Review question

Researchers reviewed the evidence about the effectiveness and safety of metformin and other drugs that improve the body’s sensitivity to insulin, for inducing ovulation in women with polycystic ovary syndrome (PCOS). Of interest were live birth rate, adverse effects and additional reproductive and metabolic outcomes.

Background

Women with PCOS typically have infrequent or absent periods due to a lack of ovulation, which can result in infertility. Women with PCOS are also at risk of developing metabolic problems, such as diabetes, high blood pressure and high cholesterol levels. High insulin levels are thought to play a role in PCOS and are generally worse with obesity. The treatments, which increase the sensitivity to insulin that are considered in this review are metformin, rosiglitazone, pioglitazone and D-chiro-inositol.

Study characteristics

The search for suitable studies was completed on 12 January 2017. We have analysed a total of 48 randomised controlled trials (4451 women) in this review. The current review update includes five additional studies, which all investigated metformin in women with PCOS. The studies compared insulin-sensitising drugs with placebo, no treatment, or the ovulation-induction agent, clomiphene citrate.

Key results

Our updated review showed that metformin may be beneficial in improving the chances of having a live birth compared with either no treatment or placebo. It is not clear from the available evidence whether metformin or clomiphene citrate is superior for live birth rate, although pregnancy and ovulation rates are improved with clomiphene citrate, and women taking clomiphene citrate have fewer side effects. However, it is possible that a woman’s body mass index may affect which treatment she should take for the greatest benefit, although further research is required to establish this. Metformin did not appear to increase the risk of miscarriage.

The limited improvement in metabolic outcomes with metformin treatment highlights the importance of weight loss and lifestyle adjustment, particularly in overweight women with PCOS.

Quality of the evidence

The quality of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of study methodology and incomplete outcome data), imprecision and inconsistency.