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Polycystic Ovary Syndrome (PCOS)
(Hyperandrogenic Chronic Anovulation; Stein-Leventhal Syndrome)
Polycystic ovary syndrome is a clinical syndrome characterized by mild obesity, irregular menses or amenorrhea, and signs of androgen excess (eg, hirsutism, acne). In most patients, the ovaries contain multiple cysts. Diagnosis is by pregnancy testing, hormone measurement, and imaging to exclude a virilizing tumor. Treatment is symptomatic.
Polycystic ovary syndrome (PCOS) occurs in 5 to 10% of women. In the US, it is the most common cause of infertility. It is usually defined as a clinical syndrome, not by the presence of ovarian cysts. But typically, ovaries contain many 2- to 6-mm follicular cysts and sometimes larger cysts containing atretic cells. Ovaries may be enlarged with smooth, thickened capsules or may be normal in size.
This syndrome involves anovulation or ovulatory dysfunction and androgen excess of unclear etiology. However, some evidence suggests that patients have a functional abnormality of cytochrome P450c17 affecting 17-hydroxylase (the rate-limiting enzyme in androgen production); as a result, androgen production increases.
PCOS has several serious complications. Estrogen levels are elevated, increasing risk of endometrial hyperplasia and, eventually, endometrial cancer. Androgen levels are often elevated, increasing the risk of metabolic syndrome (see Metabolic Syndrome) and causing hirsutism. Hyperinsulinemia due to insulin resistance may be present and may contribute to increased ovarian production of androgens. Over the long term, androgen excess increases the risk of cardiovascular disorders, including hypertension.
Symptoms typically begin during puberty and worsen with time. Premature adrenarche, characterized by excess dehydroepiandrosterone sulfate (DHEAS) and often early growth of axillary hair, body odor, and microcomedonal acne, is common. Typical symptoms include mild obesity, slight hirsutism, and irregular menses or amenorrhea. Body hair may grow in a male pattern (eg, on the upper lip and chin, around the nipples, and along the linea alba of the lower abdomen). Some women have other signs of virilization, such as acne and temporal balding. Areas of thickened, darkened skin (acanthosis nigricans) may appear in the axillae, on the nape of the neck, in skinfolds, and on knuckles and/or elbows; the cause is high insulin levels due to insulin resistance.
Ovulatory dysfunction is usually present at puberty, resulting in primary amenorrhea; thus, this syndrome is unlikely if regular menses occurred for a time after menarche.
Examination usually detects abundant cervical mucus, reflecting high estrogen levels. PCOS is suspected if women have at least two typical symptoms.
Testing includes pregnancy testing; measurement of serum total testosterone , follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH); and pelvic ultrasonography to exclude other possible causes of symptoms. Serum free testosterone is more sensitive than total testosterone but is technically more difficult to measure (see Diagnosis of primary and secondary hypogonadism). Normal to mildly increased testosterone and normal to mildly decreased FSH levels suggest PCOS.
The diagnosis requires at least two of the following three criteria:
In women meeting these criteria, serum cortisol is measured to exclude Cushing syndrome, and early-morning serum 17-hydroxyprogesterone is measured to exclude adrenal virilism. Serum DHEAS is measured. If DHEAS is abnormal, women are evaluated as for amenorrhea (see Amenorrhea : Evaluation). Adult women with PCOS are evaluated for metabolic syndrome by measuring BP and usually serum glucose and lipids (lipid profile).
Treatment aims to relieve symptoms and to correct hormonal abnormalities and thus reduce risks of estrogen excess (eg, endometrial hyperplasia) and androgen excess (eg, cardiovascular disorders).
Women who do not desire pregnancy are usually given an intermittent progestin (eg, medroxyprogesterone 5 to 10 mg po once/day for 10 to 14 days every 1 to 2 mo) or oral contraceptives to reduce the risk of endometrial hyperplasia and cancer. These treatments also reduce circulating androgens and usually help make menstrual cycles more regular.
For hirsutism (see Hirsutism), physical measures (eg, bleaching, electrolysis, plucking, waxing, depilation) can be used. Eflornithine cream 13.9% bid may help remove unwanted facial hair. In adult women who do not desire pregnancy, hormone therapy that decreases androgen levels or spironolactone can be tried. Acne can be treated with the usual drugs (eg, benzoyl peroxide, tretinoin cream, topical and oral antibiotics).
Weight loss is encouraged. It may help induce ovulation, make menstrual cycles more regular, increase insulin sensitivity, and reduce acanthosis nigricans and hirsutism.
Metformin 500 to 1000 mg bid is used to help increase insulin sensitivity if weight loss is unsuccessful or menses do not resume. Metformin can also reduce free testosterone levels. When metformin is used, serum glucose should be measured, and kidney and liver function tests should be done periodically. Because metformin may induce ovulation, contraception is needed if pregnancy is not desired.
For women who desire pregnancy, infertility treatments (eg, clomiphene, metformin) are used (see Ovulatory Dysfunction : Treatment). Weight loss may also be helpful. Hormone therapy that may have contraceptive effects is avoided.
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