gynaecology.Sec amenorrhea.(dr.hana)

Secondary AmenorrheaSecondary 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 secondaryamenorrhea.

I. Diagnosis of secondary amenorrheaA. 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

B. Step 2: Assess the history1. Recent stress; change in weight, diet or exercisehabits; or illnesses that might result in hypothalamicamenorrhea should be sought.2. Drugs associated with amenorrhea, systemicillnesses that can cause hypothalamic amenorrhea, -recent initiation or discontinuationof an oral contraceptive, -androgenic drugs(danazol)- high-dose progestin,-antipsychotic drugs should be evaluated.

3. Headaches, visual field defects, fatigue, or polyuria and polydipsia may suggesthypothalamic-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.

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.

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 easybruisability.

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.

E. Step 5: Follow-up laboratory evaluation1. High serum prolactin concentration.Prolactin secretion can be transiently increasedby stress or eating. Therefore, serum prolactinshould be measured at least twice before cranialimaging is obtained, particularly in thosewomen with small elevations (<50 ng/mL).These women should be screened for thyroiddisease with a TSH and free T4 becausehypothyroidism can cause hyperprolactinemia.

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.

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.

4. High serum androgen concentrations. A high serum androgen value may suggest the diagnosis of polycystic ovary syndrome or may suggestan androgen-secreting tumor of the ovary oradrenal 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 dexamethasonesuppression test. Elevation of 17-ketosteroids, DHEA-S, or 17-hydroxyprogesterone is more consistent with an adrenal, rather than ovarian, source of excess androgen.

5. Normal or low serum gonadotropin concentrations and all other tests normala. 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.

6. Normal serum prolactin and FSH concentrations with history of uterine instrumentation preceding amenorrheaevaluation 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 beenruled out. If bleeding does not occur, estrogenand progestin should be administered.

b. Oral conjugated estrogens (0.625 to 2.5 mgdaily for 35 days) with medroxyprogesteroneadded (10 mg daily for days 26 to 35); failureto bleed upon cessation of this therapystrongly suggests endometrial scarring. Inthis situation, a hysterosalpingogram orhysteroscopy can confirm the diagnosis ofAsherman syndrome.

II. TreatmentA. Athletic women should be counseled on the needfor increased caloric intake or reduced exercise.Resumption of menses usually occurs.B. Nonathletic women who are underweightshould receive nutritional counseling and treatmentof eating disorders.C. Hyperprolactinemia is treated with a dopamineagonist. Cabergoline (Dostinex) or bromocriptine(Parlodel) are used for most adenomas. Ovulation,regular menstrual cycles, and pregnancy may usuallyresult.D. Ovarian failure should be treated with hormonereplacement therapy.

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

HYPERANDROGENISM, HIRSUTISM AND POLYCYSTIC

OVARY SYNDROME

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 .

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.) .

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

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.

causes

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

.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

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

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 %) .

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

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

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

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.

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 .