AMENORRHEA

Dr.Nousheen Bhatti
 AMENORRHEA

 It is the absence of menstrual flow.

 Primary
 Secondary
PRIMARY AMENORRHEA

 It is the failure to develop spontaneous

periodic menstruation by the age of 16
regardless of whether secondary sex
characteristics develop.
Diagnostic Evaluation for
Primary Amenorrhea:

DETAILED HISTORY
 Normal pubertal development?

 Was patient’s neonatal/childhood health normal?

 Family history of delayed/absent menarche?

 Any symptoms of virilization?

 Any galactorrhea? (hyperprolactinemia)

More history questions…

 Any recent increase in stress, or change in

weight, diet, or exercise habits?

 Is patient taking any medications or drugs?

 Short stature compared to family members?

 Any symptoms of other hypothalamic-pituitary

disease (headaches, visual field defects, fatigue,
polyuria or polydipsia?)
PHYSICAL EXAMINATON

 Evaluation of pubertal development –

 Pelvic examination to check for presence of cervix,

uterus, ovaries (may need ultrasound)

 Check skin for signs of androgen excess (virilization,

hirsutism, acne, & striae) and vitiligo (thyroid
disorders)

 Check for physical features of Turner syndrome

(short stature , low hair line, web neck)
LABORATORY EVALUATION

Serum Gonadotrophin levels:

 Low concentrations indicate pituitary failure
 Higher concentrations indicate definite gonadal
failure.
Chromosomal analysis :
 With gonadal failure chromosome studies are
indicated to rule out Turner syndrome(45X) or
pure gonadal dysgenesis (either 46XX or XY
karyotype)
Rule out CAH :17ά - hydroxylase
deficiency is suspected if
 Serum progesterone is >3ng/ml
 Serum hydroxyprogesterone is
<0.2ng/ml.
 Aldosterone is low
 11-deoxycorticosterone is elevated.
 11deoxycoticosterol,testosterone,
estradiol and DHEA-S are also low.
ACTH STIMULATION TEST

 The diagnosis of 17ά - hydroxylase

deficiency is confirmed by ACTH
stimulation test.
 Procedure: After baseline progesterone
and 17 άά hydroxyprogesterone
concentrations are measured, 0.25mg of
ACTH is administered and levels are
again measured after 60 minutes
Interpretation :
 If serum concentration of progesterone
are significantly elevated 17ά
hydroxyprogesterone concentrations are
unchanged at 60 minutes after ACTH
Stimulation then 17ά hydroxylase
deficiency is confirmed.
PELVIC U/S:
 If normal vagina or uterus not obviously
present on physical examination , a
pelvic U/S is performed to confirm the
presence or absence of ovaries, uterus,
and cervix.
SECONDARY
AMENORRHEA

 It is the absence of periodic

menstruation for atleast 6 months in
women who were previously
menstruating or for 12 months in women
with prior oligomenorrhea.
 Oligomenorrhea is infrequent
menstruation, occuring less than nine
times per year.
Pertinent history in work-up of
secondary amenorrhea

 The complete description of menstrual pattern

 Recent stress, weight loss, diet or exercise
changes, or illness?
 Medications (Recent OCP initiation, danazol,
meto-clopramide, anti-psychotics?)
 Symptoms of other hypothalamic-pituitary
disease, including headaches, visual field
defects, fatigue, or polyuria and polydipsia?
 Symptoms of estrogen deficiency, including hot
flashes, vaginal dryness, poor sleep, or
decreased libido?
 Galactorrhea, hirsutism, acne, and/or a history
of irregular menses?
 An history of obstetrical catastrophe, severe
bleeding, dilatation and curettage, or
endometritis or other infection that might have
caused scarring of the endometrial lining ?
Physical examination findings

 Height & weight, BMI

 Any evidence of systemic illness or cachexia

 Breast exam – check for galactorrhea

 Check for hirsutism, acne, striae , vitiligo, skin

thickness or thinness, and easy bruisability
 Visual fields
 Thyroid size and function
 Cushingoid appearance
 Any evidence of malnutrition
 LAB EVALUATION

 Urine or serum B-HCG to rule out

pregnancy.
 Serum prolactin levels : If they are >
20ng/ml hyperprolactinemia may be the
cause of amenorrhea. CT Scan/MRI can
be done to rule out prolactinomas.
 Serum TSH levels are measured to rule
out hyper or hypothyrodism.
 If cushing syndrome is suspected , a 24
hour urine sample for cortisol
measurement and overnight
dexamethasone stimulation test is
performed.
 To rule out PCOS serum gonadotrophins
testosterone and DHEA-S levels are
measured. Elevated LH ,
dispropotionately low FSH with LH : FSH
ratio>2.5 and raised testosterone &
DHEA-S levels indicate PCOS.
High serum FSH

 Indicates the presence of ovarian failure.

 This test should be repeated monthly on three

occasions to confirm persistent elevation.

 A karyotype should be considered in most women

of secondary amenorrhea age 30 years or
younger to r/o complete or partial deletion of the
X chromosome, or presence of any Y chromosome
material
 In patients with low FSH,LH and Oestradiole
levels GnRH stimulation test assists in
differentiating hypothalamic disease from
pituitary disease.
 100µg of GnRH is given and gonadotrophin
levels are measured . If levels are increased >
or equal to 7 delayed or significant response . it
indicates hypothalamic disease . If no
stimulation occurs and low gonadotrophins
indicate pituitary disease. normal response is >
or equal to 10mIU/ml.
 When the cause of amenorrhea is unclear after
after the initial assessment estrogen status
should be determined either by progesterone
challenge test or serum oestradiol.
 Progesterone Challenge test
Principle: Women with an oestrgen primed uterus
menstruate after treatment with oral progestin.
Procedure: 30mg daily for 3 days ,or 10mg for 5-
10 days , or 100mg of progesterone in oil given
intramuscularly.
Interpretation : If withdrawal bleeding
occurs with progesterone it indicates
normal outflow tract.
 Measurement of serum oestradiol
concentrations can be made but it is not
preferred because estrogen
concentrations fluctuate throughout the
day.
Polycystic Ovarian
Syndrome

 It is clinically defined by
hyperandrogenism with chronic
anovulation in women without underlying
disease of the underlying disease of the
adrenal or pituitary glands.
Polycystic Ovarian
Syndrome

 Characterized by:
 Menstrual disturbances ( Oligomenorrhea ,
Amenorrhea , regular menstrual cycle )
 Infertility
 Hirsutism
 Acne
 Obesity
 Hyperinsulinemia/insulin resistance,
 Bilateral ovarian enlargement & multiple cysts
LABORATORY FINDINGS

 LH concentrations are frequently

elevated while FSH concentrations are
normal or dispropotionately low. A ratio
of LH to FSH > 2.5 indicates PCOS.
 Serum testosterone (total and free
concentrations) are moderately elevated
while DHEA-S is normal or slightly
elevated.
 Low SHBG
 Plasma oestradiol concentrations are
usually in the mid- follicular range of
approximately 40 pg/ml and therefore
exhibit a positive progesterone
stimulation test.
 Hyperinsulinemia and dyslipidemias
 Pelvic ultrasonography is done to look
for polycystic ovaries.
 Hirsutism – excessive growth of terminal hair in
women and children similar to that occurring in
postpubertal men. It is associated with normal or
slightly elevated androgens.

 Virilization – development of male features:

Deepening of voice, frontal baldness, increased
muscle mass, clitoral hypertrophy and menstrual
irregularities.
 Substantial increase in production of adrenal and ovarian
androgens
 CAUSES OF HIRSUTISM

 OVARIAN
PCOS
Androgen producing ovarian tumour
Menopause
 ADRENAL
CAH
Androgen secreting adrenal tumours.
Cushing syndrome
 Hormonal
Hyperprolactinemia
Acromegay
 Idiopathic hirsutism
 Iatrogenic
androgens
progestogens
minoxidil
LABORATORY EVALUATION

 Serum total or free testosterone and

DHEA-S levels are the most important
screening tests. Elevated DHEA-S level
indicate adrenal origin of androgens
while elevated testosterone suggests
adrenal or ovarian source.
 If testosterone to SHBG ratio < 55 it
means that androgen overproduction is
unlikely and if it is >55 its suggestive of
androgen excess (adrenal/ovary)
 If testosterone is < 10nmol/L then
consider PCOS , CAH and testosterone
adminstration.
 If testosterone is > 10nmol/L then
consider androgen producing tumour
(ovary or adrenal)
 PCOS is confirmed by LH to FSH ratio >
2.5 and elevated testosterone levels.
 Prolactin levels to rule out
prolactinomas.
 To rule out CAH : Morning plasma 17α-
hydroxyprogesterone concentrations are
measured to evaluate late onset 21-
hydroxylase deficiency
 A concentration of <200 ng/dL excludes
the diagnosis and >1500ng/dL confirms
the diagnosis