Insulin‐sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome

Background Insulin‐sensitizing drugs (ISDs) have recently been advocated as possibly a safer and more effective long‐term treatment than the oral contraceptive pill (OCP) in women with polycystic ovary syndrome (PCOS). It is important to directly compare the efficacy and safety of ISDs versus OCPs in the long‐term treatment of women with PCOS. Objectives To assess the effectiveness and safety of ISDs versus the OCP (alone or in combination) in improving clinical, hormonal, and metabolic features of PCOS. Search methods We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2005), Cochrane Central Register of Controlled Trials (CENTRAL (Ovid), third quarter 2005), MEDLINE (1966 to September 2005), CINAHL (1982 to September 2005), and EMBASE (1988 to September 2005). References of the identified articles were handsearched, and pharmaceutical companies and experts in the field were also contacted for additional relevant studies. Selection criteria Randomised controlled trials which compared ISDs versus the OCP (alone or in combination). Data collection and analysis Performed independently by two review authors. Main results Six trials were included for analysis, four of which compared metformin versus OCP (104 participants) and two of which compared OCP combined with metformin versus OCP alone (70 participants). Limited data demonstrated no evidence of difference in effect between metformin and the OCP on hirsutism and acne. There was either insufficient or no data on the relative efficacy of metformin or the OCP (alone or in combination) for preventing the development of diabetes, cardiovascular disease, or endometrial cancer. Metformin was less effective than the OCP in improving menstrual pattern (Peto odds ratio (OR) 0.08, 95% CI 0.01 to 0.45). Metformin resulted in a higher incidence of gastrointestinal (Peto OR 7.75, 95% CI 1.32 to 45.71), and a lower incidence of non‐gastrointestinal (Peto OR 0.11, 95% CI 0.03 to 0.39), severe adverse effects requiring stopping of medication. Metformin was less effective in reducing serum androgen levels (total testosterone: weighted mean difference (WMD) 0.54, 95% CI 0.22 to 0.86; free androgen index: WMD 3.69, 95% CI 2.56 to 4.83). Metformin was more effective than the OCP in reducing fasting insulin (WMD ‐3.46, 95% CI ‐5.39 to ‐1.52) and not increasing triglyceride (WMD ‐0.48, 95% ‐0.86 to ‐0.09) levels, but there was insufficient evidence regarding comparative effects on redu