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Polycystic Ovary Syndrome (PCOS)

(Hyperandrogenic Chronic Anovulation; Stein-Leventhal Syndrome)

By JoAnn V. Pinkerton, MD, Professor of Obstetrics and Gynecology and Director, Division of Midlife Health, University of Virginia Health System

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Polycystic ovary syndrome is a clinical syndrome characterized by mild obesity, irregular menses or amenorrhea, and signs of androgen excess (eg, hirsutism, acne). Most patients have multiple cysts in the ovaries. 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.

PCOS 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.

Complications

Polycystic ovary syndrome 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 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 and hyperlipidemia. Risk of androgen excess and its complications may be just as high in women who are not overweight as in those who are.

Symptoms and Signs

Symptoms of polycystic ovary syndrome 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. However, in up to half of women with PCOS, weight is normal, and some women are underweight. Body hair may grow in a male pattern (eg, on the upper lip, chin, back, thumbs, and toes; around the nipples; and along the linea alba of the lower abdomen). Some women have other signs of virilization, such as acne and temporal hair thinning.

Other symptoms may include weight gain (sometimes seemingly hard to control), fatigue, low energy, sleep-related problems (including sleep apnea), mood swings, depression, anxiety, and headaches. In some women, fertility is impaired. Symptoms vary from woman to woman.

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.

If women with PCOS become pregnant, risk of pregnancy complications is increased, and complications are worse if women are obese. These complications include gestational diabetes, preterm delivery, and preeclampsia.

Diagnosis

  • Clinical criteria

  • Serum testosterone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone levels

  • Pelvic ultrasonography

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 Male Hypogonadism : 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 2 of the following 3 criteria:

  • Ovulatory dysfunction causing menstrual irregularity

  • Clinical or biochemical evidence of hyperandrogenism

  • > 10 follicles per ovary (detected by pelvic ultrasonography), usually occurring in the periphery and resembling a string of pearls

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.

Adult women with PCOS are evaluated for metabolic syndrome by measuring BP and usually serum glucose and lipids (lipid profile).

Pearls & Pitfalls

  • PCOS is unlikely if regular menses occurred for a time after menarche.

Treatment

  • Intermittent progestogens or oral contraceptives

  • Management of hirsutism and, in adult women, long-term risks of hormonal abnormalities

  • Infertility treatments in women who desire pregnancy

Treatment aims to

  • Correct hormonal abnormalities and thus reduce risks of estrogen excess (eg, endometrial hyperplasia) and androgen excess (eg, cardiovascular disorders)

  • Relieve symptoms and improve fertility

Weight loss and regular exercise are encouraged. They may help induce ovulation, make menstrual cycles more regular, increase insulin sensitivity, and reduce acanthosis nigricans and hirsutism. Weight loss may also help improve fertility. However, weight loss is unlikely to benefit normal-weight women with PCOS.

Hormonal contraceptives are first-line therapy for menstrual abnormalities, hirsutism, and acne in women who have PCOS and who do not desire pregnancy. Women 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.

Metformin 500 to 1000 mg bid is used to help increase insulin sensitivity in women with PCOS, irregular menses, and diabetes or insulin resistance if lifestyle modifications are ineffective or if they cannot take or cannot tolerate hormonal contraceptives. 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. Metformin helps correct metabolic and glycemic abnormalities and makes menstrual cycles more regular, but it has little or no beneficial effect on hirsutism, acne, or infertility.

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 women who desire pregnancy, infertility treatments (eg, clomiphene) are used. Clomiphene is currently the first-line therapy for infertility. Weight loss may also be helpful. Hormone therapy that may have contraceptive effects is avoided. Women with PCOS have a higher risk of pregnancy complications, including gestational diabetes, preterm delivery, and preeclampsia, which are exacerbated by obesity. Preconception assessment of body mass index (BMI), BP, and oral glucose tolerance is recommended.

For 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).

Management of comorbidities

Because risk of depression and anxiety is increased in PCOS, women and adolescents with PCOS should be screened for these problems based on history, and if a problem is identified, they should be referred to a mental health care practitioner and/or treated as needed.

Overweight or obese adolescents and women with PCOS should be screened for symptoms of obstructive sleep apnea using polysomnography and treated as needed.

Because PCOS can increase the risk of cardiovascular disorders, women with PCOS and any of the following should be referred to a cardiovascular specialist for prevention of cardiovascular disorders:

  • A family history of early-onset cardiovascular disorders

  • Cigarette smoking

  • Diabetes mellitus

  • Hypertension

  • Dyslipidemia

  • Sleep apnea

  • Abdominal obesity (see Metabolic Syndrome : Diagnosis)

Women with abnormal vaginal bleeding should be screened for endometrial carcinoma using endometrial biopsy and/or transvaginal ultrasonography or office hysteroscopy.

Key Points

  • PCOS is a common cause of ovulatory dysfunction.

  • Suspect PCOS in women who have irregular menses, are mildly obese, and are slightly hirsute, but be aware that weight is normal or low in many women with PCOS.

  • Test for serious disorders (eg, Cushing syndrome, tumors) that can cause similar symptoms and for complications (eg, metabolic syndrome)

  • If pregnancy is not desired, treat women with hormonal contraceptives and recommend lifestyle modifications; if lifestyle modifications are ineffective, add metformin.

  • Screen for comorbidities, such as endometrial cancer, mood and anxiety disorders, obstructive sleep apnea, diabetes, and cardiovascular risk factors (including hypertension and hyperlipidemia).

More Information

  • Legro RS, Arslanian SA, Ehrmann DA, et al: Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 98 (12):4565–4592, 2013, https://doi.org/10.1210/jc.2013-2350.

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