Table 2.

Anticipated Effects of Common Therapeutic Options for the Polycystic Ovary Syndrome.^*

Therapeutic Option	Clinical Hyperandrogenism	Ovulatory Function	Endometrial Protection	Reliable Contraception	Cardiovascular Risk	Practical Considerations
Weight loss (if patient overweight)	Reduced androgen levels likely, but effect on hirsutism uncertain	Variable improvement	Yes, if normal ovulatory function is restored†	No (may increase pregnancy risk)	Expected improvement	No specific diet or exercise regimen has been proved to be superior in the polycystic ovary syndrome.
Mechanical hair removal	Improvement expected	—	—	—	—	Typically required even when pharmacologic therapy is used.
Oral combined hormonal contraceptives	Improvement expected	Reliable suppression	Yes	Yes	Increased risk of venous thromboembolism; potential increase in blood pressure, triglyceride, and HDL cholesterol levels; possible increase in cardiovascular events (all effects reversed after discontinuation)‡	One example is ethinyl estradiol (35 μg) plus norgestimate (0.25 mg), but no specific estrogen–progestin combination has been proved to be superior in the polycystic ovary syndrome. Daily ethinyl estradiol doses of 20 to 35 μg are acceptable. Progestins with low androgenic potential include norgestimate, desogestrel, gestodene, and drospirenone; among these, norgestimate may be associated with lower risk of venous thromboembolism.31 Medical eligibility (i.e., potential contraindications) should be considered before and during treatment.§
Spironolactone¶	Improvement expected	—	—	—	—	Spironolactone may be started at 50 mg twice daily, increasing to 100 mg twice daily as needed. Pregnancy must be strictly avoided in patients who receive spironolactone.
Metformin║	Reduced androgen levels likely, but effect on hirsutism unlikely	Variable improvement	Yes, if normal ovulatory function is restored†	No (may increase pregnancy risk)	Reduced hyperinsulinemia; probable reduced risk of impaired glucose tolerance and type 2 diabetes mellitus; favorable effects on lipid levels possible; possible weight loss (modest); theoretical but unproven benefit with respect to long-term risk of cardiovascular disease	Gastrointestinal side effects of metformin may be limited by starting at a low dose (500 mg daily with a meal), gradually increasing to 1000 mg twice daily with meals.
Progestin (episodic administration)	—	—	Yes**	—	—	Oral micronized progesterone (200 mg at bedtime) or oral medroxyprogesterone acetate (5–10 mg daily) for 10–14 days every 1–3 mo.
Progestin-only contraceptive pills	—	Variable suppression ††	Yes	Yes	—	Only norethindrone (0.35 mg/day without a hormone-free week) is available in the United States.
Levonorgestrel-releasing intrauterine device	—	—	Yes	Yes	—

^*Dashes indicate that clinically significant effects are not expected. HDL denotes high-density lipoprotein.

^†A midluteal progesterone value of 3 to 4 ng per milliliter (10 to 13 nmol per liter) or greater is often described as being adequate evidence of prior ovulation.

^‡Observational data suggest that the use of oral combined hormonal contraceptives may double the risk of myocardial infarction and ischemic stroke. Although any excess risk attributable to oral combined hormonal contraceptives would be minimal among generally healthy women of reproductive age, data to specifically address these risks among women with the polycystic ovary syndrome are lacking.³⁰

^§According to the Medical Eligibility Criteria for Contraceptive Use of the U.S. Centers for Disease Control and Prevention (2010),³² the risks of combined hormonal contraceptives probably outweigh advantages among women with a number of characteristics and conditions, including (but not limited to) the following: cigarette smoking in women 35 years of age or older, hypertension (even if adequately controlled), hyperlipidemia (depending on the type and severity), diabetes with microvascular disease (e.g., retinopathy, nephropathy, and neuropathy) or a duration of more than 20 years, multiple risk factors for arterial cardiovascular disease, a history of ischemic heart disease or stroke, an increased risk of venous thromboembolism (e.g., a personal history of venous thromboembolism, known thrombophilia, major surgery with prolonged immobilization, and active cancer), a history of malab-sorptive bariatric procedures, migraine headaches in women 35 years of age or older or with an aura, and a history of breast cancer.

^¶The 5α-reductase inhibitor finasteride may also be effective for hyperandrogenism.^33,34 As with spironolactone, finasteride must be used with reliable contraception. Use of the androgen-receptor antagonist flutamide is generally inadvisable because of potentially severe hepatotoxicity and high cost.³³

^║Thiazolidinediones may provide similar benefits, but they are not generally recommended for patients with the polycystic ovary syndrome.^24,26,28

^**Induction of withdrawal bleeding every 1 to 3 months is recommended to prevent endometrial hyperplasia.^25-27 It is not clear whether a reduction in the risk of endometrial cancer differs according to treatment frequency (e.g., monthly vs. quarterly).

^††The contraceptive effect of progestin-only contraceptive pills also includes thickening of cervical mucus and endometrial atrophy.