Secondary amenorrhea is the absence of menses for more than three cycles or six months in women who previously had menses. Pregnancy is the most common cause. The document outlines the step-by-step process for evaluating secondary amenorrhea, including ruling out pregnancy, assessing medical history, performing a physical exam, basic lab tests, and follow-up testing and evaluation if initial results require further investigation. Treatment options are provided for common causes like hyperprolactinemia, ovarian failure, hyperandrogenism, and Asherman's syndrome.

1. Secondary Amenorrhea
Secondary amenorrhea is defined as absence of menses
for more than three cycles or six months in women
who previously had menses.
Pregnancy is the most common cause of secondary
amenorrhea.

2. I. Diagnosis of secondary amenorrhea
A. Step 1: Rule out pregnancy.
A pregnancy test is the first step in
evaluating secondary amenorrhea.
Measurement of serum beta subunit of hCG is
the most sensitive test

3. B. Step 2: Assess the history
1. Recent stress; change in weight, diet or exercise
habits; or illnesses that might result in hypothalamic
amenorrhea should be sought.
2. Drugs associated with amenorrhea, systemic
illnesses that can cause hypothalamic amenorrhea,
-recent initiation or discontinuationof an oral contraceptive,
-androgenic drugs(danazol)
- high-dose progestin,
-antipsychotic drugs should be evaluated.

4. 3. Headaches, visual field defects, fatigue, or
polyuria and polydipsia may suggest
hypothalamic-pituitary disease.
4. Symptoms of estrogen deficiency include
hot flashes, vaginal dryness, poor sleep, or
decreased libido.
5. Galactorrhea is suggestive of
hyperprolactinemia.
6-Hirsutism, acne, and a history of irregular
menses are suggestive of hyperandrogenism.

5. 7. A history of obstetrical
catastrophe, severe bleeding, dilatation
and curettage, or endometritis or other
infection that might have caused scarring of
the endometrial lining suggests Asherman's
syndrome.

6. C. Step 3: Physical examination.
Measurements of height and weight, signs of
other illnesses, and evidence of cachexia should
be assessed. The skin, breasts, and genital
tissues should be evaluated for estrogen
deficiency. The breasts should be
palpated, including an attempt to express
galactorrhea. The skin should be examined for
hirsutism, acne, striae, acanthosis
nigricans, vitiligo, thickness or thinness, and easy
bruisability.

7. D. Step 4: Basic laboratory testing.
• measurement of serum hCG to rule out
pregnancy
• serum prolactin to rule out hyperprolactinemia,
• TSH thyroid disease
• FSH to rule out ovarian failure (high serum
FSH).
• If there is hirsutism, acne or irregular
menses, serum dehydroepiandrosterone sulfate
(DHEA-S)
and testosterone should be measured.

8. E. Step 5: Follow-up laboratory evaluation
1. High serum prolactin concentration.
Prolactin secretion can be transiently increased
by stress or eating. Therefore, serum prolactin
should be measured at least twice before cranial
imaging is obtained, particularly in those
women with small elevations (<50 ng/mL).
These women should be screened for thyroid
disease with a TSH and free T4 because
hypothyroidism can cause hyperprolactinemia.

9. 2. Women with verified high serum
prolactin values should have a cranial MRI
unless a very clear explanation is found for
the elevation (eg,antipsychotics). Imaging
should rule out a hypothalamic or pituitary
tumor.

10. 3. High serum FSH concentration.
A high serum FSH concentration indicates
the presence of ovarian failure. This test
should be repeated monthly on three
occasions to confirm. A karyotype should be
considered in most women with secondary
amenorrhea age 30 years or younger.

11. 4. High serum androgen concentrations.
A high serum androgen value may suggest the
diagnosis of polycystic ovary syndrome or may suggest
an androgen-secreting tumor of the ovary or
adrenal gland.
Further testing for a tumor might include a 24-hour urine
collection for cortisol and 17-ketosteroids, determination
of serum 17- hydroxyprogesterone after intravenous
injection of corticotropin (ACTH), and a dexamethasone
suppression test.
Elevation of 17-ketosteroids, DHEA-S, or 17-
hydroxyprogesterone is more consistent with an
adrenal, rather than ovarian, source of excess androgen.

12. 5. Normal or low serum gonadotropin
concentrations and all other tests normal
a. This result is one of the most common outcomes
of laboratory testing in women with amenorrhea. Women with
hypothalamic amenorrhea (caused by excessive exercise or
weight loss) have normal to low serum FSH values.
Cranial MRI is indicated in all women without a clear
explanation for hypogonadotropic hypogonadism and in most
women who have visual field defects or headaches. No further
testing is required if the onset of amenorrhea is recent or is
easily explained (eg, weight loss, excessive exercise) and
there are no symptoms suggestive of other disease.

13. 6. Normal serum prolactin and FSH
concentrations with history of uterine
instrumentation preceding amenorrhea
evaluation for Asherman's syndrome should
be completed.
a-A progestin challenge should be performed
(medroxyprogesterone acetate 10 mg for 10
days). If withdrawal bleeding
occurs, an outflow tract disorder has been
ruled out. If bleeding does not occur, estrogen
and progestin should be administered.

14. b. Oral conjugated estrogens (0.625 to 2.5 mg
daily for 35 days) with medroxyprogesterone
added (10 mg daily for days 26 to 35); failure
to bleed upon cessation of this therapy
strongly suggests endometrial scarring. In
this situation, a hysterosalpingogram or
hysteroscopy can confirm the diagnosis of
Asherman syndrome.

15. II. Treatment
A. Athletic women should be counseled on the need
for increased caloric intake or reduced exercise.
Resumption of menses usually occurs.
B. Nonathletic women who are underweight
should receive nutritional counseling and treatment
of eating disorders.
C. Hyperprolactinemia is treated with a dopamine
agonist. Cabergoline (Dostinex) or bromocriptine
(Parlodel) are used for most adenomas. Ovulation,
regular menstrual cycles, and pregnancy may usually
result.
D. Ovarian failure should be treated with hormone
replacement therapy.

16. E. Hyperandrogenism is treated with
measures to reduce hirsutism, resume
menses, and fertility and
preventing endometrial hyperplasia, obesity, and
metabolic defects.
F. Asherman's syndrome is treated with
hysteroscopic lysis of adhesions followed by
longterm estrogen administration to stimulate
regrowth of endometrial tissue.

18. hyperandrogenism is any clinical or laboratory
evidence of androgen excess in women. The most
common clinical presentation of
hyperandrogenism in reproductive-aged women is
hirsutism or acne with or without evidence of
anovulation such as oligoamenorrhea - or
amenorrhea or dysfunctional uterine bleeding.
Elevated blood levels of androgens without clinical
symptoms is referred to as cryptic
hyperandrogenism.

19. Hirsutism refers to the presence of course terminal
hairs in androgen-dependent areas on the face
and body in women.
hypertrichosis, which is excessive growth of thin
vellus hair at any body site. Hypertrichosis is
usually familial or associated with endocrine
disturbances such as anorexia nervosa or thyroid
dysfunction, or with medications such as
phenytoin, minoxidil or cyclosporin ).
.

20.  Hirsutism affects between 2-10% of
women between the ages of 18 and 45.
It is often a source of psychological
discomfort and may be a sign of a
significant medical disorder as will be
discussed

21. Hirsutism develops when follicles in androgen
sensitive areas start to form thick, pigmented
(terminal) hair as opposed to thin, short, non-
pigmented (vellus) hair normally seen in those
areas in women.

22. causes
The causes of hyperandrogenism in
reproductive aged women can be
divided into five categories in
descending order of prevalence.

23. . Causes of Hyperandrogenism
Common
Polycystic Ovary Syndrome 80%
Idiopathic Hirsutism 15%
Uncommon
Late-Onset 21-Hydroxylase Deficiency1- 5%
Rare < 1%
 Steroidogenic Enzyme Deficiencies
3b-hydroxysteroid dehydrogenase
17-ketosteroid reductase
 aromatasen
Androgen Secreting Tumors of Ovary or Adrenal
Ovarian Hyperthecosis (a PCOS variant)
 Other Endocrine
Hyperprolactinemia
Cushing syndrome
Defects in cortisol metabolism
Acromegaly

24. Idiopathic Hirsutism
Idiopathic hirsutism is excess terminal hair
production in androgen dependent areas in the
presence of regular ovulation and normal
androgen levels .It is the second most common
cause of hirsutism after PCOS and occurs in
about 15% of hirsute women.
The pathophysiology of this disorder still needs to
be fully elucidated, but is thought to be secondary
to increased 5a-reductase activity in the skin or its
appendages, to other alterations in androgen
metabolism or to increased sensitivity of the
androgen receptor

25. Polycystic Ovary
Syndrome
PCOS is the most common cause of
hirsutism and the most common
endocrinopathy in reproductive aged
women. It has a prevalence of about 5%
in Caucasian and African Americans and
in European populations (8-10 %).

26. Adrenal and Ovarian
Steroidogenic Enzyme
Deficiencies
Adrenal or ovarian steroidogenic enzyme
deficiencies are the most common
cause of hyperandrogenism in post-
menarcheal women after PCOS and
idiopathic hirsutism. Nevertheless these
conditions are uncommon to very rare.
Late-onset 21-hydroxylase deficiency
occurs in 1-5% of hirsute women, with
the greatest prevalence in women of
Askenazi Jewish descent

27.  Ovarian and Adrenal Tumors
 Both adrenal adenoma and carcinoma may
present with virilization and hyperandrogenemia
.
 Androgen secreting ovarian tumors include
Sertoli-Leydig cell tumors, Leydig cell tumors,
lipoid or lipid cell tumors and granulose-theca
cell tumors

28. Typically women with androgen secreting tumors
have abrupt onset of symptoms distinct from
menarche and a more rapid progressions of
symptoms compared to PCOS.
Signs of virilization such as clitoromegaly, frontal
balding and deepening of the voice are also more
common. Testosterone levels are usually greater
than 200 ng/dl or 2 1/2 times the upper limit of
normal, but there is clearly overlap between
testosterone levels found in tumors and those
seen in severe cases of PCOS or hyperthecosis,
If a tumor is suspected, both ovarian ultrasound and
adrenal CT scan should be done to localize it

29. Other Endocrine Disorders
 Hirsutism may be present in hyperprolactinemia
with or without pituitary adenoma, Cushing
syndrome and acromegaly. However it is usually
not the primary complaint in these disorders.
Prolactin should be determined in all patients
with anovulation.

30. Cushing syndrome can be ruled out by a normal
24 hour urinary cortisol or normal overnight
dexamethasone suppression test . If there is any
suspicion of acromegaly, a somatomedin-C level
(IGF-I) and/or growth hormone suppression test
should be done.