (1996) found
models; BPA was found to adversely affect sexual that the female offspring of guinea pigs subjected to
development, including disrupting androgen pro- unstable social environments while pregnant exhib-
duction (Akingbemi, Sottas, Koulova, Klinefelter, & ited more male-typical courtship and play behavior
Hardy, 2004), reducing fertility (Herath et al., 2004), compared to the offspring from mothers that had
causing abnormal ovarian development (Adewale, been in stable social environments. Such studies
Jefferson, Newbold, & Patisaul, 2009), and contrib- demonstrate long-lasting effects that environmental
uting to recurrent miscarriages (Hunt et al., 2003). stressors can have on pregnant animals and their off-
As evidence began to emerge that traces of spring, in part because of the hormones produced
phthalates and BPA were being detected in preg- when mammals experience distress.
nant and nursing mothers (e.g., Sun et al., 2004; Among humans, initial evidence suggested that
Swan et al., 2005), public concern began to mount prenatal stress may also influence sexuality. A team
regarding how plastics could be affecting infants from Germany recruited 60 homosexual men, 40
and children, especially given the coverage by the bisexual men, and 100 heterosexual men, and they
popular press (Matthews, 2016; O’Callaghan, 2009). asked them to consult with their parents regarding
Many of these fears were rooted in what research on stressful events while their mothers had been pregnant

206 Hormones, Sexual Orientation, and Gender Identit y

with them. Significantly more of the homosexual key periods of development because androgens
and bisexual men reported that their mothers had differentiate the fetus in male-specific ways. Yet, no
experienced moderately to severely stressful events— significant variations were found in AR when com-
mostly related to World War II—compared to the paring heterosexual and homosexual participants
heterosexual men (68 percent, 40 percent, and (Macke et al., 1993). In regard to gender identity,
6 percent, respectively; Dörner, Schenk, Schmiedel, Hare and her colleagues (2009) found that trans-
& Ahrens, 1983). Yet, subsequent retrospective stud- women had a significant variation of the AR gene that
ies failed to properly replicate this association among would cause the receptors to be less effective; however,
gay men and lesbian women (e.g., Bailey, Willerman, two subsequent groups failed to replicate that find-
& Parks, 1991; Ellis, Ames, Peckham, & Burk, 1988). ing (Fernández et al., 2014b; Ujike et al., 2009).
Furthermore, a longitudinal study of 13,998 pregnan- Overall, molecular studies that have focused on
cies in England showed no significant relationship genes that affect the endocrine system among persons
between prenatal stress among male offspring and without disorders of sex development have yet to
gender atypical behavior, and they found only small provide evidence that they influence sexual orienta-
correlations among girls (Hines et al., 2002). tion or gender identity. Yet, emerging technologies
and our evolving understanding of what influences
Genetics gene expression may lead the way to solving the ques-
The role that genes play in our lives is a constantly tion of how our DNA influences these traits (Rice,
evolving area of research, especially with the emer- Friberg, & Gavrilets, 2016). Furthermore, it is likely
gence of research on epigenetics. Science has identi- that different mechanisms are involved for different
fied several genes that play a critical role in human subsets of the LGBT community, whereby genes that
sex development—especially the role of the SRY contribute to a transwoman identity, for instance,
gene (i.e., the sex-determining region on the Y chro- will be markedly different from genes that contrib-
mosome). Yet, there is uncertainty regarding how ute to a transman identity (Fernández et al., 2014a).
genes influence sexual orientation and gender iden-
tity. Most genetics research in this area has focused Association Studies
on sexual orientation. This is in part because of the Studies focused directly on hormones have yielded
higher prevalence of people who identify as gay or more questions than answers, in part because of
lesbian compared to those who identify as transgen- the limitations of studying people versus animals.
der, which makes it easier to use established methods Although it may be some time before technology
that rely on large samples (e.g., for genome-wide advances enough to make definitive conclusions, here
association studies; e.g., Sanders et al., 2017) or the we highlight association studies that have received
co-occurrence of specific traits within families (e.g., substantial attention and for which hormones may
for linkage analyses; e.g., Hamer, Hu, Magnuson, Hu, have played a role. These studies have relied on cross-­
& Pattatucci, 1993) and among twins (e.g., Sánchez, sectional, correlational approaches, which prohibit
Bocklandt, & Vilain, 2013). Details on general causative conclusions. Research in this area encom-
­genetics research can be found elsewhere (e.g., Ngun passes a broad range of topics, each with varying
et al., 2011). Here we briefly mention studies that degrees of differences that are potentially related
have focused on molecular genetics related to hor- to hormones.
mones among people who do not have disorders of
sex development. Birth Order Studies
Numerous genes that play a role in sex develop- In 1996, Blanchard and Bogaert first reported a
ment have been considered as candidate genes for phenomenon known as the fraternal birth order
sexual orientation and gender identity. Some of these effect. They found evidence that, on average, homo-
included CYP19 (converts androgens into estrogens), sexual men had a greater number of older brothers
ERα and ERβ (encodes for estrogen receptors), PGR when compared to heterosexual men (Blanchard &
(encodes for progesterone receptors), and SRD5A2 Bogaert, 1996, 1997). In several follow-up studies,
(converts testosterone into dihydrotestosterone). they concluded that each older brother increases the
Yet, molecular studies focused on these have yielded odds that a male will be homosexual by 33 percent
mixed results. For instance, the androgen receptor (Blanchard & Bogaert, 2004). Although this sounds
gene (AR) is located on the X chromosome and exceptionally large, this increase is relative to the
it encodes for the protein that allows the body to small baseline rate of approximately 2.5 percent
­respond to androgens. This receptor is critical during among the general population for men. Nevertheless,

Neibergall, Swanson, and Sánche z 207

a statistical analysis suggested that an estimated hypothesis for this sex difference—which lacks direct
15 percent of homosexual men could attribute their evidence—is that the ratio is sensitive to prenatal
sexual orientation to this effect (Cantor, Blanchard, androgen exposure (Manning et al., 1998).
Paterson, & Bogaert, 2002), though several caveats Consequently, studies have been conducted to deter-
exist (e.g., the trend is limited to right-handed mine if this trend is associated with sexual orientation
men). Interestingly, the same effect is not found for and gender identity.
homosexual women, whereby older sisters do not In terms of sexual orientation, several studies
increase the likelihood of homosexuality (Blanchard initially found a difference: Both homosexual women
& Lippa, 2007). and homosexual men were found to have a digit ratio
Since the publication of these findings, research- more consistent with the opposite sex when com-
ers have opined why this relationship exists among pared to heterosexual controls (Williams et al., 2000).
men. The leading theory suggests that the mother’s Yet, subsequent studies either found no difference
immune system may be affecting the developing brain between groups (e.g., Lippa, 2003; Kraemer et al.,
of male fetuses via an immune response to male- 2006) or the finding was found to be in the opposite
specific biomolecules produced by the male fetus direction of what was expected (e.g., homosexual
(Blanchard, 2001). Specifically, the developing testes men had more “masculine” ratios compared to het-
produce H-Y antigens that play a hormone-like role erosexual men; Robinson & Manning, 2000). In
in differentiating the reproductive system and are terms of gender identity, two studies found the
foreign to a woman’s body (Graves, 2010; Wolf, 1998). 2D:4D ratio to be “feminized” in transwomen com-
Thus, a mother’s immune system may become more pared to control males, but did not find a “mascu-
efficient at producing antibodies to “attack” a male linized” pattern among transmen (Kraemer et al,
fetus with each successive male conception, which 2006; Schneider, Pickel, & Stalla, 2006). A separate
can adversely affect the “masculinization” of the study found transmen had a more “masculinized”
brain (Blanchard & Bogaert, 1996; Blanchard & pattern but did not find a “feminized” pattern
Klassen, 1997). Yet, there is no firm data to support among transwomen (Leinung & Wu, 2017). Thus,
this hypothesis. as with sexual orientation, uncertainty remains re-
Some research has investigated the possibility garding the degree to which 2D:4D is associated
of a fraternal birth order effect among transgender with gender identity.
people. However, the limited findings seem to only Interest in the finger-length ratio continues with
show a trend among transwomen who are attracted a variety of studies associating this ratio with other
to men (Blanchard & Sheridan, 1992; Poasa, human traits. Yet, the debate about whether this
Blanchard, & Zucker, 2004). Further evidence for ratio, which plays no critical role in sexual reproduc-
this effect was found among a non-Western sample tion, is sensitive to androgens continues (Berenbaum,
of transwomen in Spain and Turkey (Gómez-Gil Bryk, Nowak, Quigley, & Moffat, 2009; Wallien,
et al., 2011; Bozkurt, Bozkurt, & Somnez, 2015). Zucker, Steensma, & Cohen-Kettenis, 2008).
However, there were mixed results in a Korean
sample (Zucker, Blanchard, Kim, Pae, & Lee, 2006). Brain Research
Consequently, the limited evidence within the tran- Perhaps the strongest biological findings come from
gender community so far seems to suggest that this brain studies. Intrigue in this area began with findings
effect is related to sexual orientation and not gender among animal models. In addition to the aforemen-
identity given that the findings have been limited to tioned studies in which hormones were manipulated
those who were sexually attracted to people who in rodents, a curious finding was reported among
were of the same birth sex as the participant. sheep, where approximately 8 percent of male rams
exhibited a sexual preference for other rams (Roselli,
Finger-Length Ratio Reddy, & Kaufman, 2011). Studies based on autop-
One of the most frequently cited lines of studies sied brains found that the sexually dimorphic
relates to the finger-length ratio between the index ­nucleus in the preoptic area of the hypothalamus
finger (2D) and ring finger (4D). This ratio has been (SDN-POA) in these male rams was comparable
shown to be sexually dimorphic, whereby men on in size to female rams (Katz, Price, Wallach, &
average have a shorter 2D than 4D, and women have Zenchak, 1988; Roselli, Larkin, Resko, Stellflug, &
about equal lengths (Manning, Scutt, Wilson, & Stormshak, 2004). This area is associated with
Lewis-Jones, 1998; Phelps, 1952). The dominant sexual behavior and its size is sensitive to hormones

208 Hormones, Sexual Orientation, and Gender Identit y

during critical periods of development (Rhees, (p. 2041). Although promising, these results should
Shryne, & Gorski, 1990a, 1990b). Consequently, as be taken with caution because in both studies the
science continues to explore how brain development transwomen had varying degrees of exposure to
affects animal behavior (e.g., Ngun et al., 2014), hormonal treatments, which were shown to alter
­attention has also been given to the role of brain the brain anatomy of transgender patients (Hulshoff
structures in humans. Pol et al., 2006).
Autopsy studies. Initially, three sexually dimorphic Brain imaging. Whereas earlier autopsy studies were
brain structures were found to correlate with in- unclear due to confounds and the difficulty in con-
creased rates of homosexuality: the third interstitial ducting them—chiefly because they relied on
nucleus of the anterior hypothalamus (INAH-3; people donating their bodies to science—advances
LeVay, 1991), the anterior commissure (Allen & in brain imaging have led to multiple studies based
Gorski, 1992), and the arginine vasopressin n­ euronal on significantly larger sample sizes. Numerous regions
population of the suprachiasmatic nucleus (Swaab, have been studied in relation to sexual orientation
Zhou, Fodor, & Hofman, 1997). For each of these and gender identity, including cortical thickness,
brain areas, homosexual men were found to have the corpus callosum, cerebral asymmetry, and the
structures that were more similar to control females putamen. Here we briefly highlight functional stud-
than heterosexual males. LeVay’s (1991) finding ies that have focused on responses to two specific
received the most attention and criticism due to types of stimuli. Readers interested in information
possible confounds. He obtained his results via on other areas are referred elsewhere (LeVay, 2016).
postmortem autopsy analyses in which all of his
First, researchers have compared how brains
nonheterosexual participants had died from AIDS
r­espond to scent. Numerous species secrete phero-
complications. A subsequent study by Byne and
mones or signaling chemicals to influence the behav-
colleagues (2001) found that AIDS was not associ-
ior of organisms within range of detecting the signal
ated with alterations in INAH-3 and that there was
(e.g., to signal an alarm or availability for breeding).
a statistical trend in the direction that LeVay found
Although the existence of human pheromones re-
when comparing the brains of heterosexual and non-
mains a disputed topic (Wyatt, 2015), researchers
heterosexual men.
have examined how men and women respond to
In regard to gender identity, an early key study cross-sex scents given that humans have a good sense
(Zhou, Hofman, Gooren, & Swaab, 1995) compared of smell. For instance, a Swedish research team found
the autopsied brains of heterosexual men, heterosex- that the cerebral activation patterns for homosexual
ual women, homosexual men, and six transwomen. men smelling male perspiration was both similar to
Results showed that the sexually dimorphic bed patterns shown by heterosexual women and signifi-
nucleus of the stria terminalis of the hypothalamus cantly different from the patterns of heterosexual
(BSTc) in homosexual men was similar in size to men (Savic, Berglund, & Lindström, 2005). Likewise,
heterosexual men in the sample, and the BSTc of the researchers found that the cerebral activation
both these groups of men was significantly larger patterns for homosexual women smelling male per-
than heterosexual women. This showed that sexual spiration and female urine was both similar to pat-
orientation was not associated with this area. However, terns shown by heterosexual men and significantly
the size of the BSTc in the transwomen was signifi- different from the patterns of heterosexual women
cantly smaller than both groups of men and more (Berglund, Lindström, & Savic, 2006). Finally, the
similar in size to the heterosexual women (Zhou et Swedish group found that among a sample of trans-
al., 1995). A subsequent study on the brains of the women who were attracted to other women, their
transwomen found that they had neuronal density response to odors was “in between” both male and
in the BSTc that was consistent with that of hetero- female controls (Berglund, Lindström, Dhejne-
sexual women (Kruijver, Fernández-Guasti, Fodor, Helmy, & Savic, 2008).
Kraan, & Swaab, 2002). Considering the results of Second, researchers have compared how brains
these studies together, Kruijver and his colleagues respond to visual sexual stimuli. Numerous studies
suggested that “transsexualism may reflect a form have found that brain activation while viewing
of brain hermaphroditism such that this limbi erotic videos demonstrated arousal consistent with
­nucleus itself is structurally sexually differentiated their sexual orientation (Hu et al., 2008; Ponseti
opposite to the transsexual’s genetic and genital sex” et al., 2006; Rieger, Chivers, & Bailey, 2005; Safron

Neibergall, Swanson, and Sánche z 209

et al., 2007) and aversion when inconsistent American Psychological Association (2009). Report of the Task
with their sexual orientation (Paul et al., 2008). Force on Gender Identity and Gender Variance. Washington,
DC: Author.
Although this finding was reported among a group Arnold, A. P. (2009). The organizational-activational hypothesis
of transwomen, the effect was not as marked as the as a foundation for a unified theory of sexual differentiation
findings among cisgender participants (Gizewski of all mammalian tissue. Hormones & Behavior, 55, 570–578.
et al., 2009). doi:10.1016/j.yhbeh.2009.03.011
Bailey, J. M., Willerman, L., & Parks, C. (1991). A test of the
maternal stress theory of human male homosexuality.
Conclusion Archives of Sexual Behavior, 20, 277–293. doi:10.1007/
There continues to be fascination over what factors BF0154184
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lighted past and current biological research related Bell, F. P. (1982). Effects of phthalate esters on lipid metabolism in
to each with an emphasis on the role of hormones. various tissues, cells and organelles in mammals. Environmental
Although most research in this area has focused on Health Perspectives, 45, 41–50.
people who develop in atypical ways relative to the Berenbaum, S. A., Bryk, K. K., Nowak, N., Quigley, C. A., &
Moffat, S. (2009). Fingers as a marker of prenatal androgen
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advances in science—including epigenetics and Berglund, H., Lindström, P., Dhejne-Helmy, C., & Savic, I.
neuroplasticity—continue to unlock some of the (2008). Male-to-female transsexuals show sex-atypical
mysteries of human development and spark fur- hypothalamus activation when smelling odorous steroids.
Cerebral Cortex, 18, 1900–1908. doi:10.1093/cercor/bhm216
ther fascination regarding the influence of hormones Berglund, H., Lindström, P., & Savic, I. (2006). Brain response
during critical periods in our lives (e.g., Aure, Fuss, to putative pheromones in lesbian women. Proceedings of the
Höhne, Stall, & Siever, 2014; Chavarria, Sánchez, National Academy of Sciences of the United States of America,
Chou, Thompson, & Luders, 2014). It may be some 103, 8269–8274. doi:10.1073/pnas.0600331103
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immune hypothesis of male homosexuality. Hormones &
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214 Hormones, Sexual Orientation, and Gender Identit y

 CH A PT E R

13 Intersexual and Intrasexual Competition

and Their Relation to Jealousy
Abraham P. Buunk, Karlijn Massar, Pieternel Dijkstra, and Ana Maria Fernandez

Abstract

This chapter discusses sex differences in intersexual competition and describes particularly the
­consequences of such competition for conflict between the sexes, as well as for sex differences in mate
guarding and, relatedly, in the types of infidelity that evoke jealousy, including online infidelity. It also
discusses individual differences in jealousy as related to attachment styles and describes the effects
of height, hormones, and the menstrual cycle on jealousy. Next, the chapter moves on to intrasexual
competition and discusses, among other topics, intrasexual competition among men and among
women, the role of sex differences in rival characteristics in evoking jealousy, the role of attachment
styles and hormones, and individual differences in intrasexual competitiveness.
Keywords: intrasexual competition, intersexual competition, women, jealousy, infidelity, hormones

Intrasexual competition refers to rivalry with same-sex females are also competing with same-sex conspecifics
others that is ultimately driven by the motive to to attract and keep mates who have the willingness
obtain and maintain access to mates. In his theoriz- and potential to invest in offspring (e.g., Campbell,
ing on sexual selection, Darwin (1871) suggested 2013).
that intrasexual competition led to important Nevertheless, despite the fact that human
­adaptations to compete effectively with same-sex males do invest heavily in their offspring after
conspecifics to attract mates. It has often been noted birth (Geary, 2000), according to Trivers’s (1972)
that in most species males can sire offspring with a Parental Investment Theory, in part the reproduc-
single sexual act, whereas females need to invest in tive interests of males and females do not overlap,
the gestation and birth of her offspring and, after resulting in a considerable degree of intersexual
birth, in lactation and childcare. As a consequence, competition. Due to their higher physiological
according to Trivers’s (1972) well-known Parental ­investments and the costs associated with these in-
Investment Theory, females are a scarce resource over vestments, both a woman and her offspring would
which males compete (Andersson, 1994). Therefore, benefit most from a long-term, highly investing
in most species males usually engage in quite fierce male, whereas for men, short-term mating might
competition with other males over the access to yield more reproductive benefits than for women,
­females, whereas females show fewer signs of intra- even when they are already investing in offspring
sexual competition. However, even in mammals in a long-term relationship. Indeed, numerous
where males invest little in their offspring, female studies have shown that, compared to women, men
competition for resources and mates is widespread report a greater desire for short-term relationships
(Stockley & Bro-Jørgensen, 2011). Because overall, (e.g., Schmitt, Shackelford, & Buss, 2001), have
human males also need—at least compared to other more permissive attitudes toward casual sex (Petersen
species—to invest heavily in their offspring, human & Hyde, 2010), are more interested in short-term

215
extra-dyadic sexual relationships (Buunk, 1980), relationship (i.e., the commitment skepticism bias).
and report desiring up to three times as many Conflicts over sexual access—men’s greater desire
­lifetime sexual partners (Buss & Schmitt, 1993; and women’s greater hesitation—can cause anger and
Schmitt, 2003). In a now-famous study, R. D. Clark frustration in men (Shackelford & Goetz, 2004),
and Hatfield (1989) showed that 75 percent of the which in turn increases the likelihood of sexual
men, but 0 percent of the women, approached by ­coercion.
an attractive stranger of the opposite sex con-
Jealousy-evoking events. The notion of intersexual
sented to a request to have sex that evening—
competition has important implications for sex dif-
clearly illustrating the possible degree of intersex-
ferences in the events that evoke jealousy in more or
ual conflict.
less committed relationships. Overall, men will be
In the present chapter, we first discuss intersexual
more interested than women in engaging in uncom-
competition and describe particularly the conse-
mitted extra-dyadic sex as this may enhance their
quences of such competition for sex differences in
reproductive success. However, such behavior when
mate guarding and, relatedly, in the types of infidel-
engaged in by their female partner would be partic-
ity that evoke jealousy, including online infidelity.
ularly threatening for men. Because from an evo-
We also pay attention to individual differences in
lutionary perspective men have over the course of
jealousy as related to attachment styles, and to the
evolution faced the problem of paternity confidence,
effects of height, hormones, and the menstrual
and women of securing the partner’s investment of
cycle on jealousy. Next, we move on to intrasexual
resources, one would predict that male jealousy
competition and discuss, among others, intrasexual
would be specifically focused on the sexual aspects
competition among men and among women, the
of the partner’s extra-dyadic activities, and female
role of sex differences in rival characteristics in
jealousy on the emotional involvement of the part-
evoking jealousy, the role of ­attachment styles and
ner with the rival (e.g., Buss, Shackelford, Choe,
hormones, and individual differences in intrasexual
Buunk, & Dijkstra, 2000; Bjorklund & Shackelford,
competition.
1999). For men, any act of intercourse of his partner
with a third person is a potential threat to his repro-
Intersexual Competition
ductive success. In contrast, for women, an act of
Conflict between the sexes. The pursuit of qualita-
intercourse by her partner may especially, or only,
tively different mating strategies and the behaviors
be a threat when the investment of the partner in
that follow from this may lead to considerable
the relationship is in jeopardy. Indeed, when the
conflict between the sexes—after all, women might
partner has been unfaithful a number of times while
not be willing to consent to men’s desires for casual
maintaining his commitment, a woman may, under
sexual relationships, and men may not always give
some conditions, adapt to her partner’s infidelity
in to women’s desire for commitment. Women
(see, e.g., Buunk, 1995).
will more often withhold sex—since this is the
­resource men value most—until they can be sure To test the gender difference predicted by
of a man’s commitment, whereas men will more e­ volutionary theorizing, Buss, Larsen, Westen, and
often deceive women about their commitment to Semmelroth (1992) developed a research paradigm
obtain sexual access (e.g., Haselton, Buss, Oubaid, in which participants were presented with dilem-
& Angleitner, 2005). Buss (1989) focused on the mas, in which they had to choose a partner’s sexual
specific emotions evoked by these kinds of conflict unfaithfulness or a partner’s emotional unfaithful-
and showed that women were most likely to be ness as the most upsetting event. Buss et al. did
upset and ­angered by men’s greater sexual asser- indeed find that more men than women selected a
tiveness and persistence. Men, on the other hand, partner’s sexual infidelity as the most upsetting
were more likely to be angered and upset by wom- event, whereas more women than men reported a
en’s tendency to require an emotional commit- partner’s emotional infidelity as the most upsetting
ment before engaging in sexual behaviors. More event. This pattern of results has since then been
recent studies have shown that men, particularly replicated many times across cultures, and for both
those who are focused on short-term mating and conventional and online infidelity (e.g., Buss et al.,
who rate themselves as attractive, tend to overperceive 1999; Buunk, Angleitner, Oubaid, & Buss, 1996;
women’s sexual i­nterest (i.e., the overperception Dunn & McLean, 2015; Groothof, Dijkstra, &
bias; Haselton & Buss, 2000). Conversely, women Barelds, 2009). Schützwohl and his colleagues con-
tend to underestimate men’s desire for a committed ducted a series of studies that shed a more specific

216 Intersexual and Intrasexual Competition

light on the cognitive processes that take place would be considered. However, a meta-analysis by
before, during, and following responses to a part- Sagarin et al. (2012) shows that across 45 inde-
ner’s infidelity, and found that these cognitive pro- pendent samples, the gender differences emerge
cesses were in line with the sex difference in distress on continuous measures and in response to expe-
reported by Buss et al. (1992). First, Schützwohl rienced infidelities. Indeed, sex differences have
(2006) found that, even before any incident of infi- been found in studies using different methods,
delity has occurred, women more than men are pre- such as reaction times (Schützwohl, 2005) or
occupied with thoughts about a partner’s emotional audio records of partner interrogations in the
infidelity, whereas men more than women are more face of an actual infidelity threat (Kuhle, 2011).
occupied with thoughts about a partner becoming Noteworthy is the finding that the sex difference
sexually unfaithful. Once suspecting a partner’s
­ in emotional and sexual ­infidelity generalizes to
­infidelity, men more than women tend to seek in- online infidelity. More specifically, Guadagno and
formation that may indicate a partner’s sexual Sagarin (2010) found sex differences both when
­infidelity, whereas women more than men tend participants were asked to choose between the
to seek information that is indicative of emotional classic scenarios of sexual and emotional infidelity,
infidelity. Once individuals notice they start to and when they were asked to choose between a sce-
feel jealous, for feelings of jealousy to become nario in which the partner engaged in cybersex
­intolerable, men need significantly fewer cues to and a scenario in which the partner formed a close
sexual infidelity than women, whereas women need emotional attachment with someone else online.
significantly fewer cues to emotional infidelity than
The role of conception risk. Nevertheless, when there
men (Schützwohl, 2005). Finally, following an
is no risk of conception—such as when an infidelity
­incident of infidelity, men and women differ in
between an opposite-sex partner occurs with a
what they remember about the incident. When un-
same-sex rival—the sex differences in jealousy tend
expectedly asked about an imaginary story about
to be attenuated (e.g., Harris, 2002; Sagarin, Becker,
their partners’ infidelity participants listened to
Guadagno, Nicastle, & Millevoi, 2003). For in-
a week ago, Schützwohl and Koch (2004) found
stance, the sex difference disappears when men are
that women recalled significantly more cues to
compared to women who are using hormone-based
emotional than to sexual infidelity, whereas men
birth control. The use of hormone-based birth con-
recalled significantly more cues to sexual than to
trol may change women’s psychological and social
emotional infidelity.
behavior in ways that differ from the influence of
Remarkably, in Sweden and Norway, both
natural estrogens or progesterone. This is, among
among the most egalitarian societies in the world,
other things, reflected in the intensity to which
strong sex differences in response to emotional
women respond to information about a partner’s in-
and sexual infidelity have been found (Bendixen,
fidelity, especially in the case of emotional infidelity.
Kennair, & Buss, 2015; Walum, Larsson, Westberg,
More specifically, Geary, DeSoto, Hoard, Sheldon,
Lichtenstein, & Magnusson, 2013). Contradictory
and Cooper (2001) found that the majority (70 per-
to what a learning perspective would predict—
cent) of women not using hormone-based birth
that is, an attenuation of the differences between
control indicated that the emotional infidelity of
men and women in the domain of jealousy—an
their partner was more distressing than their part-
evolutionary perspective holds that in these soci-
ner’s sexual infidelity, whereas only about one-half
eties sex differences might be expressed to a larger
(56 percent) of women using a hormone-based
degree due to expected larger paternal investments.
birth control responded in the same way. In this
Bendixen, Kennair, and Buss (2015) argued that
latter case, women no longer significantly differed
as men’s investment in childrearing increases, for
from men in their choice of the type of infidelity
women the costs of losing these investments to
they experience as most distressing. When there is
another woman and for men the costs of paternal
no risk of conception, the reproductive stakes of
uncertainty also increase. It must be noted that
­infidelity are much lower than when sex is highly
the findings with the paradigm developed by Buss
likely to result in pregnancy and to have long-term
et al. (1999) have been questioned (e.g., DeSteno &
consequences.
Salovey, 1996; Harris, 2003), assuming that most
gender differences would disappear when actual in- Especially under these last conditions—high
fidelity experiences and ­responses on continuous risk of pregnancy in the context of infidelity—the
measures (rather than forced-choice dilemmas) universal sex difference seems to emerge. Illustrative

Buunk, Massar, Dijkstra, and Fernande z 217

in this context is a study by Scelza (2014), who Likewise, it has often been suggested that jealousy
studied the responses to emotional and sexual in- as a motive in homicide also seems more common
fidelity among the Himba, a small-scale, natural among male than among female perpetrators (e.g.,
fertility population in the northwest of Namibia Stöckl & DeVries, 2013). However, after reviewing
where rates of infidelity are high and, at the time the literature, Harris (2003) concluded that the
of study, only 30 percent of inhabitants had ever existing data on homicide offers no support for the
heard of a modern method of contraception, and belief that male murderers are more often motivated
no one actually used it. Scelza found that although by jealousy than female murderers. Moreover, sev-
Himba men and women both reported being sig- eral conditions may moderate the occurrence of
nificantly more distressed about the possibility of homicide by men due to jealousy. For instance,
a partner’s sexual infidelity than a partner’s emo- Mize, Shackelford, and Shackelford (2009) found
tional infidelity, men were more likely to choose that men are more likely to kill their partners by
sexual infidelity as more distressing than women, beating when the relationship is dating or non-
whereas women were more likely to choose emo- marital cohabiting versus legal marriage. According
tional infidelity as more distressing than men. Also, to these authors, a lack of formal commitment in
other factors may moderate the gender difference the form of a marriage certificate may fuel feelings
in emotional versus sexual jealousy. For example, the of jealousy that may give rise to higher levels of
gender difference has been found to be attenuated aggression that, consequently, are more likely to
when controlling for variables such as personal result in murder.
­experiences as a victim or perpetrator of infidelity
(e.g., Bendixen, Kennair, Ringheim, et al., 2015; The incidence of male partner violence due
Tagler, 2010), attachment style (Burchell & Ward, to mate guarding and jealousy may also differ as a
2011; Levy & Kelly, 2009), and participant age function of culture. There are considerable cul-
(IJzerman et al., 2014). More specifically, IJzerman tural differences in the frequency and intensity of
et al. (2014) found the gender difference in samples mate guarding. For example, in cultures where
consisting of individuals in their early 20s, but parents control the mate choice of their offspring,
not in samples of individuals over 50. Likewise, mate guarding is much more common (Buunk &
Tagler (2010) found that, in contrast to individuals Castro Solano, 2012), and honor cultures often
who had not experienced adultery in their current establish strict norms for female chastity and virginity,
or past relationships, among men and women with a transgression of these norms being perceived
who did experience adultery, no gender difference as a threat to a family or husband’s honor. Illustrative
emerged in the choice of most upsetting infidelity is the Arab expression that a man’s honor “lies
scenario. In a similar vein, whereas the gender dif- ­between the legs of a woman.” As a consequence,
ference among individuals with a secure attach- especially in cultures where honor is a salient orga-
ment style is relatively small, among individuals nizing theme, such as most Arab countries (Vandello
with a dismissing attachment style it is relatively & Cohen, 2003), physical violence against women
large (e.g., Levy & Kelly, 2009). is seen as an acceptable and appropriate means of
restoring male reputation and identity when dam-
Mate guarding. The male focus on preventing sexual aged by a female’s (potential) infidelity.
contact between their partners and other males is In addition to physical aggression, veiling is
quite manifest in the extreme forms of mate guard- used in many Arab honor cultures as a method of
ing, in which males in many cultures may engage. mate guarding by which men try to reduce the
In his now-classic review, Murdock (1967) noted risk of a partner’s infidelity. Recently, Pazhoohi
that only 4 out of 849 societies did not show any and Hosseinchari (2014) studied the effectiveness
sign of male mate guarding (i.e., keeping close tabs of different types of veiling on ratings of female
on their mates, sometimes even when she is uri- attractiveness. This study examined three types of
nating or defecating). A recurrent finding is the veils that cover up the female body to different
relatively high incidence of physical violence that is degrees: (1) a black hijab headscarf that covers up
used by men as a means of mate guarding or as an the hair, neck, and shoulders with tight clothing
expression of jealousy, both in response to their covering bodily curves; (2) a head scarf plus offi-
partner and in response to same-sex rivals, in the cial clothing covering bodily curves; and (3) the
latter case turning into intrasexual competition chador, a traditional wide body-length fabric that
(Graham & Wells, 2001; M. Wilson & Daly, 1993). covers the whole body except the face. Results

218 Intersexual and Intrasexual Competition

showed that Muslim men were more motivated buying gifts), whereas men with a low mate value
to view women exhibiting less veiling and rated are more likely to engage in behaviors that function
them more attractive than those women whose by inflicting or threatening to inflict costs on a
bodily curves were less apparent, and that, thus, woman for not remaining invested in the current
veiling seems to constitute an effective mate-guarding relationship (e.g., by isolating her).
tactic for men.
Mate retention intensifies when the costs of
Although often neglected in the literature,
losing a partner increase. For instance, Buss and
women may also engage in mate guarding, and
Shackelford (1997) found that both men married
not only to retain a mate. In our ancestral past,
to attractive women and women married to high-
and even in the not-so-distant past, sexually trans-
income men reported more frequent and intense
mitted infections (STIs) constituted a major
mate guarding. Also, men’s mate retention efforts
threat, more for women than for men, because
increase the more time they spend apart from their
such diseases might lead to infertility (e.g.,
partners (Shackelford, Goetz, McKibbin, & Starratt,
Mackey & Immerman, 2001). Currently, because
2007) and when their partner is near ovulation—a
extra-dyadic sex often happens without a condom
time when a female infidelity would be most costly
(e.g., Dew, Brubaker, & Hays, 2006), individuals
(Gangestad, Thornhill, & Garver, 2002). Across
engaging in extra-dyadic sex run the risk of get-
animal species, the use of aggression can be seen as
ting infected with STIs and of infecting their
a form of punishment that deters the targeted in-
partner (e.g., Buunk & Bakker, 1997; Pulerwitz,
dividual from repeating a behavior that conflicts
Izazola-Licea, & Gortmaker, 2001), which is par-
with the interests of the aggressor (Clutton-Brock
ticularly risky for women of adulterous spouses
& Parker, 1995). Similarly, among humans, sexual
because STIs are much more easily transmitted
coercion can be seen as an extreme mate retention
from males to females than vice versa. In addition,
tactic, aimed at preventing the partner from com-
when infected with an STI and others learn about
mitting a sexual infidelity, and thereby reducing
this, women run the risk of being perceived as im-
the risk of cuckoldry. Sexual coercion as the result
moral and promiscuous (Neal, Lichtenstein, &
of sexual jealousy can take on subtle forms (e.g.,
Brodsky, 2010), decreasing their attractiveness as a
threatening to leave the relationship or withhold-
partner. Although men also run the risk of being
ing gifts if a partner does not consent to sexual
stigmatized when infected with an STI, women
intercourse) but may escalate to partner-directed
are more severely stigmatized than men, even when
violence and forcibly raping one’s partner (Goetz,
their partner is responsible for infecting them
Shackelford, Romero, Kaighobadi, & Miner, 2008).
(Lichtenstein, Hook, & Sharma, 2005).
Influence of life history and attachment. In life history
Mate retention. Men and women differ also in the theory, a distinction is made between two strategies:
types of tactics they employ to retain their mate an r- versus K-strategy (Roff, 1992; Stearns, 1992).
when jealous. Among others, Buss and Shackelford The r-strategy is characterized by fast development:
(1997) showed that mate retention parallels mate short growth, early sexual maturation, having many
preferences, such that men will attempt to retain offspring of low quality, and an overall short lifes-
their mate by engaging in resource displays like pan. The K-strategy, in contrast, is characterized by
buying expensive gifts for their partner, whereas slow development: a long growth span, late sexual
women are more likely to enhance their appearance. maturation, few offspring of high quality, and an
Moreover, men more than women try to keep their overall long lifespan. A disrupted attachment his-
partner away from other men and will verbally and tory would likely foster an r-strategy, accompanied
physically threaten their rivals (thus showing direct by relatively high levels of jealousy. However, few
intrasexual competition), whereas women are more studies have examined the relationship between
likely to flirt with other men to evoke jealousy in adult jealousy and attachment history in terms of
their partners. More recently, research (e.g., Miner, objective indicators, such as separation from a
Starratt, & Shackelford, & Starratt, 2009) has parent during childhood. Using the scales devel-
shown that a man’s mate value is associated with oped by Buunk (1997), Van Brummen-Girigori,
specific types of mate retention tactics: Men with a Buunk, and Dijkstra (2016) found that on Curaçao,
high mate value are more likely to use mate reten- a Caribbean island where relatively many children
tion behaviors that focus on enticing a woman to grow up without a father in the home, women who
stay invested in the current relationship (e.g., by were abandoned by their father during childhood

Buunk, Massar, Dijkstra, and Fernande z 219

reported significantly more anxious and possessive health, as well as with morphological symmetry
jealousy (an index of mate guarding) than females (Manning, 1995; Silventoinen, Lahelma, &
who grew up in the presence of their father. Many Rahkonen, 1999). Tall men and women of medium
other studies have shown that individuals with an height have the highest mate value and are consid-
insecure attachment style are more jealous than ered the most attractive. For example, in speed
individuals with a secure attachment style (e.g.,
­ dating experiments tall men and women of medium
M. J. Miller, Denes, Diaz, & Buck, 2014), inde- height receive the most positive responses from the
pendent of the influence of personality characteristics opposite sex (Stulp, Buunk, Kurzban, & Verhulst,
such as self-esteem and neuroticism (Buunk, 1997). 2013). It seems self-evident that individuals with a
In particular, individuals with an anxious-ambivalent high mate value will feel they have less to fear from
attachment style have been found to experience rivals. Indeed, Buunk, Park, Zurriaga, Klavina, and
greater jealousy in response to a Facebook wall post Massar (2008) found that as men were taller, they
sent by a rival for their partner’s attention (e.g., reported on a single-item, global measure less jealousy,
Fleuriet, Cole, & Guerrero, 2014; Marazziti et al., whereas average-height women reported lower
2010), possibly because communication on Facebook levels of jealousy than short and tall women (see also
(e.g., a winking emoticon) is often quite ambiguous Buunk, Pollet, Klavina, Figueredo, & Dijkstra, 2009).
in terms of a partner finding someone else appeal- Not only are objective differences in height related
ing. This ambiguity may trigger jealousy especially to jealousy, but also subjective ­beliefs about one’s
in those already anxious about their relationship. As body: When individuals believe their body is less
a consequence, such individuals tend to closely attractive, they tend to be more jealous (e.g.,
monitor their partner’s activities on Facebook (e.g., Ambwani & Strauss, 2007).
Muise, Christofides, & Desmarais, 2014; Marshall,
Bejanyan, Di Castro, & Lee, 2013). As an anxious- Although the effects of height on jealousy may
ambivalent attachment style implies a “clinging” to be mediated by psychological processes, there is also
the relationship out of fear of losing the partner, the clear evidence for a more direct biological basis of
link between this style and jealousy seems self-­ jealousy. First, twin research suggests that emotional
evident. Less self-evident is the finding that avoid- and sexual jealousy have a strong genetic compo-
antly attached individuals are often relatively jealous. nent (Walum et al., 2013). Second, several studies
A possible explanation is that such individuals are have shown that among women, jealousy is associ-
actually quite dependent on their partner but feel ated with hormone levels. Geary et al. (2001) showed
that they are not meeting the needs of their partner that among women, jealousy correlated with estro-
by their distant attitude, and are therefore concerned gen concentration assessed in the second week of
with losing their partner. the cycle. Cobey et al. (2012) found with a within-
subjects design that in both single and partnered
Influence of physical characteristics. Not only psy- women, jealousy varied as a function of menstrual
chological but also physical characteristics may be phase, with higher levels of jealousy reported when
­related to jealous mate guarding. The reproductive women were fertile than when they were nonfertile.
advantages of height for males are apparent in the An explanation for this is that, given the importance
female preference for taller males (Kurzban & of male investment, protection, and provisioning
Weeden, 2005; Pawlowski, 2003; Shepperd & during and after pregnancy (for a review, see Geary,
Strathman, 1989). Indeed, taller men receive more 2005a), the risk of losing, or not receiving, the neces-
replies to dating announcements (Pawlowski & sary investment from one’s mate would be especially
Koziel, 2002), have more physically attractive girl- threatening for women when they are fertile.
friends (Feingold, 1982), and have more reproduc- Consequently, women will be especially keen at pre-
tive success (Mueller & Mazur, 2001; Nettle, 2002; venting the involvement of their partner with an-
Pawlowski, Dunbar, & Lipowicz, 2000). Given that other woman. The findings by Cobey et al. (2012)
height is highly heritable (one recent estimate from were replicated in the Afro-Caribbean population of
a study using the Danish Twin Registry found her- Curaçao, where it was found that especially preventive
itability coefficients of 0.69 for men and 0.81 for or possessive jealousy (an index of mate guarding)
women; Schousboe et al., 2004), females choosing was higher among women who were fertile. In addi-
tall males are more likely to have tall male offspring, tion, this type of jealousy was higher the later the
who in turn would be preferred by females. Male age of the first menarche, also suggesting hormonal
height has been found to be correlated with physical effects (Buunk & Van Brummen-Girigori, 2016).

220 Intersexual and Intrasexual Competition

Jealousy and Intrasexual Competition inventory of threatening rival characteristics, com-
Jealousy in response to a rival. Because jealousy often posed of five factors: social dominance, physical
implies the explicit presence of a rival when two attractiveness, seductive behavior, physical domi-
­individuals are vying for the attention of the same nance, and social status. The main finding was that
other, jealousy has a strong component of intrasex- jealousy in men was, more than in women, evoked
ual competition. Arnocky, Sunderani, Miller, and by the rival’s social and physical dominance, whereas
Vaillancourt (2012) found indeed that among jealousy in women was, more than in men, evoked
women, intrasexual competition is enhanced among more by the rival’s physical attractiveness. These
those with relatively high jealousy levels, who made findings were obtained in Dutch college samples
more appearance comparisons and engaged more and were cross-validated in Dutch community
often in competitor derogation than their less jeal- samples. In addition, Dijkstra and Buunk (1998)
ous peers. When looking at the themes that indi- presented participants with a scenario in which
viduals from different cultures mention when asked their partner was flirting with the opposite-sex indi-
to provide a description of a jealousy-evoking event, vidual. Next, participants received a profile of the
four common dominant themes emerge: (1) fear of rival who was either high or low in physical attrac-
or actual infidelity, (2) violated expectations con- tiveness and either high or low in dominance.
cerning a partner’s time and commitment, (3) a Jealousy in men was particularly influenced by the
partner paying attention to a rival through social rival’s social dominance, whereas jealousy in women
media, and (4) loss of self-esteem due to a partner was particularly influenced by the rival’s physical
paying attention to a rival (Zandbergen & Brown, attractiveness. Subsequent research has shown that
2015). In line with this, a study in the Netherlands such differences occur especially in the case of emo-
(Buunk, 1981) found that, although this was by far tional rather than sexual jealousy (Buunk & Dijkstra,
not the most important concern, 20 percent of the 2003). Moreover, the assessment of the threat of a
individuals who had experienced actual infidelity rival seems such a basic process that it may be per-
via their partner having an extra-dyadic affair said ceived outside cognitive awareness. For example, in
they felt threatened because they regarded the rival a study focusing on rivals’ bodily features, Massar
in certain respects as better than themselves. Thus, and Buunk (2009) used a subliminal priming pro-
across different cultures, the elicitors of jealousy all cedure to expose participants to silhouettes of
seem to reflect in part feelings of competition with bodies that were either attractive (a waist-to-hip
a rival. ratio [WHR] of 0.7 for women and a shoulder-to-
hip ratio [SHR] of 1.4 for men) or unattractive (a
Sex differences in the importance of rival characteristics. WHR of 0.9 for women and an SHR of 1.2 for
Overall, a rival who possesses qualities that are be- men). The results showed that even though partici-
lieved to be important to the opposite sex or to one’s pants indicated not being aware of the content of
partner tends to evoke more feelings of jealousy the primes, their jealousy was influenced by the
than a rival who does not possess those qualities primes: Both men and women responded with the
(e.g., DeSteno & Salovey, 1996; Dijkstra & Buunk, most jealousy after being exposed to the attractive
1998). Men and women report comparable amounts body shapes. Similar findings were obtained in a
of jealousy as their rivals possess more self-relevant study in which words relating to attractiveness or
attributes, such as intelligence, popularity, athleti- social status were used as subliminal primes (Massar,
cism, and certain professional skills (e.g., DeSteno Buunk, & Dechesne, 2009), such as pretty, slender,
& Salovey, 1996; Rustemeyer & Wilbert, 2001). success, and money. The results from this study re-
However, given the sex differences in mate prefer- vealed the predicted sex differences in the character-
ences, with physical attractiveness more valued by istics that evoke jealousy. That is, whereas women’s
men, and status- and dominance-related character- jealousy increased after exposure to the attractive-
istics more valued by women, from an evolutionary ness words but not after priming with social domi-
psychological perspective one would expect women nance words, males showed the reverse pattern and
to feel more jealous than men when their rival sur- reported increased jealousy after being primed with
passes them on bodily and facial attractiveness, and words relating to social dominance but not after
men to feel more jealous than women when their priming with attractiveness words. Finally, a study
rival possesses status- and dominance-related char- using photographs of an attractive or an unattrac-
acteristics. Based on a series of open interviews, tive female (Massar & Buunk, 2010) showed that
Dijkstra and Buunk (2002) constructed a 56-item exposure to a female face outside their awareness

Buunk, Massar, Dijkstra, and Fernande z 221

affected women’s jealousy such that they reported responded with more jealousy to physically domi-
significantly higher levels of jealousy after exposure nant, socially dominant, and physically attractive
to an attractive face than after priming with an rivals. Although females responded with more jeal-
unattractive face. ousy in response to physically attractive, physically
dominant, and high-social-status rivals, average-
Cross-cultural similarities and differences. Similar sex
height women (i.e., those most preferred by men)
differences in the threatening nature of rival charac-
tended to be less jealous of physically attractive
teristics as in the Netherlands have been observed
rivals but more jealous of rivals with “masculine”
in studies in other cultures, including the United
characteristics of physical dominance and social
States, South Korea (Buss et al., 2000), Spain, and
status. An explanation for this finding is that women
Argentina (Buunk, Solano, Zurriaga, & González,
may be least jealous of rivals who have features they
2011). However, although a factor analysis in a
have themselves and most jealous of rivals who have
sample of young people in Iraqi Kurdistan (Buunk
features they do not have themselves. As women of
& Dijkstra, 2015) showed exactly the same five di-
average height are, as noted above, preferred by men,
mensions or rival characteristics as found by Dijkstra
in part because they tend to be more fertile and
and Buunk (2002), in contrast to the Dutch, the
healthy (Nettle, 2002; Silventoinen et al., 1999),
Kurdish men and women did not differ in which
they would be less jealous of women with features
characteristics evoked the most jealousy. A possible
signaling fertility and health such as physical attrac-
explanation for this lack of gender differences is that
tiveness but more jealous of women possessing
the overall high level of jealousy was much higher,
“masculine” features.
and that this may have overruled the effects of spe-
cific rival characteristics. Nevertheless, at least in
Male Intrasexual Competition
Western cultures, sex differences in the rival charac-
Intrasexual competition occurs among males and
teristics occur not only in intimate relationships but
females to establish their position in a hierarchy.
also in relationships at work with one’s supervisor in
Dominance hierarchies revolve around relative rather
which a rival interfered. A study in Argentina showed
than absolute positions, and individuals are more
that among men, physical dominance of a same-sex
sensitive about getting ahead of another rather
rival evoked more jealousy than among females, and
than about achieving an absolute position (Buunk
among females physical attractiveness evoked more
& Ybema, 1997). S. E. Hill and Buss (2006) report
jealousy than among males (Buunk, Aan ‘t Goor,
studies that show that men and women possess a
& Castro Solano, 2010). This occurred only when
positional bias, making them attend to the posi-
the supervisor was of one’s own sex. These findings
tional rather than to the absolute value of resources
suggest that intrasexual competition has a dynamic
that are known to affect survival or reproduction,
of its own and is induced more by the presence of
and to personal attributes that affect others’ abilities
same-sex others than by the presence of opposite-sex
to acquire such resources. When choosing between
others (cf. Campbell, 2002; Geary, 1998).
having an absolutely larger income or an income
Hormonal and physical characteristics. Although that was absolutely less but larger than one’s rivals’
there is thus far no evidence that testosterone is incomes, both men and women chose the greater
associated with jealousy, jealousy in response to par- positional income. Moreover, the positional bias
ticular types of rivals seems to be clearly associated seems to be sex differentiated, evident in the finding
with prenatal exposure to male hormones. Such that women preferred to be less attractive in an
exposure affects the second-to-fourth-digit ratio absolute sense but more attractive than their rivals
(2D:4D), with masculinity associated with a lower (e.g., scoring a 5 when rivals score a 3) over being
and femininity with a higher ratio. Park, Wieling, more attractive in an absolute sense but less attrac-
Buunk, and Massar (2008) found that men with tive than their rivals (e.g., scoring a 7 when rivals
more feminine 2D:4D ratios were most jealous in score a 9).
response to physically and socially dominant rivals, Among humans, male–male intrasexual com-
whereas women with more masculine 2D:4D ratios petition is a quite complex and multifaceted
were most jealous in response to physically attractive phenomenon. Overall, men compete with other
­
rivals. In a related vein, a study by Buunk et al. (2008) men for access to reproductive resources, includ-
in Spain showed that height was differently related ing resources such as political influence and social
among men and women to the threatening nature status that can be converted into reproductive
of rival characteristics. As males were shorter, they opportunities, either because these are directly
­

222 Intersexual and Intrasexual Competition

a­ ttractive to females or because these help conquer that men made more generous offers when pitted
rival males (Barkow, 1999; Sidanius & Pratto, 1999). against a woman as opposed to a man. Women,
In preindustrial societies in which male–male com- on the other hand, made equal offers independ-
petition has been studied, it has consistently been ently of the sex of the recipient. In the same vein,
found that a man’s status is directly related to his Buunk and Massar (2014) had participants engage
reproductive success (Betzig, 1982, 1986). Even in a series of decomposed social games in which
in contemporary Western society, high-income they had to divide resources between themselves
men have more biological children than low-in- and either a same-sex or an opposite-sex other.
come men, whereas among women the opposite is Males behaved more competitively toward another
true (Hopcroft, 2005; Nettle & Pollet, 2008). man than toward a woman, whereas women did
Costly signaling. One type of intrasexual com- not distinguish between men and women in their
petition is quite indirect and consists of showing degree of competitiveness. At the same time, men
off to females those characteristics that may signal behaved more prosocially toward women than
good genetic quality. This type of intrasexual com- women did toward men. In addition, after divid-
petition is driven by intersexual selection (i.e., the ing resources between themselves and another
selection by females for male traits that are indica- man in the decomposed game task, men showed
tors of good genes). For instance, in birds of paradise, higher levels of intrasexual competitiveness than
females’ preference for male ornamentation has after dividing resources between themselves and
resulted in intrasexual competition between males a woman.
for the most attractive plumage (Andersson, 1994). There is abundant evidence that male costly sig-
In a similar vein, one way in which intrasexual naling via conspicuous consumption is common in
competition among males can take place is via traditional societies (Bird, Smith, & Bird, 2000;
ritualized displays. As Veblen noted in 1899, con- Hawkes & Bliege Bird, 2002). Some have even
spicuous consumption and conspicuous leisure argued that men’s hunting has evolved, in part, as a
might be ways of engaging in status competition. signaling strategy (Hawkes & Bliege Bird, 2002).
Saad and Vongas (2009) found that men’s testos- Hunting is not necessarily an effective activity.
terone levels are responsive to fluctuations in Although it may result in obtaining food and ward-
their status as triggered by acts of conspicuous ing off starvation, often the time spent hunting
consumption. That is, male testosterone levels could in many cases be better allocated to gathering
­increased after driving an expensive sports car, food. Hunting does, however, appear to provide
whereas they decreased after driving an old family some cues about an individual’s quality to relevant
sedan, and male testosterone levels increased audiences: good hunters are subsequently preferred
when men’s social status was threatened by the as mates or allies. Also, in modern society men use
wealth displays of a male rival in the presence of a conspicuous consumption as a strategy of intrasex-
female. This study suggests that showing off by ual competition (G. F. Miller, 2009). Lycett and
means of conspicuous consumption is an evolved Dunbar (2000) demonstrated this by showing that
mechanism for responding to intrasexual challenges. mobile phones could be construed as lekking devices
Building on Veblen (1934 [1899]), G. F. Miller (i.e., as in grouse; e.g., Gibson & Bradbury, 1985),
(2000) suggested that conspicuous consumption whereby human males aggregate and conspicuously
could be seen as a handicap signal. Handicap sig- display their features to attract females. In this
naling refers to the evolution of an honest signal, study, males were more ­inclined to conspicuously
which cannot be copied because it is costly to pro- display their mobile phones as the composition of
duce (Zahavi & Zahavi, 1997). In this way, for their group became more male biased. Thus, men
example, human males could show off and signal may aggregate in groups and compete via ritualized
to other men and potential mates: “I can afford displays, such as by showing off their mobile phones.
all this.” In relation to this, Saad and Gill (2001) Nevertheless, intrasexual competition among
conducted a two-person ultimatum game in which males may become more salient and prevalent in
one was the allocator and the other the recipient, the presence of women, which tends to make
and the allocator had to split a given sum of money men more aware of their status, and more eager to
with the recipient. The recipient could either ­demonstrate that they can beat other men. For
accept or reject the offer. If accepted, both players ­example, an experiment showed that men increased
received their respective splits, but if rejected, nei- their cooperation in an economic game when ob-
ther of them got anything. The results showed served by women (Iredale, Van Vugt, & Dunbar,

Buunk, Massar, Dijkstra, and Fernande z 223

2008). Thus, men may exhibit competitive altruism: demonstrate that a male is in a good condition. Bar,
they compete by being generous and forego indi- Neta, and Linz (2006) showed that first impressions
vidual benefits (Van Vugt, Roberts, & Hardy, 2007). of males, especially those that are perceived as a threat,
Behaving altruistically may improve one’s reputation are usually made within the first 39 milliseconds,
and status; others often attribute charisma to those solely on the basis of visual information. Research
who sacrifice their own needs to those of others or the using the zero-­ acquaintance paradigm, in which
group (De Cremer & Van Knippenberg, 2004). participants are asked to judge personality attributes
of people based on short, silent video clips of often
Physical dominance and aggression. Especially among no more than 30 seconds, shows that people are
young males with few resources, intrasexual com- often quite accurate when making judgments about,
petition is to a large extent driven by direct physical for instance, someone’s self-esteem, status, and level
competition (Barber, 1995; K. Hill & Hurtado, of altruism (e.g., Yeagley, Morling, & Nelson, 2007).
1996; Kemper, 1990). Males may engage in fierce In addition, body-related stereotypes that men with
threats and fights to attain a high status in the an athletic (or mesomorph) body build are stronger,
group, and to prevent other males from access to more sportive, more competitive, more dominant,
females, and as such maintain exclusive sexual access healthier, and more energetic (Butler, Ryckman,
to females (Andersson, 1994). Among primates such Thornton, & Bouchard, 1993; Lerner & Korn,
as baboons, such conflicts are common (Walters & 1972; Ryckman, Robbins, Kaczor, & Gold, 1989)
Seyfarth, 1987; Wrangham & Peterson, 1996). It tend to be relatively accurate. As a result, during in-
requires individuals to be healthy, physically strong, trasexual competition, body-related stereotypes may
and aggressive (i.e., exactly those characteristics facilitate men to form fast and relatively accurate
that are signaled by an athletic body; Frederick & impressions of their rivals and, in so doing, may en-
Haselton, 2007). The strategy of physical domi- hance competitive success and prevent a possible
nance is effective in p ­ articular for younger men: loss of status (Fiske, 1992). More specifically, as in
Whereas they do not possess a high status yet in a many other species, by ­assessing the physical fea-
larger social context, they are at their peak with regard tures and deriving conclusions from these features
to health and fitness (Kemper, 1990). The degree to in other males, men may challenge those who can
which men are able to engage in the strategy of be beaten so as not to miss out on opportunities to
physical dominance is related to their physical ap- raise their status (or their reproductive success in
pearance. Athletic men have been found to be rela- other ways) that could be available, while it may
tively competitive (Quinn & Wilson, 1989) and to prevent them from competing with superior males,
like physical adventure, exercise, risk, and car speed as that would be a waste of energy and would bring
relatively more than nonathletes (Child, 1950; substantial costs. In support of this line of reasoning,
Quinn & Wilson, 1989; Sheldon & Stevens, 1942). Tiedens and Fragale (2003) found that men changed
Compared to men with a less athletic body build, their behavior when being in the same room as a
athletic men show lower anxiety and may therefore male who, due to his bodily posture, was perceived
be high in sensation seeking, and have been found as dominant. When confronted with such a male,
to engage often in impulsive, aggressive, antisocial, men behaved relatively submissively.
and disorderly behavior (see Domey, Duckworth, & Although one might assume that physical domi-
Morandi, 1964; Verdonck & Walker, 1976). nance would not matter in modern organizations
The male face also signals the degree of physical with only white-collar work, there is substantial
dominance (Zuckerman, 1986). For instance, men evidence that it still does. Height, especially, has a
who are high in testosterone—an important hor- greater effect on attaining status in organizations
mone regulating aggressive behavior—have larger than is often thought, whereby taller men tend
jaws and a more prominent brow ridge than other to attain higher positions in organizations. In
men, and as a result are perceived as more mascu- humans, height is one of the first features that
line and dominant (Penton-Voak & Chen, 2004). others notice and is associated with status. For in-
According to Frederick and Haselton (2007), a stance, one study found that full professors were
man’s body morphology signals his fitness and the 0.47 inches taller than associate professors, who
presence of genes that could potentially increase his were 0.26 inches taller than assistant professors,
reproductive success (see also Geary, 2005a). An who were 1.24 inches taller than the average non-
athletic build characterized by a high degree of academic (Hensley, 1993). The relationship between
­muscularity and broad shoulders, for i­nstance, could height and status also leads individuals to distort

224 Intersexual and Intrasexual Competition

their perceptions of men’s height and, as a result, to by fast development and a short-term strategy, and
hold—relatively accurate—stereotypes about height eminence reflecting a K-strategy, characterized by
(P. R. Wilson, 1968; Jackson & Ervin, 1992). slow development and a long-term strategy.
Research, for instance, shows that the same male
is perceived to be taller as his status increases: Female Intrasexual Competition
when, for instance, a man is described as a stu- Although female sociality and same-sex bonding is a
dent, he is estimated to be about 2.5 inches recurring characteristic of group social living that
shorter than when he is described as a professor substantially increases fitness (e.g., Cheney, Silk, &
(P. R. Wilson, 1968). Seyfarth, 2012), it also results in a higher rate of same-
sex reproductive rivals, which affects female mating
Eminence. However, males compete not only
motivation and intrasexual competition for mates and
through conspicuous consumption and physical
their resources. This competition may in turn cause
dominance but also through achieving eminence,
group instability and intrasexual aggression. Indeed,
which refers to the elevated rank that is achieved,
rivalry among females in socially monogamous spe-
more gradually, through socially approved accom-
cies is a well-documented phenomenon. In many
plishments, such as education and political career
socially living species, such as baboons (Huchard &
making. It requires individuals to be intelligent
Cowlishaw, 2011) and bonobos (Hohmann & Fruth,
and to invest in intellectual activities, rather than
2003), rates of female–female aggression increase as
in their physical prowess. There is some evidence
the proportion of especially fertile females in the
that a lean and relatively weak body in terms of
group increases, with pregnant females showing the
muscularity—a so-called ectomorph body—is pos-
highest rates of aggression. In insects, for example,
itively correlated with cognitive abilities (Case &
intrasexual competition extends to precopulatory
Paxon, 2006), which may translate into higher
struggles for accessing a mate, postcopulatory com-
wages (Judge & Cable, 2004; Loh, 1993). In addi-
petition for access to and protection of the eggs, and
tion, ectomorphism has been found to correlate
the destruction of rival fertilized cells (Buss, 1988);
positively with interest in high status and intellectu-
in mammals a similar pattern of female competition
ally challenging vocations, such as school superin-
for resources and mates is the norm (Stockley &
tendent, physician, minister, lawyer, and researcher
Bro-Jørgensen, 2011). In the human species, female
(Cupcea, 1939; Deabler, Hart, & Willis, 1975;
intrasexual competition over males is also quite
Garn & Gertler, 1950; Tanner, 1954), and negatively
prevalent (Campbell, 2004, 2013; Fisher, 2004) and
with lower status and less intellectually challenging
often centers on access to mates, but also concerns
occupations, such as bus driver (Deabler et al.,
status enhancement or avoidance of victimization.
1975). Stereotypes about ectomorph men seem, at
Burbank (1987), who surveyed 137 societies in the
least partially, to parallel actual relationships between
Human Relations Area File, concluded that compe-
the ectomorph body build and personality traits.
tition over mates was the single most frequent
For instance, ectomorph men are usually perceived—
reason for female–female fights (121 out of the 297
with relative accuracy—as more intelligent and
fights for which reasons were recorded). However,
scholarly than men with different body builds
according to Campbell (2013), sexual selection in
(Butler et al., 1993; Ryckman et al., 1989).
women shaped intrasexual competition to favor
With age, as men’s physical dominance declines, indirect aggression over direct female–female combat,
the strategy of eminence will have greater success largely because in all known cultural groups, the
(Kemper, 1990; K. Hill & Hurtado, 1996). That is, mother is the principal caregiver of the offspring.
men relying on the strategy of eminence, although
they may not be successful early in life, often reach Indirect aggression and rival derogation. To elaborate
their peak later in life (Buss, 1994). Therefore, a on the previous reasoning, in social species, females
trade-off with age seems to take place between the provide most of the obligatory parental care, and the
strategies of physical dominance and eminence. In death of the mother results in a dramatic decrease in
contrast to the strategy of physical dominance, the survival rate of the offspring and the potential
the strategy of eminence requires individuals to diverting or loss of resources from male investment
delay the gratification of needs. This can be placed (Campbell, 2004). The costs of direct competition
within the earlier mentioned life history framework are thus higher for females than for males, and as a
(Roff, 1992; Stearns, 1992), with physical domi- result, women are more risk averse than men and
nance reflecting an r-strategy, as it is characterized have a lower fear threshold, which prevents women’s

Buunk, Massar, Dijkstra, and Fernande z 225

involvement in direct physical aggression (Campbell, derogation can take on various forms and range
1999; Hrdy, 2009). Therefore, women’s competi- from quite subtle—taking over conversations in-
tion for the provision of resources and the access to volving the rival—to blatant, such as pointing out
suitable available mates often takes on the form of a rival’s flaws to a male in whom one is interested
self-enhancement and indirect aggression in the (Fisher & Cox, 2011). Indeed, attractiveness in-
form of rival derogation, as well as other ways of creases the odds of being the victim of verbal der-
manipulating the mate and the rival (Campbell, ogation up to 35 percent for adolescent girls, and
2004; Fisher, 2004; Fisher & Cox, 2011). To be girls’ recent sexual activity increases the risk for in-
more specific, women compete with each other direct aggression (e.g., social exclusion or spread-
by employing two strategies at the same time: As ing rumors; Leenaars, Dane, & Marini, 2008). In
well as advertising their own strong points through addition to derogating women’s attractiveness, fe-
the enhancement of their appearance (e.g., by males tend to derogate other women’s intelligence or
wearing make-up or tight clothes), they engage in professional competence. Indeed, the “tall poppy
indirect aggression toward other women to damage syndrome” refers to the tendency for successful
their reputation, mate value, and social standing women to be “clipped” down to the level of less
(Campbell, 2004). successful female peers through verbal attacks and
gossip (e.g., Dellasega, 2009). Recently, Grabe,
Women’s indirect aggression is mainly di- Bas, Pagano, and Samson (2012) found that when
rected toward intrasexual rivals, particularly young, women were confronted with an attractive and
attractive, and sexually available females, who may sexualized female news presenter, they tended to
be able to capture the mating effort and resources derogate her intelligence and her efforts to en-
of the most valuable men available at a given time hance her appearance, whereas men’s reactions
(Vaillancourt, 2013). Although self-promotion is showed an opposite pattern.
an effective tactic to retain the attention and invest- In social contexts with a skewed sex ratio, and
ments of a mate, rival derogation allows women to where suitable male partners are thus scarce, rival
prevent direct confrontation with their rivals, derogation has been shown to specifically target
thereby lowering the risk of physical harm while rivals’ sexuality: gossiping and accusing other
simultaneously attempting to lower their rival’s women of being promiscuous, “easy,” or sexually
mate value. For example, Li, Smith, Yong, and unfaithful (Campbell, 2004). Since men looking
Brown (2014) reviewed evidence that young women’s for a long-term mate place a premium on finding
desire for thinness and the sometimes resulting a reproductively exclusive mate, accusing com-
­development of eating disorders may be the result petitors of promiscuity and sexual availability may
of young girls’ self-promotion tactics to appear be a useful weapon in such contexts (Campbell,
physically fit and attractive to potential mates, but 2004). Experimental research (Arnocky, Ribout,
may at the same time be a result of competition Mirza, & Knack, 2014) indicates that mere per-
with other physically attractive women (see also ceptions of mate scarcity—induced by a bogus
Fisher & Cox, 2011). Rival derogation often di- newspaper article—increased women’s intrasexual
rectly targets other females’ mate value, and since competitiveness, jealousy, and willingness to aggress
female mate value is to a large extent determined indirectly against a same-sex rival. Moreover, in
by her physical attractiveness, attractive women are mate-scarce contexts, there is a risk that female
the largest threat, and much of women’s intrasexual indirect aggressive behaviors—including rival
­
competition revolves around derogating other derogation—escalate into female–female direct
­
women’s appearance. Fink, Klappauf, Brewer, and (physical) aggression (Campbell, 2004).
Shackelford (2014) report that in a context of in- Regarding the effectiveness of these intrasexual
trasexual competition, the physical features men competitive tactics, research has shown that at-
value the most in women are perceived by other tractive women have a credibility advantage over
women as most threatening: a feminine face, larger their less attractive peers; after hearing derogatory
breasts, and a low WHR. As a way to counter the remarks about another woman’s appearance, men
threat of such attractive rivals, women report often tended to decrease their ratings of the facial at-
making derogatory comments about the unattrac- tractiveness of this person when the remarks came
tiveness of highly appealing other women and from an attractive woman (Fisher, 2004). Fisher,
verbal derogation tends to focus mainly on their Shaw, Worth, Smith, and Reeve (2010) report that
appearance and sexual health. These acts of rival such derogatory comments cause men to devalue

226 Intersexual and Intrasexual Competition

not only a woman’s attractiveness but also her women suitable mates are not interested in them
kindness, trustworthiness, and overall desirability to making the rival women believe these men are
as a mate. In sum, attractive women seem to have bad lovers.
a strategic advantage over less attractive women Gossip, or spreading rumors, is a common
when it comes to influencing male perceptions of intrasexual competitive tactic used by women
­
other women’s attractiveness. This also provides and tends to focus on topics like other women’s
an additional explanation for the finding that at- appearance or sexual conduct (for a review, see
tractive females are often the target of derogation, McAndrew, 2014). Gossip between females is more
whereas women who are unattractive or have a negative than gossip between men or mixed-sex
lower self-perceived mate value are more often the pairs, and women in particular respond encourag-
perpetrators of same-sex indirect aggression (Arnocky ingly and positively to gossip they hear from their
et al., 2012; Vaillancourt, 2013). However, although female friends (Leaper & Holliday, 1995). Younger
rival derogation may be an effective strategy to women tend to engage more in gossip than older
­influence perceptions of a rival’s attractiveness or women: In a study among women aged 20 to 50,
sexual permissiveness, it simultaneously decreases Massar, Buunk, and Rempt (2012) found that the
the perpetrator’s reputation or mate value for men, younger women were, the more likely they were to
as well as her appeal as a same-sex ally for women engage in derogatory gossip about a woman who
(Fisher et al., 2010; Vaillancourt, 2013). Moreover, was interested in the same man as they were. The
women are aware of the fact that direct, blatant, or finding that younger women engage more in
unreasonable attacks on another woman’s appearance ­intrasexual competition is consistently reported
are inappropriate and likely to be counterproductive in the literature. For example, in a study con-
(Fisher, Cox, & Gordon, 2009). ducted in South America, younger women reported
Indirect—or social—aggression refers to the significantly more intrasexual competition than
purposeful, but often covert, manipulation of in- women who were past their reproductive peak
terpersonal relationships and includes behaviors (Fernandez, Muñoz-Reyes, & Dufey, 2014), and
such as social exclusion, breaking confidences, premenopausal women are more likely to derogate
spreading rumors, and gossip. Relative to direct, other women’s attractiveness than are postmeno-
and especially physical, aggression, these acts are pausal women (Vukovic et al., 2009).
less risky since there is a lower likelihood of retali-
ation or social consequences, and are equally or Hormonal influences. The effects of hormones on in-
more often employed by women than by men (Hess trasexual competition, as well as the influence of
& Hagen, 2006). For example, Benenson et al. intrasexual rivals on hormone levels, have increas-
(2013) observed that “the formation of temporary ingly been studied over the past years. Ovulatory
exclusionary coalitions provides an elegant means shifts in intrasexual competition have by now been
by which females, either directly or indirectly, can firmly established. For example, Fisher (2004) showed
minimize competition without incurring large that women tested during the fertile phase of their
costs” (p. 5). The overall goal of the various forms cycle rated other women’s facial attractiveness as
of indirect aggression usually is to exclude rivals lower compared to menstruating women. Moreover,
from one’s social group while simultaneously women are less willing to bargain with other women
damaging their ability to form or maintain a social when they are fertile (Lucas, Koff, & Skeath, 2007),
network of their own (Geary & Flinn, 2002). and tend to report increased dehumanization of
In addition to social exclusion, other intrasexual other women—but not men or elderly women—
competition strategies involve manipulation of during the ovulatory phase of their cycle (Piccoli,
the mate and the potential rivals (Fisher & Cox, Foroni, & Carnaghi, 2013). Moreover, during fer-
2011). Manipulation of a potential mate functions tile days in their cycle, women “dress to impress”
to secure his exclusive attention relative to rivals (i.e., they dress more revealing and sexy than
and varies from lying to a potential mate about during nonfertile days of their cycle; Durante, Li,
the availability or interest of another woman to & Haselton, 2008). These results suggest that to
socializing with the potential mate’s friends. maximize the likelihood of obtaining a mate
Manipulation of the rival, on the other hand, in- with suitable qualities when this is most relevant
volves behaviors that are aimed at other women (i.e., when conception risk is highest), women are
with the intent to make them appear less attrac- driven by a motivation to outcompete attractive
tive or interesting, and varies from telling other rivals and show increased intrasexual attitudes

Buunk, Massar, Dijkstra, and Fernande z 227

and behaviors. Research further suggests that these Individual Differences in Intrasexual
effects may be driven by estrogen levels in particu- Competitiveness
lar: Piccoli, Cobey, and Carnaghi (2014) showed Although it seems clear that both sexes tend to com-
that as the level of synthetic estrogen in women’s pete largely with same-sex others, there are important
hormonal contraceptives was higher, their intrasex- individual differences in the extent to which males
ual competition also increased, in particular their and females engage in intrasexual competition.
tendency to objectify other women. Similarly, it has Some individuals seem to have as their major goal to
been established that among women using hormonal “beat” others, whereas others seem to have as their
contraceptives, higher levels of synthetic estrogen— major goal to develop collaborative relationships
but not synthetic progesterone—predict higher levels with others. As noted by Buunk and Fisher (2009),
of self-reported jealousy (Cobey, Pollet, Roberts, some evolutionary psychologists have argued that
& Buunk, 2011) and increased mate guarding individual differences in such adaptations are merely
tendencies (Welling, Puts, Roberts, Little, &
­ noise. According to Tooby and Cosmides (1990),
Burriss, 2012). “Heritable variation in a trait generally signals a lack
of adaptive significance” (p. 38 [italics in original]).
In addition to their own menstrual cycle influ- However, other authors have suggested that such
encing intrasexual competition, a same-sex rival’s heritable variation may continue to exist because
fertility status might increase women’s intrasexual ­individual differences may reflect equally adaptive
competition and mate retention efforts. In yellow strategies (e.g., Buss, 1991; Gangestad & Simpson,
baboons, for example, females try to monopolize 1990; MacDonald, 1995). From an evolutionary-
the attention of males when same-sex rivals are psychological point of view, individual differences
fertile (Wasser & Barash, 1983). In a similar vein, such as these may exist for several reasons. First,
Krems, Neel, Neuberg, Puts, and Kenrick (2016) combinations of specific individual differences may
showed that women in a relationship who were result in equally viable behavioral strategies (Penke,
exposed to photographs of other women taken Denissen, & Miller, 2007). Although each behav-
during their ovulatory cycle phase reported they ioral strategy has its specific costs and benefits, the
would try to avoid or even socially exclude these net effect may be the same (Nettle, 2006). For in-
women, but only when they rated their own part- stance, both competition and altruism may help
ners as highly desirable. Moreover, the presence individuals gain higher group status and can, as
of especially fertile intrasexual competitors may such, both be considered adaptive strategies. Second,
affect women’s hormonal levels. It already has Figueredo et al. (2005) argued that personality
been established that anticipation of competition ­differences may be adaptive in social competition
(e.g., watching or playing soccer matches) elevates because of the operation of frequency-dependent
testosterone levels not only among men (e.g., Van selection. Frequency-dependent selection implies
der Meij et al., 2012) but also among women that a single optimal strategy does not exist, and
(Oliveira, Gouveia, & Oliveira, 2009). Recent re- that various distinct strategies may all be heritable.
search shows that intrasexual or social competition Different strategies may have developed because,
also affects female testosterone levels. For example, under different conditions, different strategies may
Maner and McNulty (2013) report that women who be adaptive. For example, in a population with pre-
were exposed to the scent of a fertile woman sub- dominantly cooperative individuals, there would be
sequently displayed higher levels of testosterone a niche for competitive individuals, and vice versa.
than women exposed to the scent of a nonfertile Indeed, it seems probable that being strongly intra-
woman. A study tracking women’s testosterone and sexually competitive and selfish may be adaptive
intrasexual competition levels during five weeks under certain conditions, when, for instance, life
(Hahn, Fisher, Cobey, DeBruine, & Jones, 2016) expectancy is low, others are low in altruism as
revealed that women reported greater intrasexual well, and the level of social organization is low. Yet
competitiveness in the test sessions when their tes- the same competitive behavior may be maladaptive
tosterone levels were high (as it is near ovulation). under other conditions, for instance, when others
There was no association between other hormones are high in altruism or in complex social groups
(estradiol, progesterone, cortisol) and intrasexual (Rushton, 1985). Findings from studies on species
competition, suggesting a unique role for testosterone as diverse as great tits (Parus major) to big-horn sheep
in regulating women’s intrasexual competitiveness (Oviscanadensis) demonstrate that traits such as ag-
(see also Cobey, Klipping, & Buunk, 2013). gressiveness toward conspecifics, boldness, and risk

228 Intersexual and Intrasexual Competition

taking have different fitness payoffs in different that intrasexual competitiveness was associated with
environments (Dingemanse & Réale, 2005). Finally, a lack of agreeableness and neuroticism (although in
it has been argued that individuals are genetically a regression neuroticism was only marginally signif-
predisposed to have personality characteristics that, icant) among women, and with a high level of neu-
to a certain extent, are malleable. As a result, situa- roticism and extraversion among men, with neurot-
tional demands may push individuals to develop icism making the strongest contribution. In a study
certain strategies and traits over other ones (Penke among 140 adults in Uruguay with a mean age of
et al., 2007; Saad, 2007), a phenomenon Gangestad nearly 37, these findings were replicated and were
and Simpson (2000) refer to as strategic pluralism. even stronger, with clear independent significant
To assess individual differences in intrasexual effects of lack of agreeableness and neuroticism
­
competition, Buunk and Fisher (2009) developed among women, and extraversion and neuroticism
the Intrasexual Competition Scale (ICS). The scale among men (Buunk, FornariBucksath, & Cordero,
assesses intrasexual competition as an attitude that 2017). Thus, an intrasexual competitive attitude is
may be referred to as intrasexual competitiveness typical for neurotic extraverted men and for neurotic
and concerns the degree to which individuals view nonagreeable women. A possible theoretical expla-
the confrontation with same-sex individuals in com- nation for this sex difference is that among males,
petitive terms. It implicates a number of phenomena these are the traits that were the first individual dif-
that have been well described in the psychological ferences to evolve in freely moving species (Figueredo
literature, albeit not in a mating context, includ- et al., 2005), and that intrasexual competition among
ing the desire to outperform others rather than to males has a longer evolutionary history than among
perform well (Van Yperen, 2003); the desire to view females, due to which the adaptive value of different
oneself as better than others (cf. self-enhancement; levels of the same trait may have had more time to
Zuckerman & O’Loughlin, 2006); envy and frus- evolve (cf. Nettle, 2006). As noted by Costa and
tration when others are better off and negative McCrae (1992), the disagreeable or antagonistic
feelings toward such others (Smith & Kim, 2007); person is egocentric, skeptical of others’ intentions,
and malicious pleasure or schadenfreude when high and competitive rather than cooperative. Given their
achievers (“tall poppies”) lose face (Feather, 1994). longer evolutionary history of intrasexual competi-
The ICS operationalized these phenomena, par- tion, men may find agreeing with statements reflecting
ticularly on dimensions relevant to mating, and negative attitudes to other men relatively normal,
only formulated with respect to same-sex others. whereas women need to have a disagreeable person-
However, in addition, following up on a study by ality in order to agree with such statements. Indeed,
Luxen and Van de Vijver (2005), who showed that more than women, men seem to consider competi-
women often reject attractive women as candi- tion with same-sex others a more normal fact of life,
dates for a position in their department, questions which is for them not incompatible with maintain-
were included on the resistance to having others ing collaborative relationships with same-sex others
with higher mate value as close colleagues. The 12- (cf. Buunk & Massar, 2014; Campbell, 2013).
item scale was constructed simultaneously in the Although intrasexual competitiveness is clearly
Netherlands and Canada and proved to be sex an individual difference characteristic, the level
neutral, to possess high reliability, to have a high of it is dependent on environmental conditions.
degree of cross-national equivalence, and to be First, among both sexes, intrasexual competitiveness
­related to self-report of sibling rivalry in one’s will be enhanced when there is a relative shortage
childhood (Buunk & Fisher, 2009). of potential acceptable partners. Correspondingly,
Intrasexual competitiveness appears among men Buunk, Stulp, and Ormel (2014) found in a large
in a different way rooted in personality than among representative sample of adolescent women that
women. In a study among Canadian students, such women were c­ onsistently more intrasexually
Buunk and Fisher (2009) assessed the relationship competitive the higher the socioeconomic status
between intrasexual competitiveness and the Big of their parents, assumedly because young women
Five personality traits, using Costa and McCrae’s are nowadays on average more highly educated
(1992) scales for the Big Five personality traits, in- than young men, intensifying female competition
cluding neuroticism, extraversion, openness, agree- over highly educated males. In contrast, males
ableness, and conscientiousness. These traits have with parents with the lowest socioeconomic status
been recognized in many species (see also Andersson, tended to be more intrasexually competitive than
1994; Buss, 1991). Buunk and Fisher (2009) found those with parents with a medium socioeconomic

Buunk, Massar, Dijkstra, and Fernande z 229

status, assumedly because females can “marry up,” and nature of intersexual and intrasexual competi-
and lowly educated males have to compete not tion among humans. Among many species, includ-
only with other males with a low education but ing humans, the basic reproductive interests of
also with males with a higher education. A second males and females do in part diverge, resulting
type of condition that will enhance intrasexual com- in intersexual conflict. Specifically relevant in the
petitiveness is ecological conditions (e.g., Nettle, present context, both men and women in steady
2006) such as a low life expectancy, a low perceived ­relationships may for various reasons be interested
chance of attaining a high status in the long run, in involvement with opposite-sex partners other
and a low mate value. In line with this, Van than their steady partner, which may be a threat to
Brummen-Girigori and Buunk (2016) found that the reproductive interests of the steady partner. This
girls who had grown up without their biological conflict manifests in not only the occurrence of jeal-
father before the age of 14 reported overall more ousy as such, but also the different foci of men and
intrasexual competitiveness than girls who had grown women in jealousy, with men focusing more on
up in intact families (while there were no differences sexual infidelity and women more on emotional in-
in socioeconomic level between both groups). fidelity. In the case of the presence of actual rivals,
In addition, this intrasexual competitiveness was jealousy has a strong component of intrasexual com-
strongly correlated with a variety of nonverbal petition, with men and women paying attention to
strategies to attract males, probably mostly for different characteristics of the rivals. These sex differ-
short-term mating, including direct flirtation, ences in attention to specific rival characteristics even
the use of hairstyles with waves, the use of facial occur outside conscious awareness, and have a physi-
make-up, the use of conspicuous nail care, and cal and hormonal basis. Intrasexual competition is,
active and restless behavior in the presence of males. however, more than jealousy; it is manifest in many
Intrasexual competitiveness was a significant medi- ways and differs considerably between men and
ator between father absence and the expression of women. Male intrasexual competition is evolutionar-
most nonverbal seduction strategies. ily probably more ancient and is more characterized
Although human females high in intrasexual by physical dominance and direct aggression, conspic-
competitiveness may try to enhance their attractive- uous consumption, and aims of attaining eminence,
ness to attract males, in many species males in intra- whereas female intrasexual competition is more char-
sexually competitive situations tend to e­ nhance their acterized by indirect aggression, self-promotion, and
body size. Various studies have provided evidence of rival derogation. Both male and female intrasexual
the association between dominance and an expanded competitions have hormonal bases, with the fertile
posture both in primates and in humans (Weisfeld & stage of the cycle playing an important role among
Linkey, 1985). Consistently, Duguid and Goncalo women. Finally, we have paid attention to a phenom-
(2012) reported that the e­ xperience of power influ- enon that has thus far received little attention—the
enced individuals’ perceptions of their own height, considerable individual differences in the tendency
such that individuals experiencing more power over- to be intrasexually competitive, which are related to
estimated their height. In a similar vein, Mailhos, personality factors and environmental conditions.
Buunk, and Del Arca (2017) reasoned that males In sum, the present chapter outlined the multifaceted
high in intrasexual competitiveness might overesti- nature of intrasexual and intrasexual competition,
mate their own height. Indeed, in a sample of junior including hormonal, physical, cognitive, sex-specific,
soccer players from a First Division Uruguayan soccer and personality aspects.
team, they found that intrasexual competitiveness
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236 Intersexual and Intrasexual Competition

 CH A PT E R

14 Synthetic Hormones
The Influence of Hormonal Contraceptives and Hormone Replacement
Therapy on Aspects of Women’s Mating Psychology

Amanda C. Hahn and Kelly D. Cobey

Abstract

Following the invention of the hormonal contraceptive pill in the mid-20th century, there has been a
rise in exogenous hormone use worldwide. Across the lifespan, many women will utilize synthetic
hormones in the form of hormonal contraceptives and/or hormone replacement therapy. It is
estimated that 100 million women worldwide use combined oral contraceptives, whereas 20 million
women worldwide use hormone replacement therapy. Although extensive research has been done
investigating the health side effects of these synthetic hormones, relatively little is known about their
potential cognitive and behavioral consequences. This chapter reviews knowledge regarding the
potential impact of these synthetic hormones on women’s psychology. Much of this work derives from
the field of evolutionary psychology, which considers potential adaptive functions of behavior and their
underlying mechanisms. This chapter emphasizes the need for randomized within-subject clinical trials
to better understand the true causal effects they may have on women’s behavior.
Keywords: hormonal contraceptives, pill, estrogen, progesterone, testosterone, hormone replacement
therapy

The notion that women’s mating psychology is Palm-Fischbacher, Gossweiler, Stucky, & Ehlert,
­influenced by their hormonal status has received a 2017; Grebe, Emery Thompson, & Gangestad, 2016;
great deal of attention from both scientists and the Hahn, Fisher, Cobey, DeBruine, & Jones, 2016;
media over the last several decades. Early work in Holzleitner et al., 2017; Roney & Simmons, 2013,
this area relied primarily on inferred or estimated 2016), including several “big N” studies using very
hormone levels by focusing on changes across the large samples (e.g., Jones, Hahn, Fisher, Wang,
menstrual cycle. This work produced landmark papers Kandrik, Han, et al., 2018; Jones, Hahn, Fisher,
in Nature (Penton-Voak et al., 1999), Psychological Wang, Kandrik, & DeBruine, 2018; Marcinkowska,
Science (Gangestad, Simpson, Cousins, Garver-Apgar, Galbarczyk, & Jasienska, 2018).
& Christensen, 2016; Macrae, Alnwick, Milne, & Although new research continues to elucidate
Schloerscheidt, 2016), Proceedings of the Royal Society the role of endogenous (i.e., naturally occurring)
Biology (Gangestad, Thornhill, & Garver, 2002), hormones in regulating behavior, modern medicine
and Proceedings of the National Academy of Sciences has allowed for the artificial influence of hormones
(Dreher et al., 2007), and has been the source of through the consumption of synthetic, exogenous
much recent debate (see Welling & Burriss, this hormones—the most widespread examples of this
volume, for an in-depth review of this topic). More are the use of the combined oral contraceptive pill
recent work has begun to focus on measured hor- (“the pill”) and hormone replacement therapy
mone levels in an attempt to clarify the potential (HRT). The current chapter explores our knowl-
underlying hormonal mechanisms of observed cy- edge of how the use of these two interventions
clical shifts in women’s mating psychology (Ditzen, ­impacts women’s psychology, with a focus on aspects

237
of women’s relationship or mating psychology. pill report discontinuing use due to side effects
After providing an overview of the current evidence (Mosher & Jones, 2010). In light of the ubiquitous
for how these interventions are thought to influence nature of hormonal contraceptives, and the pill in
women’s psychology, we provide a critique of the particular, it is critical that scientific research works
study designs used to generate this evidence base. to better understand how synthetic hormones may
We conclude with a call to action for researchers or may not impact women’s psychology. Here, we
to remedy these design limitations to improve the outline existing evidence on this topic. We empha-
quality of evidence in this area. Given their wide- size findings describing effects of the COC pill,
spread use, it is our view that women would benefit simply because such studies are most represented in
from continued discovery on how intake of exoge- the literature.
nous hormones impacts their psychology.
How Do Hormonal Contraceptives Work?
Combined Oral Contraceptives—“The Pill” Hormonal contraceptives alter endogenous hormone
Described as the invention that defined the 20th levels through the introduction of exogenous steroid
century,1 “the pill” was first introduced in the early hormones, namely, estrogens and progestins. All
1960s as a method of preventing unintended preg- forms of hormonal contraception contain ­synthetic
nancy (Burrows, Basha, & Goldstein, 2012). This progestins, whereas not all forms of hormonal con-
medical advancement revolutionized the lives of traception contain synthetic estrogens. Forms of hor-
women, allowing them increased access to education monal contraception that administer both estrogen
and a stronger foothold in the workforce (Bailey, and progestins are termed combined (oral) contracep­
2006; Traulsen, Haugbølle, & Bissell, 2003). tives. Hormonal contraceptive use leads to a reduction
Hormonal contraception is even credited with nar- of endogenous estradiol and progesterone levels via
rowing the gender wage gap (Bailey & Hershbein, negative feedback mechanisms (Sahlberg, Landgren,
2012; Chiappori & Oreffice, 2015). Since its induc- & Axelson, 1987) and have been shown to sup-
tion, the pill has been the leading form of contra- press endogenous testosterone levels (Zimmerman,
ception in the United States (Mosher, Martinez, Eijkemans, Coelingh Bennink, Blankenstein, &
Chandra, & Abma, 2004), and is used by more Fauser, 2014; see Box 14.1). Estrogen, progesterone,
than 100 million women worldwide (Petitti, 2003). and testosterone have all been implicated in the reg-
The pill is now available in many forms and dosages, ulation of social-emotional behavior and women’s
and combined contraceptives can be delivered via psychology (Bos, Panksepp, Bluthé, & Honk, 2012;
alternative routes of administration (e.g., the trans- Bos, Terburg, & van Honk, 2010; Ellison & Gray,
dermal contraceptive patch, the vaginal contraceptive 2009; Garver-Apgar, Gangestad, & Thornhill, 2008;
ring). Although we will touch on hormonal contra- Hahn et al., 2016; Pisanski et al., 2014; Roney &
ceptives other than the combined oral contraceptive Simmons, 2013; Roney, Simmons, & Gray, 2011;
(COC) pill, COCs are the focus of this review, given Van Wingen, Ossewaarde, Bäckström, Hermans, &
that the vast majority of ­research regarding potential Fernández, 2011; Wang, Hahn, Fisher, DeBruine,
psychological effects of contraceptive use has focused & Jones, 2014; Welling et al., 2007). The suppres-
on women using COCs. sion of these endogenous hormones and introduction
In the United States, a staggering 82 percent of of synthetic exogenous hormones could, therefore,
women have used the pill at some point in their life- result in potential b­ ehavioral and/or psychological
time (Mosher & Jones, 2010), and research suggests side effects of hormonal contraceptive use.2 Indeed,
that modern adolescent girls have begun using recent reviews have suggested that synthetic exoge-
hormonal contraceptives earlier in the lifespan, nous hormones may affect the regulation of affective
typically shortly after the onset of puberty (Parkes, responses and social-emotional b­ ehavior (Hamstra,
Wight, Henderson, Stephenson, & Strange, 2009). De Rover, De Rijk, & Van der Does, 2014; Montoya
Although physical side effects of hormonal contra- & Bos, 2017; Oinonen & Mazmanian, 2002;
ceptive use have been the focus of a tremendous Radke & Derntl, 2016).
amount of research (reviewed in Welling, 2013),
relatively little is known about the potential psycho- 2
Assuming synthetic, exogenous hormones affect neural
logical consequences of hormonal contraceptive path­ways in a similar way to endogenous hormones, allowing for
use. Yet, 30 percent of women who have used the some effect on psychological outcomes. That these synthetic
hormones are able to act on brain systems to suppress ovulation
centrally (Frye, 2006) suggests they are, indeed, capable of
1
http://www.economist.com/node/347484. affecting neural pathways.

238 Synthetic Hormones

 Box 14.1. Ovarian Hormone Levels During the Menstrual Cycle and Combined Oral Contraceptive Use

The typical menstrual cycle is approximately 28 days in length and is characterized by fluctuations in the ovarian
steroid hormones estradiol (hereafter simply referred to as estrogen) and progesterone. The cyclical fluctuation
in these hormones is regulated by the hypothalamic-pituitary-ovarian (HPO) axis. The cycle begins at the onset
of menstrual bleeding (i.e., the menstrual phase), at which time both estrogen and progesterone levels are low. After
menstrual bleeding ceases, the follicular phase begins and follicle-stimulating hormone (FSH), released from the
pituitary, promotes the growth of immature egg follicles in the ovary. The follicular phase is characterized by a steady
increase in estrogen levels that peak just before ovulation. A surge in luteinizing hormone (LH) instigates the release
of a mature follicle at ovulation, typically around day 14 of the cycle. The corpus luteum, a temporary structure, forms
at the follicle release site and produces high amounts of progesterone (and some estrogen) in the second half of the
cycle, referred to as the luteal phase. Note that although estrogen levels may dip after ovulation, they remain relatively
high during the luteal phase. If implantation of a fertilized egg does not occur, the corpus luteum regresses, causing
both progesterone and estrogen levels to steeply decline in the final days of the cycle. This hormone decline triggers
the onset of menstruation and the beginning of a new menstrual cycle.
The primary mechanism of action of the combined oral contraceptive (COC) pill is to suppress ovulation (American
College of Gynecologists and Obstetricians, 1998) via negative feedback mechanisms that block the release of the
gonadotropins (i.e., FSH and LH) that normally promote growth and release of the ovarian follicle each month.
COCs contain exogenous estrogen and progestin that suppress the HPO axis. The suppression of these hormones
decreases ovarian activity and results in lower levels of endogenous estrogen and progesterone (in the context of high
levels of exogenous estrogen and progestin). Notably, however, reactivation of the HPO axis can occur during the
pill-free interval, called the pill break, that is characteristic of many COC regimens (Van Heusden & Fauser, 1999).

(A)
Hormone concentration

5 10 14 22 25

(B)

5 10 14 22
Menstrual cycle (days)

Figure 14.1 Representative levels of endogenous estrogen (gray lines), progesterone (black lines), luteinizing hormone (LH; light
gray lines), and follicle-stimulating hormone (FSH; dotted lines) levels across the menstrual cycle in (A) normally cycling women
and (B) women using combination oral contraceptive (COCs). By providing a steady daily level of both progestin (a substitute for
progesterone) and ethyl estradiol (a substitute for endogenous estradiol), oral contraceptives prevent gonadotropin-releasing hormone
(GnRH) secretion from the hypothalamus, blocking a signal to the pituitary gland to produce FSH and LH. Because FSH stimulates
the ovaries to grow egg follicles and LH triggers ovulation, their absence causes the ovary to be relatively dormant, and no egg is produced
to a point where it could be released. Hormonal contraception thus maintains the menstrual cycle at the same late phase of the natural
cycle on a continuous basis. Image & caption adapted with permission from Alvergne and Lummaa (2010).

Hahn and Cobey 239

Hormonal Contraception and Mate side effects of the pill not currently addressed by
Preferences ­traditional medical research looking at side effects
Perhaps the most well-researched aspect of potential during use.
COC effects on women’s psychology is of the study of Retrospective studies investigating this issue have
mate preferences (reviewed in Alvergne & Lummaa, found that COC use does appear to be related to
2010; Welling, 2013). Popular media commonly relationship stability, or lack thereof (Birnbaum et al.,
makes bold claims about the potential behavioral 2017; Roberts et al., 2012). Roberts et al. (2012)
side effects of hormonal contraceptives based on found that women who used COCs at the time of
­research on this topic—claims including “Women partner choice reported lower sexual satisfaction
choose different partners when on the Pill,”3 “Birth (across multiple measures) than did women who
control pills affect women’s taste in men,”4 and did not use COCs at the time of partner choice
“How the Pill could be seriously ruining your love (note, however, that these same women reported
life,”5 to highlight a few. Although these headlines higher general satisfaction with their partner choice
imply a causal link between the use of synthetic hor- than did women not using COCs at the time of
mones and changes in women’s psychology, relatively partnership formation). However, another study by
little causal evidence actually exists. this same group found that women who met their
Existing studies on this topic suggest that women partner while using COCs reported significantly
using COCs may have a greater interest in short- higher partner-specific attraction and sexual desire
term mating opportunities (Guillermo, Manlove, during pregnancy than did women who met their
Gray, & Zava, 2010) and may not show the same partner while naturally cycling (Cobey et al., 2016).
cyclical fluctuation in putative cues of men’s mate This seemingly opposing pattern of results has been
quality including masculinity preferences (Feinberg, attributed to changes in contraceptive congruency,
DeBruine, & Jones, 2008; Puts, 2006; Smith rather than simply COC use, whereby women are
et al., 2009), symmetry preferences (Gangestad & predicted to be more satisfied with their partner
Thornhill, 1998; Thornhill, 1999), and preferences choice if their current contraceptive or hormonal
for cues of health (Jones et al., 2005), including status is congruent with their status at the time of
preferences for major histocompatibility complex relationship formation (see Roberts et al., 2014 and
(MHC) dissimilarity (Roberts, Gosling, Carter, & Jern et al., 2018, for an expanded discussion of the
Petrie, 2008; Wedekind & Seebeck, 1995). Because congruency hypothesis). With respect to relation-
these mate preferences are thought to be adaptive ship stability, results are again mixed. Roberts et al.
(i.e., potentially enhance reproductive success and/ (2012) found that separation rates were lower in
or offspring quality), some researchers have argued couples who met while the woman was using
that COC use may disrupt women’s adaptive mate COCs—23.6 percent of couples who met when the
preferences, which could have downstream repro- woman was using COCs separated compared to a
ductive consequences (reviewed in Welling, 2013), 33.3 percent separation rate among couples who
including ­effects on relationship stability (Birnbaum, met when the woman was not using COCs. A more
Birnbaum, & Ein-Dor, 2017; Roberts et al., 2012; recent study, however, found the opposite pattern of
Taggart, Hammett, & Ulloa, 2016), sexual behavior results, reporting separation among 11.5 percent of
(Cobey, Havlicek, Klapilová, & Roberts, 2016; the couples who met while the woman was using
Roberts et al., 2012), and potentially even offspring COCs compared to a 3.5 percent separation rate
health (Birnbaum et al., 2017). Indeed, if COCs are among couples who met when the woman was not
affecting women’s mate preferences, it is possible using COCs (Birnbaum et al., 2017). Curiously,
that attraction toward an existing partner could ­although they did not find that relationship dissolu-
change over time if a woman alters her contracep- tion was more common among COC users, Roberts
tive status (i.e., initiates or discontinues COC use). et al. (2012) did find that if a separation occurred
This possibility raises the potential for psychological for those couples who met when the woman was
using COCs, the woman was disproportionately
more likely to have initiated the separation (84.8
3
http://www.telegraph.co.uk/women/sex/9173543/Women- percent of separations initiated by the woman,
choose-different-partners-when-on-the-Pill.html whereas only 73.6 percent of separations among the
4
https://www.scientificamerican.com/article/birth-control- non-COC group were initiated by the woman).
pills-affect-womens-taste/
5
http://www.cosmopolitan.com/uk/love-sex/relationships/ These results suggest that COC use could have
news/a31308/gone-right-off-him-blame-the-pill/ some effect on partner choice; however, the question

240 Synthetic Hormones

remains as to whether or not COC use actually mate preferences is ambiguous, often limited by use
causes any change in women’s mate preferences. Few of between-participant study designs, low power,
studies have explored this issue within women, and and a failure to control for COC brand and other
those that have yield equivocal results. Little, potential confounding variables. Comparing women
Burriss, Petrie, Jones, and Roberts (2013) examined who use the pill to women who do not is problem-
preferences for cues of facial masculinity in 18 atic as these groups of women may differ from one
women before COC use (during the follicular phase another on a whole host of factors, including age,
of their menstrual cycle, when masculinity prefer- relationship status, sexual activity, sociosexual ori-
ences are believed to be at their peak) and after ini- entation, and so forth. These potentially confound-
tiating COC use. Here, participants were asked to ing variables are not always controlled for in the
alter men’s faces along a masculinity continuum to ­existing literature, especially within the same model
make the face most attractive in a short- and long- to account for potential interaction effects. Although
term mating context (i.e., all participants completed there are numerous clinical trials addressing the
both the short- and long-term task). When compar- impact of COCs on women’s physiology, compa-
ing the women’s masculinity preferences before and rably powered randomized trails addressing the
during COC use, they found that women’s mascu- potential for changes in women’s psychology and
linity preferences decreased following COC initia- behavior during COC use are only just beginning
tion, regardless of the relationship context sought. to be conducted.
Similarly, Roberts et al. (2008) found that prefer-
ences for MHC dissimilarity in odor samples Hormonal Contraception and Sexual
­decreased in a sample of 37 women who initiated Behavior
COC use, although they did not detect any signifi- Sexual behavior6 is another aspect of women’s
cant MHC-associated preferences at either the pre- ­psychology that may potentially be subject to the
or post-COC initiation test sessions. Together, these influence of synthetic hormones given the reported
two studies do provide evidence for the notion that impact of circulating endogenous hormone levels
initiation of COC use may cause a disruption in on various aspects of female sexual behavior in both
women’s adaptive mate preferences. However, a humans (Grebe, Emery Thompson, & Gangestad,
recent study by Jones, Hahn, Fisher, Wang, Kandrik, 2016; Jones, Hahn, Fisher, Wang, Kandrik, &
Han, et al. (2018) tested for potential COC use ef- DeBruine, 2018; Matteo, 1984; Roney & Simmons,
fects on women’s facial masculinity preferences in 2013; see Cappelletti & Wallen, 2016, or Motta-
both a short-term and long-term mating context, Mena & Puts, 2017, for recent reviews of this liter-
using multiple measures during both COC use and ature) and nonhuman primates (Wallen, 1984, 1990,
a period without COC use in a sample of 45 women. 2001). Indeed, concern about the impact of COC
They did not detect any changes in women’s facial use on women’s sexual behavior, particularly concern
masculinity preferences as a function of COC use. regarding decreased libido, has been expressed for
This study incorporated both women who initiated almost as long as hormonal contraceptives have
COC use, testing their preferences before and after been available. An early report from the Royal
using COCs, and women who ceased COC use, test- College of General Practitioners Survey (1974)
ing their preferences during COC use and after they found that women using the COC pill were nearly
had discontinued using COCs. Regardless of the four times more likely to complain of sexual diffi-
direction of the change (i.e., initiating or discon- culties than women using other, nonhormonal
tinuing COCs), no change in women’s masculinity methods of contraception. Since this early report, a
preferences was observed. This study also reports number of between-subject studies have reported
analyses of women’s preferences for additional facial similar decreases in aspects of sexual behavior in
cues, including facial symmetry, facial prototypicality, women using the COC pill as compared to women
and perceived health (see study supplemental mate- not using hormonal contraception (Adams, Gold, &
rials) and again found no effect of COC use on Burt, 1978; Alexander, 1990; Bancroft & Sartorius,
women’s preferences for any of these traits. 1990; McCoy & Matyas, 1996; Wallwiener et al.,
It is difficult to draw any definitive conclusions 2010). One potential explanation for the observed
about the impact of synthetic hormones on wom- negative effects of COCs on women’s sexual behavior
en’s mate preferences from the limited longitudinal
research conducted thus far. The evidence to date 6
The term sexual behavior is used in this review to broadly
regarding the causal effects of COC use on women’s encompass sex drive or libido, sexual activity, and sexual functioning.

Hahn and Cobey 241

is that COCs could be altering women’s sexual women’s sexual behavior. Different patterns of results
­cognition. Studies comparing attention to sexual have been observed when considering uncontrolled,
stimuli (Rupp & Wallen, 2007) and neural re- prospective studies versus placebo-controlled studies
sponses to sexual stimuli (Abler et al., 2013) or (Davis & Castaño, 2012). Additionally, differences
images of one’s romantic partner (Scheele, Plota, & in the length of time women have been using COCs
Stoffel-Wagner, 2015) among COC users and non- when post-COC initiation data is collected may
users have suggested that COC use may be linked to further influence reported findings. For example,
decreased processing of sexually relevant stimuli. Caruso et al. (2011) reported significant improve-
Although many studies report a decline in wom- ments in aspects of women’s sexual functioning
en’s sexual behavior that is assumed to be the result when comparing women’s responses before COC
of COC use, systematic reviews of the existing liter- use and six cycles after COC initiation. The majority
ature indicate that the evidence for an effect of of these effects, however, were nonsignificant when
COCs on female sexual behavior is highly mixed, the same women were assessed only three cycles
including reported negative and positive effects, after COC initiation. There may even be placebo
­reported mixed effects, and/or reports that there effects to consider; one study administered a contra-
are no effects of COCs on sexual behavior (Bancroft ceptive placebo to 147 young women. These women
& Sartorius, 1990; Bancroft, Sanders, Warner, & were surveyed monthly over the next year and 29.5
Loudon, 1987; Burrows et al., 2012; Davis & percent reported decreased libido due to their “pill
Castaño, 2012; Dei, Verni, Bigozzi, & Bruni, 1997; use” (Aznar-Ramos, Giner-Velázquez, Lara-Ricalde,
Pastor, Holla, & Chmel, 2013; Robinson, Dowell, & Martínez-Manautou, 1969).
Pedulla, & McCauley, 2004; Zethraeus et al., 2016). These mixed findings have led researchers to often
Indeed, one review noted that COC users reported conclude that the effects of COC use on women’s
an increase in sexual desire in 15 studies, no impact sexual behavior are complex and likely due to a
on sexual desire in 12 studies, and a decrease in combination of psychological, biological, and social
sexual desire in 9 studies (reviewed in Pastor et al., factors. Although undoubtedly complex, it is critical
2013). In addition to these mixed findings across that researchers continue to investigate the potential
studies, there is also often considerable variation impact of COC use on women’s sexual behavior
within the population of a single study, whereby given that perceived changes in sexual behavior,
large proportions of women within a study sample ­especially libido, are often reported as important
experience an increase or decrease in desire, whereas contributors to discontinuation of COCs and/or
others are apparently unaffected by COC use switching contraceptive methods (Sanders, Graham,
(Burrows et al., 2012; Davis & Castaño, 2012; Bass, & Bancroft, 2001). Because the quality of
Pastor et al., 2013; Schaffir, 2006). For example, evidence obtained from a well-designed within-
­
in a study of 61 women, Graham, Bancroft, Doll, subject study is higher than that of a between-subject
Greco, and Tanner (2007) found that one-third study, we will emphasize these studies for the pur-
of the women tested reported negative sexual side poses of this review.
effects, one-third reported positive sexual side effects, Several studies have explored potential changes in
and one-third reported no sexual side effects associ- women’s sexual behavior utilizing a within-subject
ated with COC use. design, although methods for assessing sexual behav-
One possibility for these mixed findings is that ior vary across these studies, including interviewer
there are multiple forms of COC, meaning that ratings of sexual functioning and self-administered
there is no single “pill” to study—the available questionnaires to assess various aspects of sexual
COCs on the market today differ vastly in terms ­behavior (Bancroft et al., 1987; Caruso et al., 2004,
of both their chemical composition and delivery 2005; Graham, Ramos, Bancroft, & Maglaya,
schedule (Mark, Leistner, & Garcia, 2016). A recent 1995; Graham & Sherwin, 1993; Greco, Graham,
study found that women in the United States alone Bancroft, Tanner, & Doll, 2007; Sabatini & Cagiano,
reported using over 80 different COC brands (Hall 2006; Sanders et al., 2001; Strufaldi et al., 2010).
& Trussell, 2012), highlighting the potential varia- Although these studies report mixed findings re-
bility that may exist within a study sample. Another garding various aspects of sexual behavior (see
possibility is that differences in methodology be- Table 14.1), there is some evidence for a negative
tween studies, or in instrumentation used to assay impact of COC initiation on sexual desire or interest
sexual desire and related variables, may contribute (Caruso et al., 2004; Graham et al., 1995; Graham
to the lack of clarity regarding an effect of COCs on & Sherwin, 1993; Sabatini & Cagiano, 2006;

242 Synthetic Hormones

Table 14.1. Summary of Findings Across Within-Subject Studies Exploring the Impact of Combined Oral Contraceptive Initiation on Aspects of Women’s Sexual Behavior

Study N Assessment of COC formulation Sexual desire Sexual Sexual Sexual Orgasm
sexual behavior or interest activity arousal enjoyment ­frequency
or satisfaction
Graham et al., 1993 45 Visual analog 35 µg EE Decreased — — — —
scale ratings 0.1 mg norethisterone
Graham et al., 1995 50 IRSF 30 µg EE Decreased (marginal Decreased — No change —
SEQ 0.15 mg levonorgestrel effect in Filipino (Scottish
sample) sample)
Sanders et al., 2001 76 IRSF 30 µg EE Decreased Decreased — — —
SEQ 0.25 mg norgestimate OR
0.180 mg, 0.215 mg,
0.250 mg norgestimate
Caruso et al., 2004 48 PEQ 15 µg EE Decreased Decreased Decreased Decreased No change
60 µg gestodene
Caruso et al., 2005 80 PEQ 30 µg EE No change Increased Increased Increased Increased

20 μg of EE
3 mg drospirenone

150 μg desogestrel
Guida et al., 2005 28 IRSF Increased Increased — Increased Increased

Oranratanaphan et al., 42 FSFI 30 µg EE Increased — Increased Increased No change

20 μg of EE
2006) 3 mg drospirenone

75 μg gestodene
Oranratanaphan et al., 44 FSFI Increased — Increased Increased
2006
Sabatini et al, 2006 94 Self-report 20 µg EE Decreased — — Decreased —
100 µg levonorgestrel
Sabatini et al., 2006 92 Self-report 15 µg EE Decreased — — Decreased —
60 µg gestodene
Graham et al., 2007 61 IRSF 25 µg or 35 µg EE No change No change No change or No change or No change
SDI 0.18, 0.215, and 0.25 mg increased (groups increased (groups
norgestimate lumped) lumped)

(continued )
Table 14.1. Continued

Study N Assessment of COC formulation Sexual desire Sexual Sexual Sexual Orgasm
sexual behavior or interest activity arousal enjoyment ­frequency
or satisfaction
Greco et al., 2007 24 SDI 25 µg EE No change — — — —
SEQ 0.18, 0.215, and 0.25 mg
norgestimate
Greco et al., 2007 24 SDI 35 µg EE No change — — — —
SEQ 0.18, 0.215, and 0.25 mg
norgestimate
Westhoff et al., 2007 1716 Interview Varied — — — No change —
Caruso et al., 2009 56 SPEQ 30 µg EE No change — No change Increased Increased
2 mg chlormadinone a­ cetate
Brucker et al., 2010 1063 Interview 20 µg EE No change — — — —
2 mg chlormadinone a­ cetate
Strufaldi et al., 2010 49 FSFI 30 µg EE Increased — No change Increased§ No change
150 µg levonorgestrel
Strufaldi et al., 2010 48 FSFI 20 µg EE Increased§ — No change No change No change
100 µg levonorgestrel
Caruso et al., 2011 54 SPEQ 20 µg EE No change No change No change No change No change
3 cycles post-COC 3 mg drospirenone
initiation 21/7 regime
Caruso et al., 2011 54 SPEQ 20 µg EE No change Increased Increased Increased No change
6 cycles post-COC 3 mg drospirenone
initiation 21/7 regime
Caruso et al., 2011 61 SPEQ 20 µg EE Increased No change Increased No change Increased
3 cycles post-COC 3 mg drospirenone
initiation 24/4 regime
Caruso et al., 2011 61 SPEQ 20 µg EE Increased Increased Increased Increased Increased
6 cycles post-COC 3 mg drospirenone
initiation 24/4 regime
Battaglia et al., 2012 22 MFSQ 30 µg EE –- Decreased — — Decreased
3 mg drospirenone
Studies reporting on combined contraceptives with alternate administration routes

15 μg/day EE 120 μg/day

Guida et al., 2005 20 IRSF NuvaRing Increased Increased — Increased Increased

etonogestrel

15 μg/day EE 120 μg/day

Sabatini et al., 2006 94 Self-report NuvaRing Increased — — Increased —

etonogestrel

Note: A study may appear multiple times if it reports analyses of multiple COC brands. § A reported effect that failed to reach statistical significance. FSFI, Female Sexual Function Index; IRSF, Interviewer Ratings of
Sexual Functioning; MFSQ, McCoy Female Sexuality Questionnaire; SDI, Sexual Desire Inventory; SEQ, Side-Effects Questionnaire; (S)PEQ, (Short) Personal Experience Questionnaire.
Sanders et al., 2001; Zethraeus et al., 2016), sexual regional and ethnic variation. However, relatively
activity (Caruso et al., 2004; Graham et al., 1995; few studies have investigated potential individual or
Sanders et al., 2001), sexual arousal (Caruso et al., cultural differences. One study has suggested that
2004; Zethraeus et al., 2016), and enjoyment or sat- prenatal testosterone exposure, measured through
isfaction (Caruso et al., 2004; Sabatini & Cagiano, the second-to-fourth-digit ratio (2D:4D), may be
2006). linked to the experience of negative side effects and,
The evidence for a potential negative impact of particular relevance here, the experience of
of COC initiation on women’s sexual behavior is changes in sex drive (Oinonen, 2009). Another study
strongest for assessments of sexual desire or interest, has reported evidence of individual differences in
although methodological differences in assessing COC-related changes in affect, with women younger
sexual behavior may contribute to conflicting than age 20 reporting greater negative affect following
findings here. Studies using interviewer ratings of COC initiation (Bancroft et al., 1987). Although
sexual functioning (IRSF) and those using self-­ these results add to an already-complex picture,
administered questionnaires regarding sexual desire they highlight the importance of considering indi-
have consistently reported negative effects of COC vidual factors when assessing potential psychobe-
initiation on sexual desire/interest (Caruso et al., havioral consequences of synthetic hormones.
2004; Graham et al., 1995; Graham & Sherwin,
1993; Sabatini & Cagiano, 2006; Sanders et al., Hormonal Contraception and Other
2001); however, one study utilizing the Female Aspects of Relationship Behavior
Sexual Function Index (FSFI) reported a positive Although sexual behavior and mate preferences are
impact of COC initiation on sexual desire/interest among the best studied components of the psy-
in two separate samples (Strufaldi et al., 2010). chobehavioral effects of synthetic hormones, a
Importantly, however, many of these same studies number of additional aspects of relationship-related
report no effect of COC initiation on some of the behavior have also been studied in the last few
individual aspects of sexual behavior assessed (Caruso ­decades. Intrasexual competition (i.e., competition
et al., 2004, 2005; Graham et al., 1995; Greco et al., between members of one sex for access to mating
2007; Strufaldi et al., 2010). opportunities with members of the opposite sex;
The findings from Graham et al. (1995) suggest Andersson, 1994) occurs in females of many species
that cultural and/or individual differences may par- and has been shown to be influenced by endogenous
tially contribute to the discrepant findings reported hormone levels (Cobey & Hahn, 2017), suggesting
across studies. They performed a placebo-controlled, that this aspect of relationship behavior may also be
double-blind study to explore differences among susceptible to the influence of synthetic hormones.
COC and progestin (P)-only pill users (note: only Indeed, nonhuman primates have shown COC-
the results from the COC group are discussed here). linked decreases in intrasexual competition for access
Within the COC group, 25 of the women were to a male conspecific (Shively, Manuck, Kaplan, &
­recruited in Scotland and 25 women were recruited Koritnik, 1990) and elimination of cyclical changes
in the Philippines. A negative effect of COC initia- in aggressive behaviors (Sarfaty, Margulis, & Atsalis,
tion on sexual activity and sexual interest was con- 2012). In humans, COC initiation has similarly
sistently observed across the four months following been shown to reduce intrasexual competition, at
COC initiation, but only in the Scottish women. least in partnered women (Cobey, Klipping, &
No change in sexual interest or activity was reported Buunk, 2013). In a sample of 14 partnered women
among the Filipino women. The authors offer two tested before and after COC initiation, Cobey et al.
possible explanations for this cultural difference— (2013) observed a significant reduction in reported
the first, that the Scottish sample reported more intrasexual competition following COC initiation.
positive sexual experiences at baseline than did the Intriguingly, although intrasexual competition appears
Filipino sample, which would allow for a greater to be decreased by COC use, self-reported mate
scope of negative outcomes for the Scottish women; ­retention behaviors have been observed to be higher
the second, that any lack of consistency in assess- in COC users than nonusers (Welling, Puts, Roberts,
ment across the samples could have impacted the Little, & Burriss, 2012), although this has yet to be
accuracy of the results, especially in the Filipino investigated within subject as a function of COC
sample, where translation is an issue. Another possi- initiation.
bility, however, is that COCs may affect individuals Another aspect of relationship behavior that may
differently and such differences may be impacted by be influenced by both endogenous and exogenous

246 Synthetic Hormones

hormones is relationship jealousy (i.e., thoughts, both the specific synthetic progestin used and
emotions, or behaviors that occur as a result of the ­variation in the dosage (of both estrogen and pro-
perceived threat of losing a potential mate to an gestin) across different brands of the combined
actual or imagined rival). One early study reported oral contraceptive pill, collapsing data from all
that COC users report greater levels of relationship “pill users” into a single, homogenous group may
jealousy than do nonusers (Geary, DeSoto, Hoard, present a significant design concern. A large-scale
& Sheldon, 2001). Subsequent work utilizing a study of COC use in the United States recently
within-subject design found that reported levels of demonstrated that women aged 15 to 44 report
jealousy were not affected by COC initiation when using over 80 different brands of COCs (Hall &
compared to those same women’s reported jealousy Trussell, 2012). In this sample of over 12,000 women,
during the fertile phase of their natural menstrual high-dose estrogen pills were more common than
cycle, but were significantly increased following COC low-dose, 58 percent of women used a COC with
initiation when compared to those same women’s an older generation progestin, and two-thirds used
reported jealousy during the nonfertile phase of monophasic pills. This study highlights the impor-
their natural menstrual cycle (Cobey et al., 2012). tance of considering the specific COC used in future
The study sample was modest and the finding was research, and of the need for within-participant
also qualified by an interaction with relationship ­research examining the potential differential impact
status, whereby the impact of COC initiation was of different COCs.
only seen among partnered women. Recent studies have begun to investigate poten-
tial differences among contraceptive users as a func-
Effects of Dosage, Formulation, and Route tion of the estrogen dosage of the combined oral
of Administration contraceptive used. Circulating levels of EE have
Since its introduction in the early 1960s, the pill been positively linked to aspects of sexual desire in
has undergone significant changes in formulation. young women (Jones, Hahn, Fisher, Wang, Kandrik,
The initial pill of the early 1960s was G. D. Searle & DeBruine, 2018; Roney & Simmons, 2013),

ing 150 μg of mestranol (an estrogen) and 10 mg of

& Company’s Enovid, a combination pill contain- suggesting that COCs with higher doses of EE may
be associated with more positive outcomes regard-

varies from 15–5 μg in the studies summarized in

norethynodrel (a progestin), approved by the U.S. ing women’s sexual desire or interest. The EE dosage
Food and Drug Administration (FDA) in 1959 for

lowest EE dose (15 μg EE) were associated with neg-

distribution in the United States. Shortly thereafter, Table 14.1. Although both studies reporting the
Bayer Schering introduced Anovlar, a combined
pill containing 50 μg ethinylestradiol (an estrogen) ative effects on reported sexual desire/interest, it

of the vaginal ring, which also contains 15 μg/day

and 4 mg norethisterone acetate (a progestin), should also be noted that women who initiated use
which became available in Australia and Europe in
1961 (Rabe et al., 2011). The combined oral con- EE, report positive effects on various aspects of their
traceptive pill has continued to be developed since sexual behavior (Guida et al., 2005; Sabatini &
its initial release; today, the combined oral contra- Cagiano, 2006). Studies investigating the effects of
ceptive pill contains lower concentrations of the COCs with higher EE doses were not consistently
synthetic hormones than were present in its initial associated with positive effects on women’s sexual

20 and 35 μg ethinylestradiol (EE) and varying

form. Current formulations typically contain between desire/interest or other aspects of sexual behavior.

women using COCs with 20 μg and 30 μg EE;

Increases in sexual desire/interest were observed in
levels of synthetic progestins, classified by their

women using COCs with 15 μg, 20 μg, 30 μg, and

generation (Pletzer & Kerschbaum, 2014). The ­decreases in sexual desire/interest were observed in

35 μg EE; and no change in sexual desire/interest

older generation progestins (e.g., desogestrel, levo-

was observed in women taking COCs with 20 μg,

norgestrel) are androgenic (i.e., they are capable of

25 μg, 30 μg, and 35 μg EE. Regarding other as-

exerting androgenic effects), whereas the newer
progestins (e.g., drospirenone) are antiandrogenic
and bind specifically to the progesterone receptor. pects of relationship behavior, a more consistent
Additionally, there are monophasic pills, which pattern of EE-dose effects has emerged based on
­deliver a constant level of synthetic hormones across current evidence. That is, estrogen may act to in-
the 21-day regimen, and multiphasic pills, which crease mating behaviors associated with partner
deliver various phases of progesterone doses across ­fidelity. The EE dose in COCs has been positively
the 21-day regimen. In light of these differences in linked to reported jealousy (Cobey, Pollet, Roberts,

Hahn and Cobey 247

& Buunk, 2011) and mate retention behavior (containing an androgenic progestin, g­ estodene),
(Welling et al., 2012), as well as aspects of women’s but did not observe any significant d ­ ifferences in
personality, such as neuroticism and extroversion post-COC initiation reports of sexual desire, sexual
(Welling, 2016). However, there were no effects of arousal, orgasm frequency, or general sexual satis-
the progestin dose in the COC used observed on any faction (Oranratanaphan & Taneepanichskul, 2006).
of these behaviors, although it should be noted that Given that estrogens and progestins are predicted
all these studies used a between-participants design. to have opposing effects on general sexual desire
When considering potential effects of the pro- (Roney & Simmons, 2013), it is difficult to assess
gestin component of COCs, the story becomes in- the effects of COCs, which contain both estrogen
creasingly complex because the specific progestin and progestins. A recent study investigating the ef-
used and the dose varies widely across COC brands fects of synthetic hormones on sexual behavior in a
(Hall & Trussell, 2012). Circulating levels of en- large sample of Norwegian women developed a
dogenous progesterone have been negatively linked novel procedure for estimating the effective dose of
to aspects of sexual desire in young women (Jones, both the synthetic estrogen and progestin on con-
Hahn, Fisher, Wang, Kandrik, & DeBruine, 2018; tinuous scales while simultaneously controlling for
Roney & Simmons, 2013), suggesting that syn- the androgenic properties of the progestin (Grøntvedt,
thetic progestin may be associated with some neg- Grebe, Kennair, & Gangestad, 2017). Although they
ative outcomes regarding women’s sexual desire or did not observe any direct effects of EE or P-dose
interest. One study has reported significantly more on reported frequency of sexual intercourse using
sexual thoughts and fantasies in women using a this method, Grøntvedt et al. did demonstrate an
triphasic COC compared with a monophasic interaction between these synthetic hormones and
COC—the difference in pill composition being a loyalty/faithfulness on women’s reported frequency
lower dose of progestin in the triphasic regimen of sexual intercourse. As EE levels decreased and pro-
(McCoy & Matyas, 1996). This finding supports gestin levels increased, women’s loyalty/faithfulness
the notion that higher progestin doses could be became more positively associated with frequency
linked to negative outcomes regarding women’s sexual of sexual intercourse. There were mixed results for
behavior. These results should be interpreted with the effect of the androgenic activity on frequency of
caution, however, given that the study was done sexual intercourse, with no association observed in
retrospectively. In addition to the potential for var- Study 1, but a significant negative association ob-
ious progestin doses to impact behavior, COCs served in Study 2 and reported in many of the
contain a variety of synthetic progestins. Given the models included in the supplemental materials
differences in the androgenic properties of these (Grøntvedt et al., 2017). Future research is needed
synthetic progestins, there is the potential for these to attempt to clarify the impact of the androgenic
to differentially affect aspects of women’s sexual effects of contraceptives on sexual interests.
behavior. Indeed, various synthetic progestins have Although the pill was the first hormonal contra-
been shown to have significantly different effects ceptive (HC) on the market, today there exists a
on circulating concentrations of sex hormone– wide variety of HC options, including long-lasting
binding globulin (Jung-Hoffmann, Heidt, & methods (e.g., the implant, Depo-Provera, the in-
Kuhl, 1988). The studies shown in Table 14.1 sug- trauterine device [IUD]). These long-lasting meth-
gest that women who use COCs that utilize the ods have gained popularity due to their superior
antiandrogen chlormadinone acetate (CMA) performance in preventing unwanted pregnancy
report no change in sexual desire/interest (Brucker (Winner et al., 2012). A recent survey in the United
et al., 2010; Caruso, Rugolo, Agnello, Romano, & States found that 22 percent of women report having
Cianci, 2009), whereas those using the antiandrogen used an injectable, long-lasting contraceptive (Mosher
drospirenone (DRSP) report no change or positive & Jones, 2010). While the pill is a COC containing
effects. The other progestins listed (desogestrel, both an estrogen and a progestin, many of these
gestodene, levonorgestrel, norethisterone, and additional contraceptive methods rely solely on pro-
norgestimate) are primarily androgenic and were gestin (Rivera, Yacobson, & Grimes, 1999). As such,
not associated with any clear pattern of changes in studying the effects of these additional HCs offers
sexual desire/interest (Schneider, 2003). One novel insight into the potential psychobehavioral
study directly compared women who initiated use effects of synthetic progesterone. Decreased libido
of Yasmin (containing an antiandrogenic progestin, and other sexual side effects are commonly cited as
DRSP) versus women who initiated use of Meliane reasons for discontinuing use of progesterone-only

248 Synthetic Hormones

HCs (Sergent, Clamageran, Bastard, Verspyck, & the decline of circulating levels of estrogen and
Marpeau, 2004). Indeed, the Depo-Provera injection ­progesterone (Hunter, 1990), with a later decline
has even been used to decrease sexual drive in men in testosterone (Burger, Dudley, & Cui, 2000).
suffering from pedophilia (Murray, 2010). Empirical Women undergoing menopause or those who are
studies directly assessing the effects of these alternate postmenopausal often report a variety of cognitive
HCs on women’s behavior are much less common and behavioral symptoms, including changes in
than studies assessing COCs, and those that do exist mood, memory, and libido (González, Viáfara,
primarily rely on between-subject designs. A recent Caba, & Molina, 2004; reviewed in Pearce, Hawton,
comparative study assessing multiple forms of HCs & Blake, 1995). Many medical professionals pre-
in a sample of nearly 10,000 women found that scribe HRT during the menopause transition to
women who use Depo-Provera and the implant ­alleviate some of these physical and psychological
more commonly report lack of interest in sex when discomforts (Stadberg, Mattsson, & Milsom,
compared to women using the nonhormonal copper 2009; Taavoni, Unesie Kafshgiry, Shahpoorian, &
IUD (Boozalis, Tutlam, Robbins, & Peipert, 2016). Mahmoudie, 2005).
However, previous studies of both Chinese (Li et al., HRT first became available in the 1940s with the
2004) and Chilean (Barnhart, Furman, Pommer, introduction of Premarin, an estrogen-only supple-
Coutinho, & Devoto, 1997) women did not report ment derived from horse urine. Premarin was often
any negative effects of the contraceptive implant on combined with progestin-containing Provera until
women’s sexual behavior, and analyses of clinical the release of Prempro, which included both estro-
trial data for women initiating use of the implant gen and progestin. HRT usage rates grew to upward
suggests that only 3 to 5 percent of women report of 30 million in the mid-1970s (Kennedy, Baum, &
experiencing decreased libido (Brache, Faundes, Forbes, 1985) through the early 1990s (Wysowski,
Alvarez, & Cochon, 2002). 1995), with an estimated 40 percent of perimeno-
Studies of additional progesterone-only methods pausal women reporting having used HRT at some
of hormonal contraception have also failed to find point during menopause at that time (Keating,
negative effects on women’s sexual behavior. Women Cleary, Rossi, Zaslavsky, & Ayanian, 1999), prima-
using P-only oral contraceptives report no change rily during the age 50 to 54 window (Rosenberg,
in libido following HC initiation (Graham et al., 1998). HRT usage suffered a sharp decline after the
1995), and women using the hormonal IUD7 do publication of preliminary findings of the Women’s
not report changes in their sexual interest (Boozalis Health Initiative (Writing Group for the Women’s
et al., 2016) or sexual functioning (Li et al., 2004). Health Initiative Investigators, 2002) suggested that
In their study of the estrogenic and progesterogenic the risks of combined HRT exceeded their benefits
effects of contraceptives, Grøntvedt et al. (2017) because HRT may be linked to increased rates of
tested for an effect of pill versus other delivery (see breast cancer, heart disease, and stroke. Some of
supplemental materials), but no significant differ- these findings were further supported by the Million
ence in frequency of sexual intercourse was observed Woman Study (Million Women Study Collaborators,
for women using the pill versus other HCs. 2003; for an expanded discussion of the history of
these studies see Hersh, Stefanick, & Stafford, 2004;
Hormone Replacement Therapy Jyotsna, 2013). Sales of HRT dropped by nearly
in Menopause 50 percent following the publication of these studies
In addition to the common use of synthetic hormones (Jyotsna, 2013). However, this work has been criti-
in reproductively aged women as a form of contra- cized for overestimating the risks associated with
ception, synthetic hormones are used by older HRT use (Jyotsna, 2013). More recent evidence from
women as hormone replacement therapy (HRT) to the Women’s Health Initiative (Manson et al., 2013)
help ease the menopause transition. Menopause is the and additional longitudinal studies (Schierbeck
permanent cessation of menstruation that results et al., 2012) has demonstrated that HRT may actu-
from the loss of ovarian follicular activity (World ally benefit women’s health, leading clinicians and
Health Organization, 1996). Menopause typically researchers to re-evaluate recommendations for HRT
occurs around age 50 to 51 in women (McKinlay, use (North American Menopause Society, 2010).
Brambilla, & Posner, 1992) and is characterized by Today there are over 50 different types of HRT
available to women, with varying synthetic hormone
7
The hormonal IUD acts locally rather than systemically and doses and administration methods (Women’s Health
delivers a much smaller dose of synthetic progesterone. Concern, 2015).

Hahn and Cobey 249

How Does Hormone Replacement of orgasm were unchanged or improved in compar-
Therapy Work? ison with their own experience during the premen-
The purpose of HRT is to compensate for the natu- opausal period. Conversely, the majority of women
ral decrease in estradiol production by the ovaries. in the non-HRT group reported decreases in all
Similar to hormonal contraceptives, HRT regimens measured aspects of their sex lives. For all variables
may consist of some combination of synthetic estro- measured, these differences were statistically signifi-
gen alone or a combination of synthetic estrogen cant, suggesting that HRT may protect or shield
and progestin (Greendale et al., 1999), with many women from the negative impact of menopause on
women also incorporating the use of a synthetic tes- their sexual behavior. It should be noted, however,
tosterone supplement (Hersh et al., 2004). HRT that the potential issue of women’s motivation for
administration is typically achieved through an oral using HRT cannot be controlled for here. Indeed,
or transdermal route, although additional adminis- these groups of women differed in their views on
tration routes exist (Voican et al., 2012). The addi- the importance of sex—nearly 86 percent of women
tion of a synthetic progestin is primarily used to in the HRT group believed sex is relatively important
balance estrogen’s proliferative effects on the endo- in a relationship, whereas only 42 percent of women
metrium (Voican et al., 2012), whereas the addition in the non-HRT group reported the same.
of testosterone may decrease the risk of breast cancer Additional work has supported the notion that
(Dimitrakakis, Jones, Liu, & Bondy, 2004) and im- HRT use improves aspects of women’s sexual
prove aspects of well-being and sexuality (Flöter, behavior postmenopause; HRT use is associated
­
Nathorst-Böös, Carlström, & von Schoultz, 2009). with improved sexual function, although not always
Indeed, the addition of testosterone is thought to consistently across variables used to assess sexual
specifically address issues of reduced sexual desire ­behavior (González et al., 2004). However, women
during menopause (but see Dennerstein, Dudley, using HRT report higher sexual desire (Borissova
Hopper, & Burger, 1997; Flöter et al., 2009; Simon et al., 2001; Donaldson, Welling, & Reeve, 2017;
et al., 2005). but see González et al., 2004), sexual arousal (Borissova
et al., 2001; but see González et al., 2004), sexual
Hormone Replacement Therapy satisfaction (Donaldson et al., 2017; González et al.,
and Sexual Behavior 2004), orgasm frequency/experience (Borissova et al.,
Use of HRT supplementation during menopause 2001; Donaldson et al., 2017; González et al., 2004),
has been suggested to improve women’s sexual func- and sociosexual orientation (Donaldson et al., 2017).
tion and genital health (Borissova, Kovatcheva,
Shinkov, & Vukov, 2001; González et al., 2004; Hormone Replacement Therapy
Kingsberg, 1998; Taavoni et al., 2005). Indeed, two and Mate Preferences
studies have reported that postmenopausal HRT Evolutionary psychologists have argued that
users fared better than nonusers in all aspects of their ­menopause is accompanied by a shift from mating-
sex life, including libido, sexual activity and orgasm oriented psychology to family-oriented psychology
frequency, sexual satisfaction, and sexual pleasure (Hawkes, O’Connell, Jones, Alvarez, & Charnov,
(Borissova et al., 2001; Taavoni et al., 2005), while 1998). Indeed, mating-related behaviors, such as
an additional study found that including testoster- intrasexual competition, appear to be diminished
one supplementation further enhanced sexual satis- in postmenopausal women (Vukovic et al., 2009).
faction when compared to an estrogen-only HRT Given this purported shift in women’s psychology
regimen (Simon et al., 2005). In a longitudinal during menopause, we might expect other aspects
study of 154 women who elected to use HRT during of women’s reproductive psychology to undergo
menopause and 130 women who did not, Taavoni changes during the menopause transition and to
et al. (2005) assessed women’s libido, sexual activity, be subject to effects of HRT, although the potential
pleasure and frequency of orgasm, and attitudes effects of HRT on many of these additional rela-
toward sex on multiple occasions, providing a within- tionship behaviors (e.g., intrasexual competition)
woman analysis of these changes and the potential have yet to be investigated. HRT users report sig-
effects of HRT use. Women using HRT fared better nificantly more in-pair and extra-pair sexual interest
in all aspects of their sex life—with the majority of than nonusers (Donaldson et al., 2017). They also
these women reporting that their libido, sexual activ- report slightly increased feelings of jealousy, although
ity, sexual pleasure, sexual satisfaction, and frequency this difference was not significant (Donaldson et al.,

250 Synthetic Hormones

2017). Still, relatively little work has been conducted and potentially offer insight into how these inter-
in this area and future research is needed to fur- ventions may be modified to reduce side effects.
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256 Synthetic Hormones

 PA RT
3
Social and Affective
Behavior
 CH A PT E R
The Endocrinology of Social Relationships
15 and Affiliation

Christine Anderl, Shimon Saphire-Bernstein, and Frances S. Chen

Abstract

Scientific understanding of the neuroendocrine foundations of human social behavior has grown
substantially in recent decades. Methodological advances now allow for empirical research on
neuroendocrine contributors to both stable differences between individuals (e.g., personality traits)
and fluctuations within individuals (e.g., situational influences) in how social relationships are formed
and maintained. This chapter will provide an overview of recent research documenting the role of
(1) oxytocin and vasopressin; (2) estrogen, progesterone, and testosterone; and (3) cortisol on
romantic, parental, and friendship relationships in humans.
Keywords: social behavior, relationships, affiliation, hormones, peptides, steroids

Introduction Neuropeptides and Human Relationships

The desire to establish and maintain warm and The neuropeptides oxytocin (OT) and vasopressin
­intimate social bonds with other individuals is (AVP) have long been associated with bonding and
considered a basic human need (Baumeister & close relationships in animal research (reviewed in
Leary, 1995) and is typically referred to as the affili- Young, Gobrogge, Liu, & Wang, 2011), although
ation motive in the psychological literature (e.g., greater attention has typically been paid to OT
McClelland, 1987). According to Feldman (2012), (Carter, 1998, 2014). Synthesized primarily in the
affiliation hereby consists of two key aspects: On the preoptic and paraventricular nuclei of the hypo-
one hand, it refers to a close, selective interpersonal thalamus, OT and AVP are released peripherally
relationship, such as the bond between a parent and into the bloodstream via the pituitary and centrally
child (i.e., a parent–child relationship) or between via direct projections to a number of brain areas
two romantic partners (i.e., an intimate relation- ­involved in social cognition. The actions of OT are
ship); on the other hand, it refers to the processes exclusively mediated by a single oxytocin receptor,
or actions required to establish and maintain these which is ­expressed throughout the brain and body.
relationships, such as caregiving/nurturing, but also By contrast, there are three known cognate receptors
more general processes such as behavioral approach, for AVP, including two (the vasopressin receptors
emotion recognition, and trustworthy behavior 1a and 1b) that are expressed in the brain and a
toward others. Inspired by decades of research estab- third (the vasopressin receptor 2) that is primarily
lishing that the endocrine system is crucially involved ­expressed in the kidney and regulates renal function
in regulating social affiliation in nonhuman animals, (for reviews see Ebstein, Knafo, Mankuta, Chew, &
research has recently begun to address the rela- Lai, 2012; Feldman, Monakhov, Pratt, & Ebstein,
tionship between hormones and social affiliation 2016). This section discusses research linking
in humans (cf. McCall & Singer, 2012). OT and AVP to parental behavior and to romantic

259
relationships in humans, but first we begin with a controversy over extraction.1 Therefore, when
brief description of the methods most commonly ­discussing studies of peripheral OT, we will briefly
used to assess the functioning of the OT and AVP summarize the more abundant findings from studies
systems. measuring OT in unextracted samples before going
on to highlight findings using extracted samples
wherever these are available.
Oxytocin and Vasopressin Assessment
Methods Pharmacological manipulation of OT (and AVP). In
Peripheral assessment of OT and AVP. The interplay the past decade, research on oxytocin in humans has
of OT and AVP with close relationships in humans been greatly advanced by the widespread adoption
has most often been studied by assessing peripheral of intranasal oxytocin administration as a means of
levels of these hormones (i.e., in blood, saliva, or experimentally manipulating central OT levels under
urine). Of these peripheral pathways, human OT controlled laboratory settings. Various studies have
has been most commonly studied in plasma, which now documented, respectively, that increased levels
refers to the portion of blood that remains after an- of OT are detected in rhesus macaque cerebrospinal
ticoagulant agents have been removed. fluid (CSF) after intranasal administration (Chang,
Barter, Ebitz, Watson, & Platt, 2012), that the struc-
However, the literature on plasma OT has recently
turally similar neuropeptide AVP is detected in
been marked by controversy, with the most heated
human CSF after intranasal administration (Born
debate centering on extraction, a procedure that
et al., 2002), and, most recently and most rele-
aims to separate OT from the other proteins and
vantly, that OT levels in human CSF rise after intra-
molecules contained in the plasma (McCullough,
nasal administration of OT (Striepens et al., 2013).
Churchland, & Mendez, 2013). A thorough review
This method has now been combined with a wide
of the methodological details is beyond the scope of
array of tasks and measures targeting a variety of
the present chapter (see McCullough et al., 2013;
specific cognitions and behaviors (for broad reviews,
Robinson, Hazon, Lonergan, & Pomeroy, 2014;
see Bos, Panksepp, Bluthé, & van Honk, 2012;
Szeto et al., 2011), but the issue must be raised
Striepens, Kendrick, Maier, & Hurlemann, 2011).
­because the vast majority of research on close rela-
A similar approach has been used to study the
tionships and plasma OT has not used extraction
­effects of AVP, albeit to a much lesser extent (cf.
(reviewed later in the sections on “Oxytocin and
Bos et al., 2012). Although beyond the scope of
Human Parental Behavior” and “Oxytocin and
the present review, it should be noted that the ques-
Human Romantic Intimate Relationships”). Debate
tion of whether intranasally administered neuro-
on the topic is ongoing, and some have argued
peptides are able to cross the blood–brain barrier
that it is preferable to test unextracted OT because
continues to be debated (see Leng & Ludwig, 2016).
extraction removes a large portion of the oxytocin
Other critics note that larger sample sizes and a
that is present in plasma and other body fluids
greater emphasis on replication are needed (Walum,
(Carter, 2014; Carter et al., 2007). The critics are
Waldman, & Young, 2016), and it is hard to disa-
correct in noting that OT values obtained from
gree with these recommendations. These criticisms
unextracted plasma are typically 10- to 100-fold
notwithstanding, however, intranasal administra-
larger than those obtained from extracted plasma
tion remains as the best established method for
(McCullough et al., 2013), but this does not consti-
­experimentally manipulating levels of OT and AVP
tute evidence that assays on unextracted plasma are
in humans, so its use is likely to continue for the
invalid per se. Moreover, it is noteworthy that
foreseeable future.
­intranasal OT administration increases levels of OT
as measured using unextracted plasma (Weisman,
Zagoory-Sharon, & Feldman, 2012) and extracted
plasma (Domes et al., 2010; Gossen et al., 2012;
1
Additional methodological concerns have been raised
regarding between-study variation in the type of assay used
Striepens et al., 2013). Thus, OT measured from (radioimmunoassay vs. enzyme-linked immunoassay; Szeto et
unextracted plasma appears to bear some relation to al., 2011) and in the chemicals used as preservatives in the
actual levels of OT as manipulated by experimenters. tubes used to collect the plasma (lithium heparin vs. EDTA;
see Robinson et al., 2014). However, these factors do not
Nevertheless, it bears consideration that much of appear to affect the results as strongly as extraction, which has
the foundational research on the OT–relationships been the focus of the controversy and is the only factor
link is currently in doubt as a result of this ongoing considered here.

260 Endocrinology of Social Rel ationships and Affiliation

 The genetics of the OT-AVP system. Several candidate during interactions with their 6-month-old infants
genes in the OT-AVP system have been studied in (Gordon, Zagoory-Sharon, Leckman, & Feldman,
relation to close relationships in humans, and the 2010b). Further work found that plasma OT
focus in this review is on two genes that have been levels were positively correlated with the extent of
most extensively examined: the vasopressin receptor affectionate contact provided by mothers and fa-
1a gene (AVPR1A) and the oxytocin receptor gene thers during a 15-minute play period with their­
(OXTR; for reviews see Ebstein et al., 2012; Feldman 4- to 6-month-old infants (Apter-Levi, Zagoory-
et al., 2016). In view of the need for brevity, we Sharon, & Feldman, 2014). Parental interactions
do not discuss the influence of other genes here, with infants have also been associated with in-
but we note that research has begun to accumulate creases in OT relative to baseline, but this tendency
on the effects of variants in the gene encoding the appears to vary depending on individual differences
CD38 protein involved in OT secretion (Bartz & in the parent. Mothers providing high levels of
McInnes, 2007) on parental (Feldman et al., 2012) ­affectionate contact during an interaction with
and romantic relationships (Algoe & Way, 2014). their 4- to 6-month-old infant child showed in-
Additional work has investigated variants in the creases in plasma and salivary OT following the
genes encoding OT and AVP2 with respect to ­interaction, and fathers displaying higher levels of
­maternal behavior (e.g., Mileva-Seitz et al., 2013). stimulatory contact during the ­interaction showed
The research on parenting in relation to these similar elevations in plasma and salivary OT follow-
genes and to other genetic markers unrelated to the ing the interaction (Feldman, Gordon, Schneiderman,
OT-AVP system has recently been reviewed else- Weisman, & Zagoory-Sharon, 2010).
where (see Mileva-Seitz, Bakermans-Kranenburg,
Fewer studies have been published on OT in
& van IJzendoorn, 2016). Candidate gene studies
e­xtracted plasma and parental behavior, but one
and studies relying on individual single nucleotide
such study found that mothers with higher levels of
polymorphisms (SNPs) have been criticized for
separation anxiety and depression during pregnancy
being underpowered to detect effects that, when
had significantly lower plasma OT postpartum
present, are generally quite small. For this reason,
(Eapen et al., 2014). Another study using extracted
we focus on questions of sample size and replication
plasma did not report on associations with basal
in our coverage of this line of research.
levels of OT, but did find that a mother’s OT response
following exposure to her infant was significantly
associated with increased gaze toward the infant and
Oxytocin and Human Parental Behavior
decreased gaze away from the infant during a subse-
Peripheral OT and parental behavior. Studies of OT
quent interaction (Kim, Fonagy, Koos, Dorsett, &
in unextracted plasma have found increased levels in
Strathearn, 2014). Additional research using extracted
men and women who have recently become parents
plasma to replicate the myriad associations found
(Ulmer-Yaniv et al., 2016). Moreover, a series of
with unextracted plasma is greatly needed.
studies using behavioral coding of parent–infant
­interactions have found correlations of basal plasma Intranasal OT and parental behavior. In consonance
OT levels with affectionate parenting behavior with the findings from unextracted plasma, intranasal
in mothers (Feldman, Weller, Zagoory-Sharon, & OT infusion has been found to increase o­ bserver-rated
Levine, 2007; Gordon, Zagoory-Sharon, Leckman, parental sensitivity and warmth in fathers’ i­ nteractions
& Feldman, 2010a) and with stimulatory parenting with their children (Naber, Poslawsky, van IJzendoorn,
behavior in fathers (Gordon et al., 2010a). Subsequent van Engeland, & Bakermans-Kranenburg, 2013;
studies found that the latter two trends emerged for Naber, van IJzendoorn, Deschamps, van Engeland, &
measures of OT in unextracted saliva as well, but Bakermans-Kranenburg, 2010; Weisman et al.,
not for urinary OT (Feldman, Gordon, & Zagoory- 2012). However, OT administration to mothers
Sharon, 2011), and that plasma OT in fathers was with postnatal depression increased their self-reported
also associated with higher levels of father–infant intention to use a “harsh caregiving strategy” in
coordinated exploratory play and affect synchrony ­response to the sound of an infant crying (Mah, van
IJzendoorn, Out, Smith, & Bakermans-Kranenburg,
2017). A previous report from this group had indi-
2
The two genes, known by the symbols OXT and AVP, are
close to one another in the genome and are therefore best cated that postnatally depressed mothers reported
treated as a single locus. greater depressive symptoms following intranasal

Anderl, Saphire-Bernstein, and Chen 261

OT, but also that OT administration was associated well-conducted meta-analyses will be necessary before
with increased self-reported levels of bonding with the firm conclusions can be drawn regarding the influ-
infant (Mah, van IJzendoorn, Smith, & Bakermans- ence of rs53576 on human parenting behavior.
Kranenburg, 2013).
A number of additional SNPs in OXTR have
OXTR and parental behavior. One of the first been linked with parenting behavior. Feldman and
and most influential studies associating variants in colleagues (2012) found that two OXTR SNPs
OXTR with social behavior investigated the influ- were significantly associated with sensitive parenting
ence of the SNP rs53576 on sensitive mothering in (N = 272 mothers and fathers): a SNP in intron
a relatively small sample (N = 159; Bakermans- 3 named rs2254298 and a SNP in the 3-prime
Kranenburg & van IJzendoorn, 2008). These authors untranslated region of the gene named rs1042778.
reported a significant negative effect of the A allele Most recently, rs968389, a SNP in the first exon of
at rs53576 on sensitive mothering when entered OXTR, was also associated with observer-coded
into a simultaneous regression with the serotonin maternal warmth, as well as with extracted plasma
transporter gene–linked promoter repeat variant OT (Mehta et al., 2016). This variant is particularly
(entered on its own, there was a similar but marginal intriguing because of its location in a probable reg-
trend). Subsequent efforts to replicate this finding ulatory region for the gene, and because the authors
have been mixed. One study has replicated the provided functional validation by associating the
­association of the G allele of rs53576 with warm SNP with known regulatory elements and demon-
and sensitive parenting in a large sample of mothers strating a genotype-based difference in transcription
(N = 500), finding a significant additive effect of the levels of the gene. However, it must be noted that the
A allele such that A-allele homozygotes reported the sample in this study was relatively small (N = 127)
least maternal sensitivity, heterozygotes reported for a genetic association study.
intermediate levels of sensitivity, and G-allele homo-
zygotes reported the highest levels of sensitivity Oxytocin and Human Intimate
(Klahr, Klump, & Burt, 2015). This effect appeared Relationships
to be sex specific in the latter study (fathers were Peripheral OT and intimate relationships. In monog-
tested too, but there were no significant effects). amous prairie voles, OT has long been implicated in
Encouraging as this replication may be, it should be maternal behavior and partner preference formation
noted that the precise contrast used (additive effect (for reviews see Carter, 2014; Young et al., 2011).
of the A allele) was different from the one used in the In humans, however, research on OT in unex-
original study (A-allele carriers vs. G-allele homozy- tracted plasma has yielded seemingly contradictory
gotes), and the largest difference appeared to be ­results. On one hand, some researchers have r­ eported
­between A-allele homozygotes and G-allele carriers. that plasma OT levels are elevated in members
However, other studies have not replicated the effect of newly formed long-term romantic partnerships
of the G allele at rs53576 on sensitive parenting. In (Schneiderman, Zagoory-Sharon, Leckman, &
one study with a small sample (N = 35), the A-allele Feldman, 2012; Schneiderman, Kanat-Maymon,
homozygotes demonstrated the highest levels of Zagoory-Sharon, & Feldman, 2014), and one study
sensitive parenting (Michalska et al., 2014), whereas found that a relationship partner’s plasma OT levels
a second study with a larger sample (N > 700) found were correlated with the other partner’s degree of
nonsignificantly reduced levels of maternal sensitivity empathic behavior during a laboratory-based discus-
in A-allele homozygotes but nonsignificantly ele- sion of problems in the relationship (Schneiderman,
vated levels of maternal sensitivity in heterozygotes, Kanat-Maymon, Zagoory-Sharon, & Feldman,
relative to G-allele homozygotes (Cents et al., 2014). 2014). However, other research has found a seemingly
Lastly, a study with a sample of 201 mothers sug- contradictory pattern of results, such that levels of
gests that the effect of rs53576 may depend on the plasma OT were elevated in women whose relation-
social context; mothers who were G-allele homozy- ships were distressed (Taylor et al., 2006; Taylor,
gotes demonstrated the highest levels of maternal Saphire-Bernstein, & Seeman, 2010), and there was
sensitivity in the presence of low levels of interpa- no association between measures of relationship
rental conflict, but they showed the lowest levels of quality and plasma OT in men (Taylor et al., 2010).
maternal sensitivity in the presence of high levels In the latter study, the authors proposed that the
of interparental conflict (Sturge-Apple, Cicchetti, increased OT might serve to increase the motivation
Davies, & Suor, 2012). Additional research and to either repair the relationship or find a new one.

262 Endocrinology of Social Rel ationships and Affiliation

 α-amylase following couple conflict in male part-
Thus, OT might be an indication of the need for in female partners but increased levels of salivary
greater bonding, whether in the context of a newly

α-amylase in males was associated with increased

formed relationship (Schneiderman et al., 2012) or ners (Ditzen et al., 2013). This increase in salivary
in the context an established relationship that is no
longer as close and reliable as it might once have emotional arousal and positive behavior during the
been (as in Taylor et al., 2010). conflict discussion, whereas no such effects were
found in females. These two studies were the first
Recently, Grebe and colleagues (2017) sought to
to explore the possibility of using intranasal OT as
harmonize these findings by proposing the “identify
an adjunct to couples therapy, a possibility that is
and invest” model of OT, which posits that OT
worthy of additional, more extensive investigation
levels are elevated when important relationships are
(cf. Wudarczyk, Earp, Guastella, & Savulescu, 2013).
threatened or are in some way in need of attention.
The authors presented initial support for this theo- Another connection between OT and relation-
retical framework in two studies investigating levels ships that has recently been explored concerns the
of unextracted salivary OT. Changes in salivary OT operation of relationship maintenance ­mechanisms,
following the completion of a task in which partici- which are cognitive processes that serve to maintain
pants were asked to write down thoughts about their and enhance intimate relationships. In one study
romantic partner were positively correlated with the of men in long-term relationships, those given
extent of an individual’s commitment to the rela- ­intranasal OT preferred to maintain greater inter-
tionship, but they were negatively correlated with personal distance from a female experimenter (but
the individual’s perception of his or her partner’s not from a male experimenter), relative to partnered
commitment to the relationship. For more on this men given a placebo (Scheele et al., 2012). A second
research, see Grebe and Gangestad (this volume). study used an approach/avoidance paradigm (pushing
Studies measuring OT in extracted plasma and or pulling on a joystick in response to positive or
saliva have also found significant associations of negative stimuli, respectively) to show that partnered
plasma OT with measures of intimate relationship men given OT were slower to “approach” an image
quality (Holt-Lunstad, Birmingham, & Light, 2015; of an attractive alternative than were partnered
Smith et al., 2013; Turner, Altemus, Enos, Cooper, men given placebo. The authors interpreted these
& McGuiness, 1999). One of these studies reported ­behavioral indicators of avoidance following OT
significant positive correlations between relationship administration as arising from a relationship defense
quality and OT in plasma and saliva (Holt-Lunstad mechanism that guides committed individuals away
et al., 2015), whereas a second study found that OT from the threat to the relationship posed by attractive
levels in plasma were elevated in people with dis- alternatives. Subsequent work from this group has
tressed primary relationships (Turner et al., 1999), shown increased activation in the nucleus accum-
and a third study found a negative but nonsignifi- bens (a region of the brain primarily associated with
cant association between relationship quality and reward processing) when viewing images of one’s
plasma OT (Smith et al., 2013). partner’s face following intranasal OT relative to
Intranasal OT and intimate relationships. Two studies placebo both in partnered men (Scheele et al., 2013)
have assessed the ability of OT to reduce the nega- and in naturally cycling partnered women (but
tive consequences of intracouple conflict (Ditzen not in partnered women using hormonal contra-
et al., 2009, 2013). In the first of these, OT was given ceptives; Scheele, Plota, Stoffel-Wagner, Maier, &
to both members of a couple, followed by a “stand- Hurlemann, 2016). These latter findings suggest
ard instructed couple conflict discussion” (Ditzen that intranasal OT may also increase the tendency
et al., 2009). Relative to couples that received pla- for partnered individuals to enhance perceptions of
cebo, couples that received OT showed more positive their partners’ attractiveness and positive character-
communication behavior, relative to negative behav- istics. Other, similar work designed to investigate
ior, during the conflict discussion. In addition, the this question using a relationships memory para-
couples that received OT showed lower levels of digm did not find increased recall of positive (nor
cortisol following the conflict discussion. These decreased recall of negative) memories involving one’s
patterns were evident in both men and women. By partner, but did find that participants given OT
contrast, a second study using the same procedure ­recalled fewer positive memories of their past part-
found that intranasal OT was related to decreased ners (Cardoso, Kalogeropoulos, Brown, Orlando, &
levels of salivary α-amylase following couple conflict Ellenbogen, 2016). This might be construed as

Anderl, Saphire-Bernstein, and Chen 263

contributing to relationship maintenance by deval- child (Apter-Levi et al., 2014). Similarly, intranasal
uing previous romantic partners, but the results AVP administered to expectant fathers increased their
would be stronger if significant effects had also been interest (as indexed by viewing time) in baby-related
detected for memories of the current partner. Even avatars, relative to controls (Cohen-Bendahan, Beijers,
so, the totality of the evidence to date suggests that van Doornen, & de Weerth, 2015), although there
OT may support or enable the increased expression was no significant effect of intranasal OT on expect-
of both positive (partner-enhancing) and negative ant fathers’ interest in baby-related avatars.
(alternative-derogating) relationship maintenance
AVPR1A and parental behavior. A microsatellite
mechanisms.
marker3 known as RS3 has been associated with
OXTR and intimate relationships. Walum and measures of maternal behavior in a handful of stud-
­colleagues (2012) found an association between ies (Avinun, Ebstein, & Knafo, 2012; Bisceglia
the 3-prime-UTR-proximal SNP rs7632287 and et al., 2012; Leerkes, Su, Calkins, Henrich, &
partner bonding in an initial “discovery” sample Smolen, 2017). However, there is an impediment to
(N = 1,240), and the same SNP was also significantly integrating the findings across these studies owing
associated with a global measure of relationship qual- to inconsistencies in the approach to code RS3,
ity in a subsequent “replication” sample (N = 1,771). which can have 15 to 20 alleles in any given sample.
Carriers of the minor A allele reported lower levels Some researchers have zeroed in on specific alleles,
of partner bonding or relationship quality, relative particularly one known as 334, as prospective risk
to G-allele homozygotes. Other SNPs, including alleles (e.g., Avinun et al., 2012; Walum et al., 2008),
rs53576, rs2254298, and rs1042778, were not signif- whereas others have adopted a splitting approach
icantly associated with partner bonding in this study. to derive “short” and “long” alleles (e.g., Bisceglia
et al., 2012; Leerkes et al., 2016). Using the former
A second study on the role of OXTR in inti-
approach, Avinun and colleagues (2012; N = 135
mate relationships investigated the effects of five
mothers and their twins) found that mothers who
SNPs in the gene on communicative empathy
were carriers of the 334 allele demonstrated reduced
­between ­relationship partners (N = 60 couples)
maternal sensitivity during a laboratory-based “free
during the ­completion of a standardized laboratory
play” session with their 3.5-year-old children. Other
paradigm designed to study intimate relationships
studies have used the splitting approach, however,
(Schneiderman, Kanat-Maymon, Ebstein, &
finding in one case that mothers with two copies of
Feldman, 2014). Communicative empathy was
the long allele (which includes 334 in these studies)
rated by independent judges based on video record-
is associated with reduced maternal sensitivity
ings of participants’ behavior in a support-giving
(Bisceglia et al., 2012; N = 151 mothers) and in
interaction with their relationship partners. Possessing
­another case that long allele carriers engaged in less
more “risk” alleles across the five SNPs was signifi-
positive cognitive responses to infant crying, which
cantly correlated with less empathic communica-
in turn predicted lower levels of sensitive maternal
tion while supporting a relationship partner, both
behavior (Leerkes et al., 2016; N = 207 mothers).
in males and in females. However, rs1042778 was
Unfortunately, there is no legitimate basis for splitting
the only SNP that was significantly associated with
the continuously distributed RS3 marker, as there is
empathic communication in tests of single-marker
no functional evidence to support such a physiolog-
associations. Other research supports a role for
ical threshold. Moreover, the application of a gen-
rs1042778 in social relationships generally (Creswell
eral rule, such as “split allele groups at the median,”
et al., 2015) and, as noted earlier, in sensitive par-
may hamper the ability of scholars to compare
enting in particular (Feldman et al., 2012).
findings across samples with different medians and
therefore with different split points. Future stud-
Arginine Vasopressin and Parental
ies would be well advised to utilize the allele-wise
Relationships
approach instead of the questionable splitting
­
Peripheral and intranasal AVP and parental behavior.
­approach (cf. Walum et al., 2008).
Very little research has examined the relationship
between AVP and human parental behavior. Plasma
AVP was correlated with the extent of stimulatory
contact by both mothers and fathers during three-way 3
A microsatellite is a tract of repetitive DNA in which certain
family interactions including both parents and their DNA sequence motifs are repeated.

264 Endocrinology of Social Rel ationships and Affiliation

Arginine Vasopressin and Human Intimate of marital satisfaction. Further exploration of 334
Relationships allele carriers showed that they were significantly
Peripheral and intranasal AVP and intimate rela- more likely to be in unmarried cohabiting relation-
tionships. Peripheral AVP has been far less frequently ships rather than in marriages and that they were
studied, relative to peripheral OT, but a few investi- significantly more likely to be at risk for divorce.
gations have yielded suggestive findings. Taylor Importantly, the effects of the 334 allele were only
and colleagues (2010) found a positive correlation found to be significant for the male participants in
between plasma AVP levels and distress to men’s the study, whereas a similar pattern was tested but
primary pair-bond relationships. Interestingly, not found for the twins’ female partners, who were
these effects were not found in women, suggesting also typed in the investigation. This suggests that
that AVP may play a sex-specific role in influenc- the 334 allele may only influence the relationships
ing human reproductive strategies. Another study of male carriers, but not those of female carriers.
found that, in both men and women, plasma AVP
The only attempt to directly replicate the find-
levels were positively correlated with a self-report
ings of Walum et al. (2008) remains unpublished,
measure of social support received from one’s spouse
although preliminary results appear negative
and negatively correlated with the frequency of
(Jern, Westberg, & Walum, 2016; N=647 men).
negative social interactions with their spouse over
However, some degree of corroboration has been
the preceding month (Gouin et al., 2012). Both of
provided by an investigation into SNPs associated
these studies measured AVP in unextracted plasma,
with the prevalence of drug use disorders in a large
and so the criticisms reviewed earlier regarding the
case-control study (Maher et al., 2011). The authors
use of unextracted plasma in OT assessment may
typed a few hundred SNPs in and around several
well be applicable to the measurement of AVP (see
dozen preselected candidate genes in a discovery
McCullough et al., 2013). In general, the state of
sample of 359 males with substance use disorder
knowledge regarding the measurement of peripheral
and 138 male controls and found that several tightly
AVP is considerably less advanced by comparison
linked SNPs in the second exon of AVPR1A were
with the measurement of OT.
significantly associated with both drug use disorder
The literature on intranasal AVP remains simi- and a measure of relationship quality. The authors
larly underdeveloped in comparison to the literature then selected one of the tightly linked SNPs,
on intranasal OT. However, a pioneering study on rs11174811, and functionally validated it using bio-
military families struggling with posttraumatic stress informatics analyses, which showed that the SNP
disorder (PTSD) found that AVP administration affects the ability of certain micro-RNA molecules
improved the ability of the male partner to detect (miRNAs) to bind with the DNA at that particular
the female partner’s expressions of anger (i.e., they spot, thus reducing the ability of these miRNAs to
showed more rapid attentional engagement with interfere with the transcription of the gene. Finally,
their partner’s expressions of anger; Marshall, 2013). Maher and colleagues (2011) replicated the associa-
Whether the effect would extend to relationship tion of rs11174811 with drug use disorder in two
functioning more broadly or to populations not ­additional samples, and in one of these samples
characterized by PTSD remains to be determined. (N = 2,231 European American male twins) found
that the SNP was also associated with a measure of
AVPR1A and intimate relationships. The first doc- marital warmth (the other follow-up sample did not
umented association between a genetic variant measure relationship quality). This study is somewhat
and an aspect of human intimate relationships limited by the fact that it is difficult to infer the
­investigated the length of the microsatellite marker ­direction of the effects of rs11174811 on relationship
RS3 in a sample of 552 Swedish twins and tested quality in the two samples based on the information
whether carriers of any of the most frequently presented. Even so, this study strengthens the case
­observed alleles had significantly different scores on for AVPR1A as a candidate gene influencing the
measures of relationship quality, relative to noncar- quality of human intimate relationships.
riers of that particular allele (Walum et al., 2008). On a somewhat different note, Zietsch and col-
This study found that the 334 allele was associated leagues (Zietsch, Westberg, Santtila, & Jern, 2015)
with significantly lower scores on an ad hoc measure found nominally significant associations between
of partner bonding and on a well-established measure several SNPs in AVPR1A, including rs11174811, and

Anderl, Saphire-Bernstein, and Chen 265

extra-pair mating, defined as whether or not women brain, including limbic areas known to be crucially
in committed relationships reported having more involved in the regulation of social-affiliative behav-
than one sex partner during the course of the pre- ior such as the amygdala and the hippocampus
ceding year (the same association was not significant (see, e.g., Cushing, Perry, Musatov, Ogawa, &
in men in this study). Moreover, this study found Papademetriou, 2008; Hebbard, King, Malsbury,
that overall variation in AVPR1A was also signifi- & Harley, 2003).
cantly associated with extra-pair mating according
to a gene-based test. However, it should be noted Sex Hormone Assessment Methods
that the overall incidence of extra-pair mating in Most of the knowledge on the relationship between
this sample was relatively rare. Thus, while female sex steroid hormones and social-affiliative behavior
A-allele homozygotes at rs11174811 were relatively to date has been established in animal models, but
more likely to report extra-pair mating, the total methodological advances now allow for systematic
number of A-allele homozygotes in the sample was empirical research on this link directly in humans.
only 13 (out of an overall sample of 1,563 females), The three most commonly used methods to study
with 5 of those having engaged in extra-pair mating relationships between sex steroid hormones and social
(accounting for 5.4 percent of the 92 women behavior in humans are briefly introduced and dis-
reporting extra-pair mating) and the remaining
­ cussed in the following.
8 having not engaged in extra-pair mating (account-
Peripheral assessment of sex hormones. Sex steroid hor-
ing for only 0.5 percent of the 1,471 women who
mones can be measured peripherally via blood serum/
did not engage in extra-pair mating). Whether this
spots, saliva, or urine samples, thereby a­llowing
finding is related to the results of the study by
the examination of associations between endogenous
Maher and colleagues (2011) remains to be deter-
levels of these hormones and behavior. Peripheral
mined. No significant associations were found
assessment is widely used in the study of sex
­
­between the RS3 variant in AVPR1A and extra-pair
­hormone–behavior relationships and has led to great
mating in this study.
advances in understanding the role of sex steroid hor-
mones in social-affiliative behavior. Most commonly,
Sex Hormones and Human Relationships
this method is used to relate differences in baseline
Besides the neuropeptides oxytocin and vasopressin,
levels between individuals to stable interindividual
sex steroid hormones, that is, androgens (e.g., testos-
differences in social behavior at longer time scales
terone), estrogens (e.g., estradiol), and progestogens
(i.e., over weeks or months). However, peripheral
(e.g., progesterone), show associations with human
assessment also renders it possible to i­nvestigate
social behavior. Originally mainly discussed in the
associations between the reactivity (i.e., deflection
context of sexual maturation and the (physiological)
from baseline concentration after a hormone-eliciting
regulation of sexual behavior and pregnancy, a poten-
intervention; e.g., Carré, Campbell, Lozoya, Goetz,
tial bidirectional relationship between these hor-
& Welker, 2013; Welling, Moreau, Bird, Hansen, &
mones and the formation and maintenance of close
Carré, 2016) or natural fluctuations (e.g., during the
social bonds (especially intimate relationships and
menstrual cycle; see, e.g., Derntl, Kryspin-Exner,
parenting) and more general social-affiliative processes
Fernbach, Moser, & Habel, 2008) of a specific sex
has been increasingly recognized over the last decade.
steroid hormone with social behavior.
Sex steroid hormones are primarily released by
the gonads (i.e., testes in men and ovaries in Despite its multiple valuable applications for the
women) and to a lesser degree by adrenal glands; study of sex hormone–behavior associations, several
furthermore, they can be produced both centrally limitations and challenges should be kept in mind
and ­peripherally through conversion from precur- when planning or interpreting empirical studies
sor hormones. Whereas androgens, estrogens, and using peripheral hormone assessment (for more
progestogens are all present in both sexes, pro- detailed discussions of these challenges, see, e.g.,
nounced sex differences exist in the concentrations Granger, Shirtcliff, Booth, Kivlighan, & Schwartz,
of these hormones; androgen levels are higher in 2004; Shirtcliff, Granger, & Likos, 2002; Shirtcliff
men and estrogens and progestogens are higher in et al., 2000). For instance, although sex hormone
women (see, e.g., van Anders & Gray, 2007). Sex concentrations obtained with the different periph-
steroid hormone action occurs via binding to class- eral measurement methods (i.e., blood serum/spots,
specific receptors (i.e., androgen, estrogen, and pro- saliva, or urine samples) are correlated, they are not
gesterone receptors) that are widespread in the identical and the validity of these methods seems to

266 Endocrinology of Social Rel ationships and Affiliation

differ depending on sex (cf. Shirtcliff et al., 2002); that are characterized by different hormonal profiles
as a result, findings are sometimes hard to compare (with low estradiol and progesterone levels in the
between studies and sexes. Additionally, peripheral early follicular phase, high estradiol and low proges-
levels do not reflect the (regionally specific) availa- terone levels in the late follicular/ovulatory phase,
bility of the respective hormone in the brain, and and high estradiol and progesterone levels in the
individual differences in receptor sensitivity and midluteal phase), often combined with peripheral
(regionally specific) density are expected to moder- sex hormone assessment (e.g., Derntl et al., 2008)
ate hormone–behavior associations (cf. van Wingen or counting methods to estimate individual hormone
et al., 2008). Moreover, sex hormone levels are not levels on a single test day based on typical hormone
static, but are subject to substantial fluctuations due fluctuation patterns across the menstrual cycle (e.g.,
to biological rhythms (e.g., menstrual cycle, diurnal Anderl et al., 2015). All of these approaches have
patterns) and context dependence. Therefore, when their unique benefits and limitations. For instance,
investigating relationships between sex hormone within-subjects designs are typically preferable to
concentrations and stable interindividual differences between-subjects approaches as they take into
in behavior (e.g., personality traits), it is of crucial account interindividual differences in baseline
­
importance to thoroughly control for these factors. hormone levels and variability across the cycle.
Furthermore and most important, as natural hor- However, they are susceptible to memory and
mone levels are measured without direct experimental learning effects (and other effects related to repeated
manipulation, this method inevitably precludes causal testing), a problem that might be particularly pro-
conclusions about hormone–behavior effects. nounced in the social domain. Similarly, whereas
counting methods are more cost efficient than
Menstrual cycle variation in sex hormones. Another
methods involving actual hormone measurement
method that has become increasingly common in
and often less susceptible to belief or memory effects
the study of sex hormones and affiliation is exam-
than methods that require pretest determination of
ining social processes across the female menstrual
cycle phases or repeated testing, they are less accu-
cycle and relating it to the naturally occurring, sys-
rate due to high inter- and intrapersonal variability
tematic fluctuations in sex hormone levels. As this
in cycle lengths and therefore only recommended in
method provides a systematic and ecologically valid
large samples and/or in combination with an ovula-
way to investigate hormone–behavior relationships
tion test (cf. Gangestad et al., 2016). Importantly
within the same individual, it is often referred to
and independent of the particular approach used,
as a “natural experiment” (e.g., Eisenlohr-Moul,
whereas hormone–behavior associations across the
DeWall, Girdler, & Segerstrom, 2015). The natural
menstrual cycle may help to identify likely hormonal
hormonal variations observed across the cycle are
candidates driving these relationships, causal inter-
essential for reproduction, since sexual intercourse
pretations are generally not possible for findings
can only result in conception during a relatively short
from menstrual cycle studies because sex steroid
fertile time window around ovulation. Consequently,
hormonal levels are not experimentally manipulated
it has been suggested that natural selection may
with this method (for more detail on menstrual
have established cycle-related psychological adapta-
cycle effects, see Welling & Burriss, this volume).
tions that help to enhance reproductive fitness by
promoting behaviors that increase the likelihood of
Pharmacological manipulation of sex hormone action.
mating with males of high genetic quality during
It is possible to investigate the effects of androgens,
the fertile phase and/or support the fetus’s odds
estrogens, and progestogens on social-affiliative
of survival after conception/in the luteal phase
processes by manipulating the levels of these hor-
(e.g., Conway et al., 2007; Gangestad, Thornhill, &
mones in pharmacological experiments (typically
Garver-Apgar 2005). Therefore, from an evolution-
via exogenous sublingual or subcutaneous adminis-
ary psychology perspective, investigating behavioral
tration of the hormone itself, although several
fluctuations across the menstrual cycle is particu-
more advanced methods/combinations of methods
larly interesting.
have been introduced recently; see, e.g., Goetz et
Studies examining hormone–behavior associa- al., 2014). When appropriately applied in a (dou-
tions across the menstrual cycle have applied a ble-blind) placebo-controlled design, systematic
­variety of approaches. Common approaches include pharmacological manipulation is the only ­approach
between- and within-subjects designs comparing available for research in humans that allows for
behavior between phases of the menstrual cycle causal inference about how a specific hormone

Anderl, Saphire-Bernstein, and Chen 267

a­ ffects social behavior. Therefore, this approach is terone levels may r­eflect the strength of romantic
generally promising for the study of sex hormone commitment rather than regular direct contact
effects on social behavior and has been used over with a romantic partner. Interestingly, in the same
the last decade at least for testosterone (reviewed in study, women and men differed in this respect as
Bos et al., 2012). same-city partnered women had lower testoster-
one levels compared to both single women and
When interpreting findings from administration
women in long-distance r­elationships (van Anders &
studies, it should, however, be kept in mind that it
Watson, 2007).
presently remains unknown what proportion of
administered hormones in fact enters the brain/
Generally, findings regarding the relationship
specific brain areas of interest (cf. McCall & Singer,
between testosterone and intimate partnerships are
2012). Furthermore, administration studies induce
more mixed among women than in men: Whereas
relatively unnatural stimulations with regard to dosage
some studies suggest that relationship satisfaction
and dynamics of absorption, so it is currently unclear
and commitment are negatively related to testoster-
how the distribution of exogenously delivered
one in women (e.g., van Anders & Goldey, 2010),
hormones relates to their endogenous release and
others indicate that the association between tes-
whether some of the described effects for one hor-
tosterone levels and relationship status might be
mone may actually be generated by their metabo-
reversed in women, at least during the early stages of
lites rather than by the hormone itself (see, e.g.,
the relationship (e.g., Marazziti & Canale, 2004).
Bos et al., 2012).
Notably, recent studies provide first evidence for
dyadic associations between both partners’ testos-
Sex Hormones in Intimate Relationships
terone levels; in a study in romantic couples, relation-
Converging lines of empirical evidence suggest that
ship satisfaction and commitment were negatively
the role of sex steroid hormones for psychological
related to their partners’ testosterone concentra-
processes may go beyond their modulating role on
tions in both women and men, consistent with the
sexual motivation and behavior. In line with the
notion that high testosterone may be detrimental
theoretical assumption that there is an evolutionary
for maintenance of nurturing/close social relation-
trade-off between the amplifying effects of testoster-
ships (Edelstein, van Anders, Chopik, Goldey, &
one for “mating success” (i.e., the successful estab-
Wardecker, 2014).
lishment of sexual relationships) and its deleteri-
In sum, the available evidence supports the
ous effects on caregiving/nurturance, often referred
­assumption that there is a (negative) bidirectional
to as the challenge hypothesis (Wingfield, Hegner,
relationship between testosterone and commitment
Dufty, & Ball, 1990), research suggests that there
in intimate relationships, at least among men, in ac-
are bidirectional associations between testosterone
cordance with the challenge hypothesis. Interestingly,
and committed romantic relationships that may
in contrast to the substantial empirical evidence on
be sex dependent (for reviews see, e.g., Gray,
the association between the “male” sex hormone
McHale, & Carré, 2017; Roney & Gettler, 2015;
testosterone and romantic relationships, studies on
van Anders & Gray, 2007).
the relationship between the “female” sex hormones
Testosterone. Several cross-sectional studies show estradiol and progesterone and ­romantic commit-
that testosterone levels are lower in men who are ment are almost entirely lacking at present. There is
married or in a committed romantic relationship a clear need to address this topic in future research.
compared to men who are single; partnered men
with high testosterone have furthermore been found Sex Steroid Hormones in ParentalBehavior
to report lower relationship quality and to be more Testosterone. The challenge hypothesis posits that
likely to divorce compared to partnered men with there are also bidirectional links with testosterone
low testosterone (e.g., Booth & Dabbs, 1993; van levels and parental caregiving/nurturance. Evidence
Anders & Goldey, 2010). Importantly, a recent from a variety of species that exhibit high paternal
study comparing men and women who were single, investment in caregiving supports this notion
in a long-distance relationship, or in a same-city ­(reviewed in Saltzman & Ziegler, 2014). In humans,
­relationship found that single men had higher both mothers and fathers have been found to
­testosterone levels compared to both long-distance have lower testosterone levels than nonparents in
and same-city partnered men; this has been inter- cross-sectional comparisons, again in accordance
preted as evidence that differences in men’s testos- with findings on romantic relationships (e.g., Barrett

268 Endocrinology of Social Rel ationships and Affiliation

et al., 2013; Gray, Kahlenberg, Barrett, Lipson, & whereas it is reversed in situations that elicit chal-
Ellison, 2002; see also Boyette & Gettler, this lenge or threat.
volume). Importantly, two recent longitudinal inves-
Estradiol and progesterone. In addition to the empirical
tigations provided first evidence on the directional-
evidence relating parenting behavior to testoster-
ity of the observed relationship (i.e., the question
one levels, a number of studies suggest that both
whether men with lower testosterone levels are more
estradiol and progesterone might also play a role
likely to become fathers and/or whether fatherhood
in modulating parental behavior, even though the
suppresses testosterone levels). Specifically, in a large,
specific contributions of the particular hormones
representative study in Philippine men, single men
and effects of timing are not well understood at
with higher testosterone levels were more likely to
present. For instance, whereas the levels of these
become fathers within the following 4.5 years; after
hormones in expecting mothers were not related
transition to fatherhood, however, their testosterone
to feelings of attachment toward their child through-
levels decreased. These decreases in testosterone were
out pregnancy, the pattern of change in the ratio
furthermore substantially stronger in fathers who
of estradiol to progesterone from early to late preg-
interacted more regularly with their children (Gettler,
nancy was associated with feelings of attachment
McDade, Feranil, & Kuzawa, 2011). Correspondingly,
postpartum in a longitudinal investigation. In partic-
expectant U.S. fathers’ testosterone (and estradiol)
ular, mothers showing a more pronounced decline
levels were found to decrease throughout their part-
in the ratio of estradiol to progesterone (or of estra-
ner’s pregnancy, and larger declines in these hor-
diol levels) from pregnancy to the early postpartum
mones were associated with greater involvement in
period reported lower feelings of attachment toward
caregiving toward their child postpartum (Edelstein
their newborn child (Fleming, Ruble, Krieger, &
et al., 2017). Together, these findings support the
Wong, 1997). Furthermore, higher quality mater-
notion that higher testosterone levels may be bene-
nal behavior at one year postpartum was found to be
ficial for mating success but detrimental for care-
predicted by unique gestational profiles of estradiol,
giving. Thus, the decrease in testosterone levels
progesterone, and the estrogen-to-progesterone
typically observed in (expectant) fathers may serve
ratio throughout pregnancy in another longitudinal
as a proximate mechanism preparing men to provide
study (Glynn, Davis, Sandman, & Goldberg, 2016).
nurturant care for their infants, thereby ultimately
Thus, similar to testosterone, estradiol and proges-
increasing their chances of survival.
terone may play a role in modulating paternal
However, in apparent contrast to these findings,
­behavior. However, future research will be needed
studies on testosterone reactions to baby cries in
to better understand the contributions of each
men (Fleming, Corter, Stallings, & Steiner, 2002;
particular hormone and their interactions, as well as
Storey, Walsh, Quinton, & Wynne-Edwards, 2000)
the degree to which the observed effects are moder-
and on the effects of testosterone administration on
ated by timing (e.g., during different stages of preg-
the neural responses to baby cries in women (Bos,
nancy or postpartum).
Hermans, Montoya, Ramsey, & van Honk, 2010)
suggest that baby cries in fact increase parental
testosterone levels, which in turn seem to enhance Sex Hormones and General Social-
neural responsivity to the cries, putatively to pre- Affiliative Processes
pare for parental caregiving behavior. A recent study In addition to their putative role in regulating specific
may, however, help to resolve the apparent paradox: kinds of social relationships such as intimate and
van Anders, Tolman, and Volling (2012) found that parental partnerships, sex hormones may be involved
men’s testosterone levels only increased when they in modulating more general social processes or
were listening to infant cries when no caregiving motivational states that can facilitate or impede the
response was possible. In contrast, when put in a successful initiation and maintenance of close social
situation in which it was possible to show a nurturing relationships (without necessarily being considered
response, men’s testosterone levels in fact decreased to be “affiliation” or “bonding” hormones per se; see
in the presence of baby cries. This pattern of results Gangestad & Grebe, 2016). Indeed, there is increas-
has been interpreted in light of the steroid/peptide ing evidence from well-controlled laboratory studies
theory of social bonds (van Anders, Goldey, & that several general social processes that are known
Kuo, 2011), suggesting that the typically observed to be important for the formation and maintenance
negative association between testosterone levels and of close social bonds, such as social approach–
parenting in fact only holds for nurturant behavior, avoidance motivation, social cognitive and evaluative

Anderl, Saphire-Bernstein, and Chen 269

processes, and cooperative behavior, may be modu- studies over the last decade, less is known about
lated by sex steroid hormones in humans. the degree to which estradiol and progesterone are
involved in these processes. In fact, to our knowl-
Testosterone. Testosterone administration alters social
edge, no study has yet explored the effects of pro-
evaluations by both enhancing ratings of facial
gesterone and only one study has explored the
dominance and reducing ratings of other individ-
­effects of estradiol on social-affiliative processes in
uals’ facial trustworthiness in those who are high
a placebo-controlled administration study (Olsson
in dispositional trust (Bos, Terburg, & van Honk,
et al., 2016; reviewed in Bos et al., 2012). Regarding
2010; Olsson Kopsida, Sorjonen, & Savic, 2016).
estradiol, baseline levels of this hormone have been
Converging lines of evidence suggest that, at least
reported to be related to unique combinations of
in women, testosterone is involved in regulating
attachment style and intimacy motivation in both
social approach and avoidance tendencies (e.g., Enter,
women and men (Edelstein, Stanton, Henderson, &
Spinhoven, & Roelofs, 2014), reduces e­mpathic
Sanders, 2010), and attenuated estradiol responses
mimicry of emotional facial expressions (Hermans,
were observed in women with an avoidant attach-
Putman, & van Honk, 2006), and decreases the abil-
ment style (Edelstein, Kean, & Chopik, 2012).
ity to recognize emotions and infer mental states in
Furthermore, several recent studies suggest that
others (e.g., Olsson et al., 2016; van Honk et al., 2011;
women may be more demanding/less generous
for reviews, see Bos et al., 2012; Eisenegger, Haushofer,
toward others at times in their menstrual cycle when
& Fehr, 2011). In ­accordance with these findings,
estradiol levels are typically elevated, even though
a recent study provided initial evidence that lower
estradiol levels were not directly assessed in these
basal testosterone levels and decreases in testoster-
studies (e.g., Anderl et al., 2015; Eisenbruch &
one throughout a get-to-know-you task with a
Roney, 2016). Whether estradiol may indeed be
stranger were associated with increased closeness
involved in the regulation of intimacy motivation,
toward this stranger after the task (Ketay, Welker, &
interpersonal demandingness, and generosity, as
Slatcher, 2016).
these studies may indicate, should be addressed in
Findings from a study conducted in a large, future acute estradiol administration studies.
U.S. sample of middle-aged to older men further
Progesterone. Moreover, studies relating baseline pro-
suggest that men who feel emotionally supported by
gesterone levels/reactivity to social-affiliative be-
a greater number of individuals have lower testos-
havior, as well as studies observing social-affiliative
terone levels than men who report less emotional
behavior across the menstrual cycle, support the
support, independent of their marital and parenting
view that in addition to testosterone (and putatively
status (Gettler & Oka, 2016); this supports the
estradiol), progesterone may be involved in regulating
view that by lowering social cognitive abilities, tes-
processes relevant to the initiation and maintenance
tosterone might impede the maintenance of sup-
of close social bonds beyond parental (and potentially
portive social relationships. In contrast, however, a
romantic) relationships. In particular, several studies
recent study conducted among members of a male
have provided evidence that at least in women,
rugby team found that team members with higher
progesterone concentrations are elevated during or
endogenous testosterone levels were actually more
after a variety of situations presumed to increase
popular than team members with lower testosterone
affiliation arousal, including social inclusion, social
levels, at least when their cortisol levels were low
rejection, and intimate conversations (e.g., Brown
(Ponzi, Zilioli, Mehta, Maslov, & Watson, 2016).
et al., 2009; Seidel et al., 2013). Together with
These studies may indicate that testosterone levels
­evidence obtained across the menstrual cycle, these
and the successful establishment and maintenance
findings have been interpreted as suggesting that pro-
of social relationships are associated, but that the
gesterone may increase sensitivity to social informa-
direction of this link may be moderated by the
tion to help women consolidate their social support
specific social setting (e.g., a more or less compet-
networks during pregnancy, when progesterone levels
itive environment and/or a mixed-sex vs. purely
are high and support from others is particularly
male group).
needed (Maner & Miller, 2014). However, as noted
Estradiol. Whereas effects of testosterone on general by Gangestad and Grebe (2016), this interpretation
social-affiliative processes such as social cognition, may be challenged by the observation that even
evaluation, and motivation have been studied quite though increased support from others would still
intensively in placebo-controlled administration provide important fitness benefits postpartum,

270 Endocrinology of Social Rel ationships and Affiliation

l­ actating women’s progesterone levels are in fact low. time of day (cortisol exhibits a diurnal pattern,
Furthermore, the ability to recognize other individ- rising upon waking and then falling throughout the
uals’ facial emotions, which can be interpreted as an day). Especially when repeated measurements are
indicator of sensitivity to social information and is taken at different time points, this approach can
known to be highly relevant for successful social provide a profile of the individual’s chronic exposure
interactions, was in fact found to be negatively to cortisol in daily life. Chronic elevated exposure to
­associated with naturally fluctuating progesterone cortisol has been linked to tissue damage and dys-
levels across several studies (e.g., Derntl et al., 2008; regulation of biological systems (reviewed in Miller,
Derntl, Hack, Kryspin-Exner, & Habel, 2013). Chen, & Zhou, 2007). Like most chronic-assessment
Whereas these findings also support the idea that, methodologies, however, this approach is correla-
much like testosterone and potentially estradiol, tional and is thus limited in its ability to shed light
progesterone may be an important modulator of on causal pathways and directionality of effects. In
social-affiliative behavior, they might point to a more fact, most research in this domain assumes that psy-
complex relationship than previously assumed. Future chological events (e.g., trauma) precipitate broader
studies will therefore be needed to address the appar- changes in the chronic functioning and activation
ent inconsistencies in findings, ideally using a phar- patterns of the HPA axis, rather than the other
macological manipulation approach. way around (see Miller et al., 2007). Time-lagged
analyses can ameliorate the inherent limitations of
Cortisol and Human Relationships this approach to reveal evidence for the opposite
Cortisol is a steroid hormone released by the ­direction of causality (i.e., of cortisol on psychology).
­adrenal glands. It is typically released during the For example, cortisol levels can be measured at
mammalian stress response—commonly called the an earlier time point and used to predict social
“fight or flight” response. Physiologically, this outcomes at a later time point, while controlling
­response includes activation of the hypothalamic- for other variables.
pituitary-adrenal (HPA) axis, so named because it
Peripheral assessment of acute cortisol reactivity.
involves a cascade of hormonal messengers including
A second method for studying the effects of corti-
corticotropin-releasing hormone (CRH) by the
sol on human psychology involves laboratory-
hypothalamus, followed by adrenocorticotropic
based acute stress induction. The most widely used
hormone (ACTH) by the pituitary gland, and
lab-based psychosocial stress induction method is
­finally—as the primary end-product—cortisol by the
the Trier Social Stress Task (TSST; Kirschbaum,
adrenal glands. In addition to its numerous effects
Pirke, & Hellhammer, 1993), in which the partic-
on peripheral organs (e.g., influences on metabolic
ipant gives a speech in front of a panel of judges
and immune function), cortisol also exerts central
(see also Dickerson & Kemeny, 2004, for a review
effects by binding to glucocorticoid receptors that
of acute stress methodologies). The logic of the
are located throughout in the brain. Effects of cortisol
stress induction approach is to elicit a natural in-
on human memory processes have been widely doc-
crease in cortisol levels that can then be linked to
umented (reviewed in Het, Ramlow, & Wolf, 2005;
downstream consequences on cognition and be-
Wolf, 2009; see also Ervin & Choleris, this volume).
havior. As laboratory conditions can be kept highly
Of more direct relevance to this chapter, recent re-
standardized, this approach provides greater exper-
search has also begun to explore whether and how
imental control than daily assessment methods,
cortisol may influence social cognition and affilia-
though it sacrifices a degree of ecological validity.
tive behavior.
However, it does not provide a fully controlled
­experimental means of investigating the effects of
Cortisol Assessment Methods
cortisol on cognition and behavior. Stress precipi-
Three methods are commonly used to examine the
tates other physiological and psychological pro-
systematic effects of cortisol on human psychology.
cesses in addition to cortisol release, and these
Each of the methods has unique strengths and
­additional processes (e.g., release of CRH, ACTH,
weaknesses, reviewed briefly next.
oxytocin, and other hormones) may also contribute
Peripheral assessment of basal levels of cortisol. One to the downstream consequences of acute stress.
widely used cortisol assessment method involves Measuring and statistically controlling for such
assessing baseline levels of cortisol present in the ­additional processes can help to rule out alternate
periphery, typically using saliva, during a particular mechanisms of action.

Anderl, Saphire-Bernstein, and Chen 271

Pharmacological manipulation of cortisol action. A another large mixed-sex social network (a competi-
third methodology used to investigate the effects of tive collegiate marching band), higher cortisol levels
cortisol on psychological processes is exogenous near the beginning of an academic year in September
administration. Most commonly, cortisol is admin- were associated with greater turnover in friend-
istered orally through a caplet containing hydrocor- ship ties in the following two months (Kornienko,
tisone, at a dosage that will yield salivary cortisol Schaefer, Weren, Hill, & Granger, 2016). In con-
levels in the upper range of that obtained through trast, a study conducted on children aged 5 to 12 in
physical or psychological stress an hour after inges- a small rural village in Dominica revealed no
tion. This method provides greater experimental ­relationship between cortisol levels and children’s
control than diurnal assessment and stress induc- network size (Ponzi, Muehlenbein, Geary, & Flinn,
tion, as it is possible to administer an exact dosage 2016), though it is worth noting that the sample
in a placebo-controlled design. However, it is also size in this study (N = 40) was substantially smaller
less ecologically valid than the other methods (pre- than in the two studies that reported positive asso-
cisely because the exogenous cortisol is introduced ciations. However, findings regarding a relation-
artificially, or outside the typical context in which it ship between basal cortisol and network density
would be naturally released by the body), and simi- (i.e., the extent to which one’s friends are friends
lar concerns that have been discussed in the prior with each other) are equivocal, with the study con-
sections with respect to other hormones apply to ducted in Dominica suggesting that children with
cortisol as well (e.g., ambiguity regarding the pro- higher basal cortisol had lower network density
portion of administered hormones that in fact enter (Ponzi, Muehlenbein et al., 2016), whereas the
the brain/specific brain areas of interest, dynamics study with nursing students revealed a nonsignificant
of absorption). trend in the opposite direction (Kornienko, Clemans,
Out, & Granger, 2013). Overall, the social network
Effects of Cortisol on Social Relationships literature provides some initial evidence that higher
and Affiliation levels of basal cortisol are associated with lower
Here, we review research using all three cortisol assess- social activity and less stability in friendships. One
ment methodologies, operating under the assumption interpretation of these results is that high basal or
that converging evidence from the combination of chronic levels of cortisol may hinder social activity,
approaches—rather than any one singly—provides consistent with a study showing that in romanti-
a richer and more nuanced picture about the under- cally unattached young adults, higher basal cortisol
lying processes of interest. In contrast to emerging is linked to greater self-reported attachment anxiety
evidence about the social effects of oxytocin and tes- (Gordon et al., 2008).
tosterone, but similar to the current state of research
Cortisol, impulsivity, and risk taking. Although cortisol
on vasopressin, estradiol, and progesterone, there is
administration typically does not cause changes in
currently little evidence to suggest that the effects of
subjective affect or mood (Putman & Roelofs, 2011),
cortisol are specific to intimate or parental relation-
it has been linked to impulsivity and risk-taking
ships (and potentially friendships). Instead, the effects
behavior—particularly in men—in a number of
of cortisol on social cognition and social behavior
studies. In one study, young men who received a
seem to be broader and perhaps mediated by increased
pill containing 20 mg hydrocortisone showed im-
risk tolerance. Therefore, this section is primarily
paired performance after 45 minutes on the Cognitive
organized by the methodology used in the studies,
Reflection Test, responding in a less deliberative and
starting with relevant correlational studies and fol-
more intuitive (but incorrect) manner than men
lowed by experimental designs using stress induc-
who had received placebo (Margittai et al., 2016).
tion and exogenous administration methods.
In another study, young men showed a greater pref-
Cortisol and social network activity. A handful of erence to make risky choices with large potential pay-
studies suggest that basal levels of cortisol are associ- offs in a gambling task after receiving a 40-mg dose
ated with social activity and status within a social of hydrocortisone relative to when they received
network. For example, in a cohort of largely female a placebo (Putman, Antypa, Crysovergi, & van der
students in a competitive nursing program, higher Does, 2010). Men receiving 10 mg hydrocortisone
salivary cortisol levels were associated with less social made more impatient choices 15 minutes later in a
network activity (i.e., fewer self-reported friends; temporal discounting task relative to men receiving
Kornienko, Clemans, Out, & Granger, 2014). In placebo (the effect was not seen after 195 minutes;

272 Endocrinology of Social Rel ationships and Affiliation

Cornelisse, van Ast, Haushofer, Seinstra, & Joels, particular may have promoted the development of
2013). Men and women who showed a robust cor- a response to stress that contrasts with fight or
tisol response to the TSST showed greater risk seek- flight—namely, the tendency to “tend and befriend.”
ing for gains in an economic decision-making task This theory suggests that women might be more
than participants who did not undergo the stressor inclined than men to engage in protective behaviors
or who did not show a robust cortisol response to it toward offspring (“tend”) and assistance seeking
(Buckert, Schwieren, Kudielka, & Fiebach, 2014). (“befriend”) when faced with threat. This pattern of
In both men and women, 20 mg of hydrocortisone affiliative behavior is assumed to have evolved as
decreased the acoustic startle response (Buchanan, an effective strategy to protect offspring and one-
Brechtel, Sollers, & Lovallo, 2001); indeed, one self from harm, thereby increasing the likelihood
possible mechanism through which cortisol is thought of survival.
to increase risk taking is by reducing fear and anxi-
A classic series of studies (Schachter, 1959) doc-
ety (Soravia et al., 2006).
umented women’s tendency to affiliate when stressed
Cortisol and sensitivity to social threat. The research (demonstrated by a preference to sit in proximity
reviewed previously suggests that cortisol may with strangers while anticipating an experiment that
reduce fear and promote greater risk taking. How was described as involving electric shocks). More
might these cognitive and emotional shifts play out recent research has demonstrated that healthy men
in the domain of social cognition? A small number show a greater tendency to engage in prosocial
of studies have tested participants’ response to ­behavior (trust, trustworthiness, and sharing) after
social stimuli (e.g., photos of emotional faces) after undergoing the TSST (von Dawans, Fischbacher,
administration of cortisol. Two studies using different Kirschbaum, Fehr, & Heinrichs, 2012). Men who
methodologies suggest that cortisol administration ­release more cortisol in response to the TSST subse-
diminishes preconscious attention to threatening quently report greater feelings of closeness with a
social information in the form of faces displaying stranger after a get-to-know-you task (Berger,
angry or fearful expressions (Putman, Hermans, Heinrichs, von Dawans, Way, & Chen, 2016). There
Koppeschaar, van Schijndel, & van Honk, 2007; may, however, be sex differences in how TSST-
van Peer, Spinhoven, & Roelofs, 2010). In both male induced cortisol elevations are linked to social cogni-
and female participants, cortisol administration tion (Smeets, Dziobek, & Wolf, 2009). Specifically,
was associated with decreased neural responses to there is a positive correlation between the amount
angry faces (but also faster reactions to all facial of stress-induced cortisol release and subsequent
expressions after being provoked in an aggression performance on a mindreading task (involving in-
induction paradigm; Bertsch, Böhnke, Kruk, ferring the mental states of characters in a film)
Richter, & Naumann, 2011). In general, cortisol among men, whereas women demonstrate the op-
may reduce sensitivity to social threat, which may posite pattern.
in turn either promote aggression (Böhnke, Bertsch, Open questions. In sum, recent research provides
Kruk, Richter, & Naumann, 2010) or—in contrast— some evidence that cortisol release may promote
promote affiliative tendencies. ­behavioral patterns of response to stress that could
Cortisol and “tend and befriend” psychology. Research be characterized as consistent with fight or flight or
on the effects of cortisol in the social domain suggests tend and befriend. The unifying link between these
that it may promote either aggression or affiliation two apparently opposing patterns of response may
(see Mogilski et al., this volume), raising the ques- be the connection between the presence of cortisol
tion of when, and for whom, these contrasting and a higher general tolerance for risk. It is possible
effects might be more likely. Traditionally, the
­ that in the social domain, presence of cortisol may
HPA axis response to acute stress has been described encourage a disinhibition of social fears that can
as a psychological mechanism that prepares the promote either aggression or social approach depend-
organism to mobilize a rapid response to a threat ing on the specific circumstances. Although sex dif-
(i.e., the fight-or-flight response; Cannon, 1932). ferences in these domains have been documented,
Behaviorally, this response can be characterized the evidence reviewed here also suggests that fight-
by aggression toward, or defensive withdrawal from, or-flight and tend-and-befriend responses to stress
the source of the stress. Taylor et al. (2000) pro- are both readily available as part of the repertoire of
posed that evolutionary pressures on women in men and women. More research incorporating both

Anderl, Saphire-Bernstein, and Chen 273

male and female participants will be necessary to majority of studies investigating possible uni- or
­examine the conditions that tend to elicit these di- bidirectional links between hormones and social-
vergent responses and shed light on remaining open affiliative processes have focused on the neuropeptide
questions about sex differences in this domain. Also, oxytocin and the sex hormone testosterone, whereas
more work will be necessary to disentangle the evidence on potential associations between vaso-
broader effects of stress (and the entire suite of phys- pressin, estradiol, progesterone, and cortisol with
iological changes that accompany it) versus the more social-affiliative processes remains scarce and clearly
specific effects of cortisol. Some studies showing an needs further study.
effect of acute stress on cognition or ­behavior report Although we have mainly highlighted research
no correlation between the magnitude of observed focusing on each hormone in isolation, a multiple-
cognitive or behavioral response and the magnitude hormone integrative approach is ultimately needed,
of the cortisol response. In these cases, it is possible despite the many challenges standing in the way of
that a different ­mechanism of action besides cortisol a more complete integration of these disparate strands
secretion is responsible for the reported changes in of endocrinological findings. As hormonal systems
cognition or behavior. Another possibility is that some are highly interdependent, an important direction
effects of cortisol are dichotomous in nature (i.e., for future research will be to systematically assess,
occurring at a certain threshold of cortisol release, or manipulate, hormone levels in combination,
which is typically passed in the context of an exper- for example, cortisol and oxytocin (e.g., Heinrichs,
imentally induced stressor). A combination of Baumgartner, Kirschbaum, & Ehlert, 2003; see also
methods, for example comparing the effects of stress- Taylor et al., 2000, for discussion about the possible
induced cortisol secretion versus exogenous admin- role of oxytocin in affiliative responses to stress),
istration of cortisol within the same samples and cortisol and testosterone (e.g., Coates & Herbert,
using the same designs, may be necessary to shed 2008; Sherman, Lerner, Josephs, Renshon, &
light on this issue. Gross, 2016), oxytocin and testosterone (van Anders
et al., 2011), cortisol and estradiol (Tackett et al.,
Furthermore, more research that systematically
2015), and estradiol and progesterone (e.g., Derntl
manipulates the timing of cortisol administration
et al., 2008).
and the subsequent assessment of social responses
Future research might furthermore benefit from
will be necessary to reconcile some of the results
measuring or manipulating hormone levels in com-
that have been documented. Given that cortisol is
bination with assessing hormone receptor genes
the primary end product of the HPA response and
(see, e.g., Chen et al., 2015, for OXTR combined
is part of an inhibitory feedback loop that blocks
with intranasal OT administration; for the andro-
the secretion of CRH, high levels of cortisol may
gen receptor gene [AR] CAGn repeat polymorphism
initially indicate a heightened stress response yet
and salivary testosterone levels, see Eisenegger,
also suggest a more efficient “shutdown” of the
Kumsta, Naef, Gromoll, & Heinrichs, 2017; Roney,
same response after a time lag. Just as the effects of
Simmons, & Lukaszewski, 2010). A combined
cortisol on memory seem to vary substantially
approach may not only help to resolve apparent
­depending on whether the cortisol administration
inconsistencies between earlier findings but also help
occurs before or after memory encoding (see Het et
to address which of the effects observed after acute
al., 2005), the effects of cortisol on social cognition
hormone administration are in fact caused by the
and behavior may vary substantially depending on
hormone itself as opposed to their metabolites (cf.
the social context and timing of administration.
Eisenegger et al., 2011; van Wingen, Ossewaarde,
Another potentially productive avenue for research
Bäckström, Hermans, & Fernández, 2011).
in this domain may be to systematically vary the
Moreover, existing research does not always sug-
context (social vs. nonsocial) to determine the spec-
gest a direct correspondence between the cognitive
ificity of some of the effects of cortisol.
or behavioral effects of chronically elevated hormone
levels and the effects of a single dose or a naturally
Conclusions and Future Directions elicited deflection of the same hormone. For exam-
Together, the evidence presented in this chapter ple, one study suggested that exogenous cortisol
indicates that the endocrine system is crucially enhances aggressive behavior in women, whereas basal
­involved in regulating human social-affiliative pro- cortisol was negatively associated with aggressive
cesses, thereby contributing to the initiation and behavior in women (Böhnke et al., 2010). It is likely
maintenance of close social bonds. At present, the that acute and chronic processes have different

274 Endocrinology of Social Rel ationships and Affiliation

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actions) may help to shed light on these differences. of human behavior: Effects of prenatal and pubertal
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that hormones can regulate behavior not only by Berger, J., Heinrichs, M., von Dawans, B., Way, B., & Chen,
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280 Endocrinology of Social Rel ationships and Affiliation

 CH A PT E R

16 Hierarchy and Testosterone

How Can Testosterone Promote Upward Mobility in Status Hierarchies?

Shawn N. Geniole and Justin M. Carré

Abstract

Hierarchy, the relative ranking of individuals with respect to status or other social dimensions, is
ubiquitous across human social groups. However, relatively little is known about the biological factors
that may promote or inhibit mobility in status hierarchies. Prominent theoretic perspectives suggest
that concentrations of testosterone in the bloodstream fluctuate dynamically in anticipation of and
in response to social challenges, serving to promote behaviors aimed at gaining/maintaining status.
This chapter reviews studies that have directly examined the extent to which endogenous, competition-
induced surges in testosterone predicted subsequent competitiveness and aggressiveness. Studies
suggest that testosterone surges promote competitiveness, but that this effect is complex and
depends on several factors. More consistent was evidence that testosterone surges predicted
subsequent aggressive behavior. Testosterone–behavior links were also specific to men, suggesting
that surges in this hormone may serve different functions, or may promote alternative behavioral
strategies for gaining and maintaining status, in women.
Keywords: dominance, aggression, testosterone, hierarchy, status

Hierarchy, defined as the ranking of individuals other, less hierarchically organized, groups (reviewed
relative to one another on status or other social in Van Vugt et al., 2008; there may be limits to
dimensions (Magee & Galinsky, 2008), is ubiquitous such benefits, however—e.g., see Anderson &
across human social groups (Mazur, 2015), present Willer, 2014). Hierarchy influences many aspects of
even in the smallest, least complex, most isolated social life (e.g., conflict resolution, resource allocation,
of human societies (Diamond, 1999; van Vugt, and mating, reviewed in Cheng, Tracy, Foulsham,
Hogan, & Kaiser, 2008), as well as in groups of Kingstone, & Henrich, 2013), and gaining high
children as young as 3 years (Boyce, 2004; Strayer & status within a hierarchy improves subjective well-­
Strayer, 1976; Thomsen, Frankenhuis, Ingold- being (Anderson, Kraus, Galinsky, & Keltner, 2012),
Smith, & Carey, 2011). The prominence of hierarchy access to valued or scarce resources, and health
in human social systems has been attributed to the (Ellis, 1994). In short, hierarchy is ubiquitous across
benefits it may provide for group functioning social groups, emerges spontaneously, and influences
(Darwin, 1871; van Vugt et al., 2008). For example, the way we think, feel, and interact with each other.
hierarchy promotes cooperative goal attainment by Although the pursuit of status is considered a fun-
reducing intragroup conflict (e.g., Ronay, Greenaway, damental human motivation (Anderson, Hildreth, &
Anicich, & Galinsky, 2012) and enhancing coordi- Howland, 2015; Griskevicius & Kenrick, 2013;
nation when there are conflicting goals within the Mazur & Booth, 1998), likely because of the afore-
group (e.g., De Kwaadsteniet & Van Dijk, 2010). mentioned benefits that it confers, little is known
Further, groups that are structured with a clearer hier- about the situational and individual difference fac-
archy and chain of command tend to outperform tors that influence upward mobility within status

281
hierarchies. One factor that may be particularly trations rise and fall in response to cues of social
relevant to the pursuit of status is an individual’s challenge and threat in the environment, preparing
circulating testosterone levels in the bloodstream the organism for aggressive encounters over resources
(Carré & Olmstead, 2015; Eisenegger, Haushofer, & important for reproduction and status (e.g., mates,
Fehr, 2011; Hamilton, Carré, Mehta, Olmstead, & territory). This model was proposed to explain fluc-
Whitaker, 2015; Knight & Mehta, 2014; Mazur, tuations in testosterone levels in birds but has since
2015).1 Testosterone is the most frequently investi- been applied to humans (Archer, 2006). The model
gated hormone in status-related research (Hamilton posits that testosterone concentrations rise from a
et al., 2015; Knight & Mehta, 2014) and has been low baseline (nonbreeding baseline) to a higher base-
psychometrically validated as a biological, individ- line for the breeding season (breeding baseline), an
ual difference variable in humans (Sellers, Mehl, & increase that functions to promote spermatogenesis,
Josephs, 2007) that may represent one’s motivation the development of secondary sexual traits, and repro-
to gain and maintain status (reviewed in Eisenegger ductive behavior (an increase akin to the male puber-
et al., 2011; Hamilton et al., 2015; Josephs, Sellers, tal surge in testosterone in humans; Archer, 2006),
Newman, & Mehta, 2006; Knight & Mehta, 2014; but not aggression. More important for antagonistic
Mazur & Booth, 1998).2 contests, however, concentrations of testosterone
also surge from this breeding baseline to a higher,
The Challenge Hypothesis and the Biosocial physiological maximum, promoting the expression of
Model of Status aggressive behavior, which functions to secure mates
The two most prominent theoretical perspectives and territory important for breeding. Relevantly,
that guide most research on testosterone and status- these fluctuations are thought to support most aggres-
related behaviors are the challenge hypothesis and sion that serves these goals (acquisition and protec-
the biosocial model of status. According to the chal- tion of resources or status valuable for mating)
lenge hypothesis (Wingfield, 2012, 2017; Wingfield, specifically, rather than other goals (e.g., predator
Hegner, Dufty, & Ball, 1990), testosterone concen- deterrence). These effects of testosterone surges on
reproductive aggression are posited to be strongest
1
The system responsible for the regulation of testosterone for monogamous (vs. polygamous) birds during peri-
secretion is the hypothalamic-pituitary-gonadal (HPG) axis. ods of social instability, such as when social hierar-
When gonadotropin-releasing hormone is secreted from the
hypothalamus, it stimulates the pituitary gland, which in turn chies, mates, or territories important for mating are
secretes luteinizing and follicle-stimulating hormones. These being established or challenged by conspecifics. After
hormones then function to stimulate the release of testosterone the breeding season, testosterone concentrations drop
from the gonads (Vadakkadath Meethal & Atwood, 2005). Once
back down to the nonbreeding baseline (a decline that
released, testosterone binds to androgen receptors either directly
or indirectly through its conversion to dihydrotestosterone by may be akin to the age-related declines seen in older
the enzyme 5-α reductase (Askew, Gampe, Stanley, Faggart, & adulthood in humans; e.g., Harman, Metter, Tobin,
Wilson, 2007). Testosterone can also be converted into estradiol Pearson, & Blackman, 2001). This flexibility in
by the aromatase enzyme, after which it can bind to estrogen
receptors (Ronde & Jong, 2011). Once circulating in the
testosterone is thought to exist in monogamous birds
bloodstream, testosterone and its metabolites bind to receptors because of trade-offs associated with testosterone;
of target cells to influence gene transcription. Testosterone and its whereas high levels increase aggressiveness (important
metabolites can also bind to receptors on the hypothalamus and the for securing mates and thus repro­ducing), they
pituitary, acting as a negative feedback loop and suppressing the
release of luteinizing and follicle-stimulating hormones (Hayes,
also decrease parental care (Wingfield et al., 1990)
Decruz, Seminara, Boepple, & Crowley, 2001), and ultimately and immune system function (see, e.g., Folstad &
regulating the secretion of testosterone. Karter, 2011).
2
A strength of investigating status-related motives through The challenge hypothesis has been applied to
testosterone rather than self-report questionnaires is that such
questionnaires are often prone to response biases (e.g., socially
many species (see meta-analysis and review in
desirable responding; Johnson, Leedom, & Muhtadie, 2012), Hirschenhauser & Oliveira, 2006), including non-
whereas the investigation of status-related motivations through human primates (e.g., Muller & Wrangham, 2004)
testosterone (assessed via saliva or blood sampling) precludes and humans (see review and meta-analyses in
such biases. Additionally, because the strength of one’s motivation
to gain and maintain status can vary from situation to situation Archer, 2006; see also Carré & Olmstead, 2015).
and also, in some circumstances, operate outside of conscious When applied to humans, one prediction derived
awareness (e.g., see Schultheiss, Dargel, & Rohde, 2003; from the challenge hypothesis is that situational
Terburg, Aarts, & Van Honk, 2012), testosterone concentrations,
cues of competition, especially those related to
which fluctuate dynamically throughout the day, may be better
suited to the measurement of these motivations than self-report mating or status, should trigger a surge in testoster-
questionnaires (see Josephs et al., 2006). one (Archer, 2006). Most studies have not examined

282 Hierarchy and Testosterone

this research question within the context of mating, driven by winners showing a significant increase in
but instead examine anticipatory surges in testoster- testosterone (mean weighted d = 0.21) and losers show-
one that occur before the start of a competition. In a ing no meaningful changes (mean weighted d = 0.01).
review and meta-analysis of such anticipation effects, In women, winners and losers showed divergent
Archer (2006) reported significant increases in testos- changes, with winners slightly increasing (mean
terone leading up to competitions (after removal of weighted d = 0.10) and losers slightly decreasing
two outliers, mean weighted d = 0.27), which became (mean weighted d = –0.12). Therefore, the winner–
slightly stronger (mean weighted d = 0.30) when loser effect in men is driven by pre–post increases in
including only studies that involved actual sports con- winners and negligible changes in losers, whereas in
tests (rather than contrived laboratory tasks). More women it is driven by divergent (albeit weaker)
recent studies not captured by this meta-analysis also changes, with winners increasing and losers decreas-
provide some support for an anticipation effect, show- ing. It was also discovered that this winner–loser effect
ing that prematch testosterone concentrations are was strongest in studies conducted in the field, rather
higher than are prepractice or control day concentra- than in the lab, possibly because the outcomes of
tions (e.g., in male basketball players, Arruda, competitions in the field are more meaningful and
Aoki, Carolina, & Moreira, 2017; male rugby salient to athletes/participants than are those in con-
players, Cunniffe, Morgan, Baker, Cardinale, & trived laboratory tasks (Geniole, Bird, et al., 2017).
Davies, 2015; in female soccer players, there is an Other moderators not examined in the meta-analy-
effect in some cases, e.g., T. Oliveira, Gouveia, & sis but that are likely important and account for
Oliveira, 2009, but not others, e.g., Casto & some of the heterogeneity include one’s implicit
Edwards, 2016a). power motives (e.g., Schultheiss et al., 2005;
Another prominent model is the biosocial model Schultheiss, Campbell, & McClelland, 1999;
of status (Mazur, 1985, 2015; Mazur & Booth, 1998). Vongas & Al Hajj, 2017), self-construal (Welker
In addition to the anticipation effects outlined pre- et al., 2017), anxiety (although evidence is mixed:
viously in the challenge hypothesis, the biosocial see Maner, Miller, Schmidt, & Eckel, 2008 vs.
model of status posits that concentrations of testos- Norman, Moreau, Welker, & Carré, 2014), concen-
terone fluctuate in response to the outcomes (win trations of other hormones (e.g., cortisol, Zilioli &
vs. loss) of competitive interactions such that winners Watson, 2012), whether the opponents are friends
experience increases in testosterone, promoting future or members of an out-group (e.g., Flinn, Ponzi, &
aggressive and assertive behaviors aimed at gaining Muehlenbein, 2012), whether the outcome is
and maintaining status, whereas losers experience ­attributed to skill versus luck (e.g., van Anders &
decreases, promoting future deferent and submissive Watson, 2007), and whether the victory was close or
behaviors aimed at avoiding further injury and/or decisive (e.g., Zilioli, Mehta, & Watson, 2014; see
loss of status. Consistent with this idea, an earlier also Wu, Eisenegger, Zilioli, Watson, & Clark, 2017;
meta-analysis provided some evidence that winners of reviewed in G. A. Oliveira & Oliveira, 2014).
competitive interactions experience greater increases
in testosterone than do losers (mean weighted ds The Function of Competition-Induced
ranged from 0.31 to 0.36, depending on the inclusion Surges in Testosterone
or exclusion of an outlier, Archer, 2006; for additional An additional prediction that can be derived from
reviews of this literature, see Carré & Olmstead, 2015; the biosocial model of status is that competition-
G. A. Oliveira & Oliveira, 2014). More recently, induced fluctuations in testosterone play a functional
Geniole, Bird, Ruddick, and Carré (2017) conducted role in promoting subsequent behaviors aimed at
an updated meta-analysis on 60 different effect sizes gaining and maintaining status. The challenge
examining these potential winner–loser differences in ­hypothesis also posits that such fluctuations should
testosterone. In short, they found that winners experi- promote male-to-male aggression aimed at securing
enced greater increases (or lesser decreases) in testos- mates and territory important for mating. Neverthe­
terone than did losers from pre- to postcompetition, less, this aspect of these models—that competition-
an effect that was of similar magnitude for men (mean induced fluctuations in testosterone should function
weighted d = 0.23) and for women (mean weighted to promote behaviors that help the organism secure
d = 0.22). The nature of these differences was also mates and status (e.g., competitiveness and aggres-
characterized by examining the specific direction of sion)—was not often investigated in earlier studies
the pre- to postcompetition changes in winners and in humans (Archer, 2006; Carré, McCormick, &
losers separately. In men, this winner–loser effect was Hariri, 2011). Instead, most of the earlier work on

Geniole and Carré 283

testosterone and aggression focused on baseline or approach is to measure surges in testosterone and
resting-level concentrations of the hormone, which determine if these surges predict future behavior
share rather weak associations with aggression (r = on subsequent tasks. Although this approach does
0.08 in meta-analysis by Archer, Graham-Kevan, & not solve the third variable problem—that another
Davies, 2005). Based on the hypothesis that testoster- variable may be causing both the increase in tes-
one surges function to promote upward mobility in tosterone and the subsequent competitiveness or
status hierarchies (or the maintenance of high-status aggressiveness—the temporal ordering of the meas-
positions), we would predict that fluctuations in ures provides some reassurance that the subsequent,
concentrations of this hormone drive a variety of future behavior did not cause the preceding surge in
subsequently measured behaviors and decisions testosterone. Here, we review evidence from studies
that are important for climbing status hierarchies. that used such designs.
According to the dual-strategies theory, there are
two primary routes through which people can gain Do Competition-Induced Surges in
and maintain their standings in a social hierarchy Testosterone Predict Subsequent Decisions
(Cheng et al., 2013; Henrich & Gil-White, 2001; to Compete?
for recent review, see Case & Maner, 2016): through The first investigation of the relationship between
dominance, which involves intimidation, coercion, testosterone fluctuations and subsequent behavior in
and aggression and functions by eliciting fear and humans involved a laboratory competition in which
deference in others; and through prestige, which participants’ outcomes (win vs. loss) were predeter-
involves the use of skills or knowledge critical for mined through random assignment (Mehta &
group advancement and success and functions by Josephs, 2006). The researchers had participants
helping the individual gain respect and admiration compete against one another in a number-tracing
from others. Given the centrality of competition to task. To rig the outcomes of the competition, the
both the biosocial model of status and the challenge researchers gave half of the participants an easy ver-
hypothesis, and the importance of aggression in the sion of the task (win condition) and the other half of
challenge hypothesis, here we focus on the extent to participants a difficult version of the task (loss condi-
which testosterone surges motivate competitiveness tion) such that, in each testing session, one partici-
and aggressiveness, behaviors more consistent with pant of the competition was likely to lose and the
the first route to high status: dominance.3 other was likely to win. Testosterone concentrations
We also focus, primarily, on studies involving were determined through saliva samples obtained
natural, endogenous fluctuations in testosterone, before and after the competitive task. After the task
rather than studies employing pharmacological and postcompetition saliva sample, participants
manipulations that modulate testosterone experimen- were asked if they wished to compete again against
tally (for reviews of studies that employed pharma- the same participant (competitive choice) or to com-
cological manipulations, see Bos, Panksepp, Bluthé, plete an unrelated questionnaire (noncompetitive
& van Honk, 2012; for a recent review of literature choice). If testosterone surges function to promote
on endogenous and exogenous testosterone, see status-related behaviors (e.g., competitiveness aimed
Zilioli & Bird, 2017). at gaining additional status), then changes in testos-
terone throughout the task should predict one’s
Endogenous Testosterone Surges willingness to compete in a second task. The results
One limitation to this research on endogenous fluc- were partially consistent with this prediction: Changes
tuations in testosterone and competition and aggres- in testosterone predicted the subsequent decision to
sion is that because testosterone and behavior are compete again against the competitor, but only
proposed to share reciprocal links (i.e., surges in tes- among the participants randomly assigned to the
tosterone promote competition and aggression, and loss condition (Mehta & Josephs, 2006); losers (but
competitiveness and aggressiveness promote surges not winners) who experienced an increase in testos-
in testosterone), studies that measure testosterone terone were more likely to compete again than were
changes concurrently with behavior are rather ambig- losers who experienced a decrease in testosterone.
uous with respect to the direction of causality. A better Therefore, this study provided some initial evidence
for the hypothesis that fluctuations in testosterone
3
Nevertheless, there is emerging evidence that testosterone
function to promote subsequent behaviors aimed
also promotes prosocial behavior, which may be more consistent
with the prestige route to high status. We also close this chapter at gaining and maintaining status, and also high-
with a brief review of this emerging literature. lighted the importance of considering whether the

284 Hierarchy and Testosterone

testosterone surge was accompanied or driven by a same or a new opponent or complete an unrelated,
preceding win or a loss, which may be especially noncompetitive task. The decisiveness of the preced-
important for predicting participants’ decisions to ing victory interacted with testosterone surges to pro-
have a rematch against the same opponent. In such mote competition: Among those who won decisively,
rematches, testosterone-induced competitiveness may testosterone surges predicted a greater likelihood of
not be as functional for winners, who only stand to competing again,4 whereas among those who won
lose the increased rank they just gained (i.e., they narrowly, testosterone surges predicted (albeit non-
have little to gain and everything to lose against the significantly) a decreased likelihood of competing
same opponent), compared to losers, who can poten- again. Therefore, testosterone–behavior links may be
tially regain their lost status (i.e., have little to lose functionally tuned to information about the previous
but everything to gain against the same opponent). competition and the subsequent competition, increas-
The asymmetry in these costs and benefits across ing competitiveness only when such decisions are
winners and losers may explain the differential role advantageous for climbing a social hierarchy.5
of testosterone in this study. In certain contests, however, there are no clear
What about situations in which it is advantageous winners or losers. How does testosterone promote
for winners to compete again? One possibility is that subsequent competitiveness when the outcomes of a
if winners can compete against a new opponent, preceding competition are ambiguous? Another study
rather than the same one, they may have an additional (Carré & McCormick, 2008) investigated testoster-
opportunity to enhance their status further and, as one fluctuations and subsequent competitive behav-
such, testosterone may more strongly promote ior using a competitive computer game in which
competition. The decision to compete would still, participants, throughout the task, rapidly pressed
however, depend on the individual’s chances of a key to earn points that were later exchangeable
winning a subsequent competition, something that for money. Participants were told, however, that at
may be determined, in part, by the decisiveness of random intervals their point counter may decrease
his or her last victory. For example, if the individual by 1 point, indicating that another participant had
barely won his or her last competition, he or she stolen a point from them (a salient provocation or
may perceive his or her status as unstable, and com- challenge). Participants could ignore the provocations
peting again may be more risky than beneficial. If, and continue earning or switch keys to either protect
however, the individual decisively won, he or she may their points for a variable amount of time or steal
perceive his or her status as more stable and enduring, points back from the other player (although such
increasing the perceived benefit of competing again behavior is costly as participants are told they do not
and potentially gaining additional status. In such get to keep points they steal). This task, known as the
situations, testosterone may more strongly promote Point Subtraction Aggression Paradigm (PSAP, orig-
competitiveness. inally developed by Cherek, 1981), induces highly
A more recent study conducted by Mehta, Snyder, variable testosterone changes, making it well suited
Knight, and Lassetter (2015) examined these possi- to the investigation of links between competition-
bilities using the same number-tracing task described induced testosterone fluctuations and subsequent
earlier. Rather than manipulating whether partici- behavior (for review, see Geniole, MacDonell, &
pants won or lost in this task, the researchers instead
manipulated the ease with which participants won. 4
Given that so few participants chose to compete against the
In the task, participants were asked to compete against same opponent (6.5 percent), the authors collapsed across these
a research confederate posed as another participant. two “compete” groups and examined the extent to which
During each round of the task, participants were testosterone surges during close versus decisive victories predicted
willingness to choose one of the two competitive options in general
asked to shout “done” once they had finished each (competing against the same or a new opponent) versus the
trial of the task. In the close victory condition, the noncompetitive option. The same pattern of results was obtained
research confederate acted as if he or she had finished when the authors restricted the analysis to those who chose to
the task only moments after the participant, shouting compete against a new opponent. The authors also examined
whether victory type interacted with cortisol concentrations to
“done” one to three seconds after the participant. In predict decisions to compete again but found no evidence for such
the decisive victory condition, the research confeder- interactions or main effects of baseline or changes in cortisol.
ate acted as if he or she had finished much later than 5
This process is likely operating outside of conscious
awareness, however: When the researchers asked participants to
the participant, instead shouting “done” 6 to 10 sec-
predict their likelihood of winning the subsequent competition,
onds after the participant. After the rigged competi- this variable was associated with neither testosterone fluctuations
tion, participants could compete again against the nor their decision to compete again in a subsequent competition.

Geniole and Carré 285

McCormick, 2017). During the task, participants compete again. Testosterone surges after narrow
could see their own point counter, but not the point victories may thus promote status maintenance (or
counter of the competitor, and the outcome was status defense, the avoidance of future opportunities
never announced to the participants. Instead, after to lose status) rather than future attempts at further
the task, participants were simply asked if they status enhancement (e.g., Mehta, Snyder, et al., 2015).
wished to compete again in a second but different
task against the same opponent (puzzle completion Testosterone Fluctuations and Aggressive
task) or to help the experimenter validate a different and Antagonistic Behavior
program (noncompetitive choice). In addition to driving the willingness to compete,
Carré and McCormick (2008) found that partici- testosterone surges may also promote the expression
pants who experienced greater increases in testoster- of aggressive behavior, which can assist the individ-
one during the task were more likely to choose to ual in climbing a status hierarchy, primarily through
compete again in the subsequent task than were the dominance route of the dual-strategies model of
participants who experienced lesser increases (or status outlined previously. Researchers define aggres-
decreases) in testosterone. Although the outcome sion as any behavior intended to cause harm to
was neither announced nor manipulated, participants another individual who would rather avoid such
may still have formed beliefs about how they per- treatment, with the behavior not necessarily being
formed relative to the competitor. The authors also physical but at least being aversive to the recipient
asked participants about these beliefs but found no (Baron & Richardson, 1994).
associations between this measure and testosterone Several studies have assayed aggression using the
changes, nor did the beliefs interact with testosterone PSAP (described earlier). Recall that when partici-
to predict competitiveness. Therefore, testosterone pants are provoked in this task (i.e., the other player
surges during competitions in which the outcome is steals a point from them), they can (1) continue earn-
ambiguous appear to promote subsequent competi- ing points, (2) protect their points, or (3) steal points
tiveness. It should be noted, however, that this from the other participant. Because the points are
association between testosterone fluctuations and exchangeable for money (monetary loss is aversive)
subsequent competitiveness may have still depended and because participants do not financially benefit
on certain characteristics of the PSAP competition; from retaliating and stealing points in the task (they
for example, in other versions of the task in which are specifically told they do not get to keep any of
participants were not provoked and/or retaliatory the points they steal from the fictitious opponent),
stealing was beneficial (rather than costly), links steal presses represent a behavioral measure of
between testosterone fluctuations and decisions to aggression. Indeed, the task has been well validated,
compete were weaker/reversed (Carré, Gilchrist, with steal presses higher among clinical and forensic
Morrissey, & McCormick, 2010). populations known for violent and aggressive tenden-
Together, these studies provide some evidence cies and those who self-report being more aggres-
that endogenous surges in testosterone, which occur sive, compared to control populations and those who
during competitive interactions, may function to self-report being less aggressive (reviewed in Geniole,
influence subsequent competitive behavior. Whereas MacDonell, et al., 2017). Men who steal more (vs.
both the biosocial model of status and the challenge less) in the task are more likely to report using retalia-
hypothesis posit that surges in testosterone promote tory steals as a means to protect their status (Geniole,
subsequent competitive or aggressive behaviors, this Cunningham, Keyes, Busseri, & McCormick, 2015).
relationship does not appear to be so straightforward. In one study (Carré, Putnam, & McCormick,
Instead, testosterone surges may interact with other 2009), participants competed against one another
situational factors such as the challenge, competitive- in a number-tracing task in which the outcomes
ness, or outcome of the preceding competition that were rigged (half of participants won and half lost).
induced the testosterone fluctuations and, if the After the task, participants played against the same
outcome involved a victory, the decisiveness of the individual in the PSAP. Men (but not women)
victory. Although losers who experience increases in who experienced greater increases in testosterone
testosterone appear more willing to compete again, during the number-tracing task were more aggres-
winners who show similar increases only compete sive against their opponent in the PSAP (stole more
again if their preceding victory was decisive. If their points) than were those who experienced lesser
preceding victory was narrow, surges in testosterone increases (or greater decreases). Although there was no
may instead promote a decrease in the willingness to interaction between these changes in testosterone

286 Hierarchy and Testosterone

and the outcome of the number-tracing contest operate through the dampening of testosterone reac-
(win vs. loss), the effect was nonetheless driven by tivity to competition? One study (Carré, Iselin,
men assigned to the loss condition. Conversely, Welker, Hariri, & Dodge, 2014) examined the
among men who were assigned to the win condi- ­efficacy of a 10-year aggression intervention program,
tion, the association between changes in testoster- which started when children were in kindergarten.
one and subsequent behavior was not significant At 26 years of age, participants were contacted for a
and was instead moderated by an additional per- follow-­up experiment in which they played three
sonality factor (see section on moderators later). rounds of the PSAP against a fictitious opponent.
Vongas and Al Hajj (2017) also investigated Participants assigned to the intervention program
how testosterone fluctuations during the number- showed less testosterone reactivity to competition
tracing task would predict subsequent aggressive during the first round of the PSAP and less aggres-
behavior in men, this time using both the Hot Sauce sive responding in the second and third rounds of
paradigm (Lieberman, Solomon, Greenberg, & the PSAP. Consistent with the idea that testosterone
McGregor, 1999) and the PSAP. Testosterone reactivity may mediate the effect of intervention on
increases during the number-tracing task predicted reduced aggression, when testosterone surges during
greater aggression during both tasks, but neither of the first round were entered into the statistical model,
the associations was significant. Although direction- the effect of intervention on the second and third
ally consistent with the study reviewed earlier (Carré round aggression levels was no longer significant. In
et al., 2009), the effects may have been weaker because other words, the intervention was successful at reduc-
of differences in methodology; in Carré and col- ing aggression in rounds 2 and 3 because it reduced
leagues (2009), points earned in the PSAP were con- testosterone reactivity during the task. Thus, inter-
verted to money at the end of the study (thus, steals vention programs aimed at reducing aggression may
represented a form of financial aggression), whereas function by dampening testosterone reactivity to
in Vongas and Al Hajj (2017), the points were not provocation, at least in men for whom testosterone–
exchangeable for money. Without financial conse- aggression links appear more consistent.
quences associated with stealing, provocations may Recall that the PSAP is also used to induce var-
not have been as meaningful and aversive, and retalia- iability in testosterone responses and to examine
tory stealing may not have tapped into the construct whether such variability predicts competitiveness
of aggression as much as it does in the standard (e.g., Carré et al., 2010; Carré & McCormick, 2008)
version of the task. or aggressiveness on subsequent tasks. In one study
In another study (Carré, Campbell, Lozoya, employing such a design (Geniole, Busseri, &
Goetz, & Welker, 2013), researchers examined McCormick, 2013), participants completed the
changes in testosterone that occurred during an inter- PSAP against a fictitious opponent and were then
active video game in which participants either fought asked to decide the honorarium of the opponent
or played volleyball against computer opponents. In (participants could give as much or as little of a $5
the task, participants had to use their actual body honorarium to their opponent; giving lower amounts
movements to control the avatars, which better sim- can be considered a form of financial aggression).
ulates competitive interactions that occur in the real Testosterone increases during the PSAP predicted
world, compared to other more standard lab tasks. lower allocations to the opponents, an effect that
Results indicated that male winners were more aggres- became stronger when controlling for concurrent
sive and demonstrated a larger increase in testosterone changes in cortisol and estradiol, which may have
concentrations related to losers. Moreover, the effect suppressed the main effects of testosterone (changes
of competition outcome on subsequent aggression in testosterone were associated positively with changes
was statistically mediated by changes in testosterone in estradiol, but such estradiol changes were corre-
concentrations. Specifically, winners tended to be lated positively, albeit marginally, with the amount
more aggressive than losers were, in part because of money given, see Table 3 in Geniole et al., 2013).
they demonstrated a larger increase in testosterone Therefore, testosterone surges during competi-
relative to losers. Again, there was no significant asso- tions appear to promote subsequent aggressive
ciation between testosterone surges and subsequent behavior across different measures (the PSAP: Carré
PSAP aggression in women. et al., 2009, 2013, 2014; a money allocation para-
If testosterone surges during competition pro- digm: Geniole et al., 2013), effects that may function
mote subsequent aggressive behavior, at least in men, to assist the individual in climbing a status hierarchy
could interventions designed to reduce aggression through the dominance route outlined in the dual

Geniole and Carré 287

strategies model of status (Cheng et al., 2013; both men and women (as in Carré et al., 2009, 2013;
Henrich & Gil-White, 2001; for recent review, see Geniole et al., 2013) predict both types of behaviors
Case & Maner, 2016). (prosocial vs. aggressive and competitive). One
exciting possibility is that testosterone promotes high
Important Moderators of the Links status in both men and women, but through different
Between Testosterone, Competition, and routes (e.g., the dominance route in men and the
Aggression prestige route in women), the examination of which
A number of studies suggest that testosterone does will be important in future studies.
not share straightforward links with competitive and Situational factors are also important. Some of the
aggressive behavior, but instead interacts with sex and evidence reviewed earlier suggests that competition-
situational and individual difference factors. The induced fluctuations in testosterone may have differ-
studies reviewed previously suggest that competition- ent effects depending on the outcome of the competi-
induced fluctuations in testosterone are a stronger and tion (e.g., win vs. loss, see Carré & McCormick, 2008;
more consistent predictor of subsequent competi- Mehta & Josephs, 2006; for effects in samples of win-
tion and aggression in men than in women, with ners only, see Geniole et al., 2013; Study 1 of Norman
several of the studies testing associations in both et al., 2014) and its decisiveness (close vs. decisive
sexes but findings effects only in men (e.g., Carré et outcomes, Mehta, Snyder, et al., 2015). Testosterone
al., 2009, 2013; Geniole et al., 2013). This discrep- may also share differential links with subsequent
ancy may be related to differences in the sensitivity competitive behavior depending on the types of
of the testosterone determination methods often used future competitions that are actually available,
(e.g., salivary testosterone assessed using enzyme- promoting competitiveness only when a future
linked immunosorbent assays), with testosterone con- victory helps one climb the hierarchy (e.g., when
centrations in women being much lower than men’s against a new opponent, as discussed in Mehta &
and thus detected less reliably, introducing additional Josephs, 2006; Mehta, Snyder, et al., 2015). The
error in female versus male testosterone samples. inducer of testosterone may also be important; cues or
Effects in women may also be obscured by additional challenges that signal the potential for violence (e.g., a
variability related to menstrual cycle or the use of handgun) may promote testosterone surges that func-
hormonal contraceptives, both of which may influ- tion to increase aggression (e.g., Klinesmith, Kasser,
ence aggression (e.g., Geniole et al., 2013) or hor- & McAndrew, 2006), whereas cues or challenges
mones directly (e.g., Arslan et al., 2008; Sowers, that signal the potential for nurturance (e.g., a baby
Beebe, McConnell, Randolph, & Jannausch, 2001) crying, as in van Anders, Tolman, & Jainagaraj, 2014)
or interact with testosterone (Dougherty, Bjork, may not. Future studies may benefit from testing
Moeller, & Swann, 1997) to influence aggression. this possibility directly.
It is also possible that such sex differences in the Other moderators of the testosterone–competition
link between testosterone and aggression and between and testosterone–aggression link may include more
testosterone and competition exist because testos- stable, individual difference factors. Some research
terone serves different functions in men and in in rodents and humans, for example, suggests that
women (although see Hahn, Fisher, Cobey, anxiety may be an important factor for understanding
DeBruine, & Jones, 2016). Whereas competition- links between testosterone and behavior. Social
induced surges in testosterone in men may promote challenges elicit greater aggression and testosterone
subsequent competitiveness, aggression, and antag- responses among male rats bred for low versus high
onistic behavior, such surges in women may promote anxiety (Veenema, Torner, Blume, Beiderbeck, &
less direct forms of aggression (e.g., ostracism, rumor Neumann, 2007), and in humans, there is some evi-
spreading, gossiping), not often investigated with dence that the winner–loser effect is moderated by
respect to testosterone. These behaviors, however, social anxiety (such that losing men show decreases,
may be more common expressions of dominance but only to the extent that they are high in social
and aggression in women (see review in Archer, 2009). anxiety, Maner et al., 2008). In a more recent study
Another possibility is that testosterone promotes (Study 1, Norman et al., 2014), testosterone surges
other, more prosocial behaviors aimed at gaining during a victory predicted greater aggression in a sub-
and maintaining status, such as reconciliation after sequent task, the PSAP, but only among individuals
a conflict or competition in women (Casto & low in trait anxiety (in fact, testosterone surges pre-
Edwards, 2016b). Additional studies would benefit dicted marginal decreases in aggressive behavior
from examining how testosterone fluctuations in among those high in trait anxiety). In a follow-up

288 Hierarchy and Testosterone

investigation (Study 2, Norman et al., 2014), the not moderate the association between testosterone
authors reanalyzed an archival dataset, finding the fluctuations and subsequent antagonistic behavior
same pattern of results in men (but not women) who (Geniole et al., 2013). One possibility for this discrep-
both won or lost a preceding competition. Specifically, ancy may be the different tasks used to measure sub-
those with greater testosterone increases during the sequent aggressive/antagonistic behavior. In Carré
competition (irrespective of the outcome) were more and colleagues (2009), the postcompetition m ­ easure
aggressive in a subsequent task, but only if they were of aggression (PSAP) also involved competition and
also low in trait anxiety.6 a dynamic interaction between the participant and
Another important moderator of the testosterone– the (fictitious) opponent, during which counterre-
aggression link may be one’s level of ­independent taliation was possible and aggression was costly to
versus interdependent self-construal. Those high in personal earnings. Conversely, in Geniole and col-
independent self-construal view their identity as sepa- leagues (2013), the postcompetition measure of
rate or independent from a larger social group, valuing aggressive/antagonistic behavior was a one-shot deci-
and striving for this independence and autonomy. sion in which aggressiveness (giving lower amounts)
Conversely, those higher in interdependent self- was not costly and the opponent could not retaliate.
construal see themselves as part of a larger social group One possibility is that the moderating role of dom-
and value and are cognizant of their role within the inance only applies to aggressive behaviors that are
group (Markus & Kitayama, 1991). Because of this costly to the actor and/or may elicit retaliation. More
value placed on one’s role within a larger social group, recently, using pharmacological manipulations,
individuals high in interdependent self-construal may researchers have shown that the effects of exogenous
avoid using aggression (especially direct/overt forms testosterone on competition and aggression are
of aggression) as it may jeopardize such relationships, strongest among men (Carré et al., 2017) and
whereas those higher in independent self-construal women (Mehta, van Son, et al., 2015) high in trait
may see aggression as an opportunity to establish or dominance. Self-control also emerged as a moderator
solidify their position within a social hierarchy (for in Carré and colleagues (2017), buffering against
review, see Cross & Madson, 1997). Consistent with the effects of testosterone on aggression. In other
this idea, interdependent self-construal is negatively words, for those low in self-control, testosterone
associated with meanness, a psychopathic personality promoted aggression. For those high in self-control,
trait reflecting one’s ability to callously exploit others however, this effect was not significant. Although
(Blagov, Patrick, Oost, Goodman, & Pugh, 2016). more work is needed, it appears that testosterone
Therefore, higher scores on this trait, and lower scores may promote the impulse to aggress, which manifests
on independent self-construal, may buffer against the in behavioral displays of aggression especially among
effects of testosterone and aggression. Indeed, in a those high in the desire to outcompete and impose
recent set of studies, Welker and colleagues (2017) their will on others (i.e., those high in trait domi-
found that testosterone changes during a rigged nance) and among those who find it difficult to exer-
boxing game in men predicted subsequent aggressive cise self-control over impulses in general (e.g., those
behavior in the PSAP, but only among men high in low in self-control).
­independent versus interdependent self-construal. In
a reanalysis of Carré and colleagues (2013), the Conclusion
authors again found the same effect (irrespective of The research reviewed in this chapter suggests that
whether participants won or lost the preceding testosterone surges during competitive interactions
competition), but only among men. influence subsequent status-related behaviors. First,
Individual differences in dominance may also there is evidence that testosterone surges during com-
play a role. Testosterone surges in male winners pre- petition function to promote subsequent attempts
dicted subsequent aggression, but only among male at additional status enhancement (through increased
winners high in trait dominance (Carré et al., 2009). willingness to compete). Importantly, however, this
In another study, however, a psychopathic personality relationship depends on several factors: Rather than
factor involving a combination of low anxiety, fear, promoting a willingness to compete across all con-
and high social dominance (fearless dominance) did texts, testosterone surges appear to drive this will-
ingness among individuals who lost a preceding
competition or decisively (vs. narrowly) won and
6
The authors suggested that this interaction may have emerged
because of differences in the interpretation of, or ability to suppress could compete against a new opponent (and further
anger in response to, provocation during the PSAP. elevate status), in particular.

Geniole and Carré 289

 In addition to increasing the willingness to Naef, Snozzi, Heinrichs, & Fehr, 2010, 2012; Van
c­ompete, testosterone fluctuations also appear to Honk, Montoya, Bos, van Vugt, & Terburg, 2012;
drive aggressive behavior. Men who experienced larger for other evidence of prosocial effects, see Wibral,
increases in testosterone, across various tasks (e.g., a Dohmen, Klingmüller, Weber, & Falk, 2012).
number-tracing task, the PSAP, and a more ecologi- Accordingly, researchers have proposed a model
cally relevant fight simulation), were more aggres- of testosterone in which its actions are posited to
sive toward their competitors on a subsequent task guide behaviors more generally aimed at status
than were men who experienced lesser increases or attainment and maintenance, which can be either
decreases in testosterone. Further, in addition to prosocial or antisocial, depending on the context
promoting aggression in the PSAP, men who experi- (Eisenegger et al., 2011). Nevertheless, the circum-
enced greater increases in testosterone were more stances (i.e., situational factors) in which and
likely to allocate a smaller honorarium to participants people (i.e., individual difference factors) for whom
after a competition than those who experienced lesser testosterone flexibly promotes prosocial versus anti-
increases or decreases. Interventions that reduced social behaviors aimed at gaining and maintaining
aggression appeared to act by suppressing these testos- status remain poorly understood and an important
terone surges in response to competition. area for future research (Hamilton et al., 2015;
The most consistent finding in these studies is Knight & Mehta, 2014).
that whereas many of these effects were significant
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 CH A PT E R
Competition, Dominance,
17 and Social Hierarchy

Kathleen V. Casto and Pranjal H. Mehta

Abstract

This chapter reviews literature having to do with the social-behavioral neuroendocrinology of

competition, dominance, and status hierarchies in humans. After defining these terms, their importance,
and everyday relevance, the chapter discusses the major research findings that suggest a bidirectional
influence between these social behaviors and the steroid hormones cortisol and testosterone.
Specifically, the association between cortisol and social rank and cortisol’s reactivity to social challenges
are discussed. Further, this chapter discusses research that tests the predictions that basal
testosterone is related to status-motivated behavior, that testosterone levels are transiently altered
during contests for status, and that these changes function to promote subsequent status-seeking
behavior. Noting the nuance of these findings, the personality and context factors that appear to
moderate testosterone–status relationships are highlighted. Finally, this chapter includes both a new
theoretical model for the testosterone–social status relationship that captures this complexity and, in
closing, summarizes promising areas of future research.
Key words: competition, dominance, status, social hierarchy, testosterone, cortisol, dual-hormone
hypothesis

In ancient Egyptian society, formalized social social relationships across cultural boundaries
­hierarchy was manifested in the ritualistic burial of (Diefenbach, 2013; Sidanius & Pratto, 1999).
the dead. Social status was symbolized in almost Formalized and highly stratified hierarchies exist
every aspect of the mortuary arrangement—how within political and government structures, such
close in proximity one’s tomb was to the king, as traditional monarchies, dictatorships, capitalist
height from the ground, size of the tomb, level of systems, and resulting socioeconomic status (SES).
artistic decoration, and material accoutrements There are also less large-scale yet pervasive social
(Romano, 1990; Taylor, 2001). Male members of hierarchical systems: class or grade in school, work-
the elite class would begin constructing a tomb at the place title or position, finish place in a competition,
peak of their career, even setting aside an endow- veteran or rookie status on a professional sports
ment for upkeep and offerings after death (Baines & team, the lead versus backup role in a play or dance
Lacovara, 2002). These preemptive structures served assemble, and even the naming system for increas-
as status symbols for the living as the “tomb was ingly luxurious seats on an airplane (first class, busi-
a central vehicle for peer competition (Baines & ness class, and main cabin). These systematic rankings
Lacovara, 2002, p. 10). For Egyptians, death was as within everyday life are representative of the fun-
important as life; it was imperative that social status damental human need to formally classify social
attained in life be maintained in death. position based on level of distinction, wealth, talent
Social hierarchy remains a pervasive and funda- or ability, and assumed power and privilege within
mental framework of modern human society and each role. Some evolutionary psychologists even

295
suggest that it was the emergence of increasingly Center, 2017) to attempt to outrank their peers in
complex social dominance interactions that provided quality of life, personal achievements, travel,
the selection pressure for the more sophisticated number of friends, and perceived happiness (Chua
human intelligence and capacity for language & Chang, 2016). Though seemingly nonconse-
(Alexander, 1989; Flinn, Geary, & Ward, 2005). quential, these small and sometimes subtle everyday
Importantly, society-level social hierarchies result gestures may serve to reinforce larger scale hierarchi-
in stepwise differences among the upper and increas­ cal social systems and represent the pervasiveness of
ingly lower echelons (Dasgupta, 2015; Sidanius & the fundamental human striving for status.
Pratto, 1999) in access to resources directly linked Like other basic psychological drives, such as
to survival, such as food, water, housing, land, and thirst, hunger, and sexual desire, the motivation for
health care (e.g., “food deserts” common in low- status has biological underpinnings in the form of a
income neighborhoods, lack of access to potable cascade of bidirectional brain–body interactions
water in certain developing nations; Montgomery communicated via chemical messengers, specifically
& Elimelech, 2007; Walker, Keane, & Burke, 2010). steroid hormones. Testosterone was first recognized
In review of the adverse physiological effects of for its long-term impact on the development of
stress resulting from “dominance hierarchies” in male secondary sexual characteristics and sexual
primates, Sapolsky (2005, p. 652) states that despite behavior (August, Grumbach, & Kaplan, 1972;
the complexities of human social structure, “the Phoenix, Goy, Gerall, & Young, 1959; Phoenix, Slob,
SES gradient of health among Westernized humans & Goy, 1973). Given the more physically dominant
is a robust example of social inequalities predicting nature of male-typical behavior in male primates,
patterns of disease.” Indeed, there appears to be a including humans, early research on social hierar-
strong positive relationship in primates, including chies proposed that testosterone would increase
humans, between both objective and subjective with status rank and social dominance (Ehrenkranz,
social status ranking and psychological stress, health, Bliss, & Sheard, 1974; Purifoy & Koopmans, 1979;
and, ultimately, the quality of life and survivability Rose, Bernstein, & Gordon, 1975; Sapolsky, 1982).
of individuals (Demakakos, Nazroo, Breeze, & Cortisol, well known for its link to physical and psy-
Marmot, 2008; Sapolsky, 2004). Thus, aside from chological stress, was also linked in earlier research to
the basic science motivation to discover patterns of rank within the social hierarchy (Sapolsky, 1982).
human behavior and related causes, there is also a Subsequent research in the decades that followed
perhaps more important ethical responsibility to has revealed a complex relationship between testos-
understand the psychological and interacting bio- terone, cortisol, and dominance rank and related
logical processes involved in social dominance behav- behaviors (Casto & Edwards, 2016a; Hamilton,
ior and resulting social hierarchies. Carré, Mehta, Olmstead, & Whitaker, 2015;
Not all dominance-motivated social ordering is Mazur & Booth, 1998).
easily recognized. There are subtler hierarchies that This chapter will review literature having to do
individuals form naturally among social groups in with the social-behavioral neuroendocrinology of
various contexts (e.g., spontaneously emerging competition, dominance, and status hierarchies,
leader–follower relationships and popularity among first defining these terms and then discussing the
peers). Everyday acts of dominance and deference major research findings that have emerged in this
(e.g., eye contact, the firmness of a handshake, the field. There is a vast research literature on these
giving and taking of verbal directives) are used to concepts pertaining to nonhuman animal behavior
attain and maintain social standing (Tiedens & (e.g., Gleason, Fuxjager, Oyegbile, & Marler,
Fragale, 2003). People also go to great lengths to 2009); however, this chapter focuses primarily on
advertise status ranking with luxury goods like the ­research involving human participants with
clothes, shoes, jewelry, cars, and houses (a term implications for human behavior. The literature
known as conspicuous consumption; O’Cass & discussed here lies at the crossroads of social-­
McEwen, 2004); we even have objects that serve no personality psychology and behavioral endocrinology
other purpose than to advertise status (e.g., trophies, (two otherwise quite distinct fields), wherein the
diplomas, and award ribbons). Even more subtle, complexity of human socially, culturally, and con-
social media platforms provide individuals far-­ textually embedded behavior is predicted by elegant,
reaching opportunity (70 percent of Americans yet primitive, and evolutionarily adaptive hormonal
polled used some form of social media; Pew Research fluctuations.

296 Competition, Dominance, and Social Hierarchy

Defining Social Hierarchy, Dominance, status gained by the demonstration of dominance.
and Competition However, the precise definition of dominance and
That valuable resources (e.g., food, water, land, related terms appears to depend on the specific lit-
sexual partners) are limited stratifies social order: erature within which it is discussed—social psy-
Some (dominants/superiors) have more access to chology, personality psychology, sociobiology, or
these resources than others (subordinates). Those evolutionary psychology (Cheng et al., 2013).
who command these resources do so because they One can possess dominance (i.e., have physical or
possess qualities that are attractive to or more psychological qualities that others defer to or
dominant than others, qualities that confer greater admire, such as strength or competence), be con-
attention, influence, or power over those that are sidered dominant (i.e., rank higher), behave dom-
lower ranking (Anderson, Hildreth, & Howland, inantly (e.g., verbal and nonverbal signaling of
2015; Berger, Cohen, & Zelditch, 1972; Berger, dominance, acting as a leader, refusal to submit),
Rosenholtz, & Zelditch, 1980; Kemper, 1990). The or dominate an opponent (soundly defeat, outper-
compilation of these relationships within social form, or display considerably greater strength than
group results in social hierarchy, the rank ordering an opponent; Burgoon, Johnson, & Koch, 1998;
“of individuals or groups on a valued social dimen- Cheng et al., 2013; Cheng, Tracy, & Henrich, 2010;
sion” (Magee & Galinsky, 2008, p. 354; as cited by Cheng, Tracy, Ho, & Henrich, 2016; Ellyson &
Cheng, Tracy, Foulsham, Kingstone, & Henrich, Dovidio, 1985). Additionally, dominance is often
2013). A higher rank order indicates that an indi- used to describe a general style of relating to others
vidual or group has higher social status (Berger that expresses the explicit and implicit motivation
et al., 1972, 1980; Ellyson & Dovidio, 1985). An for status and ­status-seeking behavior more broadly
individual’s actual rank is not necessarily fixed— (Anderson & Kilduff, 2009): A social hierarchy may
some hierarchies can be rather unstable—and is be a “status hierarchy” or a “dominance hierarchy”
often context dependent (e.g., at work vs. among (Chase, Tovey, Spangler-Martin, & Manfredonia,
peers or family). Attaining a higher position within 2002; see Sapolsky, 2005; Mazur, Welker, & Peng,
a social hierarchy can predict increases in subse- 2015). Figure 17.1 visually demonstrates the rela-
quent status-seeking behavior in an effort to main- tionships between the terms competition, dominance,
tain this high status and attain even higher positions deference, social hierarchy, status ranking, and status-
in the future (e.g., Zilioli & Watson, 2014). Because seeking behavior.
of its notable survival advantages, direct reward Although “dominance” is typically used as the
value, universality, and long-term impact on psy- catch-all concept for general behavior involved in
chological well-being, social status is considered a the attainment and maintenance of high status,
fundamental human motive (Anderson et al., 2015). recent research has determined that there are at least
Indeed, social hierarchies are a universal and evolu- two distinct, yet equally viable, cognitive and behav-
tionarily conserved characteristic of most human ioral strategies for gaining influence—dominance
societies (Chiao, 2010; Diefenbach, 2013; Gledhill, and prestige (Cheng et al., 2010, 2013; Cheng &
Bender, & Larsen, 1988). Additionally, neuroscien- Tracy, 2014). In this view, dominance refers to a
tists have revealed distinct neural networks in the more coercive, physical or psychologically aggres-
brain for the perception and maintenance of social sive, intimidating, and conflict-based style in which
hierarchy (Chiao, 2010). an individual attains power by demanding deference.
Status is often decided through competition, “a Eminence (Kemper, 1990) or prestige (Cheng et al.,
social interaction in which access to something 2013) is a style of achieving high status through
valued is contested between individuals and groups” the demonstration of competence, likability, and
(Casto & Edwards, 2016a, p. 21). The “something prosociality and is characterized by the voluntary
valued” could be the resource that is in limited deference, attention, and respect of others. Given
supply or the simple feeling that one possesses rank this distinction, continued research on the complex-
or power over others. Prevailing over one’s oppo- ities of competition- and status-related behavior,
nent signals dominance, whereas failing to prevail or including the underlying biological influence, will
conceding defeat signals deference (Mazur, 1985). expand understanding of these important and con-
In an everyday sense, the motivation for engaging sequential social interactions. Due to the more broad
in competition may be the simple joy of winning— interpretation of “dominance” (meaning status-
undoubtedly resulting from the inherent reward of seeking behavior) in the social neuroendocrinology

Casto and Mehta 297

 Sorting into the
Social

ce
Competition Hierarchy

an
in
om

Social Status
DD
efe
re
nc
e
Status-Seeking

Figure 17.1 Visual description of terms related to status and social hierarchy.

literature, the remainder of this chapter will operate & Mehta, 2014; Sapolsky, 2005). Early studies
under this generalized definition. with nonhuman animals supported this notion; for
example, Sapolsky (1982) showed that high-ranking
Cortisol, Stress, the Social Hierarchy, males demonstrated significantly lower baseline
and Competition cortisol in baboons than their more subordinate
Cortisol is well known for its positive relationship counterparts. One of the first studies in humans
with stress, both psychological and physical. Acute corroborated this finding: Among a relatively small
psychological experiences of stress, particularly sample of male Dominican villagers, lower cortisol
social-evaluative stress combined with a perceived levels were related to higher peer ratings of likabil-
lack of control over one’s environment and outcomes, ity and influence (Decker, 2000). At the society
produces reliable and transient increases in cortisol level, there is a reliable and robust negative rela-
(reviewed by Dickerson & Kemeny, 2004). Short- tionship between basal cortisol levels and SES
term elevations in cortisol, secreted as an end-prod- (Cohen, Doyle, & Baum, 2006; reviewed by
uct of the hypothalamic-pituitary-adrenal axis and Knight & Mehta, 2014).
via rapid and direct sympathetic stimulation of the Recent research in humans has expanded on the
adrenal gland (Engeland & Arnhold, 2005; Tsigos cortisol–status relationship. In a relatively large
& Chrousos, 2002), provide immediate advan- sample of individuals enrolled in an executive
tages for escaping or managing a stressful stimulus ­education program, Sherman et al. (2012) showed
(e.g., mobilization and breakdown of glucose). that leaders (those responsible for managing others)
Long-term activation or dysregulation of this system had significantly lower cortisol and anxiety than
is energetically costly and can result in deleterious nonleaders. In a follow-up study among leaders,
effects on physical and psychological health and leadership level (having and managing more subor-
immune system functioning (Cohen et al., 2012; dinates and with greater authority) produced the
McEwen, 1998; Whitworth, Williamson, Mangos, same effect. Additionally, sense of control (gener-
& Kelly, 2005)—a process known as “­ allostatic ated using a measure of personal sense of power)
load” (McEwen, 1998, 2000, 2004). Thus, individ- mediated the relationship between leadership level
ual differences in basal cortisol are interpreted as a and cortisol, as well as anxiety. However, studies of
reliable predictor of allostatic load (e.g., Goymann collegiate athletes have shown no direct relationship
& Wingfield, 2004). between cortisol and peer ratings of leadership
ability, a proxy for status (Edwards & Casto, 2013;
Basal Cortisol and Social Rank Edwards, Wetzel, & Wyner, 2006). Using social
Social hierarchy rank is thought to be inversely network analysis, Kornienko, Clemans, Out, and
­related to basal cortisol due to the increasing life Granger (2014) demonstrated that among a compet-
adversity and resulting allostatic load experienced itive pool of first-year nursing students, high cortisol
by increasingly lower ranking individuals (Knight levels were associated with low gregariousness, the

298 Competition, Dominance, and Social Hierarchy

number of perceived friends within the network of contexts where risk taking is advantageous (i.e.,
nursing students, but not popularity, the number of choosing to fight rather than flee when status is rel-
network members who perceived them as friends. atively high), but could be deleterious in other con-
In a follow-up study among members of a large texts (e.g., choosing to fight rather than flee when
mixed-sex collegiate marching band, higher basal cor- status is relatively low). However, there is some evi-
tisol was also related to an inability to maintain dence in men and women dyads that transiently
friendships within the network (i.e., greater turnover increased cortisol levels predict subsequent prosocial
in friendships over a two-month period; Kornienko, behaviors and cognitive states such as affiliation (in
Schaefer, Weren, Hill, & Granger, 2016). women dog handlers, Sherman, Rice, Jin, Jones, &
Josephs, 2017) and feelings of interpersonal closeness
Cortisol Reactivity to a Status Challenge (in men participating in the TSST, Berger, Heinrichs,
The direction and strength of the cortisol response von Dawans, Way, & Chen, 2016) that effectively
to stress depends on a multitude of psychological buffer the negative psychological and physiological
and contextual factors (Dickerson & Kemeny, 2004; effects of stress (Cohen & McKay, 1984).
Knight & Mehta, 2014; Kudielka, Hellhammer, & Situational factors also appear to moderate the
Wüst, 2009). Cortisol increase in response to a relationship between status and cortisol reactivity.
stressor could be considered adaptive (e.g., benefiting In at least two studies, individuals who were high
social status) or maladaptive (e.g., a sign of dysregu- on indices of dominance motivation (basal testos-
lation or overreactivity) depending on the context terone; implicit power motivation) showed greater
(e.g., competition) and the timing and magnitude cortisol increases across a competition for status,
of the response (Aschbacher et al., 2013; Shirtcliff, but only when that competition resulted in defeat
Peres, Dismukes, Lee, & Phan, 2014). (Mehta, Jones, & Josephs, 2008; Wirth, Welsh, &
Social rank appears to be one important factor Schultheiss, 2006). Directly testing the moderating
for predicting patterns of cortisol reactivity to effects of social context on the status–cortisol reac-
stress (e.g., Hellhammer, Buchtal, Gutberlet, & tivity relationship, Knight and Mehta (2017) manip­
Kirschbaum, 1997; Sapolsky, 1982), with higher ulated both the status position and hierarchy stabil-
social status producing what researchers interpret as ity of men and women competing in a mock job
more adaptive responses, depending on the task and interview. Participants assigned to a high-status role
context (Akinola & Mendes, 2014; Shirtcliff et al., (“manager”) showed reduced cortisol reactivity
2014). In one study, women whose cortisol levels and better performance compared to participants
did not habituate after repeated exposure to a stres- assigned to the low-status role (“builder”), but only
sor (i.e., a maladaptive response) subjectively rated if the assigned roles were fixed (i.e., a stable hier-
themselves lower in SES (Adler, Epel, Castellazzo, archy). When told that the assigned roles could
& Ickovics, 2000). Under the condition of social- change based on performance in the interview (i.e.,
evaluative threat, men and women with high subjec- an unstable hierarchy), high status increased cortisol
tive social status (perceived rank among dormitory reactivity and did not result in better performance
peers) showed significantly larger cortisol increases compared to low status.
in a single session of the Trier Social Stress Test In real-world athletic competition, where status
(TSST) than men and women who rated themselves is formally contested, cortisol significantly increases
low in status (Gruenewald, Kemeny, & Aziz, 2006). over the match period in men and women (e.g.,
Cortisol increase, in this sense, could reflect a greater Casto, Elliott, & Edwards, 2014; Edwards et al.,
mobilization of energy and activity required to 2006; Edwards & Kurlander, 2010; reviewed by
defend one’s status when status is indeed at stake, Casto & Edwards, 2016a), an effect that is likely
with a nonincrease in cortisol reflecting a more influenced, to some degree, by the physical stress of
maladaptive (i.e., blunted) physiological response exercise (Copeland, Consitt, & Tremblay, 2002; M. S.
threat. However, the adaptive function of elevated Tremblay, Copeland, & van Helder, 2005; Viru et al.,
cortisol would likely depend on the social context. 2010). Contrary to the aforementioned study where
For example, increased cortisol in response to social high rank predicted a higher cortisol increase across
stressors, in some studies, appears to predict sub- the TSST, competition losers appear to show relatively
sequent risky decision making (van den Bos, higher increases in cortisol compared to winners
Harteveld, & Stoop, 2009; reviewed by Starcke & (e.g., Bateup, Booth, Shirtcliff, & Granger, 2002;
Brand, 2012), a behavior that could be beneficial in Jiménez, Aguilar, & Alvero-Cruz, 2012).

Casto and Mehta 299

Testosterone, Status, and Status-Seeking research testing specific predictions from these
Behavior models in the context of human competition. There
Several decades of research have revealed a generally are several recent comprehensive reviews and meta-
positive and bidirectional relationship between tes- analyses that summarize the findings from this liter-
tosterone, social status, and status-related behavior. ature (Carré & Olmstead, 2015; Casto & Edwards,
Initial observationally and empirically based models 2016a; Geniole, Bird, Ruddick, & Carré, 2017;
of this relationship, the biosocial model of status Hamilton et al., 2015; G. A. Oliveira & Oliveira,
(Mazur, 1985) and the challenge hypothesis 2014). Table 17.1 provides a list of specific hypoth-
(Wingfield, Hegner, Dufty, & Ball, 1990), have eses that can be derived from the biosocial model of
provided a theoretical basis for this research. Detailed status and challenge hypothesis regarding the rela-
historical accounts and an extended description of tionships between testosterone and status ranking,
these models are published elsewhere (biosocial model status-seeking motivation, and status-seeking be-
of status—Mazur & Booth, 1998; Mazur, 2017; havior. Some of these hypotheses have been tested
challenge hypothesis—Archer, 2006; Wingfield, empirically more than others (e.g., #1 and #2 more
2017). The challenge hypothesis asserts that baseline than #5). Among the specific hypotheses that have
levels of testosterone in monogamously mating birds been well tested, nearly all of them have been sup-
regulate reproductive development during breeding ported by some studies but also not supported
season, increase with periods of territorial aggression by others (#1: Burnham, 2007; Cashdan, 2003;
under conditions of social instability (in response to Dabbs & Morris, 1990; Josephs, Sellers, Newman,
male–male contests for status and sexual partners), & Mehta, 2006; Mehta, DesJardins, van Vugt, &
and decrease with the expression of parental care Josephs, 2017; R. E. Tremblay et al., 1998; van
(Wingfield, 2017). This hypothesis has been extended Bokhoven et al., 2006; Wirth & Schultheiss, 2007;
to humans to explain, more generally, testosterone #2—Carré, Putnam, & McCormick, 2009; Grant
increases in response to “competitive situations & France, 2001; Schultheiss, 2007; Sellers, Mehl,
between young men” (Archer, 2006, p. 322). & Josephs, 2007; Welker & Carré, 2015;
The biosocial model of status, initially informed #3—Cashdan, 1995; Purifoy & Koopmans, 1979;
by empirical studies with nonhuman primates and Zyphur, Narayanan, Koh, & Koh, 2009; Apicella,
men engaged in athletic competition, proposes that Dreber, & Mollerstrom, 2014; Bateup et al., 2002;
stable baseline levels of testosterone predict status- #4—Carré, Campbell, Lozoya, Goetz, & Welker,
related behavior. Furthermore, this model proposes
that testosterone should increase in response to
Table 17.1. Hypotheses Derived from the Biosocial
status gained and decrease in response to status Model for Status and the Challenge Hypothesis
lost. Specifically, high-testosterone individuals are
expected to behave more dominantly and, as a result 1. High-testosterone (T) individuals behave more
of status gained from this dominance, demonstrate dominantly than low-T individuals; low-T individuals
rising levels of testosterone to promote future behave more submissively.
competitive behavior. Likewise, low-testosterone 2. High-T individuals are high in dominance motivation
individuals are expected to behave more submis- (dominant personality, motivated for status); low-T
sively and, as a result of status lost from this defer- ­individuals are low in dominance motivation.
3. Individuals with high status have higher T than
ence, demonstrate falling levels of testosterone. That
individuals with relatively lower status.
is, transient shifts in testosterone represent the phys-
4. Winning a competition increases T; losing a
iological mechanism underlying each stage of the ­competition decreases T.
competition, status-sorting, and status-seeking pro- 5. Behaving dominantly increases T; behaving submissively
cesses depicted in Figure 17.1. Although originally decreases T.
thought to be an acute mechanism regulating even 6. Engaging in a competition (a threat/challenge to
subtle dominance and deference signals in everyday status) increases T.
interactions with others (Mazur, 1985), evidence 7. Individuals high in dominant personality/motivation
of substantial testosterone fluctuations resulting for status show increases in T across a competition;
from status contests may be specific to more formal ­individuals low in dominant personality/motivation
competitive contexts (Mazur et al., 2015). for status show decreases in T across a competition.
8. Increased T promotes an increase in subsequent
The decades that followed the dissemination of
­status-seeking behavior or cognitive states that would
the biosocial model for status and the challenge
benefit social status seeking.
hypothesis have produced an abundance of empirical

300 Competition, Dominance, and Social Hierarchy

2013; Costa & Salvador, 2012; Jiménez et al., 2012; Meij et al., 2016), managers did not have higher
Norman, Moreau, Welker, & Carré, 2015; #5— testosterone levels on average than their subordinate
Peters, Hammond, Reis, & Jamieson, 2016; workers. Rather than directly predicting status
#6—Apicella et al., 2014; Carré & McCormick, position, basal testosterone appears to predict how
2008; Casto & Edwards, 2016b; Casto et al., 2014; individuals respond to shifts in status. That is,
Edwards et al., 2006; Guezennec, Lafarge, Bricout, high-testosterone individuals respond negatively
Merino, & Serrurier, 1995; Steiner, Barchard, (e.g., poorer performance on a spatial or verbal
Meana, Hadi, & Gray, 2010; van der Meij, Buunk, test) to a drop in status, whereas low-testosterone
Almela, & Salvador, 2010; #7—Schultheiss, individuals respond neutrally or negatively to a rise
Campbell, & McClelland, 1999; Schultheiss & in status (Josephs, Newman, Brown, & Beer, 2003;
Rohde, 2002; Schultheiss et al., 2005; #8—Bos, Josephs et al., 2006; Mehta et al., 2008; Newman
Hermans, Ramsey, & Van Honk, 2012; Carré, et al., 2005).
Baird-Rowe, & Hariri, 2014; Carré & McCormick, Due to the complexities of achieving high-status
2008; Hermans, Ramsey, & van Honk, 2008; or leadership positions, basal testosterone may better
Mehta & Josephs, 2006; Mehta, van Son, et al., predict personality characteristics and behaviors
2015; Welling, Moreau, Bird, Hansen, & Carré, motivated toward achieving status (whether or not
2016). To clarify general concepts that have emerged those efforts are successful). Indeed, basal testoster-
from the research testing these hypotheses, we one is considered an important “personality variable”
summarize the three main empirically supported that predicts dominance behaviors in various con-
predictions from this literature next. texts (Newman & Josephs, 2009; Sellers et al., 2007;
Mehta et al., 2008). In competition, testosterone
Prediction #1: Basal Testosterone Is levels have been positively related to perceptions of
Related to Status-Motivated and one’s personal success (Casto, Rivell, & Edwards,
Dominance Behavior 2017), competitive decision making and subsequent
One of the original and more simplistic predictions task confidence (Eisenegger, Kumsta, Naef, Gromoll,
of the biosocial model of status is that individuals in & Heinrichs, 2017, but see Apicella et al., 2011),
high-status positions in a social hierarchy would and competitive task persistence (Welker & Carré,
have relatively higher baseline testosterone levels. 2015). However, testosterone has been found to be
Higher testosterone would not only motivate behav- negatively related to the ability to accurately judge
iors to achieve such a high-status position but also the thoughts and feelings of others (empathic accu-
increase further as a result of its attainment. racy) in laboratory and real-world settings, an aspect
Although some earlier research supported this pre- of cognition that may have negative consequences
diction in humans and other species (Dabbs & on other’s perceptions of one’s leadership ability
Morris, 1990; Purifoy & Koopmans, 1979; Sapolsky, (Ronay & Carney, 2013). A recent study employing
1982), subsequent research has shown that hierar- an economic decision-making task in which dyadic
chical social ranks such as socioeconomic status and status relationships are determined during play
peer-rated ranking are not directly related to testos- (dominant–submissive, dominant–dominant, and
terone levels in men and women (Cashdan, 1995; submissive–submissive; the hawk-dove game)
Edwards et al., 2006; Mehta & Josephs, 2010; earlier showed that baseline testosterone was positively cor-
work reviewed by Mazur & Booth, 1998; Newman, related to taking a dominant position (Mehta et al.,
Sellers, & Josephs, 2005). However, those who want 2017). Although there are mixed reports on the
status may not always have it, and the complexities direct relationship between testosterone and self-
(e.g., context ­dependence) of a social hierarchy may reported dominance (e.g., Cobey, Nicholls,
make it difficult to directly link social status and ab- Leongómez, & Roberts, 2015; Grant & France,
solute testosterone levels. Indeed, a recent study of 2001; Neave, Laing, Fink, & Manning, 2003), trait
male employees working for corporate businesses re- dominance has emerged as an important moderator
vealed that testosterone levels among these men of testosterone’s relationship to dominant, competi-
were positively related to self-reported authoritarian tive, or aggressive behavior (Mehta, van Son, et al.,
leadership style, but only for those who were not in 2015; for review, Carré & Archer, 2017). For exam-
management (leadership) positions (van der Meij, ple, in one study of men competing for the affection
Schaveling, & van Vugt, 2016). Consistent with of a woman, high-testosterone individuals displayed
meta-analytic data on the relationship between more dominant behaviors, but the relationship was
actual leadership position and testosterone (van der specific to those who self-identified as dominant

Casto and Mehta 301

(Slatcher, Mehta, & Josephs, 2011). Furthermore, (Geniole et al., 2017). Even though each of these
the relationship between testosterone and social moderators ­independently accounted for effect size
status or dominance behaviors appears to also be differences in the winner–loser effect, they are not
moderated by basal levels of cortisol (see the section mutually exclusive factors; studies of the hormonal
on the dual-hormone hypothesis). response to naturally occurring athletic competition
are always outside the laboratory, where the compe-
Prediction #2: Testosterone Levels Are tition outcome cannot be manipulated, and usually
Transiently Altered During Contests for last longer than 15 minutes. Thus, the winner–loser
Status, More Often in the Positive effect is less well supported in experimental designs
Direction for Winners Than Losers outside of formal athletic competition. As a matter
A second main prediction of the biosocial model of convenience and limited access to athletes imme-
of status is that gaining status through winning a diately prior to and following a match, participants
dominance contest should increase testosterone in studies of athletic competition are often asked
levels from baseline, whereas losing should decrease to give their precompetition sample more than
testosterone levels (i.e., the winner–loser effect, also 10 minutes before the match begins and more than
referred to as the winner effect; reviewed by Casto & 10 minutes after the competition has ended (e.g.,
Edwards, 2016a). Support for this prediction has Jiménez et al., 2012). These studies have been more
been found in studies of laboratory competition, likely to show dramatic win–loss differences in tes-
where testosterone levels increased across competi- tosterone change. For studies that acquired samples
tion for those who won but decreased for those who immediately prior to and following competition
lost (e.g., Apicella et al., 2014; Carré et al., 2013; (mostly with women athletes), testosterone increases
Costa & Salvador, 2012; Norman et al., 2015). significantly across the competition period regard-
However, other studies have found that testosterone less of outcome (e.g., Casto et al., 2014, 2017;
increases across competition regardless of the Casto & Edwards, 2016b; Edwards et al., 2006;
outcome (Carré & McCormick, 2008; Henry,
­ Edwards & Kurlander, 2010).
Sattizahn, Norman, Beilock, & Maestripieri, 2017; The issue of lab versus nonlab competition in
Steiner et al., 2010; van der Meij et al., 2010). determining the emergence of the winner–loser
Summarizing the extant literature on the winner– effect is currently unresolved. What the laboratory
loser effect, Carré and Olmstead (2015) concluded context gains in experimental control, it perhaps
that a number of studies have reported that male loses in being able to sufficiently activate competi-
winners had elevated testosterone levels relative to tive motivation and in being able to create a more
losers, but that a nearly equal number of studies realistic social setting where actual status is at stake.
have failed to find such an effect. For women, less What field studies gain in ecological validity, they
studied in general, the proportion of studies that lose in experimental control. One of the most impor-
show null findings is even greater (Carré & tant potential confounds in the hormonal response
Olmstead, 2015). However, a recent meta-analysis to athletic competition is physical exertion, a
of 60 effect sizes on the winner–loser effect (Geniole factor that can elevate testosterone levels independ-
et al., 2017) determined that winners do in fact ent of competition and the psychological experience
show an increase in testosterone compared to losers, of gaining or losing social status (Copeland et al.,
who on average experience no change in testosterone. 2002; M. S. Tremblay et al., 2005; Viru et al., 2010).
Although the effect was not moderated by sex, However, efforts to quantify physical exertion in
the effect was only significant in men (men Cohen’s studies of the testosterone response to athletic
d = 0.23; women d = 0.14). competition (e.g., blood lactate, number of minutes
However, the winner–loser effect in this meta- played, self-reported physical exertion, observer-rated
analysis appears to depend on important contextual physical exertion) have not found any significant
factors; average effect sizes were moderately large correlations between these metrics of exertion and
only when the studies were conducted in nonlabo- testosterone (Aguilar, Jiménez, & Alvero-Cruz,
ratory testing locations (e.g., athletic competitions), 2013; Casto & Edwards, 2016b; T. Oliveira,
when the outcome (win or loss) was determined Gouveia, & Oliveira, 2009; Suay et al., 1999).
naturally (not contrived or manipulated), when the Furthermore, one of us (KVC) has recently col-
competition duration was greater than 15 minutes, lected saliva samples from trained men and women
and when the precompetition saliva sample was rifle shooters competing in intra- and intersquad
taken more than 10 minutes before competition rifle competition, a sport that requires the athletes

302 Competition, Dominance, and Social Hierarchy

to remain as still as possible. As with other sporting van Honk, 2006; Mehta, van Son, et al., 2015;
competitions that require more movement, rifle com- Radke et al., 2015; van Honk, Montoya, Bos, Van
petition results in significant elevations in testoster- Vugt, & Terburg, 2012; reviewed by Eisenegger,
one on average and for the majority of the athletes Haushofer, & Fehr, 2011). For example, a series of
sampled over the course of competition (+6 to 41 studies by van Honk and colleagues suggests that tes-
percent change, Casto & Edwards, unpublished). tosterone administration, after several hours, increases
threat vigilance and reduces fear-potentiated startle,
Prediction #3: Transient Increases in responses that are matched, in some cases, with
Testosterone (Associated With a Status activation of brain areas associated with emotional
Challenge) Promote Future or Subsequent reactivity (Hermans et al., 2006, 2008; van Honk
Status-Seeking Behavior et al., 1999; for review, see Carré & Olmstead, 2015).
More recently, researchers have begun to explore the Testosterone administration also may reduce cog-
functional significance of transient increases in tes- nitive reflection in men (Nave, Nadler, Zava, &
tosterone, that is, the adaptive consequence on sub- Camerer, 2017) and behaviors thought to reflect
sequent cognition and behavior (for initial review, empathy in women (Hermans et al., 2006; van
see Carré, McCormick, & Hariri, 2011). If, in fact, Honk & Schutter, 2007; van Honk et al., 2011;
testosterone increases in some individuals and under Wright et al., 2012). Additionally, other research
certain contexts, does this change serve a beneficial has shown that after receiving a dose of exogenous
purpose for attaining or maintaining status in the testosterone, men appear to perceive themselves as
future? The desire to compete again may reflect ele- more physically dominant (Welling et al., 2016).
vated dominance motivation when the individual
has the potential to improve status rank (i.e., when Testosterone and Cortisol Interact to
the potential benefits outweigh the risks). In men, Predict Social Status: The Dual-Hormone
increases in testosterone during competition predict Hypothesis
the subsequent decision to compete again against the Early predictions that testosterone should directly
same opponent in losers (Mehta & Josephs, 2006) and positively predict social status have failed to
and aggressive individuals (Carré & McCormick, garner unanimous empirical support (e.g., Neave
2008), or a different opponent in decisive winners et al., 2003; review by Mazur & Booth, 1998;
(Mehta, Snyder, Knight, & Lasseter, 2015). Mehta & Josephs, 2010). Evidence that cortisol
Testosterone increase during competition may inhibits, suppresses, or otherwise antagonizes testos-
also predict subsequent aggressive behavior in men terone secretion and action at target tissues (Burnstein,
(Carré et al., 2009), an effect that appears to be Maiorino, Dai, & Cameron, 1995; Chen, Wang,
moderated by trait anxiety (Norman et al., 2015). Yu, Liu, & Pearce, 1997; Johnson, Kamilaris,
Also in men, testosterone increases associated with Chrousos, & Gold, 1992) combined with initial
monetary wins and losses relate to future financially behavioral evidence that these two hormones might
risky choices (Apicella et al., 2014). Increased tes- interact to predict aggression (Dabbs, Jurkovic, &
tosterone has also been related to a more positive Frady, 1991; Popma et al., 2007) suggests that a
subsequent performance in athletic contexts (Cook more integrative approach to the hormone–social
& Crewther, 2012a, 2012b). In one study of women status relationship was necessary. Following these
soccer players, the higher an athlete’s testosterone early indications, Mehta and Josephs (2010) proposed
remained within the 30 minutes after competition, that “only at low levels of cortisol should higher
the greater her willingness to reconcile with her testosterone encourage higher status” (p. 898)—a
opponent—a prosocial strategy for status mainte- statement that serves as the basis of the dual-hormone
nance (Casto & Edwards, 2016c). Extending hypothesis. Testing this hypothesis, Mehta and
beyond correlational evidence, studies of exogenously Josephs (2010) indeed showed that only if an indi-
administered testosterone have shown that, for peri- vidual was relatively low in cortisol did testoster-
ods of time up to four hours after administration, one positively relate to dominance behaviors when
participants administered testosterone demonstrate instructed to act as a leader (Study 1, in men and
altered cognitions and behaviors that may promote women) and when deciding to compete again
status seeking or aid in status maintenance in ­following a defeat in a rigged puzzle competition
competitive contexts (e.g., Bos, Terberg, van Honk, (Study 2, in men).
2010; Eisenegger, Naef, Snozzi, Heinrichs, & Fehr, Several novel replications of the dual-hormone
2010; Hermans, Putman, Baas, Koppeschaar, & effect have been published (for an earlier review, see

Casto and Mehta 303

Mehta & Prasad, 2015). In varsity women athletes, How a high-testosterone/low-cortisol individual
Edwards and Casto (2013) showed that testosterone (or group) behaves in everyday interactions with
positively related to actual status as ranked by others to result in higher status is not yet fully
teammates, but only if the athlete had relatively low ­understood. This hormone profile may manifest in
levels of cortisol. As with the original studies con- a style of interacting that balances a desire for status
ducted by Mehta and Josephs, the relationship with a desire to affiliate and promote social bonding
trended toward an inverse relationship between among others in the group or network. Or these
testosterone and status for those with high levels of individuals could have a personality that balances
cortisol. In a sample of male business executives, status and power motivation with relaxed confidence
testosterone positively predicted the number of sub- and low anxiety—a personality profile that is likable,
ordinates over which an executive had authority and therefore more likely to garner the support
(but not income or education level) only if the indi- of others required to attain and maintain status.
vidual had relatively low cortisol (Sherman, Lerner, Perhaps high-testosterone/high-cortisol individuals
Josephs, Renshon, & Gross, 2016). Using social interact with others with high anxiety, low confi-
network analysis, Ponzi, Zilioli, Mehta, Maslov, dence, aggression, or desperation, effectively thwart-
and Watson (2016) showed that among profes- ing attempts to actually achieve status. Future
sional male rugby players, participants with low ­research should explore, more in depth, personality
cortisol (but not those with high cortisol) demon- correlates and behavioral interaction styles of high-
strated higher network centrality (a proxy for social testosterone/low-cortisol and high-testosterone/
status) in measures of “betweenness” and popular- high-cortisol individuals. It is also possible that the
ity. Recently published research has even extended mechanism explaining the dual-hormone effect is
the dual-hormone hypothesis to collective hormone an interaction between the negative effects of chron-
profiles in groups. Akinola, Page-Gould, Mehta, ically elevated cortisol and physiological processes
and Lu (2016) measured basal testosterone and involved in testosterone’s ability to drive status-
cortisol in a large sample of MBA students organ- seeking behavior. That is, perhaps allostatic load–
ized into (diverse and mixed-sex) groups of three to related stress and resulting high basal cortisol
six members and asked to compete against other dampens or inhibits mechanisms for status motiva-
groups in a business-related decision-making task. tion and related behaviors (i.e., a high-testosterone–
Collectively high testosterone was significantly and status relationship). Future research should expand
positively related to group performance, but only if the theoretical basis and practical applications of the
that group had relatively low collective cortisol. dual-hormone hypothesis. Additionally, although
Although null findings are less likely to be pub- this hypothesis originally concerned the interaction
lished, there have been other studies that have also between basal testosterone and basal cortisol, how
failed to support the dual-hormone hypothesis (e.g., testosterone and cortisol changes interact to predict
Geniole et al., 2013; Mehta et al., 2017). status and performance-related behavior (e.g.,
A high-testosterone/low-cortisol profile has Mehta, Mor, Yap, Prasad, 2015) is a topic of interest
also been found to relate to antisocial attitudes for future research.
(Sollberger, Bernauer, & Ehlert, 2016) and exter-
nalizing psychopathology in adolescents (Tackett, Moderators of the Relationships Between
Herzhoff, Harden, Page-Gould, & Josephs, 2014), Competition and Testosterone
factors that would seem to be detrimental to social Recent research has exposed increasingly complex
status in modern society. However, other studies qualifiers, moderators, and extenuating circumstances
have shown that a high-testosterone/high-cortisol that impact both the effect of competition on
profile (the inverse of the original dual-hormone ­testosterone change and the effect of testosterone
effect) predicts deviant or psychopathic traits change on subsequent behavior. These moderating
(Welker, Lozoya, Campbell, Neumann, & Carré, variables fall under two broad categories: (1) person
2014), reactive aggression, and self-reported feelings and (2) context factors (reviewed by Carré et al.,
of dominance (Denson, Mehta, & Ho Tan, 2013). 2010; Casto & Edwards, 2016a; Hamilton et al.,
However, at least one study has shown that the 2015; G. A. Oliveira & Oliveira, 2014, Salvador &
interaction between testosterone and cortisol has no Costa, 2009). Table 17.2 provides a categorical list
relationship to antisocial, socially deviant behavior of the person and context factors that have been
in a large sample (4,462) of male U.S. Army vet- studied and appear to be important for influencing
erans (Mazur & Booth, 2014). either the relationship between basal testosterone

304 Competition, Dominance, and Social Hierarchy

 Table 17.2. Potential Moderators of the Relationship Between Testosterone and Status or Dominance

Person Context

Physiological Performance related

Basal cortisol1 Win/loss14
2D:4D digit ratio2 Status relations
Sex3 History of wins and losses against same
Personality traits opponent15
Implicit power motivation4 Closeness or decisiveness of win/loss16
Dominance5 Situational aspects of competition design
Aggressiveness6 Intra- or intergroup nature of a
Competitiveness7 competition17
Social anxiety8 Group versus individual-based
Self-construal9 competition18
Psychological/cognitive states Outcome is determined by chance or
Mood10 ability19
Task-related self-efficacy11 Geographical/territorial
Cognitive appraisal of performance or opponent12 Home versus away location of
Task enjoyment13 competition20

1
Edwards and Casto (2013); Mehta and Josephs (2010); Ponzi et al. (2016); Sherman et al. (2016); Wu et al. (2017).
2
van Honk et al. (2012).
3
Carré et al. (2013).
4
Schultheiss and Rohde (2002); Schultheiss et al. (2005).
5
Mehta, van Son, et al. (2015).
6
Carré and McCormick (2008).
7
Costa and Salvador (2012).
8
Maner et al. (2008); Norman et al. (2015).
9
Welker et al. (2017).
10
Mazur and Lamb (1980); Mehta and Josephs (2006); Mazur et al. (1997); Zilioli and Watson (2013).
11
Costa, Serrano, and Salvador (2016); Salvador and Costa (2009).
12
Casto et al. (2017); Gonzalez-Bono et al. (1999); Oliveira et al. (2014).
13
Mehta, Snyder, et al. (2015).
14
Apicella et al. (2014); Carré et al. (2013); Costa and Salvador (2012); Jiménez et al. (2012); Norman et al. (2015); Zilioli and
Watson (2014).
15
Zilioli and Watson (2014).
16
Mehta, Snyder, et al. (2015); Zilioli, Mehta, and Watson (2014).
17
Oxford, Ponzi, and Geary (2010); Wagner, Flinn, and England (2002).
18
Mehta, Wuehrmann, and Josephs (2009).
19
van Anders and Watson (2007).
20
Carré (2009); Carré et al. (2006); Neave and Wolfson (2003).

and dominance behavior, the testosterone response to have a rise in testosterone” (p. 236). Although sub-
competition, or the effect of testosterone change on sequent research has shown the importance of
subsequent status-seeking behavior. mood as an intervening factor (Mehta & Josephs,
Early studies of the testosterone response to 2006; Zilioli & Watson, 2013), state-level mood
competition included mood as an additional vari- may serve only as a proxy for a more important
able based on the notion that testosterone should personality factor: dominance motivation. Arguably,
increase when dominance is achieved through only those who have a strong motivation for dom-
winning, but only if the individual experienced inance would experience elation upon achieving
high positive emotions regarding the win (Gladue, it through competition. Indeed, Schultheiss et al.
Boechler, & McCaul, 1989; Mazur & Lamb, 1980; (1999) wrote, “It would seem reasonable to assume
McCaul, Gladue, & Joppa, 1992; Mazur, Susman, that personality factors may moderate individuals’
& Edelbrock, 1997). In the first study published on testosterone responses to succeeding or failing at a
the testosterone response to status enhancement dominance contest” (p. 234).
and competition in humans, Mazur and Lamb Implicit power motivation is the degree with
(1980) stated that “when a man achieves a rise in which an individual derives reward from “having
status through his own efforts, and he has an elation physical, and mental or emotional impact” on
of mood over the achievement, then he is likely to others (Stanton & Schultheiss, 2009, p. 942). Those

Casto and Mehta 305

higher in implicit power motivation tend to be status instability, there should be a reversal of the
more likely to show an increase in testosterone (and winner–loser effect, whereby winners should de-
cortisol) in response to competition, particularly crease in testosterone and losers should increase.
under the context of a win (Schultheiss & Rohde, This amendment to the biosocial model of status,
2002; Schultheiss et al., 1999, 2005; Wirth et al., termed the status instability hypothesis, is based on
2006). However, this relationship appears to depend the notion that if the function of a testosterone
on sex—with stronger, more consistent relation- increase is to promote future status-seeking behavior,
ships found for men than for women (Stanton & then winners who just barely won should be less
Schultheiss, 2007). Although implicit power motivated to compete again because of a high
­motivation has received the most empirical atten- chance of moving down in status. However, losers
tion, self-reported trait dominance (e.g., Carré et al., who just barely lost should be more motivated to
2009; Mehta, van Son, et al., 2015) and competitive- compete again because of a high chance of moving
ness (Casto, 2016; Costa & Salvador, 2012) may up in status. Testing this hypothesis with women,
also play an equally important role in regulating Zilioli et al. (2014) showed that women competing
testosterone–status relationships and testosterone in a number-tracing task who won by only a small
response to competition. In Mehta, van Son, et al. margin (given feedback of their narrow win through-
(2015), testosterone administration in women out multiple trials in the task) decreased in testoster-
­resulted in increased competitive decision making one from before to after the task, whereas women
(i.e., a greater percentage of the trials in which the who lost by a narrow margin slightly increased in
competitor chose to compete again afterward), but testosterone (Study 1). In a second companion
only if the participant scored high on a personality study, under conditions of relative performance un-
measure of dominance motivation and also won certainty, women competing in Tetris showed
the competition. For participants who lost the greater competition-related declines in testosterone
competition, testosterone administration decreased than women who lost (Study 2). A simultaneous
competitive decision making regardless of individ- study in men competing in Tetris on two consecu-
ual differences in dominance motivation. tive days (Zilioli & Watson, 2014) found evidence
Social context also moderates the relationship that day 2 testosterone increased significantly more
between testosterone and competitive performance. across the competition period for those whose status
In one of the first demonstrations of this, Newman reversed from the day 1 competition (i.e., a day 1 win
et al. (2005) showed that high-testosterone indi- followed by a day 2 loss, or vice versa; an unstable
viduals placed in a high-status position performed hierarchy) compared to men who won both days or
well on a spatial and verbal task, but high-testosterone lost both days (a stable hierarchy). When wins and
individuals placed in a low-status position per- losses where manipulated to be either “clear” or
formed poorly in comparison. This effect, dubbed “narrow,” Wu, Eisenegger, Zilioli, Watson, and Clark
the mismatch effect (Josephs et al., 2006), explains (2017) showed that testosterone levels decreased
how situational constraints that contrast with self- ­significantly for narrow winners, but only if their
perceptions hamper status-seeking efforts or com- basal cortisol levels were relatively high. Despite
petitive performance when status is threatened. The some ­empirical support in these studies for the status
mismatch effect is also relevant for group-level instability hypothesis with regard to the direction of
performance. Among college students assigned to testosterone change, no studies have demonstrated
work in a group on class assignments for an entire the reverse win–lose effect pattern ­consistent with
semester, the greater the mismatch between testos- this hypothesis nor have any studies shown that this
terone and status rank within the group (i.e., the pattern of testosterone change predicts subsequent
more negative the relationship), the lower the group’s motivation to compete again—a main tenet of the
collective self-efficacy (i.e., the lower their shared hypothesis. To make more i­nformed inferences
confidence in ability to succeed), a measure that is about the functional significance of testosterone
indicative of group functioning and performance ­increases and decreases r­esulting from status gained
(Zyphur et al., 2009). and lost within stable and unstable social hierarchies,
Another social context factor that could affect future research should attempt to corroborate testos-
that relationship between testosterone and status is terone reactivity with postcontest motivational states
hierarchy stability, the degree with which one’s related to social status.
status could readily be changed. Zilioli, Mehta, and The wide array of moderating factors compli-
Watson (2014) proposed that under conditions of cates attempts to understand relationships between

306 Competition, Dominance, and Social Hierarchy

 Subsequent
competitive
Social Context motivation &
Biological Sex cognitive
states

Power Motivation
Basal & Trait Psychological
Testosterone & Cognitive Testosterone
Dominance
State Dominance & change in
status-seeking response to a
behavior status
Gender Socialization, challenge
Genetics, & life
Experiences
Basal
Cortisol

Social Status

Figure 17.2 Theoretical model for the testosterone–social status relationship.

hormones and competition, but is rightly indicative status is determined, individual differences in
of the complexity of human nature and the intricate competitiveness, the “desire to win in interpersonal
social context of status striving. Figure 17.2 displays situations” (Smither & Houston, 1992, p. 408),
an updated theoretical framework for future studies may be a direct predictor of relative social status or
testing both basal and dynamic testosterone–status the motivation to acquire it. Given the apparent
relationships. For a more complete understanding connection between status seeking and testosterone,
of the role of person and context factors, future competition-related changes in testosterone levels
research will require relatively large sample sizes to may depend on individual differences in trait
properly test moderation and other complex inter- competitiveness. Welker and Carré (2015) recently
actions. reported that basal testosterone in men correlates
with ­ persistence in attempting to solve puzzles
Additional Future Directions made intentionally unsolvable by the experimenters.
The field of social-behavioral neuroendocrinology is Although conceptually different than competitive-
a burgeoning area of scientific inquiry. Although the ness per se, task persistence is a core quality of highly
last three decades have produced foundational dis- competitive individuals. Future research should con-
coveries, there are many unanswered questions and sider including competitiveness as a person factor
new directions for future research. regulating hormonal response to competition and
explore conceptual and statistical relationships
The Role of Trait Competitiveness in ­between competitiveness and trait dominance, as
Predicting Testosterone Response to well as power motivation.
Competition
According to social comparison theory, the drive to Group Dynamics and Social Network
compete is derived from the basic human need to Analysis
reduce uncertainty between one’s own performance Real-world and everyday contests for social status
and the performance of others in order to maintain occur in the context of complex social networks
superior relative position (Festinger, 1954; Garcia, involving multilayered social group interactions
Tor, & Schiff, 2013). For some, this drive is suffi- with others. Despite the importance of group
ciently strong to prompt greater efforts to engage ­dynamics in status attainment and maintenance,
and succeed in situations where relative judgments previous research on the social neuroendocrinology
about performance are made. Because comparison of dominance has largely focused on the individ-
to others through competition is how relative social ual—testing participants in solitary rooms with

Casto and Mehta 307

little to no interaction with their “opponent.” It is with aspects such as gender and dominance-related
reasonable to assume that status lost or gained in facial features, and information about that opponent’s
contexts where participants have no current or skill level and history of success in competition
future potential interaction with each other would could be manipulated). Another area of interest
have, at best, a minor impact on one’s physiology or involves moving beyond just the categorical choice
behavior (i.e., relative standing to an unknown of willingness to compete again or not and devising
person may have little relevance to perceptions of a quantifiable measure of competitive effort follow-
social status). Indeed, individuals who are more ing testosterone elevation (i.e., a subsequent task of
characteristically similar and closer in a social network competitive persistence). As researchers expand
typically have amplified social comparison and the postcompetition repertoire of status-related
competitiveness with each other (e.g., sibling rivalry; behaviors, both antisocial and prosocial means of
Garcia et al., 2013). Thus, behaviors driven by status maintenance should be considered, as these
status motivation are most effectively employed are opposing yet equally viable strategies (Cheng
when relevant to others in a social group, one that et al., 2013). It is also important to understand the
the individual identifies with. Recognizing the role potential benefit of testosterone change, in relation
of group processes and social influence on competi- to both physiology and psychology, with the purpose
tive efforts and hormonal responses will be important of expanding the relevance, reach, and applicability
for a comprehensive understanding of the social of social neuroendocrinology more generally. That
neuroendocrinology of competition. Status motiva- short-term testosterone elevations can advantageously
tion and underlying hormonal correlates should alter future behaviors and cognitions suggests that
be considered within the context of social groups there could be some marketable use in developing
(e.g., Oxford, Ponzi, & Geary, 2010) with reference evidence-based interventions, tasks that could relia-
to factors such as an individual’s level of group bly produce endogenous testosterone increases in
identification, status ranking within the group, inter- contexts where this response could prove beneficial
and intragroup competition, and need for affiliation. for performance. Researchers in other fields, policy-
Social neuroendocrinologists could consider imple- makers, and organizations interested in how social
menting group social psychology techniques (e.g., groups function (e.g., corporate business and sports
Cheng et al., 2010, 2013; Ronay, Greenaway, teams) would better understand the value of imple-
Anicich, & Galinsky, 2012) to explore relationships menting social neuroendocrinology methods with
among group members and group-level interac- proper tools for taking advantage of the testoster-
tional characteristics of social hierarchies. Advanced one–status relationship.
statistical techniques could also prove helpful in
implementing more comprehensive social group Other Areas of Future Research
dynamics (e.g., social network analysis; Kornienko Other future directions include pursuing a better
et al., 2014, 2016). understanding of hormonal modulation of reward
circuitry in the brain (e.g., Bless, McGinnis,
The Functional Significance of Transient Mitchell, Hartwell, & Mitchell, 1997; Frye,
Elevations in Testosterone Rhodes, Rosellini, & Svare, 2002; Hermans et al.,
Another fruitful area of future research involves 2010; Montoya, Bos, Terburg, Rosenberger, & van
increasing our understanding of the adaptive purpose Honk, 2014; Packard, Cornell, & Alexander, 1997;
of testosterone reactivity in status-relevant contexts. Salvador & Costa, 2009). Although researchers
Thus, it is important to expand research on the have a growing understanding of how testosterone
immediate and subsequent benefits of rapid and tran- and other sex steroids relate to behavior, less is
sient elevations in testosterone during competitive known about the neural mechanisms of this rela-
behavior and as a result of status shifts. As discussed tionship. Additionally, social neuroendocrinology,
earlier, previous research has shown that testoster- discipline-wide, is challenged with the vital goal
one elevations, under certain contexts, increase of improving assay methodologies to increase the
subsequent willingness to compete again and appear validity of hormone measurement (Granger,
to alter cognitions in ways that could benefit status Shirtcliff, Booth, Kivlighan, & Schwartz, 2004;
seeking. Going further, researchers could explore Granger et al., 2007; Welker et al., 2016). Perhaps
testosterone-related competitive decision making there is no more pressing task than this given that
when manipulating aspects about one’s opponent the accuracy of hormone data is the basis of all
(e.g., photos of potential opponents could be shown other assumptions about hormone–behavior rela-

308 Competition, Dominance, and Social Hierarchy

tionships. Finally, future research should make Anderson, C., & Kilduff, G. J. (2009). The pursuit of status in
greater efforts to explore how the research discussed social groups. Current Directions in Psychological Science, 18,
295–298.
in this chapter is dependent on sex, gender, gender Apicella, C. L., Dreber, A., Gray, P. B., Hoffman, M., Little,
identity, and gender socialization and expand theo- A. C., & Campbell, B. C. (2011). Androgens and
retical models to include a more comprehensive competitiveness in men. Journal of Neuroscience, Psychology,
understanding of the endocrinology of status moti- and Economics, 1, 54–62.
vation and social hierarchies among women (Casto Apicella, C. L., Dreber, A., & Mollerstrom, J. (2014). Salivary
testosterone change following monetary wins and losses
& Prasad, 2017). predicts future financial risk-taking. Psychoneuroendocrinology,
39, 58–64.
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 CH A PT E R

18 Oxytocin
An Evolutionary Framework

Nicholas M. Grebe and Steven W. Gangestad

Abstract

Substantial excitement surrounds the mammalian peptide hormone oxytocin (OT) due to its potential
to be a “hormone of love”—and more generally, a biological foundation for the diverse classes of
intimate social bonds. Yet, theoretical models have struggled to absorb inconsistent, even
contradictory, findings. Evolutionary theory will guide a coherent functional interpretation of the
OT system. This chapter focuses on life history theory, a branch of theoretical biology that seeks
to identify how natural selection shapes organisms’ efforts to optimally allocate limited resources.
Endocrine hormones are important mediators of this process. A review of the psychological and
physiological literature regarding OT suggests a number of possible trade-offs negotiated by
oxytocinergic activity. This chapter proposes a provisional life history model in which OT is central to
the regulation of important but vulnerable social relationships. It outlines implications of this model,
addresses a number of caveats, and suggests directions for future research.
Keywords: oxytocin, life history theory, trade-offs, behavioral endocrinology, evolutionary biology

Evolutionary psychologists, in the tradition of OT is a mammalian protein hormone. It evolved

Tinbergen’s (1963) “four questions,” are interested within a larger family of structurally similar “-tocin”
in the physiological underpinnings of psychological peptides (e.g., vasotocin, mesotocin) that is observed
mechanisms. Hormones have become a point of in birds, reptiles, and invertebrates, which likely de-
focus as theoretically powerful tools for building buted 600+ million years ago (Gruber, 2014). OT
a conceptually coherent evolutionary framework is well known within medical circles for its func-
linking physiology to behavior. Life history theory, tions in parturition and lactation, and it has well-­
a branch of theoretical biology, identifies hormones established effects on maternal behavior (e.g., Numan,
as components of a system that evolved to solve 2017). Since the discovery that OT may also be cru-
contingent allocation problems—that is, they are cial to the formation of sexual pair-bonds in certain
solutions to demands that organisms adaptively species (e.g., Williams, Insel, Harbaugh, & Carter,
­allocate energetic and other resources differently de- 1994) in ways similar to how it affects mother–­
pending on conditions, as assessed by cues external offspring bonds (Nelson & Panksepp, 1998), scien-
or internal to the organism (e.g., Finch & Rose, tists and laypeople alike have been fascinated by the
1995). Though some hormonal systems have been possibility that this biological messenger is integral
analyzed in this manner (e.g., Bribiescas, 2001; to the most meaningful, “close,” social relationships
Ellison, 2003), oxytocin (OT) has not. Here, we in our lives. Indeed, the hormone has been labeled,
­advance a conceptualization of the OT system derived variously, as the “love,” “cuddle,” or “trust” hormone
from life history theory, as a demonstration of (e.g., Uvnäs-Moberg, 2003; Zak, 2012). About
the significance this approach has for evolutionary 15 years ago, means of experimentally administering
behavioral endocrinologists. OT via nasal spray were developed, and today over

317
500 experimental administration studies of OT can to propose an integrative model for understanding
be found in the literature. Contrary to some initial how OT functions to affect resource allocations.
expectations, OT does not uniformly promote Our proposals are necessarily preliminary, but, we
­prosocial behavior and feelings of warmth. Mixed think, proposals of the kind we offer are needed for
findings have led to a proliferation of attempts to further progress toward conceptual integration; our
conceptualize OT’s many and contrasting effects proposals illustrate this broader point.
within a single, coherent framework (see, e.g., Fourth, we discuss caveats, unanswered ques-
Bethlehem, Baron-Cohen, van Honk, Auyeung, & tions, and future directions of theory and research.
Bos, 2014; Churchland & Winkielman, 2012; Crespi,
2016; Numan & Young, 2016). New perspectives A Life History Framework for
continue to appear and evolve (e.g., Hurlemann & Understanding the Function of
Scheele, 2016), and no consensually agreed-upon Endocrine Hormones
resolution has been reached. Life History Theory
We review the major conceptual frameworks Organisms allocate energy harvested from the envi-
for understanding OT, but, more fundamentally, ronment to fitness-enhancing activities. Energy allo-
we step back and try to view OT and its manifesta- cated to one kind of activity is not available for
tions with a wider lens. The OT system is an ­allocation to other kinds. Organisms hence inevita-
evolved one. Though this system has a range of bly face allocation problems. As some systematic ways
psychological effects, it also controls physiological of allocating energy promote a particular organism’s
outcomes that are nonpsychological in nature via ­fitness, given its circumstances, better than others,
effects on a wide array of bodily tissues. Psychological solutions to these allocation problems evolve through
and nonpsychological manifestations of the OT natural selection. In other words, selection sifts
system likely have effects coordinated to serve its through the myriad possible allocation “strategies”
functions. Hence, a full, coherent explanation of that organisms within a species utilize; solutions that
the functions of the OT system should also account make it through selection’s sieve tend to be ones that,
for OT’s nonpsychological effects. In early mamma- relative to others, maximize fitness. Other limited re-
lian species, these functions likely regulated partic- sources such as micronutrient building blocks, time,
ular relationships, notably the mother–offspring and neural or other tissue-specific resources also give
one; only more recently did it acquire functions rise to allocation problems. Life history theory seeks
that promote other relationships. A broader, evo- to identify how selection shapes organisms’ solutions
lutionary view suggests the OT system coordinates to these allocation problems (e.g., Charnov, 1993;
a host of effects, which likely evolved initially in Del Giudice, Gangestad, & Kaplan, 2015).
the context of certain relationships—this, we feel, How an organism can best use limited resources
guides a coherent interpretation. In addition to depends on life circumstances. Optimal allocation
­reviewing the major psychological conceptualiza- solutions hence embody contingencies. For in-
tions put forward to date, we develop and emphasize stance, an organism’s relative body size, current state
the argument for this framework. of pathogen load, level of imminent threat from a
Our chapter has four sections. First, we start with predator or conspecific, and immediate opportunities
some foundational notions—specifically, a broad life to potentially mate may all affect how the organism
history framework for understanding the evolved should best allocate resources. Because energy and
functions of endocrine hormones. This framework other resources are limited, any decision to allocate
offers reasons that, when seeking to explain the func- additional energy toward certain activities (e.g.,
tion of any particular hormonal effect, other effects growth, immune function, defense or flight, mating
are pertinent. It also integrates phylogenetic perspec- display or intrasexual competition) inevitably re-
tives that pertain to how endocrine systems evolve. quires, simultaneously, decisions to draw energy away
Second, we give an overview of the literature from alternative current or future activities.
on OT’s psychological effects. We begin with well-­
established neuromodulatory effects in nonhuman Endocrine Hormones Within a Life
mammals and end with a special focus on humans. History Framework
Third, we attempt to place OT’s neuromodula- Endocrine hormones are released by a gland (e.g.,
tory effects in the broader evolutionary framework the gonads, the pituitary) into the circulatory system.
emphasizing hormonal modulation of resource They then travel to and bind to receptors located in
­allocation. That is, we use a life history framework multiple bodily tissues. Binding initiates chains of

318 Oxy tocin

reactions that affect cellular activity, typically in a allocation of neural resources (e.g., allocation of
tissue-specific manner. Changes in cellular activity attention to competing stimuli, the appraisal of
­
then produce phenotypic changes. A hormone’s those stimuli, the potency of particular rewards and
phenotypic manifestations may be numerous and punishments). OT, like some other hormones, is
diverse across the many tissues it affects, a phenom- projected directly into brain regions, where it acts as a
enon referred to as hormonal pleiotropy (e.g., Flatt, neurotransmitter that up-regulates or down-regulates
Tu, & Tatar, 2005). specific neural networks.
In essence, then, hormones are chemicals that
relay messages to multiple cellular “recipients.” This Conditional Responsivity and Internal
essential character of hormones gives rise to a straight- Regulatory Variables
forward conceptualization of what endocrine systems Once again, allocation solutions should be sensitive
have been shaped by selection to do: These systems to circumstances perceived and interpreted by the
were shaped to coordinate simultaneous shifts of ener- organism. The concept of “internal regulatory vari-
getic and other limited resources from one set of activities ables” (Del Giudice et al., 2015; Tooby, Cosmides,
to another, contingent on life circumstances (e.g., Ellison, Sell, Lieberman, & Sznycer, 2008) reflects appraisals
2017; Finch & Rose, 1995; Ketterson & Nolan, regarding the timing and magnitude of allocation
1999; Lancaster & Sinervo, 2011). That is, endocrine modifications (e.g., of environmental predictability,
systems were designed to ­mediate allocation decisions. exogenous mortality risk, the state of social rela-
We can systematically identify the components tionships, and potentially many other conditions).
of an endocrine system shaped by selection to Organismal systems are designed to secrete hormones
achieve optimal allocations. Subject to selection are in response to these appraisals, which then coordinate
(1) the mechanisms that dictate the circumstances reallocations.
under which a hormone will be released (and then
“shut off ”), (2) the distribution of receptors that re- Functional Reverse Engineering
ceive signals, and (3) how tissues respond to receipt of Hormonal Coordination
of signals. Hormonal effects are phenotypically integrated to
Two additional concepts flesh out this life his- yield particular benefits. Hence, nonpsychological
tory view. The first is phenotypic integration (e.g., effects of hormones, as well as psychological effects,
Ketterson, Atwell, & McGlothlin, 2009). The mul- critically inform an understanding of a hormone’s
tiple phenotypic changes that hormones coordinate specific way of achieving functions. That is, both
have been selected to “work together” to produce constrain the range of plausible interpretations of
benefits. For example, Ketterson and Nolan (1999) how selection shaped the endocrine system to mod-
found that, during dark-eyed juncos’ mating season, ulate allocations.
male testosterone increases both attractiveness to
females and range size, each of which foster mating Phylogeny and Adaptation
success. The second is allocation trade-offs. To “pay Phylogenetic perspectives complement adaptationist
for” up-regulated effort toward some ends, organ- ones. A hormonal system present now also existed,
isms must down-regulate effort toward others. in some form, in deep evolutionary time. But most
Some phenotypic changes induced by hormones, likely, it did not coordinate the exact same suite of
then, are beneficial not because they directly pro- coordinated outcomes, activated by the exact same
duce benefits, but rather because they pay the costs circumstances. Co-option has occurred when a hor-
for other beneficial changes. For instance, once monal system gains a new benefit that did not exist
again in dark-eyed juncos, male testosterone leads in previous species in a lineage. Co-opted outcomes
to decrements in parental efforts (e.g., feeding of have been shaped by previous benefits and must
offspring), not because there is inherent value in serve the new benefit sufficiently well. Secondary
doing so, but rather because other efforts—for ex- adaptation occurs when the new function (or benefit)
ample, toward finding and attracting mates—are leads to modification of the system in ways that serve
prioritized (Ketterson & Nolan, 1999). the new function better while maintaining previous
functionality (see Gould & Vrba, 1982).
Neuromodulation as Part of an Adaptive OT illustrates these points well. OT-like peptides
Complex of Modulatory Responses had functions in ancestors common to vertebrates
Receptors for a host of hormones reside within and some invertebrates (e.g., mollusks, arthropods,
the brain, such that hormonal “messages” regulate annelids; Gruber, 2014), often pertaining to control

Grebe and Gangestad 319

of specialized smooth muscle contractions. In an Williams et al., 1994; see also Young & Wang, 2004).
early vertebrate, both OT and vasopressin homo- This work led to more recent work on human pair-
logs emerged and evolved to acquire distinct, but bonded couples. OT administration leads to more
sometimes overlapping, functions (e.g., Hoyle, engaged, constructive communication about rela-
1999). OT per se debuted in placental mammals tionship conflicts (Ditzen et al., 2009); more intense
~250 million years ago (Donaldson & Young, orgasms; and greater contentment with a partner
2008; but see also Gwee, Amemiya, Brenner, & following intercourse (Behnia et al., 2014). OT
Venkatesh, 2008), in which it induces uterine con- levels predict success of emotional support relation-
tractions (e.g., Bell, 1909; Dale, 1906), reduces the ship interventions (Holt-Lunstad, Birmingham, &
severity of postpartum hemorrhage (e.g., Elbourne, Light, 2008) and overall relationship satisfaction
Prendiville, & Chalmers, 1988; Weitzman, Glatz, & (Holt-Lunstad, Birmingham, & Light, 2015; but
Fisher, 1978), and activates the milk letdown reflex see T. W. Smith et al., 2013). New lovers have ele-
during lactation (e.g., McNeilly, Robinson, Houston, vated OT compared to singles, and OT levels at a
& Howie, 1983; Wakerley & Lincoln, 1973). These ­relationship’s outset predict its success half a year
events set the stage for an important co-option. In later (Schneiderman, Zagoory-Sharon, Leckman, &
particular, the presence of OT in mothers with new- Feldman, 2012). (For related effects in marmosets,
borns, owing to its peripheral reproductive func- see Seltzer & Ziegler, 2007; T. W. Smith et al., 2010).1
tions facilitating parturition and lactation, may have OT perhaps has been co-opted to play roles in
led it to acquire functions coordinating behavioral yet other interdependent social relationships, such
aspects of maternal care through OT projections in as those between kin, friends, and in-group mem-
the central nervous system (Carter, 2014; Crespi, bers (e.g., Crespi, 2016). The OT homologs in birds
2016; Feldman, Monakhov, Pratt, & Ebstein, 2016). appear to have acquired some such social functions
OT is now well established as a key mediator of the (Goodson, 2013). And OT may play such roles in
mother–offspring bond forged during parturition some mammals as well (Anacker & Beery, 2013).
(Carter, 2014), lactation (Crowley & Armstrong, Although such roles in humans are possible, we
1992), emotionally “warm” touch (Feldman, Gordon, offer a cautionary note: As emphasized previously,
Schneiderman, Weisman, & Zagoory-Sharon, 2010), co-option of OT should not affect social relation-
and responses to infants’ cries (Riem et al., 2011; see ships in ways that would markedly compromise its
also Elmadih et al., 2014). Classic work on rodents role in the mother–infant relationship. We believe it
demonstrates roles for OT in both establishing and is more likely that co-option occurred for pair-
maintaining maternal behavior via particular brain bonding than for other kinds of social relationships.
regions (e.g., the nucleus accumbens; e.g., Numan, More work is needed along these lines.
2017). OT plays a role in infant responses to mothers
too, and the success or failure of this bond’s formation
early in an infant’s life may have long-lasting effects on
Oxytocin’s Psychological Effects
the OT system (e.g., Fries, Ziegler, Kurian, Jacoris, and Correlates
A vast literature examining the psychological effects
& Pollak, 2005).
of OT has accumulated over the last 15 years.
OT likely regulates responses to partners in inter-
Although the literature on the associations between
dependent social relationships aside from the
levels of OT and behavior or context (outside of
mother–infant one (e.g., Carter, 2014; Crespi, 2016;
maternal behavior) is defined by perhaps a couple
Numan & Young, 2016). These effects reflect addi-
dozen studies, over 500 published intranasal ad-
tional co-options. Crucially, OT’s effects on social
ministration studies (including some clinical trials)
behavior likely stem from the “biological prototype”
have appeared in scientific journals (see Bos,
for mammalian sociality: the mother–infant bond
Panksepp, Bluthé, & van Honk, 2012). The former,
(e.g., Carter, 2014; Numan & Young, 2016).
observational studies typically speak to the causes or
Most notably, OT has been co-opted for pair-
bonding. Seminal studies focused on voles. Prairie
voles form enduring sexual pair-bonds. Montane 1
The OT homolog present in passerine birds (mesotocin)
and meadow voles do not. OT receptors are much may or may not play similar roles in pair-bonding. Although
denser in members of the monogamous species, in some research suggests it does (Klatt & Goodson, 2013; Lowrey
which OT production during mating affects pref- & Tomaszycki, 2014; Pedersen & Tomaszycki, 2012; for effects of
vasotocin, see also Baran, Tomaszycki, & Adkins-Regan, 2016),
erences for pair-bond partners (Cho, DeVries, whether mesotocin’s role in either maternal care or pair-bonding
Williams, & Carter, 1999; Insel & Shapiro, 1992; is widespread across bird species remains unknown.

320 Oxy tocin

concomitants of OT production, whereas the latter, finding social connection between people—a “calm
experimental studies speak to effects of increased OT. and connect” system (Uvnäs-Moberg, 2003). As
search for connection purportedly promotes proso-
The Maternal Brain in Rats cial motivation (e.g., trust and trustworthiness;
Before we review the literature on human OT, we Kosfeld, Heinrichs, Zak, Fischbacher, & Fehr, 2005;
briefly describe classic work on the neurobiology of Zak, Kurzban, & Matzner, 2005), OT has also been
maternal behavior in rats, as it offers a foundation proclaimed to be a “moral molecule” (Zak, 2012).
for understanding proximate mechanisms of OT’s OT may indeed shape a neurobiological system
psychological effects. Whereas nulliparous female to promote positive valence of an infant or romantic
rats actively avoid rat pups, new mothers engage in partner (though, as noted earlier, other hormones
well-established maternal behaviors with them (e.g., promote nurturing behavior too; Numan, 2017).
nursing, licking, retrieval from the nest), even when The view that OT generically or unconditionally
their own pups are experimentally removed and re- promotes social connection and prosociality, however,
placed with another mother’s pups. Various hor- is simply no longer viable. A recent meta-analysis of
mones (e.g., estradiol, progesterone, prolactin) pres- the effects of OT administration on trust in experi-
ent at birth alter maternal brain structures and lead mental trust games found no robust overall effect
to these effects (see Numan, 2017). (Nave, Camerer, & McCullough, 2015). Hence,
OT too plays a crucial role in the neurobiologi- while found to increase trust in some experimental
cal alterations behind maternal behavior. OT pro- games (Kosfeld et al., 2005), OT has been reported
jections to the medial preoptic area (MPOA) and to decrease it in others (Bartz et al., 2011). OT ad-
ventral tegmental area (VTA) modulate neural ministration has sometimes been found to disrupt
input to the nucleus accumbens (NAc). When co- social connection, for example, by prompting envy
occurring with mesolimbic dopaminergic (DA) ac- and gloating (Shamay-Tsoory et al., 2009), leading
tivity, OT inhibits NAc activity, which has the effect men to perceive less warmth in faces (Hoge et al.,
of releasing inhibition of the ventral pallidum (VP). 2014), promoting self-interested moral judgments in
Resultant VP activity promotes maternal behavior men (Scheele et al., 2014), and derogating out-groups
(partly via sensory processing of offspring stimuli, (De Dreu et al., 2011). Relatedly, some ­correlational
such as scent cues; see Numan et al., 2005; Numan studies report OT to be positively associated with
& Stolzenberg, 2009; Stolzenberg & Numan, relationship distress (Taylor, Saphire-Bernstein, &
2011; Numan, 2017; for similar effects in sheep, see Seeman, 2010) and anxiety about r­omantic rela-
Numan & Young, 2016). These neurobiological tionships (Marazziti et al., 2006; Weisman, Zagoory-
­networks fundamentally regulate motivation. OT Sharon, Schneiderman, Gordon, & Feldman, 2013).
affects pair-bonding in prairie voles through near- After women were asked to think about relational
identical networks (e.g., once again, OT and DA distress, their OT levels increased (Tabak,
work together to inhibit NAc control of VP; e.g., McCullough, Szeto, Mendez, & McCabe, 2011).
Aragona, Liu, Curtis, Stephan, & Wang, 2003; Liu The mixed nature of findings regarding OT’s
& Wang, 2003; see also Numan & Young, 2016). ­effects on social bonding and connection gives rise
OT not only establishes maternal behavior to the oxytocin paradox (Bethlehem et al., 2014).
but also maintains it. Though maternal behavior How can a unified, coherent conceptualization of
­persists even if OT is withdrawn, variations in OT OT explain its contrasting effects?
levels postestablishment affect its quality (e.g.,
Numan, 2017; for correlational work on humans, Toward Resolving the Oxytocin Paradox
see Elmadih et al., 2014). OT likely also affects, A number of views about what OT does, funda-
downstream, cortical systems regulating attentional, mentally, to produce its psychological effects have
cognitive, or emotional processes. been put forward.
She Loves Me, She Loves Me Not: OT is fundamentally anxiolytic. In one view, OT
The OT Paradox dampens reactivity of the hypothalamic-pituitary-
One popularized view is that OT is, metaphorically, adrenal (HPA) axis to threats and, hence, suppresses
the neurobiological “cement” that bonds an indi- cortisol responses to stress (e.g., Windle, Shanks,
vidual to another, whether it be mother to infant or Lightman, & Ingram, 1997). Relatedly, OT may
one pair-bond partner to another. The OT system reduce amygdala activity and, thus, suppress fear
has been characterized as one that fosters interest in responses (e.g., Kirsch et al., 2005). Fundamentally,

Grebe and Gangestad 321

in this view, its psychological effects—for example, state (Hurlemann & Scheele, 2016). Like the social
on interpersonal trust, perceived trustworthiness of salience hypothesis, this view proposes that
others, willingness to cooperate with in-group mem- OT’s ­effects build off of pre-existing psychological
bers, and interest in affiliation with others—all stem appraisals. The difference is that, in this view, self-­
from generalized dampening of stress responses referential processing, not simply situational con-
(e.g., Churchland & Winkielman, 2012; Neumann strual, is key. Hurlemann and Scheele argue that
& Slattery, 2016). Influenced by OT, people see representations of the self often include close social
other people as less threatening (for details, see partners (see Aron & Fraley, 1999). Accordingly,
Churchland & Winkielman, 2012). people may be especially sensitive to social informa-
tion emanating from close social partners, who are
Although OT does suppress anxiety and fear in
seen as part of the “self.”
some circumstances, other findings challenge this
view. First, once again, OT administration sometimes OT modifies reward sensitivity. Neurobiological
leads to diminished trust (see Bethlehem et al., 2014). studies of rats, once again, establish that OT recep-
Second, OT administration may not always sup- tors populate dopaminergic mesolimbic structures,
press stress responses; in some research paradigms, it ­notably the VTA and NAc, which are known to
has promoted episodic memory for aversive events ­importantly regulate reward sensitivity: detection of
(Striepens et al., 2012), anxiety responses to unpre- rewarding stimuli, tracking and reinforcement of
dictable events (Grillon et al., 2013), emotional in- behaviors leading to reinforcing consequences, and
tensity in response to conflict with partners in men attention to discriminative cues upon which rein-
(Ditzen et al., 2012), and Pavlovian fear conditioning forcement is contingent. OT, then, may exert its
(Eckstein et al., 2015). To explain mixed findings, major psychological effects through modification of
Eckstein et al. (2015) propose that OT has targeted these reward circuits (see Bethlehem et al., 2014;
anxiolytic effects—specifically, to promote extinction Numan & Young, 2016).
of stress responses (see also Neumann & Slattery,
A cascade of effects. Naturally, OT need not have psy-
2016). In absence of conditions conducive to ex-
chological effects through just one route. Indeed, at
tinction (e.g., when social support is absent), OT
a neurobiological level, OT affects, directly and
may have no effect (e.g., Heinrichs, Baumgartner,
through downstream influences, multiple structures
Kirschbaum, & Ehlert, 2003) or even potentiate
and systems (Numan, 2017). Perhaps the most sen-
threat responses.
sible view, then, is that OT affects motivation and
OT promotes social salience. Another view is that OT cortisol responsivity and attention (both to external
heightens the salience of social cues and information stimuli and interoceptively). Of course, this view,
(e.g., Bartz et al., 2011; Striepens et al., 2012), largely while likely, requires that key questions be answered:
via effects on dopaminergic reactivity, especially in Through what processes does it do so? How are
mesolimbic regions (see Shamay-Tsoory & Abu-Akel, these effects functionally coordinated? How does
2016). In this view, OT’s effect on perceived safety the OT system “work”? Answers to these questions,
or threat is context dependent. When social threats in our minds, require an understanding of the
are minimal, OT administration should bolster a sense evolved (and likely current) contexts in which OT
of safety. However, in the presence of social threats, exerted its important psychological effects.
OT should augment perception of those threats.
Although the social salience hypothesis expects
The Mother–Infant Prototype Revisited
that OT will only selectively promote prosociality,
Once again, OT’s effects on social behavior in
it does not uniformly render correct predictions (see
mammals likely debuted evolutionarily in the con-
Bethlehem et al., 2014). Hence, for instance, whereas
text of maternal–infant interactions. And, although
OT has been found to promote in-group favoritism,
its psychological effects may have been co-opted
regardless of how the in-group and out-group are
and modified for other social contexts, modification
appraised (De Dreu et al., 2011), the social salience
of the OT system should not seriously disrupt its
hypothesis would seem to predict that group ap-
functionality within the maternal–infant relation-
praisals matter.
ship. That is, OT’s psychological effects likely evolved
OT enhances self-referential processing. Yet another because they promoted maternal care for and pro-
view argues that OT enhances emotional interocep- tection of an infant, and, in a maternal–infant rela-
tion—awareness of one’s own subjective emotional tionship, they should still do so.

322 Oxy tocin

 With this assumption in mind, let us reflect Two important implications follow. First, the
on proposed conceptualizations about how OT specific effects of OT will depend on the exact nature
­affects psychological processing. The social salience of the circumstances in which the OT response
hypothesis argues that OT renders social cues salient occurs (e.g., differ across mother–infant and pair-
and nonsocial cues less salient. A related view claims bond relationships). Second, we cannot fully un-
that OT potentiates social rewards and de-potentiates derstand how OT functions without knowing the
nonsocial ones. Would these effects promote maternal contexts in which OT increases are naturally experi-
care for an infant in the context of a maternal– enced. The second implication derives from the
infant relationship? OT may facilitate proficient first: If OT’s specific effects are contingent on the
maternal care if it were to render salient social cues context in which an OT response occurs, then OT’s
emitted by the infant or promote the social reward functionality is tied to the contexts in which the OT
value of cues of infant responsiveness and well-being. system is designed to activate.2
Yet generalized salience of social cues or potentiation
of social rewards could be expected to degrade the Natural Circumstances Producing Oxytocin
quality of maternal care (e.g., if mothers attended to Responses in Romantic Relationships
other social partners rather than their infants). What, then, are the natural circumstances in which
Similarly, one can ask about how OT would promote an OT response is produced? For instance, what
pair-bonding in these views. Although attention to ­circumstances in romantic relationships lead to OT
social cues emitted by a partner or potentiation of responses? Once again, multiple proposals exist.
rewards in the context of the pair-bond may facilitate The calm-and-connect model (Uvnäs-Moberg, 2003)
bond formation, attention to social cues emitted by expects positive associations between OT levels and
others or potentiation of rewards garnered from romantic relationship quality. Some research finds
other social relationships could disrupt pair-bonding. that relationship bonding (expressed by touch or
OT’s effects, then, may well be expected to social cues) leads to OT production, which may re-
target particular relationships. The salience of social inforce nurturing behaviors and thereby facilitate
cues or modification of social rewards should be connection between partners (e.g., Grewen, Girdler,
“tagged” to specific partners. Indeed, one might Amico, & Light, 2005). By contrast, the tend-and-
expect attention to social cues emitted by some in- befriend model (see also Mogilski et al., this volume)
dividuals to be diminished. Consistent with this proposes that distress or anxiety within relation-
notion, experimental work on rats examining OT’s ships leads to OT release, which in turn increases
effects on maternal behavior finds that maternal “appetite” for social affiliation outside of the dis-
motivations are specially affected: It facilitates mater- tressful bond (Taylor, 2006). Some studies report
nal care (e.g., pup carrying, attentiveness to pups, associations between OT and relationship distress
feeding of pups, maternal protective aggression; (e.g., Taylor, 2006; Taylor et al., 2010; see also Tabak
see, e.g., Numan & Young, 2016). et al., 2011). (See also T. W. Smith et al., 2013, who
found no support for one model over the other.)
Targeting of Oxytocin-Facilitated Behavior
How might targeted social attention and motivation
emerge? In a species in which OT has been co-opted
2
Methodologically, this means that the functionality of the
OT system cannot be understood through experimental adminis­
to function in multiple social contexts (e.g., pair- tration studies alone. In administration experiments, OT’s effects
bonding, as well as maternal care), OT’s effects are examined within contexts chosen by the experimenters, not
should not be tagged to specific phenotypic cues of contexts in which OT secretions and projections naturally
one class of social targets, such as the faces of in- occur. Furthermore, OT administration outside the presence of
a natural circumstance that would produce OT secretion may
fants. Such a system would not permit OT’s effects evoke a response, but one that bears little similarity to the
to be tagged to another class of individuals, such as response produced in any natural circumstance leading to OT
adult pair-bond partners. A more sensible design secretion.
might tag OT’s effects on social relationships that Other methodological limitations of OT administration studies
have recently received attention. The typical administration
otherwise exert potent motivational effects within study is woefully underpowered to detect small to moderate
the context in which an OT response occurs. For effects (power ~15 percent; Walum, Waldman, & Young, 2016).
instance, in the context of maternal care, the potent Moreover, intranasal administration results in massive increases
in peripheral levels, but only a small amount is absorbed
relationship figure is the infant; in the context of
centrally, such that some effects may be downstream behavioral
pair-bonding, it is the acquired or potential pair- outcomes arising from peripheral effects (e.g., on heart rate;
bond partner. Leng & Ludwig, 2016).

Grebe and Gangestad 323

 In collaboration with others, we propose a third infants against threats (e.g., predators, threatening
model, the identify-and-invest model (Grebe et al., conspecifics; e.g., Bosch, Meddle, Beiderbeck,
2017). It follows from the notions we laid out pre- Douglas, & Neumann, 2005).
viously. In this view, events that prompt motivation OT may promote maternal aggression through
to attend and respond to a relationship partner lead its anxiolytic effects (specifically, via inhibition of
to OT release—most notably, cues that a valued the effect of corticotropin-releasing factor [CRF] in
­relationship is threatened—which then functions the amygdala on generalized fear responses; Numan,
to reorient psychological resources toward the rela- 2017). As defense should be targeted to threats to an
tionship. Romantic relationship threat may arise infant, however, it seems likely that OT’s effects on
when individuals themselves are highly invested in maternal aggression are also mediated through mo-
those relationships yet their partners are less invested tivation to protect the infant and, hence, motivated
or attentive to them. Grebe et al. (2017) asked ro- attentional monitoring of threats to the infant. This
mantically involved women and men to think line of thinking suggests OT may similarly motivate
about ways their relationship partners were respon- protective responses (and aggressive responses to
sive to them or not and measured the rise or fall of threatening outside parties) in the context of pair-
OT as a function of this task. We also administered bonding, fostered by attentional monitoring to rela-
a battery of measures of relationship involvement tionship threats. The identify-and-invest model fits
to both members of the couple. We regressed indi- well with the view that one major function of OT
viduals’ OT response to the task on both self- and within close relationships is the protection against
partner reports of relationship involvement. Analyses threats. Circumstances that threaten a relationship are
revealed positive associations between self-reports of precisely those in which attention to those threats
relationship involvement and OT, yet negative as- and action to defend against them are called for.3
sociations between an individual’s OT and his or Some scholars propose that OT has been co-opted
her partner’s reports of investment. Consistent in humans to regulate social relationships. For in-
with the identify-and-invest model, peripheral OT stance, OT may facilitate prosocial behavior toward
release was predicted by a discrepancy between an in-group members and defensive behavior toward
individual’s own and his or her partner’s relation- out-group members (De Dreu et al., 2010, 2011).
ship involvement. Discrepancy prompts motivation This view similarly interprets OT’s antisocial behav-
to attend to the relationship, which OT purportedly ioral effects toward specific parties in terms of its
functions to do. protective or prosocial effects toward other parties.
In our view, the identify-and-invest model is When individuals were presented with mixed
compatible with the idea that OT-regulated maternal praise and criticism from others, Gao et al. (2016)
care constitutes the foundation from which the OT found that OT administration enhanced salience of
system was co-opted to function to regulate other praise in women, but fostered salience of criticism
relationships, such as pair-bonds. OT should function in men. They propose that the sex difference may be
to lead mothers to attend to their infants’ needs and rooted in different parental roles that women and
protect them in the face of threats. It may make sense, men played ancestrally and, hence, stem from basic
then, that OT’s effects co-opted to pair-bonding evolved functions of OT. Whereas women’s parental
should lead to attention to the threatened relationship duties may have more centrally involved direct care-
(and not the desire to forge new relationships, as the giving, men may have played a more protective role,
tend-and-befriend model proposes). guarding against potential harm and threat. (For
similar sex differences, see Hoge et al., 2014; Scheele
et al., 2014.)
Nonprosocial and Aggressive Responses
The perspective that OT’s prosocial effects should
be targeted to specific relationships also facilitates 3
Earlier, we emphasized a limitation of OT administration
an understanding of OT’s nonprosocial and aggres- studies: OT may be administered in contexts in which OT is
never naturally projected centrally (at levels attained). Though
sive effects. If and when third parties represent OT may have effects in such contexts, their effects may not
threats to infant well-being, adaptive prosocial be understandable in terms of adaptive response to particular
­responses with regard to the infant may constitute circumstances. The point may be illustrated by antisocial effects:
These effects may actually be prosocial or protective with regard to
defensive or aggressive responses to third parties. other relationships, but if OT administration occurs in the absence
Indeed, in some nonhuman species, OT is widely of such a relationship, the study does not readily lend itself to
recognized to promote maternal aggression to protect such an interpretation.

324 Oxy tocin

Toward a Life History Model of the et al., 2013; see also Blevins et al., 2015). Indeed, a
Oxytocin System: Integrating single-dose intranasal OT administration decreased
Psychological and Physiological Effects men’s caloric intake during a meal by an average of
As laid out earlier, within a life history perspective, 122 kcal (Lawson et al., 2015). Another study found
hormonal systems have fundamentally been shaped effects specific to consumption of carbohydrate-rich
by selection to carry out resource allocation decisions; foods (Ott et al., 2013). At the same time, OT may
when activated, they lead energy and other resources increase energy expenditure. OT knockout mice de-
to be directed toward certain fitness-enhancing velop obesity, even when nutrient intake is constant
­activities, while shunting them away from other (Takayanagi et al., 2008; see also Deblon et al.,
­activities. The many simultaneous effects are pheno- 2011). Cardiac muscle cells in particular utilize more
typically integrated, working together to promote a glucose-fueled energy in response to OT exposure
benefit or set of benefits in certain conditions— (Gutkowska & Jankowski, 2012). OT administration
those in which the adjustments paid off ancestrally to rhesus monkeys increases resting energy expendi-
when the system was shaped. As we furthermore ture too (Blevins et al., 2015). Little research has
discussed, hormonal systems often adjust both examined metabolic changes as a function of OT
psychological and nonpsychological physiological
­ administration in humans. H. Zhang et al. (2013)
phenotypes. Even when one is interested in under- reported no evidence for changes in resting energy
standing the function of psychological outcomes, expenditure, though more research is needed.
nonpsychological effects can inform an understand- OT appears to stimulate lipolysis specifically.
ing of a hormonal system’s design. Having discussed Rats centrally infused with OT, compared to con-
OT’s psychological effects, we now turn to physio- trols, have greater expression of several enzymes
logical effects of peripherally circulating OT. involved in fat metabolism, produce more oleoyle-
thanolamide (a lipid that itself increases fatty acid
oxidization), and have lower respiratory exchange
Physiological Effects of Oxytocin
ratios, indicating a shift toward fat—rather than
Energy intake and expenditure. OT reduces energy
carbohydrate—metabolism (Deblon et al., 2011).
intake and, possibly, increases expenditure. OT ad-
OT might act directly upon adipocytes, which con-
ministration to rodents, centrally or peripherally,
tain OT receptors (Yi et al., 2015; also reviewed in
decreases food intake (see Blevins & Baskin, 2015,
Blevins & Baskin, 2015; Chaves, Tilelli, Brito, &
for an extensive review). The inactivation of OT,
Brito, 2013).
either via antagonist administration or receptor
Taken together, evidence clearly indicates that,
blocking, promotes caloric consumption (e.g., Arletti,
outside of pregnancy and lactation, OT negatively
Benelli, & Bertolini, 1989; Kublaoui, Gemelli, Tolson,
affects energy balance. In this sense, then, OT is
Wang, & Zinn, 2008; G. Zhang & Cai, 2011). The
similar to cortisol, though the sources of mobilized
neural mediators implicate many of the same brain
energy differ (lipolysis of triglycerides stored in fat
structures that mediate outcomes on maternal mo-
cells vs. gluconeogenesis of energy stored in the
tivation produced by OT: Hypothalamic projections
liver). In any event, OT releases energy to be used
affect the VTA and subsequently, with dopamine,
toward some end.
the NAc (e.g., Lawson et al., 2015; Sabatier, Leng,
& Menzies, 2013). Increases in central OT selectively Immunological modulation. In animal models, OT
affect consumption of carbohydrate-rich foods; administration reduces inflammation in peripheral
they do not affect appetite for fat-rich foods (e.g., tissues (e.g., Nation et al., 2010; Szeto et al., 2013),
Herisson, Brooks, Waas, Levine, & Olszewski, 2014). and it has similar effects on human cells in vitro
In male and nonlactating female rats, circulating in- (Szeto et al., 2008). Yet OT may modulate immune
sulin and glucose activate this system, resulting in function rather than suppress it (see review in Li et
diminished rates of feeding (Sladek, Stevens, Song, al., 2017; Wang et al., 2015). OT may facilitate wound
Johnson, & MacLean, 2016). OT sensitivity to in- healing (Detillion, Craft, Glasper, Prendergast, &
sulin and glucose is blunted in pregnant and lactating DeVries, 2004), which in turn results primarily
female rats, who maintain eating behavior (func- from repair mechanisms operating in the absence of
tionally, to nourish offspring; Sladek et al., 2016; inflammation (Guo & DiPietro, 2010). Immuno­
Olszewski et al., 2016). logists contrast “­resistance” functions, such as in-
Researchers have proposed that OT administra- flammation, which operate to eradicate pathogens,
tion may promote weight loss in humans (H. Zhang with “tolerance” functions, such as repair, which

Grebe and Gangestad 325

clean up harm done by pathogens (Schneider & et al., 2011; Prehn et al., 2013); the former may
Ayres, 2008). Resistance is immediately more ener- function to enhance vigilant attention (Kassam,
getically costly than tolerance (and hence the former Koslov, & Mendes, 2009).
may be accompanied by “sickness behavior” that en-
ergetically “pays for” increased allocation to immune In fact, the findings that OT perfusions reduce
function; Shattuck & Muehlenbein, 2015). OT may heart rate, strength of contraction, and blood
shift effort away from resistance and toward tolerance pressure in rodents and dogs are mediated, at least
and repair, perhaps to limit immediate allocation of in part, by atrial natriuretic peptide (ANP; e.g.,
energy toward immune function. Indeed, OT reduces Gutkowska et al., 1997)—which, when released in
sickness behavior in rats injected with lipopolysac- heart muscle, sensitizes it to parasympathetic control
charide (LPS; Reyes-Lagos et al., 2016). Such mod- (Atchison & Ackermann, 1990). All in all, OT’s
ulation could be adaptive if OT release occurred in ­effects on heart rate may reflect its role in active,
circumstances that demanded energy allocation to motivated information processing and vigilance for
other activities. These effects parallel effects of cortisol indications of threat, especially in the social envi-
on costly inflammatory responses; cortisol similarly ronment, an interpretation that contrasts with it re-
shifts immune function from resistance functions to flecting calmness and a sense of safety. This role may
tolerance functions (e.g., Garbers et al., 2012), per- be especially important if the natural circumstances
haps because it often functions to facilitate adaptive that lead to peripheral release of OT call for active,
responses to external threats. motivated vigilance (e.g., for emotionally significant
events). In particular, OT-induced parasympathetic
Cardiac function. OT receptors richly populate control of heart rate may permit rapid modulation
heart tissue. In research on injured and healthy of heart rate in response to stimuli pertinent to
nonhuman animals, OT perfusions into the heart threats. As we have already argued, the OT system
slow heart rate, decrease the force of cardiac myo- may respond to potential threats within a relationship
cyte contraction, and suppress blood pressure context, thereby attuning other systems to detect
(Gutkowska & Jankowski, 2012; Hicks et al., 2014). these potential threats, as well as prepare systems to
One interpretation is that OT protects and main- adaptively respond to threats that are detected by
tains cardiac function through these actions (e.g., by making energy available for utilization, suppressing
reducing oxidative stress in the heart; Gutkowska & costly immune function, and rendering the cardiac
Jankowski, 2012). At the same time, under some system ready to respond quickly to emergent events
conditions, OT administration in lab animals may that demand attention and, potentially, action.
increase heart rate and blood pressure (reviewed in
Blevins & Baskin, 2015). An alternative conceptu- Insulin production and sensitivity. In rodents and
alization emerges from recent studies. Gamer and humans, OT increases the rate of insulin secretion
Büchel (2012) administered OT to men who were in response to glucose (e.g., Björkstrand, Eriksson,
presented with neutral, positively valenced (happy), & Uvnäs-Moberg, 1996; Chiodera et al., 1984;
or negatively valenced (fearful) faces and asked to Klement et al., 2017) and boosts insulin sensitivity,
perform an emotional classification task. The effect thereby enhancing glucose uptake by skeletal and
of OT depended on the emotional valence of stim- heart muscle (e.g., Camerino, 2009; Deblon et al.,
uli; it increased heart rate especially when men were 2011; Florian, Jankowski, & Gutkowska, 2010; Lee
confronted with fearful faces. Gamer and Büchel et al., 2008; H. Zhang et al., 2013).
(2012) propose that OT potentiates the signifi- Cortisol has opposite effects in this regard; it in-
cance of stimuli that evoke approach or avoidance duces insulin resistance. Arguably, it does so to main-
responses. OT administration enhances attention tain levels of circulating glucose needed to fuel the
to others’ eye region (e.g., Gamer, Zurowski, & brain during fight or flight; unlike muscles, the
Büchel, 2010) and performance in recognizing brain’s uptake of glucose is not insulin dependent
emotional expression in others, especially avoidance- (e.g., Ellison, 2017). OT may respond to threats
related (Feeser et al., 2014) or negative emotions that do not immediately require energetic exertion.
(e.g., Striepens et al., 2012; see also Schulze et al., Possibly, then, it prepares the body to be able to have
2011). When OT leads to reductions in heart rate, energy available for action, should the need arise.
it may do so through increased parasympathetic
control rather than reduced sympathetic control HPA axis responsivity. We noted that OT may sup-
(e.g., Tattersall & Hockey, 1995; see also Norman press HPA responses to threats and other stressors

326 Oxy tocin

and resulting increases in plasma cortisol levels, the cortisol system, as the kinds of threats these
mediated by blunted CRF-stimulated release by ­systems respond to are different.
adrenocorticotropic hormone (ACTH) into circu-
The OT system responds to potential threats to a valued
lation (e.g., A. S. Smith et al., 2016). Yet OT’s effect
relationship or relationship partner. We argued this
on the HPA axis appears to be context specific (Yee
claim, captured by the identify-and-invest model,
et al., 2016). In prairie voles pretreated with OT,
earlier. The original context in which the OT system
corticosterone response to a stressor (walking in
evolved to affect behavior is the mother–infant rela-
shallow water) was not dampened by OT. Rather,
tionship. From the mother’s perspective, the infant
OT pretreatment decoupled hypothalamic para-
is a valued relationship partner. The infant is, by its
ventricular nucleus activity to the stressor from the
nature, vulnerable to threats—threats that stem
resulting rise in corticosterone levels and coupled
from outside agents (e.g., predators, conspecifics),
it to autonomic nervous system responses. There,
but also threats owing to the fact that the infant’s
OT permits a glucocorticoid and autonomic response
well-being and viability depend on maternal care
to a stressor when an energetically expensive response
and responsiveness. In this context, the OT system
(fight or flight) is called for.
up-regulates (1) vigilance for signs of potential
OT, then, is not simply a “de-stressor.” It may threats to this relationship and relationship partner
promote vigilance to possible threats and, should an (e.g., outside agents, infant need states), and atten-
external threat emerge, permit a robust HPA re- tion to those threats, and (2) motivations to respond
sponse to it. That might well be an attunement that to these threats. This system was co-opted to operate
would promote, for instance, maternal protection in the context of pair-bonding. In that context, the
against intruders (Bosch et al., 2005).4 OT system operates to protect a valued relationship
with a pair-bond partner and, accordingly, is re-
The OT system conceptualized as an alternative threat-
sponsive to conditions that threaten the relationship
sensitive system. Based on OT’s psychological effects,
(e.g., when a highly valued partner’s relationship in-
the circumstances in which OT is released peripher-
volvement is low or uncertain; Grebe et al., 2017).
ally, and OT’s physiological effects, we have provi-
sionally proposed a conceptualization of how the The psychological consequences of OT under naturally
OT system has been shaped by selection to carry out occurring conditions are multiple and depend on the
resource allocation decisions (Grebe & Gangestad, precise context eliciting an OT response. OT likely af-
unpublished). Specifically, we propose that the OT fects motivational states through neurobiological
system is responsive to particular kinds of threats or networks that it fundamentally affects. At the same
potential threats, and is designed to (1) monitor time, it likely also influences vigilance and atten-
those threats and (2) respond to them. Hence, we tion downstream, sensitizing individuals to evi-
argue, the OT system is itself a threat-sensitive dence regarding the presence or absence of poten-
system, much like the cortisol system is a threat- tial threats. Additionally, it may promote perceived
sensitive system. Yet the OT system is distinct from integration of an important other into a sense of
self. Yet, we argue, these effects should be defined
4
In addition to these major physiological effects, OT has by the context in which an OT response occurs:
several others, which we mention briefly. Most notably, it has Mothers should attend to information pertinent to
effects consistent with its fundamental role as a smooth muscle the safety of their infants, and threatened relation-
contractor (Altura & Altura, 1977)—during labor, lactation,
ship partners should attend to that relationship.
and orgasm/ejaculation, OT binds to receptors on the respective
muscle fibers, inducing calcium ion mobilization and subsequent Figure 18.1 depicts the routes through which OT
contraction (Tahara et al., 2000; see also Conklin, Smith, & may affect psychological processes, as provisionally
Olson, 1999). These effects, however, need not be coordinated proposed within our model.
with the physiological effects we describe. OT’s well-established
role in parturition (indeed, its name derives from Greek roots Physiological effects are key components of the OT
for “quick birth”) results partly from a rapid and transitory system for modulating allocation trade-offs. Physiological
proliferation of OT receptors in uterine tissue, where OT is
locally synthesized (at least in primates; Gimpl & Fahrenholz, effects of OT importantly inform our proposal
2001). OT is produced in male testes too, where it is involved in that the OT system is a threat-sensitive system.
sperm transport and androgen synthesis (Gimpl & Fahrenholz, OT mobilizes energy for utilization. It reduces
2001). Naturally, OT produces milk letdown through smooth
allocation of energy to energetically expensive
­
muscle control. As already noted, some effects of OT (e.g.,
decrease in eating) are blocked during lactation and, hence, are immune function. It promotes vigilance to threat-
decoupled from other coordinated outcomes. ening stimuli while readying the cardiac, insulin,

Grebe and Gangestad 327

 key brain regions

mPOA VTA

NAc VP
Threatened,
valued
relationships
Attentional/
cognitive
OT Motivation attunement to
Competing threats
motivations (e.g.,
eating, establishing
new relationships)

HPA modulation

Parasympathetic
cardiac control

Insulin secretion Immuno-

and sensitivity Lipolysis modulation
(tolerance) Physiology of
threat perception

other
physiological
effects

Figure 18.1 A schematic representation of oxytocin’s (OT’s) functions, with an emphasis on motivational circuits. OT is
conceptualized as a system that responds to actual or potential threats to certain classes of relationships via its proximate effects on
motivational circuits. These motivational circuits are roughly divided into (1) key regions originally identified as part of the “maternal
brain” (see Numan, 2017) and (2) pathways that regulate the physiology of threat perception. Both of these circuits, initiated by OT
activity, are proposed to (1) attune motivation toward investment in threatened, valued social bonds and (2) increase vigilance to
certain present or future threats. The OT system has other physiological manifestations that may function in part to “free up”
resources allocated to the relationship demands responsible for engagement of the OT system. mPOA, medial preoptic area; VTA,
ventral tegmental area; NAc, nucleus accumbens; VP, ventral pallidum.

and glucocorticoid systems for rapid responses to Other Outstanding Issues

demands for action. To be clear, in suggesting that Additional Roles
the OT system is an “alternative threat-sensitive” The OT system may well have specialized design
system, we do not mean to suggest that, similar to features to deal with particular kinds of problems,
an HPA reaction to a threat, an OT response often while still playing other roles. The HPA system is a
leads to a state of active readiness to act, alertness, threat-sensitive system, but more functions as a
and subjective feelings of tenseness and anxiety. To metabolic hormone (e.g., Ellison, 2017). Similarly,
the contrary, consistent with others’ suggestions, the OT system may regulate basic metabolic function
OT may often dampen subjective feelings of anxi- (de Jong et al., 2015; Hew-Butler, Noakes, Soldin,
ety or tenseness. Our proposal that the OT system & Verbalis, 2008; Onaka, Takayanagi, & Yoshida,
is a threat-sensitive system is a functional design ar- 2012; see also Grebe & Gangestad, unpublished).
gument: We argue that the system is designed to
support adaptive responses to potential threats of The Range of Relationships to Which the
particular kinds (e.g., potential threats to the via- Oxytocin System Has Been Co-opted to
bility of a vulnerable infant) at the cost of reduced Respond
capacity to deal with other problems (e.g., reduced In mammals and perhaps birds, OT has been adapted
inflammatory responses). to function within the context of parent–offspring

328 Oxy tocin

and pair-bond relationships. But some scholars have regulating a trade-off between dedicated attention
argued that it has been co-opted and secondarily to an infant and attention to competing demands.
modified to function adaptively in many other rela- Ancestrally, mothers with greater resources and
tionship contexts as well: with friends, kin, in-group social support may have benefited from (or, in effect,
members, out-group members, and strangers. Some been able to afford) greater attention to infants.
evidence is consistent with these proposals. Hence, The OT system may have accordingly evolved to
for instance, Feldman et al. (2010) found that young be sensitive to information pertaining to resources
children’s reciprocity with friends positively covaried and social support.
with their OT levels, themselves predicted by ma-
ternal hormone levels and behavior. At the same Conclusion
time, in our view there currently exists little evi- OT is now a hot topic within social endocrinology
dence for (or, for that matter, against) OT playing a and psychology, more generally. Hundreds of pub-
critical role in these relationships. Much more re- lished empirical studies have examined its effects.
search is needed to ­establish its precise role and At the same time, consensus on an overarching
range of involvement. perspective—how empirical findings should be
organized under an umbrella of how the OT
­
Interactions With Other Hormones system fundamentally works—remains elusive. In
OT has well-known interactions with other hor- this chapter, we have reviewed the primary propos-
mones. In rats, both estradiol and progesterone als that have been put forward. We have also
cause a proliferation of OT receptors in certain brain argued that a perspective rooted in evolutionary
­regions (e.g., hypothalamus) and thereby enhance biology, in which OT is understood as a mediator
the effect of infused OT on sexual receptivity of life history trade-offs, offers one potentially
(McCarthy, 1995; Schumacher, Coirini, Frankfurt, fruitful way forward. We offer one possible inter-
& McEwen, 1989; Schumacher, Coirini, Pfaff, & pretation along these lines and discuss evidence
McEwen, 1990). Griffin and Flanagan-Cato (2011) consistent with it. Nonetheless, key questions remain
note that estradiol and progesterone have different unanswered. Perhaps most foundationally, a life
structural effects on the ventromedial nucleus in history perspective’s fundamental strength is that
rats, such that the latter should especially enhance it seeks to understand any particular hormonal
OT-primed sexual receptivity. Testosterone has been system in ways guided by what is known about the
claimed to have effects that oppose those of OT evolutionary forces that give rise to and shape the
(e.g., Crespi, 2016), but some evidence showing design of hormonal systems. Ultimately, an ade-
positive covariation between these hormones in quate social endocrinological understanding of
men might lead one to wonder about this concep- OT will be an evolutionary social endocrinological
tualization (Jaeggi, Trumble, Kaplan, & Gurven, understanding.
2015). Interactions between testosterone and OT
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 CH A PT E R

19 Social Bond Paradoxes

Lynea R. Witczak, Trenton C. Simmons, and Karen L. Bales

Abstract

An emergent literature illustrates some mechanisms by which social bonds are maintained throughout
the animal kingdom. Examples of social bonds include parent–offspring bonds, monogamous pair-bonds,
and friendships. Each type of bond involves a set of behaviors that can impose paradoxical physiological
consequences. Testosterone levels, for example, are generally low during displays of parental care and
high for infant defense, two behaviors that are necessary for maintaining parent–offspring bonds. This
chapter details instances where social bonds may force physiological trade-offs in oxytocin, vasopressin,
testosterone, and cortisol signaling. Specifically, it examines the endocrine trade-offs necessary for
balancing mating and parenting behaviors; affiliation with mating and parenting; group stability among
dominant and subordinate individuals; and multiple strong, simultaneous bonds across individuals. The
synthesis provides evidence of physiological trade-offs as an explanation for social paradoxes and
provides a framework for further exploration into the understanding of hormone mediation of social
bond maintenance.

Keywords: social bond paradoxes, vasopressin, oxytocin, testosterone, cortisol, social behavior,
physiological trade-offs

Social Bonds extensively. Like any other social bond, mother–

A social bond is a close, selective, enduring, interper- offspring bonds depend on both neurological and
sonal relationship that is maintained by physiological physiological mechanisms, such as individual recog-
and behavioral mechanisms (Feldman, 2012b; Lim nition and selective attachment (Numan, 2015).
& Young, 2006; Numan, 2015). Bowlby (1977a,b) Oxytocin (OT) may have a particularly important
argued that humans display attachment behaviors role in regulating close social bonds. Species-specific
(e.g., seeking proximity with preferred individuals) affiliative behaviors, such as mutual gaze in humans
throughout their lives. Bonded individuals often dis- and chimpanzees (Feldman, 2007; Tomonaga et al.,
play synchronous activation of these two mechanisms, 2004) and licking in rodents (Rilling & Young, 2014;
and the degree of this activation has previously been Van Anders, Goldey, & Kuo, 2011), are necessary
shown to be predictive of bonding strength (Feldman, for the maintenance of parent–offspring bonds. It
2007, 2012a, 2012b). Various types of social bonds has been hypothesized that adult pair-bonds may
exist across species, including mother–offspring have evolved from the physiological mechanisms
bonds, pair-bonds, and friendships. Ainsworth (1985, mediating parent–offspring bonds (Carter, 1998;
1989) examined these various bonds, which develop Fernandez-Duque, Valeggia, & Mendoza, 2009) but
throughout one’s entire life, through the lens of modified to include additional systems that promote
attachment theory. reproductive behaviors (Van Anders et al., 2011).
Mother–offspring bonds, for example, are com­ A monogamous pair-bond is a bond between two
mon across mammal species and have been studied adults, exemplified by a preference for close physical

335
proximity to a specific individual (Carp et al., 2015), r­ egulation. These findings suggest a role for dopa-
aggression toward unfamiliar intruders (Winslow, mine and serotonin in promoting positive social
Hastings, Carter, Harbaugh, & Insel, 1993), distress development (Güroğlu et al., 2008).
upon separation from the pair-bonded individual
(Mendoza & Mason, 1986a), and the ability of Social Paradoxes
partners to buffer each other from stressors (Cohen Coordination of physiology and behavior is neces-
& Wills, 1985). Mating also plays a large role in sary for the maintenance of social bond stability.
facilitating and maintaining strong affiliative bonds Given the complexity of sociality, there are often
between adults (Lim & Young, 2006; Numan, 2015). times where the costs and benefits of one behavior
Studies on monogamy in prairie voles and New supplant those of another behavior. Balancing behav-
World primates, such as tamarins, marmosets, and iors that conflict with each other may help maintain
titi monkeys, have demonstrated the importance of an overarching social bond. For example, parent–
OT and arginine vasopressin (AVP) for pair-bonding offspring bonds are maintained by engaging in both
(e.g., Bales, Mason, Catana, Cherry, & Mendoza, infant defense and infant care, two behaviors that
2007; Carter, 1998; Smith, Ågmo, Birnie, & French, are marked by low blood testosterone levels. But,
2010; Young, Wang, & Insel, 1998). OT and AVP are although it may seem paradoxical for two compet-
also clearly involved in social attachment in humans ing behaviors to elicit similar hormone activation
(Insel & Young, 2001). profiles, they may actually reflect trade-offs that are
Bonds between siblings are also regulated by physiologically mediated by multiple hormones.
physiological mechanisms. In cooperatively breeding Trade-offs occur when the benefits of one behavior
species, older offspring help parents raise younger outweigh the costs of another. Using the example of
siblings (Riedman, 1982). Administration of ex- infant defense and infant care, the benefits of protect-
ogenous OT has been found to enhance offspring ing offspring when the occasion arises may outweigh
guarding and feeding in meerkats (Madden & the costs of a temporary reduction in the quality of
Clutton-Brock, 2010) and food sharing in marmo- other forms of parental care. Although both behaviors
sets (Saito & Nakamura, 2011). OT similarly has are necessary for offspring survival, certain contexts
been found to promote alloparental care of younger force the individual to make a choice.
siblings (Bales, van Westerhuyzen, et al., 2007). Context and previous experience are also impor-
Correspondingly, administration of an OT antagonist tant to consider when examining correlations between
inhibits alloparental care in male prairie voles (Bales, hormones and behavior. For example, early-life
Kim, Lewis-Reese, & Carter, 2004). adversity, low baseline AVP (Veenema, 2009), and
Friendship is a strong, rewarding bond to unre- high AVP reactivity in response to social stressors
lated individuals that can incorporate bidirectional (Veenema, Blume, Niederle, Buwalda, & Neumann,
links between social cognition, emotions, behav- 2006) predict increased aggression in animals. For
iors, and goal orientations (Bigelow, 1977; Bigelow primiparous female rats, high AVP during the early
& La Gaipa, 1975; Güroğlu et al., 2008). The dif- lactation period is correlated with decreased aggres-
ference between a friendship and a stronger attach- sion, and low AVP later in the lactation period pre-
ment (e.g., parent–offspring bond, pair-bond) is dicts increased aggression (Nephew & Bridges, 2008;
the duration of the bond (affectional bonds are Nephew, Byrnes, & Bridges, 2010). Females bred
typically enduring, whereas friendship may or may for high-anxiety-related behaviors, though, exhibit
not last long), the interchangeability of individuals positive correlations between AVP and maternal
within a friendship dyad (whereas affectional bonds aggression (Bosch & Neumann, 2010; Bosch,
­
tend to be more specific to a single individual), Pförtsch, Beiderbeck, Landgraf, & Neumann, 2010).
and the history of interactions between friends, These differences in hormone functioning may reflect
which may include components not related to trade-offs that are evolutionarily beneficial under
friendship (Ainsworth, 1989). A functional mag- varying social and environmental contexts.
netic resonance imaging (fMRI) study found in-
creased activity in the ventromedial prefrontal Chapter Outline
cortex, hippocampus, amygdala, and nucleus ac- In this chapter, we describe how levels of OT, AVP,
cumbens following interactions between friends testosterone, and cortisol are mediated to support
(Güroğlu et al., 2008). All of these brain areas have and suppress certain behaviors to uphold multiple
been linked to reward processing and emotion bonds. First, we examine the endocrine trade-offs

336 Social Bond Paradoxes

necessary for balancing mating and parenting In other words, sexual intimacy may come at the
­behaviors. In particular, we outline the challenge and cost of attenuated parenting behavior. To better un-
steroid/peptide hypotheses and the role of testoster- derstand these trade-offs, testosterone emerges as a
one in infant care versus infant defense. Second, we key component due to its role in both sexuality and
describe the roles of OT and AVP in harmonizing nurturance (van Anders & Watson, 2006a).
affiliation with mating and parenting. Examples
­include balancing a pair’s need to mate during post- The Challenge Hypothesis
partum estrus with the need to provide for offspring, In exploring seasonal variation in male bird testos-
as well as maintaining an affiliative pair-bond while terone levels, Wingfield, Hegner, Dufty, and Ball
exhibiting agonistic behaviors such as pair-mate (1990) theorized that testosterone increases may only
restraint. Third, we discuss how context and indi- be predictive of behaviors that emerge in response
viduals’ perception of events determines whether to direct challenges to reproductive fitness. These
high or low cortisol and testosterone levels predict challenges may come in the form of intrasexual
social dominance. Finally, we identify examples of rivals, which necessitate aggressive behaviors like
how social bonds within individuals can be in compe- mate guarding. In the absence of such challenges,
tition with each other. Specifically, we investigate why testosterone levels would be expected to decrease to
some bonds are stronger than others in certain species, promote the maintenance of pair-bonds and parent–
and how humans are able to maintain strong attach- offspring bonds. These observations collectively form
ments to multiple individuals simultaneously. the challenge hypothesis, which has been used to
explain the complicated role testosterone plays in
Mating Versus Parenting modulating social contexts.
Overlap in Mechanism, Trade-Offs Over the past few decades, the challenge hy-
in Function pothesis has been studied extensively, and there is
Hormones are co-opted across social contexts to a growing body of supportive evidence (Wingfield,
­accomplish specific behavioral goals. Such is the case 2017). However, certain nuanced behaviors seem to
with the maintenance of pair-bonds and parent– be at odds with the challenge hypothesis, depicting
offspring bonds, which may overlap evolutionarily a somewhat paradoxical role for testosterone in
in aspects of function and mechanism (van Anders mating and parenting. A few of the most widely
et al., 2011). Both bond styles share aspects of attach- debated deviations include offspring defense, ag-
ment and intimacy, which likely explains the overlap- gression, and sexual intimacy. Although parental
ping hormonal circuitry employed by these bonds care would be expected to decrease testosterone
(Carter, 1998). Given such overlap and the likelihood levels, engaging in offspring defense has been shown
that parent–offspring bonds evolved first in mamma- to increase testosterone levels (Teichroeb & Sicotte,
lian species, the manifestation of pair-bonding be- 2008; van Anders, Tolman, & Volling, 2012).
havior may depend in part on the neuroendocrine Similarly, testosterone has been shown to promote
system supplied by parent–offspring bonds (Carter, aggression when beneficial to reproductive compe-
1998; Fernandez-Duque et al., 2009). This idea is tition while concurrently stimulating certain aspects
supported by the fact that species that engage in of prosocial behavior, which are two opposing be-
pair-bonding behavior are also more likely to exhibit havioral states. Testosterone has also been shown
biparental care (Kleiman, 1977; Wittenberger & to stimulate sexual intimacy while inhibiting pair-
Tilson, 1980). Indeed, the nurturance and defense bonding behavior, which complicates the fact that
of offspring often co-occurs with the nurturance and sexual intimacy is often necessary for both the for-
defense of a pair-bonded mate, but certain aspects mation and maintenance of pair-bonding behavior
of the two social bonds may not entirely overlap. across species (Carter, 1998; Snowdon, Ziegler,
Despite the existence of similarities between pair Schultz-Darken, & Ferris, 2006).
and parent–offspring bonds, pair-bonds involve the
attachment and intimacy aspects of parent–offspring Paradoxes as Trade-Offs
bonds while still giving space for sexual facilitation Although these paradoxes may simply represent the
and reproductive potential. Given the co-occur- nuanced effects of social bond tradeoffs, it is more
rence of pair-bonding behavior and biparental care, likely that they represent nuanced behaviors that
there may be circumstances where the needs of one fall outside the standards of the challenge hypothesis.
system take precedence over the needs of the other. van Anders and colleagues (2011) proposed the

Witcz ak, Simmons, and Bales 337

steroid/peptide theory of social bonds (S/P theory), As for the contrasting roles of testosterone in
building on the challenge hypothesis to resolve such mutually exclusive behaviors like aggression and
nuanced behaviors by subdividing aggression and sociality, S/P theory postulates that the differential
intimacy into specific categories. According to S/P results may be explained by the presence or absence
theory, and in relation to social bonds, aggression of coreleased peptides (van Anders et al., 2011).
can either be antagonistic or protective in nature. Like testosterone, AVP contributes to infant defense
Intimacy, on the other hand, can be either sexual and aggressive behavior (Bosch, 2011). Both of these
or nurturant (van Anders et al., 2011). Using this behaviors could situationally fall under the cate-
framework, both types of aggression and sexual in- gory of protective aggression, a category that should
timacy would be expected to increase testosterone, increase both AVP and testosterone levels. However,
whereas nurturant intimacy should decrease testoster- antagonistic aggression would only be expected to
one. Partitioning aggression and intimacy by context increase testosterone levels. The presence of AVP
facilitates explanations for the seemingly paradoxical thereby could help explain how increases in testos-
role of testosterone in certain behaviors. terone could contextually be prosocial if facilitating
Although the challenge hypothesis holds that all defensive behaviors (Figure 19.1).
parental behaviors belong in a low-testosterone cate- As mentioned before, the challenge hypothesis
gory (Kuzawa, Gettler, Muller, McDade, & Feranil, positions sexual activity as a high-testosterone behav-
2009; Kuzawa, Gettler, Huang, & McDade, 2010; ior and pair-bonds in a low-testosterone category
E. S. Barrett et al., 2013), S/P theory maintains that despite pair-bonding behavior often necessitating
low testosterone might be better predictive of only sexual intimacy. As with aggression, the presence of
certain aspects of parental behavior rather than of coreleased peptides and the salience of the context
parenting in general. Given the presence of a chal- might help explain the paradoxical testosterone sig-
lenge that solicits offspring defense behavior, it would naling. As predicted by S/P theory, both sexual and
make sense that testosterone activation might be em- nurturant intimacies increase OT levels, but only
ployed to help prepare the body for aggressive rivals sexual intimacy would be expected to increase tes-
by stimulating muscle hypertrophy and protective tosterone. Given the importance of sexual intimacy
aggressive responses. Subsequently, any situation that for reproductive fitness, there are likely stronger se-
presents a challenge in the context of parenting might lective pressures for a testosterone response to sexual
be associated with high testosterone, whereas any intimacy (van Anders et al., 2011). Therefore, the
nurturant behaviors should be associated with low ability of sexual intimacy to increase testosterone
testosterone. Although higher testosterone levels may supplants the ability of nurturant intimacy to de-
not be conducive to nurturant responses to infant crease testosterone. Alternatively, testosterone and
stimuli, the trade-off manifests in the increased ability sexual activity usually go down over the course of
to react appropriately to challenging stimuli. a pair-bond as affiliation goes up, which may also

Steroid/Peptide Theory
of Social Bonds
Challenge
Hypothesis Sexual Protective Nurturant
Intimacy Aggression Intimacy
Sexual Infant
Intimacy Defense OT AVP OT AVP
Higher plasma
hormone levels
T T T
Lower plasma
hormone levels
OT AVP OT AVP
Nurturant Infant
Intimacy care
Antagonistic Social
Aggression Withdrawal

Figure 19.1 Comparison of behavioral outcomes predicted by concentrations of testosterone (T), arginine vasopressin (AVP), and
oxytocin (OT) based on the challenge hypothesis and the steroid/peptide (S/P) Theory.

338 Social Bond Paradoxes

explain the differential testosterone levels (Gray et al., OT and AVP play an important role in facilitat-
2004; Prior et al., 2016). ing paternal behavior as well (Feldman, Gordon,
Schneiderman, Weisman, & Zagoory-Sharon, 2010;
Affiliation Versus Parenting and Mating Zimmermann-Peruzatto, Lazzari, de Moura, Almeida,
Maintenance of Affiliative Bonds Across & Giovenardi, 2015). Acute administration of AVP
Social Contexts in male prairie voles increases licking and grooming
Several hormones have been implicated in the main- behavior, and blockade of V1aR in the lateral septum
tenance of affiliation. OT in particular has been blocks this form of paternal care (Wang et al., 1994).
associated with the formation of close social bonds Genetic variation of the V1aR gene may predict in-
(Gimpl & Fahrenholz, 2001; Insel, 1997; Ross creased activation of reward neural circuitry in the
& Young, 2009). AVP has also been found to be left hemisphere anterior prefrontal cortex (APFC) in
­involved with certain aspects of sociality, like paternal human fathers (Nishitani et al., 2017). Specifically,
care (Bester-Meredith, Young, & Marler, 1999; male AVPR1ARSC-non-334 carriers showed greater
Goodson & Bass, 2001; Wang, Ferris, & De Vries, APFC activation than male AVPR1ARSC-334 carri-
1994). Additionally, low testosterone has also been ers when viewing video clips of their own child smil-
tied to nurturing behaviors in human mothers ing (Nishitani et al., 2017).
(Fleming, Ruble, Krieger, & Wong, 1997; Kuzawa Physiology and behavior can exert bidirectional
et al., 2010), human fathers (Kuzawa et al., 2009), effects on each other (Cohen & Wills, 1985). Hor­
and monogamous male nonhuman primates (Prudom mone manipulation studies in humans have observed
et al., 2008). To maintain an overall affiliative bond an increase in peripheral OT levels in infants inter-
with offspring and mates, individuals must also acting with fathers who had been treated with exog-
display aggressive behaviors such as mate guarding enous OT (Feldman, Gordon, & Zagoory-Sharon,
(Fisher-Phelps et al., 2015) and infant defense 2011; Weisman, Zagoory-Sharon, & Feldman, 2012).
(Teichroeb & Sicotte, 2008), which are coordinated In addition to exhibiting physiological synchrony,
with changes in peptide and steroid hormone activity parents and offspring also display coordination of
(Van Anders et al., 2011). Thus, physiological trade- behaviors (Feldman et al., 2007; Feldman, 2012b).
offs underlying aggressive behaviors facilitate and This coordination of affiliative behaviors and in-
maintain strong affiliative bonds. creased OT may reflect a positive feedback mechan-
ism underlying parent–offspring bonds (Crockford
Affiliative Versus Aggressive Behaviors et al., 2013).
in Parenting In addition to affiliative parental behaviors, ag-
OT plays a large role in maternal behaviors (Feldman, gressive behaviors are necessary to successfully rear
2007; Finkenwirth, van Schaik, Ziegler, & Burkart, offspring (Bosch, 2011; Numan & Insel, 2003). This
2015; Kendrick, 2000). In particular, studies that phenomenon is observed across the animal kingdom,
manipulated OT levels have demonstrated that including fish (Taborsky & Limberger, 1981), birds
­elevated OT facilitates motivation to engage in (Lynn, Hayward, Benowitz-Fredericks, & Wingfield,
maternal behaviors in rats (Fahrbach, Morrell, & 2002), and mammals (Trainor & Marler, 2001).
Pfaff, 1984; Pedersen, Caldwell, Walker, Ayers, & Both OT and AVP are involved in aggressive paren-
Mason, 1994) and sheep (Kendrick, Keverne, & tal behavior. Studies by Bosch, Krömer, Brunton, and
Baldwin, 1987). AVP has also been found to be a Neumann (2004) and Bosch, Meddle, Beiderbeck,
regulator of maternal care, as demonstrated by Douglas, and Neumann (2005) demonstrated a rise
chronic and acute intracerebroventricular (ICV) in OT release from the hypothalamic paraventricu-
administration of AVP in lactating rodents (Bosch & lar nucleus (PVN) and the central amygdala when
Neumann, 2008; Kessler, Bosch, Bunck, Landgraf, female rats display aggression toward intruders. Local
& Neumann, 2011). Mater­nal care is reduced when manipulations of V1aR show a positive correlation
AVP V1a receptor (V1aR) activity is acutely blocked between AVP and maternal aggression in lactating
with selective antagonists (Bosch & Neumann, rats bred for high-anxiety-related behaviors (Bosch &
2008). V1aR activity in the paraventricular nucleus Neumann, 2010; Bosch et al., 2010); this relationship
(PVN) may be particularly important for nursing may be affected by lactation state. For example, ICV
behavior, but not maternal motivation (Bayerl, administration of AVP decreased maternal aggression
Hönig, & Bosch, 2016). V1bR activation in the on day 5 of lactation, whereas V1aR antagonists
PVN, however, does not seem to play a role in ma- increase maternal aggression on day 15 (Nephew
ternal care (Bayerl et al., 2016). & Bridges, 2008; Nephew et al., 2010). Low AVP

Witcz ak, Simmons, and Bales 339

during lactation may suppress attack behaviors to driving paternal care (Wynne-Edwards & Timonin,
facilitate increased maternal care during early infancy 2007). For example, prolactin has been found to be
(Nephew et al., 2010). positively correlated with paternal care in rodents
van Anders and colleagues (2011) describe the (Brown, Murdoch, Murphy, & Moger, 1995;
“aggression paradox” as the knowledge gap that fails Gubernick & Nelson, 1989; Sakaguchi et al., 1996)
to explain why peptides like AVP and OT, which and nonhuman primates (Dixson & George, 1982;
are positively correlated with affiliative behaviors, are Ziegler, Wegner, Carlson, Lazaro-Perea, & Snowdon,
also linked to aggressive behaviors. They argue that 2000). In several species, testosterone is positively
coordination between steroid hormones and pep- correlated with mating behavior and negatively cor-
tides may explain this paradox. Specifically, OT and related with paternal behavior and prolactin (Nunes,
AVP may rise in response to a need for protective Fite, & French, 2000; Van Roo, Ketterson, & Sharp,
aggressive behaviors, whereas testosterone activity 2003). This trade-off in testosterone and prolactin
may be positively correlated with antagonistic ag- activity is particularly true for seasonally breeding
gression (van Anders et al., 2011). Findings from birds, where breeding and parenting behaviors do
Trainor and Marler (2001) support this theory, not co-occur.
demonstrating that affiliative aspects of paternal care Wynne-Edwards and Timonin (2007) suggest that
were positively correlated with aggressive infant the timing of fluctuations of various hormones may
defense in a monogamous rodent, independent of be important for facilitating coordination of post-
testosterone levels. At first glance, it appears that partum mating and offspring care. For tamarins,
increases in AVP and OT, but not testosterone, may males will care for infants at the same time that
simultaneously promote nurturing care of infants and ­females are ovulating and therefore able to con-
defense behaviors against intruders. However, Trainor ceive (Ziegler, Bridson, Snowdon, & Eman, 1987).
and Marler (2002) followed up on these findings Ziegler et al. (2000) did not find any hormonal
and found that the aromatization of testosterone changes in male tamarins immediately following the
to estrogen was essential for facilitation of paternal birth of their infant. They suggest this may be be-
care in this species. California mice, however, do seem cause hormonal changes occur immediately prior to
to be an exception to many of the usual findings infant birth to facilitate the onset of infant care.
regarding testosterone and parenting, and it would There did not appear to be a trade-off between pro-
be worthwhile to study all three hormones in concert lactin and testosterone in tamarin males, suggesting
in other species. that testosterone levels were at reproductively func-
tional levels without interfering with paternal care
Postpartum Estrus Versus Infant Care behaviors (Ziegler et al., 2000).
AVP, OT, and testosterone may also play a role in It is possible that no trade-off may be necessary
coordinating mating behaviors and infant care while between parental and mating effort if the two be-
females are in postpartum estrus. In some species, haviors are compatible, for instance, in species with
females begin sexual cycling while still lactating low levels of mating competition (Stiver & Alonzo,
and caring for infants (Gubernick, 1988; Kholkute, 2009). For example, defensive behaviors like infant
1984). As previously discussed, OT and AVP are defense and mate guarding involve the same suite of
positively correlated with infant care in males and behaviors driven by the same hormones, whereby
females. Testosterone, conversely, is negatively linked the only difference is who is being defended (Stiver
to nurturing behaviors and positively linked to & Alonzo, 2009). In species like the California mouse
sexual behaviors (Bales, French, McWilliams, Lake, (Peromyscus californicus), aggressive attacks on in-
& Dietz, 2006; van Anders & Watson, 2006b; truders lead to both successful mating and infant
Ziegler, Prudom, Zahed, Parlow, & Wegner, 2009). rearing (Trainor & Marler, 2001). Within a species,
Van Anders et al. (2011) argue that sexual behavior individual differences in mating and parenting strate-
is a more salient stimulus for testosterone; therefore, gies may result in differing hormone profiles (Stiver
sexual intimacy will correlate with a rise in testoster- & Alonzo, 2009). One exemplary species is the
one and a decrease in infant care. striped mouse (Rhabdomys pumillio). Male striped
Males in biparental species need to balance the mice display three discrete mating and parenting
need to reproduce with the need to care for new tactics: (1) males who remain in breeding groups to
infants in the early postpartum period. It has been care for young but do not mate, (2) males who hold
proposed that the neuroendocrine pathways that smaller territories and mate and rear offspring with
mediate maternal behavior may be the same as those partners, and (3) males who sneak copulations and

340 Social Bond Paradoxes

do not raise offspring (Schradin, Scantlebury, Pillay, adult pair-bonds observed in prairie voles (Microtus
& König, 2009). Males who exclusively care for off- ochrogaster; Ross et al., 2009).
spring have the lowest levels of endogenous testos- In conjunction with neurobiological interactions,
terone, whereas males who sneak copulations have mating behaviors, and affiliative behaviors, evolved
the highest levels, and those who mate and care agonistic behaviors such as mate guarding have been
for offspring have intermediate levels of testosterone hypothesized to help maintain pair-bonds in mo-
(Schradin et al., 2009). Further investigation is nogamous species (Fisher-Phelps et al., 2015). In the
required to better understand the coordination of wild, extra-pair copulations occur occasionally in
mating and parenting behaviors. monogamous titi monkeys (Callicebus moloch), and
males have been observed restraining their mates
Pair-Bonding Versus Mating to prevent females from mating with other males
Sexual activity can strengthen pair-bonds in monoga- (Mason, 1966). Based on results from live intruder
mous species (Carter, 1998; Snowdon et al., 2006; tests, males are more responsive to perceived same-
van Anders et al., 2007). However, testosterone, sex competitors than females, displaying aggres-
which is positively correlated with sexual activity, has sive behaviors such as tail lashing and back arching
been found to inhibit pair-bonds (van Anders & (Fernandez-Duque, Valeggia, & Mason, 2000;
Watson, 2006a). Physiological trade-offs are there- Mendoza & Mason, 1986a). Mate guarding could
fore necessary to maintain pair-bonds while facilitat- lead to additional partner-directed agonistic behaviors
ing mating behaviors. Indeed, human couples who such as mate restraint.
are involved in nurturant pair-bonds exhibit lower AVP, in particular, has been associated with ag-
levels of testosterone than single individuals (van gression in non-human animals (Delville, Mansour,
Anders & Gray, 2007; van Anders, 2009). Van Anders & Ferris, 1996) and humans (Marshall, 2013).
et al. (2011) theorize that trade-offs in testosterone Because AVP has dual roles in facilitating aggressive
levels may coordinate affiliative behaviors between behaviors toward unfamiliar conspecifics (Numan,
pair-mates and reproductive behaviors. Specifically, 2015) and maintaining persistent selective attraction
testosterone may be aromatized to estradiol through toward a familiar pair-mate (Donaldson, Spiegel, &
peptide activities to promote nurturant behaviors Young, 2010), it is essential to take into account
(van Anders et al., 2011) and may be positively context when measuring plasma AVP. Gouin et al.
correlated with sexual contexts due to its link to (2010) ­measured plasma OT and AVP following a
competitive behavioral contexts. 30-minute session where couples were asked to de-
Other hormones, including OT, are also involved scribe the history of their relationship. Couples with
in sexual behavior. OT has also been found to be higher baseline AVP and OT showed more positive
positively correlated with sexual intimacy (Carter, interactions than those with low baseline AVP and
1992; Insel, Winslow, Wang, & Young, 1998; Young, OT (Gouin et al., 2010). Conversely, individuals
Liu, & Wang, 2008; Snowdon et al., 2010). The with low baseline AVP displayed a greater number
S/P theory proposed by van Anders et al. (2011) of negative interactions with their partners. When
posits that increased OT in conjunction with in- examining AVP responses to social stressors, though,
creased testosterone may facilitate sexual intimacy, plasma AVP is elevated in pair-bonded men experi-
whereas high OT and low testosterone may facilitate encing distress (Taylor, Saphire-Bernstein, & Seeman,
nurturant intimacy. Context, therefore, is essential for 2010). This positive relationship between AVP and
understanding the coordination of hormones driving social stress has also been observed in rodents (Carter,
pair-bonding and mating (van Anders et al., 2011). Grippo, Pournajafi-Nazarloo, Ruscio, & Porges,
2008). Based on these findings, low AVP in the ab-
Pair-Bonding Versus Mate Guarding sence of social stressors and high AVP in the pres-
OT and AVP underlie pair-bonding in monogamous ence of relationship distress predict greater agonistic
mammals (Bales et al., 2013; Insel & Hulihan, partner interactions.
1995; Winslow et al., 1993). Although OT is sen- Increased testosterone activity may up-regulate
sitive to estrogens and AVP to androgens, both AVP, due to the permissive effects of testosterone
hormones are necessary for facilitating and main- on AVP (Carter, 2007; van Anders et al., 2011), and
taining monogamy in both sexes (Cho, DeVries, result in an increase in aggressive responses to social
Williams, & Carter, 1999). These neuropeptides stimuli. Positive correlations between testosterone and
can bind to each other’s receptors, and their coor- AVP may facilitate competitive behaviors that may
dinated activation has been found to develop the be important for maintaining pair-bonds (e.g., mate

Witcz ak, Simmons, and Bales 341

guarding, territory defense, rejection of unfamiliar Rejection of out-group members, though, seems
conspecifics). Therefore, although the behaviors cor- to be fluid and can change based on social context,
related with changes in testosterone and AVP are physiological state, social status, and sex of conspe-
categorized as aggressive, the outcome of the behav- cifics (French, 1986; Koenig & Rothe, 1994). As
ior is the maintenance of an affiliative pair-bond. individuals become more familiar, they may be more
readily admitted to the group, as demonstrated in
In-Group Versus Out-Group nonhuman primate studies (Hubrecht, 1985; Koenig
Part of maintaining a strong, selective affiliative bond & Rothe, 1994). Mechanistically, trade-offs between
with an individual includes exclusion of unfamiliar OT and testosterone may facilitate this switch from
individuals. This is seen in monogamous rodents and aggressive to affiliative conspecific-directed behaviors
primates, which reject strangers and prefer to spend as individuals become more familiar.
more time in close social proximity to familiar in-
dividuals (e.g., Aragona et al., 2006; Gubernick & Dominance Versus Submission
Nordby, 1993; Koenig & Rothe, 1994). The differ- Defining Social Dominance
entiation of in-group versus out-group also exists on In many species, social groups are organized into
a larger scale in nonmonogamous social structures. status hierarchies. Individuals who obtain and main-
Physiological trade-offs may exist that facilitate tain high status within a hierarchy may receive
­affiliation with in-group members and rejection of many benefits, including power and status (Magee
out-group members. & Galinsky, 2008). Central to the idea of power is
OT is positively correlated with trust, empathy, the preferential access to important resources, while
and cooperation (Heinrichs, von Dawans, & Domes, status is defined as a large sphere of influence over
2009; Israel et al., 2009; Rodrigues, Saslow, Garcia, others (Magee & Galinsky, 2008). However, to
John, & Keltner, 2009). Several human studies achieve a high social rank, individuals must first dis-
have found that OT administration increased play dominance. Across animal species, dominance
­empathy toward in-group members, but not out- rank is typically defined as the ability to successfully
group members (De Dreu et al., 2010; De Dreu, control social interactions with other individuals
Greer, Van Kleef, Shalvi, & Handgraaf, 2011; on both a quantitative and qualitative scale. Conse­
Abu-Akel, Fischer-Shofty, Levkovitz, Decety, & quently, there is a linear relationship between the
Shamay-Tsoory, 2014). In one study, it was dem- number of defeated opponents and the individual’s
onstrated that increased exogenous OT led to in- subsequent rank (Sapolsky, Alberts, & Altmann,
creased protection of in-group members and distrust 1997). Qualitatively speaking, displays of dominance
of out-group members, but not increased aggression are often assertive and self-assured, and have been
toward out-group members (De Dreu et al., 2010). associated with higher status across both animal and
A follow-up study by De Dreu and colleagues human groups (Anderson & Kilduff, 2009; Sapolsky,
(2011) supported these findings and postulated 2005). Thus, understanding the biological basis for
that OT functioning may serve an evolved need to dominance is key to explaining the motivational
give preferential treatment to one’s own in-group. forces that define a hierarchical society.
They warn that this bias toward in-group members
may promote intergroup aggression and conflict Dual Hormones of Dominance
(De Dreu et al., 2011). A large body of literature implicates testosterone
Testosterone has been shown to mediate in- and cortisol as two of the primary factors that drive
group and out-group dynamics. Flinn, Ponzi, and displays of dominance. Testosterone release is stim-
Muehlenbein (2012) found that precompetition ulated through the actions of the hypothalamic-
testosterone levels were lower in males who were pituitary-gonadal (HPG) axis, and its recruitment
competing against close friends compared to when is most commonly associated with sexual behavior
they were competing against out-group members. in males. Testosterone stimulates muscle hypertro-
Additionally, they found that testosterone levels phy, aggressive behavior, negative feedback on the
increased only after males defeated individuals endocrine system, and spermatogenesis (Wingfield,
whom they did not consider to be friends. Hence, Lynn, & Soma, 2001). However, the benefits of acute
friendship, or perception of an individual being testosterone activation can be lost with chronic
part of one’s in-group, may modulate testosterone stimulation. For example, the high energetic costs
reactivity to facilitate switches between aggressive of prolonged testosterone levels have been associ-
and affiliative behaviors. ated with reduced fat stores, increased injury and

342 Social Bond Paradoxes

mortality, suppression of the immune system, and with cortisol; winners were more likely to experi-
interference with pair-bonding and parental be- ence decreased cortisol, whereas losers experienced
havior (Wingfield et al., 2001). Therefore, optimal an increase.
testosterone activation depends on context, with Yet, despite the wealth of information our current
higher testosterone acutely helpful for challenge- body of literature has regarding these two hormones,
related contexts such as territorial and reproductive it still would be difficult to predict social behavior
aggression (Wingfield et al., 1990). across species using only cortisol and testosterone
Cortisol, on the other hand, is the primary samples. For example, testosterone has been positively
hormonal output of the hypothalamic-pituitary-
­ correlated with aggressive and dominant behaviors
adrenocortical (HPA) axis, and its activation in many animal species (Archer, 1991, 2006; Carré
­embodies the dualistic nature of the stress response & Olmstead, 2015). However, several other studies
(Sapolsky, 1990). On the one side, cortisol activation have failed to replicate these findings (Alonso, Honji,
is vital for surviving physical stressors, playing a Moreira, & Pandolfi, 2012). Similar inconsistencies
role in ­mobilizing energy, increasing cardiovascular have been found in the cortisol literature, with tradi-
tone, and suppressing unessential anabolic activities. tional studies supporting a negative relationship with
An excess, however, has been implicated in a vari- dominance (Shively, Laber-Laird, & Anton, 1997),
ety of pathological diseases like steroid diabetes others finding no association (Proctor, Freeman, &
(Björntorp, Holm, & Rosmond, 1999), myopathy Brown, 2010; Maestripieri, Klimczuk, Seneczko,
(Golding, Murray, Pearce, & Thompson, 1961), hy- Traficonte, & Wilson, 2013; Dong-Dong et al.,
pertension (Fraser et al., 1999), and suppression of 2013), and several others suggesting a positive rela-
reproductive (Ziegler, Scheffler, & Snowdon, 1995) tionship (G. M. Barrett, Shimizu, Bardi, Asaba, &
and immune systems (McEwen, 2004; see also Mori, 2002; Carlson et al., 2004). The idea that two
Mogilski et al., this volume). Thus, optimal HPA individuals of greatly differing social rank can have
functionality must involve a robust activation during identical endocrine profiles seems paradoxical. Recent
stressors and marginal activation at baseline (Sapolsky, research, however, confirms that in regard to social
1990), although depending on social context, an hierarchies, both testosterone and cortisol activation
individual’s physiological response may be forced to may depend on the context in which a certain rank
make trade-offs. If it is more probable for an indi- occurs and the social tactics employed.
vidual to encounter physical stressors, chronic acti-
vation of the stress response may be useful as an An Interplay of Context and Character
­anticipatory response. But although this individual It is worth explicitly stating that there is no current
may be better prepared to react to a stressor at any consensus on whether dominant or subordinate an-
given time, the trade-off manifests in an increased imals are more “stressed.” Studies on olive baboons
likelihood of acquiring the detrimental effects of suggest that although physiological reactions arise
cortisol excess. from rank, they are sensitive to the rank and social
Given the benefits and risks (Maestripieri & setting in which the rank occurs (Sapolsky, 1990).
Georgiev, 2016; Muehlenbein & Watts 2010) of Generally speaking, dominant phenotypes experi-
testosterone and cortisol activation, it is likely that ence the highest amount of psychological stress in
these two hormones operate under a delicate balance species with transient periods of major rank insta-
to regulate dominance interactions (Carré & Mehta, bility and where dominant individuals must physi-
2011; Mehta & Josephs, 2010; Pfattheicher, 2017; cally reassert their dominance or employ cooperative
Turan, Tackett, Lechtreck, & Browning, 2015). breeding strategies (Bartos, Schams, Bubenik, Kotrba,
Robust activation upon acute stimulation likely op- & Tománek, 2010). On the contrary, subordinate
timizes the body’s response to a stressor while mini- phenotypes experience the most psychological stress
mizing long-term health impairments. For dominant when hierarchies stabilize and in species where higher
individuals, the stressor often manifests in the form ranks are maintained through nonphysical intimida-
of a competitive challenge that provides an oppor- tion or with low availability for social support (Bartos
tunity for a change in status. Humans, for example, et al., 2010).
who won competitive interactions (e.g., sports) Despite these trends that exist across many
had increased basal testosterone levels, whereas the ­species, research continues to add support to the
opposite was seen in those who lost the interactions importance of individual variation. Although cortisol
(Aguilar, Jiménez, & Alvero-Cruz, 2013; Zilioli profiles may be explained by the context in which
& Watson, 2012, 2013). The opposite was seen dominance occurs, they may be better explained by

Witcz ak, Simmons, and Bales 343

an individual’s social tactics in coping with stressful of testosterone and cortisol activation (Feng et al.,
contexts. For example, rank instability may generally 2016; Maruska, 2015).
be anxiogenic for a dominant individual, but the
stress might depend on whether or not the male is Social Bonds Versus Social Bonds
rising or declining in the hierarchy (Sapolsky, 1992). Maintenance of Multiple Social Attachments
Rank stability, therefore, could also potentially be Social networks across human societies can be ex-
anxiogenic for a dominant individual that does not tremely complex and include multiple types of rela-
have the social fortitude to differentiate between tionships and attachments simultaneously, including
winning and losing fights (Sapolsky, 1990). Similarly, parent–child bonds, pair-bonds between partners,
subordinate individuals may also employ a set of and friendships (Flinn et al., 2012). Forming and
social tactics that alter their perception of a stressful maintaining social bonds can have survival and re-
context. Subordinate baboons, for example, which productive benefits (Ainsworth, 1989; Axelrod &
displace aggression after losing fights, affiliate the Hamilton, 1981; Baumeister & Leary, 1995). The
most with nonestrus females, engage in the highest alliance hypothesis posits that maintaining relation-
rates of overt consortship, and have lower basal corti- ships with nonkin in addition to kin may result in a
sol levels than other subordinates who do not have greater sense of protection and act as a buffer from
these traits (Virgin & Sapolsky, 1997). These same attacks from those outside of one’s alliance (DeScioli
individuals were more likely to be in the dominant & Kurzban, 2009).
cohort in coming years and to have elevated basal Although nonhuman animals may also form
testosterone (Virgin & Sapolsky, 1997). It is possible friendships and alliances, the difference for humans
that this subset of males was beginning the successful is that they are capable of supporting several strong,
transition into dominance. selective social bonds simultaneously. For example,
Given the interplay between context and individ- humans can maintain bonds with their partners,
ual variation, there can be considerable overlap in the parents, siblings, and close friends. This capability
frequency of dominant and subordinate individuals of humans to maintain multiple strong bonds is
experiencing the same trends for testosterone and exemplified by the propensity of humans to form
cortisol activation. Congruent cortisol profiles can social bonds rather than dissolve existing bonds,
be expected for dominant and subordinate individ- as demonstrated by the tendency for humans in all
uals when stressors or social tactics are shared (Abbott cultures to respond to dissolutions of social bonds
et al., 2003; Pavlidis, Sundvik, Chen, & Panula, with distress (Baumeister & Leary, 1995; Hazan &
2011). Corresponding testosterone profiles, on the Shaver, 1994). In addition to the number and strength
other hand, might be expected when individuals of social bonds in humans, they are also uniquely
maintain similar perceptions of agonistic challenges. motivated to maintain these bonds long term, which
Therefore, individuals might experience low cortisol allows for the existence of simultaneous strong
and high testosterone if the perceived stress of an ­attachments. But, although cognitive approaches
agonistic encounter is low. Bartos et al. (2010) have been used since the 1930s to study the mainte-
­provided evidence for this idea by observing the ag- nance of multiple bonds (Baumeister & Leary, 1995),
onistic interactions of red deer. Control and exper- the physiological mechanisms driving these com-
imental groups of adult red deer were sequestered plex social networks are greatly understudied (Flinn
and allowed to establish stable dominance hierarchies et al., 2012).
while hormone concentrations and behaviors were As detailed in the previous sections, OT and AVP
­measured. Once stability had been achieved, younger systems may support bonding behaviors, whereas
conspecifics were added to the experimental group. androgens such as testosterone may detract from
The addition of subordinate deer gave the more them. Low levels of testosterone may be important
dominant, adult deer increased opportunities to re- for facilitating affiliation among in-group members,
direct their aggression without introducing social whereas high testosterone concentrations are posi-
instability. Prior to adding the younger deer, domi- tively correlated with antisocial behaviors (Flinn et al.,
nant deer in the experimental group had lower 2012). In certain contexts, however, testosterone can
testosterone and higher cortisol. After the addition, promote social-emotional processing, and plays an
these same dominant deer experienced higher testos- important role in enhancing sympathetic arousal
terone and lower cortisol than control deer. The social in response to angry faces (Eisenegger, Haushofer,
environment, therefore, was the strongest predictor & Fehr, 2011). High OT may similarly play a role

344 Social Bond Paradoxes

in promoting affiliative interactions among in-group in response to social cues may also allow for the
members and exclusion of outsiders (De Dreu et al., maintenance of affiliative bonds while facilitating
2010). Additionally, the coordinated activation of aggressive behaviors necessary for maintaining
OT and AVP is important for driving both affilia- those bonds. Social dominance is also dependent
tive and aggressive behaviors necessary for maintain- on context, and high testosterone and cortisol, as
ing monogamous pair-bonds (Bales et al., 2004). well as low testosterone and cortisol, can be related
According to Flinn et al. (2012), all three of these to dominance status. The perception of another in-
hormones may be necessary to maintain coalitionary dividual being part of one’s in-group or out-group
relationships in humans. More research is necessary also alters hormone functioning underlying inter-
to elucidate how trade-offs between OT, AVP, and actions between individuals. Finally, humans appear
testosterone facilitate multiple strong social attach- relatively unique among primates in their ability
ments in humans. to balance multiple social bonds simultaneously.
Although humans are capable of maintaining Further investigation is necessary to fully under-
several strong bonds simultaneously, many other stand the mechanisms that cause a switch in hormone
animals appear capable only of maintaining one levels to facilitate different behaviors necessary for
strong bond at a time. For example, the primary maintaining social bonds.
attachment figure for monogamous titi monkey
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350 Social Bond Paradoxes

 CH A PT E R

20 Stress Hormones, Physiology, and Behavior

Justin K. Mogilski, Anna Wysocki, Simon D. Reeve, Virginia E. Mitchell,

Jenna Lunge, and Lisa L. M. Welling

Abstract

Stress, be it physical or psychological, can have a devastating long-term impact on an individual’s

development, health, and well-being, and yet can be adaptive in the short term (e.g., promoting
immediate survival, triggering the desire to remedy social conflict). The stress response system involves
physiological processes in reaction to a real or perceived threat, which serve a variety of purposes.
This chapter reviews pertinent topics and research within the social neuroendocrine study of stress,
including acute versus chronic stress, and how stress influences social behavior and status. Where
appropriate, it offers critiques of current theoretical models and includes suggestions for future
directions within this research area.
Key words: stress, hormones, glucocorticoids, cortisol, health, behavior

Stress is any real or interpreted threat to the o­ xygenation, glucose release), which divert energy
­physiological or psychological integrity of an individ- from nonessential processes, such as reproduction
ual that results in physiological and/or behavioral and food digestion, to those that promote imme­
responses (McEwen, 2000). It occurs in reaction to diate survival (e.g., muscle innervation, threat
somatic challenges such as competition, environ- processing).
mental harshness, and disease, and is mediated by Although the stress response can be adaptive in
catecholamines (e.g., epinephrine and norepi- the short term, it can have maladaptive conse-
nephrine) and glucocorticoids (GCs; e.g., cortisol quences for long-term functioning and health. In
in humans and fish; corticosterone in amphibians, this chapter, we review several of the most well-re-
reptiles, and birds). GCs are a class of corticoste- searched topics within the social neuroendocrine
roids, which are steroid hormones that are released study of stress, provide an overview and critical
by the adrenal cortex as part of a physiological analysis of current theoretical models (where appro-
feedback system known as the hypothalamic- priate), and provide a summary of potential future
pituitary-­adrenal (HPA) axis. The HPA axis regu- directions within the current literature.
lates so-called stress hormones through positive and
negative feedback systems initiated by neural input Acute Stress Response
to the hypothalamus. Initial hypothalamic release of The stress response is vital to an organism’s survival
corticotropin-releasing hormone (CRH) to the an- and has coevolved with a number of other physiolog-
terior pituitary causes release of adrenocorticotropic ical systems (e.g., dopaminergic reward systems,
hormone (ACTH) to the adrenal cortex. Next, attachment and social buffering systems) to permit
GCs produced by the adrenal cortex enter the dynamic redistribution of somatic resources when
bloodstream and promote a number of physiolog- the demands of internal or external events exceed
ical changes (e.g., increased respiration, blood immediately available resources (see, e.g., Lazarus &

351
Folkman, 1984). Acute stress can trigger survival-­ catecholamines epinephrine and norepinephrine
related and other adaptive behaviors, such as increases increase respiration, heart rate, and blood pressure,
in attention and memory. For example, amygdala and improve blood flow to muscles (Everly &
arousal from watching emotional films enhances ep- Lating, 2013). Likewise, they increase blood glu-
isodic memory for these films compared to neutral cose levels and blood oxygenation and improve
controls (Cahill et al., 1996). Acute stress also reduces alertness, learning, and memory (Usdin, Kvetnansky,
attention toward irrelevant information during a & Kopin, 1976).
Stroop task (Booth & Sharma, 2009), suggesting that During this process, the adaptive fight-or-flight
acute stress redirects attention toward temporally response halts biological functions that are unnec-
imperative information, but reduces more flexible essary for immediate survival, including reproduc-
attentional processing (Gagnon & Wagner, 2016). tive efforts, bladder muscle innervation, digestion,
Similarly, other work has shown that acute stress im- and blood flow to the skin and kidneys (Everly &
pairs recall of complex informational arrays and hin- Lating, 2013). Conversely, fight-or-flight increases
ders performance during delayed recall and memory heart rate to improve circulation, rate and depth of
tasks (Olver, Pinney, Maruff, & Norman, 2015). breathing to improve the exchange of gases, synthe-
Together, this evidence suggests that acute stress sis of glucose to provide energy, blood perfusion of
functionally redirects cognitive effort toward imme- muscles to increase strength and endurance, and
diate threats to enhance immediate survival at the cost blood clot reduction to minimize tissue damage
of dampening long-term neural plasticity (Farmer, (Nesse, Bhatnagar, & Ellis, 2016). Although it was
Park, Bullard, & Diamond, 2014). However, acute originally believed that the fight-or-flight response
stress can also act as a prompt to compel an organism decreased the function of the immune system to
to act in several ways, depending on various personal conserve energy (similar to its suppression of diges-
and contextual factors. Research has largely focused tion and ovulation at times of stress), there is ex-
on two specific threat responses: the fight-or-flight panding evidence that immune responses actually
and the tend-and-befriend threat responses. increase in response to specific types of stressors
(e.g., Dhabhar, 2002). Because some types of stress
Fight-or-Flight Versus Tend-and-Befriend can lead to infection (e.g., an injury), immune
Throughout evolutionary history, humans and other system enhancement would be most beneficial for
organisms have recurrently encountered situations survival after specific types of acute stress such as an
that required split-second decision making (e.g., an infection or injury (e.g., Dhabhar & McEwen, 2001).
approaching predator, an aggressive competitor). However, long-term exposure to this process may
Stressful situations present an energy allocation also intensify autoimmune and inflammatory dis-
problem: one may either divert resources to (1) con- eases (Dhabhar, 2002), and thus, there likely exists
fronting the threat (if there is a high probability of an optimal balance that encourages the immune-
overpowering the threat) or (2) fleeing from it (when enhancing or -suppressive responses depending on
the threat is likely to win). This process, known as the situation. Indeed, during acute stressors like
the fight-or-flight response, innervates the body to injury, glucocorticoids can enhance immune func-
respond to immediate stress and is thus adaptive in tioning, purportedly to prepare the immune system
situations of acute stress (Cannon, 1929). for potential infection (e.g., Dhabhar, Miller, Stein,
Upon recognition of a stressor, the sympathetic McEwen, & Spencer, 1994). However, upon expo-
nervous system activates the fight-or-flight response sure to acute stressors such as a final examination
(i.e., the sympathetic adrenal medullary [SAM] (Glaser, Kiecolt-Glaser, Speicher, & Holliday, 1985)
­response) to begin redirecting energy. First, the dorso- or life change (Cohen-Cole, Cogen, & Stevens,
medial amygdalar complex recognizes that a potential 1981), the immune system suppresses its response
threat is near and sends neural impulses to the lateral to conserve the energy needed to navigate the
and posterior hypothalamic regions (Roldan, Alvarez- ­immediate stressor (McEwen et al., 1997). Overall,
Pelaez, & de Molina, 1974). The hypothalamus sig- rather than acting specifically as an immune suppres-
nals to the adrenergic neurons of the thoracic spinal sant (e.g., Auphan, DiDonato, Rosette, Helmberg,
cord to secrete norepinephrine, and to the chromaffin & Karin, 1995), it appears glucocorticoids modulate
cells of the adrenal medullae to produce catechol- their function to enhance or suppress the immune
amines in a process known as catecholaminogenesis system response depending on the type of stress ex-
(Everly & Lating, 2013). The adrenal medullary perienced (McEwen et al., 1997).

352 Stress Hormones, Physiology, and Behavior

 Similar to fight-or-flight, the tend-and-befriend parental responsibility for early offspring care, and
threat response is a hormone-driven behavioral pregnancy and nursing make women especially vul-
­reaction to stress that typically occurs more often in nerable to external threats (see Sear & Mace, 2008).
females (Taylor et al., 2000). Via the release of oxy- Forming a network not only provides protection
tocin (OT), this response manifests as an increased and help with raising offspring, but also serves to
motivation to protect offspring (tend) and seek out secure resources, such as housing and food. Given
social group members for mutual defense and aid that a group is more likely than an individual to
(befriend). Testosterone and arginine v­asopressin overcome or deter a threat, a social-support-seeking
(AVP) released during the fight-or-flight stress response is likely a protective mechanism for both
­response have been found to exhibit the opposite the woman and her offspring. Correspondingly,
effects of OT (see Taylor, 2006; Taylor et al., 2000, evidence suggests that women, more than men, are
2006). The original model developed by Taylor geared for fostering and maintaining social relation-
et al. (2000) describes tend-and-befriend as a female ships. For example, although the need for interper-
counterpart to the fight-or-flight response in males sonal connection seems to be a near-universal human
(Cannon, 1929). These authors highlight that, before trait, women tend to socialize more in new environ-
1995, research investigating the fight-or-flight ments (Wheeler & Nezlek, 1977) and are more
­response had been conducted predominantly on focused on maintaining belongingness than men
male participants, with females constituting a mere (Baumeister & Leary, 1995). Even as children, girls
17 percent of the participants, which may have led have a stronger interest in maintaining meaningful
researchers to overlook the more female-typical tend- and nurturing relationships, resulting in a higher
and-befriend response. number of relationships than male counterparts
In response to threat, both males and females (Galambos, 2004; Nichols & Good, 1998). Also,
show increased activation of the autonomic ­nervous women tend to score higher on measures of emo-
system, which causes the release of OT, AVP, and tional intelligence and social skills than men (Bindu
CRH. However, OT is released in greater quantities & Thomas, 2006; Petrides & Furnham, 2000),
in females (Taylor et al., 2000). OT is believed by suggesting that women have specialized cognitive
some to encourage affiliative behavior, including mechanisms for maintaining affiliation. Together,
maternal nurturance and seeking social contact this research suggests that women compared to men
from peers (e.g., Insel, 1997; Carter, 1998; see also are more likely to overtly prioritize social support
Grebe & Gangestad, this volume), and may actively responses to stress over fight-or-flight responses
alleviate the biological stress responses by, for (e.g., Turton & Campbell, 2005) because evolutionary
­example, decreasing heart rate, blood pressure, HPA pressures favored an affiliative response.
activity (Light et al., 2000), and cortisol level Although, as noted, OT is associated with seeking
(Uvnas-Moberg, 1997, 1998). In addition, estrogen social support in response to stress, which can in
enhances the effects of OT, whereas androgens inhibit turn alleviate stress, it is important to emphasize
OT release (McCarthy, 1994), which may contribute that the social environment itself can also be the
to why women are more likely to respond to stress source of stress. For example, cortisol has been
via tend-and-befriend than men. Certainly, women shown to increase after social rejection in both
who report more deficiencies in their social relation- men and women (Blackhart, Eckel, & Tice, 2007),
ships (i.e., reduced contact with various social sup- although women show elevated cortisol responses to
port sources) and marital dissatisfaction have elevated social rejection versus achievement failure manipu-
OT levels (Taylor et al., 2006). lations compared to men (Stroud, Salovey, & Epel,
Overall, women consistently show a stronger 2002), suggesting they may be more physiologically
affiliative response to stress than men do (Tamres, reactive to social rejection than men. The relation-
Janicki, & Helgeson, 2002; Taylor et al., 2000), and ship between OT and cortisol led Taylor (2006) to
therefore a social-support-seeking response to stress propose a potential model for a stress affiliation,
may be particularly adaptive for females. Both men which is ­dependent on the success or failure of gaining
and women rely on group living for successful social support via the tend-and-befriend stress
­defense against predators and outgroup members, ­response (see Figure 20.1 for a simplified iteration
but human females also face greater threats from of Taylor’s [2006] conceptual model). Although the
in-group human males (e.g., rape, assault, abuse of buffering influence of OT on stress is discussed in
offspring). Furthermore, women often take on more more detail later (see Social Buffering), the model

Mogilski, Wysocki, Reeve, Mitchell, Lunge, and Welling 353

 hormonal mechanism designed to promote surviving
Stress and thriving.

Increased
Chronic Stress
Oxytocin In contrast to acute stress, chronic stress is mal­
adaptive. One of the first studies on chronic stress
(Selye, 1956) found that repeated shocks produced
Increased
stomach ulcers and a lowered immune system
Affiliative Efforts
­response in rats. Prolonged exposure to GCs lowers
immune response by suppressing cytokines, blocking
Negative Positive cytokine receptors, disrupting lymphocyte develop-
Social Outcome Social Outcome
ment, and destroying lymphocytes (for review, see
Segerstrom & Miller, 2004). As such, individuals
Increased HPA- Decreased HPA- who experience chronic stress are more likely to get
axis activity axis activity the common cold and have more frequent cold sore
flare-ups (Cohen, Tyrrell, & Smith, 1991, 1993).
Increased Decreased Additionally, chronic stress has been associated with
Stress Stress an increased likelihood of getting a respiratory
­infection, the acceleration of autoimmune disorders,
Figure 20.1 A theoretical cascade model of an affiliative and increased recurrence of chronic allergies (Boyce
responses to stress, extrapolated from Taylor (2006). In this et al., 1977, 1993; Monroe & Hadjiyannakis, 2002;
model, stress increases oxytocin (OT), which leads to increased
affiliative efforts. When these efforts yield negative social
Pereira & Penedo, 2005).
outcomes, increased hypothalamic-pituitary-adrenal (HPA) Since Selye’s (1956) study, considerable research
axis activity leads to increased stress. When affiliative efforts has investigated and confirmed the maladaptive
yield positive social outcomes, HPA activity and, by effects of chronic stress (e.g., Coe & Lubach, 2003;
extension, stress decrease. Repetti, Taylor, & Seeman, 2002; Stowell, Kiecolt-
Glaser, & Glaser, 2001; Taylor, Repetti, & Seeman,
proposes that stress triggers increased affiliative efforts 1997). The stress response is a trade-off between
via increased OT in line with the tend-and-befriend long-term and short-term functioning. Processes
stress response system. The subsequent effect on essential for long-term survival (e.g., the immune
stress is then dependent on the outcome of this system) are suspended to increase the likelihood of
effort; negative outcomes (e.g., failure to gain immediate survival. Because the stress response sup-
social support) will increase stress, whereas positive presses functions that are not vital for immediate
­outcomes (e.g., success at gaining social support) survival, chronic stress can result in an increased
will decrease stress. Taylor provides a selection of susceptibility to infectious disease, psychological
available evidence for each component of the model deficits, growth reduction, and reproductive issues
in support, although much of this evidence is derived (Ader, Felton, & Cohen, 1991; Glaser & Kiecolt-
from animal studies. However, recently a body of Glaser, 2014). Chronic stress continually mobilizes
evidence in humans has begun to emerge, further energy at the cost of energy storage, and the result is
supporting the theory (e.g., Cardoso, Ellenbogen, fatigue, muscle loss, and weakness (Bower et al., 2005,
Serravalle, & Linnen, 2013; von Dawans, Fischbacher, 2007). Additionally, the prolonged increase in heart
Kirschbaum, Fehr, & Heinrichs, 2012). rate weakens the heart muscles over time and in-
Hence, acute stress likely evolved to promote creases plaque buildup (Booth-Kewley & Friedman,
adaptive outcomes under difficult circumstances. 1987; Rozanski, Blumenthal, & Kaplan, 1999). An
Whereas the fight-or-flight response readies the body increase in GCs is also associated with greater appe-
for action to escape or combat a threat, the tend- tite and blockage of glucose reuptake, which can
and-befriend response encourages the individual to result in increased fat depositions, particularly in
seek social support to combat threat and provide the midsection (Brindley & Rolland, 1989). As such,
additional attention to vulnerable d ­ependents chronic stress is associated with an increased risk for
(e.g., children, kin), thus shielding their genetic cardiovascular disease, diabetes, and obesity (Booth-
(or social) assets from the threat. Either response Kewley & Friedman, 1987). Growth functions are
highlights that, despite its unpleasant sensation, also suspended during the stress response by inhib-
acute stress is typically an adaptive cognitive and iting the release of growth hormone (GH; Kosten,

354 Stress Hormones, Physiology, and Behavior

Jacobs, Mason, Wahby, & Atkins, 1984). When this by the overproduction of GCs. Individuals with
occurs over a prolonged period in children, the Cushing’s syndrome have lower hippocampal volume
result is psychosocial dwarfism, where a child typi- than average and perform worse on verbal recall
cally grows to only one-half of the expected height tasks (Bourdeau et al., 2002; Starkman, Gebarski,
for his or her age group (Green, Campbell, & David, Berent, & Schteingart, 1992). Furthermore, the
1984). These children have low endogenous GH HPA axis can be damaged by chronic stress, resulting
and, depending on both their age and the duration in a stunted cortisol response to stressors (Glaser
of the chronic stress, can be unresponsive to exoge- & Kiecolt-Glaser, 2014). This is particularly true
nous GH supplementation (Albanese et al., 1994; when the stress occurs early in development; pre-
Sapolsky, 1998). and perinatal chronic stress has been linked to HPA
Chronic stress can also lead to a variety of repro- axis malfunction in both rats and rhesus macaques
ductive issues (Rabin, Gold, Margioris, & Chrousos, (Clarke, 1993). Similarly, individuals who were sex-

in stress-related hormones (e.g., β-endorphins and

1988; Whirledge & Cidlowski, 2010). An increase ually abused as children have been found to have
damage to their HPA axis, which is thought to be
CRH) inhibits the release of gonadotropin-releasing linked to the chronic stress the child experienced as
hormone (GnRH), resulting in reduced gonadotro- a result of the abuse (Heim, Newport, et al., 2000).
pins such as luteinizing hormone (LH) and folli- In sum, there is a plethora of evidence supporting
cle-stimulating hormone (FSH; Briski & Sylvester, the link between consistent stressors in one’s envi-
1991; Dubey & Plant, 1985). Both LH and FSH ronment and its negative impact on health.
are involved in reproductive processes in males and Although chronic stress has negative effects on
females. In females, GCs inhibit the release of, and health and bodily functions, the body has protective
reduce sensitivity to, gonadotropins, which increases methods of preventing these effects (Kang, Coe, &
the likelihood of anovulatory cycles (i.e., menstrual McCarthy, 1996; Liu et al., 2002). There are a
cycles where an ovum is not released; Whirledge & number of characteristics that modulate the body’s
Cidlowski, 2010). GCs also inhibit the secretion of resilience to the side effects of chronic stress (Coe &
progesterone, which is involved in the maturation of Lubach, 2003). One such characteristic is age,
the uterine wall in preparation for egg implantation, whereby children and the elderly are most suscepti-
decreasing the likelihood of successful implantation ble to negative health outcomes from stress. An
if ovulation occurs and in extreme cases halting increased risk of disease when faced with a stressful
menstruation completely. In males, GCs decrease environment was found in both elderly humans and
testicular sensitivity to LH and lower testosterone, monkeys (Bailey & Coe, 2002; Coe & Ershler, 2001;
which can decrease sperm count and quality (Bambino Kiecolt-Glaser, Marucha, Mercado, Malarkey, &
& Hsueh, 1981; Saez, Morera, Haour, & Evain, Glaser, 1995; Uno, 1997). Infants also show a marked
1977). Moreover, chronic stress activates the sympa- drop in immune function when removed from their
thetic nervous system and deactivates the para- mother in humans, rats, and squirrel monkeys (Ader
sympathetic ­nervous system, which increases the & Friedman, 1965; Coe & Lubach, 2003). Another
likelihood of erectile dysfunction and premature factor is the duration of the stressor; if a stressor is
ejaculation (Agarwal, Nandipati, Sharma, Zippe, & present for less than one month, there is no signifi-
Raina, 2006; Bancroft & Janssen, 2000). cant increase in the risk of illness. However, if a
Chronic stress likewise has negative consequences stressor is present for one month or more, then the
on the brain and peripheral nervous system due to risk of the individual developing an illness increases
high levels of GCs causing cellular atrophy and significantly (Cohen et al., 1998; Lepore, Miles, &
impaired neurogenesis. Specifically, chronic stress Levy, 1997). This suggests that the body may be
has been linked to neural degeneration in areas of the effective at combating the negative effects of chronic
brain such as the hippocampus, which is involved stress for a certain period of time only.
in learning and memory functions (McEwen & Although there is compelling evidence that
Sapolsky, 1995; Sapolsky, Krey, & McEwen, 1985). chronic stress is maladaptive, other specifics regarding
Several studies have supported the link between how chronic stress impacts health are less clear.
decreased hippocampal volume and decreased per- Some research suggests that cortisol is the main
formance on spatial tasks in rats (Luine, 2002; catalyst for the negative health outcomes associated
Luine, Villegas, Martinez, & McEwen, 1994). In with stress (Cohen, Kessler, & Gordon, 1995). There
humans, this has best been studied in individuals are two major theoretical models for the relation-
with Cushing’s s­ yndrome, a disorder characterized ship between stress, cortisol, and health. The first

Mogilski, Wysocki, Reeve, Mitchell, Lunge, and Welling 355

model posits that chronic stress results in elevated impact on cortisol levels is time since the onset of
cortisol (i.e., hypercortisolism) due to HPA axis the stressor, whereby time since onset is negatively
hyperactivity. The increase in cortisol results in tissue related to cortisol level (Fries, Hesse, Hellhammer,
damage and dysregulation of biological systems & Hellhammer, 2005; Hellhammer & Wade, 1993;
(Cohen et al., 1995; Schaeffer & Baum, 1984). The Miller, Cohen, & Ritchey, 2002). If the chronic
second model postulates that chronic stress results stressor is no longer a part of the environment (e.g., a
in decreased levels of cortisol (i.e., hypocortisolism) soldier coming home from a war zone), there is a
due to HPA axis habituation. Decreased cortisol greater likelihood of hypocortisolism. By comparison,
results in fatigue and increased pain sensitivity and someone who continues to experience the stressor
leaves the body more vulnerable to disease (Heim, (e.g., unemployment) is more likely to have hyper-
Ehlert, & Hellhammer, 2000; Raison & Miller, cortisolism (Fries et al., 2005; Hellhammer & Wade,
2003; Sternberg, Chrousos, Wilder, & Gold, 1992; 1993; Miller et al., 2007). This may explain why
Yehuda, 2000). For decades, it was accepted that Yehuda and colleagues (1996, 1998, 2005) found
chronic stress resulted in hypercortisolism, and a hypocortisolism in those who were suffering from
considerable number of studies have provided evi- PTSD after experiencing a trauma. Thus, hypocor-
dence to support this link (e.g., Arnetz et al., 1987; tisolism seems to develop after a period of hyperac-
Baum, Gatchel, & Schaeffer, 1983; Schaeffer & tivity of the HPA axis, which would explain the
Baum, 1984). For example, stressful tasks such as perceived contradiction in previous research.
public speaking or mental arithmetic can increase
cortisol levels (Kirschbaum, Pirke, & Hellhammer, Status
1993). However, recent studies by Yehuda and col- Social Dominance and Dominance
leagues (Yehuda, 2000; Yehuda, Resnick, Schmeidler, Hierarchies
Yang, & Pitman, 1998; Yehuda, Golier & Kaufman, Not only are stress hormones implicated in physio-
2005) have called into question whether there are logical reactions to stressful environmental cues, but
exceptions to this relationship. Hypocortisolism has also they appear to play an important role, along
been most consistently found in individuals who with the androgen testosterone, in the maintenance
have experienced a traumatic event and, subsequently, of social dominance and dominance hierarchies
developed posttraumatic stress disorder (PTSD; see (Eisenegger, Haushofer, & Fehr, 2011; Mehta &
Yehuda, 1997). This relationship was first observed Josephs, 2010). Dominance hierarchies form in social
in Vietnam veterans and then replicated in Holocaust groups where individuals must compete to obtain
survivors, sexually abused women, and Bosnian resources (e.g., food, mating opportunities) and each
prisoners of war (Bourne, Rose, & Mason, 1967, individual’s ability to compete is different (Sapolsky,
1968; Dekaris et al., 1993; Yehuda, 2000; Yehuda 2005). Dominance hierarchies can be described in
et al., 1998, 2005). Hypocortisolism has also been terms of both their linearity (i.e., the number of
found in individuals who have experienced chronic binary dominance relationships established within a
medical disorders, such as chronic pain, fibromyalgia, group and how permanent those relationships are)
and asthma (Catley, Kaell, Kirschbaum, & Stone, and their steepness (i.e., how successful an individual
2000; Crofford et al., 1995). Furthermore, hypo- of one rank will be against another in a competitive
cortisolism has been found in people without med- encounter; DeVries, Stevens, & Vervaecke, 2006). In
ical conditions who have other forms of chronic these scenarios, dominant individuals (i.e., those who
stress in their lives, for example, parents who had a are best able to acquire and monopolize resources)
child with a fatal illness (Friedman, Chodoff, and subordinate animals (i.e., those who are not as
Mason, & Hamburg, 1963) or individuals with a capable) have distinctive physiological and psycholog-
high amount of work stress (Caplan, Cobb, & ical states. This, in part, is because one’s rank deter-
French, 1979). mines how much physical and psychological stress an
What these two major findings suggest is that individual typically encounters. How different these
chronic stress has the ability to both increase and states are, however, depends on the type of hierarchy
decrease cortisol levels in the body. Considering the that is formed in each species and within each sex.
strong evidence backing each of these models, the Dominance hierarchies exist on a spectrum rang-
best explanation is an integration of the two (Gunnar ing from egalitarian, where no individual is assigned
& Vazquez, 2001; Heim, Ehlert, & Hellhammer, a rank and dominance is achieved with the support
2000; Miller, Chen, & Zhou, 2007; Raison & Miller, of subordinate animals, to despotic, where one in-
2003). One factor that appears to have the greatest dividual is dominant and suppresses subordinate

356 Stress Hormones, Physiology, and Behavior

animals (van Schaik, 1989). In egalitarian hierarchies, 2005) primates. For example, aggressive behavior
subordination is not associated with increased levels in male rhesus monkeys is positively associated
of physiological stress, whereas rank can influence with elevated levels of plasma testosterone (Rose,
how much stress an individual is exposed to in Holaday, & Bernstein, 1971), and higher ranking
­despotic hierarchies (although this relationship de- chimpanzees exhibit more aggressive behaviors and
pends on the stability of the hierarchy; Sapolsky, have higher levels of testosterone compared to their
2005). Despotic hierarchies can also be stable or lower ranking counterparts (Muller & Wrangham,
­unstable, depending on whether or not rank is in- 2004; Muehlenbein, Watts, & Whitten, 2004).
herited in that species (reviewed in Sapolsky, 2005). Testosterone level is also positively associated with
When rank is inherited, subordinate animals con- aggressive behaviors (Archer, 2006) and self-perceived
sistently experience the highest levels of stress. In dominance (Welling, Moreau, Bird, Hansen, &
groups where rank is fluid, whether or not domi- Carré, 2016) in human males, although the rela-
nants or subordinates experience the most stress tionship between dominant behavior and testosterone
depends on the stability of the hierarchy. In these in humans is more mixed (e.g., Johnson, Burk, &
types of h ­ ierarchies, high rank can be maintained Kirk, 2007; Mazur & Booth, 1998).
through either physical aggression or psychological It has recently been proposed that these discrep-
intimidation. In species where aggression is used to ancies in findings between testosterone and domi-
maintain rank, dominant animals at the top of the nant behaviors and rank in dominance hierarchies
hierarchy bear a higher burden (e.g., increased can be reconciled when also considering the role of
­parasite load) due to continually elevated levels of cortisol in dominance interactions and cortisol’s
cortisol (Muehlenbein & Watts, 2010), putatively relationship with testosterone (Mehta & Josephs,
as a r­esponse to the d ­ emands of maintaining that 2010). Cortisol is known to interact with testoster-
dominance (e.g., via fighting, protecting resources, one in multiple physiological ways (reviewed in
having to remain on high alert; Cavigelli & Caruso, Viau, 2002). For example, cortisol is known to dis-
2015). Conversely, in groups where psychological rupt the hypothalamic-pituitary-gonadal (HPG)
intimidation is used by dominants to suppress sub- axis and reproductive function in both males and
ordinates, subordinates experience more stress, pre- females (Handa, Burgess, Kerr, & O’Keefe, 1994).
sumably because of their decreased access to necessary The HPG axis controls testosterone production,
physical resources (Sapolsky, 2005). and increased levels of cortisol suppress the produc-
Males and females also tend to have different tion of endogenous testosterone (Cumming, Quigley,
types of intrasexual dominance hierarchies. For males, & Yen, 1983). Accounting for these interactions
maintaining social rank is associated with more between cortisol and testosterone, Mehta and
frequent aggressive behaviors that may result in Josephs (2010) proposed a dual-hormone hypoth-
injury due to enhanced male weaponry (e.g., increased esis, wherein cortisol modulates the effect that tes-
body size, specialized teeth or claws; Cavigelli & tosterone has on behavior, such that higher levels of
Caruso, 2015). In female hierarchies, on the other testosterone are associated with more dominant
hand, rank is maintained by more complex, subtle behaviors, but only in individuals who also have low
aggression and affiliative behaviors (Sapolsky, 2005). levels of cortisol. They found that cortisol and tes-
Additionally, whereas males are more driven by access tosterone coregulate leadership (i.e., dominance)
to mates and reproductive opportunities (Ellis, 1995), behavior in men and women, and that testosterone
female dominance hierarchies determine access to and cortisol levels influenced men’s competitive
quality food resources and protection (Sterck, Watts, behaviors. Importantly, the ratio of cortisol to tes-
& van Schaik, 1997). tosterone was not a significant predictor of an indi-
Acts of dominance and rankings in dominance vidual’s dominant behavior: Testosterone was only
hierarchies appear to be associated with the andro- associated with increased dominant behaviors in
gen testosterone, and testosterone may motivate individuals low in cortisol. Indeed, either there was no
individuals to perform behaviors that help them relationship between testosterone and dominance
attain and maintain status within social groups behaviors in individuals with both high testosterone
(Eisenegger et al., 2011). Testosterone is produced and cortisol or the relationship was actually reversed,
by both sexes in primate species, and is positively such that participants with high testosterone and
correlated with aggression and rank in dominance cortisol displayed less dominant behaviors. Overall,
hierarchies in male (Muller & Wrangham, 2004) cortisol appears to strongly influence dominance
and female (Beehner, Phillips-Conroy, & Whitten, and status in primates, including humans, but these

Mogilski, Wysocki, Reeve, Mitchell, Lunge, and Welling 357

effects may depend on interactions with other 2001). Other studies have shown that peripheral
­hormones, such as testosterone. Similarly, several and intranasally administered OT levels are positively
hormones appear to provide a buffering effect that associated with circulating cortisol, particularly
alleviates some of the harm of stress hormones. when subjects expect a stressful experimental ma-
nipulation (Brown, Cardoso, & Ellenbogen, 2016).
Social Buffering By comparison, AVP has anxiogenic effects (Heinrichs,
Oxytocin and Arginine Vasopressin von Dawans, & Domes, 2009). Rats who naturally
OT and AVP share a long evolutionary history and or transgenically fail to produce AVP demonstrate
mediate a number of socioemotional behaviors in lower anxiety (Bielsky, Hu, Szegda, Westphal, &
both humans and nonhumans (Carter, Grippo, Young, 2004; Zelena et al., 2008). Moreover, ele-
Pournajafi-­ Nazarloo, Ruscio, & Porges, 2008; vated plasma AVP is present in several anxiety disor-
Heinrichs & Domes, 2008; Meyer-Lindenberg, ders (Surget & Belzung, 2008) and is associated
Domes, Kirsch, & Heinrichs, 2011). OT neural with territoriality (Caldwell et al., 2008; Donaldson
systems are believed to have originally emerged in & Young, 2008; Young & Wang, 2004) and behav-
mammals to promote affiliative, prosocial, and ioral aggression in men after exposure to stress
nurturing behaviors between mothers and infants (Moons, Way, & Taylor, 2014). Together, this evi-
(Donaldson & Young, 2008) and have putatively dence suggests that OT and AVP play an important
been co-opted to regulate basic aspects of sexuality role in regulating physiological stress; however, the
(i.e., sexual arousal, motivation, and orgasm; Borrow exact mechanism by which this function is accom-
& Cameron, 2012; Garrison et al., 2012) and other plished has yet to be conclusively identified.
social bonds (Feldman, 2012; Feldman, Monakhov, Recent efforts at consolidating the disparate effects
Pratt, & Ebstein, 2016). Indeed, receptor distribu- of OT and AVP on HPA activity have focused on
tion for mesotocin (i.e., the functional analogue their role in attenuating psychosocial stress (i.e., social
of OT in birds) is associated with flock size, and buffering; Hostinar, Sullivan, & Gunnar, 2014).
mesotocin administration increases flock formation, Social support and the presence of conspecifics
whereas mesotocin antagonists reduce this social appear to dampen the HPA axis response in both
behavior (Goodson, Schrock, Klatt, Kabelik, & humans (e.g., Heinrichs, Baumgartner, Kirschbaum,
Kingsbury, 2009). Likewise, AVP has been shown & Ehlert, 2003; Rosal, King, Ma, & Reed, 2004;
to mediate prosocial behaviors, aggression, and ter- Taylor et al., 2008) and nonhuman animals (e.g.,
ritoriality in several species, particularly in males Hennessy, 1984; Vogt, Coe, & Levine, 1981). For
(Caldwell, Lee, Macbeth, & Young, 2008; Donaldson example, maternal contact appears to be formative
& Young, 2008; Young & Wang, 2004). OT and during HPA axis development in infancy (Gunnar,
AVP also appear to aid in social synchrony (Apter- Hostinar, Sanchez, Tottenham, & Sullivan, 2015).
Levi, Zagoory-Sharon, & Feldman, 2014). For Indeed, maternally deprived infant rats show chronic
­instance, Bowen and McGregor (2014) found that HPA hyperresponding compared to control rats
rats treated with OT and AVP increase defensive (Suchecki, Nelson, Van Oers, & Levine, 1995).
aggregation when exposed to an environmental Likewise, peers also reduce psychosocial stress, though
stressor (i.e., cat fur), suggesting that these molecules this effect is moderated by individual and interper-
coordinate social behaviors that assist in responding sonal features (e.g., gender, familiarity, species-typical
to environmental threats. social organization; Hennessy, Kaiser, & Sachser,
OT and AVP receptors are distributed through- 2009). This social buffering appears to be mediated,
out various brain regions associated with stress and in part, by circulating levels of OT and AVP
anxiety regulation (Landgraf & Neumann, 2004), (Hostinar et al., 2014). Social activities enhance OT
and their activation has been shown to modulate release (Carter, 1998) and, in humans, social sup-
experiences of stress in a­ daptive ways alongside the port paired with OT administration dampens HPA
dopaminergic reward system (Ludwig & Leng, axis activity in males (Heinrichs et al., 2003).
2006). Some evidence suggests that OT attenuates Likewise, Ditzen et al. (2007) found that support
HPA activity in rodents and nonhuman primates from a romantic partner lowers salivary cortisol, but
(Neumann & Landgraf, 2012; Parker, Buckmaster, only when paired with physical contact (i.e., a mas-
Schatzberg, & Lyons, 2005) and is associated with sage). In a sample of international migrants whose
lower plasma and salivary cortisol in response to envi- OT and AVP were m ­ easured shortly after arrival
ronmental stressors (Cardoso, Ellenbogen, Orlando, in their host country and reassessed two and five
Bacon, & Joober, 2013; Ditzen et al., 2009; Legros, months later, greater baseline levels of OT predicted

358 Stress Hormones, Physiology, and Behavior

increases in social relationship satisfaction and social has a high concentration of opiate receptors;
support and decreases in loneliness over time. By e.g., Wise & Herkenham, 1982) has been found to
comparison, greater social integration was associ- play a primary role in the induction of separation
ated with higher plasma AVP over time in the calls (Robinson, 1967).
same study (Gouin, Pournajafi-Nazarloo, & Carter, In addition to endogenous opioids, exogenous
2015). Collectively, this evidence suggests that opioids also alter DVs produced by infants. Low
OT and AVP are functionally similar but will atten- doses of morphine (an opioid receptor agonist;
uate or enhance stress in a manner that depends Eisenberger, 2012) reduce DVs from separated
on characteristics of an organism’s social and physi- infant rats (Carden & Hofer, 1990b), guinea pigs
cal environment. (Herman & Panksepp, 1978), chicks (Panksepp,
The actions of OT and AVP in promoting and Vilberg, Bean, Coy, & Kastin, 1978), dogs (Panksepp
regulating social behavior and stress also appear to et al., 1978), and primates (Kalin et al., 1988). By
differ between sexes and depend on interactions comparison, the administration of naloxone (an
with gonadal steroids. OT and its receptor are ex- opioid antagonist; MacDonald & Leary, 2005)
pressed in higher quantity in women (Carter, 2007), increases DVs in guinea pigs and chicks (Panksepp
and OT gene promoters are stimulated by exposure et al., 1978) and reverses the mitigating effects of
to estrogen (Lee, Macbeth, Pagani, & Young, 2009; littermate presence and morphine administration
Mohr & Schmitz, 1991; Richard & Zingg, 1990), on reduced DVs in infant rats (e.g., Carden &
whereas AVP synthesis is stimulated by androgens Hofer, 1990a, 1990b). Exogenous opioids also alter
(DeVries & Villalba, 1997). Plasma OT is associ- social affiliation in primates, guinea pigs, and rats
ated with relationship dissatisfaction in women but (MacDonald & Leary, 2005). For example, opioid
not men, whereas plasma AVP is associated with receptor agonists reduce social interactions with
relational distress in men but not women (Taylor, conspecifics, likely by mimicking the rewards of
Saphire-Bernstein, & Seeman, 2010). These sex dif- social interactions and thus removing the motiva-
ferences may underlie the previously noted divergent tion of pursuing social interactions (Eisenberger,
responses in males and females to social stressors, 2012). Conversely, opioid receptor antagonists in-
whereby women exhibit more OT-based affiliative crease social interaction attempts, likely by blocking
responses to threat (i.e., tend-and-befriend) than do the rewards of social interaction and thus motivating
men (Taylor et al., 2000). its pursuit (Eisenberger, 2012). Furthermore, the

are regulated by μ-opioid receptors. Infant mice

effects of both endogenous and exogenous opioids

lacking the μ-opioid receptor gene, for example,

Opioids
Although commonly associated with analgesic effects
(e.g., D’Amato, 1998; D’Amato & Castellano, 1989; do not experience pain relief from morphine
Kieffer & Gavériaux-Ruff, 2002; Panksepp, 2004), (Eisenberger, 2012), and infant rats lacking the
opioids can also promote social attachments and same gene do not exhibit DVs when separated from
buffer the experience of stress. The brain opioid sys- their mother and littermates (Kehoe & Blass, 1986;
tems are activated during play in rat pups (Panksepp Moles, Kieffer, & D’Amato, 2004). It is apparent
& Bishop, 1981), social grooming in nonhuman that social isolation reduces endogenous opioid
primates (Panksepp, 2004), and positive social levels, inducing social distress and DVs in many
­interactions in humans (Eisenberger, 2012; Hsu vertebrates. On the other hand, social interaction
et al., 2013). Additionally, opioids are released in increases endogenous o­ pioids, which reduces social
infants upon social (Blass & Fitzgerald, 1988; distress and simultaneously reinforces later social
Panksepp & Bishop, 1981) and physical contact interactions (e.g., Nelson & Panksepp, 1998).
with mothers (Weller & Feldman, 2003) and are Ultimately, the opioid system is essential in social
known to moderate infant distress vocalizations behavior, as it both mediates stress response and
(DVs; e.g., Kalin, Shelton, & Barksdale, 1988). encourages further social affiliations by rewarding
DVs are produced by infants separated from their prior social interactions and attachments.
normal social environment (e.g., their mother, lit-
termates) and are seen in many vertebrate species, Future Directions
such as mice, rats, chickens, guinea pigs, kittens, Evidently, chronic stress is maladaptive for a variety
puppies, monkeys, and humans (Panksepp, Herman, of physical and psychological processes. However,
Conner, Bishop, & Scott, 1978). Furthermore, in the negative effects of chronic stress are mediated by
rhesus macaques, the anterior cingulate cortex (which factors such as age and duration of chronic stress,

Mogilski, Wysocki, Reeve, Mitchell, Lunge, and Welling 359

as well as other hormones like OT. Furthermore, hormone secretion in children with psychosocial dwarfism.
future research should work to further integrate Clinical Endocrinology, 40(5), 687–692.
Apter-Levi, Y., Zagoory-Sharon, O., & Feldman, R. (2014).
the hypo- and hypercortisolism models. At present, Oxytocin and vasopressin support distinct configurations of
endocrinologists have a basic theoretical framework social synchrony. Brain Research, 1580, 124–132.
(Miller et al., 2007), but it would be beneficial Archer, J. (2006). Testosterone and human aggression: An
to understand the catalysts for how the HPA axis evaluation of the challenge hypothesis. Neuroscience &
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Arnetz, B. B., Wasserman, J., Petrini, B., Brenner, S. O., Levi, L.,
need for a better understanding of the role that cor- Eneroth, P., . . . Theorell, T. (1987). Immune function in
tisol has in dysregulating bodily functions, breaking unemployed women. Psychosomatic Medicine, 49(1), 3–12.
down tissue, and increasing susceptibility to disease. Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., &
Research should further investigate the relation- Karin, M. (1995). Immunosuppression by glucocorticoids:
Inhibition of NF-kappaB activity through induction of
ship between stress hormones and dominance, partic-
IkappaB synthesis. Science, 270, 286–290.
ularly with respect to the interaction with testosterone Bailey, M. T., & Coe, C. L. (2002). Endometriosis is associated
(Mehta & Josephs, 2010), in both humans and with an altered profile of intestinal microflora in female
nonhuman primates. Furthermore, possible interac- rhesus monkeys. Human Reproduction, 17(7), 1704–1708.
tions with other hormones, such as those involved Bambino, T. H., & Hsueh, A. J. (1981). Direct inhibitory effect
of glucocorticoids upon testicular luteinizing hormone
in social buffering, could be explored. Similarly, the
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response to both long-term and short-term stress Bancroft, J., & Janssen, E. (2000). The dual control model of
could lead to important clinical applications for the male sexual response: A theoretical approach to centrally
treatment of PTSD and other anxiety-related disor- mediated erectile dysfunction. Neuroscience & Biobehavioral
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whereby women are more likely to suffer from an behavioral, and physiological effects of chronic stress at Three
anxiety disorder during their lifetime compared to Mile Island. Journal of Consulting and Clinical Psychology,
men (e.g., McLean, Asnaani, Litz, & Hofmann, 51(4), 565–572.
2011; see also Pigott et al., this volume). It is possible Baumeister, R. F., & Leary, M. R. (1995). The need to belong:
Desire for interpersonal attachments as a fundamental
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differences in stress-related coping strategies, such as Beehner, J. C., Phillips-Conroy, J. E., & Whitten, P. L. (2005).
the increased tend-and-befriend response among Female testosterone, dominance rank, and aggression in an
women compared to men (Tamres et al., 2002; Ethiopian population of hybrid baboons. American Journal of
Primatology, 67(1), 101–119.
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Mogilski, Wysocki, Reeve, Mitchell, Lunge, and Welling 365

 CH A PT E R
Hormones, Circadian Rhythms,
21 and Mental Health

Yasmine-Marie Cissé, Jeremy C. Borniger, and Randy J. Nelson

Abstract

Circadian rhythms permit adaptations to predictable temporal environmental changes. Daily 24-hour
rhythms are controlled by molecular clockworks within the brain that are set by the daily light–dark
cycle. Downstream endocrine signaling conveys temporal information throughout the body. Mood
disorders often present with disruptions in circadian clock-controlled responses, such as sleep and
cortisol secretion, whereas circadian rhythm disruptions via jet lag, night-shift work, or light at night
increase disordered affective symptoms. Evidence suggests strong associations between circadian
rhythms and mental health, but only recently have studies begun to discover the direct interactions
between the circadian system and mood regulation. This chapter provides an overview of circadian
rhythms and the circadian regulation of the endocrine system. It discusses how the circadian and
endocrine systems interact to affect depressive, anxious, and addictive responses. Finally, it discusses
the potential detrimental effects the widespread use of nighttime light has for mood and cognition.

Keywords: mental health, circadian rhythm, diurnal rhythm, mood, depression, anxiety

The earth’s revolution, axial tilt, and elliptical orbit maximally activated by short-wavelength light
around the sun have remained essentially constant (~460 to 484 nm, violet to blue) and are signifi-
for the last several billion years. During this time, cantly less responsive to long-wavelength (i.e., red)
life has evolved under precise day–night cycles of light (Berson, Dunn, & Takao, 2002). Importantly,
24 hours. Organisms have been selected to develop ipRGCs also project directly or indirectly to brain
endogenous time-keeping mechanisms (i.e., circa- structures that control emotional behavior and
dian systems that have self-sustaining rhythms of memory (e.g., amygdala and hippocampus; LeGates
about 24 hours) that ensure survival and reproductive et al., 2012; Vandewalle, Maquet, & Dijk, 2009),
success in the face of predictable changes in the en- providing a direct link between light exposure and
vironment. cognitive function. The SCN can also be entrained
In mammals, environmental light is used to by nonphotic cues such as food restriction or phys-
­entrain or synchronize the circadian system to pro- ical exercise (Edgar & Dement, 1991; Mistlberger,
duce precise 24-hour rhythms. Environmental light 1994), but the focus for this chapter will be on
(i.e., zeitgeber/time-giver) acts through a unique light-mediated changes to the circadian system
population of intrinsically photosensitive retinal and downstream alterations to endocrine function
ganglion cells (ipRGCs; Hattar, Liao, Takao, Berson, and mental health.
& Yau, 2002). These cells relay light information Most of the experimental work presented in this
along the retinohypothalamic tract (RHT) to the chapter is based on animal model research. Animal
master circadian clock in the hypothalamus: the models can be useful to understand the endocrine
­suprachiasmatic nuclei (SCN). The ipRGCs are mechanisms underlying affective disorders, but there

367
are limitations in their applicability to humans, information to the rest of the brain and body through
especially in the context of disordered mood.
­ direct synaptic connections and neuroendocrine
Importantly, any animal model for affective disorders pathways. Many targets of SCN signaling are impor-
must have face validity (i.e., how well the animal tant nodes regulating arousal and emotional process-
model resembles the human disorder), predictive ing, including the locus coeruleus, ventral tegmental
validity (i.e., the expected responses to treatment area, and multiple hypothalamic nuclei that control
that are effective in humans), and construct validity endocrine signaling along the hypothalamic-pituitary-
(i.e., the similarity of the underlying mechanisms of adrenal (HPA) axis. At the molecular level, circadian
the disorder). Understanding the mechanisms of rhythms in gene expression are driven by a primary
the human disorder and the development of ther- autoregulatory transcriptional/translational feedback
apeutic interventions requires construct validity. loop with a period of approximately 24 hours (Figure
Because of the difficulties associated with assessing 21.1). In mammals, the core clock genes Clock and
emotions and mood in nonverbal individuals, many Bmal1 (Arntl) serve as the “positive” arms of the clock.
studies of humans, rather than nonhuman animals, Their protein products (CLOCK and BMAL1)
have been conducted to understand the causes and heterodimerize (i.e., join two different products to
treatments of affective disorders. Studies that at- become a single compound) and bind to the pro-
tempt to correlate human affective changes with en- moters of their own negative regulators, Per (1,2,3)
docrine events typically involve people reporting and Cry (1,2), to enhance their transcription (i.e., the
their moods, which are then correlated with mea- copying of DNA into RNA). Once transcribed and
surements of hormone concentrations. The effects translated, PER and CRY proteins hetero- and ho-
of endocrine manipulations or natural endocrine modimerize (i.e., join two of the same product to
fluctuations are then assessed. become a single compound), re-enter the nucleus,
and inhibit their own transcription, creating the
Review of Circadian Rhythms “negative” arm of the clock. Ancillary loops further
The master clock has an endogenous rhythm of modulate the period and phase of the rhythm. For
~24 hours in the absence of all environmental cues example, RAR-related orphan receptor alpha (RORα)
(Welsh, Takahashi, & Kay, 2010), reflecting genetic and reverse-ErbA alpha (REV-ERBα) nuclear recep-
programs that drive the clockwork independent of tors act as transcription factors (i.e., proteins ­involved
external stimuli. The SCN are composed of mainly in transcribing DNA into RNA) to influence and
inhibitory (GABAergic) cells that transmit photic stabilize Bmal1 expression (Guillaumond, Dardente,

Clock
Npas2

Bmal1 RORE PER

CLOCK/
BMAL1 CRY
NPAS2

RORα
E-box Per 1, 2, 3 REV-
ERB
E-box Cry 1, 2
E-box RORα
E-box REV-ERB

E-box CCGs

nucleus cytoplasm

Figure 21.1 Molecular components of the circadian clock. The CLOCK/NPAS2:BMAL1 heterodimer binds to the E-box element
in the promoter region of Per, Cry, ROR, and Rev-ERB, as well as a host of clock-controlled genes (CCGs). Once translated, PER
and CRY proteins heterodimerize in the cytoplasm, translocate to the nucleus, and act as negative regulators to inhibit their own
transcription. Nuclear receptors provide additional modulation to the main transcriptional translation feedback loop. ROR-α and
Rev-ERBs bind to the RORE element in the promoter region of the Bmal 1 gene and promote or repress gene expression.

368 Hormones, Circadian Rhy thms, and Mental Health

Giguère, & Cermakian, 2005). Because CLOCK sub-PVN. The SCN can affect glucocorticoid release
and BMAL1 additionally control the transcription of independently of the HPA axis. Direct and indirect
hundreds of so-called clock-controlled genes (CCGs) SCN innervation of the PVN regulates sympathetic
involved in immunity, metabolism, endocrine, and and parasympathetic efferent nerve fibers, resulting
neuronal responses (Bozek et al., 2009), rhythmic in a circadian pattern of peak sympathetic tone
gene expression is essential for health. Dysregulation early in the active phase and a trough during rest.
of this network via circadian disruption can have The circadian rhythm in autonomic tone is respon-
far-reaching effects throughout the organism (Laing sible for setting the phase of rhythmicity in the
et al., 2015). ­periphery: immune organs, liver, and endocrine
More generally, circadian rhythms in body tem- organs such as the adrenal cortex (Bartness, Song,
perature, blood pressure, glucocorticoid secretion, & Demas, 2001; Elenkov, Wilder, Chrousos, &
immune responses, motor activity, and cognitive Vizi, 2000; Ishida et al., 2005; Kalsbeek, La Fleur,
performance are disrupted in patients with mental Van Heijningen, & Buijs, 2004).
illness (Lanfumey, Mongeau, & Hamon, 2013; Cortisol appears to play a multifaceted role in
Turek, 2007), suggesting that this system is vital for major depressive disorder (MDD; Herbert, 2013).
mental health. Many animal models of circadian First, increased resistance to the feedback actions
disruption (environmental and genetic) demonstrate of glucocorticoids is often observed. Second, daily
a causal relationship between aberrant biological rhythms in cortisol are perturbed. Finally, resting
rhythms and development of addictive behavior and cortisol concentrations and the postawakening cor-
bipolar-, depressive-, and anxiety-like phenotypes tisol surge are increased in people at risk for MDD
(Spencer et al., 2013). To follow, we discuss the pri- (Herbert, 2013).
mary evidence linking circadian rhythms to mental The negative feedback features of the HPA axis
health disorders. We further outline the potential appear to be impaired in depressed patients. Excessive
detrimental effects of circadian disruption on mood cortisol production has been reported in nearly
and cognition. Because of the rapid and unprece- 50 percent of depressed patients examined (Carroll
dented rise and widespread use of electric lights, et al., 2007). Cortisol concentrations are often at
special emphasis is placed on aberrant light exposure their highest three to four hours after sleep onset in
as a circadian disruptor and important contributor depressed people, and decrease throughout the day-
to the rise of affective disorders. light hours (Carroll, 1980). Because cortisol is nor-
mally secreted in a pronounced circadian p­ attern, with
Circadian Regulation of Hormones peak concentrations measured in the early morning,
Glucocorticoids this disturbance of the diurnal rhythm of cortisol
The HPA axis regulates the host of adaptive physio- secretion suggests an abnormal disinhibition of the
logical processes initiated in response to physical and neural centers regulating the release of adrenocorti-
psychological stressors. Descending input from the cotropic hormone (ACTH), the tropic hormone
limbic system, in response to a stressor, stimulates from the anterior pituitary gland that stimulates ad-
corticotropin-releasing hormone (CRH) neurons of renal output. Chronic dysregulation of the HPA axis
the paraventricular nucleus of the hypothalamus and the resultant high cortisol concentrations are
(PVN) to release CRH into the hypophyseal portal common findings in depression (see Carroll et al.,
system. CRH acts on the pituitary and triggers the 2007). In cases of hormonal changes in depressed
release of adrenocorticotropic hormone (ACTH) patients, it is unclear whether depression causes
into the bloodstream. ACTH induces synthesis and changes in hormone production or whether changes
release of glucocorticoids from the adrenal cortex. in hormone production cause depression. When de-
In addition to limbic input to the HPA axis, the pression is secondary to some endocrine or immune
SCN exerts an organizational force on HPA activity. dysfunction, then more definitive statements can be
CRH, ACTH, and glucocorticoids exhibit robust made about the direction of causality. For example,
circadian rhythms peaking at the onset of the active patients with Cushing syndrome have adrenals that
phase (Kalsbeek et al., 2012). produce excessive cortisol, and depression is often a
The SCN exerts both direct and indirect influ- symptom of this disorder; however, patients with
ence on the circadian rhythm of the HPA axis Addison disease have adrenal glands that produce
(Figure 21.2). The SCN inhibits CRH synthesis insufficient cortisol, and depression is a defining
through indirect activation of GABAergic neurons symptom of this disease as well (see Disruption of
in the dorsomedial hypothalamus (DMH) and the Circadian Rhythms and Mental Health section).

Cissé, Borniger, and Nelson 369

 (A) (B)
Hypothalamus PVN
Hippocampus
Sub-
PVN
3r
d
Pituitary DMH V

SCN

IML

Cortisol
Adrenal

6AM 12PM 6PM 12AM 6AM

Figure 21.2 Suprachiasmatic nucleus (SCN) regulation of the hypothalamic-pituitary-adrenal (HPA) axis/glucocorticoid secretion.
The SCN directs glucocorticoid secretion through HPA-dependent and -independent pathways through projections to both
neuroendocrine and preautonomic centers of the paraventricular nucleus (PVN), respectively (A). Neuroendocrine projections direct
the production and release of corticotropin-releasing hormone (CRH) and initiation of the HPA axis, whereas autonomic fibers directly
act on the adrenal medulla to induce glucocorticoid release. Within the hypothalamus, the SCN directly innervates both the dorsomedial
hypothalamus (DMH) and the sub-PVN to differentially regulate subsets of cells in the PVN (B). SCN, suprachiasmatic nucleus; DMH,
dorsomedial hypothalamus; PVN, paraventricular nucleus; 3rd V, Third ventricle; IML, intermediolateral column of the spinal cord.

All peripheral organs contain endogenous directly bind to GRs or competitively bind to GREs
c­ircadian clocks. The phase setting of peripheral and prevent GR transcriptional activity (Lamia et al.,
clocks is dependent on neural or humoral cues 2011). Disruption of clock gene expression can
from the SCN, namely, rhythmic autonomic tone, have down­stream effects on typical HPA function
glucocorticoids, and melatonin (Dibner, Schibler, & and signaling.
Albrecht, 2010). Endogenous rhythmic clock gene Single clock gene mutants exhibit altered HPA
expression in the adrenal cortex drives circadian function. Clock null mice exhibit decreased and
gating of ACTH sensitivity (Oster, Damerow, nonrhythmic glucocorticoid secretion (Takita et al.,
Hut, & Eichele, 2006; Oster, Damerow, Kiessling, 2013). Bmal1 mutant mice similarly decrease serum
et al., 2006). Clock gene expression in all tissues glucocorticoid concentrations, have a flattened
can provide temporal gating of glucocorticoid daily rhythm, and have a blunted physiological and
­sensitivity (Balsalobre et al., 2000). Several clock behavioral response to ACTH, forced swim, and
genes have been implicated in rhythmic gating of repeated restraint challenge (Leliavski, Shostak,
glucocorticoid receptor (GR) expression, sensitivity, Husse, & Oster, 2014). Period and cryptochrome
and function. The CLOCK:BMAL1 heterodimer mutants also display flattened daily rhythms, but
acetylation of the GR prevents associations with conversely increase serum glucocorticoid concen-
glucocorticoid-responsive elements (GREs; Nader, trations (Dallman et al., 1993; Destici et al., 2013;
Chrousos, & Kino, 2009). CRY proteins can either Lamia et al., 2011).

370 Hormones, Circadian Rhy thms, and Mental Health

 PG

PVN

Lig SCN
ht IML

Eye

SCG

Figure 21.3 Suprachiasmatic nucleus (SCN) regulation of melatonin secretion. In the absence of light at night, GABAergic signals
from the SCN are inhibited allowing for the activity of the preautonomic cells of the paraventricular nucleus (PVN). These PVN
neurons project to the preganglionic cells of the intermediolateral column of the spinal cord (IML), which synapse onto the
postganglionic cells of the superior cervical ganglion (SCG), driving melatonin synthesis in the pineal gland (PG).

Melatonin or genetically crossed onto melatonin-deficient strains

Melatonin is the humoral signal of night. The pineal to produce “melatonin proficient” mice. Mice har-
gland synthesizes and secretes the indoleamine hor- boring a mutation (exon 19 [Δ19]) in the gene Clock
mone, melatonin, into blood and cerebrospinal fluid crossed to be melatonin proficient have functional
exclusively during the night (Reiter, 1993). In the melatonin rhythms (Kennaway, Owens, Voultsios,
absence of light, glutamatergic preautonomic par- & Varcoe, 2006). The authors suggest a functional
vocellular cells of the PVN activate preganglionic homolog of CLOCK, NPAS2, may be compensating
cells of the intermediolateral (IML) cell column for the nonfunctional CLOCK. Additional studies
(Figure 21.3). These preganglionic cells in turn acti- identify a distinct lack of NPAS2 specifically in the
vate postganglionic sympathetic cells of the superior pineal gland and the SCN (Garcia et al., 2000), sug-
cervical ganglion (SCG), which project directly to gesting that NPAS2 may not play a role in the SCN
the pineal gland and drive melatonin synthesis and at baseline. There are no data, however, on its role in
release (Moore, 1995). Light inhibits melatonin se- the absence of CLOCK. In vitro, melatonin can
cretion (in mammals) by depolarizing GABAergic reset the SCN and alter clock gene expression;
cells within the SCN (through the RHT), which melatonin decreases Per1 and Clock and increases
inhibit the autonomic cells of the PVN (Teclemariam- Npas2 expression in striatal neurons (Imbesi et al.,
Mesbah, Ter Horst, Postema, Wortel, & Buijs, 1999). 2009). Considered together, these data suggest that
In this way, light-induced inhibition of the pineal melatonin feedback may play a role in maintaining
gland is relinquished during extended darkness, en- central clock function.
suring that melatonin is only secreted in the absence Melatonin acts as a messenger of the circadian
of photic stimulation to the SCN. system. It conveys time-of-day information to the
Although the pineal gland exhibits rhythmic clock rest of the body to synchronize central and peripheral
gene expression in vitro (Maronde & Stehle, 2007), circadian clocks, acting through multiple G-protein-
these rhythms are not apparent in vivo in the ab- coupled receptors (GPCRs) termed MT1 and MT2,
sence of SCN input. Investigating pineal function as well as nuclear receptors (ROR/RZR). Melatonin
in laboratory mice can be difficult due to the lack of is an ancient and pleiotropic hormone, and its recep-
melatonin production in most commercially avail- tors are located on cells throughout the neuroendo-
able mouse strains. C3H mice retain appreciable crine and immune systems (Weaver, Rivkees, &
melatonin synthesis and are generally used as a model Reppert, 1989; Weil, Borniger, Cisse, Abi Salloum,

Cissé, Borniger, and Nelson 371

& Nelson, 2015). In the absence of exogenous mel- clock may represent an important mediator of SAD
atonin, melatonin-deficient mouse strains exhibit and point to additional effective treatments (reviewed
decreased amplitudes of peripheral clock gene ex- in Roecklein et al., 2013b). Indeed, people diagnosed
pression in the pituitary and adrenal cortex (Torres- with SAD showed an impaired postillumination pupil
Farfan, Seron-Ferre, Dinet, & Korf, 2006). response compared with healthy controls (Roecklein
et al., 2013a). Individuals with variations in the
Circadian and Seasonal Rhythms melanopsin gene (OPN4) who may suffer from SAD
For many mammals, annual shifts in behavioral and may display differences in alertness, circadian entrain-
physiological phenotypes increase fitness in season- ment, and melatonin secretion.
ally shifting environmental conditions. Melatonin
conveys time-of-year information; the duration of Disruption of Circadian Rhythms
melatonin secretion, rather than amplitude, conveys and Mental Health
night length as a proxy of duration of seasonal changes Prevalent anxiety-mood disorders include major
in day length. Although humans do not e­ xhibit many depression, specific or social phobias, posttrau-
overt seasonal rhythms, some individuals are suscep- matic stress disorder, generalized anxiety disorder,
tible to seasonal changes in mood. panic disorder, agoraphobia, bipolar disorder, and
Seasonal affective disorder (SAD) presents during obsessive-compulsive disorder. Among these, the
the late autumn or winter and is characterized by chances of an adult in the United States developing
depressed affect, lethargy, loss of libido, hypersomnia, major depression or an anxiety-mood disorder over
excessive weight gain, carbohydrate cravings, anxiety, a lifetime vary between 9 and 30 percent, represent-
and inability to focus attention or concentrate ing a sizeable portion of the population (Kessler,
(Rosenthal, Sack, Skwerer, Jacobsen, & Wehr, 1988). Petukhova, Sampson, Zaslavsky, & Wittchen, 2012).
In the Northern Hemisphere, symptoms usually In some disorders, such as SAD, a clear link between
begin between October and December and go into the circadian system and affective behavior is evi-
remission during the spring. Individuals suffering dent, as SAD patients show altered sensitivity to light
from SAD in the Southern Hemisphere display and timed light therapy is efficacious in the treatment
symptoms six months out of phase with Northern of SAD (Golden et al., 2005; Thompson, Stinson,
Hemisphere residents (Terman, 1988). With the & Smith, 1990). Light therapy also modestly reduces
onset of summer, SAD patients regain their energy symptoms of nonseasonal depression, suggesting
and become active and elated, often to the point of some benefit to enhancing signals to the circadian
hypomania or mania. Three features atypical of system (Golden et al., 2005; Martiny, Lunde,
depression—hyperphagia, carbohydrate cravings,
­ Unden, Dam, & Bech, 2005; Wirz-Justice et al.,
and hypersomnia—set SAD apart from nonsea- 2005). In this section we will discuss the influence
sonal d­ epression. SAD is frequently diagnosed as of the c­ ircadian system in regulating mood and ad-
“bipolar II” depression or “atypical bipolar disorder,” dictive behavior.
particularly if hypomania or mania is present
(DSM-5, 2013). Exposure to at least 1,500 lux is Depression
necessary for the inhibition of human melatonin se- Patients diagnosed with MDD often display circadian
cretion (Lewy et al., 2001). This requirement may rhythm disruptions in sleep, immune, and endocrine
explain why standard indoor levels of artificial illu- systems (Thase, 1999; Turek, 2007). As noted, many
mination are insufficient to relieve the symptoms of patients with MDD present with arrhythmic hyper-
SAD; much brighter light must be used for effective cortisolism that is resistant to feedback inhibition by
treatment. Thus, people who develop SAD, who are dexamethasone (Beck-Friis et al., 1985; Keller et al.,
mainly female and in their 20s through 40s, may 2006). Rhythms in glucocorticoid set the phase of
have defects in the light transduction pathways. clocks in various peripheral tissues and provide a
One study suggests that people suffering from SAD circadian pattern of glucocorticoid sensitivity
have a small genetic mutation in the melanopsin (Leliavski, Dumbell, Ott, & Oster, 2015). Loss of
molecule; people diagnosed with SAD were 5.6 times rhythmicity and phase of glucocorticoid secretion can
more likely than people with no history of psycho- alter extra-SCN clock function and HPA responses.
pathology to have a missense variant (rs2675703 Indeed, patients with MDD experience disrupted
[P10L]) of the melanopsin gene (Roecklein et al., sleep, body temperature, and serum cytokine rhythms,
2009). Thus, genetic deficits in the nonvisual light as well as poor HPA feedback inhibition (Alesci et al.,
input pathway from the eye to the central biological 2005; Beck-Friis et al., 1985; Thase, 1999).

372 Hormones, Circadian Rhy thms, and Mental Health

 harboring the Δ19 mutation in the gene Clock dis-
Aberrant rhythms in melatonin production also molecular clock components. For instance, mice
underlie mood disorders such as bipolar disorder and
depression, as patients have overall reduced melato- play mania-like behavior, have reduced anxiety-like
nin concentrations or greatly disrupted rhythms in behavior, and are less fearful of aversive stimuli than
melatonin secretion (Claustrat, Chazot, Brun, wild-type (i.e., control) mice (Roybal et al., 2007).
Jordan, & Sassolas, 1984; Nurnberger et al., 2000; These changes seem to stem from disruptions in
Srinivasan et al., 2006). Loss of a nighttime melato- CLOCK-regulated cholecystokinin (CCK) expres-
nin peak eliminates signals of time of day to the body, sion in the ventral tegmental area (VTA; Arey et al.,
including mood centers. Indeed, knockout of the 2014). Reciprocally, mice lacking both Per1 and
melatonin receptor MT1 increases depressive-like Per2 (but not either alone) have increased anxiety-
behavior in mice (Weil et al., 2006). Similarly, con- like behavior, increased social-defeat stress responses
stant exposure to light or dim light at night decreases (a paradigm used to induce anxiety in rodents), and
nocturnal melatonin secretion and increases depres- reduced Per1/2 gene expression within the nucleus
sive-like behavior (Bedrosian, Fonken, Walton, Haim, accumbens (NAc; Spencer et al., 2013). Subsequent
& Nelson, 2011; Bedrosian et al., 2013). Melatonin RNA interference-mediated inhibition of Per1/2 ex-
alters the adrenal cortex glucocorticoid response to pression in the NAc of wild-type mice produced
ACTH (Campino et al., 2011; Torres-Farfan et al., anxiety-like behavior, suggesting a causal role for
2003), whereby the loss of melatonin contributes to these core clock components in the NAc for regu-
the dysregulation in HPA feedback from hypercor- lating anxiety. Lesions of the SCN produce antide-
tisolism. Antidepressant treatment returns melatonin pressant-like behavior in tests of behavioral despair,
and glucocorticoid rhythms to baseline in MDD independent of alterations in anxiety (Tataroğlu,
patients (Golden et al., 1988; Linkowski et al., 1987). Aksoy, Yılmaz, & Canbeyli, 2004; Tuma, Strubbe,
Agomelatine, an MT1/MT2 agonist and serotonin Mocaër, & Koolhaas, 2005), suggesting that clock
receptor 2C (5HT2C) antagonist, decreases symptom gene actions outside the SCN are important for
severity in patients with MDD (Olié et al., 2007). regulating anxiety-like behavior.
Together, these data suggest that a functional inter- Other studies have investigated how environ-
play between the melatonin and glucocorticoid mental disruption of circadian rhythms (i.e., with
rhythm may be necessary to regulate mood. atypical light exposure) contributes to the develop-
Research in humans demonstrates marked changes ment of anxiety-like behavior. In adult rats, chronic
in circadian function throughout the lifespan, coin- constant light induces depressive- and anxiety-
cident with the development of mental disorders. like behavioral responses (Tapia-Osorio, Salgado-
In two studies using high-quality postmortem brain Delgado, Angeles-Castellanos, & Escobar, 2013).
tissue sampled at different times of the day, researchers However, results are inconsistent across species
were able to directly investigate clock gene expression (Ashkenazy, Einat, & Kronfeld-Schor, 2009; Castro
in aged people and those with MDD (Chen et al., et al., 2005; Fonken et al., 2009) and depend on
2016; Li et al., 2013). Because aging is associated the developmental window during which circadian
with impaired sleep, cognition, and mood, under- disruption occurs, as well as the type of light and
standing the contributions of circadian deregulation its intensity (Bedrosian et al., 2013; Borniger,
to the emergence of these problems is important for McHenry, Abi Salloum, & Nelson, 2014; Cissé,
developing treatments. During the course of normal Peng, & Nelson, 2016). Additional covariates are
aging, the majority of genes become less rhythmic, the extent to which light exposure alters sleep be-
but some compensatory transcripts increase their tween different species of diurnal and nocturnal
rhythmic expression (Chen et al., 2016; Li et al., rodents (e.g., Borniger, Weil, Zhang, & Nelson,
2013). Furthermore, brains from people with MDD 2013; Stenvers et al., 2016), as sleep disruption
displayed dramatically reduced rhythmicity in many can be an independent contributor to the develop-
core clock components, suggesting that targeting the ment of affective disorders (Jagannath, Peirson, &
circadian system could be a viable strategy for the Foster, 2013; LeGates, Fernandez, & Hattar, 2014).
treatment of mental disorders.
Addiction
Anxiety Addiction, in common with other mental disorders,
Relationships among the circadian system and anx- is associated with circadian disruption, though much
iety-like disorders were first established from basic of the disruption has been attributed to the types of
research in mice with targeted disruption of core drugs themselves, especially opiates and stimulants,

Cissé, Borniger, and Nelson 373

even during withdrawal (Johanson, Roehrs, Schuh, & clock genes in the VTA and the NAc alters reward
Warbasse, 1999; Schierenbeck, Riemann, Berger, & behavior, suggesting that clock function in individ-
Hornyak, 2008; Watson, Bakos, Compton, & ual regions of the reward pathway is important to
Gawin, 1992). Specifically, drugs and alcohol alter mediating drug reward.
clock gene expression in mice and circadian rhythms Clock genes are not the sole messengers of the
in rodents and humans (Perreau-Lenz & Spanagel, circadian system. Glucocorticoids modulate addic-
2008; Spanagel, Rosenwasser, Schumann & Sarkar, tive behaviors via the reward system (Becker-Krail
2005). Addictive behaviors cycle in a circadian fash- & McClung, 2016). Tyrosine hydroxylase (TH),
ion and certain clock genes are necessary for drug the rate-limiting enzyme in dopamine production,
responses in mice (Parekh & McClung, 2015). contains a glucocorticoid response element, and
Mice with deletions of Clock increase cocaine reward glucocorticoids increased TH mRNA (Barrot et al.,
and increase dopamine in the VTA (McClung et al., 2000; Fossom, Sterling, & Tank, 1992; Hagerty,
2005; Ozburn, Larson, Self, & McClung, 2012; Morgan, Elango, & Strong, 2008; Lewis, Harrington,
Roybal et al., 2007). Per genes have similarly been & Chikaraishi, 1987). Deletion of GR in dopamine
implicated in regulation of alcohol consumption receptor 1a–expressing neurons decreases self-­
and altered locomotor and reward response to cocaine administration and VTA dopamine cell firing
(Abarca, Albrecht, & Spanagel, 2002; Spanagel, (Ambroggi et al., 2009). Moreover, melatonin mod-
Pendyala, et al., 2005). The association between clock ulates the reward system at the behavioral, dopa-
genes and cocaine addiction is weaker in humans mine content, release, and receptor sensitivity levels
(Malison, Kranzler, Yang, & Gelernter, 2006), but (Alexiuk & Vriend, 1993; Hamdi, 1998; Papp, Litwa,
alcohol and heroin dependence are associated with Łasoń-Tyburkiewicz, & Gruca, 2010; Zisapel,
polymorphisms in Bmal1 and Per3, respectively Egozi, & Laudon, 1982). MT1 exhibits circadian
(Kovanen et al., 2010; Zou et al., 2007). rhythms in expression in the central dopaminergic
The majority of the reward response–altering system (Uz et al., 2005), whereas MT2 is necessary
mutations mentioned previously are whole-body for the reversal of morphine reward (Han, Xu, Yu,
clock gene knockouts. The SCN indirectly inner- Shen, & Wei, 2008), and deletion of either mela-
vates reward centers of the brain such as the ventral tonin receptor eliminates the methamphetamine
tegmental area (VTA; Luo & Aston, 2009). The reward response (Clough, Hutchinson, Hudson, &
VTA is a part of the mesolimbic dopamine system, Dubocovich, 2014; Hutchinson, Hudson, &
commonly termed as the VTA-NAc (nucleus accum- Dubocovich, 2012).
bens) circuit. The VTA is a major concentration of
dopaminergic neurons that integrates external Conclusion
stimuli and, depending on the resulting dopamine Life evolved on a rotating planet, and circadian
release, designates whether a situation is rewarding rhythms in physiology and behavior developed as
or aversive (Russo & Nestler, 2013). Under normal adaptations to predict day and night. The appropri-
conditions, this modulates the rewarding response ate synchronization of the light–dark cycles with
to food and sex but is also directly acted upon by brain function is critical for appropriate endocrine
drugs of abuse. The NAc is a direct target of dopa- function. Hormone secretion is synchronized by the
minergic VTA projections. Together these brain circadian clocks to coincide with optimal receptor
regions project to and get reciprocal input from availability and overall physiological and behavioral
the amygdala, hippocampus, hypothalamus, and functionality. The biological clock can be consid-
medial prefrontal cortex to mediate memory and ered the conductor of the hormonal orchestra, keep-
response to rewarding and aversive stimuli. ing the endocrine system synchronized. Exposure to
Global clock gene knockouts may alter reward bright light during the day and dark environments
responses due to lack of descending clock input to at night has shaped how hormones and mood are
the reward system or altered clock gene expression in regulated. Presumably, this arrangement harmo-
reward centers of the brain. Recent studies indicate nized with the lifestyles of our ancestors to optimize
that specific deletion of NPAS2 in the NAc decreases human functioning.
cocaine reward response and self-administration The introduction of electric lights was a mile-

of Clock Δ19 resolves the increase in cocaine reward

(Ozburn et al., 2015). Restoring Clock in the VTA stone in evolutionary history, allowing humans to
control both inside and outside environments. The
(Roybal et al., 2007). Indeed, specific deletion of ability to illuminate the night led to safer, wealthier,

374 Hormones, Circadian Rhy thms, and Mental Health

and more productive individuals and societies. The Arey, R. N., Enwright, J. F., Spencer, S. M., Falcon, E., Ozburn,
study of circadian biology developed decades after A. R., Ghose, S., . . . McClung, C. A. (2014). An important role
for cholecystokinin, a CLOCK target gene, in the development
the widespread adoption of electric lights. Only re- and treatment of manic-like behaviors. Molecular Psychiatry,
cently are we learning about the effects of artificial 19(3), 342–350. http://doi.org/10.1038/mp.2013.12
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in 2016, the American Medical Association issued a in the dark here: Induction of depression- and anxiety-like
report cautioning against blue-rich LED streetlights, behaviours in the diurnal fat sand rat, by short daylight or
melatonin injections. International Journal of Neuro­
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Barrot, M., Marinelli, M., Abrous, D. N., Rougé-Pont, F., Le
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Acknowledgments
and ACTH in patients with major depressive disorder and
Preparation of this review was supported by NIH NRSA grant
healthy humans with special reference to the outcome of the
F31 ES026890 (YMC), a Pelotonia graduate student support
dexamethasone suppression test. Psychoneuroendocrinology,
grant (JCB), and NIH grants R01NS092388 and R21CA202745
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 CH A PT E R

22 Hormones and Major Depressive Disorder

Mark A. Ellenbogen, Virginia Tsekova, and Lisa Serravalle

Abstract

Hormonal influences figure prominently in the development of major depressive disorder (MD).
The chapter addresses the hypothalamic-pituitary-adrenal (HPA) axis and gonadal (i.e., estrogen and
testosterone) hormones that are most relevant to MD. There is substantial evidence of HPA
dysfunction in persons with MD, including adrenal hypersensitivity leading to elevated cortisol levels
and deficient negative feedback control of the axis. These abnormalities may represent a marker of
vulnerability for MD, as they are observed in high-risk populations prior to the development of the
disorder. Gonadal hormones are related to specific presentations of MD. Estrogen sensitivity appears
to underlie a “reproductive” form of MD in women, as seen during the menstrual cycle, postpartum
period, and perimenopausal transition. Low testosterone, as occurs during normal aging, is associated
with an increased risk for MD in men. These hormonal changes may be important in defining subtypes
of MD that might be treated with targeted interventions.

Keywords: hormones, depression, estrogen, testosterone, major depressive disorder

Approximately 16 percent of adults in North America below cerebrovascular disease but well ahead of
suffer from major depressive disorder (MD) and an ­alcohol use disorders, Alzheimer and other demen-
additional 10 percent from minor forms of depres- tias, and road traffic accidents. The burden of MD
sion over the course of their lifetime (Kessler et al., around the world is based on five factors: high life-
2003). Similar lifetime prevalence rates (14.6 percent) time prevalence, high rate of recurrence, prolonged
have been reported in other high-income countries role impairment, frequent co-occurrence with other
around the world, with lower rates (11 percent) in low- chronic diseases, and early age of onset (15 to 30
to middle-income countries (Bromet et al., 2011). years; Bromet et al., 2011; Kessler, 2012; Van der
Additionally, recurrence rates of depression are as Kooy et al., 2007). Depression in youth constitutes
high as 80 percent, and 60 percent of persons with a major social-developmental problem because it
MD report significant role impairment (Kessler et al., co-occurs with social maladjustment, academic prob-
2003; Kessler & Wang, 2009). The Global Burden lems, family dysfunction, and interpersonal difficul-
of Disease study of the World Health Organization ties that transfer from one generation to the next
reported that MD in the year 2000 was the most (Joiner & Timmons, 2009; Lewinsohn, Rohde,
burdensome disease in the Americas, ahead of ische- Seeley, Klein, & Gotlib, 2003; Ostiguy, Ellenbogen,
mic heart disease, perinatal conditions, violence, road & Hodgins, 2012). Thus, MD is a recurrent, debil-
traffic accidents, and cerebrovascular disease (Üstün, itating, and, to some extent, chronic disorder, despite
Ayuso-Mateos, Chatterji, Mathers, & Murray, 2004). the many advances in treatment (Segal, Pearson, &
In Europe, MD was the third most burdensome Thase, 2003). These facts highlight the importance
disease in disability-adjusted life-years, falling just of studying the etiology and developmental course of

381
this disorder, and the need for more efficacious use of an arbitrary number of criteria for defining
treatments and prevention strategies. the diagnosis (five out of nine symptoms rather than
In this chapter, we review the relationship between four, for example). There is accumulating evidence
MD and different hormonal systems, a key facet of in prospective studies that “subclinical” depression is
the etiology of MD. Specifically, we show how hor- associated with significant negative outcomes at later
monal systems are dysregulated in MD and propose follow-up assessments (Fergusson, Horwood, Ridder,
that subtle changes in hormone functioning, such as & Beautrais, 2005; Klein et al., 2013), which argues
rising levels of the glucocorticoid cortisol in youth, against a categorical approach to MD. Because most
may serve as a marker of risk for MD. The latter point of the studies reviewed in this chapter use the MD
is particularly important as it demonstrates the pos- diagnosis, conclusions put forth in this chapter should
sibility that changes in hormonal systems may rep- be considered with these limitations in mind.
resent an etiological risk factor for developing MD, MD is perhaps the prototype of a heterogeneous
rather than just a correlate or endocrine “symptom” condition arising from a complex etiology. There
of having MD. This chapter will focus on MD and are many variations of symptom presentation, from
will not review the literature on other affective dis- the melancholic subtype characterized by severe
orders such as bipolar disorder or persistent depressive ­anhedonia, weight loss, and a lack of reactivity to
disorder (dysthymia), despite the fact that there are pleasurable events to the atypical subtype character-
similar endocrine changes associated with these dis- ized by reactivity to pleasurable events, weight gain,
orders (Watson, Gallagher, Ritchie, Ferrier, & Young, and a sensitivity to interpersonal rejection. There
2004). Although there are many endocrine factors may be important psychobiological differences be-
that might be associated with MD, the chapter ad- tween these presentations (Harkness & Monroe,
dresses those most relevant to MD, notably adrenal 2006). Heritability estimates of 40 to 60 percent
(i.e., cortisol) and gonadal (i.e., estrogen and testos- have been reported in large twin studies of MD,
terone) hormones. For reviews of other hormones, with substantial variance attributed to nonshared
such as those from adipose tissue (leptin) and the unique environmental factors (influences that may
gastrointestinal tract (­ghrelin), we refer the reader be different between twins, such as stressful life
to Carvalho and colleagues (2014) and Wittekind events, peer groups, etc.; Kendler & Prescott, 1999;
and Kluge (2015). McGuffin et al., 2003). Early family factors, in-
MD is defined as a syndrome characterized by cluding maltreatment, maternal depression, and a
depressed mood and/or anhedonia (loss of interest parenting style characterized by unresponsiveness
or pleasure in previously rewarding activities) that and low warmth, are linked to the development of
persists for at least two weeks, but typically longer, MD (Goodman & Brand, 2009; Harkness &
most of the day and nearly every day. Along with the Lumley, 2008; McLeod, Weisz, & Wood, 2007).
two cardinal features of depression, other symptoms Transactional developmental theories that incorpo-
include weight loss or weight gain, insomnia or rate vulnerability factors (genetic risk, neurobiolog-
­hypersomnia, psychomotor agitation or retardation, ical factors), early environmental adversity, and
fatigue or loss of energy, diminished concentration proximal risk factors such interpersonal stress and
or indecisiveness, feelings of worthlessness or exces- cognitive factors (i.e., rumination, depressogenic
sive or inappropriate guilt, and recurring thoughts attributions, etc.) are perhaps the most important and
of death or suicidal behavior. The diagnosis of MD relevant models of the etiology of MD (Goodman
requires that persons display at least five of the & Brand, 2009; Hammen, 2015). Endocrine fac-
aforementioned nine symptoms, with one of them tors are central in these models in that they are sen-
sad mood or anhedonia, and that they report signif- sitive to developmental and environmental factors
icant distress or impairment in social, occupational, and have an important impact on neural circuits
or other important areas of functioning. Although associated with depressive affect and anhedonia
the MD diagnosis has proven to be useful clinically, (Heim, Newport, Mletzko, Miller, & Nemeroff,
there are problems with the use of a categorical di- 2008; Lupien, McEwen, Gunnar, & Heim, 2009).
agnostic system such as the Diagnostic and Statistical In the next section, we address the hypothalamic-
Manual for Mental Disorders, 5th edition, in studying pituitary-adrenal (HPA) axis, because this system
the etiology of MD (Lupien et al., 2017), including appears to be dysfunctional during episodes of MD
high rates of comorbid presentations (Kessler & and may represent a key biological marker of risk
Wang, 2009) among patients with MD and the for developing an affective disorder.

382 Hormones and Major Depressive Disorder

Hypothalamic-Pituitary-Adrenal Axis the hypophyseal transport system that guides the
and Major Depressive Disorder neuropeptide to the anterior portion of the pituitary
The Hypothalamic-Pituitary-Adrenal Axis gland, situated at the base of the brain. Adreno­
Along with the fast-acting sympathetic nervous corticotropic hormone (ACTH) is then synthesized
system, the HPA axis is a principal actor in orches- and released into circulation, where it stimulates the
trating the mammalian stress response to prolonged adrenal cortex, just above the kidneys, to produce
challenges. The HPA axis is regulated via a complex and then secrete glucocorticoids, particularly cortisol
interplay of serotonergic, noradrenergic, and supra- in humans. Once in circulation, cortisol targets dif-
chiasmatic nucleus circadian input, as well as corti- ferent organs to increase the availability of glucose
cal and limbic brain regions that detect and appraise through gluconeogenesis, promotes lipid and carbo-
threat and contextual factors (Chrousos, 1998; hydrate metabolism, and activates anti-inflammatory
De Raedt & Koster, 2010; Holsboer, 1995; van de and other immunosuppressive effects. All these
Werken et al., 2014). The sequence of events un- changes increase the availability of energy stores in
derlying the HPA stress response is as follows (see circulation to promote short-term survival in threat-
Figure 22.1). ening circumstances.
Real or perceived stress in response to a difficult Glucocorticoid actions occur through the stimula-
challenge, typically those perceived to be beyond tion of intracellular mineralocorticoid and glucocor-
one’s ability to cope, activates a number of neural ticoid receptors (GRs), distributed widely through
circuits including the prefrontal cortex, hippocampus, the brain with high concentrations in the hippocam-
amygdala, septum, and hypothalamus. The neural pus, amygdala, and hypothalamus. Once activated,
response to an ongoing threat in the amygdala acti- these receptors in the cytosol of the cell migrate to
vates the HPA axis through the synthesis of corti- the nucleus and enact changes in gene expression.
cotropin-releasing hormone (CRH) and arginine In this way, the stimulation of mineralocorticoid
vasopressin in the paraventricular nuclei of the hy- and glucocorticoid receptors have short-term (i.e.,
pothalamus, which leads to the release of CRH into gluconeogenesis) and long-term effects (i.e., changes

Amygdala CRH
+
– PFC
Hypothalamus
–
Hippocampus +
CRH Vasopressin Monoamines
– – GABA

Pituitary

– ACTH
BBB

Adrenal cortex

Cortisol
Figure 22.1 The hypothalamic-pituitary-adrenal (HPA) axis is depicted here, with the different factors that influence its functioning.
In the context of a stressful or threatening situation, the amygdala both produces corticotropin-releasing hormone (CRH) in the
central nucleus, which will stimulate other stress- and anxiety-related brain circuits, and activates the paraventricular neurons of
hypothalamus to produce CRH and arginine vasopressin. These hormones are then released into the hypophyseal portal system,
which delivers them to the anterior pituitary, at the base of the brain. Activation of the anterior pituitary causes the production and
release of adrenocorticotropic hormone (ACTH), which then crosses the blood–brain barrier (BBB), enters the general circulation,
and stimulates cells in the adrenal cortex to produce and release the glucocorticoid hormone cortisol. Because cortisol in the periphery
crosses the BBB and enters the brain, levels of the hormone are regulated by negative feedback via activation of glucocorticoid
receptors at various brain areas, most notably the hippocampus. The HPA system is also regulated by different neurotransmitter
systems including monoamines and GABA, as well as the prefrontal cortex, which is involved in emotion regulation.

Ellenbogen, Tsekova, and Serravalle 383

in gene expression) that can alter how the system a­ ppears to be hypersensitive to ACTH, as approx-
responds to subsequent stressors (McEwen, 2004; imately 50 percent of depressed patients, relative to
Sapolsky, Romero, & Munck, 2000). It is for this nondepressed controls, show elevated basal levels of
reason that there is interest in the effects of early- plasma or urinary cortisol (Halbreich, Asnis,
life experiences on the development of the HPA Shindledecker, Zumoff, & Nathan, 1985; Nemeroff
system and its effects on physical and mental health & Vale, 2005; Young, 2004). There may be impor-
(Heim et al., 2008; Lupien et al., 2009; McEwen & tant differences in HPA dysfunction across different
Gianaros, 2010). presentations of MD. Cortisol hypersecretion, for
Because prolonged exposure to glucocorticoids can example, is greater in MD with psychotic features
be neurotoxic and elicit negative effects such as the than nonpsychotic depression (Duval et al., 2006;
suppression of the immune system, there are restrain- Keller et al., 2006). Consistent with the evidence
ing forces that decrease HPA activation following of cortisol hypersecretion, persons with MD have a
acute stress. These effects occur through the stimu- larger adrenal gland than nondepressed volunteers,
lation of GR at multiple levels of the axis, including based on structural imaging studies (Kessing, Willer,
the pituitary, hypothalamus, hippocampus, and fron- & Knorr, 2011). In a meta-analysis of 354 studies
tal cortex, all of which inhibit the HPA response and 18,374 participants (Stetler & Miller, 2011),
to stress. In addition to the HPA glucocorticoid re- cortisol levels were higher in persons with MD than
sponse to stress, there are cognitive, behavioral, and nondepressed controls, and the group difference
autonomic aspects to the stress response (Nederhof, was estimated to be a medium effect size (d = 0.60).
Marceau, Shirtcliff, Hastings, & Oldehinkel, 2015; There is conflicting evidence, however, in the
van den Bos, Harteveld, & Stoop, 2009). These coor- literature. A meta-analysis revealed that, when con-
dinated responses occur through CRH and its pro- sidering all published studies, CRH levels were not
jections to a wide range of brain regions other than consistently elevated in depressed persons relative
the HPA axis. Activation of CRH in the paraventric- to nondepressed controls (Stetler & Miller, 2011).
ular hypothalamus stimulates neural projection to the Elevated CRH in depression may be limited to cer-
thalamus, amygdala, and other parts of the limbic tain types of studies. For example, CRH levels were
system, which serves to coordinate the autonomic and elevated in MD when the study did not exclude per-
behavioral responses to threat. There is accumulat- sons on antidepressant treatment (Stetler & Miller,
ing evidence that these circuits are fundamental in 2011). Perhaps CRH overdrive is characteristic
understanding the expression of different forms of of severe MD where discontinuing antidepressant
psychopathology, but particularly MD (Kormos & medication is not possible. CRH was also higher in
Gaszner, 2013). In the following sections, we high- depressed patients relative to controls for studies
light key facets of HPA dysregulation in persons with using blood rather than cerebrospinal fluid (Stetler
MD and among those who are at risk for MD. & Miller, 2011). It is not clear why these differences
are present, but they point to the need for further
Studies of the Hypothalamic-Pituitary- research on CRH in MD. Inconsistent findings have
Adrenal Axis in Persons With Major also been observed in the measurement of cortisol
Depressive Disorder in persons with MD. Although many of the studies
Converging evidence indicates that the HPA axis of basal cortisol have used inpatient samples and
is severely compromised in persons with MD, with measures of the hormone in plasma, HPA dysregu-
a cascade of related deficits and adaptations (Chrousos, lation may be different in outpatients with MD, who
1998; Holsboer, 1995; Lopez-Duran, Kovacs, & make up the large majority of patients, and in studies
George, 2009; Nemeroff & Vale, 2005). The pri- measuring cortisol in saliva. To start, group differ-
mary dysfunction is believed to be increased CRH ences in basal cortisol levels are greater in hospitalized
activity, as has been shown in studies of cerebrospinal depressed patients relative to outpatients with MD,
fluid of depressed and suicidal patients (Nemeroff, and this does not appear to be due to differences in
1996; Nemeroff, Owens, Bissette, Andorn, & Stanley, depression severity (Stetler & Miller, 2011). Studies
1988; Pitts, Samuelson, Meller, & Bissette, 1995; of the cortisol response following awakening (CAR),
Waters et al., 2015). In response to high CRH levels, assessed in saliva rather than blood, have found
the pituitary gland appears to become hyposensitive ­evidence of both elevated (Bhagwagar, Hafizi, &
to CRH (Holsboer, Spengler, & Heuser, 1992). Cowen, 2005; Pruessner, Hellhammer, Pruessner,
Adding to this dysregulation, the adrenal cortex & Lupien, 2003; Ulrike, Reinhold, & Dirk, 2013;

384 Hormones and Major Depressive Disorder

Vreeburg et al., 2009) and attenuated levels adolescents and young adults with MD underwent
(Ellenbogen & Ostiguy, 2017; Huber, Issa, Schik, & the Trier Social Stress Test (TSST; Kirschbaum, Pirke,
Wolf, 2006; Knight, Avery, Janssen, & Powell, 2010; & Hellhammer, 1993), a well-known psychosocial
Stetler & Miller, 2005) of the hormone in depressed stress induction, on two occasions approximately
samples relative to age-matched controls. Other six months apart. Although controls showed the
studies have found no differences in the cortisol re- expected attenuated cortisol response on the second
sponse following awakening between depressed and TSST relative to the first (i.e., habituation), persons
control samples (Hellgren, Åkerud, Skalkidou, & with MD showed no such effect. Thus, both poor
Sundström-Poromaa, 2013; Vammen et al., 2014). habituation to stress and weakened negative feed-
As alluded to earlier, there is heterogeneity in de- back control of the axis may underlie more general
pressed populations and some of the d ­ iscrepancies self-regulation problems in depression, including
in the literature may be due to clinical differences deficits in emotion regulation and cognitive con-
in the populations studied. For example, the trol, which influence HPA functioning (Ellenbogen,
Netherlands Study of Anxiety and Depression as- Schwartzman, Stewart, & Walker, 2006; Joormann
sessed cortisol levels in saliva at awakening and 30, & Tanovic, 2015; LeMoult & Joormann, 2014).
45, and 60 minutes later in 233 patients with MD A recent and larger meta-analysis found a small
and 543 controls (Lamers et al., 2013). The cortisol attenuation of the cortisol response to psychosocial
rise following awakening was larger in MD patients stress in the MD group compared to controls (Zorn
with melancholic features than controls, but there et al., 2017). More important, a robust sex differ-
were no differences between the control group and ence among persons with MD was found: Depressed
MD patients with atypical features. These data were women exhibited attenuated cortisol reactivity to
consistent with other studies that have shown that psychosocial stress, whereas depressed men displayed
HPA hyperactivity is associated with melancholic increased reactivity (Zorn et al., 2017). Interestingly,
features in depression (Stetler & Miller, 2011; Wong there were few robust differences between remitted
et al., 2000). and currently depressed patients, consistent with the
view that some HPA dysfunctions may persist beyond
Studies of the Cortisol Response to the acute depressive state. In sum, there are mixed
Psychosocial Stress in Adults With findings in studies examining the HPA response
Major Depressive Disorder to stress in persons with MD. Tentatively, HPA dys-
A number of studies have assessed the cortisol re- regulation of the stress response consists of a weak-
sponse to stress in persons with MD (Burke, Davis, ened ability to mount a strong cortisol response to
Otte, & Mohr, 2005; Ciufolini, Dazzan, Kempton, stress, particularly in women with MD, and possible
Pariante, & Mondelli, 2014) and MD in remission deficits in regulating and normalizing cortisol levels
(Morris, Rao, Wang, & Garber, 2014). The findings poststress. In the next section, we focus on laboratory
have been mixed. Two meta-analyses of studies as- neuroendocrine challenge studies aimed at highlight-
sessing the cortisol response to psychosocial stress ing HPA dysfunctions and deficits in the negative
found no evidence of increased stress reactivity across feedback control of the axis.
nine studies (Burke et al., 2005; Ciufolini et al., 2014),
but one of the meta-analyses found evidence of Neuroendocrine Challenge Studies in Adults
increased cortisol levels during the recovery phase With Major Depressive Disorder
following the stress exposure (Burke et al., 2005). The Along with CRH hyperactivity, the GR-mediated
effect size for group differences during the recovery shutdown of the axis has been identified as a key def-
phase (d = 1.39) was approximately five times higher icit associated with MD (Holsboer & Ising, 2010).
than the effect size for the acute stress phase (d = 0.27), A number of neuroendocrine challenges have been
although it should be noted that the larger effect developed to identify deficient negative feedback
size was based on only four studies and was not rep- control of the HPA axis. Dexamethasone (DEX), a
licated by Ciufolini et al (2014). The putative deficit potent and long-lasting synthetic glucocorticoid,
in poststress recovery observed in persons with MD stimulates glucocorticoid and mineralocorticoid
may reflect a deficit in the negative feedback control ­receptors and elicits a negative feedback suppression
of the axis (see later). Moreover, this finding parallels of the HPA axis, resulting in robust decreases in
a recent study showing poor habituation to repeated levels of ACTH and cortisol for approximately
stressors in MD (Morris & Rao, 2014). In this study, 24 hours. In early studies, these hormones remained

Ellenbogen, Tsekova, and Serravalle 385

elevated in patients with MD relative to controls Hypothalamic-Pituitary-Adrenal
following DEX administration, which was termed Functioning Prior to the Development
DEX nonsuppression and considered to be a clini- of Major Depressive Disorder
cal biomarker of MD, particularly the melancholic Despite the evidence that the HPA axis is severely
subtype (Bowie, Beaini, & Bowie, 1987; Holsboer, compromised in MD, it has been uncertain whether
1995; Rush et al., 1996). Unfortunately, it was soon HPA abnormalities precede the onset of the disorder.
realized that the reliability of the DEX test to identify The distinction is important because HPA abnor-
MD was rather poor; identifying only 20 to 50 per- malities may represent part of the symptom expres-
cent of patients, and it was abandoned as a possible sion of the disorder but have nothing to do with its
diagnostic marker of the disorder (Nierenberg & etiology. Two strategies have been used to address the
Feinstein, 1988). However, DEX nonsuppression question of whether premorbid HPA abnormalities
may be more robust in patients with psychotic MD precede the development of MD. First, birth cohort
than those with no psychotic features (Nelson & and other large community-based longitudinal stud-
Davis, 1997), and it may have predictive value in ies track large samples of children over time and de-
identifying a poor prognosis following treatment termine predictors of negative health outcomes.
(Ribeiro, Tandon, Grunhaus, & Greden, 1993). Unfortunately, only a few such studies have assessed
The DEX test was adapted into the DEX/CRH HPA function. The Tracking Adolescents’ Individual
test (Holsboer, von Bardeleben, Wiedemann, Muller, Lives Survey (TRAILS) followed a large cohort of
& Stalla, 1987), which proved to be a more sensitive children in the Netherlands from early adolescence to
and reliable means of identifying HPA abnormali- adulthood and assessed daytime cortisol levels in the
ties and deficient negative feedback control of the natural environment. The findings from the TRAILS
HPA axis. Patients are given DEX in the evening, study are mixed. Although cross-sectional positive as-
which reduces levels of ACTH and cortisol over the sociations were found between measures of cortisol in
next 24 hours. On the next day, patients are chal- the morning, including the CAR, and depressive
lenged with intravenous CRH, activating the HPA symptoms at age 11 years (Dietrich et al., 2013), the
axis in the context of DEX suppression. Following CAR at 13 years of age did not predict MD at age 16
this procedure, cortisol levels remain high in 60 to (Nederhof, van Oort, et al., 2015). Another 18-month
80 percent of untreated patients with MD (Heuser, longitudinal study of young adolescents found a
Yassouridis, & Holsboer, 1994; Kunugi et al., 2006; ­positive relationship between cortisol reactivity to
Zobel et al., 2001), which has been confirmed in a stressors in the environment and the development of
recent meta-analysis (Mokhtari, Arfken, & Boutros, depressive symptoms one year later (Susman, Dorn,
2013). The DEX/CRH test distinguishes remitted Inoff-Germain, Nottelmann, & Chrousos, 1997),
patients from controls (Schmider et al., 1995), which is c­ onsistent with the TRAILS’s findings of the
predicts treatment response (Kunugi et al., 2006; cohort in early adolescence. Perhaps the relationship
Paslakis, Heuser, Schweiger, & Deuschle, 2010), between high cortisol levels and depression is specific
and prospectively predicts relapse (Zobel et al., 2001; to early adolescence, but there are too few studies to
Zobel, Yassouridis, Frieboes, & Holsboer, 1999). put forth strong conclusions.
Thus, it holds promise as a putative biological marker The second approach to studying premorbid HPA
of MD and treatment outcome. Cortisol and ACTH abnormalities prior to the development of MD is
nonsuppression following the test, however, are not to identify select samples of youth who do not have
specific to MD, as it has been observed in other psy- MD but are at high risk for the development of the
chiatric disorders (Lammers et al., 1995) and during disorder. Different strategies have been used to iden-
stressful circumstances (Wirtz et al., 2010). Also, tify target populations, including the recruitment of
the mechanism underlying cortisol nonsuppression youth (1) exposed to multiple adversities (e.g., poverty,
in patients in MD is not known. Although nonsup- family conflict; Goodyer, Croudace, Dudbridge, Ban,
pression may be due to deficient GR-mediated neg- & Herbert, 2010), (2) who have high trait neuroti-
ative feedback control of the HPA axis, it may also cism (Adam et al., 2014), or (3) who have a parent
be related to the amplification of CRH release at with a mental disorder. Studying children whose
the level of the pituitary by arginine vasopressin or parents have an affective disorder, either MD or bi-
changes in the sensitivity of the adrenal cortex to polar disorder, is a strategy commonly used because
ACTH (Modell, Yassouridis, Huber, & Holsboer, these children are at high risk for developing an
1997; Spijker & van Rossum, 2012). ­affective disorder and other mental disorders, with

386 Hormones and Major Depressive Disorder

particularly high rates of MD (Nijjar, Ellenbogen, Nondepressed young adults having a parent with
& Hodgins, 2014; Rasic, Hajek, Alda, & Uher, 2014). MD secreted higher levels of cortisol in response
Offspring of parents with an affective disorder are to the DEX/CRH challenge than healthy controls,
approximately two and a half times more likely to but less than those who had MD (Holsboer, Lauer,
be diagnosed with any mental disorder and three Schreiber, & Krieg, 1995). As described previously,
to four times more likely to be diagnosed with an high cortisol in response to the DEX/CRH test in-
affective disorder, particularly before the age of dicates, in part, deficient negative feedback control
20 years, than offspring of parents with no mental of the HPA axis. Interestingly, the increased response
disorder (Lapalme, Hodgins, & LaRoche, 1997; to the DEX/CRH test persisted in a four-year
Rasic et al., 2014). ­follow-up of a subsample of at-risk participants who
underwent the challenge a second time (Modell
Cortisol Levels in High-Risk Youth et al., 1998), which suggests that the response to the
With some exceptions (Ising, Lauer, Holsboer, DEX/CRH challenge might be a stable vulnerability
& Modell, 2005; Ronsaville et al., 2006), there is marker for MD. In contrast, a study of the response
evidence that subtle HPA abnormalities exist in to CRH alone in offspring of parents with MD or
populations at high risk for MD, and that these ab- bipolar disorder failed to uncover any evidence of
normalities may represent a marker of vulnerability increased sensitivity to CRH (Ronsaville et al., 2006).
for the disorder (Ellenbogen, Hodgins, Walker, Adam, Thus, the increased sensitivity in young adults having
& Couture, 2006; Goodyer, Herbert, Tamplin, & a parent with MD to the DEX/CRH challenge
Altham, 2000; Lundy et al., 1999; Mannie, Harmer, (Holsboer et al., 1995) is likely due to the nonsup-
& Cowen, 2007; Modell et al., 1998). Elevated levels pression of cortisol release following pretreatment
of daytime cortisol measured in the natural environ- with DEX, rather than other CRH-related effects.
ment may represent one such marker of vulnerability.
The offspring of parents with bipolar disorder, for Studies of the Hypothalamic-Pituitary-
example, had higher daytime cortisol levels assessed Adrenal Response to Stress in
in adolescence (Ellenbogen, Hodgins, et al., 2006), High-Risk Youth
at 18 years of age (Ellenbogen, Santo, Linnen, Walker, For studies of stress reactivity, the findings are mixed.
& Hodgins, 2010), and at 20 years of age (Ostiguy, A number of studies indicate that infants and chil-
Ellenbogen, Walker, Walker, & Hodgins, 2011) com- dren exposed to postnatal maternal depression show
pared to an age-matched control group having par- increased cortisol reactivity to various normative
ents with no mental disorders. Elevated cortisol levels challenges (i.e., immunization; Brennan et al., 2008;
show trait-like stability and appear to persist over Dougherty, Klein, Rose, & Laptook, 2011; Dougherty,
time, with evidence of stable high cortisol levels in Tolep, Smith, & Rose, 2013; Essex, Klein, Eunsuk,
high-risk youth sampled across 14 consecutive days & Kalin, 2002; Lundy et al., 1999; C. S. Waters
(Ellenbogen et al., 2010; Owens et al., 2014). The et al., 2013). In a study of 7- and 8-year-olds, children
higher cortisol levels among the offspring of a parent with both internalizing problems and a depressed
with bipolar disorder were not related to the small mother exhibited an increased cortisol response to a
number of participants diagnosed with a mental dis- mild laboratory stressor and elevated baseline corti-
order, nor were they associated with self- or parent sol levels measured in the laboratory relative to the
reports of clinical symptoms, age, self-reported com- offspring of nondepressed parents (Ashman et al.,
pliance with the saliva sampling protocol, time of 2002). Young adult offspring of parents with MD
awakening, smoking, food consumption, exercise, demonstrated an increased cortisol response to the
or oral contraceptive use. Similar findings have been TSST relative to a control group having parents with
reported in infant, adolescent, and young adult no mental disorder (Barry et al., 2015). The group
offspring of parents with MD (Halligan, Herbert, differences in cortisol reactivity were independent
Goodyer, & Murray, 2004; Lundy et al., 1999; of group differences in the offspring’s current levels of
Mannie et al., 2007). depression, anxiety, or stressful life events. However,
other studies have not replicated these findings. In a
Exogenous Challenge Studies in study of 257 infants, no evidence of increased corti-
High-Risk Youth sol reactivity to stress was observed, but offspring of
Other aspects of HPA functioning have also been mothers with MD showed poor acclimatization to a
studied in persons at high risk of developing MD. novel environment (participating in a laboratory

Ellenbogen, Tsekova, and Serravalle 387

e­ xperiment) compared to offspring of parents with no prospective development of MD (Adam et al., 2010;
mental disorder (Waters et al., 2013). Other studies Colich, Kircanski, Foland-Ross, & Gotlib, 2015;
of high-risk adolescents and young adults, in contrast, Ellenbogen, Hodgins, Linnen, & Ostiguy, 2011;
have found no evidence of a heightened response to Goodyer et al., 2000, 2010; Harris et al., 2000) and
stress (Bouma, Riese, Ormel, Verhulst, & Oldehinkel, depressive symptoms (Halligan, Herbert, Goodyer,
2011; Ellenbogen, Hodgins, et al., 2006). Although & Murray, 2007; Susman et al., 1997). Odds ratios
the adolescent offspring of parents with bipolar dis- from these studies indicate that having elevated cor-
order did not show increased stress reactivity to the tisol levels in the natural environment increase rates
laboratory-based TSST relative to youth having par- of depression by a factor of 1.6 to 7.1, although one
ents with no mental disorders (Ellenbogen, Hodgins, study demonstrated that this relationship declines
et al., 2006), they did show increased sensitivity substantially at 2.5 years or more from the assessment
to stressors occurring in the natural environment of cortisol levels (Vrshek-Schallhorn et al., 2013).
(Ostiguy et al., 2011). Offspring of parents with Given that the study by Carnegie and colleagues
­bipolar disorder who experienced high chronic (2014) was the largest study to date (N = 668) and
stress displayed a larger CAR than the offspring of found no evidence of a prospective relationship be-
parents with bipolar disorder reporting low chronic tween measures of cortisol and the development
stress. In addition, the offspring of parents with of depression at age 15 years, further research in this
bipolar disorder who reported experiencing severe area is warranted, with an emphasis on moderators
interpersonal episodic stress exhibited higher levels of the relationship. Pubertal status may represent one
of daytime cortisol than the offspring of parents with such moderator, as interactions between gonadal
bipolar disorder reporting low levels of interpersonal hormones and the HPA system may fundamentally
episodic stress. These relationships were substantially change relations between cortisol levels and depressive
more robust in the offspring of parents with bipolar symptoms (Colich et al., 2015; Hankin et al., 2010).
disorder than control offspring, even after control- It is also possible that the positive relationship
ling for psychopathology in the offspring. In sum, between cortisol levels in youth and the later devel-
there are likely age-related and task-related factors opment of MD is limited to studies of high-risk
that obfuscate the study of stress reactivity in high- populations and/or persons with a vulnerability to
risk youth (Hankin, Badanes, Abela, & Watamura, develop the disorder, which would be consistent
2010). Despite the mixed findings, there is some with studies of the offspring of parents with an
evidence of altered HPA reactivity to stress in the ­affective disorder (Ellenbogen et al., 2011; Halligan
offspring of parents with an affective disorder, and it et al., 2007) and youth with high neuroticism
may be important to study how high-risk youth (Adam et al., 2010) or multiple risk factors (Goodyer
respond to naturalistic stress in their environment, et al., 2000). The sample studied by Carnegie et al
rather than artificial laboratory stressors. (2014), in contrast, was a birth cohort. Studies of
at-risk adolescents that used genotyping support
Prospective Studies Linking Cortisol Levels this hypothesis (Goodyer, Bacon, Ban, Croudace, &
to the Development of Depression Symptoms Herbert, 2009; Goodyer et al., 2010). High cortisol
Although the identification of group differences levels in the morning predicted the development of
in HPA functioning between high-risk and control MD one year later, but the strongest effects were
youth is consistent with the view that persons at risk found in adolescents having either the short allele of
for affective disorders exhibit subtle premorbid HPA the ­serotonin transporter–linked promoter region
abnormalities, it does not demonstrate that these polymorphism (5-HTTLPR) or the Val66Met vari-
markers are associated with the development of MD. ant of the brain-derived neurotropic factor gene
For example, HPA abnormalities may simply high- polymorphism. The short allele 5-HTTLPR geno-
light the fact that environmental adversities com- type is particularly relevant, as it is widely viewed
monly aggregate in families having parents with MD as a marker of enhanced sensitivity to stress (Gibb,
(Goodman & Brand, 2009), and environmental Beevers, & McGeary, 2013; Gotlib, Joormann,
­adversity is known to alter the HPA system, either Minor, & Hallmayer, 2008). Adolescents having
as sensitization (Heim et al., 2008) or blunted reac- both the risky 5-HTTLPR genotype and elevated
tivity (Lovallo, Farag, Sorocco, Cohoon, & Vincent, cortisol levels in the morning over four days of sam-
2012). Fortunately, a number of studies, but not pling were 7.6 times more likely to develop MD in
all (Carnegie et al., 2014; Keenan et al., 2013), the following year relative to adolescents with neither
have shown that elevated cortisol levels predict the risk factor (Goodyer et al., 2010). By comparison,

388 Hormones and Major Depressive Disorder

adolescents having high cortisol levels, irrespective puberty (Hankin & Abramson, 1999). Women
of their genotype, were 4.6 times more likely to de- remain at a higher risk for MD relative to men until
velop MD than adolescents without elevated cortisol menopause (Payne, 2003; Weissman et al., 1993).
levels. In addition to genetic risk, other types of vul- Estrogen fluctuations associated with different peri-
nerability, such as subclinical depressive symptoms ods in the lifespan of women may play a role in the
(Fergusson et al., 2005), may be equally important emergence and maintenance of the sex differences
in understanding the relation between cortisol levels in the prevalence of MD. In addition to monthly
and risk for MD (Ashman, Dawson, Panagiotides, variations of estrogen levels related to the menstrual
Yamada, & Wilkinson, 2002). In a large study of cycle, the main periods associated with estrogen
adolescents, the combination of depressive symp- fluctuation in women are pregnancy, postpartum,
toms and high morning cortisol levels in boys was and perimenopausal periods.
associated with the development of MD over the
next year, but not high cortisol levels alone Late Luteal Phase of the Menstrual Cycle
(Owens et al., 2014). In adolescent boys, but not The greatest monthly hormonal fluctuations occur
girls, both risk factors increased the risk for MD at the end of the luteal phase of the menstrual cycle,
by a factor of over 14. In sum, elevated cortisol during which levels of plasma estrogen fall sharply,
levels in adolescence may represent a biomarker of and rise up subsequently during menstruation.
risk for the affective disorders, particularly in vul- During this period some women experience premen-
nerable populations. strual dysphoric disorder (PMDD), a condition char-
acterized by depressed mood, anxiety, irritability,
Gonadal Hormones and Major changes in appetite and sleep, and different physical
Depressive Disorder symptoms (e.g., breast pain, headaches; Payne, 2003).
The gonadal hormones estrogen and testosterone The prevalence of PMDD in the general population
have been extensively studied in persons with MD is 1.3 to 9 percent (Gehlert, Song, Chang, & Hartlage,
and may represent another key neuroendocrine 2009; Halbreich, Borenstein, Pearlstein, & Kahn,
system associated with risk for MD in vulnerable 2003), and there is a high rate of comorbidity
populations. (30 percent) with other affective disorders (Soares
& Zitek, 2008). Known risk factors associated with
Estrogen PMDD include a history of MD and posttraumatic
Estrogen is involved in the regulation of the female stress disorder, smoking, and fewer years of schooling
reproductive system and the development of sec- (Soares & Zitek, 2008).
ondary female sex characteristics. The three main Regarding the role of estrogen in the develop-
forms of estrogen are estrone, estradiol, and estriol, ment of late luteal depressive symptoms, there is no
with estradiol being the principal gonadal sex hor- consistent evidence that levels of estrogen differ be-
mone. Estrogen synthesis in women is regulated tween normal participants and those with PMDD
primarily by the hypothalamic-pituitary-gonadal (Rubinow, Schmidt, & Craft, 2013). Although estro-
(HPG) axis. Gonadotropin-releasing hormone se- gen levels are not directly associated with PMDD,
creted by the hypothalamus stimulates the pituitary fluctuations in estrogen levels associated with the
gland to release follicle-stimulating hormone. In turn, menstrual cycle may trigger PMDD in women who
follicle-stimulating hormone stimulates the ovaries are at risk for the development of an affective disor-
to produce estrogen. The liver, adrenal glands, breasts, der by virtue of having had past episodes of MD or
and fat cells also secrete small amounts of estrogen vulnerabilities in neurobiological systems associated
(Nelson & Bulun, 2001). In addition to its role in with MD such as the serotonergic system or hypo-
the reproductive cycle, estrogen may play a role in thyroidism (Rubinow et al., 2013). In a classic study
the development of MD in women (Newhouse & manipulating ovarian hormones (Schmidt, Nieman,
Albert, 2015). Danaceau, Adams, & Rubinow, 1998), women with
PMDD treated with a GnRH agonist, which sup-
Depressive Symptoms in Women and presses ovarian function, exhibited a decrease in
Periods of Estrogen Fluctuation PMDD symptoms relative to women on placebo.
Although rates of depression in boys and girls are Symptoms reoccurred when the women with PMDD,
comparable before puberty, girls become twice as but not controls, were given add-back estrogen
likely to develop depressive symptoms or MD com- or progesterone. These findings have since been
pared to their male counterparts during and after ­replicated in subsequent studies and confirmed via

Ellenbogen, Tsekova, and Serravalle 389

meta-analysis (Wyatt, Dimmock, Ismail, Jones, & the 12-month prevalence rates of MD in the adult
O’Brien, 2004). There is evidence that it is the change female population of childbearing age, which is in
in ovarian hormones that precipitates PMDD the range of 13 to 16 percent (Bennett, Einarson,
symptoms, and not simply the prolonged exposure Taddio, Koren, & Einarson, 2004; Brummelte &
to elevated ovarian hormone levels that occur fol- Galea, 2016; Kessler, McGonagle, Swartz, Blazer, &
lowing the add-back estradiol or progesterone treat- Nelson, 1993). The postpartum period, however, is
ment. Schmidt et al. (2017) first suppressed ovarian well known for its perceived heightened risk for the
function before adding back combined estradiol development of MD, although there is some
and progesterone in women with PMDD for three ­controversy over the veracity of this claim in part
months and found that PMDD symptoms increased because of the wide range of prevalence estimates of
in response to the add-back ovarian hormone treat- postpartum depression (O’Hara & McCabe, 2013).
ment during the first menstrual cycle, but not Rates of postpartum depression vary from 10 to
during the second or third cycles when plasma levels 30 percent depending on the criteria used for diagno-
of estradiol and progesterone were elevated but sis in the general population (Brummelte & Galea,
stable. Thus, changes in ovarian hormones such as 2016; Vesga-Lopez et al., 2008). Of importance,
estrogen may represent an important trigger of rates of antenatal and postpartum depression are
PMDD symptoms and stabilizing ovarian hormone elevated in women who have a history of MD. In a
levels may reduce PMDD symptoms, which suggests prospective study, 43 percent of women with a his-
that women with PMDD may be more sensitive to tory of MD experienced a relapse during pregnancy
normal fluctuations in hormone levels. This hy- (Cohen, Altshuler, et al., 2006). Having a history
pothesis was further tested by studying the effective- of MD prior to pregnancy and having depressive
ness of combined oral contraceptives, containing or anxious symptoms during pregnancy are the
estradiol and other hormones (e.g., drospirenone or strongest predictors of the development of a post-
levonorgestrel), as a means of reducing PMDD partum depressive episode (O’Hara & McCabe,
symptoms. Oral contraceptives dampen fluctuations 2013; Robertson, Grace, Wallington, & Stewart,
in ovarian hormones. Unfortu­nately, the results of 2004). Other risk factors associated with postpartum
these studies have been inconsistent. Typical use of depression are neuroticism, low self-esteem, stress-
oral contraceptives, with 21 days of active hormones ful life event, marital problems, poor social support,
and 7 days hormone-free, has been ineffective in low socioeconomic status, being single, unwanted
treating women with PMDD relative to placebo pregnancy, obstetrical problems, and difficult infant
(Freeman et al., 2001; Graham & Sherwin, 1992). temperament (Gelaye, Rondon, Araya, & Williams,
However, oral contraceptives with short hormone- 2016; O’Hara & McCabe, 2013; Robertson et al.,
free periods elicited greater symptom reduction in 2004), highlighting the important role psychosocial
women with PMDD than placebo in some studies factors play in the etiology of this disorder.
(Freeman et al., 2012; Pearlstein, Bachmann, Zacur, There is little empirical evidence that women with
& Yonkers, 2005; Yonkers et al., 2005), but not in postpartum depression vary in their levels of estrogen
others (Eisenlohr-Moul, Girdler, Johnson, Schmidt, or progesterone from euthymic women in the post-
& Rubinow, 2017). Thus, the use of oral contracep- partum period (Bloch, Daly, & Rubinow, 2003;
tives to stabilize fluctuations in ovarian hormones has Mehta et al., 2014; Workman, Barha, & Galea, 2012).
produced mixed findings with respect to reducing As described for PMDD, it has been hypothesized
PMDD symptoms. that women at risk for postpartum depression are
sensitive to changes in ovarian hormone levels, and
Pregnancy and Postpartum women in pregnancy are exposed to a sudden decrease
Pregnancy and the postpartum period are also char- in levels of estrogen and progesterone following
acterized by robust changes in ovarian and other childbirth. Bloch and colleagues (2000) found that
hormones. Levels of estrogen gradually rise during women with a history of postpartum depression were
pregnancy, reaching levels that are 200 to 300 times more likely to experience depressive symptoms
higher than nonpregnant women at week 20 of following an induced hypogonadal state, elicited by
gestation (Brummelte & Galea, 2016). Estrogen levels, the administration of a GnRH agonist, compared to
as well as progesterone, remain high until parturition, never-depressed women. Furthermore, the women
and then they precipitously decline to levels lower with a history of postpartum depression were more
than any time during pregnancy. Antenatal depres- likely to experience depressive symptoms follow-
sion, with a prevalence of 12 percent, is similar to ing add-back estradiol or progesterone treatment,

390 Hormones and Major Depressive Disorder

suggesting that it is the change in ovarian steroid levels of estradiol did not differ between groups. Thus,
hormones that is critical for the development of women at risk for MD who develop postpartum de-
depressive symptoms in vulnerable women, not the pression show evidence of a heightened sensitivity
withdrawal of these hormones. In another study to estrogen signaling relative to high-risk women
(Frokjaer et al., 2015), the prolonged administration who are euthymic during the postpartum period,
of a GnRH agonist was used as a model of the es- both when comparing group differences and when
trogen fluctuations occurring from pregnancy to conducting within-subject changes in gene expres-
postpartum because this procedure elicits an initial sion across the pregnancy and postpartum periods.
increase followed by a robust decrease in estradiol,
but not progesterone, due to the desensitization of Menopausal Transition
GnRH receptors. Relative to placebo, the prolonged During the menopausal transition, there are periods
administration of a GnRH agonist increased clini- of low and high estrogen levels caused by great var-
cian-rated depressive symptoms, and this increase iability in follicle-stimulating hormone concentra-
in symptoms was significantly and positively associ- tions. Rates of MD and depressive symptoms increase
ated with the magnitude of change in estradiol and substantially during this period (Bromberger et al.,
change in the level of the serotonin transporter in 2007, 2011; Freeman et al., 2004), by a factor of
neocortex, as measured by positron emission tomog- 1.3 to 1.8 (Gordon et al., 2015). However, one study
raphy with a radiotracer. These findings demonstrate reported that the menopausal transition, estimated
that an experimentally induced fluctuation in ovar- via vasomotor symptoms (i.e., hot flashes and night
ian steroid hormones can trigger subclinical de- sweats), was no longer a significant predictor of first
pressive symptoms in healthy volunteers. Moreover, lifetime episodes of MD in a sample of premeno-
the study raises the possibility that the serotonergic pausal and perimenopausal women when account-
system is implicated in the relation between estrogen ing for other factors, such as whether the women
and depression, as high ­serotonin transporter indi- reported a highly stressful life event in the past year
cates lower serotonergic functioning, a known risk (Bromberger et al., 2009). Thus, despite strong ev-
factor for MD (Benkelfat, Ellenbogen, Dean, Palmour, idence linking the menopausal transition to increased
& Young, 1994). One issue that should be raised risk for MD, there is still debate on the nature of
with studies of GnRH agonists is that it also acts this relationship.
on GnRH receptors in brain areas outside the HPG As described previously, the fluctuations of ovar-
axis and on synaptogenesis in the hippocampus, ian steroid hormones, rather than the stable low levels
both of which may be related to depression (Prange- that occur during the postmenopausal period, play a
Kiel et al., 2008; Skinner et al., 2009). Finally, a role in the development of MD in women during the
genome-wide association study compared gene menopausal transition. There is little ­ evidence of
­expression during the first and third trimesters of stable differences in estradiol between perimenopau-
pregnancy in women who were euthymic during sal women with and without MD (Barrett-Connor,
pregnancy but developed postpartum depression von Muhlen, Laughlin, & Kripke, 1999). In con-
versus women who were euthymic throughout the trast, longer exposure to fluctuating levels of estradiol
study, all of whom had a history of MD or bipolar caused by a prolonged menopausal transition may
disorder (Mehta et al., 2014). One hundred and be a risk factor for perimenopausal depression
­sixteen gene transcripts were differentially expressed (Avis, Brambilla, McKinlay, & Vass, 1994; Freeman,
between the women with postpartum depression Sammel, Boorman, & Zhang, 2014; Schmidt,
and the euthymic women in the third trimester, Murphy, Haq, Danaceau, & St. Clair, 2002). Because
and this gene expression profile was able to classify fluctuations in estradiol correlate with vasomotor and
women in their respective categories with 88 percent other menopausal symptoms (Freeman et al., 2007),
accuracy. The observed gene expression included an the reported association b­ etween these symptoms
overrepresentation of transcripts linked to estrogen and depression found in some (Cohen, Soares,
signaling among the 116 transcripts predicting Vitonis, Otto, & Harlow, 2006; Freeman et al., 2004)
postpartum depression. Gene expression changes but not all studies (Bromberger et al., 2009) provides
for the transcripts associated with estrogen signaling further evidence of a link between ovarian hormone
from the first to the third trimester and from the fluctuations and risk for depression. In terms of direct
third trimester to the postpartum period were evidence linking depression and fluctuating ovarian
larger in the group with postpartum depression hormones levels, the findings have been mixed
than the euthymic women, despite the fact that the (Bromberger et al., 2011; Freeman, 2010; Freeman,

Ellenbogen, Tsekova, and Serravalle 391

Sammel, Lin, & Nelson, 2006; Woods et al., 2008). system in mice through gene knockout similarly in-
Inconsistent findings might be because many studies creased the expression of 5-HT2A receptors, but not
have not collected enough samples, or have collected other serotonergic receptors. Because 5-HT2A recep-
them at infrequent intervals, to precisely quantify tors are increased in persons with MD (Shelton,
change in ovarian hormone levels (Gordon et al., Sanders-Bush, Manier, & Lewis, 2009), these studies
2015). In the one study that supports the link be- provide evidence that dramatic changes in estrogen
tween depression and fluctuating estradiol levels levels or estrogen receptor function can stimulate
(Freeman et al., 2006), sampling occurred at 10 changes in the serotonergic system associated with
time points across eight years, with two samples MD. In sum, vulnerable women, particularly those
one month apart at each time point. More compre- with a history of MD, may have a heightened sensi-
hensive sampling protocols using advanced statistical tivity to fluctuations in estrogen levels, which may
modeling are needed to effectively measure within- lead to symptoms of depression either directly through
subject changes in ovarian hormones. estrogen effects in brain areas associated with MD or
in interaction with the 5-HT system or other systems
Possible Mechanisms Underlying Link (e.g., HPA) implicated in MD. Although progress
Between Estrogen and Depression has been made in this area, research is needed to
Across the three reproductive periods described clarify the exact mechanisms that make certain
previously, there is no consistent evidence for ab- women more susceptible than others to changes in
normalities in ovarian steroid hormone levels in estrogen levels, and to better delineate the pathway
women suffering from MD compared to controls from estrogen to the expression of symptoms of MD.
(Payne, 2003). Oftentimes, women who experience
perimenopausal depression have also experienced Testosterone
PMDD and postpartum depression, suggesting that Testosterone is an androgen secreted by the gonads
there is a subgroup of women who are highly suscep- in both males and females and is responsible for the
tible to intense changes in estrogen levels (Gordon development of male reproductive tissues such as
et al., 2015). Some researchers have postulated that the testes and prostrate, as well as male secondary
these episodes of depression constitute a specific sex characteristics. In men, testosterone synthesis is
“reproductive” subtype of MD and may require mostly regulated by the HPG axis. GnRH secreted
treatment that is different from those for nonrepro- by the hypothalamus stimulates the pituitary gland,
ductive depression (Payne, Palmer, & Joffe, 2009; which then releases follicle-stimulating hormone
Soares & Zitek, 2008). It has been proposed that and luteinizing hormone to stimulate Leydig cells in
reproductive MD may reflect an inability to success- the testes to produce testosterone. In women, about
fully adapt to changing levels of ovarian steroid half of the testosterone is secreted by the adrenal
hormones (Payne et al., 2009). The precise biologi- glands and ovaries, with the other half produced
cal substrate of the putative sensitivity to fluctuating from circulating precursor molecules (Burger, 2002).
ovarian steroid hormones is still largely unknown, One important difference between testosterone and
although there is evidence that it may be related estrogen levels in humans is that testosterone de-
to the estrogen receptor and/or estrogen signaling clines gradually with age (Davidson et al., 1983), in
pathways in areas known to be associated with mood contrast to the precipitous decline of estrogen in the
and depression, such as the prefrontal cortex, amyg- postpartum period and following menopause (Soares
dala, and hippocampus (Borrow & Cameron, 2014; & Zitek, 2008). However, testosterone changes are
Mehta et al., 2014). There is also evidence that re- substantive during the process of aging. Between
productive subtypes of MD may be closely related the ages of 40 and 70 years, testosterone levels can
to sensitivity in the serotonergic system and its decrease by as much as 40 percent (Seidman, 2007).
interactions with sex steroid hormones (Borrow & In addition to its role in the development of male
Cameron, 2014; Payne et al., 2009). Estrogen can reproductive functioning and other physiological pro-
increase the activity of serotonergic (5-HT) neurons cesses, testosterone has also been implicated in MD.
and alter the expression of specific serotonin receptors
involved in depression (Moses et al., 2000; Robichaud Testosterone Levels and Depression
& Debonnel, 2005). For example, Moses and col- in Men
leagues (2000) found an increase in 5-HT2A receptor A number of studies conducted in male participants

to baseline. Inactivation of the estrogen receptor β

density following estrogen administration compared indicate an increased risk for depression in men
with low levels of testosterone (Almeida, Waterreus,

392 Hormones and Major Depressive Disorder

Spry, Flicker, & Martins, 2004; Christiansen, 2001; t­estosterone has also been used as an augmentation
Giltay et al., 2017; McIntyre et al., 2006), although agent in conjunction with antidepressants in male
there are inconsistencies in this literature (Ebinger, patients with MD. A systematic review conducted
Sievers, Ivan, Schneider, & Stalla, 2009; Johnson, by Kleeblatt and colleagues (2017) concluded that
Nachtigall, & Stern, 2013). For example, a prospec- testosterone administration is a viable method to
tive study of over 3,000 older men showed that enhance antidepressant efficacy, particularly in hy-
those with lower baseline levels of testosterone were pogonadal and older men. However, it is important
twice as likely to have developed MD nine years later to note that there are risks associated with repeated
relative to men with normal androgen levels, even testosterone administration, which include polycy-
after controlling for medical comorbidities, lifestyle themia, prostate cancer, and cardiovascular problems
factors, and age (Ford et al., 2016). Similarly, in a (Surampudi, Wang, & Swerdloff, 2012). Thus, the
prospective study of 469 participants over 65 years use of testosterone as a treatment for MD in men has
of age, men with MD had lower plasma testosterone an important caveat, which may prevent its wide-
levels than nondepressed men, and low testosterone spread use in patients with MD.
predicted a worse course of the disorder over the
two-year follow-up (Giltay et al., 2017). Other stud- Testosterone Levels and Depression
ies of men with atypically low levels of testosterone in Women
have found similar results. Men with hypogonadism, The association between testosterone levels and
a condition characterized by low levels of testoster- ­depressive status in women remains inconclusive
one, exhibit a higher prevalence of major depressive (McHenry et al., 2014). For example, a large study
disorder compared to men with normal androgen found lower salivary testosterone levels in women
levels (McHenry, Carrier, Hull, & Kabbaj, 2014). diagnosed with MD relative to controls (Giltay et al.,
Over half of men referred to a hospital clinic for 2012). In an even larger study of elderly women,
borderline total testosterone levels also had MD or serum testosterone was inversely related to depressive
depressive symptoms based on a recorded diagno- symptoms (Morsink et al., 2007). However, results
sis during a chart review, self-report questionnaire, from a large multisite longitudinal study indicated
or documented use of antidepressant medication that perimenopausal women with higher baseline
(Westley, Amdur, & Irwig, 2015). Men with hypo- serum testosterone levels were at greater risk to
gonadism were approximately four times more likely display elevated depressive symptoms eight years
to develop a depressive illness (MD, dysthymia, or later (Bromberger et al., 2010). Furthermore, only
depressive disorder not otherwise specified) during marginally lower testosterone levels were found in
a two-year follow-up compared to men with normal women with MD relative to nondepressed women
androgen levels (Shores et al., 2004). In sum, despite in a recent two-year prospective study (Giltay et al.,
some inconsistent findings, there is increasing evi- 2017). Other studies have reported no difference in
dence, particularly among larger prospective studies serum testosterone levels between women with and
(Ford et al., 2016), that men with low levels of without MD (Erdincler, Bugay, Ertan, & Eker, 2004;
testosterone are at higher risk to develop MD. Matsuzaka et al., 2013), and studies of exogenous
In addition to naturalistic studies of testosterone testosterone administration in women have been
levels, researchers have investigated the effects of ­inconclusive (McHenry et al., 2014). One possible
­administering exogenous testosterone to men with explanation of these contrasting findings is that the
MD, either as a standalone treatment or as an ad- relative ratio of testosterone to estradiol may be more
junct to traditional pharmacotherapy. With respect relevant in the context of depression in women than
to the former, two meta-analyses have indicated testosterone levels alone (Bromberger et al., 2010).
a positive effect of testosterone administration on
­depression in hypogonadal, but not eugonadal, Possible Mechanisms Underlying
men compared to placebo (Amanatkar, Chibnall, the Link Between Testosterone
Seo, Manepalli, & Grossberg, 2014; Zarrouf, Artz, and Depression
Griffith, Sirbu, & Kommor, 2009). In addition, the Testosterone’s putative relationship with MD is
route of administration should be taken into con- likely due to its influence on different neuropeptide
sideration, as the transdermal application of tes- and neurotransmitter systems and its role in neuro-
tosterone appears to be more effective at alleviating genesis in the hippocampus, both of which are known
depression than intramuscular injections (Zarrouf to be dysregulated in MD (Ebinger et al., 2009).
et al., 2009). The exogenous administration of One possible specific link between testosterone and

Ellenbogen, Tsekova, and Serravalle 393

 depression involves the extensive relationship r­eviewing the literature on the HPA axis and the
­between androgen and monoamine systems, which gonadal hormones estrogen and testosterone.
have repeatedly been implicated in the neurobiol- Although these hormones are central in under-
ogy of ­depression (McHenry et al., 2014; Robichaud standing the etiology of depression, other adrenal
& Debonnel, 2005). In rodents, testosterone ad- hormones such as dehydroepiandrosterone and
ministration increases the release of dopamine in the dehydroepiandrosterone-sulfate (Mocking et al.,
­
mesolimbic dopaminergic system (Alderson & Baum, 2015), growth hormone (Birmaher & Heydl, 2001),
1981; de Souza Silva, Mattern, Topic, Buddenberg, thyroid hormone (MacQueen & Joffe, 2002), and
& Huston, 2009; but see Triemstra, Sato, & Wood, hormones from other tissues (i.e., leptin and ghrelin;
2008). Difference across studies may be due to Carvalho et al., 2014; Wittekind & Kluge, 2015)
methodological factors, as one study found that in- may also be implicated in MD. Despite this limita-
tranasal administration of testosterone in rats was tion, two important trends in the neuroendocrine
superior to the subcutaneous injections of oxytocin literature on MD were highlighted. First, MD is
in stimulating dopamine release (de Souza Silva characterized by HPA dysfunction at multiple
et al., 2009). Results from animal studies have levels of the system, and there is evidence that
shown that testosterone can modify the expression subtle changes in HPA functioning, such as ele-
of various serotonergic receptors and alter the func- vated cortisol levels or an increased CAR, indicate a
tioning of the serotonergic system (Fink, Sumner, vulnerability for the disorder. Understanding the re-
Rosie, Wilson, & McQueen, 1999). For example, lationship between neuroendocrine function and
testosterone administration in rats increases the the subsequent development of MD will require a
firing of serotonergic neurons located in the dorsal developmental approach to the study of the HPA
raphe nucleus (Robichaud & Debonnel, 2005) and axis, with a focus on the effects of stress and adver-
5-HT2A receptor binding site densities (Sumner & sity across the lifespan (Lupien et al., 2009). Despite
Fink, 1998). Further translational research on how the progress in this area of research, inconsistencies
testosterone interacts with monoamine systems im- across studies continue to pervade the literature and
plicated in depression is needed to test these many key questions remain unanswered. It is un-
­hypotheses in human populations. clear, for example, whether deficits in mounting the
As another possibility, the role of testosterone in CAR (Knight et al., 2010) or an elevated CAR
depression may be explained in part by the interac- (Bhagwagar et al., 2005) are associated with risk for
tion between the HPA and HPG axes (Viau, 2002). MD and other health problems. It is not known
Specifically, stress inhibits the production of testos- how different vulnerabilities for affective disorders
terone precursors (gonadotrophins), which in turn lead to, or interact with, subtle changes in the HPA
lowers testosterone levels (McHenry et al., 2014). system in the development of MD. Vulnerabilities
Testosterone has also been shown to decrease glu- might be genetic (Goodyer et al., 2010) or related
cocorticoid levels in rats (Viau & Meaney, 1996). to familial risk (Ostiguy et al., 2011) or associated
However, the mechanism by which testosterone with exposure to adversity (Rao, Hammen, Ortiz,
dampens HPA axis functioning is yet to be deter- Chen, & Poland, 2008), and understanding these
mined. This effect is probably indirect, as few gonadal types of risk will be critical in designing early inter-
steroid receptors are found in cells secreting CRH ventions. We have designed, for example, a preven-
in the paraventricular nucleus of the hypothalamus. tion program aimed at reducing salivary cortisol
Testosterone might dampen the functioning of the levels and the development of internalizing symp-
HPA axis by acting on regions other than the para- toms in the offspring of parents with affective disor-
ventricular nucleus, such as the medial preoptic area ders, who are high risk for developing MD and
and the amygdala (McHenry et al., 2014). Again, other mental disorders. Preliminary evidence indi-
identifying how neuropeptides influence behavior cates that the 12-week program, entitled Reducing
in humans, whether via the activation or dampening Unwanted Stress in the Home (RUSH), which aimed
of brain circuits, via interactions with other hormonal to teach adaptive coping and emotion regulation
and neurotransmitter systems, or via neurogenesis, strategies to families, successfully reduced internaliz-
represents the next phase of this research. ing symptoms in children at a six-month follow-up
in those families whose parent–child interactions
Conclusion and Future Directions improved at the end of treatment (Iacono et al.,
The chapter examined how hormones are implicated 2018). We will be testing the hypothesis that children
in the development and expression of MD by showing the greatest intervention-related lowering

394 Hormones and Major Depressive Disorder

of cortisol levels in the natural environment will the response to antidepressant medication, however,
show the greatest long-term reductions in internal- has not been particularly successful. A recent meta-
izing symptoms. These types of targeted prevention analysis found no strong evidence that pretreatment
programs aimed at high-risk children or interven- measures of HPA functioning, such as basal cortisol
tions in persons showing early HPA markers of risk or CRH levels, robustly predict treatment response
might be useful strategies in decreasing the preva- to a variety of antidepressant medications (Fischer,
lence of MD. Of course, these proposals require Macare, & Cleare, 2017). One promising avenue
continued study of HPA abnormalities in high-risk might involve matching genetic markers associated
populations to further delineate what are the best with HPA axis functioning with the response to
markers of risk (e.g., CAR, daytime cortisol mean, treatment. For example, a recent large-scale treatment
diurnal cortisol change/slope, cortisol response to efficacy study found that MD patients homozygous
stress, exogenous challenges) and rigorous tests for the G allele of the rs28365143 variant of the CRH-
of efficacy. At present, there are too many conflicting binding protein gene displayed better response to
findings and nonreplications to promote any one antidepressant treatment than patients having the
of the potential markers listed previously. Future re- A allele (O’Connell et al., 2017).
search will need to assess whether cortisol concen- In contrast to the HPA system, gonadal hormone
tration in hair, which allows for the assessment of abnormalities highlight specific forms of MD that
cortisol levels across months, may represent a useful are associated with different transitions or stages of
HPA biomarker for MD (Herane Vives et al., 2015). the lifespan. There is growing evidence of a “repro-
The second important theme of this chapter is ductive” form of MD that is linked to difficulties
that hormonal markers may be important in defin- successfully adapting to changing levels of ovarian
ing different types of MD that could theoretically steroid hormones, as seen during the menstrual cycle,
be treated with targeted interventions. Considering postpartum period, and perimenopausal transition
that approximately 40 to 50 percent of patients (Payne, 2003). Testosterone appears to be implicated
with MD either drop out of treatment prematurely in the development of MD in men but limited to
or do not achieve full clinical remission following the situation when testosterone levels are low, as
acute phase treatment with pharmacotherapy (Gitlin, occurs during normal aging (Ford et al., 2016). For
2014; Rush et al., 2004) or psychological treatments these specific presentations of MD, gonadal hormone
such cognitive-behavioral therapy (DeRubeis et al., augmentation shows great promise in improving
2005; Hollon et al., 2005), a hormonal-based per- the treatment of MD. The transdermal application
sonalized medicine approach might improve treat- of testosterone, either as a standalone treatment or
ment efficacy and relapse prevention (Herbert, 2013). an adjunct to traditional pharmacotherapy, appears to
For example, patients with psychotic MD exhibit be effective at alleviating depression in men, at least
robust abnormalities in the HPA system, including among older and hypogonadal men (Amanatkar
cortisol hypersecretion (Keller et al., 2006; J. C. et al., 2014). The situation with estrogen in the treat-
Nelson & Davis, 1997). Mifepristone, a glucocorti- ment of MD is, however, more complex. Although
coid receptor antagonist, administered for seven days earlier studies reported robust antidepressant effects
prior to standard antidepressant treatment improves of menopausal hormone replacement therapy (es-
efficacy over placebo in MD patients with psychotic trogen plus a progestin; Zweifel & O’Brien, 1997),
features (DeBattista et al., 2006), at least in those a review of recent studies raised questions about the
patients who show high plasma levels of mifepri- quality of evidence and concluded that estrogen
stone (Blasey, McLain, & Belanoff, 2013; Block replacement therapy might only benefit perimen-
et al., 2017). Molecules targeting CRH were also opausal women with MD, with little evidence of
viewed with the potential to improve the treatment therapeutic benefits in postmenopausal women
of MD. Despite the promise of CRH-targeted (Rubinow, Johnson, Schmidt, Girdler, & Gaynes,
therapies in preclinical data (Holsboer & Ising, 2010), 2015). There continues to be much to learn about
the use of CRH1 receptor antagonists in the treat- gonadal hormones and MD. Few studies have
ment of MD has not been successful in randomized attempted to determine predictors of treatment
­
controlled trials (Griebel & Holsboer, 2012; Spierling ­response with gonadal hormone interventions, with
& Zorrilla, 2017), although past studies have not the exception of low testosterone in men. It is not
matched CRH antagonist treatments with patients clear what length of treatment should be used,
having CRH hypersecretion (Waters et al., 2015). and whether gonadal supplementation should be
Using HPA parameters as a means of predicting viewed as adjunct or standalone treatment of MD

Ellenbogen, Tsekova, and Serravalle 395

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404 Hormones and Major Depressive Disorder

 CH A PT E R

23 Sex Differences in Anxiety Disorders

Teresa A. Piggott, Alexandra N. Duran, Isha Jalnapurkar, Tyler Kimm,

Stephanie Linscheid, and Melissa K. Allen

Abstract

Women are more likely than men to meet lifetime criteria for an anxiety disorder. Moreover, anxiety is
a risk factor for the development of other psychiatric conditions, including major depression. Numerous
studies have identified evidence of sex differences in anxiety disorders, and there is considerable
research concerning factors that may contribute to vulnerability for anxiety in females. In addition to
psychosocial influences, biological components such as the female reproductive hormone cycle have
also been implicated. Although psychotropic medication is more likely to be prescribed to women,
there is little controlled data available concerning sex differences in the efficacy and/or tolerability of
pharmacotherapy in anxiety disorders. This chapter provides an overview of the impact of gender in
the epidemiology, phenomenology, course, and treatment response in generalized anxiety disorder
(GAD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), panic disorder (PD), and
obsessive-compulsive disorder (OCD).
Keywords: anxiety disorders, sex differences, disorders in women, generalized anxiety disorder, social
anxiety disorder, posttraumatic stress disorder, panic disorder, obsessive-compulsive disorder

Nearly one-fourth of adults in the United States will (SP), social anxiety disorder (SAD), and posttrau-
meet criteria for an anxiety disorder during their matic stress disorder (PTSD) during their lifetime.
lifetime, with females having a greater risk than Anxiety disorders typically start in childhood, ad-
males (Kessler & Wang, 2008). In the National olescence, or early adulthood until they reach a peak
Institute of Mental Health (NIMH) Collaborative in middle age, and then tend to decrease in older age.
Psychiatric Epidemiology Studies (CPES) survey of More females than males meet criteria for an anxiety
over 20,000 U.S. adults, 33 percent of women met disorder at every age throughout the lifespan, al-
lifetime criteria for an anxiety disorder compared though there is a narrowing in the prevalence rate
to 22 percent of men, suggesting that women between genders after the age of 65. The cumulative
were 1.7 times more likely to have an anxiety dis- effects of anxiety-related mortality, difficulty differen-
order than men (McLean, Asnaani, Litz, & Hofmann, tiating between cognitive impairment and an anxiety
2011). An earlier population survey conducted in the disorder, and the impact of female reproductive hor-
United States, the National Comorbidity Survey mone cycle cessation have been implicated in this
(NCS), also found that women (30.5 percent) were finding (Krasucki, Howard, & Mann, 1998). Several
much more likely than men (19.2 percent) to meet studies have reported a similar age of anxiety disorder
lifetime criteria for an anxiety disorder (Kessler onset in females and males, in general, as well as
et al., 1994). The NCS also reported that women were for specific anxiety disorder (Lewinsohn, Gotlib,
also more likely than men to meet criteria for panic Lewinsohn, Seeley, & Allen, 1998; McLean et al.,
disorder (PD), agoraphobia (AG), specific phobia 2011). However, others have d ­ etected a later onset of

405
PD, GAD, and OCD in females than in males may have a substantial impact on the bioavailability
(Clayton, Stewart, Fayyad, & Clary, 2006; Lochner and absorption of psychotropic medication. Despite
et al., 2004; Ruscio, Stein, Chiu, & Kessler, 2010; these pharmacokinetic differences, there is limited
Yonkers, Bruce, Dyck, & Keller, 2003). data concerning sex differences in the efficacy and
The presence of an anxiety disorder may have tolerability of pharmacotherapy in the treatment of
important long-term consequences. Adolescents anxiety disorders (Howell, Brawman-Mintzer,
with an anxiety disorder are more likely to experi- Monnier, & Yonkers, 2001; Ronfeld, Tremaine, &
ence pregnancy and/or parenthood than those Wilner, 1997; Steiner et al., 2005).
without an anxiety disorder (Kessler et al., 1997). Sex differences reported in anxiety disorders are
Adults with anxiety disorders are reported to have likely to arise from numerous factors, including
increased functional impairment, reduced educa- genetic, neurodevelopmental, environmental, and
tional and occupational opportunities, and elevated neurobiological influences. There appears to be
morbidity and mortality rates in comparison to genetic heterogeneity within anxiety disorders such
those without an anxiety disorder (Katerndahl & that the relative contribution of hereditary factors
Realini, 1997; Kessler & Walters, 1998; Leon, Portera, may vary between individual anxiety disorders
& Weissman, 1995; Schneier, Johnson, Hornig, (Kendler, Neale, Kessler, Heath, & Eaves, 1992b;
Liebowitz, & Weissman, 1992). An anxiety disorder Kendler et al., 1995; Kessler & Walters, 1998).
diagnosis has been linked to increased emergency Although more than 98 percent of the studies inves-
medical and mental health utilization rates tigating brain structure and function pertinent to
(Wittchen, Zhao, Kessler, & Eaton, 1994). The anxiety disorders such as fear conditioning and
NIMH CPES survey also indicated that the illness exposure have focused on male subjects, structural
burden associated with anxiety disorders was greater and functional differences have been reported be-
in females than in males (McLean et al., 2011). tween males and females. Moreover, the brain regions
Comorbid psychiatric disorders are common in reported to have sex differences are those consid-
anxiety disorders. The NCS reported that two-thirds ered relevant to anxiety, including the prefrontal
of those meeting criteria for an anxiety disorder cortex, hippocampus, and extended amygdala
would also be expected to meet criteria for a mood complex (Lebron-Milad & Milad, 2012).
disorder during their lifetime, particularly major Female reproductive function and related behav-
depressive disorder (Kessler et al., 2007; Kessler & iors may also predispose women to develop anxiety
Walters, 1998; Regier et al., 1988). Women with an disorders. Various attributes observed in females,
anxiety disorder are more likely to meet criteria for including superior social cognition and nurturing
an additional lifetime anxiety disorder and are also capacity, may enhance childrearing behavior.
more likely to be diagnosed with lifetime major Researchers have suggested that these same traits
depressive disorder (MDD) or bulimia nervosa (BN), may convey more sensitivity to separation, rejec-
whereas men with an anxiety disorder were more tion, and criticism, resulting in a greater risk for
likely to be diagnosed with a lifetime substance use anxiety disorders (Altemus, Sarvaiya, & Epperson,
disorder, attention-deficit/hyperactivity disorder 2014; Cyranowski, Frank, Young, & Shear, 2000;
(ADHD), or intermittent explosive disorder in A. H. Taylor, 2000; Zahn-Waxler, Shirtcliff, &
the CPS (McLean et al., 2011). Marceau, 2008). Given their potent actions within
Sex may also have an impact on treatment re- the central nervous system (CNS), the female repro-
sponse in anxiety disorders. The hepatic P450 system ductive hormones, estrogen and progesterone, may
is critical to the metabolism of the most commonly also have a role in increasing vulnerability for de-
prescribed medications for anxiety disorders, includ- veloping anxiety disorders (Altshuler, Hendrick, &
ing antidepressants and benzodiazepines. Given Cohen, 1998; Noshirvani, Kasvikis, Marks, Tsakiris,
that sex-related phenotypic differences have been & Monteiro, 1991; Weiss, Baerg, Wisebord, &
identified within the P450 isoenzyme system, differ- Temple, 1995; Yonkers & Ellison, 1996). In turn, es-
ences in psychotropic plasma concentrations at the trogen and progesterone may provide critical CNS
same dose of medication would be expected to modulating effects that influence the presentation,
occur; this variance may have a substantial impact course, and treatment response of anxiety disorders
on efficacy and tolerability when medications are in women (McEwen & Parsons, 1982; M. V. Seeman,
prescribed in the treatment of anxiety disorders. In 1997; Shear, 1997; Stahl, 1997).
addition, the female hormone progesterone is asso- The female reproductive cycle is characterized by
ciated with reduced gastric acid production, which periodic fluctuations in estrogen and progesterone

406 Sex Differences in Anxiet y Disorders

beginning at menarche, during the menstrual cycle, for GAD (Beesdo, Pine, Lieb, & Wittchen, 2010;
pregnancy, and the postpartum period, followed by Gum, King-Kallimanis, & Kohn, 2009; McLean
the perimenopause and postmenopausal periods. et al., 2011).
These vacillations in reproductive hormones are In primary care settings, GAD is the second
greater in females than males. The female hormone most common psychiatric disorder after depression
fluctuations also precipitate changes within the (Yonkers et al., 2003). In a 14-country World Health
hypothalamic-pituitary-adrenal (HPA) axis (Altemus Organization (WHO)-sponsored study conducted
et al., 2014). The effects of the broad changes in in primary care settings, 8 percent of patients met
gonadal steroid- and glucocorticoid-responsive brain criteria for GAD in the past month. Even in the
systems have been linked to the enhanced vulnera- absence of comorbid conditions, GAD is associated
bility for anxiety disorders in females, as well as to with deficits in social and role functioning, general
changes in anxiety symptom severity observed health, and bodily pain. The patients with GAD
during puberty, pregnancy, lactation, and meno- also had more disability days and a greater number
pause (Altemus, 2006; Pigott, 1999). Indeed, of physician visits than patients without GAD
Altemus (2006) has argued that the increased (Kroenke, Spitzer, Williams, Monahan, & Löwe,
prevalence of anxiety disorders in females may be 2007; Maier et al., 2000), and GAD is associated
a recent development. That is, in evolutionary with overuse of health care resources, elevated rates of
terms, the ability of gonadal hormones to suppress medically unexplained symptoms, elevated rates
the HPA axis and the catecholamine stress response of disability and social impairment, increased psy-
system during pregnancy and lactation may have chotropic medication use, and an increased risk of
protected females against the development of anxiety suicide compared to controls (Wittchen, Zhao,
disorders. However, since present-day females spend Kessler, & Eaton, 1994; Wittchen et al., 2000).
less time pregnant or lactating between puberty Comorbid psychiatric disorders occur in up to
and menopause, the defense strategy provided by 90 percent of patients with GAD. In the NCS,
gonadal hormones is diminished and pathological mood disorders were the most common lifetime
anxiety states have become more common. In comorbid disorder among patients with GAD, with
contrast, the primary male reproductive hormone, unipolar depression (67 percent) four times more
testosterone, reduces stress responsiveness by sup- likely to occur than bipolar disorder (17 percent;
pressing HPA axis activity and as such reduces Wittchen et al., 1994). Yonkers et al. (2003) found
anxiety and enhances fear extinction in animal that 83 percent of patients with GAD had an addi-
models (McHenry, Carrier, Hull, & Kabbaj, 2014). tional psychiatric diagnosis, with PD (41 percent)
Although PTSD and OCD are no longer classi- and MDD (37 percent) the most common comorbid
fied within anxiety disorders in the most recent diagnoses. In patients with GAD seeking treatment,
edition of the Diagnostic and Statistical Manual of SAD and PD were the most common comorbid
Mental Disorders (DSM-V), there is limited research psychiatric disorders (Keller, 2002). Despite the
incorporating these changes. In contrast, there are availability of efficacious treatments, most patients
substantial data available for anxiety disorders that with GAD remain untreated. For example, in 127
included PTSD and OCD in combination with patients meeting criteria for GAD, the average in-
GAD, PD, and SAD. Therefore, this chapter will terval between the onset of GAD and the initiation
include OCD and PTSD in a review of the impact of the first adequate medication trial was 81.6 months
of sex on the epidemiology, phenomenology, course, (Dell’osso, Camuri, Benatti, Buoli, & Altamura,
and treatment response of anxiety disorders. 2013). Selective serotonin reuptake inhibitor (SSRI)
antidepressants are considered first-line pharmaco-
Generalized Anxiety Disorder therapy for GAD. However, serotonin–norepineph-
Overview and Epidemiology rine reuptake inhibitor (SNRI) antidepressants
GAD has consistently been recognized as one of the (duloxetine and venlafaxine) are also highly effective
most common anxiety disorders. Data from the pharmacotherapy for GAD. If effective, antidepres-
NCS and NCS Replication (NCS-R) studies esti- sant treatment for GAD should be continued for at
mated the lifetime prevalence of GAD between 5 least 12 months (Gelenberg, 2000). Although ben-
and 6 percent (Kessler, Chiu, Demler, & Walters, zodiazepines are effective anxiolytic agents for short-
2005; Kessler et al., 1994). There is a sex difference term use, they should not be given over the long
in lifetime prevalence rates, with women reported to term because of the danger of addiction. Buspirone
have approximately two times greater risk than men was effective for GAD in some trials. Psychotherapies,

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 407

particularly cognitive-behavioral therapy (CBT), and also demonstrated that women with GAD were
have also demonstrated significant efficacy and less likely to achieve remission than men with GAD
similar treatment effect sizes as those associated during the seven-year study. Moreover, remission
with SSRI and SNRI antidepressants in GAD occurred later in females than males with GAD
(Hunot et al., 2007; Linden et al., 2005). The range (Yonkers et al., 2003). A more recent study conducted
of response rates in GAD is 47 to 75 percent with on a sample of primary care patients also found that
CBT and 44 to 81 percent for pharmacotherapy men were more likely than women to achieve a
(Bandelow et al., 2013). Although data are limited, partial recovery from GAD (Rodriguez et al., 2006).
combination (medication plus CBT) treatment in Sex differences in the comorbid conditions
GAD has not demonstrated improved efficacy over present in GAD have also been reported. The
pharmacotherapy or CBT alone (Bond, Wingrove, 2001–2002 National Epidemiologic Survey on
Curran, & Lader, 2002; Crits-Christoph et al., 2011). Alcohol and Related Conditions (NESARC) study
was a cross-sectional survey of over 43,000 partici-
Sex Differences in Generalized pants in the United States (Vesga-López et al., 2008).
Anxiety Disorder Men in comparison to women meeting criteria for
As previously noted, women are at least twice as GAD had higher rates of comorbid alcohol and
likely as men to meet criteria for lifetime GAD drug use disorders, nicotine ­dependence, and antiso-
(Beesdo et al., 2010; Gum et al., 2009; McLean cial personality disorder, but lower rates of comorbid
et al., 2011). Women with GAD may endorse more mood disorders (except bipolar disorder) and anxiety
somatic complaints, such as fatigue and muscle disorders (except SAD) in the NESARC. The men
tension, than men with GAD (Vesga-López et al., also reported greater use of alcohol and drugs to
2008). This increase in somatic complaints may relieve GAD symptoms, whereas women with GAD
reflect the influence of social and sex-specific factors, were more likely to report a family history of depres-
as women may be more prone to internalizing disor- sion and greater levels of disability. Although few of
ders than men (McLean et al., 2011). Since traits the participants in the NESARC sought treatment for
such as negative affect and neuroticism have been GAD, men were even less likely than women to
identified as risk factors in the development of anx- pursue treatment (Vesga-López et al., 2008).
iety in general, as well as GAD in particular, some Comorbid depression in GAD has been associated
authors have suggested that this may contribute to with increased functional impairment and greater
the increased prevalence of GAD in females (Clark, risk of suicide. Since women with GAD are more
Watson, & Mineka, 1994). Psychosocial and/or likely to have comorbid depression, this may con-
cultural issues may also have an important influ- tribute to the finding that women have a more
ence on sex differences in GAD prevalence. In the chronic course of GAD and greater symptom severity.
Collaborative Study on Psychosocial Problems in Data from bivariate female twin pairs with GAD
General Healthcare (Gater et al., 1998), rates of suggest that genetic factors accounted for approxi-
psychiatric illness were examined in 26,969 patients mately 30 percent of the risk of GAD development,
attending 15 different primary care centers across with environmental factors explaining the remainder
four continents. Although the odds ratio in preva- of the variance (Kendler, Neale, Kessler, Heath, &
lence rates was higher in women than in men for Eaves, 1992a; Kendler et al., 1995).
current depression (1.60) and agoraphobia or PD In addition to genetic factors, the female repro-
(1.63), there was substantial variance in the sex prev- ductive cycle also appears to have an impact on the
alence rates associated with GAD. In fact, three course of GAD. Mixed results have been reported
distinct groups of centers were identified with odds concerning GAD symptoms and the menstrual
ratios of 0.46, 1.34, and 3.09. cycle. An early prospective study failed to detect any
Most population surveys have failed to detect a difference in GAD symptom severity across the
sex difference in age of onset or in the clinical course menstrual cycle (McLeod, Hoehn-Saric, Foster, &
or chronicity of GAD (Beesdo et al., 2010; Kessler Hipsley, 1993), but in a more recent study over half
et al., 2005; McLean et al., 2011; Vesga-López (52 percent) of the women with GAD reported
et al., 2008). In contrast, data from clinical samples premenstrual worsening (Hsaio, Hsaio & Liu, 2004).
indicate sex differences in the onset and course of Several studies suggest that the risk of GAD is in-
GAD. The Harvard/Brown Anxiety Research creased during pregnancy, with prevalence rates
Program (HARP) study found an earlier onset of during pregnancy (8.5 to 10.8 percent) exceeding
GAD in females than males (Yonkers et al., 2003) those reported for nonpregnant women (Adewuya,

408 Sex Differences in Anxiet y Disorders

Ola, Aloba, & Mapayi, 2006; Buist, Gotman, & a first prescription and repeat prescriptions for
Yonkers, 2011; Misri, Abizadeh, Sanders, & Swift, ­benzodiazepines for anxiety (Van Der Waals, Mohrs,
2015). GAD symptoms were more pronounced & Foets, 1993). Although benzodiazepines are not
during the first and third trimesters in two studies considered first-line pharmacotherapy for GAD or
that examined the course of GAD across preg- any of the other specific anxiety disorders, this sug-
nancy (Lee et al., 2007; Teixeira, Figueiredo, Conde, gests that women may be less likely than men to be
Pacheco, & Costa, 2009). In a large prospective prescribed first-line pharmacotherapy (antidepressant
study conducted in pregnant women with a history medication) for an anxiety disorder including GAD.
of MDD (n = 2,793), 9.5 percent met criteria for The previous findings indicate that sex differ-
GAD during their pregnancy and GAD symptoms ences exist in the prevalence, clinical features, and
were most severe during the first trimester and im- comorbid conditions that may complicate GAD.
proved across pregnancy. Several risk factors were The emerging picture is that GAD is more common
associated with an increased risk for GAD during in women than men and is also more likely to be
pregnancy, including a previous history of GAD, a chronic, complicated by comorbid psychiatric
lower education level and support, and a history of disorders, and associated with more functional im-
childhood abuse in the same report (Buist, Gotman, pairment. Yet, women with GAD may also be less
& Yonkers, 2011). Perinatal loss (stillbirth after likely than men to receive first-line treatment with
20 weeks of gestational age or infant death in the antidepressant medication. Pregnancy has been as-
first month) is also associated with risk of GAD sociated with an increased risk for GAD, and
(Gold, Boggs, Muzik, & Sen, 2014). women with pre-existing GAD appear to be at risk
GAD prevalence appears more variable in the for developing depression and additional anxiety
postpartum period (ranging from 4.4 to 10.8 percent; disorders during the postpartum period. Little is
Misri et al., 2015; Navarro et al., 2008; Phillips, known about sex differences in treatment response
Sharpe, & Matthey, 2007; Wenzel, Haugen, in GAD.
Jackson, & Robinson, 2003). Women diagnosed
with GAD 10 weeks after childbirth were more Social Anxiety Disorder
likely to report sexual fear, avoidance, and body Overview and Epidemiology
image self-consciousness compared to postpartum SAD is one of the most common psychiatric disorders,
controls (Blair, Glynn, Sandman, & Davis, 2011). with lifetime prevalence estimates exceeding 13
Women with GAD may also be prone to developing percent (Boyd et al., 1990; Kessler et al., 1994;
depression in the postpartum period (e.g., Wenzel Schneier, Johnson, Hornig, Liebowitz, & Weissman,
et al., 2003). In a study of perinatal women with 1992). Females are more likely than males to develop
GAD (Grigoriadis et al., 2011), 50 percent had co- SAD during their lifetime, with odds ratios between
morbid MDD and comorbid anxiety disorders were 1.2 and 1.5 (Kessler et al., 2012). Public speaking–
common, including specific phobias (20 p ­ ercent), related anxiety appears to be the most commonly
PD (10 percent), agoraphobia (9 percent), and OCD feared situation in SAD. Other anxiety-provoking
(4 percent). The presence of GAD in pregnancy circumstances include small-group activities, meeting
was also associated with lower levels of fetal brain- strangers, eating in public, cashing checks in public,
derived neurotrophic factor in one study, raising and using public restrooms.
concerns about a negative impact on fetal neuro- The onset of SAD is usually in adolescence or
development (Uguz et al., 2013), although further early adulthood, often before the age of 18; onset
data are lacking. after the age of 25 is uncommon. Younger age (18 to
There was no evidence of sex differences in 29 years), lower socioeconomic status, lack of social
GAD treatment response in a double-blind, placebo-­ support, and single marital status are linked to an
controlled trial of sertraline (Steiner et al., 2005), increased risk for SAD (Boyd et al., 1990; Schneier
but females with GAD were less likely to respond et al., 1992). SAD follows a chronic and unremit-
than males in another much smaller SSRI trial ting clinical course. The presence of a comorbid
(Simon et al., 2006). Unfortunately, there do not alcohol use disorder and an earlier age of onset have
appear to be additional reports that have specifi- been linked to a more chronic clinical course in
cally addressed this issue. Results from a survey SAD (Yonkers et al., 2003). SAD has been associ-
completed by more than 60,000 patients seen in ated with long-term functional consequences, in-
general practice settings revealed that women in cluding lower education attainment, increased
comparison to men were twice as likely to receive workplace impairment, and an increased reliance

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 409

on welfare, and these effects appear independent of social reward versus punishment in the development
the effects of depression (Abelson et al., 2004). of SAD. In a recent study, subjects with SAD in
In the DSM-IV, SAD was classified into a gener- comparison to controls had greater rates of serotonin
alized and a nongeneralized subtype. Epidemiological synthesis in the amygdala, a key site for fear regu-
data suggested that two-thirds of those meeting lation (Frick et al., 2016). Moreover, symptom
criteria for SAD were in the generalized rather than improvement was associated with a subsequent re-
the nongeneralized subtype (Kessler & Walters, 1998; duction in amygdala serotonin synthesis rates. These
Wittchen, Stein, & Kessler, 1999). However, in the results suggest that enhanced serotonergic tone in
DSM-V, the SAD subtypes were replaced by a the amygdala may exert an anxiogenic influence and
specifier for a “performance-only type” of SAD. that effective treatment in SAD may be mediated by
This change was predicated on the assumption that decreasing serotonin formation in fear management
the SAD subtypes likely represented symptom se- pathways. The complex interplay between social
verity more than distinct groups defined by shared reward and punishment is thought to be mediated
genetic, neurobiological, or other features. The through neural pathways within the striatum. Another
performance-only specifier is limited to performance functional neuroimaging study revealed that subjects
fears that are most impairing in professional settings with SAD had reduced striatal activation for reward
or in roles that require regular public speaking, al- versus punishment trials compared to the control
though they may also manifest in work, school, or group (Cremers et al., 2015). The authors postulated
academic settings. Individuals with the performance- that SAD may be characterized by an attenuated
only type of SAD do not fear or avoid nonperfor- preference for the anticipation of social reward
mance social situations. Using the DSM-V criteria, rather than punishment.
the National Survey of Mental Health and Well-Being SSRI and SNRI antidepressants are considered
(NSMHWB) conducted on over 8,800 adults in first-line pharmacotherapy in SAD (D. J. Stein,
Australia reported an overall lifetime prevalence rate Ipser, & Balkom, 2004). The clinical effects of SSRI
of 8.4 percent for SAD, with 0.3 percent meeting treatment for SAD typically require four to six
criteria for the performance-only specifier (Crome weeks to have an impact; maximal benefit can re-
et al., 2015). SAD was also characterized by higher quire as long as 16 weeks. Although less well studied
prevalence rates in females, frequent (70 percent) than the SSRIs, the SNRI venlafaxine extended-
comorbid conditions, and relatively low rates of release appeared equally effective for SAD on the
treatment seeking (20 percent). Due to the limited basis of a comparable effect size compared with
research reported using DSM-V criteria, this review various SSRIs in meta-analysis (Liebowitz, Gelenberg,
will include data derived from studies using & Munjack, 2005; Liebowitz, Mangano, Bradwejn,
DSM-IV criteria, including the generalized and & Asnis, 2005). Although there is no consensus
nongeneralized subtypes of SAD. concerning the optimal length of treatment in SAD,
The estimated lifetime risk for comorbid psychi- most guidelines suggest at least six months of phar-
atric disorders in SAD is 60 to 80 percent in most macotherapy. CBT is also a well-established first-
reports (Kessler et al., 1994; Kessler & Walters, 1998; line therapy in SAD that may be a helpful adjunct
Merikangas & Angst, 1995; Schneier et al., 1992). in nonresponders to pharmacological treatments
Lifetime mood disorders are common in SAD, with (Blanco, Bragdon, Schneier, & Liebowitz, 2013).
NCS data suggesting an increased risk of MDD, Both group and individual psychotherapy are also es-
dysthymia, and bipolar disorder; in addition, the tablished treatments for SAD. A recent meta-analysis
course of mood disorders appears to be more severe of 36 randomized controlled trials revealed medium
and chronic when comorbid with SAD (Kessler, to large positive effects for cognitive-behavioral group
Stang, Wittchen, Stein, & Walters, 1999). Patients therapies (CBGTs) in comparison to wait-list con-
with SAD and comorbid disorders also have greater trolled trials in alleviating symptoms of SAD. No
clinical severity and greater treatment utilization differences were detected in the direct comparisons of
than those with SAD alone (Merikangas & Angst, group or individual psychotherapy or pharmaco-
1995). Although an increased risk of suicide attempts therapy for SAD (Barkowski et al., 2016).
has also been associated with SAD, this appears to
be largely attributable to other comorbid conditions Sex Differences in Social Anxiety Disorder
(Schneier et al., 1992). As previously noted, there is a slightly elevated
Neuroimaging studies have implicated abnor- lifetime risk of SAD for women in comparison to
malities in serotonin and also in pathways regulating men. Some sex differences in clinical phenomenology

410 Sex Differences in Anxiet y Disorders

have also been reported. In a community sample of were predictors of substance dependence, it also
young adults, women meeting criteria for SAD were revealed that females meeting criteria for substance
more likely to endorse feared situations related to dependence were more likely to have comorbid
eating or drinking in public, writing while someone SAD than males with substance dependence (Fleury,
was watching, talking to others, and participating in Grenier, Bamvita, Perreault, & Caron, 2014).
social events than men with SAD (Wittchen et al., However, another community survey of adolescents
1999; see also Turk et al., 1998). Only two feared found that girls meeting criteria for SAD were less
situations (urinating in public bathrooms and return- likely to use drugs (Wu et al., 2010).
ing goods to a store) were reported more by males Childhood trauma has been linked to an increased
than females (Turk et al., 1998). Men with SAD may risk of SAD. In the NCS, childhood sexual assaults
also be more likely to seek treatment for SAD en- by a relative and chronic exposure to verbal out-
countered in dating situations (Hart, Turk, Heimberg, bursts between parents were linked to the onset of
& Liebowitz, 1999). SAD in females, but not males. In fact, there was no
Results from female twin studies suggest that link between childhood adverse experiences and
SAD results from the combined effect of a slightly onset of SAD in males (Magee, 1999). Findings
stronger genetic influence and nonspecific environ- from the NCS-R survey among adolescent girls
mental experiences (Kendler et al., 1992b). Family further suggest a unique interplay between early
studies also provide support for the importance of exposure to trauma, onset of menarche, and risk of
genetic factors in the development of generalized SAD. That is, trauma during puberty in comparison
SAD (Kendler et al., 1992a, 1995; Stein & Chavira, to other developmental periods conferred a greater
1998; Stein, Jang, & Livesley, 1999). Females with risk of an anxiety disorder diagnosis (primarily SAD)
SAD may be more likely than males with SAD to within two years after menarche. In contrast, trauma
have comorbid psychiatric disorders, especially occurring in grade school conferred a greater risk for
mood disorder. However, shared genetic vulnera- a depressive disorder diagnosis in the teenage girls.
bility may contribute to this association between Early onset of menarche predicted a lifetime diag-
SAD and mood disorders in women (Hettema, Neale, nosis of SAD, PTSD, and simple phobia, whereas
Myers, Prescott, & Kendler, 2006; Xu et al., 2012). late-onset menarche was associated with an increased
Of the anxiety disorders, SAD may be most im- rate of SAD. The authors suggested that menarche
pacted by social influences. Females with SAD may amplify social sensitivity in females, making
may be prone to develop comorbid internalizing them vulnerable to the effect of trauma during
disorders such as mood disorders, whereas men puberty (Weingarden & Renshaw, 2012).
with SAD may be more likely to develop “more No sex differences have been consistently re-
socially acceptable” externalizing disorders such as ported in the clinical course or outcome of SAD.
substance use disorders (Landrine, Bardwell, & After 65 weeks of observation as part of the HARP
Dean, 1988). Data from the NESARC survey con- study, clinical course and outcome were similar
ducted in the United States provide additional between the male and female patients with SAD
support for this idea. Women meeting criteria for (Reich, Goldenberg, Goisman, Vasile, & Keller,
SAD not only reported a greater number of social 1994). Remission rates were low in both sexes at an
fears but also were more likely to have comorbid eight-year follow-up. Women were more likely to
mood disorders and were more likely to seek treat- have concurrent agoraphobia, whereas comorbid
ment with medication than men with SAD. In substance use disorders were more common in men.
contrast, men meeting criteria for SAD were more Women with poor baseline functioning and a history
likely to report dating-related fears, have comorbid of suicide attempts did have a more chronic course
substance use disorders, and use alcohol and illicit than men with the same characteristics in the HARP
drugs for symptom relief (Xu et al., 2012). Indeed, study (Yonkers et al., 2003). Most studies have re-
comorbid alcohol use disorders are common in ported a similar treatment response in men and
SAD, and males are more likely than females to women with SAD, including a pooled analysis of
report greater use of alcohol and illicit drugs to relieve data from the three multicenter, placebo-controlled
SAD symptoms (Buckner, Ledley, Heimberg, & paroxetine trials (Stein, Stein, Pitts, Kumar &
Schmidt, 2008; Randall, Thomas, & Thevos, 2001). Hunter, 2002). Women with SAD report more
Although data from an epidemiologic catchment distress related to family and social functioning
area health survey found that being male, being than men (Randall et al., 2001), although men may
younger, feeling stigmatized, and being impulsive be more likely to seek treatment (Weinstock, 1998).

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 411

 There may be some differences in brain structure risk of comorbid agoraphobia, whereas men with
between men and women with SAD. In a three-­ SAD may be more likely to have coexisting sub-
dimensional structural magnetic resonance imaging stance use disorders. Consistent sex differences in
study, patients with SAD had reduced amygdala the clinical course or treatment response in patients
(13 percent) and hippocampal (8 percent) size in with SAD have not been reported. There is some
comparison to controls. Further analysis revealed evidence suggesting sex differences in brain struc-
that the reduction in amygdala size was only sta- ture in SAD. There are also data suggesting that
tistically significant in the men with SAD. Smaller childhood stress or trauma may increase risk for the
right-sided hippocampal volumes in the patients later emergence of SAD, the timing of which may
with SAD were also related to greater severity of be particularly important in females, and that SAD
SAD (Irle et al., 2010). symptoms may improve during pregnancy, but that
As summarized by Goodman, Chenausky, and the postpartum period is associated with a return to
Freeman (2014), prevalence rates for SAD reported prepregnancy SAD symptom severity.
during pregnancy have been variable, but most have
ranged from 2 to 4 percent, including those con- Posttraumatic Stress Disorder
ducted in the United States (3 percent, n = 453), Overview and Epidemiology
Italy (3.8 percent, n = 1,066; 4.1 percent, n = 590), Although PTSD is the most common psychopa-
Brazil (4.6 percent, n = 239), Sweden (2.7 percent, thology developed in response to a traumatic event
n = 453), and France (3.2 percent, n = 309). Lower (Galovski, Blain, Mott, Elwood, & Houle, 2012),
rates were reported in Sweden (0.4 percent, n = 1,556) the risk of PTSD after trauma may only be ~25
and Malaysia (0.6 percent, n = 175), whereas the percent (Kessler et al., 1994; Kessler, Sonnega,
highest rate for SAD in pregnancy was found in Bromet, Hughes, & Nelson, 1995). In the NCS,
Nigeria (I6.4 percent, n = 172). Three studies com- the lifetime prevalence rate for PTSD was estimated
pared rates of SAD in pregnant versus nonpregnant at approximately 8 percent, with a twofold greater
controls. Adewuya and colleagues (2006) reported lifetime prevalence rate for PTSD in women (10.4
a greater prevalence rate for SAD in pregnant percent) than men (5.0 percent; Kessler et al., 1995).
(6.4 percent) than in nonpregnant Nigerian females PTSD is also associated with a greater risk for a
(2.8 percent). In contrast, rates of SAD were similar family history of psychiatric illness, parental poverty,
in pregnant (3 percent) compared to nonpregnant child abuse, parental separation or divorce before the
females (2.8 percent) in studies conducted in the age of 10, and greater job instability (Karno, Golding,
United States (Vesga-López et al., 2008) and Turkey Sorenson, & Burnam, 1988; Weissman, 1998).
(3.2 percent during pregnancy versus 2.8 percent in Although PTSD can emerge at any age, certain
nonpregnant controls; Uguz et al., 2013). In a ret- traumatic events are more likely to result in PTSD
rospective analysis of the course of SAD across than others. Interpersonal violence is the most likely
pregnancy, most (59 percent) patients reported no trauma type to be associated with PTSD (Kessler,
change in SAD symptoms across pregnancy. However, 2000). In fact, Foa (1997) reported that 95 percent
in the subgroup that reported symptom change, of rape victims and 75 percent of those sustaining
pregnancy was associated with an improvement in nonsexual assaults developed PTSD within two
SAD symptoms, whereas the postpartum period weeks of the assault. Data from community samples
was associated with worsening resulting in a return suggest that the sudden, unexpected death of a
to prepregnancy levels of severity (Van Veen, Jonker, loved one is also likely to precipitate PTSD (Breslau
Van Vliet, & Zitman, 2009). The presence of SAD et al., 1998). The most common traumas associated
during pregnancy may also be associated with an with PTSD in women are sexual assault, sexual mo-
increased risk for postpartum depression (Coelho, lestation, and childhood physical abuse, whereas
Murray, Royal-Lawson, & Cooper, 2011; Mauri combat exposure is the most common trauma asso-
et al., 2010). ciated with PTSD in men (Breslau, Chilcoat, Kessler,
These findings indicate that sex differences exist Peterson, & Lucia, 1999; Breslau et al., 1998;
in the prevalence, clinical features, and comorbid Kendler et al., 1995).
conditions that may complicate SAD. Women are Numerous risk factors have been implicated in
more likely than men to meet lifetime criteria for the emergence of PTSD after trauma exposure. An
SAD, and they also have a greater number of social epidemiological cohort study (Maes, Delmeire,
anxiety–related fears and greater overall symptom Mylle, & Altamura, 2001) conducted on victims
severity. Women with SAD may also have an increased trapped in a ballroom fire found that being female,

412 Sex Differences in Anxiet y Disorders

greater amounts of previous trauma, a history of a therapeutic trial of an SSRI should be a minimum
simple phobia, the extent of trauma exposure, of six to eight weeks before concluding that the
hospitalization for trauma-related injuries, and the medication has failed. In addition, it is common
presence of burns increased the odds of PTSD. In practice to start at a low dose but eventually push
contrast, a sense of control during the trauma and the dose to the high end of the therapeutic range (to
consumption of or intoxication with alcohol de- the extent that this is tolerated by the patient) before
creased the odds of PTSD. Three of the factors (the concluding that a therapeutic trial has failed.
amount of previous trauma, a history of simple Common PTSD symptoms, such as anxiety, in-
phobia, and loss of control) independently pre- somnia, and an exaggerated startle response, often
dicted a greater risk for PTSD. These results suggest improve during SSRI treatment. Moreover, SSRI
that the emergence of PTSD after trauma exposure treatment may ameliorate the intrusive trauma-
is likely conveyed by an interaction with numerous related recollections, feelings of emotional numbing,
temporal factors including pre- (e.g., sex), peri- and avoidance behaviors (Davidson & Connor,
(e.g., alcohol consumption), and post- (e.g., trauma- 1999). Although there are fewer studies assessing
related injuries/hospitalization) trauma variables, the efficacy of SNRI than SSRI antidepressants in
although these results also suggest that certain PTSD, two randomized trials found venlafaxine
peritrauma factors (e.g., sense of control, alcohol extended-release (ER) to be more effective in re-
consumption and/or intoxication) may protect ducing PTSD symptoms than placebo (Davidson
against PTSD (Maes et al., 2001). et al., 2006).
Comorbid psychiatric conditions are common
in PTSD, with epidemiological studies suggesting a Sex Differences in Posttraumatic
70 to 80 percent lifetime risk. Mood and substance Stress Disorder
use disorders, in general, and MDD and GAD, in Although women have higher lifetime PTSD rates
particular, are common in PTSD. Individuals with than men, the sex differences in prevalence do not
PTSD are more than four times as likely as those appear to be due to differential trauma exposure
without PTSD to have substance use disorder rates. In fact, some studies have reported that men
(Leeman et al., 2017). In the NCS, both PTSD and had greater rates of lifetime trauma exposure than
trauma exposure were factors associated with ele- women (Galovski et al., 2012; Kessler et al., 1995).
vated lifetime risks for alcohol abuse (28.1 percent) Certain types of trauma are 2.30 to 2.49 times more
and alcohol dependence (6.5 percent; Kessler et al., likely to be associated with PTSD in females than
1999). The presence of certain comorbid conditions males (Frans, Rimmö, Åberg, & Fredrikson, 2005;
may also increase the risk of PTSD. Pre-existing Norris, Kaniasty, Conrad, Inman, & Murphy, 2002;
depression appears to convey an increased risk for Rosenman, 2002; Stein, Walker, & Forde, 2000).
exposure to traumatic events, as well as the devel- Females may also have greater exposure to certain
opment of PTSD once trauma occurs (Breslau traumas, such as rape and childhood sexual abuse,
et al., 1998). PTSD has also been linked to elevated than males. Women may be more likely to experi-
rates of suicide attempts (Davidson, Hughes, Blazer, ence avoidance and numbing symptoms in re-
& George, 1991). sponse to assault than men (Breslau et al., 1999).
Although the pathophysiology of PTSD is likely Women victimized by sexual assault have a high risk
multifactorial, dysregulation of the glutamatergic, of development of PTSD. For example, three months
monoamine neurotransmitter (noradrenergic and posttrauma, female rape victims were found to be
serotonergic), and neuroendocrine pathways have twice as likely to have PTSD as women victimized
been implicated (Nutt, 2000). The development of by nonsexual crimes (48 percent vs. 25 percent;
PTSD may be facilitated by an atypical biological Foa, 1997). Another report found that women were
response in the immediate aftermath of severe at an increased risk for PTSD following nonsexual
trauma exposure that may then predispose the indi- assault (e.g., mugging), but not after nonviolent
vidual to develop sustained neurobiological ab- trauma (Stein et al., 2000). Moreover, women with
normalities and a maladaptive psychological state histories of childhood abuse were reported to have a
(Yehuda, McFarlane, & Shalev, 1998). PTSD has level of functional impairment commensurate
also been associated with abnormalities in brain with that of women with recent abuse (McCauley
structure and function (Brunello et al., 2001). SSRI et al., 1997). Girls may be particularly vulnerable to
antidepressants constitute first-line pharmacother- the negative effects of childhood sexual abuse
apy for PTSD (Ballenger et al., 2004). Duration of (Walker, Carey, Mohr, Stein, & Seedat, 2004),

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 413

whereas boys may be more vulnerable to adverse almost four times as likely to meet the overall
effects from childhood neglect (Teicher et al., 2004). arousal criterion for PTSD. The sex differences
The age at which trauma exposure occurs may rep- noted in acute PTSD were not associated with
resent a particularly critical issue. For example, previous trauma, PTSD, peritraumatic dissociation,
females have higher PTSD rates than males after MDD, or anxiety disorder not including PTSD, or
childhood trauma exposure before age 15 in com- with passenger injury. However, dissociative symp-
parison with exposure after age 15 (Breslau, Davis, toms at the time of the accident were associated
Andreski, Peterson & Schultz 1997; 1998; Kessler with a higher risk for acute PTSD in women than in
et al., 1995). men. Sex differences in peritraumatic dissociation
Women victimized by domestic violence are may help explain differences in risk for PTSD and
more likely to develop anxiety symptoms as well as for some PTSD symptoms in women and men
PTSD, whereas male victims of domestic violence (Fullerton et al., 2001).
are at greater risk of developing substance use disor- Coexisting somatoform pain disorder is more
ders (Mason & O’Rinn, 2014). An elevated risk of common in women than in men with PTSD
depression and an increased number of physical and (Elklit & Christiansen, 2009). The development
psychological health problems have also been re- of conduct disorder may also increase the risk for
ported in women exposed to ongoing domestic PTSD, particularly in girls, by exposing youth to
violence. The severity of domestic violence or the situations in which they are traumatized (Reebye,
presence of injuries sustained was not predictive of Moretti, Wiebe, & Lessard, 2000). The increased
the development of psychiatric symptoms or PTSD prevalence of pre-existing anxiety or MDD in
(Sutherland, Bybee, & Sullivan, 1998). Although women has also failed to account for the sex differ-
this may seem counterintuitive, it may reflect the ence in the prevalence of PTSD. In the NCS, there
importance of “perceived threat” in the formation was substantial overlap in factors that predicted an
of PTSD. That is, a victim’s perception of danger or increased risk for trauma exposure and develop-
possibility of death during an assault or exposure to ment of PTSD. Once the overlapping risk factors
trauma may be more important for developing were excluded, only history of affective disorder
PTSD as compared to more objective assessments predicted PTSD in women, whereas history of
of life-threatening events. These findings suggest anxiety disorder and parental mental disorder were
that sexual assault, childhood abuse, and individual associated with an increased risk of PTSD in men
assessment of threat during the occurrence of (Bromet, Sonnega, & Kessler, 1998). These findings
trauma may be the strongest predictors of subse- highlight the importance of differentiating between
quent PTSD development in women. They also variables that are more predictive of trauma expo-
confirm that childhood abuse has particularly sure than PTSD.
devastating complications that are likely to persist Combat exposure is the most common trauma
into adulthood in women. Certain factors appear to associated with PTSD in men, and male military
increase the risk of development of PTSD and other veterans are diagnosed with PTSD at a much greater
complications in women, including (1) exposure to rate than female military veterans. This is attributed
sexually related trauma or aggression, (2) occurrence to higher rates of combat exposure in male than
of abuse or severe trauma during childhood or female veterans. However, there are limited data
before the age of 15, and (3) perception within the concerning the effects of combat-related exposure
victim that the traumatic event is life threatening or on women. In a retrospective chart review of military
that escape is unlikely (Breslau et al., 1998, 1999; veterans, veterans exposed to higher levels of com-
Kessler et al., 1995). bat-related stress were more likely to have increased
Fullerton and colleagues (2001) examined the PTSD symptomatology (Pereira, 2002). In the same
relationship between various factors (i.e., previous study, male and female veterans exposed to similar
trauma, PTSD, MDD, anxiety disorder besides levels of combat-related stress were equally likely to
PTSD, passenger injury, and peritraumatic dissoci- have PTSD symptoms. These results suggest that
ation) and occurrence of acute PTSD in women female veterans may be underdiagnosed with combat-
and men after a serious motor vehicle accident. related PTSD. Elevated rates of chronic medical
Women did not differ from men in meeting the illness may be one of the many adverse conse-
overall re-experiencing criterion for a diagnosis of quences that arise from failing to identify and diag-
PTSD, but women were nearly five times as likely to nose PTSD in women military veterans. In a report
meet the overall avoidance/numbing criterion and of female Vietnam War–era veterans, there was a

414 Sex Differences in Anxiet y Disorders

relationship detected between PTSD symptoms PTSD during pregnancy or the postpartum period.
and reported health problems in the women with Pregnant women with PTSD have a higher risk
previous trauma exposure (Kimerling, Clum, & for ectopic pregnancy, spontaneous abortion, hyper-
Wolfe, 2000); in addition, the hyperarousal PTSD emesis, preterm contractions, and excessive fetal
symptom cluster was most strongly associated with growth in comparison to women without PTSD
increased health complaints. These results suggest (Seng et al., 2010). There is also evidence that
that women may have a similar risk for PTSD after women who experience increased symptoms of
combat-related trauma exposure as men and that psychosocial stress after exposure to a natural disaster
persistent PTSD symptoms, particularly hyper- (flood) may be at an increased risk of pregnancy loss
arousal, may result in elevated rates of chronic and perinatal complications (Neuberg et al., 1998).
health problems in female military veterans. However, As summarized in Goodman et al. (2014), prevalence
a combination of factors is likely involved in the rates reported for PTSD during pregnancy have
expression of PTSD (Hansen & Elklit, 2011). ranged from 0.6 to 7.9 percent in cross-cultural
Sex differences have been identified in the bio- studies. Two of these studies compared rates of
logical alterations associated with PTSD. An elevated PTSD in pregnant women with nonpregnant
norepinephrine-to-cortisol ratio has been reported controls. Nigerian women in late pregnancy were
in men with PTSD, whereas women with PTSD more likely to meet criteria for a DSM-IV anxiety
demonstrated elevated daily levels of urinary norep- disorder (39 percent) than a comparison group
inephrine, epinephrine, dopamine, and cortisol (16 percent) of nonpregnant women, but rates of
(Lemieux & Coe, 1995). Cortisol appears to modu- PTSD were low and not different between the preg-
late emotionally influenced memory, and sex dif- nant (0.6 percent) and the nonpregnant (0 percent)
ferences in the relationship between stress-induced population (Adewuya et al., 2006). Another study
cortisol levels and memory have been reported (Seng et al., 2010) was conducted in 1,500 women
(Wolf et al., 2001). Low cortisol levels may also be pregnant with their first child that were interviewed
associated with specific dimensions of PTSD symp- at their first prenatal care visit. Twice as many of
tomatology, such as emotional numbing (Hawk, the pregnant women (7.9 percent) met criteria for
Dougall, Ursano, & Baum, 2000). Sex differences PTSD than in the comparison group (3.9 percent).
in reactivity to psychological stress within the HPA In another community sample of pregnant women
axis have also been reported (Biondi & Picardi, with a lifetime PTSD diagnosis, certain factors
1999; Kirschbaum, Kudielka, Gaab, Schommer, & (child abuse history, demographic risk, and lifetime
Hellhammer, 1999; Kudielka & Kirschbaum, 2005; PTSD symptom count) were associated with an
Matthews, Gump, & Owens, 2001; T. E. Seeman, increased risk of PTSD during pregnancy, whereas
Singer, Wilkinson, & McEwen, 2001; Traustadottir, gestational PTSD symptoms were best predicted by
Bosch, & Matt, 2003). Although women between interim trauma and labor anxiety (Muzik et al., 2016).
puberty and menopause show lower HPA axis re- Women with the greatest increase in PTSD symp-
sponses than men of the same age, HPA response is toms during pregnancy were most likely to suffer
higher and poststress cortisol levels approach those postpartum depression and they also reported the
of men during the luteal phase of the menstrual cycle. most impaired bonding with their infants at the six-
The HPA axis also has strong, multilevel inhibi­ week postpartum visit.
tory effects on the female reproductive hormones. There are limited data concerning sex differences
Because HPA axis alterations are implicated in PTSD, in PTSD treatment response. There was some sug-
the marked fluctuations in estrogen and progester- gestion of a sex difference in the sertraline multi-
one levels that characterize the female reproductive center PTSD trials in that women appeared to have
cycle may have a significant impact on the course of a greater degree of PTSD symptom reduction than
PTSD. The relative hypercortisolism that occurs men (Davidson, Rothbaum, van der Kolk, Sikes, &
during the third trimester of pregnancy is speculated Farfel, 2001). However, there was no evidence of
to cause a transient suppression of the adrenals during sex differences or differential response of PTSD
the postpartum period (Chrousos, Torpy, & Gold, symptom clusters reported in the paroxetine mul-
1998).This suggests that women with pre-existing ticenter, placebo-controlled PTSD trial (Marshall,
PTSD may experience changes in symptomatology Beebe, Oldham, & Zaninelli, 2001). There also
during pregnancy or the postpartum period. was no sex differences identified in the venlafaxine
There are limited data available concerning the ER multicenter, placebo-controlled trials conducted
prevalence, onset, course, risk factors, or course of in PTSD.

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 415

 In a Veterans Affairs (VA) study examining somatic and psychological criteria, and also be
prescribing patterns for psychotropic medication ­associated with avoidance behavior and/or anticipa-
(antidepressants, antipsychotics, and hypnotics) over tory anxiety (American Psychiatric Association,
an 11-year period (1999 to 2009) in veterans diag- 2013). Prior to the DSM-V, agoraphobia was classi-
nosed with PTSD (Bernardy et al., 2013), women fied as a subordinate condition within the diagnosis
were more likely than men to receive medication of PD (Wittchen et al., 2010). However, DSM-V
across all classes except prazosin, whereas men had categorized PD and AG as separate disorders, each
higher prescribing frequency. The proportion of with its own distinct diagnostic criteria. Individuals
women receiving first-line pharmacotherapy treat- with AG (from Greek for “fear of the marketplace”)
ments for PTSD (SSRI or SNRI antidepressant) experience anxiety symptoms related to real or
increased from 56 percent in 1999 to 66 percent in imagined exposure to public places. The phobic
2009, which was a higher rate than that seen in the focus associated with AG centers on the inability to
men with PTSD (49 percent with increase to escape and/or the negative outcomes that may occur
58 percent). Atypical antipsychotic prescriptions if assistance is unavailable (American Psychiatric
increased from 15 to 26 percent overall, but were Association, 2013).
more likely to be prescribed in women than men The presence of PAs alone appears to increase the
with PTSD. However, the most notable sex discrep- odds of developing phobias, GAD, OCD, or PTSD,
ancy was observed for benzodiazepines, where with the estimated risk ranging from 3- to 16-fold in
prescriptions decreased for men with PTSD (from the literature. PAs have also been associated with an
37 to 30 percent) but steadily increased for women increased risk for mood disorders, in general, and
with PTSD (from 33 to 38 percent) despite PTSD MDD, in particular, as well as personality disorders
guidelines that recommend against the use of ben- and substance use disorders (Craske et al., 2010).
zodiazepines in PTSD (Bernardy et al., 2013). PD is associated with a chronic course, high rates
These results suggest that women are twice as of comorbid disorders, and significant disability.
likely to meet lifetime criteria for PTSD. Numerous Highly comorbid with MDD, the presence of
factors including the type and time of exposure to MDD conveys an increased risk for substance use
trauma, as well as pre-existing features and sex-related disorders, as well as for additional anxiety disorders
neurobiological factors, likely contribute to this in PD (Wittchen & Essau, 1993). PD also has the
finding. Comorbid conditions are common with highest rate of medical utilization among anxiety
PTSD, and some sex differences have been identi- disorders. More than half of those with PD have
fied. There is also evidence that PTSD prevalence been reported to seek treatment; this rate is twice
may increase during pregnancy and may be associ- that associated with other anxiety disorders (American
ated with adverse consequences including an in- Psychiatric Association, 2013; Regier et al., 1993).
creased risk for postpartum depression and worse In contrast, AG in the absence of PD may have
outcomes. Sex differences have also been identified relatively less disability in comparison to PD, and
in the biological alterations associated with PTSD. while anxiety disorders may be more common,
Most pharmacotherapy studies conducted in PTSD comorbid mood or substance use disorders appear
have failed to detect sex differences. However, women not to be more common in AG alone (Wittchen,
may be more likely than men to be prescribed Gloster, Beesdo-Baum, Fava, & Craske, 2010).
benzodiazepines, even though their use is not However, PD complicated by AG was associated
­consistent with treatment guidelines for PTSD. with more severe PD, an elevated suicide risk, and
higher levels of anxiety sensitivity, neuroticism, and
Panic Disorder trait anxiety than PD without AG. Comorbid hy-
Overview and Epidemiology pomania and SAD were also more likely to occur in
PD is a condition wherein people experience multi- PD with AG (Inoue, Kaiya, Hara, & Okazaki, 2016).
ple, recurrent panic attacks (PAs), with at least some SSRI antidepressants are considered first-line
of these attacks occurring at unexpected times. The pharmacotherapy for PD. A systematic review and
overall lifetime prevalence rate of PD varies by meta-analysis of 12 trials of acute treatment for PD
country and by study (see, e.g., American Psychiatric found the SSRIs to be efficacious compared to
Association, 2013; Bandelow & Michaelis, 2015), placebo, with a medium effect size (Otto, Tuby,
but estimates are generally below 5 percent. To meet Gould, McLean, & Pollack, 2001). There appears
DSM-V criteria for a PA, it must have an acute to be comparable efficacy among the SSRI in PDs
onset, peak within minutes, fulfill a set number of (Stein et al., 2009). Venlafaxine ER has also been

416 Sex Differences in Anxiet y Disorders

found in randomized trials to be an efficacious (­reviewed in Pigott, 2003). Sex differences have also
treatment for PD (Cowley, Ha, & Roy-Byrne, 1997; been reported in patients with PD with AG (PDA).
Pollack et al., 2007). Sixteen randomized trials (11 for Women were more likely than men to have PDA
imipramine and 5 for clomipramine) have also and have a greater prevalence of comorbidities, in-
found tricyclic antidepressants (TCAs) to be supe- cluding hypomanic episodes, social phobia, and a
rior to placebo in PD. Although TCAs reduce the higher risk of suicide (Inoue et al., 2016). Women
frequency of panic attacks, their effects on anticipa- with PDA were more likely to avoid buses, enter
tory anxiety and phobic avoidance may be more ­unfamiliar situations alone, and avoid agoraphobic
variable and less robust than that seen with SSRIs situations by staying home than males with PDA,
and venlafaxine (Bakker, van Balkom, & Spinhoven, whereas the men with PDA were more likely to
2002). Numerous randomized trials have also re- avoid staying at home alone in another study
ported that benzodiazepines were efficacious for (Starcevic et al., 2008). Females with PDA appear
each of the three components of PD (attack fre- more impaired and also display more severe agora-
quency, anticipatory anxiety, and phobic avoidance; phobic avoidance than PDA males. Interestingly,
Stein et al., 2009), with effect sizes reported as PDA males were more likely to worry about their
similar to those seen for SSRIs or tricyclic antide- physical health and also about the potential for seri-
pressants in meta-analysis (Mitte, 2005; Wilkinson, ous somatic consequences from having panic attacks
Balestrieri, Ruggeri, & Bellantuono, 1991). However, than PDA females (Latas & Starcevic, 2008). No sex
benzodiazepines have the potential for abuse and differences were detected in the age of onset, illness
they also lack efficacy in the comorbid mood disorders duration, panic attack severity or frequency, or sever-
that often complicate PD, so most PD guidelines ity of anxiety, depression, or general psychiatric
suggest using venlafaxine in patients who fail to symptoms in PDA samples (Latas & Starcevic, 2008;
respond to one or more trials of an SSRI. The dura- Starcevic, Djordjevic, Latas, & Bogojevic, 1998).
tion of pharmacotherapy should be at least one year Sex differences in parenting dynamics have also
after symptom control has been attained. been reported in PD samples. Males with PD re-
ported greater rates of “overprotective mothers” as
Sex Differences in Panic Disorder measured by the Parental Bonding Instrument than
Women are 2.5 to 3 times more likely than men to control subjects, whereas the females with PD re-
meet criteria for panic disorder during their lifetime ported greater rates of fathers that were “overprotec-
(3.4 percent vs. 0.9 percent; Eaton et al., 1989). The tive” and/or had reduced “warmth” in comparison to
lifetime prevalence estimate for panic disorder was control subjects (Parker, Tupling, & Brown, 1979).
also 2.5 times greater in women (5 percent) than This combination of parental “overprotection” and
in men (2 percent) in the NCS study (Kessler “authoritarianism” has been implicated as a risk
et al., 1994). Women were reported to have higher factor for childhood trauma and perhaps increased
prevalence rates for panic disorder in the Cross- PD development by some authors (Seganfredo
National Epidemiology of Panic Disorder study et al., 2009).
(Weissman et al., 1997). Women are more likely to The preponderance of respiratory-related symp-
endorse more individual panic-related symptoms than toms in females in comparison to males with PD
men and also to display more avoidance symptoms appears to arise from sex differences in CO2 sensi-
(Pigott, 1999). Results from a National Comorbidity tivity, as well as in the threshold for panic attacks
Survey in respondents meeting DSM-III-R criteria during hypoxic and hypercapnic states (Sheikh,
for PD or PAs revealed that female respondents were Leskin, & Klein, 2002). That is, when exposed to a
more likely than males to experience respiration- CO2 concentration consistent with a panic state,
related difficulties during panic attacks. Men with healthy women and men had similar autonomic re-
PD displayed greater general fatigue symptoms and sponses, but the women reported higher subjective
reduced activity in comparison to control subjects, fear than the men, suggesting that anxiety sensitiv-
whereas women with PD scored higher for physical ity (AS) is higher in women than in men (Stewart,
fatigue but were similar to controls in general fatigue Taylor, & Baker, 1997). Not only is AS considered
symptoms and activity levels in one report (Kaiya a cognitive risk factor for PD, but also people with
et al., 2008). anxiety disorders have greater AS than those with-
Women with PD also appear more susceptible to out anxiety disorders. AS has also been shown to
comorbid conditions then men with PD including be highly predictive of the frequency and intensity
AG, MDD, GAD, and somatoform disorders of PAs (Plehn & Peterson, 2002).

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 417

 The female reproductive hormones may play a Although pregnancy and the postpartum period
critical role in mediating the sex differences reported are also times of reproductive hormone changes, the
in PD. For example, females appear to have a greater course of PD during pregnancy appears to be highly
susceptibility to anxiety-inducing challenges during variable. In a systematic review of 12 studies exam-
the late luteal or premenstrual phase of the men- ining anxiety disorders during pregnancy, Goodman
strual cycle (Donner & Lowry, 2013; Nillni, Rohan, and colleagues (2014) found that prevalence rates
& Zvolensky, 2012). A major metabolite of proges- for new-onset PD during pregnancy varied from
terone, the steroid allopregnanolone, is a potent 0 to 53.8 percent. The course of PD during pregnancy
positive allosteric modulator of GABAA receptors, a was also examined in nine studies mostly retrospec-
subset of receptors that make up the predominant tive in nature. Four (44 percent) of the studies
inhibitory neurotransmitter system in the brain demonstrated an improvement in PD symptoms,
(Nillni et al., 2012). One site rich in GABAA recep- four (44 percent) revealed minimal change in PD,
tors, the periaqueductal gray (PAG), has been im- and one (12 percent) reported worsening PD symp-
plicated in panic symptomatology as a subcortical toms. There was a single study in their review that
panic-generating brain region (Johnson, Molosh, showed decreased infant birth weight for mothers
Truitt, Fitz, & Shekhar, 2012). In animal models, with PD compared to mothers with GAD, mothers
direct GABAA antagonist injections into the PAG with depression, or controls without psychiatric
elicit panic symptoms (Graeff, Silveira, Nogueira, disorders (Goodman et al., 2014). There is also a
Audi, & Oliveira, 1993). This panic circuitry is report that the risk of cleft lip with or without
more excitable via decreased GABAergic inhibition cleft palate may be increased in infants born to
in rats during the late diestrous phase, which is a mothers with PD (Acs, Banhidy, Horvath-Puho,
state of low progesterone (and, thereby, a relative & Czeizel, 2006).
decrease in allopregnanolone). In contrast, the In contrast to the variable course of PD during
highest rates of anxiolytic and antidepressant be- pregnancy, the postpartum period appears to be
haviors in female pubertal rats as measured by behav- more consistently associated with an increased risk
ioral paradigms occur in the proestrous phase of the of onset of PD and also an increased likelihood of
estrous cycle, when allopregnanolone levels are at PD exacerbation. In the largest sample (n = 128)
their peak (Nillni et al., 2012). The increase in PD reported, there was a large rise (a 132-fold increase)
prevalence in females at puberty has been linked to in the incidence of PD occurring during the post-
the decrease in, or relative withdrawal of, allopreg- partum period and there was also an increase in
nanolone in the hippocampus during that time overall panic symptomatology during the postpar-
(Lovick, 2014). Synaptic pruning also occurs at that tum period in comparison to pregnancy and the
time, and this loss of inhibition, from the ventro- nonpregnancy period (Bandelow et al., 2006).
medial prefrontal cortex to subcortical areas, may There was also evidence that women with PDA were
also contribute to less attenuation of panic-related more symptomatic than women with PD without
circuits (Johnson, Federici, & Shekhar, 2014). AG in the same report.
A few studies conducted in women with PD Although women with PD are reported to have a
have reported an association between menstrual threefold higher rate of relapse compared to men
cycle phase and changes in PD symptom severity. In with PD (Donner & Lowry, 2013), there are limited
a retrospective study, 79 percent of women with PD data regarding sex differences in the treatment of
reported an increase in anxiety premenstrually, with PD. Clayton, Stewart, Fayyad, and Clary (2006)
58 percent reporting increased frequency of panic analyzed four double-blind, placebo-controlled
attacks and 47 percent recalling more phobic avoid- outpatient industry-sponsored trials of sertraline for
ance (Cook et al., 1990). Women with PD who the treatment of PD. The women with PD had an
endorsed premenstrual worsening of their PD increased response rate compared to the men with
symptoms were also 2.5 times more likely to be PD in terms of improvement from baseline panic
classified as suicidal when compared to women attack frequency and also in decreased time spent
without premenstrual worsening of their PD worrying about future attacks. In a post hoc analysis
symptoms in another report (Basoglu, Cetin, of a placebo-controlled trial of gabapentin in PD
Semiz, Agargun, & Ebrinc, 2000). Premenstrual (n = 103), the women with severe PD show a greater
worsening of symptoms was reported by 51 percent response than men (Pande et al., 2000).
of women with AG in another study (Breier, These results suggest that women are at least
Charney, & Heninger, 1986). twice as likely as men to meet lifetime criteria for PD.

418 Sex Differences in Anxiet y Disorders

Numerous factors including environmental and et al., 1992). Most OCD patients (60 to 70 percent)
sex-related neurobiological factors likely contribute report severe impairment in psychosocial and occu-
to this finding. Comorbid conditions are common pational functioning (Hollander & Benzaquen, 1996;
with PD and AG, and some sex differences have Koran, Thienemann, & Davenport, 1996). An
been identified. There is also evidence that the OCD diagnosis is also associated with elevated use
PD symptoms may change during the menstrual of medical and mental health services (Hollander
cycle and during pregnancy and that the postpartum et al., 1996; Kennedy & Schwab, 1997). In the
period may be associated with both an increased largest nationwide survey of consumers with OCD
risk of onset of PD and worsening in PD symp- (Hollander et al., 1997, the average delay between
toms. Sex differences have also been identified in the onset of OCD symptoms (mean age = 14.5) and
the biological alterations associated with PD. Most the initiation of appropriate treatment interventions
pharmacotherapy studies conducted in PD have (mean age = 31.5) was 17.5 years. This is a particularly
failed to detect sex differences. disturbing finding since 13 percent reported a history
of suicide attempts and most of the respondents felt
Obsessive-Compulsive Disorder their OCD was directly responsible for impaired
Overview and Epidemiology academic achievement (58 percent), lowered career
Prevalence rates for OCD range between 2 and 3 aspirations (66 percent), and disrupted family rela-
percent worldwide, and women are about 1.5 tionships (73 percent).
times more likely than men to meet criteria for Serotonin (5-HT) dysregulation has long been
OCD during their lifetime (Karno et al., 1988; considered the critical neurobiological abnormality
Weissman, 1998), although some work reports mediating OCD symptom development (Zohar &
more similar prevalence rates for OCD between Insel, 1987). Much of this assumption has been
men and women (Bekker & van Mens-Verhulst, 2007; based on the consistent finding that antidepressants
McLean & Anderson, 2009). The onset of OCD is with potent serotonin-reuptake-inhibiting (SRI)
reported to be early with two peaks of onset, the first effects have preferential efficacy in the treatment of
occurring between 10 and 19 years followed by an- OCD (Pigott, 1996; Pigott & Seay, 1999; Zohar &
other between 20 and 29 years (Kolada, Bland, & Insel, 1987). Moreover, antidepressants with nonse-
Newman, 1994). Most studies conducted on OCD lective serotonergic or primary noradrenergic actions
have identified the most commonly endorsed recur- lack efficacy in OCD. Challenge studies conducted
rent thoughts (i.e., obsessions) as those related to with serotonergic probes have also revealed evidence
aggression, contamination, symmetry, saving/collect- of altered behavioral or neuroendocrine responses
ing, sexual impulses, or religious matters. Checking, in patients with OCD compared with controls
cleaning, counting, ordering, and hoarding rituals (Aouizerate et al., 2005). In contrast, pharmacolog-
(i.e., compulsions) are the most frequent compulsive ical challenge paradigms conducted in patients with
behaviors (Antony, Purdon, Huta, & Swinson, 1998; OCD have failed to detect evidence of altered nor-
Baer, 1994; Rasmussen & Eisen, 1990, 1992). adrenergic function compared with control subjects.
The most common comorbid disorders in OCD OCD has also been linked to hypersensitivity of
are MDD (60 to 80 percent lifetime risk), an postsynaptic serotonin receptors (Gross, Sasson,
­additional anxiety disorder diagnosis (30 to 50 Chorpa, & Zohar, 1998). Genetic association
percent), eating disorders (10 to 20 percent), and studies conducted in OCD have focused on at-
Tourette’s disorder (8 to 15 percent; Antony et al., tractive candidate genes in the 5-HT pathways
1998; Fahy, Osacar, & Marks, 1993; Leckman (Enoch, Greenberg, Murphy, & Goldman, 2001).
et al., 1994; McDougle, Barr, Goodman, & Price, Inconsistent results have also been reported con-

polymorphisms in the 5-HT1D β-receptor gene

1999; Noshirvani et al., 1991; Pigott, L’Heureux, cerning the transmission of alleles associated with
Dubbert, Bernstein, & Murphy, 1994; Rasmussen
& Eisen, 1990; Rubenstein, Pigott, L’Heureux, (Di Bella, Cavallini, & Bellodi, 2002; Mundo
Hill, & Murphy, 1992). A lifetime diagnosis of et al., 2002) and the 5-HT2A receptor gene (Enoch
OCD is also associated with an increased likelihood et al., 2001). There has also been excitement about
of substance abuse, schizophrenia, body dysmorphic findings concerning the promoter region of the
disorder (BDD), hypochondriasis, and personality 5-HT transporter gene (5-HTTLPR) in OCD
disorders (Antony et al., 1998; Hollander et al., 1996; (Cavallini, Di Bella, Siliprandi, Malchiodi, &
Karno et al., 1988; Kolada et al., 1994; Pigott et al., Bellodi, 2002). However, more recent research
1994; Rasmussen & Eisen, 1992, 1994; Rubenstein (Saiz et al., 2008) failed to replicate these findings,

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 419

including a meta-analysis (Bloch et al., 2008). than men (e.g., Karno et al., 1988; Kolada et al.,
Although the meta-analysis found no evidence of 1994), but data from clinical samples fail to detect
an association between genetic variation at the sex differences in prevalence rates in adults OCD
5-HTTLPR locus and OCD, a stratified meta- (Rasmussen & Eisen, 1992). Numerous studies
analysis revealed a potential association between the have examined sex differences in the types of obses-
l-allele and specific OCD subgroups in the same sions and compulsions. Most studies have found
report (Bloch et al., 2008). In the largest meta- that males with OCD are more likely to endorse
analysis (S. Taylor, 2013) investigating the relation- symptoms related to sexual, religious, or aggressive
ship between OCD and 230 polymorphisms from content (Cherian et al., 2014; Labad et al., 2008;
113 genetic association studies, OCD was associated Lensi et al., 1996; Mathis et al., 2011; Torresan
with serotonin-related polymorphisms (5-HTTLPR et al., 2009), whereas women with OCD report
and HTR2A). more symptoms with contamination or cleaning
Neuroimaging studies have been influential in content (Labad et al., 2008; Mathis et al., 2011).
shaping neurobiological models of OCD (Atmaca, These findings have led some to conclude that the
2013). In particular, the cortico-striato-thalamo- content and clinical expression of OCD symptoms
cortical circuit has been implicated in the mediation may be influenced by sociocultural factors (Khanna
of OCD symptoms (Breiter & Rauch, 1996; Pauls, & Mukherjee, 1992; Lensi et al., 1996).
Abramovitch, Rauch, & Geller, 2014; Radua & There are also substantial data indicating sex
Mataix-Cols, 2009). In fact, numerous functional differences in the onset and clinical course associ-
neuroimaging studies have demonstrated increased ated with OCD. In a review of 63 studies concerning
metabolism in the frontal cortex, anterior cingulate, sex differences in OCD, Mathis et al. (2011) con-
caudate nucleus, and thalamus during symptom cluded that male patients were more likely than
provocation in OCD patient studies (Breiter & females to be single, have earlier symptom onset,
Rauch, 1996; Rauch et al., 1994). These key brain have a chronic clinical course, and have greater
regions are likely relevant to the pathophysiology of social impairment. The mean age of onset for OCD
OCD (Whiteside, Port, & Abramowitz, 2004). In in males (20 years) is earlier than in females (25 years),
addition, the amygdala is also implicated in OCD and males are also much more likely to develop
due to its important role in fear conditioning, and it OCD during childhood (Ruscio, Stein, Chiu, &
is also an important target of the SRIs (Atmaca, Kessler, 2010). In fact, OCD onset before the age
2013). From an evolutionary standpoint, the same of 10 is associated with being male, tic disorder, a
key brain areas implicated in OCD are activated positive family history (Leonard et al., 1992), and
during the processing of danger and threat (Steimer, symptom severity (McLean & Anderson, 2009).
2002). Thus, although OCD compulsions are exces- Comorbid tic disorder has an especially strong as-
sive and often disabling for the individual, they are sociation with the male sex and early age of onset
based on behaviors that may have increased ancestral in OCD. Boys with OCD and adult men with
survival and reproduction (see Gonda et al., 2008). childhood-onset OCD are more likely to have co-
The SRIs (SSRI antidepressants and the TCA morbid tics and attention-deficit disorders (Leckman
clomipramine) remain the cornerstone of the et al., 2010; Ruscio et al., 2010). Tourette’s syndrome
pharmacological treatment for OCD. However, is also much more pronounced in males compared
due to their favorable risk profile, preference to females with OCD (Mathis et al., 2011).
should be given to the SSRIs (Baldwin et al., 2014; In a meta-analysis of 26 studies conducted with
Bandelow, 2008; Koran & Simpson, 2013). SSRIs OCD patients, 31 percent had comorbid tic disorder,
are more effective than placebo in achieving clinical and this was associated with male sex and early age
response in reducing symptoms, with no difference of onset. The OCD group with tics was more likely
between the individual SSRI drugs and response to endorse touching, twitching, repeating, rubbing,
rates (Soomro et al., 2008), although most patients and symmetry rituals, as well as “just right” percep-
with OCD will continue to have residual symptoms tions prior to their compulsions, whereas the OCD
even after an adequate trial of treatment. group without tics was more likely to endorse con-
tamination obsessions, washing rituals, and anxiety
Sex Differences in Obsessive-Compulsive preceding their compulsive behaviors (Fibbe, Cath,
Disorder & van Balkom, 2011). Among pediatric patients,
Several major epidemiological studies reported those with OCD onset before age 12 years have a
OCD to be slightly more prevalent among women higher frequency of comorbid tic disorder and

420 Sex Differences in Anxiet y Disorders

disruptive behavior disorders, whereby symptoms (Lensi et al., 1996), whereas OCD females have
related to order/symmetry are more frequent in greater rates of comorbid mood and anxiety disor-
males and had the highest comorbidity with tics ders (de Mathis et al., 2008), eating and impulse-
(Masi et al., 2010). Consistent with other reports, control disorders (de Mathis et al., 2008; Fahy
tic comorbidity is also associated with an earlier et al., 1993; Rasmussen & Eisen, 1994; Rubenstein
onset of OCD and a heavier comorbidity with et al., 1992), depression (Noshirvani et al., 1991),
ADHD and other disruptive behavior disorders. and PD (Lensi et al., 1996). A more recent cross-­
Comorbid ADHD in turn is associated with an sectional study found that 11.3 percent of patients
earlier onset of OCD and a poorer response to treat- with OCD met criteria for comorbid eating disor-
ment. In contrast, females are more likely to endorse ders (EDs), including binge-eating disorders (7.2
OCD symptoms related to contamination or clean- percent), bulimia nervosa (2.0 percent), or anorexia
ing. Contamination/cleaning rituals are associated nervosa (2.1 percent). Compared to patients with
with the lowest clinical severity, but a greater rate of OCD without ED, the patients with OCD with
comorbid anxiety and depression (Masi et al., 2010). ED were more likely to be women with previous
Differences in comorbidity patterns in OCD psychiatric treatment (Sallet et al., 2010). Rates of
emerge at the age of 10 and are more pronounced at comorbid pathologic skin picking and trichotillo-
the age of 17 (de Mathis et al., 2008). mania may be twice as likely to occur in females as
There also appears to be differences in the co- males with OCD (Lovato et al., 2012). Sex-specific
morbidity pattern between sexes and between pre- differences in patients with OCD with prominent
pubertal and adolescent-onset cases of OCD. In a hoarding symptoms have also been reported. In a
study of children and adolescents diagnosed with study of over 470 subjects with OCD, 24 percent
OCD, most (83.6 percent) participants had at least were classified as hoarders (Wheaton, Timpano,
one comorbid psychiatric disorder, and oppositional Lasalle-Ricci, & Murphy, 2008). Although OCD
defiant disorder (ODD) and contamination/so- with hoarding was associated with greater symptom
matic obsessions were higher in boys than in girls severity and more comorbid psychiatric disorders,
(Tanidir et al., 2015). Further analysis revealed that most of the observed differences were due to sex.
disruptive behavior disorders were more frequent in That is, females with OCD who hoard had more
those with tic disorder than in those without tics severe OCD symptoms (especially compulsions)
(Tanidir et al., 2015). These findings provide further and greater rates of comorbid bipolar disorder,
support for the inclusion of tic-related OCD as a substance abuse, PD, and binge-eating disorder
specifier in the DSM-V. than females with OCD who didn’t hoard. Male
In contrast to early-onset OCD, women are hoarders had an increased prevalence of SAD com-
more likely to report later onset of OCD symptoms. pared to nonhoarding males (Wheaton et al., 2008).
Late-onset OCD is associated with being female, a Hoarding among patients with OCD is associated
history of chronic (>10 years) subclinical obsessive- with aggressive, sexual, and religious obsessions and
compulsive symptoms, the co-occurrence of PTSD, checking compulsions among men, but not women,
and a history of recent pregnancy or pregnant and male hoarders with OCD are more likely to
partner (Frydman et al., 2014). In an Indian have comorbid GAD and tics, whereas females with
sample, 37 percent reported juvenile-onset (<18 OCD who hoard are more likely to have SAD,
years), 57 percent adult-onset (18 to 39 years), and PTSD, BDD, nail biting, and pathologic skin
5 percent late-onset (≥40 years) OCD (Sharma, picking (Samuels et al., 2008).
Sundar, Thennarasu, & Reddy, 2015). Late-onset Nestadt and colleagues (2009) investigated the
OCD was again more common among women and relationship between OCD and comorbid condi-
was associated with collecting compulsions and less tions and concluded that OCD could be classified
aggressive obsessions in comparison to adult-onset into three classes based on comorbidity: (1) an
onset OCD. In addition, those with late-onset OCD simplex class, in which MDD was the most
OCD were more likely to report precipitating factors frequent additional disorder; (2) an OCD tic-related
such as triggers for OCD and endorse less aggressive class, in which tics are prominent and affective
and sexual obsessions in comparison to those with syndromes are considerably rarer; and (3) an OCD
juvenile-onset OCD (Sharma et al., 2015). affective-related class, in which PD and affective
In addition to tic disorder, males with OCD syndromes are highly represented. The OCD tic-
have greater comorbidity with substance use disor- related class is predominantly male and character-
ders (de Mathis et al., 2008) and bipolar disorder ized by high conscientiousness, whereas the OCD

Piggot t, Duran, Jalnapurkar, Kimm, Linscheid, and Allen 421

affective-related class is predominantly female and but no differences were detected between the scores
associated with a young age at onset, obsessive- of the women with OCD and healthy controls
compulsive personality disorder features, and low (Segalas et al., 2010).
conscientiousness. As noted by the authors, these Sex differences may also exist in response to sero-
results could have implications for research and tonergic probes during challenge studies conducted
clinical endeavors (Nestadt et al., 2009). Although in patients with OCD. Women administered the
comorbidity of OCD with other disorders is serotonergic probe fenfluramine have an attenuated
common, patients with OCD without comorbid cortisol response compared to men with OCD and
disorders may be more likely to be female (Torres control subjects (Monteleone, Catapano, Tortorella,
et al., 2013). & Maj, 1997). After administration of clomip-
Sex differences may exist in the genetic suscepti- ramine as a serotonergic probe, men with OCD
bility to OCD. Two studies suggested that the asso- experienced acute exacerbations in OCD symptoms,
ciation between OCD and variations in the COMT whereas women with OCD failed to demonstrate
gene were sex related, although one found a higher any substantial change in OCD symptoms (Mundo
occurrence of the genetic variation in women with et al., 1999). After 10 weeks of treatment with either
OCD (Alsobrook et al., 2002) and the other in men clomipramine or fluvoxamine, the women with
with OCD (Karayiorgou et al., 1999). A sexually OCD also exhibited a better antiobsessional response
dimorphic association has also been reported between (Mundo et al., 1999). Moreover, dopaminergic and
OCD and polymorphic variants related to monoa- neuropeptide mechanisms may be particularly
mine oxidase A (MAO-A) activity. Women with important in early-onset OCD, which is associated
OCD exhibited an excess of allele 1 polymorphism with the male sex and an elevated risk of comorbid
in the MAO-A gene compared with controls tic disorder (Rosario-Campos et al., 2001).
(Camarena, Cruz, de la Fuente, & Nicolini, 1998; As previously noted, part of the increased preva-
Camarena et al., 2001). An association between lence and severity of anxiety disorders in females has
OCD and an allele of the MAO-A gene that is been linked to the fluctuations in estrogen and
linked to high MAO-A activity has also been re- progesterone throughout the female menstrual cycle.
ported, especially in male OCD probands with Undergraduate women without demonstrable OCD
comorbid depression (Karayiorgou et al., 1999). are reported to engage in more OCD-like behav-
Structural and functional abnormalities have iors, such as excessive cleaning or cleaning of things
been reported in various brain regions in patients not usually cleaned, during the luteal phase than at
with OCD, especially in the orbitofrontal cortex, any other time during the menstrual cycle (Dillon
basal ganglia, and thalamus. Park et al. (2011) re- & Brooks, 1992). In females with pre-existing
ported that the absolute total area of the corpus OCD, the premenstrual (late luteal) phase has
callosum (CC) was greater in patients with OCD been linked to acute OCD symptom exacerbations
than in controls, but further analysis revealed that (Vulink, Denys, Bus, & Westenberg, 2006; Williams
only the male patients with OCD differed from & Koran, 1997; Yaryura-Tobias, Neziroglu, &
male controls in this regard. Structural abnormali- Kaplan, 1995). In fact, ~38 to 49 percent of women
ties in the anterior cingulate cortex (ACC) have with OCD report premenstrual worsening in their
consistently been identified in patients with OCD OCD symptoms (Vulink et al., 2006; Williams &
(Nakao, Okada, & Kanba, 2014). There is also ev- Koran, 1997), and a substantial number (21 percent)
idence that sex-specific neurochemical changes also report premenstrual dysphoria (Williams &
may exist in patients with OCD. Female patients Koran, 1997). These fluctuations not only appear to
with OCD have reduced levels of glutamate-gluta- affect HPA axis reactivity, glucocorticoid feedback
mine (Glx) in all but one subregion of the ACC sensitivity, and brain GABA connections (Altemus,
when compared to matched controls (Yucel et al., 2006) but also may account for observed changes in
2008). In addition, levels of Glx were correlated with anxiety symptom severity during puberty, pregnancy,
clinical measures of symptom severity in the female, and the postpartum period (Altemus, 2006; Pigott,
but not the male, patients with OCD. Some sex 1999). Much of the evidence that supports the
differences in neuropsychological abnormalities importance of monthly and major lifetime repro-
have also been reported in OCD such as worse ductive hormone fluctuations in anxiety in females
performance of male patients with OCD in non- comes from reported changes in OCD symptoms
verbal memory tasks as compared to healthy controls, related to the female reproductive cycle and the

422 Sex Differences in Anxiet y Disorders

occurrence of pregnancy and menopause (Altemus, Conclusion
2006; Lewinsohn, Gotlib, Lewinsohn, Seeley, & In summary, this chapter provides a review of the
Allen, 1998; Lochner et al., 2004; Pigott, 1999). available data concerning sexual differences in the
After menarche, females begin to develop OCD at a epidemiology, phenomenology, clinical course, and
much greater rate than male peers; the robust increase treatment of anxiety disorders throughout the
in prevalence rates for OCD in females eventually lifespan. Women have a higher risk of development
results in the similar prevalence rate for OCD in of anxiety disorders compared with men. Data from
adult women and men. epidemiologic studies suggest that women can have
Numerous studies have investigated the onset of a two- to threefold increase in the occurrence of
OCD in pregnancy. Indeed, a substantial portion GAD, PD, and PTSD. Sex differences in onset,
(13 to 36 percent) of women with OCD report the clinical phenomenology, comorbid conditions, and/
onset of their illness during pregnancy or the post- or underlying neurobiology have also been identi-
partum period (Altshuler et al., 1998; Buttolph & fied in GAD, PD, SAD, PTSD, and OCD.
Holland, 1990; Chelmow & Halfin, 1997; Sichel, Neuroimaging studies have also provided some
Cohen, Rosenbaum, & Driscoll, 1993).Goodman preliminary results concerning functional differ-
et al. (2014) identified seven studies that reported ences in brain function between men and women.
onset rates during pregnancy or the postpartum There is also strong evidence that female reproductive
period between 0 and 39 percent, but the three hormone cycles may influence the occurrence, se-
largest of these studies reported onsets between verity, and course of the anxiety disorders, especially
13 and 39 percent during this period. A meta-­ during pregnancy and the postpartum period.
analysis of OCD prevalence in pregnant and However, there is much less data concerning po-
­postpartum women found that pregnant and post- tential sex differences in the clinical outcome and
partum women were at greater risk for OCD treatment response in the anxiety disorders. More
c ompared to the general population (Russell,
­ research is clearly needed to improve our under-
Fawcett, & Mazmanian, 2013). However, most standing of sex differences and to develop more
studies suggest that pregnancy is not associated effective treatment interventions for women and
with substantial symptom change in most women men with anxiety disorders.
with pre-­existing OCD (Forray, Focseneanu, Pittman,
McDougle, & Epperson, 2010; Williams & Koran,
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432 Sex Differences in Anxiet y Disorders

 CH A PT E R

24 Future Directions in Human Behavioral

Endocrinology
Lisa L. M. Welling and Todd K. Shackelford

Abstract

Research within behavioral endocrinology has produced substantial advances over the past few
decades. Knowledge of the biological mechanisms involved in human behavior informs evolutionary
perspectives on selection pressures in our ancestral past, which encourages the development of more
complete theories and more refined research questions. Yet, despite these advances, many unanswered
questions remain. This chapter outlines broad suggestions for future hormone research within
the topics of development and survival, reproductive behavior, and social and affective behavior.
It concludes with several general suggestions for the field, including more research using hormonal
assays, longitudinal and experimental designs, exogenous hormone administration, and cross-cultural
work. It also suggests that researchers continue to consider the function of other endocrine traits
(e.g., carrier proteins) and measure or manipulate hormones in combination with assessing hormone
receptor genes. Behavioral endocrinology is a field replete with important future research directions
that will contribute important insights into the evolution of our own and other species.
Keywords: Behavioral endocrinology, endocrinology, evolutionary psychology, hormones, behavior,
future directions

The bidirectional relationships between hormones Development and Survival

and behavior have received attention in several fields, In addition to being responsible for growth and
such as biology (e.g., Stricker & Verbalis, 1988), the development of secondary sexual characteristics,
social psychology (e.g., Campbell, 2010), evolution- hormones mediate several development and survival
ary psychology (e.g., Welling et al., 2007), medicine behaviors across the lifespan. Although research is
(e.g., Hollander et al., 2001), and anthropology (e.g., progressing, relatively little is known about how
Whitten, Brockman, & Stavisky, 1998). Contributors hormones mediate life history strategies in humans
to this volume have outlined current research within (reviewed in Vitousek & Schoenle, this volume).
behavioral endocrinology, highlighting how these Future research should address how hormones across
findings add to our understanding of the evolution of the lifespan influence these strategies while paying
our species. However, although this diverse literature particular attention to individual differences (i.e., why
encourages the development of more complete individuals within a population differ in life history
theories and more refined research questions, much strategy; e.g., Williams, 2012) and within-subject
remains to be investigated. Here, we outline several context flexibility (i.e., how life history strategy
broad suggestions for future r­esearch within each of changes over time in reaction to environmental
the three themes of this volume: development and changes; e.g., Wingfield, 2015). Moreover, inter-
survival, reproductive behavior, and social and af- actions with biological sex across development
fective behavior. We conclude by presenting several (see Benenson, this volume) require further study,
general suggestions for the field. and animal models could be useful in this work.

433
Although there is some evidence of cross-species influences on learning and memory, see Ervin &
similarities in developmental sex differences (e.g., Choleris, this volume).
Alexander & Hines, 2002; Hassett, Siebert, & Given the importance of hormones on develop-
Wallen, 2008), a great deal remains to be explored. ment and cognition, we need additional research on
For example, comparative work could investigate endocrine-disrupting chemicals, compounds in the
hormone-mediated differences in the onset of sex- environment that block or mimic hormones (see
differentiated social behaviors across primate species. Vandenberg, this volume). The potential negative
The examination of similarities and differences across impact of endocrine-disrupting chemicals, com-
primate species affords educated inferences regarding monly found in pesticides and other modern prod-
ancestral pressures that may have applied to humans, ucts like plastics, has been known for several decades
which can further our understanding of sex-typical (Carson, 1962). Yet, endocrine-disrupting chemi-
behaviors. cals are still commonplace and can have a profound
Comparative work also provides evidence for influence on wildlife. For example, atrazine, which
the Organizational–Activational Hypothesis (e.g., is among the most common herbicides used world-
Gurney & Konishi, 1980; Phoenix, Goy, Gerall, & wide, is found in ground, surface, and drinking
Young, 1959), which posits that sex differences in water. Hayes et al. (2010) found that amphibian
cognition result from differential hormone exposure males exposed to atrazine were chemically castrated
during critical periods that organize brain circuitry and completely feminized as adults, and suggested
to later produce behavior under appropriate hormo- that atrazine and other endocrine-disrupting chem-
nal conditions (reviewed in Hampson, this volume). icals may play a role in the global decline of amphib-
There is significant empirical evidence in favor of ians. In humans, many endocrine-related disorders
organization/activational influences of hormones have increased over a relatively short period of time,
on human cognition (e.g., Puts, McDaniel, Jordan, & which suggests that environmental changes such as
Breedlove, 2008; Resnick, Berenbaum, Gottesman, increases in endocrine-disrupting chemicals may be
& Bouchard, 1986; Shute, Pellegrino, Hubert, & responsible (Bergman et al., 2013). However, the
Reynolds, 1983), but the majority of research has effect of endocrine-disrupting chemicals on human
focused on mental rotation ability, and so future behavior remains unexplored.
work might investigate other aspects of cognition in
more detail. One way to ethically investigate differ- Reproductive Behavior
ential hormone exposure on human cognition is to Considerable research on many species, including
compare populations with disorders of sex develop- humans (see, e.g., Gangestad & Thornhill, 2008;
ment (many of which are characterized by abnormal Gildersleeve, Haselton, & Fales, 2014), suggests
hormonal profiles during critical periods) with con- that hormones affect reproduction-related behaviors
trols. Use of populations such as women with con- in functional ways. Despite some disagreement
genital adrenal hyperplasia (e.g., Resnick et al., 1986), (e.g., Harris, Pashler, & Mickes, 2014; Wood,
who are exposed to higher than normal levels of Kressel, Joshi, & Louie, 2014), putative shifts in
androgens in utero, can provide an important avenue adaptive behaviors and preferences across the female
for assessing the contributions of hormones to menstrual cycle have received substantial attention
the development of psychosexually differentiated (reviewed in Welling & Burriss, this volume). As
behaviors. However, relatively few studies test these noted previously (e.g., Gangestad et al., 2016), dis-
hypotheses on clinical samples. Similarly, the impact agreement about the results of research in this area
of pubertal timing on cognition (e.g., Beltz & may be partly attributable to inconsistencies in the
Berenbaum, 2013) could be investigated using clin- methods used to estimate cycle phase. Researchers
ical populations such as those with idiopathic hypo- should use within-subject designs where possible,
gonadotropic hypogonadism, a condition whereby follow published guidelines when estimating cycle
puberty is not triggered naturally and patients are phase, and use sufficient power so that the results of
given hormone replacement therapy to begin the research will be easier to compare across studies
process (i.e., the timing of puberty is precisely known, (Gangestad et al., 2016; Jones et al., in press). This
unlike nonclinical samples). Use of clinical popula- will serve the additional benefit of reducing Type 1
tions could also inform research on other aspects of and Type 2 errors.
cognition that are influenced by sex steroids, such as Many women have chosen to control their men-
learning and memory (for a discussion on hormonal strual cycles and fertility using the synthetic hormones

434 Future Directions in Human Behavioral Endocrinology

found in hormonal contraceptives since their differences on mate preferences. Given changes in
­introduction in the 1960s (Mosher & Jones, 2010), preferences during periods characterized by marked
which may affect aspects of mate choice (e.g., hormonal changes, such as puberty (e.g., Boothroyd,
Roberts, Gosling, Carter, & Petrie, 2008; see Hahn Meins, Vukovic, & Burt, 2014) and menopause
& Cobey, this volume, for a review of synthetic hor- (e.g., Vukovic et al., 2009), hormonal mediation
mones and women’s mating psychology). Although seems likely, but the relative lack of hormonal
research into the use of these popular synthetic assays in developmental work makes it uncertain.
hormones has progressed steadily, most of this
­ Furthermore, variation in methods used to assess
work (with a few notable exceptions; e.g., Cobey, mate preferences (e.g., peer-aged vs. young adult
Klipping, & Buunk, 2013) compares women cur- stimuli; Jones, Vukovic, Little, Roberts, & DeBruine,
rently on hormonal contraceptives with women not 2011; Vukovic et al., 2009) and pubertal timing
currently on hormonal contraceptives (e.g., Welling, (e.g., puberty scales vs. age of menarche; Jones,
Puts, Roberts, Little, & Burriss, 2012), rather than Boothroyd, Feinberg, & DeBruine, 2010; Saxton
comparing the same women multiple times. Also, et al., 2010) hinders comparisons across studies. These
synthetic hormones are not identical; for example, shortcomings yield ample opportunities for future
some progestins (e.g., levonorgestrel) are androgenic, research into developmental changes across the lifes-
whereas others (e.g., drospirenone) are antiandro- pan and into how hormonal exposure during critical
genic. Hormonal contraceptives are also adminis- periods organizes mate preferences. Similarly, we
tered multiple ways (e.g., injectable, pill, vaginal ring) need additional research on the hormonal compo-
and can be monophasic (i.e., deliver a constant level nents involved in developing gendered behaviors,
of synthetic hormones) or multiphasic (i.e., the syn- gender identity, and sexual orientation (reviewed in
thetic hormone dose varies across the regimen). Some Neibergall, Swanson, & Sánchez, this volume).
research has compared different doses of synthetic In addition to influencing mate preferences,
hormones (Cobey, Pollet, Roberts, & Buunk, 2011; hormones influence parental behavior. In men,
Welling et al., 2012; Welling, 2016) or the type of aggression and mating effort are linked in that tes-
synthetic hormone (Grøntvedt, Grebe, Kennair, & tosterone is positively related to both (reviewed in
Gangestad, 2017). However, there is a need for ad- Goetz, Weisfeld, & Zilioli, this volume). Thus, it is
ditional research that considers different types of perhaps unsurprising that testosterone declines
synthetic hormones (e.g., levonorgestrel vs. drospi- with fatherhood, which likely functions to decrease
renone) and different types of hormonal contracep- aggression and mate seeking and, in turn, increase
tives (e.g., injectable vs. pill, monophasic vs. multi- investment in children (reviewed in Boyette &
phasic) on women’s mating psychology (e.g., mate Gettler, this volume). Using longitudinal data from
preferences, sexual behavior), especially using a the Philippines, Gettler and colleagues (Gettler,
within-subject design. Correspondingly, although McDade, Agustin, Feranil, & Kuzawa, 2015;
some have argued that menopause is accompanied by Gettler, McDade, Feranil, & Kuzawa, 2011; Gettler,
a shift away from mating-oriented psychology (e.g., McKenna, Agustin, McDade, & Kuzawa, 2012)
Hawkes, O’Connell, Jones, Alvarez, & Charnov, found that men experience significant declines in
1998) and a reduction in behaviors aimed at acquir- testosterone when transitioning into fatherhood,
ing and securing a mate (e.g., Vukovic et al., 2009), and that this decline is greatest among men who are
the impact of hormone replacement therapy (HRT) more involved in caregiving. More recently, this lab
on many mating and family-related behaviors has found that young men’s androgen functionality
yet to be investigated. Given their increasing pop- (i.e., androgenicity) before fatherhood predicted
ularity among women and men (i.e., androgen whether they were later involved as direct caregivers,
­replacement therapy), HRT is a fruitful area for with moderately androgenic men being more in-
­additional investigation. volved than those low or high in androgenicity
Mate preferences fluctuate across the lifespan, (Gettler et al., 2017). Other evidence suggests that
but few studies employ longitudinal within-subject other hormones, like prolactin and oxytocin (see
designs, and even fewer measure hormone concen- Gordon, Zagoory-Sharon, Leckman, & Feldman,
trations (reviewed in Boothroyd & Vukovic, this 2010), play a role in paternal behavior similar to the
volume). The lack of within-subject designs is a role these hormones play in maternal behavior
methodological weakness that needs to be addressed (e.g., Uvnäs-Mobcrg, Widström, Nissen, & Björvell,
to rule out confounding influences of individual 1990). Furthermore, maternal behavior is associated

Welling and Shackelford 435

with estradiol and progesterone, and their ratio, administration studies are becoming more common
during gestation (e.g., Glynn, Davis, Sandman, & (e.g., Bos, Panksepp, Bluthé, & Van Honk, 2012;
Goldberg, 2016), but their influence in male paternal Carré et al., 2017; Welling, Moreau, Bird, Hansen,
behavior is unexplored in humans. The independent & Carré, 2016; Wibral, Dohmen, Klingmüller,
and interdependent effects of these hormones on Weber, & Falk, 2012), but more work using exoge-
parenting and other social behaviors, including nous hormone administration, including with other
social bond paradoxes (i.e., the seemingly contradic- hormones like estradiol and progesterone, would be
tory activating function of certain hormones when useful. Also, investigations into the long-term effects
applied to different circumstances, such as nurturing of hormone surges could generate novel information.
vs. infant-defense parenting behaviors; see Witczak, Testosterone secretion and action on target tissues
Simmons, & Bales, this volume), d ­ eserves additional is influenced by cortisol level (e.g., S. Chen, Wang,
attention. Specifically, researchers should continue Yu, Liu, & Pearce, 1997), and predictions surround-
to differentiate the hormonal trade-offs involved in ing testosterone and social status have not been fully
balancing mating, parenting, and affiliative social supported (see review by Mazur & Booth, 1998).
bonds and behaviors. Research on testosterone and status (Mehta &
Josephs, 2010) and aggression (Dabbs, Jurkovic, &
Social and Affective Behavior Frady, 1991; Popma et al., 2007) suggests that the
Social and affective behaviors can be prosocial interaction between testosterone and cortisol may
(e.g., nurturance) or antisocial (e.g., aggression). The be more important than looking at a single hor-
endocrine system is important in regulating social- mone in isolation. For instance, Mehta and Josephs
affiliative processes that contribute to the initiation (2010) found that testosterone is positively related
and maintenance of human social bonds (for a review to dominance behaviors in men and women, but
of the endocrinology of social relationships, see only if the individual is low in cortisol level. Future
Anderl, Saphire-Bernstein, & Chen, this volume). research should explore this dual-hormone effect in
The Challenge Hypothesis suggests that there is a more detail by, for example, examining other behav-
dynamic relationship between testosterone and ioral and personality correlates (discussed in Casto
aggressive behavior such that testosterone promotes & Mehta, this volume). Additionally, the influence
aggression when it benefits the individual from a of these hormones on status-seeking and related
reproductive standpoint (i.e., pursuing a mate, mate behaviors should be considered with reference to
guarding, and intersexual competition to ward off the social group in which they occur (e.g., group
male rivals; Wingfield, Hegner, Dufty, & Ball, 1990). hierarchies, intergroup and intragroup competition,
Indeed, considerable research has found an associa- nonfamilial vs. familial groups) to more compre-
tion between testosterone and competitive, status- hensively investigate within-group social dynamics.
seeking behavior (reviewed in Casto & Mehta, this Evidence suggests that testosterone can promote
volume; Geniole & Carré, this volume). Competition- prosocial behaviors under certain contexts, such as
induced testosterone changes are influenced by when interacting with in-group versus out-group
competitive outcome (i.e., win vs. loss; e.g., Gladue, members (e.g., Diekhof, Wittmer, & Reimers, 2014;
Boechler, & McCaul, 1989; Mazur, Booth, & Dabbs, Reimers & Diekhof, 2015), reciprocating prosocial
1992; Mehta, Snyder, Knight, & Lassetter, 2015; behavior (Boksem et al., 2013; Dreher, Dunne,
Pound, Penton-Voak, & Surridge, 2009), and these Pazderska, Frodl, & Nolan, 2016), or (in women)
testosterone fluctuations may in turn influence future reconciling after a conflict or competition (Casto &
competitive behavior by promoting such behavior Edwards, 2016). However, despite attempts at for-
when it may enhance status (discussed in Mehta mulating models outlining the functions of testos-
­et al., 2015). A methodological limitation of this (and terone (e.g., Eisenegger, Haushofer, & Fehr, 2011;
other) work is reliance on correlations instead of van Anders, Goldey, & Kuo, 2011), the contexts
experimental manipulations, which, particularly and individual differences according to which tes-
given that the relationships between testosterone tosterone promotes positive versus negative behav-
and aggressive and competitive behavior are bidirec- iors remain unclear (see discussion in Hamilton,
tional (i.e., the behavior follows the increase in Carré, Mehta, Olmstead, & Whitaker, 2015).
the hormone and vice versa; e.g., Carré, Campbell, Other research on the endocrinology of social
Lozoya, Goetz, & Welker, 2013; Geniole, Bird, relationships has focused on the peptide hormone
Ruddick, & Carré, 2017), does not inform our oxytocin (for a review of oxytocin research, see
knowledge of causal relationships. Testosterone Grebe & Gangestad, this volume). In addition to its

436 Future Directions in Human Behavioral Endocrinology

functions in parturition and lactation, researchers stages of gestation). Also, as noted elsewhere
have argued that oxytocin evolved to facilitate paren- (e.g., Heim, Newport, Mletzko, Miller, & Nemeroff,
tal (especially maternal) behavior, but that it has 2008), there are few longitudinal studies investi-
been co-opted and modified to function in other gating these issues. Similarly, interactions between
relationship contexts (e.g., friendships, kin, in-group genetic variation and stressful experiences, and how
members; e.g., Carter, 2014; Donaldson & Young, they influence psychological behavior and psychiatric
2008). Although there is evidence in favor of this outcomes across the lifespan, deserve additional
hypothesis (e.g., Feldman et al., 2010), more work attention. Other methodological issues in this area,
is needed to clarify oxytocin’s role and range of such as inconsistent assessment, retrospective designs
functions. For instance, oxytocin is known to with adult samples, and small sample sizes, have
­attenuate the cortisol response to stress (Cardoso, been noted (McCrory, De Brito, & Viding, 2010;
Ellenbogen, Orlando, Bacon, & Joober, 2013) and Pollak, 2015; see also Deer et al., this volume) and
may interact with opioids to influence social out- hinder the comparison of results across studies.
comes (reviewed in Gangestad & Grebe, 2017). In Finally, how individual differences mediate responses
rats, estradiol and progesterone proliferate oxytocin to acute and chronic stress may have applications
receptors in the brain and enhance the influence for the treatment of certain clinical disorders.
of administered oxytocin on sexual receptivity The HPA axis (e.g., Burke, Davis, Otte, & Mohr,
(McCarthy, 1995; Schumacher, Coirini, Frankfurt, 2005; Ciufolini, Dazzan, Kempton, Pariante, &
& McEwen, 1989; Schumacher, Coirini, Pfaff, & Mondelli, 2014; Stetler & Miller, 2011), estrogen
McEwen, 1990). Also, oxytocin is related to both and progesterone (e.g., Newhouse & Albert, 2015;
prosocial and antisocial behaviors (reviewed in Schmidt, Nieman, Danaceau, Adams, & Rubinow,
Shamay-Tsoory & Abu-Akel, 2016). Mixed find- 1998; Wyatt, Dimmock, Ismail, Jones, & O’Brien,
ings have led to several attempts to conceptualize 2004), and testosterone (e.g., Almeida, Waterreus,
oxytocin’s various influences into a unified framework Spry, Flicker, & Martins, 2004; Bromberger
(e.g., Bethlehem, Baron-Cohen, van Honk, Auyeung, et al., 2010; Giltay et al., 2017) have been impli-
& Bos, 2014; Churchland & Winkielman, 2012; cated in mental health issues such as depressive
Crespi, 2016; Numan & Young, 2016; Shamay- disorders (reviewed in Ellenbogen, Tsekova, &
Tsoory & Abu-Akel, 2016), but no consensus has Serravalle, this volume). Hormones may be impor-
been achieved. Scholars should continue to test the tant causes or consequences of certain clinical disor-
different oxytocin hypotheses to determine which ders and may be useful in targeted treatments (see,
has the most support, and should integrate evidence e.g., Herbert, 2013). Research in this area has begun
of associations with other hormones (e.g., vasopres- (e.g., Block et al., 2017; DeBattista et al., 2006;
sin, estradiol, progesterone, cortisol). Guastella, Howard, Dadds, Mitchell, & Carson,
One putative function of oxytocin is that it acts to 2009; Spierling & Zorrilla, 2017), including research
protect a person from the negative effects of stress by that considers matching genetic markers associated
reducing stress hormones (Cardoso et al., 2013) and with hormone functioning with the response to
encouraging affiliative social behavior (e.g., Carter, treatment (O’Connell et al., 2018), but this research
1998). Although stress hormones may be adaptive remains sparse. Researchers could also further
under short-term acute conditions (providing energy ­examine how short-term fluctuations in hormones or
for fight-or-flight responses; e.g., Cannon, 1929), disruption of natural hormonal cycles (e.g., circadian
chronic stress can have severe long-lasting conse- rhythms; reviewed in Cissé, Borniger, & Nelson, this
quences (reviewed in Mogilski et al., this volume). volume) impact mental health and other behaviors.
However, the role that cortisol plays in dysregulat-
ing bodily functions and increasing susceptibility to Conclusion
disease through behavioral and immune function Research in behavioral endocrinology informs evo-
changes is not well understood. Recent advances in lutionary theories surrounding ultimate (“why”)
research have increased our understanding of how questions by providing the proximate (“how”) expla-
maternal/gestational stress and child maltreatment nations. Although considerable advances have been
impact the hypothalamic-pituitary-adrenal (HPA) made, much is left to uncover. We need more research
axis and mental and physical health (reviewed in using hormonal assays, longitudinal designs, and
Deer, Bernard, & Hostinar, this volume), but little experimental designs with exogenous hormone
is known about the degree to which the observed administration. Additional cross-cultural research
effects are moderated by timing (e.g., during different could illustrate important hormone interactions with

Welling and Shackelford 437

the environment, or otherwise provide important Bethlehem, R. A., Baron-Cohen, S., van Honk, J., Auyeung, B.,
replications of key findings. Another major frontier & Bos, P. A. (2014). The oxytocin paradox. Frontiers in
Behavioral Neuroscience, 8, 1–5.
in endocrine research involves exploring the complex Block, T., Petrides, G., Kushner, H., Kalin, N., Belanoff, J., &
regulatory networks that connect neuroendocrine Schatzberg, A. (2017). Mifepristone plasma level and glucocor­
systems and their connection with other physiolog- ticoid receptor antagonism associated with response in patients
ical systems (e.g., immune and metabolic systems; with psychotic depression. Journal of Clinical Psychopharma­
Martin & Cohen, 2015). Behavioral endocrinology cology, 37, 505–511.
Boksem, M. S., Mehta, P. H., Van den Bergh, B., van Son, V.,
research typically focuses on a single hormone’s Trautmann, S. T., Roelofs, K., . . . Sanfey, A. G. (2013).
influence on a given trait, but physiological systems Testosterone inhibits trust but promotes reciprocity. Psycholo­
are interconnected (e.g., Cutolo et al., 2004). Under­ gical Science, 24(11), 2306–2314.
standing the interactions between physiological sys- Boothroyd, L. G., Meins, E., Vukovic, J., & Burt, D. M. (2014).
tems and behavior would provide important insights. Developmental changes in children’s facial preferences.
Evolution and Human Behavior, 35(5), 376–383.
Correspondingly, investigating interactions between Bos, P. A., Panksepp, J., Bluthé, R. M., & Van Honk, J. (2012).
multiple hormones (e.g., Heinrichs, Baumgartner, Acute effects of steroid hormones and neuropeptides on human
Kirschbaum, & Ehlert, 2003; Mehta & Josephs, social-emotional behavior: A review of single administration
2010; Tackett et al., 2015) is imperative. These inter- studies. Frontiers in Neuroendocrinology, 33(1), 17–35.
actions should be both measured endogenously and Bromberger, J. T., Schott, L. L., Kravitz, H. M., Sowers, M.,
Avis, N. E., Gold, E. B., . . . Matthews, K. A. (2010).
manipulated exogenously in multiple samples. Longitudinal change in reproductive hormones and depressive
The literature would benefit from additional work symptoms across the menopausal transition: Results from the
on hormone gene activation and how selection shaped Study of Women’s Health Across the Nation (SWAN). Archives
the expression and function of other endocrine traits, of General Psychiatry, 67, 598–607.
such as hormone receptors and carrier proteins. Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005).
Depression and cortisol responses to psychological stress: A
Furthermore, measuring or manipulating hormones meta-analysis. Psychoneuroendocrinology, 30, 846–856.
in combination with assessing hormone receptor Campbell, A. (2010). Oxytocin and human social behavior.
genes (e.g., F. S. Chen et al., 2015; Eisenegger, Personality and Social Psychology Review, 14(3), 281–295.
Kumsta, Naef, Gromoll, & Heinrichs, 2017; Roney, Cannon, W. B. (1929). Bodily changes in pain, hunger, fear, and
Simmons, & Lukaszewski, 2010) can more thor- rage. New York, NY: Appleton-Century-Crofts.
Cardoso, C., Ellenbogen, M. A., Orlando, M. A., Bacon, S. L.,
oughly address whether it is the hormone itself or & Joober, R. (2013). Intranasal oxytocin attenuates the
other aspects of biology related to the hormone that cortisol response to physical stress: A dose–response study.
are influencing changes in behavior. Future work of Psychoneuroendocrinology, 38, 399–407.
this nature may reveal that relationships between Carré, J. M., Campbell, J. A., Lozoya, E., Goetz, S. M. M., &
hormones and behavior are more complex than Welker, K. M. (2013). Changes in testosterone mediate
the effect of winning on subsequent aggressive behaviour.
previously supposed. Certainly, there are multiple Psychoneuroen­docrinology, 38, 2034–2041.
­directions scholars can pursue moving forward, which Carré, J. M., Geniole, S. N., Ortiz, T. L., Bird, B. M., Videto, A.,
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how hormones influence development, survival, increases aggressive behavior in dominant and impulsive
reproduction, and social behaviors across the lifespan. men. Biological Psychiatry, 82(4), 249–256.
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 NAME INDEX

Note: Figures are indicated by an italic f, following the page number.

A Brunton, P. J., 339 DeSoto, C. M., 217

Achenback, G. G., 182 Büchel, C., 326 Dietrich, T., 55
Adewuya, A. O., 412 Burbank, V. K., 225 Di Fiore, A., 181
Agustin, S. S., 188 Burriss, R. P., 241 Dijkstra, P., 219–20, 221, 222
Ainsworth, M. D., 335 Burt, D. M., 144, 152 Ditzen, B., 358–59
Akinola, M., 304 Buss, D. M., 216, 217, 219, 222 Dixson, B. J., 153–54
Aleman, A., 59 Buunk, A. P., 219–20, 221, 222, 223, Doll, H. A., 242
Al Hajj, R., 287 227, 228, 229, 229–30 Douglas, A. J., 339
Altemus, M., 407 Buunk, B. P, 219, 221, 222 Draper, P., 192, 193
Anderson, K. G., 185 Byne, W., 209 Dufty, A. M., 186, 337
Archer, J., 283 Duguid, M. M., 230
Arnocky, S., 221 C Dunbar, R.I.M., 223
Aubin, S., 58 Campbell, A., 225 Dunson, D., 115
Auyeung, B., 51 Carnaghi, A., 228 Dziurawiec, S., 146
Avinum, R., 264 Carnegie, R., 388
Awasthy, M., 153–54 Carré, J. M., 132, 286, 289, 302, 307 E
Carson, R., 88–89 Eckstein, M., 322
B Caruso, S., 242 Edwards, D. A., 304
Baird, D. D., 115 Casto, K. V., 304 Eisenegger, C., 306
Ball, G. F., 186, 337 Chenausky, K. L., 412 Ellertson, C., 114–15
Bancroft, J., 242 Cherrier, M. M., 58 Ellison, P. T., 184
Bar, M., 224 Chiavetta, M. R., 48–49
Bartos, L., 344 Chisholm, J. S., 192 F
Bas, O., 226 Ciufolini, S., 385 Fales, M. R., 110
Beach, F., 2 Clark, A., 146 Fayyad, R., 418
Behrmann, M., 150 Clark, L., 306 Feldman, R., 191, 259, 328
Beiderbeck, D. I., 339 Clark, R. D., 216 Feranil, A. B., 188
Belsky, J., 192, 193 Clark A. S., 48, 52 Fernandez-Duque, E., 181
Bendixen, M., 217 Clary, C. M., 418 Field, P. M., 45
Benenson, J. F., 227 Clayton, A. H., 418 Figueredo, A. J., 228
Bereczkei, T., 152 Clemans, K. H., 298–99 Fink, B., 226
Berenbaum, S. A., 50–51 Cobey, K. D., 145, 220, 228, 246 Fisher, C. I., 241
Berthold, A. A., 2, 15 Colborn, T., 89 Fisher, M. L., 226–27, 228, 229
Bick, J., 165 Colombo, B., 117 Fisher, P. A., 169
Blanchard, R., 207 Connolly, J. M., 147 Flanagan-Cato, L. M., 328
Bliege Bird, R., 183 Cooper, L. M., 217 Flinn, M. V., 133, 182, 342, 345
Bloch, M., 390–91 Cosmides, L., 228 Foa, E. B., 412
Bockting, W. O., 202 Costa, P., 229 Fragale, A. R., 224
Bogaert, A. F., 207 Frederick, D., 224
Boothroyd, L. G., 144, 147–48, 150–51, D Freeman, M. P., 412
152 Dahl, R. E., 150 Freundl, G., 114
Bos, P. A., 194 Daly, M., 128, 185 Fullerton, C. S., 414
Bosch, O. J., 339 Darwin, C., 215
Bouchard, T. J., 50–51 Davis, R. E., 147 G
Bowen, M. T., 358 DeBruine, L. M., 153 Gamer, M., 326
Bowlby, J., 335 De Dreu, C. K., 342 Gangestad, S. W., 109, 115, 116–17, 229,
Brewer, G., 226 de Haan, M., 146 270–71
Bribiescas, R. G., 184 del Arca, D., 230 Gao, S., 324
Brooks, R. C., 154 del Guidice, M., 193 Geary, D. C., 182, 217, 220
Brown, T. A., 226 de Mathis, M. A., 420 Geddes, K., 146

443
Geniole, S. N., 289 K Meehan, C. L., 184
Gerall, A. A., 44–45, 204 Kaiser, S., 206 Mehta, P. H., 132, 285, 299, 303, 304,
Gettler, L. T., 133, 184, 185, 188, 191, 192, Kalakanis, L., 146 306, 357–58, 436
193, 435 Kandrik, M., 241 Meins, E., 144, 152
Gildersleeve, K., 110 Kaplan, H., 184, 185 Mendoza, S. P., 181
Gill, T., 223 Kayl, A. J., 147 Meyer, J. S., 48
Goldman-Rakic, P. S., 48, 52 Kennair, L. O., 217 Meyer-Bahlburg, H.F.L., 205
Goncalo, J. A., 230 Kenrick, D. T., 228 Michalek, J., 187
Goodman, J. H., 412, 415, 423 Ketterson, E. D., 319 Miller, G., 112
Gorski, R. A., 45 Klappauf, D., 226 Miller, G. F., 223
Gottesman, I. I., 50–51 Klavina, L., 220 Miller, J., 221
Gouda-Vossos, A., 154 Kleeblatt, J., 393 Mize, K. D., 218
Gouin, J. P., 341 Knight, E. L., 285, 299 Mortensen, E. L., 205
Goy, R. W., 44–45, 204 Koch, S., 217 Moses, E. L., 392
Grabe, M. E., 226 Kocsor, F., 152 Muehlenbein, M. P., 342
Graham, C. A., 242, 246 Kolodny, R., 203 Muller, N. M., 188
Granger, D. A., 298–99 Kornienko, O., 298–99 Murdock, G. P., 218
Gray, P. B., 184, 185 Kościński, K., 144, 145, 148, 150, Musselman, L., 146
Grebe, N. M., 263, 270–71, 324 151, 154
Greco, T., 242 Kozaki, T., 56 N
Griffey, J. A., 146, 147, 148 Kozlov, M. V., 154 Neel, R., 228
Griffin, G. D., 328 Krems, J. A., 228 Nestadt, G., 421
Griskevicius, V., 130 Krömer, S. A., 339 Neta, M., 224
Grøntvedt, T. V., 248, 249 Kruijver, F.P.M., 209 Neuberg, S. L., 228
Grow, D. R., 48 Kuzawa, C. W., 188 Neumann, I. D., 339
Guadagno, R. E., 217 Newman, M. L., 306
Gurven, M., 184 L Nolan, V., Jr., 319
Gyuris, P., 152 Lacreuse, A., 48
Lamb, T. A, 305 O
H Láng, A., 152 Olmstead, N. A., 302
Hagen, M. J., 168 Langlois, J. H., 146, 147 Orlewicz, M., 147
Hahn, A. C., 241 Larsen, R. J., 216 Ormel, J., 229–30
Han, C., 241 Lassetter, B., 285 Out, D., 298–99
Hare, L., 207 LeVay, S., 209
Harpending, H., 192, 193 Li, N. P., 226 P
Harris, C. R., 218 Linz, H., 224 Pagano, L. A., 226
Haselton, M. G., 110, 224 Little, A. C., 146, 147, 148, 153, 241 Page-Gould, E., 304
Hatfield, E., 216 Lu, J. G., 304 Park, J. H., 220, 222, 422
Hawkes, K., 183 Lukaszewski, A. W., 133 Pawlowski, B., 152
Hayes, T. B., 434 Luxen, M. F., 229 Pazhoohi, F., 218
Hegner, R. E., 186, 337 Lycett, J., 223 Perrett, D. I., 146
Hewlett, B. S., 184 Petrie, M., 241
Higano, C. S., 58 M Phoenix, C. H., 44–45, 204
Hill, K., 184 Maher, B. S., 265, 266 Piccoli, V., 228
Hill, S. E., 222 Mailhos, A., 230 Pintzka, C.W.S., 58
Hines, M., 52–53 Maner, J. K., 228 Ponzi, D., 304, 342
Hoard, M. K., 217 Marcinkowska, U. M., 154 Puts, D. A., 228
Hoier, S., 151 Marler, C. A., 340
Hosseinchari, M., 218 Marlowe, F., 136 Q
Hrdy, S. B., 180, 185 Marlowe, F. W., 183–84 Quinlan, M. B., 184, 193
Hurlemann, R., 322 Masarotto, G., 117 Quinlan, R. J., 184, 193
Maslov, A., 304
I Mason, W. A., 181 R
IJzerman, H., 218 Massar, K., 220, 221, 222, 223, 227 Raisman, G., 45
Maurer, D., 146, 148 Rantala, M. J., 154
J Mazur, A., 131–32, 187, 305 Reeve, C., 226–27
Jeffery, L., 146 McCormick, C. M., 132, 286 Reinisch, J. M., 205
Johnson, M. H., 146 McCrae, R., 229 Rempt, S., 227
Johnston, P., 150 McDade, T. W., 188 Rennels, J. L., 147
Jones, B. C., 115, 117, 153, 241 McGregor, I. S., 358 Resnick, S. M., 50–51
Jordan, B. D., 112 McNulty, J. K., 228 Rhodes, G., 146, 148
Josephs, R. A., 132, 303, 304, 357–58, Meaney, M., 16 Roberts, S. C., 153, 240, 241
436 Meddle, S. L., 339 Rodriguez, G., 114–15

444 Name Index

Roggman, L. A., 146 Spence-Aizenber, A., 181 Vongas, J. G., 223, 287
Ronay, R., 130 Steinberg, L., 192 von Hippel, W., 130
Roney, J. R., 133 Stewart, R. S., 418 Vukovic, J., 144, 152, 153
Rubenstein, A. J., 146 Stirnemann, J. J., 117
Stoolmiller, M., 169 W
S Stulp, G., 229–30 Walum, H., 264, 265
Saad, G., 223 Sulikowski, D., 154 Wang, H., 241
Sachser, N., 206 Sunderani, S., 221 Ward, I. L., 206
Sagarin, B. J., 217 Watson, N. V., 132, 304, 306
Samson, L., 226 T Welker, K. M., 289, 307
Sandberg, E. C., 53 Taavoni, S., 250 Welling, L.L.M., 2, 4, 5, 110–11, 116, 132,
Sanders, S. A., 205 Tagler, M. J., 218 144–45, 151, 153, 228, 238, 240, 246,
Sapolsky, R. M., 296, 298 Tam, J. C., 153–54 248, 250, 266–67, 301, 303, 357,
Saxton, T. K., 148, 150, 152 Tanner, A., 242 433–36
Scelza, B. A., 184, 217–18 Taylor, S. E., 265, 273, 353–54, 354f Westen, D., 216
Scheele, D., 322 Tiedens, L. Z., 224 Wieling, M. B., 222
Scherf, K. S., 150, 151 Timonin, M. E., 340 Wilcox, A. J., 115, 117
Schmidt, P. J., 390 Tinbergen, N., 317 Wilson, M., 128, 185
Schultheiss, O. C., 305 Titus-Ernstoff, L., 205 Wingfield, J. C., 186, 337
Schützwohl, A., 216–17 Tolman, R. M., 269 Wiszewska, A., 152
Schwartz, D., 117 Tooby, J., 228 Worth, K., 226–27
Selye, H., 354 Trainor, B. C., 340 Wu, Y., 306
Semmelroth, J., 216 Trussell, J., 114–15 Wynne-Edwards, K. E., 340
Shackelford, T. K., 218, 219, 226 Tyber, J. M., 112
Shackelford, V. A., 218 Y
Shaw, S., 226–27 V Yasukouchi, A., 56
Sheldon, W. H., 217 Vaillancourt, T., 221 Yehuda, R., 356
Sherman, V. D., 298 van Anders, S. M., 269, 337–39, 340, Yong, J. C., 226
Shirai, A.-A. C., 48 341 Young, W. C., 44–45, 204
Simmons, Z. L., 133 Van Brummen-Girigori, O., 219–20, 230
Simpson, J. A., 229 Van de Vijver, F.J.R., 229 Z
Slater, A., 151 van Honk, J., 130, 303 Zhang, H., 325
Smith, A. R., 226 van Son, V., 306 Ziegler, T. E., 340
Smith, L., 226–27 Veblen, T. B., 223 Zietsch, B. P., 265–66
Snowdon, C. T., 182 Vingilis-Jaremko, L., 146, 148 Zilioli, S., 131, 132, 304, 306
Snyder, N. A., 285 Volling, B. L., 269 Zurriaga, R., 220

Name Index 445

 SUBJECT INDEX

Note: Tables and figures are indicated by an italic t and f, following the page number.

A androgen insensitivity syndrome, 204–5 Organizational-Activational

ACTH. See adrenocorticotropic androgens, 1 Hypothesis, 3
hormone (ACTH) activational effects and, 48 reproductive behavior, 3–4
activational effects, defined, 45 congenital adrenal hyperplasia and, social and affective behavior, 4–5
acute stress induction, 271, 273 49–50, 51, 204–5 benzodiazepines, 406, 407, 409, 416, 417
acute stress response, defined, 351–52. language processes and, 52 Big Five personality traits, 229
See also stress hormones, secondary sexual traits and, 15 bioaccumulation, defined, 88f
physiology, and behavior sex differences in cognition and, 57–59 biological fitness, defined, 126n4
Adaptive Calibration Model, The, 193 spatial cognition and, 50–53 biomagnification, defined, 88f
addiction, and circadian rhythms, 373–74 Anovlar, 246 biosocial model of status, 131–32, 282–84,
Addison disease, 369 anxiety-mood disorders. See also sex 300. See also competition,
ADHD. See attention-deficit/hyperactivity differences in anxiety disorders dominance, and social hierarchy
disorder (ADHD) circadian rhythms and, 373 birth sex, defined, 202
adrenocorticotropic hormone (ACTH), 351 hormonal changes and, 5 bisexuality, 202, 203, 205
child maltreatment and, 163–64, HPA axis and, 415 BMAL1 gene, 368–69, 368f, 370, 374
166–67, 168 incidence of in U.S., 372, 405 borderline personality disorder (BPD), 168
circadian rhythms and, 369, 370, 373 anxiety sensitivity (AS), 417 BPA (bisphenol A)
in fight-or-flight response, 271 anxious attachment style, 128, 219–20 endocrine disruption by, 100, 206
major depressive disorder and, 384–86 arginine vasopressin. See vasopressin low-dose effects of, 98
affective behavior. See social and affective (AVP) varying cutoff doses of, 97–98
behavior aromatization hypothesis, 52–53 brain opioid systems, 359
affective disorders, heritability of, 387 AS. See anxiety sensitivity (AS) brominated flame retardants, low-dose
affiliation, defined, 5, 259. See also atrazine, low-dose effects of, 98 effects of, 98
social-affiliative relations and Attachment and Biobehavioral Catch-up bulimia nervosa (BN), 406
endocrine system (ABC) program, 168
aggression. See also hierarchy and attachment theory, 194, 219–20 C
testosterone; stress hormones, attention-deficit/hyperactivity disorder CAH. See congenital adrenal hyperplasia
physiology, and behavior (ADHD), 406, 421 (CAH)
defined, 286 attractiveness. See mate preferences calm-and-connect model, for OT, 323
female indirect aggression and rival across lifespan Canada, child morbidity/mortality, 185
derogation, 225–27 averageness in faces. See mate preferences cancer, due to in utero DES exposure, 93, 95
hierarchical rank among primates across lifespan CAR. See cortisol response following
and, 5 avoidant attachment style, 128, 219–20 awakening (CAR)
intrasexual competition and, 224–25 AVP. See vasopressin (AVP) Cercopithecidae families. See sex differences
male direct, 35–36 AVPR1A (vasopressin receptor 1a gene), in primate social relationships
male mating effort and, 131–32 261, 264–66 during development
pair-bonding vs. mate guarding and, cervical mucus consistency, 114, 117
341–42 B Challenge Hypothesis. See also
parental behavior and, 339–40 basal body temperature (BBT), 113–14, 117 competition, dominance,
as punishment, 219 Bayer Schering, 246 and social hierarchy
testosterone and, 4 behavior aggression in mating effort and, 131
aggression paradox, 340 parental (see parental behavior) biosocial model of status and, 282–84,
agoraphobia (AG), 405, 409, 416, 417, 419 reproductive (see headings at 300
alliance hypothesis, 344 reproductive behavior) future research and, 436
allocation trade-offs, defined, 319 social and affective (see social and mating vs. parenting paradoxes
allostatic load, 298 affective behavior) and testosterone, 187, 268–69,
American Medical Association, report on behavioral endocrinology, premises of, 1–2 337–39, 338f
LED streetlights, 375 behavior and psychology, introduction, origins of, 129–30
American Psychiatric Association, prevalence 1–9 Challenge Hypothesis (Wingfield, Hegner,
of transgender persons, 202 development and survival, 2–3 Ball, and Duffy), 186

446
chemicals. See endocrine disrupting conduct disorder, 162, 169, 170, 414 deference, defined, 297
chemicals (EDCs) and congenital adrenal hyperplasia (CAH), dehydroepiandrosterone (DHEA), 129,
hormone action 49–52, 204–5 148–50
child maltreatment. See maternal stress conspicuous consumption dehydroepiandrosterone sulfate
and child maltreatment intrasexual competition and, 223 (DHEAS), 129, 150
Child–Parent Psychotherapy (CPP), 169 social status and, 296 dendritic spines, 69
Child Trauma Questionnaire, 167 cooperative breeding social systems, Depo-Provera, 249
chlormadinone acetate (CMA), 248 180–81 depressive disorders. See also hormones
chronic stress, 354–56 co-option, defined, 319–20 and major depressive
circadian rhythms. See hormones, circadian corticosteroid-binding globulin, 17–18 disorder; major depressive
rhythms, and mental health corticosteroids, 1 disorder (MDD)
cisgender, defined, 202 corticotropin-releasing hormone child maltreatment and, 161, 168
CLOCK gene, 368–69, 368f, 370, 373, 374 (CRH), 351 circadian rhythms and, 372–73
clomipramine, 422 child maltreatment and, 163, 164, 165, HPA axis and, 170
COCs. See combined oral contraceptives 166–67, 168 incidence of, 381
(COCs) circadian rhythms and, 369 seasonal affective disorder vs., 372
coercive mating. See reproductive in fight-or-flight response, 271 DES. See diethylstilbestrol (DES)
behavior in human male major depressive disorder and, 383–85 despotic hierarchies, 357
cognition. See sex differences in cognition, cortisol. See also competition, dominance, developmental dyslexia, 52
and Organizational–Activational and social hierarchy; hormones and development and survival
Hypothesis; sex hormones in major depressive disorder; social defined, 2–3
learning and memory bond paradoxes; stress hormones, EDCs and (see endocrine disrupting
cognitive-behavioral therapy (CBT), physiology, and behavior chemicals (EDCs) and hormone
408, 410 allostatic load, 298 action)
Cognitive Reflection Test, 272 antisocial behaviors and, 5 learning and memory (see sex
Collaborative Study on Psychosocial assessment methods, 271–72 hormones in learning and
Problems in General child maltreatment and, 163–71 memory)
Healthcare, 408 chronic stress and, 356 life history traits and (see hormones
combat exposure, 414 future research and, 436 and life history traits)
combined oral contraceptives (COCs). major depressive disorder and, 369 primate social relationships and
See also synthetic hormones and prolonged activation of, 343 (see sex differences in primate
women’s mating psychology risk-taking behavior and, 272–73 social relationships during
future research and, 434–35 social-affiliative relations and, 5, 271–74 development)
mental rotation and, 55–56, 59 cortisol response following awakening sex differences in cognition (see sex
multiple brands in U.S., 242, 246 (CAR), 384–85, 386, 388 differences in cognition, and
PMDD and, 390 costly signaling. See male intrasexual Organizational–Activational
competition, defined, 297 competition Hypothesis)
competition, dominance, and social CPP. See Child–Parent Psychotherapy dexamethasone (DEX), 166–67, 168,
hierarchy, 295–315, 298f (CPP) 385–86
basal cortisol and social rank, 298–99 CRH. See corticotropin-releasing DEX/CRH test, 386, 387
competition, defined, 297 hormone (CRH) DHEA. See dehydroepiandrosterone
cortisol reactivity to status challenge, CRHR1 gene, 165, 166, 168 (DHEA)
299 Cross-National Epidemiology of Panic DHEAS. See dehydroepiandrosterone
dominance, defined, 297–98 Disorder study, 417 sulfate (DHEAS)
dual-hormone hypothesis and, 303–4 culling, in animal studies, 102 DHT. See dihydrotestosterone (DHT)
group dynamics and social network culture Diagnostic and Statistical Manual of Mental
analysis, 307–8 cultures of risk, 193 Disorders (DSM-V)
moderators of competition– honor cultures and mate guarding, agoraphobia, 416
testosterone links, 304–7, 305t 218–19 anxiety disorders, 407
role of trait competitiveness and, 307 organizational effects and, 49 major depressive disorder, 382
social hierarchy, defined, 295–97 social status in ancient Egypt burials, panic disorder, 416
testosterone, status, and status-seeking 295 social anxiety disorder, 410
behavior, 299–303 testosterone and marital status and, diarylpropionitrile (DPN), 46, 72, 75,
theoretical model for testosterone– 187–88 77–78
social status relationship, 307f Cushing’s syndrome, 355, 369 diethylstilbestrol (DES), 52–53
transient elevations in testosterone, CYP19 gene, 207 endocrine disruption by, 100, 205
308 low-dose effects of, 98
COMT gene, 422 D in utero exposure and cancer, 93, 95
conception risk. See ovulatory cycle, DADS (duration, attitude, dedication, in utero exposure and cognition, 53
research and methods and salience) model, 193 dihydrotestosterone (DHT), 43
conditional mating strategies, defined, declarative object memory, 73–76, 74f. dioxin, low-dose effects of, 98
126–27. See also reproductive See also sex hormones in learning direct paternal investment, defined, 180
behavior in human male and memory DNA methylation, 75

SUBJECT Index 447

DNA methyltransferase (DNMT) threshold of safe doses, 99–101 F
inhibitors, 75 varying definitions of EDC, 89–91 facial preferences. See mate preferences
domestic violence, 414 endocrine-disrupting chemicals, and across lifespan
dominance. See also competition, future research, 434 fatherhood. See evolution and human
dominance, and social hierarchy; Endocrine Disruption Knowledgebase fatherhood
hierarchy and testosterone; sex (FDA), 91 female intrasexual competition
differences in primate social endocrine disruptor, origin of term, 89 hormonal influences, 227–28
relationships during development; Endocrine Disruptor Screening Program indirect aggression and rival
stress hormones, physiology, and (EDSP), 90, 91t derogation, 225–27
behavior; trait dominance endocrine principles, 92–96 Female Sexual Function Index (FSFI), 246
defined, 297–98 action at low doses, 93–95, 94f female-to-male (FTM) transsexuals,
dual-hormone hypothesis, 303–4, action via specific binding to defined, 202
342–43, 357–58 receptors, 93 fertility. See also ovulatory cycle, research
hierarchies and rank, 356–58 coordination of tissues of body over and methods
male intrasexual competition and, lifetime, 93 facial attractiveness of women and,
224–25 effects dependent on life stage, 95 134–35
primate sex differences in quests for, nonlinear and nonmonotonic femininity and, 144–45
30–32 relationships between dose and fight-or-flight response, 271, 352–54.
social bonds and submission vs., effect, 95–96 See also cortisol
342–44 Endocrine Society, definition of EDC, finger-length ratio. See 2D:4D digit ratio
social dominance, 342 89–90, 91 fluvoxamine, 422
status hierarchies and, 284 Enovid, 246 fMRI. See functional magnetic resonance
DPN. See diarylpropionitrile (DPN) environmental chemicals, history of, imaging (fMRI)
drospirenone (DRSP), 248 88–89, 88f follicle-stimulating hormone (FSH), 355
DSM-V. See Diagnostic and Statistical environmental influences on hormone fostering/cross-fostering, in animal studies,
Manual of Mental Disorders action. See endocrine disrupting 102
(DSM-V) chemicals (EDCs) and hormone fraternal birth order effect, 207–8
dual-hormone hypothesis, of dominance, action frequency-dependent selection, 228–29
303–4, 342–43, 357–58 estradiol friendship, 336
dual-strategies theory, and status effects on object recognition memory, FSFI. See Female Sexual Function
hierarchies, 284 74–75 Index (FSFI)
function of, 43 FSH. See follicle-stimulating hormone
E parental behavior and, 269 (FSH)
early-life adversity. See maternal stress and social-affiliative relations and, 270 functional magnetic resonance imaging
child maltreatment estrogens, 1. See also hormones and major (fMRI)
EDCs. See endocrine disrupting chemicals depressive disorder; sex hormones of friendship and cortex activity, 336
(EDCs) and hormone action in learning and memory; of paternal neural activity, 191
EDSP. See Endocrine Disruptor Screening specific types of steroid-driven effects on brain
Program (EDSP) activational effects and, 47–48 function, 54–55
EE. See ethinylestradiol (EE) positive/negative effects of, 14–15
eminence, as high status in males, 225, 297 sex differences in cognition and, G
emotional abuse, of children, 162 52–57 GAD. See generalized anxiety disorder
emotional infidelity. See intersexual/ sexual dimorphism and, 144 (GAD)
intrasexual competition and ethinylestradiol (EE), 246–47, 248 GCs. See glucocorticoids (GCs)
jealousy European Union G. D. Searle & Company, 246
endocrine disrupting chemicals (EDCs) annual health care cost of EDCs, 102 gender dysphoria, 202
and hormone action, 3, 87–106 identification of EDCs, 90 gender identity, defined, 202. See also
controversies in study of EDCs, evolution and human fatherhood, 179–99 sexual orientation, gender identity
96–101 explanations for diversity of male and hormones
culling and fostering in studies, 102 caregiving, 192–94 generalized anxiety disorder (GAD), 407–9,
effects at low doses, 97–99 hormonal and neurobiological 413, 416, 417
endocrine principles and, 92–96 mechanisms and, 186–92 genetics. See also specific genes
exposure and health outcomes, 99 life history theory and, 182–86, 192 of OT-AVP system, 261
history of environmental chemicals, oxytocin and, 190–91 sexual orientation, gender identity
88–89, 88f paternal care, defined, 179–80 research and, 207
hormone action, defined, 92 phylogenetic distribution of paternal genistein, low-dose effects of, 98
housing and, 102 care, 180–82 glucocorticoid hormones
impacts of food and water, 101–2 prolactin and, 189–90 life history transitions and, 17
public health and, 102 social monogamy and, 180, 182 mate preferences and, 15–16
sexual orientation, gender identity testosterone and, 187–89 glucocorticoid mediated epigenetic
and, 205–6 evolutionary biology. See oxytocin, an programming, 16
sources of EDCs, 91 evolutionary framework glucocorticoid receptors (GRs), 163
stress and, 101 evolutionary psychology, premises of, 1–2 glucocorticoids (GCs), 351, 352, 354, 369

448 SUBJECT Index

gonadotropin-releasing hormone (GnRH), dual hormones of dominance, 303–4, Hot Sauce paradigm, 287
15, 355 342–43, 357–58 HPA. See hypothalamic-pituitary-adrenal
growth hormone (GH), 354–55 impact on brain and cognition, 43–44 (HPA) axis
GRs. See glucocorticoid receptors (GRs) mate preferences and, 4 HPG. See hypothalamic-pituitary-gonadal
variation of during menstrual cycle, (HPG) axis
H 267 HRT. See hormone replacement
handicap signaling, 223 hormones, circadian rhythms, and mental therapy (HRT)
Harvard/Brown Anxiety Research health, 367–79 human behavioral endocrinology,
Program (HARP) study, addiction and, 373–74 future directions, 433–41
408, 411 anxiety and, 373 development and survival, 433–34
height circadian regulation of glucocorticoids, reproductive behavior, 434–36
attractiveness and, 220, 222 369–70, 370f social and affective behavior, 436–37
growth hormone and, 354–55 circadian regulation of melatonin, Human Behavior and Evolution Society, 2
status and, 224–25 370–72, 373, 374 human species, closest genetic relatives
hierarchy. See also competition, circadian rhythms, defined, 368–69, of, 27
dominance, and social hierarchy 368f hyperarousal PTSD symptom cluster,
aggression and, 5 depression and, 372–73 414–15
defined, 281 disruption of, 372–74 hypercortisolism, 356
social hierarchy, defined, 295–97 seasonal rhythms and, 372 hypocortisolism, 356
hierarchy and testosterone, 281–93, 282n1 Hormones and Behavior (Beach), 2 hypogonadism and depression, 393
Challenge Hypothesis and biosocial hormones and life history traits, 13–26 hypothalamic-pituitary-adrenal (HPA)
model of status, 282–84 ageing and, 18–19 axis. See also hormones and
competition-induced surges in endocrine mediation and parental major depressive disorder; stress
testosterone, 283–86 investment and offspring fitness, hormones, physiology, and
endogenous testosterone surges, 284, 16–17 behavior
286 endocrine mediation and anxiety disorders and, 415
moderators of testosterone–behavior reproduction, 15–16 chronic stress and, 355–56
links, 288–89 endocrine reaction norms, 20–21, 20f depressive disorders and, 170
testosterone fluctuations and endocrine traits and reversible maternal stress and child
aggressive/antagonistic behavior, flexibility, 19f maltreatment, 161–68
286–88 evolutionary perspective on endocrine oxytocin and, 326–27
hoarding, 421 mediation, 19–21 vasopressin and, 163
Hominidae families. See sex differences in hormones as mediators of phenotypic hypothalamic-pituitary-gonadal (HPG)
primate social relationships during expression, 14–15 axis, 351. See also stress hormones,
development life history, defined, 13–14 physiology, and behavior
homosexual, use of term, 202 life history transitions and, 17–18 cortisol as disruptor of, 357
hormonal assessment, in estimation of hormones and major depressive disorder, in fight-or-flight response, 271
conception risk, 115–16, 117 381–404 functions of, 17–18
hormonal changes cortisol levels in high-risk youth, 387 mate preferences and, 15
anxiety disorders and, 5 cortisol response to psychosocial stress melatonin secretion and, 17
depressive disorders and, 5 in adults and, 385 suprachiasmatic nuclei, 367, 368, 369,
hormonal contraceptives. See synthetic estrogen and late luteal phase of 370f, 371, 374
hormones and women’s mating menstrual cycle and MDD, 389–90 testosterone and, 282n1
psychology estrogen fluctuations and, 389
hormonal IUD, 249 exogenous challenge studies in high- I
hormonal pleiotropy, defined, 318–19 risk youth, 387 ICS. See Intrasexual Competition
hormone action, defined, 92. See also HPA axis and, 383–85, 383f Scale (ICS)
endocrine disrupting chemicals HPA axis function prior to onset of identify-and-invest model, for OT, 324
(EDCs) and hormone action MDD, 386–87 immune system, and fight-or-flight
hormone replacement therapy (HRT) HPA axis response to stress in high- response, 352
future research and, 435 risk youth, 387–88 implant (contraceptive), 249
mate preferences and, 250–51 links between testosterone and MDD, implicit power motivation, 305–6
in menopause, 249–50 393–94 impulsivity, and cortisol, 272–73
sexual behavior and, 250 menopausal transition and, 391–92 independent vs. interdependent
hormones. See also sex hormones in neuroendocrine challenge studies in self-construal, 289
learning and memory; sex steroid adults and, 385–86 indirect paternal investment, defined, 180
hormones; sexual orientation, pregnancy and postpartum depression, infant defense, 336–40
gender identity and hormones; 390–91, 392 infanticide, 185
stress hormones, physiology, and reproductive MDD, 392 infidelity. See intersexual/intrasexual
behavior; synthetic hormones and studies linking cortisol to depression competition and jealousy
women’s mating psychology; symptoms, 388–89 in-group vs. out-group, 342
specific hormones testosterone in men and, 392–93 inhibitory avoidance, defined, 70
classes and characteristics of, 1 testosterone in women and, 393 insulin-like growth factor-1 (IGF-1), 18

SUBJECT Index 449

intermittent explosive disorder, 406 K man the hunter/provisioner
internal regulatory variables, defined, 319 Kinsey Scale, 202 hypothesis, 183
internal working models, 192–93, 194 MAO-A gene, 422
International Programme on Chemical L mate guarding, 218–19, 340, 341–42.
Safety (IPCS), definition of laboratory studies, environmental See also intersexual/intrasexual
EDC, 90 influences in, 101–2 competition and jealousy
intersex, defined, 202 learning, defined, 68. See also sex hormones mate preferences. See also ovulatory cycle,
intersexual/intrasexual competition and in learning and memory research and methods
jealousy, 215–36 LED lights, 375 future research and, 435
conflict between sexes, 216 lesbian, gay, bisexual, and transgender hormones and, 4
cross-cultural comparisons, in (LGBT) community, 201–2. HPG axis and, 15
intrasexual competition, 222 See also sexual orientation, mate preferences across lifespan, 143–59
female intrasexual competition, 225–28 gender identity and hormones evidence for hormonal associations in
hormonal and physical characteristics, LH. See luteinizing hormone (LH) adults, 145
in intrasexual competition, 222 life history, defined, 13–14 facial preferences and menopause,
individual differences in intrasexual life history theory. See also hormones and 152–54
competitiveness, 228–30 life history traits; reproductive facial preferences and parental features,
influence of life history and behavior in human male 151b
attachment, in intersexual allocation of resources, 318 facial preferences in infancy, 145–47
competition, 219–20 endocrine hormones and, 318–19 preferences across childhood and
intersexual competition, 216–21 human fatherhood and, 182–86, 192 puberty, 147–51, 149f
jealousy and intrasexual competition, r- versus K-strategy, 219, 225 traits typically preferred by adults,
221–22 live intruder tests, 341 143–45
jealousy-evoking events, 216–17 long-term depression (LTD), 68–69 maternal stress and child maltreatment,
jealousy in response to a rival, 221 long-term mating strategies. 161–77
male intrasexual competition, 222–25 See reproductive behavior animal models of early-life
mate guarding, in intersexual in human male maltreatment, 163–64
competition, 218–19 long-term potentiation (LTP), 68–69 definitions of maltreatment, 162
mate retention, in intersexual low dose, use of term, 97–98 HPA axis function in adults with
competition, 219 LTD. See long-term depression (LTD) maltreatment histories, 167–68
physical characteristics and intersexual luteinizing hormone (LH), 114, 116, 355 HPA axis in youth, 164–67
competition, 220 lutocyclin, 205 hypothalamic-pituitary-adrenal (HPA)
physical/hormonal characteristics and axis and, 161–68
intrasexual competition, 222 M intervention studies, 168–69
role of conception risk, in intersexual major depressive disorder (MDD). mental health disorders in adults with
competition, 217–18 See also hormones and major maltreatment histories, 169–70
sex differences and rival characteristics, depressive disorder physical health in adults with
221–22 adrenocorticotropic hormone and, maltreatment histories, 170–71
intersexual selection, 223 384–86 prevalence and risk factors for
interviewer ratings of sexual functioning circadian rhythms and, 372–73 maltreatment, 162–63
(IRSF), 246 comorbidity of, 406, 407, 413, 414, mating. See also reproductive behavior in
intranasal administration studies, 323n2 416, 417, 419, 421 human male; synthetic hormones
intrasexual competition, defined, 215. corticotropin-releasing hormone and, and women’s mating psychology
See also intersexual/intrasexual 383–85 affiliation vs. parenting and, 339–42
competition and jealousy; cortisol and, 369 hormonal fluctuations and, 3–4
ovulatory cycle, research DSM classification, 382 parenting vs., 337–39, 338f
and methods heritability study, 382 MDD. See major depressive disorder
Intrasexual Competition Scale (ICS), 229 major histocompatibility complex (MHC) (MDD)
intrinsically photosensitive retinal alleles, 110, 111, 144 medial amygdala
ganglion cells (ipRGCs), 367 male aromatase knockout (ArKO) mice, estrogenic effects on social recognition
Iowa gambling task, 130 79–80 and, 78–79
IPCS. See International Programme on male care. See evolution and human vasopressin and, 80
Chemical Safety (IPCS), fatherhood melatonin
definition of EDC male intrasexual competition, 222–25 circadian rhythms and, 370–72, 373,
ipRGCs. See intrinsically photosensitive costly signaling and, 223–24 374
retinal ganglion cells (ipRGCs) eminence and, 225 HPG axis and, 17
IRSF. See interviewer ratings of sexual physical dominance and aggression, Meliane, 248
functioning (IRSF) 224–25 memory consolidation, 68–69
IUD (intrauterine device), 249 male strategies. See reproductive behavior menopause
in human male defined, 249
J Maltreatment Classification System, 172 hormone replacement therapy in,
jealousy. See intersexual/intrasexual mammals, incidence and display of 249–51
competition and jealousy paternal care in, 180–81 major depressive disorder and, 391–92

450 SUBJECT Index

 mate facial preferences and, 152–54 National Toxicology Program, 98 social bond paradoxes; stress
spatial cognition in postmenopausal NCS. See National Comorbidity hormones, physiology, and
women, 57 Survey (NCS) behavior
menstrual cycle. See also ovulatory cycle, NESARC. See National Epidemiologic assessment methods, 260–61
research and methods Survey on Alcohol and Related fathering and, 190–91
COCs and, 239b, 239f Conditions (NESARC) future research and, 437
mental rotation and, 53–55, 55f Netherlands Study of Anxiety and genetics of OT-AVP system, 261
onset timing of menarche and anxiety Depression, 385 in mammalian birth process, 14
disorders, 411 neuropeptides and human relations, mother–offspring bond and, 320
variation in sex hormones and 259–66 the oxytocin paradox, 321–22
behavior during, 267 NIMH. See National Institute of Mental threat management and, 5
menstrual cycle paradigms, in studies, 53. Health (NIMH) oxytocin, an evolutionary framework,
See also ovulatory cycle, research 19-nortestosterone, 56 317–33
and methods nonalcoholic fatty liver disease, 93 allocation trade-offs, 319, 327–28
mental health disorders. See also hormones, nonmonotonic dose responses. conditional responsivity and internal
circadian rhythms, and mental See endocrine principles regulatory variables, 319
health; sex differences in anxiety nonpaternity rates, 135 endocrine hormones within life
disorders; specific disorders nonylphenol, low-dose effects of, 98 history theory framework, 318–19
child maltreatment and, 169–70 NSMHWB. See National Survey of function reverse engineering of
hormonal fluctuations and, 5 Mental Health and Well-Being hormonal coordination, 319
mental rotation. See also sex differences in (NSMHWB) functions of OT, 328f
cognition, and Organizational– integration of psychological and
Activational Hypothesis O physiological effects, 325–28
defined, 50 obesogens concept, 93 interactions with other hormones, 329
spatial memory and, 70 object memory, defined, 73. See also sex maternal brain in rats and, 321, 339
metamorphosis, 17 hormones in learning and memory neuromodulation as adaptive, 319
methoxychlor, low-dose effects of, 98 object memory task, 74f the oxytocin paradox, 321–22
MHC. See major histocompatibility object placement memory, 71–73. phylogeny and adaptation, 319–20
complex (MHC) alleles See also sex hormones in psychological effects and correlates,
mifepristone, 395 learning and memory 320–24
Million Woman Study, 249 object reversal, 48 range of co-opted relationships, 328–29
mineralocorticoid receptors (MRs), 163 obsessive-compulsive disorder (OCD), specialized design features, 328
Mini-K, 131 407, 409, 416, 419–23
mismatch effect, 306 opioids, 359 P
mixed mating strategies, defined, 126 OPN4 gene, 372 pair-bonding
monoamines, 1 opportunism in evolution, defined, 186 duration of lactation and paternal
monogamous marriage. See reproductive oral contraceptives. See combined oral care, 183–84
behavior in human male contraceptives (COCs); synthetic mate guarding vs, 341–42
mood disorders, 407, 413, 417 hormones and women’s mating mating vs., 341
Morris water maze, 46–47, 47f, 51, 58, psychology monogamous, 335–36, 341
69–71, 72, 73 orbitofrontal cortex, 52 oxytocin and, 190, 320, 323
MRs. See mineralocorticoid receptors Organizational–Activational Hypothesis. testosterone levels and, 134
(MRs) See also sex differences in panic disorder (PD), 405, 407, 409,
Multidimensional Treatment Foster Care for cognition, and Organizational– 416–19
Preschoolers (MTFC-P), 168–69 Activational Hypothesis panic disorder with agoraphobia (PDA),
current status of, 60–61 417
N future research and, 434 parental behavior. See also evolution and
naloxone, 359 origins of, 44–45 human fatherhood; maternal stress
National Academy of Sciences, low-dose on sex steroid hormones, 3 and child maltreatment
effects of EDCs study, 98 organizational effects, defined, 44 affiliation vs. mating and, 339–42
National Comorbidity Survey (NCS), OT. See oxytocin (OT) affiliative vs. aggressive behaviors in,
405, 406, 407, 411, 413, 417 ovulatory cycle, research and methods, 339–40
National Epidemiologic Survey on 109–23. See also menstrual cycle in human species, 30, 32, 37
Alcohol and Related Conditions conception risk and, 109–10 mating vs. parenting, 187, 268–69,
(NESARC), 408, 411 conception risk values, 116–17 337–39, 338f
National Institute of Mental Health cues to ovulation, 112–13 offspring fitness and, 16–17
(NIMH), Collaborative estimation of conception risk, 113–17 Parental Investment Theory and,
Psychiatric Epidemiology Studies preferences for male traits, 109–11 182, 215
(CPES) survey, 405, 406 sexual behavior and motivation, 111–12 reproductive behavior in human
National Institutes of Health, study on ovulatory shift hypothesis, 109–10 male and, 135–36
LED lights, 375 OXTR (oxytocin receptor gene), 262, 264 social-affiliative relations, endocrine
National Survey of Mental Health and oxytocin (OT), 1. See also social-affiliative system and, 261–62, 264
Well-Being (NSMHWB), 410 relations and endocrine system; Parental Bonding Instrument, 417

SUBJECT Index 451

Parental Investment Theory, 182, 215 prestige, as high status in females, 284, sexual orientation (see sexual
paternal care, defined, 179–80. See also 297 orientation, gender identity
evolution and human fatherhood primate species studies. See also sex and hormones)
paternal investment. See also evolution differences in primate social reproductive behavior in human male,
and human fatherhood relationships during development 125–41
direct vs. indirect, 180 behavioral sex differences, 3 adaptive plasticity in life history
endocrine mediation and, 16–17 hierarchical rank among, 5 strategies, 128
future research and, 435–36 incidence and display of paternal care aggression as manifestation of mating
in humans, 30, 32, 37 in, 181–82 effort, 131–32
varying definitions of, 180 priority-of-access model, 129 alternative mating strategies, 126–27
paternity uncertainty, 133, 135, 185 PRL. See prolactin (PRL) coercive mating strategies, 133
PD. See panic disorder (PD) progesterone, 43–44, 67 life history strategies, 127–28
PDA. See panic disorder with agoraphobia chronic stress and, 355 life history theory, 126
(PDA) oral contraceptives and, 248 long-term mating strategies, 134–35
peptide hormones, 1. See also headings at parental behavior and, 269 mate seeking, testosterone, and life
oxytocin social-affiliative relations and, 270–71 history strategy, 132–33
perchlorate, low-dose effects of, 98 progestin (P)-only pill, 246, 249 parenting effort, 135–36
pesticides, 88 progestins, 1 risk taking as function of life history
PFR. See Promoting First Relationships prolactin (PRL), 189–90, 340 strategy, 130
(PFR) Promoting First Relationships (PFR), 169 short-term mating as zero-sum
phenotypic integration, defined, 319 propyl pyrazole triol (PPT), 46, 72, 75, contest, 128–30
phthalates, 98, 100, 206 77–78, 80 reproductive MDD, 392
physical abuse, of children, 162 Provera, 249 retinohypothalamic tract (RHT), 367, 371
physical neglect, of children, 162 proximate explanations, defined, 2 risk-response model, 193
physiological trade-offs. See social bond psychosocial dwarfism, 354–55 risk sensitivity theory, 130
paradoxes PTSD. See posttraumatic stress disorder risk-taking behavior, and cortisol, 272–73
“the pill,” 238. See also combined oral (PTSD) rival derogation. See female intrasexual
contraceptives (COCs); synthetic public health competition
hormones and women’s mating endocrine disrupting chemicals Royal College of General Practitioners
psychology (EDCs) and, 102 Survey (1974), 241
pineal gland, and circadian rhythms, 371 pharmaceuticals in drinking water, 91
placebo-controlled design, 53 pure alternative mating strategies, S
plastic compounds, endocrine disruption defined, 126 SAD. See social anxiety disorder (SAD)
by, 205–6 salt-wasting CAH, 51
pleiotropy R same-sex peers. See sex differences in
hormonal, 318–19 radial-arm maze (RAM), 46–47, 47f, primate social relationships during
life history traits and, 14–15 69–71, 73 development
PMDD. See premenstrual dysphoric rank. See also competition, dominance, SDN-POA. See sexually dimorphic
disorder (PMDD) and social hierarchy; dominance nucleus in the preoptic area of
Point Subtraction Aggression Paradigm basal cortisol and social rank, 298–99 the hypothalamus (SDN-POA)
(PSAP), 285–88, 289 of eminence in males, 225, 297 seasonal affective disorder (SAD), 372
positional bias, 222 hierarchies and, 5, 356–58 seasonal and circadian rhythms, 372
postpartum depression, 390–91, 392, of prestige in females, 284, 297 selective serotonin reuptake inhibitor
409, 412 rape, during wartime, 130 (SSRI) antidepressants, 407–8,
posttraumatic stress disorder (PTSD) Reducing Unwanted Stress in the Home 409, 410, 413, 416–17, 420
child maltreatment and, 161, 165, (RUSH) program, 394 self-control, 289
167–68, 169–70 reproductive behavior. See also mating serial monogamy, 126
hypocortisolism and, 356 competition and jealousy serotonin (5-HT) dysregulation, 419
overview and epidemiology, 407, 412–13 (see intersexual/intrasexual serotonin–norepinephrine reuptake
sex differences in, 405, 413–16 competition and jealousy) inhibitor (SNRI) antidepressants,
vasopressin and, 265 defined, 3–4 407–8, 410, 413, 416
PPT. See propyl pyrazole triol (PPT) future research and, 434–36 serum/saliva assays, 53
pregnancy gender identity (see sexual sex development disorders, 202, 204
generalized anxiety disorder and, 409 orientation, gender identity sex differences in anxiety disorders, 405–32
obsessive-compulsive disorder and, 423 and hormones) generalized anxiety disorder, 407–9,
panic disorder and, 418 human fatherhood and (see evolution 413, 416, 417
postpartum depression and, 390–91, and human fatherhood) obsessive-compulsive disorder, 407,
392, 409, 412 mate preferences and (see mate 409, 416, 419–23
posttraumatic stress disorder and, 415 preferences across lifespan) panic disorder, 405, 407, 409, 416–19
social anxiety disorder and, 412 maternal stress and (see maternal posttraumatic stress disorder, 405,
Premarin, 249 stress and child maltreatment) 407, 412–16
premenstrual dysphoric disorder ovulatory cycle and (see ovulatory social anxiety disorder, 405, 407,
(PMDD), 389–90 cycle, research and methods) 409–12, 416, 421

452 SUBJECT Index

sex differences in cognition, and estrogenic enhancement of spatial sexual selection. See mate preferences;
Organizational–Activational memory in female rodents, 71 mating
Hypothesis, 43–66 estrogen receptors in estrogenic Shepard-Metzler stimuli, 50f
activational effects of sex steroids, 53 enhancement of spatial short-term mating strategies.
androgens and spatial cognition, memory, 72 See reproductive behavior in
50–53, 57–59 estrogens and social recognition, 77–78 human male
current status of Hypothesis, 60–61 neurohormonal control of social shoulder-to-hip ratio (SHR), 144, 221,
extra-hypothalamic brain areas and, learning, 78f, 80–81 224
45–48 progesterone and object recognition, show-off hypothesis, 183, 184
in humans, 48–50 75–76 sibling bonds, 336
impact of hormones on brain, 43–44 progesterone and social Silent Spring (Carson), 88–89
mental rotation and menstrual cycle, recognition, 79 simple-virilizing CAH, 51
53–55, 55f progesterone effects on spatial SNP rs53576, 262
mental rotation and oral contraceptive memory, 72–73 SNRI. See serotonin–norepinephrine
use, 55–56, 59 roles of estrogen receptors in object reuptake inhibitor (SNRI)
origins of Hypothesis, 44–45 recognition, 75 antidepressants
spatial cognition in postmenopausal social memory and, 76–81 social-affiliative relations and endocrine
women, 57 spatial memory and, 69–73, 70f system, 259–80
spatial working memory, 59, 60f sex segregation. See sex differences in cortisol and human relationships, 5,
study of activational hypothesis in primate social relationships during 271–74
humans, 53 development genetics of OT-AVP system, 261
study of congenital adrenal sex steroid hormones. See also sex intimate relationships, 262–66
hyperplasia, 49–52 differences in cognition, and neuropeptides and human relations,
sex differences in primate social Organizational–Activational 259–66
relationships during development, Hypothesis; specific hormones parental behavior, 261–62, 264
27–41 assessment methods, 266–68 peripheral assessment of OT and AVP,
interaction with adult males and, defined, 43 260
36–37 mating and, 4 pharmacological manipulation of OT
interaction with infants and, 37 Organizational-Activational (and AVP), 260
interaction with same-sex peers and, Hypothesis on, 3 sex hormones and, 266–71
33–36 phases of, 94 social and affective behavior
male direct aggression, 35–36 secondary sexual traits and, 15 defined, 4–5
physical/verbal contact with mothers sex differences and, 3 future research and, 436–37
and, 32–33 in sexual orientation and gender hierarchy and (see hierarchy and
quests for dominance and status, identity, 203–5 testosterone)
30–32 social-affiliative relations and, 266–71 mental health and (see hormones,
residence patterns and, 29 variation in during menstrual circadian rhythms, and mental
social play and, 35 cycle, 267 health; hormones and major
social structure and, 28 sexual abuse, of children, 162, 165, 170, depressive disorder; sex differences
stages of development and, 28 355, 413–14 in anxiety disorders)
sex hormones in learning and memory, 3, sexual coercion. See also reproductive oxytocin and (see oxytocin, an
67–85 behavior in human male evolutionary framework)
androgen-mediated effects on spatial mate retention and, 219 social-affiliative relations and
memory, 73 sexual dimorphism, 144, 147 (see social-affiliative relations
androgens and social recognition in in great apes, 182 and endocrine system)
male rodents, 79–80 sexual intimacy. See social bond paradoxes social bond and (see social bond
brain regions involved in estrogenic sexually dimorphic nucleus in the paradoxes)
facilitation of social recognition, preoptic area of the hypothalamus social hierarchy and (see competition,
78–79 (SDN-POA), 45, 208–9 dominance, and social hierarchy)
declarative object memory and, sexually transmitted infections (STIs), 219 stress hormones and (see stress
73–76, 74f sexual orientation, gender identity and hormones, physiology, and
endogenous hormones and rodent hormones, 201–14 behavior)
object recognition, 74 birth order studies, 207–8 social anxiety disorder (SAD), 405, 407,
endogenous hormones and spatial brain research, 208–10 409–12, 416, 421
memory, 70–71 circulating hormones and, 203 social bond paradoxes, 335–50
endogenous hormones in rodent social finger-length ratio, 208 affiliation vs. parenting and mating,
recognition and social learning, 77 genetics and, 207 339–42
estradiol effects on object recognition pharmaceuticals and EDCs, 205–6 affiliative vs. aggressive behaviors in
memory, 74–75 prenatal exposure to endogenous parenting, 339–40
estrogen action in hippocampus, hormones and, 203–5 aggression paradox, 340
71–72 prenatal stress and, 206–7 Challenge Hypothesis and paradoxes,
estrogenic action in hippocampus for research limitations, 202–3 337–39, 338f
object recognition memory, 75 terminology, 201–2 dominance vs. submission, 342–44

SUBJECT Index 453

social bond paradoxes (cont.) “State of the Science of Endocrine “the pill,” 238
dual hormones of dominance, 303–4, Disrupting Chemicals – 2012” sexual behavior and COCs, 241–42,
342–43, 357–58 (UNEP/WHO), 97 243t, 246
in-group vs. out-group, 342 status. See also competition, dominance, systematic review methodologies, 102
maintenance of multiple social and social hierarchy; dominance
attachments, 344–45 height and, 224–25 T
mating vs. parenting, 337–39 primate quests for dominance and, tall poppy syndrome, 226, 229
pair-bonding vs. mate guarding, 341–42 30–32 Tanner classification images, 150
pair-bonding vs. mating, 341 social dominance and dominance TCAs. See tricyclic antidepressants
paradoxes as trade-offs, 337–39 hierarchies, 356–58 (TCAs)
postpartum estrus vs. infant care, 340–41 social media and, 296 telomere length, 18–19
social bonds, defined, 335–36 social status, defined, 297 tend-and-befriend model
social dominance, defined, 342 testosterone and status-seeking cortisol and, 273–74
social paradoxes, 336 behavior, 299–303 fight-or-flight vs., 352–54
social bonds, defined, 335–36 status hierarchies. See competition, oxytocin and, 323
social buffering. See stress hormones, dominance, and social hierarchy; testosterone, 43. See also hierarchy and
physiology, and behavior hierarchy and testosterone testosterone; reproductive behavior
social cognition, and cortisol, 273 status instability hypothesis, 306 in human male; social bond
social comparison theory, 307 steroid receptors, 44 paradoxes
social dominance, defined, 342. See also steroids, 1 aggression and, 4
stress hormones, physiology, STIs. See sexually transmitted infections antisocial behaviors and, 5
and behavior (STIs) declines with ageing, 392
social hierarchy, defined, 295–97 Strange Situation test, 168 fathering and, 187–89
social learning, defined, 76 strategic pluralism, 229 future research and, 436
social media and status, 296 strategy, use of term, 126n3 in hormone replacement therapy, 250
social memory, defined, 76. See also sex stress affiliation model, 353–54, 354f HPG axis and, 282n1
hormones in learning and memory “stress eating” phenomenon, 14 immune function and, 129
social monogamy. See evolution and stress hormones, and future research, 437 intimate relationships and, 268
human fatherhood stress hormones, physiology, and behavior, mating and, 4
social network analysis, 304 351–65 parental behavior and, 268–69
social play. See sex differences in primate acute stress response, 351–54 during postnatal infant period, 52
social relationships during chronic stress, 354–56 prolonged activation of, 342–43
development fight-or-flight vs. tend-and-befriend, sexual dimorphism and, 144
social recognition 352–54 social-affiliative relations and, 270
defined, 76, 77f social buffering and brain opioid status and status-seeking behavior,
estrogenic effects on, 78–79 systems, 359 299–303
vasopressin and, 79–80 social buffering and OT/AVP, 358–59 testosterone-relationship cycle model, 133
social relationships. See sex differences in status, social dominance and tic disorder, 420–21
primate social relationships during dominance hierarchies, 356–58 T-maze, 73
development stress affiliation model, 354f Tracking Adolescents’ Individual Lives
social salience hypothesis, for OT, 322 stressor exposure, and telomere length, Survey (TRAILS), 386
social status, defined, 297 18–19 trade-offs. See hormones and life history
social-support-seeking response. substance use disorder, 406 traits; oxytocin, an evolutionary
See tend-and-befriend model suprachiasmatic nuclei (SCN). See framework; social bond paradoxes
Society for Behavioral hypothalamic-pituitary-gonadal trait dominance, 289, 301, 306, 307
Neuroendocrinology, 2 (HPG) axis transactional developmental theories, 382
somatoform pain disorder, 414, 417 symmetry in faces. See mate preferences transgender, defined, 202
SP. See specific phobia (SP) across lifespan transman, use of term, 202
the spare receptor hypothesis, 94 synthetic hormones and women’s mating transsexual, defined, 202
spatial cognition, 49, 50–53, 57 psychology, 237–56 transvaginal ultrasonography, 113–14, 116
spatial learning, 46–48 effects of dosage, formulation, and transwoman, use of term, 202
spatial memory, defined, 69 administration, 247–49 tricyclic antidepressants (TCAs), 417
spatial working memory, 48, 59, 60f hormone replacement therapy and Trier Social Stress Test (TSST), 166, 167,
Spatial Working Memory task (SPWM), mate preferences, 250–51 271, 299, 385, 387–88
59, 60f hormone replacement therapy and Trivers-Willard hypothesis, 32, 215
specific phobia (SP), 405 sexual behavior, 250 trust games, experimental, 321
S/P theory (steroid/peptide theory of hormone replacement therapy in twin studies
social bonds), 337–39, 338f, 341 menopause, 249–50 congenital adrenal hyperplasia, 49, 51
SRD5A2 gene, 207 mate preferences and COCs, 240–41 emotional and sexual jealousy, 220
SRY gene, 207 mechanism of hormonal heritability of MDD, 382
SSRI. See selective serotonin reuptake contraceptives, 238, 239b, 239f low-dose effects in intrauterine
inhibitor (SSRI) antidepressants other aspects of relationship behavior, hormone exposure, 97
Standard Cross-Cultural Sample, 193 246–47 rs11174811 and drug use disorder, 265

454 SUBJECT Index

2D:4D digit ratio, 49–50, 51, 208, Endocrine Disruptor Screening W
222, 246 Program (EDSP), 90, 91t waist–hip ratio (WHR), 144, 145, 147, 221
type 2 diabetes, 93 U.S. Food and Drug Administration (FDA) WAY-200070, 80
approval of Enovid, 246 WHO. See World Health Organization
U discontinuance of DES, 205 (WHO)
ultimate explanations, defined, 2 Endocrine Disruption Knowledgebase, Wingspread Conference Center
United Nations Environment Programme 91 (1991), 89
(UNEP), “State of the Science U.S. Veterans Affairs (VA), study on winner–loser effect, 131–32, 302
of Endocrine Disrupting PTSD, 414, 416 within-subject designs, 53, 110, 115, 117,
Chemicals – 2012,” 97 434, 435
United States V Women’s Health Initiative, 249
annual health care cost of EDCs, 102 V1aR gene, 339 World Health Organization (WHO)
child morbidity/mortality, 185 vaginal ring, 246 EDC, defined, 90
incidence of anxiety disorders, 372, Vandenberg and Kuse Mental Rotations Global Burden of Disease study
405 Test, 50f, 56, 58–59 (2000), 381
incidence of child maltreatment, 162 variable foraging demand (VFD) model, “State of the Science of
incidence of long-lasting 164 Endocrine Disrupting Chemicals
contraceptive use, 248 vasopressin (AVP). See also social-affiliative – 2012,” 97
incidence of use of the pill, 238 relations and endocrine system; study on GAD in primary care
military veterans study on testosterone social bond paradoxes settings, 407
and marriage, 187 assessment methods, 260–61
serial monogamy, 126 genetics of OT-AVP system, 261 Y
stressor exposure, socioeconomic HPA axis and, 163 Yasmin, 248
status and life expectancy, 18–19 social-affiliative relations and, 259–60, Y-maze, 73, 78
U.S. Army, study on cortisol-testosterone 264, 265, 336 young male syndrome, 128
interaction in veterans, 304 social recognition and, 79–80 youth, high-risk and depression, 387–88
U.S. Environmental Protection venlafaxine extended-release (ER), 413,
Agency(EPA) 415, 416–17 Z
EDC, defined, 89, 90 ventral tegmental area (VTA), 374 zero-acquaintance paradigm, 224

SUBJECT Index 455