Clinical Question

Do insulin sensitizing drugs with or without oral contraceptive pills improve clinical outcomes in women with polycystic ovary syndrome (PCOS)?

Evidence-Based Answer

Insulin sensitizing drugs are more effective than oral contraceptives alone at improving fasting insulin levels in patients with PCOS. Compared with metformin (Glucophage) alone, oral contraceptives alone better control irregular menstrual cycles and reduce androgen levels. There is insufficient evidence to recommend insulin sensitizing drugs alone or in combination with oral contraceptives to decrease the risk of diabetes, cardiovascular disease, or endometrial cancer.

Practice Pointers

PCOS is defined by the presence of two of the following criteria: oligomenorrhea or amenorrhea, clinical or biochemical hyper-androgenism, or polycystic ovaries visible on ultrasonography. Family physicians routinely treat symptoms of irregular menstrual cycles and excessive androgen levels with combination oral contraceptives. The benefit of using insulin sensitizing drugs is unclear. Ideally, treatment of PCOS would improve clinical symptoms such as hirsutism and infertility and decrease the risk of type 2 diabetes, cardiovascular disease, or endometrial cancer.

In this Cochrane review, the authors searched the literature for randomized controlled trials (RCTs) comparing treatment of PCOS with insulin sensitizing drugs with or without oral contraceptives. They found six RCTs that included 226 total patients, 20 to 52 years of age. Patients were followed for four to 12 months, with a median study duration of six months. Metformin, 500 mg orally three times per day, was the only insulin sensitizing drug studied.

Oral contraceptives were more effective at improving menstrual cycle regularity and lowering androgen levels compared with metformin. Although these findings were statistically significant, only 104 participants in three trials were analyzed for these outcomes. Metformin lowered fasting insulin levels and did not impact triglyceride levels compared with oral contraceptives. However, metformin did not lower fasting glucose levels in patients without impaired glucose tolerance and did not reduce the risk of type 2 diabetes when used alone. Combined therapy improved hirsutism in a single RCT with 34 participants.

No combined RCTs with acne as primary outcome were available. None of the trials analyzed the primary outcomes of stroke, myocardial infarction, or endometrial cancer.

This review was limited by small study sizes. Because outcomes addressed chronic disease, the studies may not have followed patients long enough to show prevention benefits. No studies were available comparing alternative insulin sensitizing drugs such as rosiglitazone (Avandia) or pioglitazone (Actos). There was insufficient evidence on the outcomes of hirsutism, acne, body mass index, blood pressure, and other cholesterol parameters.

Evaluating fertility rates as a primary outcome could provide practice-modifying information for many physicians. Expert consensus by the American Association of Clinical Endocrinologists states that metformin should be considered in the initial treatment of PCOS, especially for patients who are overweight or obese.¹ The 2002 American College of Obstetricians and Gynecologists guideline recommends metformin as one measure to improve ovulatory frequency and to treat risk factors for diabetes and cardiovascular disease.²