Chapter 050. Hirsutism and Virilization (Part 4)

PCOS is the most common cause of ovarian androgen excess (Chap. 341). However, the increased ratio of LH to follicle-stimulating hormone that is characteristic of carefully studied patients with PCOS is not seen in up to half of these women due to the pulsatility of gonadotropins. If performed, ultrasound shows enlarged ovaries and increased stroma in many women with PCOS. However, polycystic ovaries may also be found in women without clinical or laboratory features of PCOS. Therefore, polycystic ovaries are a relatively insensitive and nonspecific finding for the diagnosis of ovarian hyperandrogenism. Although not usually necessary, gonadotropin-releasing hormone agonist...
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Chapter 050. Hirsutism and Virilization (Part 4) Chapter 050. Hirsutism and Virilization (Part 4) PCOS is the most common cause of ovarian androgen excess (Chap. 341).However, the increased ratio of LH to follicle-stimulating hormone that ischaracteristic of carefully studied patients with PCOS is not seen in up to half ofthese women due to the pulsatility of gonadotropins. If performed, ultrasoundshows enlarged ovaries and increased stroma in many women with PCOS.However, polycystic ovaries may also be found in women without clinical orlaboratory features of PCOS. Therefore, polycystic ovaries are a relativelyinsensitive and nonspecific finding for the diagnosis of ovarian hyperandrogenism.Although not usually necessary, gonadotropin-releasing hormone agonist testingcan be used to make a specific diagnosis of ovarian hyperandrogenism. A peak 17-hydroxyprogesterone level ≥7.8 nmol/L (≥2.6 µg/L), after the administration of100 µg nafarelin (or 10 µg/kg leuprolide) subcutaneously, is virtually diagnosticof ovarian hyperandrogenism. Because adrenal androgens are readily suppressed by low doses ofglucocorticoids, the dexamethasone androgen-suppression test may broadlydistinguish ovarian from adrenal androgen overproduction. A blood sample isobtained before and after administering dexamethasone (0.5 mg orally every 6 hfor 4 days). An adrenal source is suggested by suppression of unboundtestosterone into the normal range; incomplete suppression suggests ovarianandrogen excess. An overnight 1-mg dexamethasone suppression test, withmeasurement of 8:00 A.M. serum cortisol, is useful when there is clinicalsuspicion of Cushings syndrome (Chap. 336). Nonclassic CAH is most commonly due to 21-hydroxylase deficiency butcan also be caused by autosomal recessive defects in other steroidogenic enzymesnecessary for adrenal corticosteroid synthesis (Chap. 336). Because of the enzymedefect, the adrenal gland cannot secrete glucocorticoids efficiently (especiallycortisol). This results in diminished negative feedback inhibition of ACTH,leading to compensatory adrenal hyperplasia and the accumulation of steroidprecursors that are subsequently converted to androgen. Deficiency of 21-hydroxylase can be reliably excluded by determining a morning 17-hydroxyprogesterone level Alternatively, 21-hydroxylase deficiency can be diagnosed by measurement of 17-hydroxyprogesterone 1 h after administration of 250 µg of synthetic ACTH(cosyntropin) intravenously. Hirsutism: Treatment Treatment of hirsutism may be accomplished pharmacologically or bymechanical means of hair removal. Nonpharmacologic treatments should beconsidered in all patients, either as the only treatment or as an adjunct to drugtherapy. Nonpharmacologic treatments include (1) bleaching; (2) depilatory(removal from the skin surface) such as shaving and chemical treatments; or (3)epilatory (removal of the hair including the root) such as plucking, waxing,electrolysis, and laser therapy. Despite perceptions to the contrary, shaving does not increase the rate ordensity of hair growth. Chemical depilatory treatments may be useful for mildhirsutism that affects only limited skin areas, though they can cause skin irritation.Wax treatment removes hair temporarily but is uncomfortable. Electrolysis is effective for more permanent hair removal, particularly inthe hands of a skilled electrologist. Laser phototherapy appears to be efficaciousfor hair removal. It delays hair regrowth and causes permanent hair removal inmost patients. The long-term effects and complications associated with lasertreatment are still being evaluated. Pharmacologic therapy is directed at interrupting one or more of the stepsin the pathway of androgen synthesis and action: (1) suppression of adrenal and/orovarian androgen production; (2) enhancement of androgen-binding to plasma-binding proteins, particularly SHBG; (3) impairment of the peripheral conversionof androgen precursors to active androgen; and (4) inhibition of androgen action atthe target tissue level. Attenuation of hair growth is typically not evident until 4–6 months afterinitiation of medical treatment and, in most cases, leads to only a modest reductionin hair growth. Combination estrogen-progestin therapy, in the form of an oralcontraceptive, is usually the first-line endocrine treatment for hirsutism and acne,after cosmetic and dermatologic management. The estrogenic component of mostoral contraceptives currently in use is either ethinyl estradiol or mestranol. Thesuppression of LH leads to reduced production of ovarian androgens. The reduced androgen levels also result in a dose-related increase inSHBG, thereby lowering ...