INDEX
• Delayed puberty
•Precocious puberty
• Heterosexual puberty
• Puberty menorrhagia
• Growth problems in puberty
3.
INTRODUCTION
NORMAL PUBERTY
• Pubertyis the period during which secondary sexual characteristics(SSC)
develop and capability for sexual reproduction is attained
ORDER OF PUBERTY
Growth spurt Thelarche (8yrs) Adrenarche (8yr) menarche (10-16 yrs)
HORMONAL CHANGES
• Levels of gonadotropins are low due to negative feedback of estrogen to HPO
axis (gonadostat) prior to puberty
• Thyroid gland has an active role in maturation of HPO axis
• Gondarche : Increased amplitude and frequency of GnRH increased FSH
and LH ovarian follicle development increased estrogen
• Kisspeptin : GnRH pulse generator
CHANGES IN GENITAL ORGANS
Uterus: cervix is 1:2 at birth becomes 1:1 when menarche ocurs
DELAYED PUBERTY
• Definedas failure of pubarche by 13-14 years
and menarche by 16 years
• Most common cause constitutional delay
13.
A.ANATOMIC ABNORMALITIES OFOUTFLOW TRACT
• Most common cause is imperforate hymen leading to
hematocolpos and hematometra associated with cyclic vague
abdominal pain
• Disorders of outflow tract occur as a part of syndrome ( MRKH
syndrome) associated with Mullerian aplasia
15.
B.HYPERGONADOTROPIC HYPOGONADISM
1.TURNER SYNDROME
•Phenotypic females with complete or absence of secondary
sexual characteristics
• 45XO karytotype
• Caused due to non disjunction due to which an abnormal
egg(empty egg) unites with a normal sperm thus embryo end
up missing one chromosome
• Mosaic variants also seen
17.
Clinical features :
General
-Shortstature (<150 cm) due absence of SHOX
gene
-Webbing of neck, lymphedema, low hair line.
- Wide shield shaped chest
- Shortened 4th
metacarpal
18.
• Reproductive system
-Poordevelopment of secondary sexual characteristics
-Uterus, vagina and fallopian tubes are small
-Streak ovaries - no potential to produce hormone
• Cardiovascular system
-Coarctation of aorta Hypertension
-Bicuspid aortic valve
-Thoracic aortic aneurysm (aortic root dilatation)
-Horse shoe kidneys (due to abnormal migration)
-Associated with autoimmune disorders :
hypothyroid,DM
19.
INVESTIGATIONS
- Absence ofBarr body
-Serum E2 is very low
- FSH and LH elevated
-Karyotyping : Reveals 45 XO
-
20.
Treatment : exogenousGH for growth
Gonadal steroids ( exogenous estrogen ) at 12-14 years
Add progesterone to low dose estrogen after some cycles
-Follow up : Annual cardiac MRI
Audiogram every 3-5 years ( Sensorineural hearing loss)
Screen for DM,Thyroid function,Lipid profile, RFT,LFT
DEXA anually for bone densitometry
2. GONADAL DYSGENSIS
-PURE GONADAL DYSGENESIS
• Primary amenorrhea with delayed SSC
• Streak ovaries
• Infantile uterus,tubes and vagina
• Karytoytype 46 XX or 46 XY
• FSH raised
• Treatment is low dose estrogen (0.625 mg) with
progestin 5mg daily for 25 days after 13 years of
age
23.
SWEYER SYNDOME (Completegonadal dysgenesis)
• 46 XY dysgenesis
• Mutation in SRY gene
• Streak testis which does not produce AMH or
androgens
• External and internal genitalia are of female
• SSC absent with primary amenorrhea
• Ectopic testis with increased risk of malignancy
25.
C.HYPOGONADOTROPIC HYPOGONADISM
• MCCconstitutional delay
• Kallmann syndrome:
- X linked recessive syndrome (KAL 1 gene)
- Partial or complete absence of olfactory bulb
- Failure of migration of GnRH neurons
- Triad of anosmia, hypogonadism and color
blindness
26.
- Associated withcerebellar ataxia, unilateral renal
agenesis, optic atrophy ,epilepsy and sensorineural
hearing loss
- MRI : olfactory bulbs and sulci (grooves) are either
absent or underdeveloped
- Diagnosed by genetic testing
- Treatment :
• Menstruation induced with combined estrogen and
progesterone therapy
• Induce ovulation with exogenous gonadotropins
PRECOCIOUS PUBERTY
• DevelopSSC before 8 years of age and menarche
before 10 years
• 90 % idiopathic in girls and 10% idiopathic boys
- Obtain complete medical , birth and family history
- Look for signs of neurological disease
- Determine bone age
- Assess basal gonadotropin levels and thyroid function
- Pelvic and CNS imaging to rule out other causes
CENTRAL PRECOCIOUS PUBERTY
•Gonadotropin dependent
• Premature activation of HPO
axis
• Isosexual (SSC same as that of
child’s sex)
• Tall stature, accelerated bone
maturation and premature
epiphyseal fusion (estrogen
mediated)
• Bone age advanced > 2 years
• GnRH stimulation test
• MRI to rule out CNS lesions
• Treatment GnRH analogues
PERIPHERAL PRECOCIOUS PUBERTY
• Gonadotropin independent
• Disordered sequence of
pubertal events
• Isosexual or heterosexual
• Rapid growth, advanced bone
age with pubic and axillary
hair with clitoromegaly
• GnRH test, estradiol,serum 17
hydroxy progesterone,
testosterone, DHEA
• Pelvic ultrasound
• Treat underlying cause
34.
CENTRAL PRECOCIOUS PUBERTY
•GnRH prematurely stimulates gonadotropin secretion
• Idiopathic most common cause
• Other causes include tumor, infection ,trauma
• Around 2% is due to hypothalamic hamartoma
-Congenital malformation of heterotopic mass of nerve tissue
containing GnRH neurosecretory neurons, fibre bundles and glial
cells
- These neurosecretory bundles produce GnRH in a pulsatile fashion
- Isodense ,abnormal fullness on MRI
- Absent tumor markers like beta hCG, AFP
35.
• TREATMENT:
-Buserlin 6.3mg every 2 months
-Goserelin 3.6 mg every month or 9.8 mg every 3
months
-Histerlin 50 mg implant every year
-Leuprolide 3.75-7.5 mg monthly or 11.25 mg every
3 months
-Triptorelin 3.0-3.75mg monthly or 11.25 mg every 3
months
36.
• Premature thelarche:
-Isolatedbreast development before 8 years of age
- Common between 2- 4 years
-Caused due to increased sensitivity of breasts to estrogen
-Self limited and only follow up required with revaluation 6 month
periodic intervals
-Uterine volume measurement may be done to discriminate
between early precocious puberty and premature thelarche
37.
• Premature adrenarche:
-Isolateddevelopment of axillary and pubic hair
before 8 years of age
- Increased risk of PCOS
- Self limiting
- Rarely may be due to CAH , adrenal tumors
- Increased serum DHEA > 40mcg/dl
38.
• Premature menarche
-Isolatedevent of cyclic bleeding before 9 years
-Unusual sensitivity of endometrium to
hormones
-Differential include vaginal foreign bodies,
trauma, sexual abuse or neoplasm like
rhabdomyosarcoma
39.
PERIPHERAL PRECOCIOUS PUBERTY
•Mc Cune Albright syndrome
- Triad of polyostotic fibrous dysplasia, irregular café du alit spots
and GnRH dependent sexual precocity
- Precocious precocity due to excessive estrogen production
- Patho : Mutation in G3 protein leading to activation of adenylyl
cylase (GNAS1 gene)
- Stimulates FSH,LH,TSH
41.
- Café aulait spots are on the same side of bone lesions
- Café au lait spots irregular margins which do not cross midline
(Coast of Maine margin)
- Associated with other endocrinopathies : hyperthyroidsim,
hyperprolactinemia and acromegaly
• Treatment : Tamoxifen reduces vaginal bleeding
Pure estrogen receptor anatagonist : Fulvestrant
42.
• Primary hypothyroidism(Van Wyk-Grumbach syndrome )
- is a rare condition characterized by prolonged hypothyroidism
(underactive thyroid) leading to precocious puberty (early onset
of puberty), ovarian cysts, and delayed bone age
- a compensatory increase in TSH from the pituitary gland.
- Only cause of precocious puberty leading to delayed bone age
- TSH and FSH share a common alpha subunit,
- the high levels of TSH can stimulate FSH receptors in the ovaries
• Heterosexual precociouspuberty
• Autosomal recessive disorder
• Female pseudohermaphordite
• Due to
-21 hydroxylase deficiency (95%)
-11 hydroxylase deficency
-3 beta hydroxysteroid dehydrodenase deficency
• Lack of cortisol production resulting n excssive ACTH
production
• ACTH further stimulates adrenal to produce androgens
which causes virilisation
• Associated aldosterone deficiency results in salt wasting
CONGENITAL ADRENAL HYPERPLASIA
45.
CLINICAL FEATURES
• Enlargedclitoris
• Advanced bone age and premature closure of
epiphysis resulting in short stature
• Labial fusion
• 11 hydroxylase deficency maybe associated with
hypertension
47.
INVESTIGATIONS
- USG showsnormal uterus, tubes and vagina
- Karytotype 46 XX
- 17 ἀ hydroxyprogesterone (17 OHP) elevated (>800 ng/dL)
- Electrolyte estimation to rule out hyponatremia and
hyperkalemia
- Cosyntropin stimulation test : Estimation of 17 ἀ
hydroxyprogesterone 30 minutes after adminstration of
0.25 mg synthetic cosyntropin (synthetic analogue of ACTH
ASYNCHRONOUS PUBERTY
• Characteristicof androgen insenstivity (testicular feminisation)
• Present with breast development out of proportion to pubic and
axillary hair
• 46 XY induviduals with bilateral testes and female external
genitalia ( Male pseudohermaphordite)
50.
ANDROGEN INSENSTIVITY SYNDROME
-X linked recessive
- Absence of androgen receptors or decreased activity
- Absent 5 ἀ reductase enzyme ( TT not converted to DHT)
- Phenotypically and psychologically female
- External genitalia female ( Absent DHT) short and blind vagina
- Enlarged breasts (estrogen)
- Absent pubic and axillary hair ( Absent AR)
- Ectopic testis - increased risk of tumors
- Serotoli cells secrete AMH – absent uterus, tubes and upper 1/3
vagina
TREATMENT
- Gonadectomy
- Longterm estrogen to prevent osteoporosis
- Incomplete variety : if surgery converted to
male Pregnancy possible by IVF
- Complete variety : vaginoplasty and long term
estrogen to prevent osteoporosis
Definition
• Menorrhagia: Menstrualbleeding lasting >7
days or >80 mL blood loss per cycle.
• Puberty menorrhagia: Heavy menstrual
bleeding occurring in adolescents (ages 10–
19), especially in the early post-menarcheal
years.
55.
• Menstrual abnormalitiesare common in adolescence.
• Puberty menorrhagia is a significant concern due to its
impact on health, academics, and quality of life.
• It typically occurs within the first few years of menarche
due to immature HPO axis.
• Considered normal for a period of up to 19 years of age or
within the first 5 years after menarche
• Evaluation indicated if menstrual cycle is < 22 days or > 44
days ,last longer than one week or causes severe anemia
56.
• Heavy menstrualbleeding at menarche and in
adolescence may be an important sentinel for an
underlying bleeding disorder.
• The frequency of bleeding disorders in the general
population is approximately 1–2%, but bleeding
disorders are found in approximately 20% of
adolescent girls who present for evaluation of
heavy menstrual bleeding and in 33% of adolescent
girls hospitalized for heavy menstrual bleeding
CLINICAL FEATURES
• Excessivebleeding during menstruation
• Menstrual cycle lasting longer than 7 days
• Passage of large clots
• Fatigue, pallor, breathlessness
• May be associated with other bleeding
symptoms (e.g., epistaxis)
60.
PHYSICAL EXAMINATION
• Generalexamination : pallor, tachycardia,
hypotension
• BMI evaluation (for PCOS or undernutrition)
• Signs of thyroid disease
• Systemic examination to rule out
comorbidities
61.
INVESTIGATIONS
• CBC, Hemoglobin,Hematocrit, Platelet count
• Peripheral smear
• Coagulation profile: PT, aPTT, INR
• Thyroid profile: TSH, T3, T4
• Specific tests for bleeding disorders: vWF assay
• USG structural causes in adoloscents rare and
hence it can be considered for patients who do not
respond to initial management
63.
TREATMENT
• Medical management
-Immediate management
- -Long term Managenement
• Non medical management
-intrauterine balloon tamponade
- suction evacuation
- suction curettage (machine or manual).
64.
MEDICAL MANAGEMENT
IMMEDIATE
1. HormonalTherapy:
• - High dose combined oral
contraceptives (COCs)
• - Cyclic progesterone
• - IV estrogen in severe cases
2. Non-hormonal:
• - Tranexamic acid
(antifibrinolytic)
• - NSAIDs like mefenamic acid
LONG TERM
Hormonal
• combined hormonal
contraceptives
• oral and injectable progestins
• LNG-IUDs.
• Transdermal contraceptive patch
• Vaginal ring
Nonhormonal
oral iron supplementation
dietary optimization
66.
• The prescribinginformation for tranexamic acid lists
concurrent use of OCs as a contraindication because of
theoretical risks of thrombosis
• Estrogen influences hemostasis by increasing the levels of
clotting factors (VII, VIII, X, fibrinogen) and plasminogen,
lowering antithrombin III and protein S levels, and altering
activated protein C resistance.
• Tranexamic acid inhibits fibrinolysis.
• Although there is a theoretical risk of thrombosis, the
concomitant administration of tranexamic acid and OCs has
been used when monotherapy has failed
• It is an important treatment option to control bleeding in
this population and a reasonable approach to management
when other options have failed.
67.
ROLE OF BLOOODTRANSFUSION
• Avoid blood transfusion as far as possible
• Transfusion only for a hemoglobin of 7 g/dL or less
• Important to initiate iron therapy because iron
packaged in transfused red cells is not immediately
available for erythropoiesis
• When a patient’s adherence to an oral medication
regimen at discharge is a concern, the use of
intravenous iron during hospitalization may be
considered
68.
NON MEDICAL MANAGEMENT
•Procedural interventions in adolescents usually are
considered second-line treatment given the
presumed desire for future fertility
• Should be considered only when there is a lack of
response to medical therapy
• Surgical options that spare fertility include
- intrauterine balloon tamponade
- suction evacuation
- suction curettage (machine or manual).
69.
Intrauterine Balloon
• Intrauterineballoons designed for obstetric use in adult women are
not appropriately sized for the adolescent patient
• Instead a Foley catheter should be placed with a 30-cc balloon that
can be inserted easily through the cervix and inflated with saline until
resistance of the myometrium is felt
• Amount of saline needed to feel resistance varies depending on
uterine size is 10 cc.
• The balloon usually can be kept in place for 12–24 hours while other
medical therapies are being administered
• Gradual deflation of the balloon by removing 5 mL of saline at a time
can be performed once bleeding has ceased, or the balloon can be
removed after 24 hours with observation for bleeding
• An advantage of the balloon is the ability to simultaneously monitor
for uterine bleeding; a leg bag can be attached to record output
• Risks : Endometritis and uterine perforation
70.
Uterine evacuation
• Sharpcurettage can result in additional blood loss for
patients with a bleeding disorder and should be avoided in
this population
• Suction curettage (machine or manual) may be appropriate if
ultrasonography identifies a clot or decidual cast
• Facilitation of the removal of structurally fragile bleeding
endometrium allows restoration of normal hemostatic events
with regeneration of the integrity of the endometrium and
restoration of the normal proliferation response
• Concomitant hysteroscopy may be of value for those patients
in whom intrauterine pathology is suspected or if a tissue
sampling is desired
• Additionally, concomitant placement of a levonorgestrel-
releasing intrauterine device (LNG-IUD) for long-term
management should be considered in this setting
73.
LONG TERM MANANGEMENT
Hormonal
•combined hormonal contraceptives
• oral and injectable progestins
• LNG-IUDs.
• Transdermal contraceptive patch
• Vaginal ring
Nonhormonal
• oral iron supplementation
• dietary optimization.
• Life style modification for PCOS
• Treatment for underlying thyroid disorders
74.
Hormonal
• Combine OCPS
-First-line : Monophasic pills that contain 30–50
micrograms of ethinyl estradiol with a second-generation
progesterone (stabilize the endometrium than lower dose
estrogen formulations)
- If there is breakthrough bleeding, double the dose of the
combined OC until the bleeding stops to allow withdrawal
bleed.
- Some patients who experience breakthrough bleeding
while taking a 30–35-microgram ethinyl estradiol-
containing combined OCP may have decreased bleeding
with the continuous use of a 50-microgram ethinyl
estradiol-containing OCP.
75.
Progestin
• Progestin therapyis another option for adolescents and
women who cannot tolerate estrogen-containing therapy or
in whom estrogen is contraindicated.
• Norethindrone (norethisterone) is available as a
progesterone-only contraceptive pill (0.35 mg daily
• Norethindrone in 5-mg tablets but can be titrated in doses
of 5–15 mg daily for menstrual suppression. Breakthrough
bleeding may occur.
• Subcutaneous formulations of medroxyprogesterone
acetate in whom intramuscular injection is contraindicated.
• Although highly effective for contraception, the
etonogestrel contraceptive implant is not recommended for
first-line therapy for heavy menstrual bleeding in girls and
adolescents with a bleeding disorder because breakthrough
bleeding is a common adverse effect.
76.
INTRAUTERINE DEVICES
- Adherenceto daily, weekly, or monthly medication may
be challenging for adolescents.
- Copper IUDs may exacerbate bleeding and should be
avoided
- The 52 mg LNG-IUD has been demonstrated to reduce
heavy menstrual bleeding in all women and is an
effective treatment when compared with usual medical
and surgical therapies
77.
NON HORMONAL
IRON SUPPLEMENTATION
-The World Health Organization defines anemia in females 12
years and older as a hemoglobin threshold of 12 g/d
- Iron deficiency generally is identified by a serum ferritin
concentration below 15 micrograms/L.
- Adolescents with heavy menstrual bleeding are at an even
higher risk of iron deficiency, with 0.4–0.5 mg of iron lost with
every 1 mL of blood.
- The incidence of iron deficiency among these adolescents is
9%, increasing to 15–20% when iron deficiency without anemia
is included
- American College of Obstetricians and Gynecologists
recommends obtaining a complete blood count and iron studies
78.
• First-line therapyfor iron deficiency anemia
includes oral iron supplementation along with
dietary counseling to increase iron intake.
• Oral dose of 60–120 mg per day of iron
• There is emerging data that once-a-day to
every-other-day dose scheduling is more
efficient than multiple doses because
increased levels of released hepcidin can
decrease iron absorption
79.
NSAIDS
• NSAIDS arecommonly used for
dysmenorrhea.
• Adolescents in whom a bleeding disorder has
been diagnosed products that prevent platelet
adhesion, such as aspirin or nonsteroidal
antiinflammatory drugs, should be used only
with the recommendation of a hematologist
80.
• Duration oftherapy should be directed by the
severity of anemia and the patient’s response
to treatment.
• If interventions to decrease menstrual flow
are successful, then a 3- to 6-month course of
iron supplementation is sufficient.
• A ferritin level should be obtained to confirm
the complete resolution of iron deficiency
81.
MANAGEMENT OF HEMORRAGHICCYSTS
• Increased incidence of hemorrhagic ovarian cysts
has been reported in adoloscents with bleeding
disorders
• The cysts occur as a result of excessive bleeding
into the corpus luteum at the time of ovulation,
and rupture of these cysts may result in
hematoperitoneum
• Systemic hormones potentially are an option for
patients with recurrent hemorrhagic cysts and
can be used in combination with an LNG-IUD.
82.
PRE PUBERTAL COUNSELLING
•Adolescents with known bleeding disorders should be
counseled before menarche
• Have a plan in place for the possibility of heavy menstrual
bleeding with menarche in conjunction with the patient’s
gynecologist and hematologist
• American College of Obstetricians and Gynecologists
recommends that adolescents have their first reproductive
health visit between the ages of 13 years and 15 years
• If reproductive concerns present before 13 years of age, an
earlier visit to the may be warranted
83.
FOLLOW-UP
• Reassessment ofhemoglobin and symptoms
• Continue iron therapy if anemic
• Long-term hormonal regulation if persistent
anovulation
• Lifestyle counseling for PCOS or thyroid
disorders
84.
CONCLUSION OF PUBERTYMENORRAGHIA
• Proportionally, adolescent girls are more likely than women to have an
underlying bleeding disorder as a cause of heavy menstrual bleeding.
• Screening for bleeding disorders and iron deficiency anemia should be
included in the initial evaluation of girls with heavy menstrual bleeding.
Hormonal therapy can include combined hormonal contraceptives, oral
and injectable progestins, and LNG-IUDs.
• Iron replacement therapy should be provided for all reproductive-aged
women with anemia due to bleeding.
• Control of heavy menstrual bleeding in girls with a bleeding disorder
may require combined therapy with hemostatic agents.
• Care of girls and adolescents with bleeding disorders should be in
consultation with a hematologist, ideally at a multidisciplinary clinic site.
85.
GROWTH PROBLEMS INNORMAL ADOLOSCENTS
• Growth in height is a continuous but not a linear process
• Three phases
-Infantile – 30-35 cm in first 2 years of life
-Childhood phase 5-7 cm/year
-Pubertal phase 8-4 cm/year
• Final adult height (MID PARENTAL HEIGHT)
- (Father’s height -13 cm) + mother’s height
2
• Basic laboratory test for abnormal height is left wrist
X ray for bone age
• Adult height can be predicted by Bayley Pinneau tables
86.
SHORT STATURE
-Height lessthen 2 SD below mean height of children of same
sex and chronological age
-Accurate growth velocity measurement most important tool
-Causes :
• Malnutrition
• Chromosomal disorders (Down’s and Turner’s)
• IUGR
• Cushing syndrome
• GH deficiency
• Familial
• Idioptahic (SHOX gene mutation)
• Primary and secondary hypothyoidism
88.
• TREATMENT
- Idiopathicshort stature : GH therapy
- Constitutional delay – exhibit catch up growth
during puberty
- Long acting GnRH agonists
89.
TALL STATURE
- Height> 2SD above the mean height of
children of same sex and chronological age
- Causes
• Familial
• Precocious puberty
• GH excess
• Hyperthyroidism
• Marfan syndrome, NF1
90.
• TREATMENT
-Serial measurementof bone age at 6- 12
months interval
- Sex steroids to promote early epiphyseal fusion
- Treatment to be started before menarche
- Typical starting dose 15-30 mcg ethinyl
estradiol to be continued till epiphysis are
closed
