2. Primary Amenorrhea
is defined either as absence of menses by
age 14 years with no development of
secondary sexual characteristics
OR as absence of menses by age 16
years with normal development of
secondary sexual characteristics.
3. Secondary amenorrhea
is defined as the cessation of
menstruation for at least 6 months
or for at least 3 of the previous 3
cycle intervals
4. Thelarche (breast development)Thelarche (breast development)
– Requires estrogenRequires estrogen
Pubarche/adrenarche (pubic hair development)Pubarche/adrenarche (pubic hair development)
– Requires androgensRequires androgens
MenarcheMenarche
Requires:Requires:
– GnRH from the hypothalamusGnRH from the hypothalamus
– FSH and LH from the pituitaryFSH and LH from the pituitary
– Estrogen and progesterone from the ovariesEstrogen and progesterone from the ovaries
– Normal outflow tractNormal outflow tract
Events of PubertyEvents of Puberty
5. Magnitude of the problem
• Secondary amenorrhea (prevalence about 3%)
• Primary amenorrhea (prevalence about 0.3%)
• Between 10 and 20% of women complaining of
infertility have amenorrhea .
• Up to 50% of competitive runners (training 80 miles
per week) and up to 44% of ballet dancers have
amenorrhea.
12. Turner's syndrome
• Turner's syndrome is
caused by either a complete
absence or a partial
abnormality of one of the
two X chromosomes. About
50% have mosaic forms
such as 45X/46XX or
45X/46XY
• Features : short stature, web
neck, lymphedema, shield
chest with widely spaced
nipples, wide carrying angle,
coarctation of the aorta, and
streak ovaries
13. Uterovaginal agenesisUterovaginal agenesis
15%15% of primary amenorrheaof primary amenorrhea
Normal secondary development & externalNormal secondary development & external
female genitaliafemale genitalia
Normal female range testosterone levelNormal female range testosterone level
Absent uterus and upper vagina & normalAbsent uterus and upper vagina & normal
ovariesovaries
Karyotype 46-XXKaryotype 46-XX
1515--30% associated renal, skeletal and middle30% associated renal, skeletal and middle
ear anomaliesear anomalies
14.
15. Androgen insensitivity syndrome
(AIS)
Formerly known as testicular feminization,
46XY
Failure of normal masculinization of the external
genitalia in chromosomally male individuals. This
failure of virilization can be either complete (CAIS) or
partial (PAIS), depending on the amount of residual
receptor function
Affected individuals have normal testes with normal
production of testosterone and normal conversion to
dihydrotestosterone (DHT), which differentiates this
condition from 5-alpha reductase deficiency
16.
17. Imperforate hymen
Imperforate hymen represents the most
common and most distal form of vaginal
outflow obstruction
Clinical presentations range from an incidental
finding on physical examination of an
asymptomatic patient to discovery on an
evaluation for primary amenorrhea or
abdominal or back pain
The differential diagnosis of uterovaginal
obstruction includes disorders of vaginal
development, such as transverse vaginal
septum or complete vaginal agenesis.
19. Constitutional delay
• In this condition there is no anatomical
abnormality and endocrine
investigations show normal results
• It is caused by immature pulsatile release of
gonadotrophin-releasing hormone;
maturation eventually occurs spontaneously
21. TSH elevated
hypothyroidism
Normal
bone age
delayed
constitutional delay
Normal
LH, FSH, and prolactin levels
elevated
karyotype.
low or within
reference range
head MRI
45,XO, the cause is gonadal dysgenesis
46,XX, the primary cause is ovarian failure
•pituitary tumor or a
brain lesion
•drug use, an eating
disorder, athleticism,
or psychosocial stress
If puberty delayed
22. TSH and prolactin levels
progestin challenge
within reference range
consider anovulatory cycles
PCO
E2/progestin challenge
outlet obstruction obtain FSH and LH levels.
low or within reference range
head MRI
exclude chronic disease,
anorexia nervosa, or
psychosocial stress
high
karyotype
Turner synd
karyotype is normal (46,XX),
the cause is ovarian failure
elevated
hypothyroidism and
hyperprolactinemia
+VE-VE
If puberty
not delayed
+-
23. genital tract
abnormalities
karyotype
If the karyotype is 46,XY If the karyotype is 46,XX
testosterone levels
male range female range
androgen insensitivity
testicular regression
or gonadal enzyme deficiency.
müllerian agenesis
(ie, Rokitansky-Kuster-Hauser
syndrome).
24. Breast development, pubertal growth spurt,
and adrenarche are delayed or
absent in persons with
hypothalamic pituitary
failure
25. adrenarche occurs normally, while
estrogen-dependent breast development and the
pubertal growth spurt are absent or delayed
isolated ovarian insufficiency
or failure
29. Features of androgen excess present
• Polycystic ovary syndrome
• Cushing's syndrome
• Late-onset congenital adrenal hyperplasia
• Adrenal or ovarian androgen-producing tumor
30. Polycystic ovary syndrome
• This condition is characterized by hirsutism, acne,
alopecia, infertility, obesity, and menstrual
abnormalities (amenorrhea in 19% of cases)
• Ultrasound examination of the ovaries typically shows
multiple, small peripheral cysts. up to a third of women in
the general population have polycystic ovaries on
ultrasound examination .
• Endocrine abnormalities include increased serum
concentrations of testosterone, prolactin, luteinizing
hormone (LH) (with normal follicle-stimulating hormone
[FSH] levels), and insulin resistance with compensatory
hyperinsulinemia
34. • Menopause/ovarian failure occurring before the
age of 40 years is considered premature
• Auto-immune disease is the most common cause;
auto-antibodies to ovarian cells, gonadotrophin
receptors, and oocytes have been reported in 80%
of cases
• Before puberty or in adolescents, ovarian failure is
usually due to a chromosomal abnormality, e.g.
Turner mosaic, or previous radiotherapy, or
chemotherapy
Premature ovarian failure
35. Ovarian failure (premature
menopause)
chromosomal
anomalies
autoimmune
disease
If the woman is under 30, a
karyotype should be
performed to rule out any
mosaicism involving a Y
chromosome
It is necessary to screen for thyroid,
parathyroid, and adrenal
dysfunction
If a Y chromosome is found the
gonads should be surgically
excised
36. Autoimmune related dysfunction
The most common association is with thyroidThe most common association is with thyroid
disease, but the parathyroids and adrenals can alsodisease, but the parathyroids and adrenals can also
be affectedbe affected
Several studies have shown laboratory evidence ofSeveral studies have shown laboratory evidence of
immune problems in about 15-40% of women withimmune problems in about 15-40% of women with
premature ovarian failurepremature ovarian failure
In general, ovarian biopsy is not indicated inIn general, ovarian biopsy is not indicated in
patients with premature ovarian failure since nopatients with premature ovarian failure since no
clinically useful information will be obtainedclinically useful information will be obtained
37. Hyperprolactinemia
• A prolactinoma is the commonest cause of
hyperprolactinemia (60% of cases)
• Other causes include non-functioning pituitary adenoma
(disrupting the inhibitory influence of dopamine on prolactin
secretion)
• dopaminergic antagonist drugs (e.g. phenothiazines,
haloperidol, clozapine, methyldopa, cimetidine); primary
hypothyroidism (thyrotrophin-releasing hormone stimulates
the secretion of prolactin), or it may be idiopathic
• Prolactin acts directly on the hypothalamus to reduce
the amplitude and frequency of pulses of gonadotrophin-
releasing hormone
38. Weight-related amenorrhoea
• A regular menstrual cycle is unlikely to
occur if the body mass index (BMI) is less
than 19 (normal range 20-25)
• Weight loss may be due to illness, exercise,
or eating disorders, among which anorexia
nervosa lies at the extreme end of the
spectrum
39. Progestogen-associated amenorrhea
• Depot medroxyprogesterone acetate inhibits the secretion of
gonadotrophins and thus suppresses ovulation
• After 1 year of use, 80% of women have amenorrhoea or very scanty,
infrequent vaginal bleeding
• There is partial estrogen deficiency in women who use depot
medroxyprogesterone acetate
• The progestogen-only pill leads to reversible long-term
amenorrhoea in a minority of women, due to complete suppression of
ovulation
• The levonorgestrel-releasing intra-uterine device commonly
results in amenorrhoea after a few months. This is thought to be
mainly a local effect, but suppression of ovulation can occur in some
women (in some cycles)
41. HistoryHistory
A good history can reveal the etiologicA good history can reveal the etiologic
diagnosis in up to 85% of cases ofdiagnosis in up to 85% of cases of
amenorrheaamenorrhea
42. • symptoms of pregnancy
• Associated symptoms, e.g.
galactorrhoea, hirsutism, hot flushes, dry
vagina, symptoms of thyroid disease
• Recent change in body weight
• Recent emotional upsets
• Previous menstrual and obstetric
history
43. • Previous surgery, e.g. endometrial
curettage, oophorectomy
• Previous abdominal, pelvic, or cranial
radiotherapy
• Family history, e.g. of early menopause
• Drug history, e.g. progestogens,
combined oral contraceptive,
chemotherapy
44. EXAMINATIONEXAMINATION
• Height and weight: calculate body
mass index if appropriate.
• Signs of excess androgens, e.g.
hirsutism, acne
• Signs of virilization, e.g. deep voice,
clitoromegaly in addition to hirsutism,
and acne
• Signs of thyroid disease
45. • Acanthosis nigricans: this
hyperpigmented thickening of the skin
folds of the axilla and neck is a sign of
profound insulin resistance. It is
associated with polycystic ovary
syndrome (PCOS) and obesity
• Breast examination for galactorrhoea
• Pelvic examination
46. Preg.test
TSH ,PROLACTIN,
Prog.challenge test
withdrawal
bleeding
without withdrawal
bleeding
hypoestrogenic compromised
outflow tract
+
+ve.est,progest,
challenge test -ve.est,progest
challenge test
FSH>30-40
Normal FSH
HSG OR hysteroscopy
asherman
FSH low
repeat
POF
hypothalamic-
pituitary failure
anovulation
-VE
47. Complications and prognosis
• Osteoporosis: women with amenorrhoea associated with estrogen
deficiency are at significant risk of developing osteoporosis. This increased
risk persists even if normal menses are resumed. Estrogen deficiency is of
particular concern in younger women as a desirable peak bone mass may
not be attained
• Cardiovascular disease
• Young women with amenorrhoea associated with estrogen deficiency
may be at increased risk of cardiovascular disease
• Women with polycystic ovary syndrome have an increased risk of
developing cardiovascular disease, hypertension, and type 2 diabetes
[Hopkinson et al, 1998]
48. • Endometrial hyperplasia: women with amenorrhoea but
no associated oestrogen deficiency are at increased risk of
endometrial hyperplasia and endometrial carcinoma
• Infertility: women with amenorrhoea generally do not
ovulate
• Psychological distress: amenorrhea often causes
considerable anxiety, many women have concerns about
loss of fertility, loss of femininity, or worry about an
unwanted pregnancy. The diagnosis of Turner's syndrome,
testicular feminization, or developmental anomaly can be
traumatic for both girls and their parents
Complications and prognosis
50. Ovarian cortical transplantationOvarian cortical transplantation
Transplantation of ovarian cortical tissue isTransplantation of ovarian cortical tissue is
performed in patients with premature ovarianperformed in patients with premature ovarian
failure, premature menopause due to sur5gicalfailure, premature menopause due to sur5gical
removal of the ovary, radiotherapy &removal of the ovary, radiotherapy &
chemotherapychemotherapy
the ovarian cortical grafts transplantedthe ovarian cortical grafts transplanted
subcutaneously functioned from the 6thsubcutaneously functioned from the 6th
postoperative month . At the long-term follow-uppostoperative month . At the long-term follow-up
of the patient, cortical grafts have still beenof the patient, cortical grafts have still been
functioning. The patient did not have anyfunctioning. The patient did not have any
complaint requiring hormonal therapy during thatcomplaint requiring hormonal therapy during that
time periodtime period
Resistant ovary syndrome aka savage syndrome: Resistant ovaries" result from a functional disturbance of the gonadotrophin receptors in the ovarian follicles
A disorder of hypogonadotropic hypogonadism, delayed puberty, and anosmia. Kallman's syndrome is a birth defect in the brain that prevents release of hormones and appears as failure of male puberty.
Congenital adrenal hyperplasia refers to a group of inherited adrenal gland disorders. People with this condition do no produce enough of the hormones cortisol and aldosterone, and produce too much of androgen
This is a very rare ovarian tumor which has classically been grouped in the sex cord-stromal cell tumors. These tumors are known for producing various hormones and about 1/3 of cases may present with virilization. In other patients, oligomenorrhea followed by amenorrhea may occur. Progressive masculinization and hirsuitism may also occur. However, 50% of these patients may have no endocrine symptomatology and instead have abdominal pain or swelling. Removal of the tumor results in a nomral menses in about 4 weeks.
Children with constitutional growth delay (CGD), the most common cause of short stature and pubertal delay, typically have retarded linear growth within the first 3 years of life. In this variant of normal growth, linear growth velocity and weight gain slows beginning as early as 3-6 months of age, resulting in downward crossing of growth percentiles, which often continues until 2 or 3 years of age. At that time, growth resumes at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.
At the expected time of puberty, the height of children with CGD begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development. Although CGD is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals. Recent studies have suggested that referral bias is largely responsible for the impression that normal short stature per se is a cause of psychosocial problems; nonreferred short children do not differ from those with more normal stature in school performance or socialization.
Pathophysiology: CGD is a global delay in development affecting every organ system of the body. Delays in growth and sexual development are quantified by skeletal age, which is determined from bone age radiographic studies of the left hand and wrist. Growth and development are appropriate for an individual's biologic age (skeletal age) rather than chronologic age. Timing and tempo of growth and development are delayed in accordance with the biologic state of maturity.
Frequency:
In the US: Approximately 15% of patients of short stature referred for endocrinologic evaluation have CGD. Individuals with CGD superimposed upon familial short stature represent another 23%. The frequency of CGD may be underestimated because individuals with milder delays and those who are not psychologically stressed may not be seen by subspecialists. In a study of 555 (out of 80,000) schoolchildren below the third percentile in height for age with growth rates below normal (<5 cm/y), twice as many boys as girls were affected. Twenty-eight percent of boys and 24% of girls affected had CDG, and another 18% of boys and 16% of girls had familial short stature in combination with CDG.
