Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility

Background Polycystic ovary syndrome ( PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. Objectives To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance. Search strategy We searched the Cochrane Menstrual Disorders & Subfertility Group trials register ( searched September 2008), the Cochrane Central Register of Controlled Trials ( Cochrane Library, third Quarter 2008), CINAHL ( searched September 2008), MEDLINE ( January 1966 to September 2008), and EMBASE ( January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification. Selection criteria Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. Data collection and analysis Thirty one trials ( 2537 women) were included for analysis, 27 of them using metformin and involving 2150 women. Main results There is no evidence that metformin improves live birth rates whether it is used alone ( Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene ( Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo ( Pooled OR = OR 3.86, 95% C. I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone ( Pooled OR = 1.48, 95% C. I. 1.12 to 1.95)). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR = 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group ( OR = 0.63, 95% 0.43 to 0.92), although there was significant heterogeneity. There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo ( Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone ( Pooled OR = 3.46, 95% CI 1.97 to 6.07). Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported. Authors' conclusions In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.