Menstrual disorders

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Menstrual Disorders
Dr.Ahmed Rashad
PGY2 Family Medicine
Under Supervision of
Dr.Leena Kadhem

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Objectives
 To understand the physiology of the normal menstrual cycle
 To know definition and types of abnormal uterine bleeding
 How to approach a case of abnormal uterine bleeding
 Amenorrhea; types and causes
 Dysmenorrhea; types and management
 When to refer to secondary care

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Introduction
 Menstrual disorders and abnormal uterine bleeding (AUB)
are among the most frequent gynecologic complaints. [1]
 Menstrual disorders frequently affect the quality of life of
adolescents and young adult women and can be indicators of
serious underlying problems.

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Normal Menstrual Cycle
 The normal menstrual cycle is a tightly coordinated cycle of
stimulatory and inhibitory effects that results in the release of
a single mature oocyte from a pool of hundreds of
thousands of primordial oocytes.

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 The average adult menstrual cycle is 28 days, with a range of
24 to 35 days , and lasts four to six days.
 The median blood loss during each menstrual period is 30
mL; the upper limit of normal is 80 mL.

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CASE 1
A 35-year-old female presents to your office with concerns
about heavy menstrual periods for the past year that occur at
irregular intervals. She explains that sometimes her menses
comes twice a month but other times will skip 2 months in a
row. Her menses may last 7 to 10 days and require 10 to 15
thick sanitary napkins on the heaviest days. She admits to some
fatigue, but she denies any lightheadedness. She has no pain
with menses or intercourse. She denies any vaginal discharge
or any other symptoms. She is a nonsmoker. She has had
normal Pap smears in the past. She is in a stable monogamous
relationship with her husband and denies a history of sexually
transmitted infections (STIs). On physical examination, her
blood pressure is 120/80 mmHg and her body mass index
(BMI) is 32. Her physical examination is normal, including
pelvic exam.

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 The patient’s bleeding pattern is best described as …?
 The most likely diagnosis is …?
 What is the most likely underlying mechanism for
this patient’s abnormal bleeding?

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Definition
Abnormal uterine bleeding refers to uterine bleeding outside
of the parameters noted below :
 Duration greater than eight days
 Flow greater than 80 mL/cycle or subjective impression of
heavier-than-normal flow (ie, more than six full pads or
tampons per day)
 Occur more frequently than every 24 days or less frequently
than every 38 days
 Intermenstrual bleeding or postcoital spotting
 Absence of menses

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 Oligomenorrhea: menstruation occurring with intervals of more than
35 days
 Polymenorrhea: menstruation occurring regularly with intervals of less
than 21 days
 Metrorrhagia: menstrual bleeding occurring at irregular intervals or
bleeding between menstrual cycles
 Menorrhagia: regular menstrual cycles with excessive flow (technically
more than 80 mL of volume) or menstruation lasting more than 7 days
 Menometrorrhagia: menstrual bleeding occurring at irregular intervals
with excessive flow or duration

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Prevalence and Impact
 In population-based studies, approximately 10 to 35 percent
of women report having menorrhagia. [2-4]
 Menorrhagia is a common reason for referral to a
gynecologist .
 Iron deficiency anemia develops in 21 to 67 percent of cases.
[2]
 Excessive and irregular bleeding can affect the quality of
life. Absenteeism from work or school is bothersome to
many women and bleeding may also interfere with sexual
activity.

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Causes throughout Woman’s
Lifetime

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Abnormal
Uterine Bleeding
Anovulatory Ovulatory

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Anovulatory Uterine Bleeding

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Pathophysiology
 Estrogen breakthrough bleeding
Anovulatory cycles have no corpus luteal formation.
Progesterone is not produced.The endometrium continues to
proliferate under the influence of unopposed estrogen.
 Estrogen withdrawal bleeding
This frequently occurs in women approaching the end of
reproductive life. Ovarian follicles in these women secrete less
estradiol. Fluctuating estradiol levels might lead to insufficient
endometrial proliferation with irregular menstrual shedding.

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In anovulatory
cycles, the
follicular
growth occurs
with the
stimulation
from FSH;
however, due to
lack of LH
surge, ovulation
fails to occur.
Ovary fails to
secrete
progesterone,
although
estrogen
production
continues
Continuous,
unopposed E
stimulation of
endometrium
Endometrium
becomes
excessively
vascular
without stromal
support
Fragility and
irregular
endometrial
bleeding

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Causes
 In Adolescents
Failure occurs secondary to delayed maturation of the
hypothalamic-pituitary axis. Normal in 1-2 years after
menarche.
 Peri-menopausal
Anovulatory bleeding in menopausal transition is related to
declining ovarian follicular function.

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 Approximately 6 to 10 percent of women with anovulation
have underlying polycystic ovary syndrome.
 Uncontrolled diabetes mellitus, hypo- or hyperthyroidism,
and hyperprolactinemia also may cause anovulation by
interfering with the hypothalamic-pituitary-ovarian axis.
 Antiepileptics (especially valproic acid [Depakene]) may
cause weight gain, hyperandrogenism, and anovulation.
 Use of typical antipsychotics (e.g., haloperidol), and some
atypical antipsychotics (e.g. risperidone [Risperdal]) may
contribute to anovulation by raising prolactin levels

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Evaluation
 First, whom to evaluate ?
Patients with irregular cycles who should be evaluated include
a) adolescents with consistently more than three months
between cycles or
b) those with irregular cycles for more than three years [3];
c) women who are likely perimenopausal and have increased
volume or duration of bleeding over baseline.

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 Initial evaluation of anovulatory uterine bleeding should
include
a) Confirm a uterine source of bleeding on physical
examination
b) Perform a pregnancy test.
c) Assess whether the woman is pre- or postmenopausal.
d) Evaluate the pattern, volume, and duration of blood loss.

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e) Assess ovulation:
• Ovulation can generally be documented clinically, based on
regular cyclic menses with molimina (eg, breast tenderness,
bloating or pelvic discomfort, mood changes, thin vaginal
discharge), or
• can be confirmed by a serum progesterone level measured
in the presumed luteal phase of the menstrual cycle; in most
laboratories, a level of >4 ng/dL confirms ovulation.
f) Perform laboratory testing for anemia
g) Perform pelvic sonography to assess for uterine or other
reproductive tract abnormalities that may contribute to
uterine bleeding.

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g) ACOG recommends endometrial tissue assessment to rule
out cancer in
i. in adolescents and in women younger than 35 years with
prolonged unopposed estrogen stimulation,
ii. women 35 years or older with suspected anovulatory
bleeding, and
iii. women unresponsive to medical therapy

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 Ovulatory abnormal uterine bleeding, or menorrhagia,
presents as bleeding that occurs at normal, regular intervals
but that is excessive in volume or duration.

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Etiologies
 Bleeding disorder
i. Factor deficiency
ii. Leukemia
iii. Platelet disorder
iv. von Willebrand disease
 Hypothyroidism
 Liver disease, advanced
 Structural lesions
i. Fibroids
ii. Polyps

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Bleeding disorders
Suspected if :
i. Menorrhagia since menarche
ii. Family history of bleeding disorders
iii. Personal history of 1 or more of the following:
• Notable bruising without known injury
• Bleeding of oral cavity or gastrointestinal tract without obvious
lesion
• Epistaxis greater than 10 minutes duration (possibly necessitating
packing or cautery.

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CASE 2
A 27-year-old nulligravida female presents to your office for
routine exam. Upon gynecological history, you discover that
she has a 5-year history of oligomenorrhea, with only
approximately two or three menses a year. She denies
intercycle spotting or premenstrual symptoms. Her last menses
was 3 months ago. Her blood pressure is 120/75 mmHg and her
BMI is 34. Her physical exam reveals a moderate amount of
facial hair and facial acne. Her pelvic examination is
unremarkable

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 What condition do you suspect in this patient?
 What are the treatment options ?

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Definition and types
 Primary amenorrhea is defined as the absence of menses at:
i. age 16 in the presence of normal growth and secondary
sexual characteristics,or
ii. age 14, if no menses have occurred and there is an
absence of secondary sexual characteristics.
 Secondary amenorrhea is the absence of menses for three
months in women with previously normal menstruation and
for nine months in women with previous oligomenorrhea.

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Etiology of 1ry Amenorrhea
Hypothalamic and Pituitary causes
① Functional hypothalamic amenorrhea.
• Abnormal hypothalamic gonadotropin-releasing hormone
(GnRH) secretion  decreased gonadotropin pulsations
i. absent LH surges
ii. absence of normal follicular development
iii. anovulation.
• Multiple factors may contribute to the pathogenesis of
functional hypothalamic amenorrhea, including eating
disorders (such as anorexia nervosa), exercise, and stress

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② Congenital GnRH deficiency or idiopathic
hypogonadotropic hypogonadism
Kallmann’s Syndrome ?
③ Constitutional delay of puberty
• characterized by both delayed adrenarche and
gonadarche.
④ Hyperprolactinemia

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Ovarian Causes
① Gonadal dysgenesis
② Turner syndrome
③ Polycystic ovary syndrome
④ Premature ovarian failure
• Loss of ovarian function before age of 40
• Idiopathic, but maybe related to a variant gene.

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Congenital disorders of the uterus and vagina
①Müllerian agenesis causes approximately 15 percent of
primary amenorrhea.[4]
②Imperforate hymen
③Transverse vaginal septum

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Diagnosis
History
 Detailed history of pubertal development
 Family history of menarche, pubertal development
 History of weight loss, stress, exercise (athletic activity)
 Detailed dietary history
 History of contraception,medications
 History suggestive of CNS disease (eg, headaches, visual
changes)
 History of chronic illnesses (eg, Crohn disease)

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Physical examination
 Height, weight, and growth charts
 Breast development, pubic hair
 Syndromic appearance (eg, short stature, webbed neck)
 Visual fields, thorough neurologic examination, optic fundi
 Evidence of hyperandrogenism (eg, acne, hirsutism,
clitoromegaly)
 Evidence of thyroid disease
 Evidence of chronic illnesses
 Evidence of pregnancy

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Evaluation
Primary amenorrhea is evaluated most efficiently by focusing
on the
a) presence or absence of breast development (a marker of
estrogen action and therefore function of the ovary),
b) the presence or absence of the uterus (as determined by
ultrasound, or in more complex cases by magnetic
resonance imaging)
c) and the follicle-stimulating hormone (FSH) level.

+Etiology of 2ry Amenorrhea
 PREGNANCY is the most common cause of
secondary amenorrhea.
 Hypothalamic dysfunction
① Functional hypothalamic amenorrhea
② Inflammatory or infiltrative diseases
(eg.Lymphoma)
③ Brain tumors (i.e. Craniopharyngioma)
④ Cranial irradiation
⑤ Pituitary stalk dissection or compression

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Pituitary dysfunction
① Hyperprolactinemia
• Prolactinomas account for 20% of secondary amenorrhea
• Account for 90% of secondary amenorrhea due to
pituitary problems
② Pituitary tumors
• Acromegaly
• Corticotroph adenomas (i.e. Cushing’s disease)
• Meningioma (of the sella), germinoma, glioma
③ Empty sella syndrome
④ Pituitary infarct/pituitary apoplexy
• Sheehan’s syndrome

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 Ovarian dysfunction
• Menopause: defined as 12 months of amenorrhea in a
woman over age 45 in the absence of other biological or
physiological causes.
• Premature ovarian failure
• Surgical removal
• Polycystic ovarian disease

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 Uterine causes
① Acquired scarring of the endometrium
• due to instrumentation e.g. Asherman’s Syndrome
• due to infection eg. tuberculosis
① Cervical stenosis, often due to instrumentation

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Prolactin ≤ 100 ng per mL (100 mcg per L)
Altered metabolism
Liver failure
Renal failure
Ectopic production
Bronchogenic (e.g., carcinoma)
Breastfeeding
Prolactin > 100 ng per mL
Empty sella syndrome
Pituitary adenoma

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CASE 3
A 15-year-old nulligravida female presents with her
mother for evaluation of painful periods. Menarche was
at age 14. Her periods are typically every 4–8 weeks and
are very painful. She has missed 1–2 days of school with
each menses because of the severe pain and has been
suspended from the volleyball team because of missed
practices. She denies intercourse. She has never had a
pelvic examination. Her review of systems is otherwise
negative.

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 What is the MOST likely etiology of her
irregular cycles?
 What is the etiology?
 What is the best first-line treatment for this
patient?

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Definition and types
 Dysmenorrhea is defined as difficult menstrual flow or
painful menstruation. It is one of the most common
gynecologic complaints in young women who present to
clinicians.[5]
 Dysmenorrhea can be divided into 2 broad categories:
primary (spasmodic) and secondary (congestive).

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Primary dysmenorrhea
 Primary dysmenorrhea is defined as menstrual pain that is
not associated with macroscopic pelvic pathology.
 It typically occurs in the first few years after menarche[6]and
affects as many as 50% of postpubertal females.
 In an epidemiologic study of an adolescent population (age
range, 12-17 years), reported that dysmenorrhea had a
prevalence of 59.7%. [7]

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Risk factors
 Early age at menarche (< 12 years)
 Nulliparity
 Heavy or prolonged menstrual flow
 Smoking
 Positive family history
 Obesity

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Pathophysiology
 Current evidence suggests that the pathogenesis of primary
dysmenorrhea is due to prostaglandin F2α (PGF2α), a potent
myometrial stimulant and vasoconstrictor, in the secretory
endometrium. [8]

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Treatment
 Treatment is directed at providing relief from the cramping
pelvic pain and associated symptoms .
 Nonsteroidal anti-inflammatory drugs (NSAIDs) are the best-
established initial therapy for dysmenorrhea. [9] They
decrease menstrual pain by lowering prostaglandin F2α
(PGF2α) levels in menstrual fluid.
 Oral Contraceptives also relieve symptoms, particularly if
contraception is required.

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Secondary dysmenorrhea
 Less common than primary dysmenorrhea
 It is associated with pelvic pathology
 It tends to occur several years after the menarche
 The woman may complain of a change in the timing and
intensity of her pain
 The pain may last throughout menstruation
 The pain may be associated with discomfort before the onset
of menstruation.

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Causes
 Leiomyomata (fibroids)
 PID
 Tubo-ovarian abscess
 Endometriosis

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Management
 Treatment of secondary dysmenorrhea involves correction of
the underlying organic cause.
 Specific measures (medical or surgical) may be required to
treat pelvic pathologic conditions (eg, endometriosis) and to
ameliorate the associated dysmenorrhea

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Resources
 [1] Caufriez A. Menstrual disorders in adolescence: pathophysiology and treatment. Horm Res 1991; 36:156.
 [2]Côté I, Jacobs P, Cumming DC. Use of health services associated with increased menstrual loss in the United States. Am J Obstet Gynecol 2003;
188:343.
 [3]Santer M, Warner P, Wyke S. A Scottish postal survey suggested that the prevailing clinical preoccupation with heavy periods does not reflect the
epidemiology of reported symptoms and problems. J Clin Epidemiol 2005; 58:1206.
 [4]Shapley M, Jordan K, Croft PR. An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract 2004; 54:359.
 [3] Speroff L, Fritz MA. Amenorrhea. In: Clinical gynecologic endocrinology and infertility. 7th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins,
2005;401–64.
 [4] ACOG Committee on Practice Bulletins—Gynecology. American College of Obstetricians and Gynecologists. ACOG practice bulletin: management
of anovulatory bleeding. Int J Gynaecol Obstet. 2001;72(3):263–271.
 [5] Hallberg L, Högdahl AM, Nilsson L, Rybo G. Menstrual blood loss--a population study. Variation at different ages and attempts to define normality.
Acta Obstet Gynecol Scand 1966; 45:320.
 [6]Diaz A, Laufer MR, Breech LL; American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists
Committee on Adolescent Health Care. Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics. 2006;118(5):2245–
2250.
 [[7] Klein JR, Litt IF. Epidemiology of adolescent dysmenorrhea. Pediatrics. Nov 1981;68(5):661-4
 [8] Willman EA, Collins WP, Clayton SG. Studies in the involvement of prostaglandins in uterine symptomatology and pathology. Br J Obstet Gynaecol.
May 1976;83(5):337-41
 [8] Slap GB. Menstrual disorders in adolescence. Best Pract Res Clin Obstet Gynaecol 2003; 17:75.
 [9] Proctor M, Farquhar C. Dysmenorrhoea. Clin Evid. 2002;(7):1639–53.

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