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Women’s Health - Polycystic Ovary Syndrome - Fast Facts | NEJM Resident 360

Polycystic ovary syndrome (PCOS) is a relatively common disorder affecting 6% to 20% of reproductive-age women.

• The hallmarks of the disease are hyperandrogenism and ovulatory dysfunction, including oligoamenorrhea and high rates of infertility.

• PCOS is associated with obesity and higher rates of abnormal glucose metabolism, dyslipidemia, depression, obstructive sleep apnea, and endometrial cancer.

• PCOS is also associated with increased risk of pregnancy complications (e.g., preeclampsia, preterm delivery, and gestational diabetes).

(Source: Polycystic Ovary Syndrome. N Engl J Med 2016.)

Diagnosis

Diagnostic Criteria

• clinical evidence of hyperandrogenism (e.g., hirsutism and acne)

• clinically, the diagnosis of PCOS is often made without an ultrasound to evaluate ovarian morphology or tests of androgen levels

The following table lists the most common diagnostic criteria for PCOS:

Diagnosing PCOS in the Primary Care Setting

• Conduct a thorough history and physical, including questions about:

• • menstrual patterns

  • acne

  • hirsutism: ask about and examine for male-pattern hair growth, including need for removal (shaving, depilatory use, waxing, laser hair removal, epilator use); ask about rapid progression of hirsutism or other signs of virilization (may require evaluation for androgen-secreting neoplasm)

• Rule out possible mimics: A basic workup for oligomenorrhea or amenorrhea should include:

• • human chorionic gonadotropin (hCG) to rule out pregnancy

  • thyroid-stimulating hormone (TSH) with reflex free T4

  • follicle-stimulating hormone (FSH) to rule out premature ovarian failure

  • prolactin

  • possible evaluation for atypical congenital adrenal hyperplasia, Cushing syndrome, hypothalamic amenorrhea, acromegaly, androgen-secreting tumors (associated with rapidly progressing hirsutism and elevated dehydroepiandrosterone sulfate levels)

• If diagnosis is unclear, consider the following:

  • biochemical confirmation: if biochemical confirmation is desired, measure testosterone levels:

    • Total testosterone assays are less accurate in the low levels seen in women, but the direct free testosterone level is also imperfect. Guidelines suggest ordering a total testosterone level if available.

  • imaging with pelvic ultrasound: If the diagnosis cannot be made by history, physical, and lab testing as described above, a pelvic ultrasound (transvaginal and transabdominal) to look for polycystic morphology may be helpful.

Management

• Glucose intolerance: Most guidelines suggest screening for glucose intolerance with oral glucose tolerance testing or measurement of hemoglobin A1c at least every 3–5 years, or more frequently as indicated by clinical features (obese BMI, weight change, symptoms of diabetes, or history of gestational diabetes).

• Depression, eating disorders, and sleep apnea: Screen all patients with a confirmed or suspected diagnosis of PCOS periodically for these conditions with a thorough history.

• Endometrial cancer: Despite the increased risk for endometrial cancer, there are no current guidelines on recommended screening for endometrial cancer in patients with PCOS. Use of routine ultrasound for measurement of endometrial thickness is not advised; however, ultrasound may be considered in patients presenting with a history of anemia and irregular cycles. Use of a progestin-containing contraceptive is advisable for all obese women who do not desire pregnancy.

• Cardiovascular disease: See the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society guidelines on assessment and screening for cardiovascular disease in PCOS.

• Fertility: 

  • Preconception counseling about the importance of lifestyle modifications (including weight reduction, smoking cessation, and reduction of alcohol consumption) is an important initial step. 

  • Letrozole has been associated with higher rates of ovulation, pregnancy, and live-births than clomiphene citrate, and has therefore become first-line treatment for ovulation induction. Treatment with letrozole or clomiphene should be considered for women who:

    • desire pregnancy

    • have difficulties conceiving for 6–12 months

    • fail a trial of weight loss

  • If neither letrozole nor clomiphene result in pregnancy, the recommendation for second-line treatment is with exogenous gonadotropins or consideration of laparoscopic ovarian surgery.

• Treatment

  • Treatment is aimed at three main targets: hirsutism, irregular menses (and endometrial hyperplasia) and infertility. 

  • Weight loss is the mainstay of therapy. No available therapies reverse the underlying disease process, but weight loss has been shown to reduce cardiovascular risk and hyperandrogenemia. 

  • Treatment of symptoms: Treatment otherwise focuses on ameliorating symptoms (e.g., hirsutism and menstrual irregularity); some therapies can decrease the rate of complications such as cardiovascular disease and infertility.

  • Nonpharmacologic treatment options include weight loss and mechanical hair removal.

  • Pharmacologic treatment options include progestin-containing contraceptives to decrease risk of endometrial hyperplasia and reduce hirsutism, spironolactone to reduce hirsutism, and metformin to reduce hyperglycemia. Letrozole, an aromatase inhibitor, has become the first-line treatment for ovulation induction to address infertility.

The following table indicates the expected effects of various therapies for PCOS:

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