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Polycystic Ovary Syndrome (PCOS)

(Hyperandrogenic Chronic Anovulation; Stein-Leventhal Syndrome)

By

JoAnn V. Pinkerton

, MD, University of Virginia Health System

Last full review/revision Dec 2020| Content last modified Dec 2020
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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.

Calcification of coronary arteries and thickening of the carotid intima media is more common among women with PCOS, suggesting possible subclinical atherosclerosis.

Type 2 diabetes mellitus and impaired glucose tolerance are more common, and risk of obstructive sleep apnea is increased.

Recent studies indicate that PCOS is associated with low-grade chronic inflammation and that women with PCOS are at increased risk of nonalcoholic fatty liver disease (1).

Complications reference

  • 1. Rocha AL, Oliveira FR, Azevedo RC, et al: Recent advances in the understanding and management of polycystic ovary syndrome. F1000Res 26;8, 2019. pii: F1000 Faculty Rev-565. doi: 10.12688/f1000research.15318.1 eCollection 2019.

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, oligomenorrhea, 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 (FSH), prolactin, and thyroid-stimulating hormone (TSH) levels

  • Pelvic ultrasonography

(For evaluation and testing related to management of comorbidities (eg, coronary artery disease, metabolic syndrome), see below.)

Ovulatory dysfunction is usually present at puberty, resulting in primary amenorrhea; thus, polycystic ovary syndrome is unlikely if regular menses occurred for a time after menarche.

In patients with polycystic ovary syndrome, 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, FSH, prolactin, and 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 algorithm 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.

Transvaginal ultrasonography can be used to check for abnormalities in the ovaries. However, transvaginal ultrasonography is not done in adolescent girls (see below).

Pearls & Pitfalls

  • Polycystic ovary syndrome is unlikely if regular menses occurred for a time after menarche.

  • In adolescents with symptoms of PCOS, measure testosterone levels.

Diagnosing PCOS in adolescent girls

Diagnosing PCOS in adolescents is complicated because physiologic changes during puberty (eg, hyperandrogenism, menstrual irregularity) are similar to features of PCOS. Thus, separate criteria for diagnosis of PCOS in adolescents (1) have been suggested: however, no consensus has been reached. These criteria require that both of the following conditions be present:

  • Abnormal uterine bleeding pattern (abnormal for age or gynecologic age or symptoms that persist for 1 to 2 years)

  • Evidence of hyperandrogenism (based on persistently elevated testosterone levels above adult norms [the best evidence], moderate-to-severe hirsutism, or moderate-to-severe inflammatory acne vulgaris as an indication to test for hyperandrogenemia)

Often, a 17-hydroxyprogesterone test is also done to screen adolescents for nonclassic congenital adrenal hyperplasia.

Pelvic ultrasonography is usually indicated only if serum androgen levels or degree of virilization suggests an ovarian tumor. Transvaginal ultrasonography is usually not used to diagnose PCOS in adolescent girls because it detects polycystic morphology in < 40% of girls and, used alone, does not predict the presence or development of PCOS.

Diagnosis reference

  • 1. Tehrani FR, Amiri M: Polycystic ovary syndrome in adolescents: Challenges in diagnosis and treatment. Int J Endocrinol Metab 17 (3): e91554, 2019. doi: 10.5812/ijem.91554

Treatment

  • Intermittent progestins or oral contraceptives

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

  • Infertility treatments in women who desire pregnancy

Treatment of polycystic ovary syndrome 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 orally once a day for 10 to 14 days every 1 to 2 months) or combination 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 twice a day 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 desire pregnancy should be referred to infertility specialists. 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. The aromatase inhibitor letrozole can also be used to stimulate ovulation. Other fertility drugs may also be tried. They include follicle-stimulating hormone (FSH) to stimulate the ovaries, a gonadotropin-releasing hormone (GnRH) agonist to stimulate the release of FSH, and human chorionic gonadotropin (hCG) to trigger ovulation.

Because 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, blood pressure, and oral glucose tolerance is recommended. If clomiphene and other drugs are unsuccessful or if there are other indications for laparoscopy, laparoscopic ovarian drilling may be considered; however possible long-term complications of drilling (eg, adhesions, ovarian insufficiency) must be considered. Ovarian drilling involves using electrocautery or a laser to drill holes in small areas of the ovaries that produce androgens. Ovarian wedge resection is not recommended.

For hirsutism, physical measures (eg, bleaching, electrolysis, plucking, waxing, depilation) can be used. Eflornithine cream 13.9% twice a day 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. Spironolactone 50 to 100 mg twice a day is effective, but because this drug may have teratogenic effects, effective contraception is needed. Cyproterone, an antiandrogen (not available in the US), reduces the amount of unwanted body hair in 50 to 75% of affected women. Weight reduction decreases androgen production in obese women and thus may slow hair growth.

GnRH agonists and antagonists are being studied as treatment for unwanted body hair. Both types of drugs inhibit the production of sex hormones by the ovaries. But both can cause bone loss and lead to osteoporosis.

Acne can be treated with the usual drugs (eg, benzoyl peroxide, tretinoin cream, topical and oral antibiotics). Systemic isotretinoin is used only for severe cases.

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, referral to a cardiovascular specialist for prevention of cardiovascular disorders is necessary if women with PCOS have any of the following:

  • A family history of early-onset cardiovascular disorders

  • Cigarette smoking

  • Diabetes mellitus

  • Hypertension

  • Dyslipidemia

  • Sleep apnea

  • Abdominal obesity (as for metabolic syndrome)

Clinicians should evaluate cardiovascular risk by determining body mass index (BMI), measuring fasting lipid and lipoprotein levels, and identifying risk factors for metabolic syndrome.

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

Tests for coronary artery calcification and thickened carotid intima media should be done to check for subclinical atherosclerosis.

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

Key Points

  • Polycystic ovary syndrome (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.

  • If women with PCOS are infertile and desire pregnancy, refer them to reproductive infertility specialists.

  • 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

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • 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. doi: 10.1210/jc.2013-2350: This evidence-based guideline uses the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.

  • Goodman NF, Cobin RH, Futterweit W, et al: American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the best practices in the evaluation and treatment of polycystic ovary syndrome–Part 1. Endocr Pract 21(11):1291–300, 2015. doi: 10.4158/EP15748.DSC: This article summarizes the best practices of 2015.

Drugs Mentioned In This Article

Drug Name Select Trade
PROVERA
No US brand names
ALDACTONE
VANIQA
SOTRET
DELATESTRYL
No US brand name
CLOMID
GLUCOPHAGE
Tretinoin
FEMARA
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