Secondary AmenorrheaSecondary amenorrhea is defined as absence of mensesfor more than three cycles or six months in womenwho 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 isthe 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, orpolyuria and polydipsia may suggesthypothalamic-pituitary disease.4. Symptoms of estrogen deficiency includehot flashes, vaginal dryness, poor sleep, ordecreased libido.5. Galactorrhea is suggestive ofhyperprolactinemia.6-Hirsutism, acne, and a history of irregularmenses are suggestive of hyperandrogenism.
7. A history of obstetricalcatastrophe, severe bleeding, dilatationand curettage, or endometritis or otherinfection that might have caused scarring ofthe endometrial lining suggests Ashermanssyndrome.
C. Step 3: Physical examination.Measurements of height and weight, signs ofother illnesses, and evidence of cachexia shouldbe assessed. The skin, breasts, and genitaltissues should be evaluated for estrogendeficiency. The breasts should bepalpated, including an attempt to expressgalactorrhea. The skin should be examined forhirsutism, acne, striae, acanthosisnigricans, vitiligo, thickness or thinness, and easybruisability.
D. Step 4: Basic laboratory testing.• measurement of serum hCG to rule outpregnancy• serum prolactin to rule out hyperprolactinemia,• TSH thyroid disease• FSH to rule out ovarian failure (high serumFSH).• If there is hirsutism, acne or irregularmenses, 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 serumprolactin values should have a cranial MRIunless a very clear explanation is found forthe elevation (eg,antipsychotics). Imagingshould rule out a hypothalamic or pituitarytumor.
3. High serum FSH concentration. A high serum FSH concentration indicatesthe presence of ovarian failure. This testshould be repeated monthly on threeoccasions to confirm. A karyotype should beconsidered in most women with secondaryamenorrhea age 30 years or younger.
4. High serum androgen concentrations.A high serum androgen value may suggest thediagnosis 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 urinecollection for cortisol and 17-ketosteroids, determinationof serum 17- hydroxyprogesterone after intravenousinjection of corticotropin (ACTH), and a dexamethasonesuppression test.Elevation of 17-ketosteroids, DHEA-S, or 17-hydroxyprogesterone is more consistent with anadrenal, rather than ovarian, source of excess androgen.
5. Normal or low serum gonadotropinconcentrations 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 FSHconcentrations with history of uterineinstrumentation preceding amenorrheaevaluation for Ashermans syndrome should be completed. a-A progestin challenge should be performed (medroxyprogesterone acetate 10 mg for 10 days). If withdrawal bleedingoccurs, 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 withmeasures to reduce hirsutism, resumemenses, and fertility andpreventing endometrial hyperplasia, obesity, andmetabolic defects.F. Ashermans syndrome is treated withhysteroscopic lysis of adhesions followed bylongterm estrogen administration to stimulateregrowth of endometrial tissue.
hyperandrogenism is any clinical or laboratoryevidence of androgen excess in women. The mostcommon clinical presentation ofhyperandrogenism in reproductive-aged women ishirsutism or acne with or without evidence ofanovulation such as oligoamenorrhea - oramenorrhea or dysfunctional uterine bleeding.Elevated blood levels of androgens without clinicalsymptoms is referred to as cryptichyperandrogenism.
Hirsutism refers to the presence of course terminalhairs in androgen-dependent areas on the faceand body in women. hypertrichosis, which is excessive growth of thinvellus hair at any body site. Hypertrichosis isusually familial or associated with endocrinedisturbances such as anorexia nervosa or thyroiddysfunction, or with medications such asphenytoin, 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 androgensensitive areas start to form thick, pigmented(terminal) hair as opposed to thin, short, non-pigmented (vellus) hair normally seen in thoseareas in women.
causesThe causes of hyperandrogenism inreproductive aged women can bedivided into five categories indescending 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 aromatasenAndrogen Secreting Tumors of Ovary or AdrenalOvarian Hyperthecosis (a PCOS variant) Other EndocrineHyperprolactinemiaCushing syndromeDefects in cortisol metabolismAcromegaly
Idiopathic HirsutismIdiopathic hirsutism is excess terminal hairproduction in androgen dependent areas in thepresence of regular ovulation and normalandrogen levels .It is the second most commoncause of hirsutism after PCOS and occurs inabout 15% of hirsute women. The pathophysiology of this disorder still needs tobe fully elucidated, but is thought to be secondaryto increased 5a-reductase activity in the skin or itsappendages, to other alterations in androgenmetabolism or to increased sensitivity of theandrogen receptor
Polycystic OvarySyndromePCOS is the most common cause ofhirsutism and the most commonendocrinopathy in reproductive agedwomen. It has a prevalence of about 5%in Caucasian and African Americans andin European populations (8-10 %).
Adrenal and OvarianSteroidogenic EnzymeDeficienciesAdrenal or ovarian steroidogenic enzymedeficiencies are the most commoncause of hyperandrogenism in post-menarcheal women after PCOS andidiopathic hirsutism. Nevertheless theseconditions are uncommon to very rare.Late-onset 21-hydroxylase deficiencyoccurs in 1-5% of hirsute women, withthe greatest prevalence in women ofAskenazi 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 overnightdexamethasone suppression test . If there is anysuspicion of acromegaly, a somatomedin-C level(IGF-I) and/or growth hormone suppression testshould be done.