Insulin‐sensitising drugs (metformin, rosiglitazone, pioglitazone, D‐chiro‐inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility
Abstract
Background
Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation (anovulation), high levels of male hormones (hyperandrogenaemia) and high levels of insulin (hyperinsulinaemia secondary to increased insulin resistance). Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. Insulin‐sensitising agents such as metformin may be effective in treating the features of PCOS, including anovulation.
Objectives
To assess the effectiveness of insulin‐sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS.
Search methods
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 3rd Quarter 2011), CINAHL (October 2011), MEDLINE (January 1966 to October 2011), and EMBASE (January 1985 to October 2011).
Selection criteria
Randomised controlled trials of insulin sensitising drugs compared with either placebo, no treatment, or an ovulation induction agent for women with PCOS, menstrual disturbance and subfertility.
Data collection and analysis
Two review authors independently assessed studies for inclusion and trial quality, and extracted data.
Main results
Forty‐four trials (3992 women) were included for analysis, 38 of them using metformin and involving 3495 women.
There was no evidence that metformin improved live birth rates, whether it was used alone (pooled OR 1.80, 95% CI 0.52 to 6.16, 3 trials, 115 women) or in combination with clomiphene (pooled OR 1.16, 95% CI 0.85 to 1.56, 7 trials, 907 women). However, clinical pregnancy rates were improved for metformin versus placebo (pooled OR 2.31, 95% CI 1.52 to 3.51, 8 trials, 707 women) and for metformin and clomiphene versus clomiphene alone (pooled OR 1.51, 95% CI 1.17 to 1.96, 11 trials, 1208 women). In the studies that compared metformin and clomiphene alone, there was evidence of an improved live birth rate (pooled OR 0.3, 95% CI 0.17 to 0.52, 2 trials, 500 women) and clinical pregnancy rate (pooled OR 0.34, 95% 0.21 to 0.55, 2 trials, 500 women) in the group of obese women who took clomiphene.
Metformin was also associated with a significantly higher incidence of gastrointestinal disturbances than placebo (pooled OR 4.27, 95% CI 2.4 to 7.59, 5 trials, 318 women) but no serious adverse effects were reported.
Authors' conclusions
In agreement with the previous review, metformin was associated with improved clinical pregnancy but there was 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 role of metformin in improving reproductive outcomes in women with PCOS appears to be limited.
PICOs
Plain language summary
Insulin‐sensitising drugs for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility
Women with polycystic ovary syndrome (PCOS) typically have infrequent or absent periods and increased hair growth and acne. Women with PCOS are also at risk of developing metabolic syndrome, 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. Insulin‐sensitising drugs considered in this review are metformin, rosiglitazone, pioglitazone and D‐chiro‐inositol. This updated review showed that the use of medications to lower insulin levels, such as metformin either alone or in combination with drugs to induce ovulation (for example clomiphene citrate), does not increase the chance of having a live birth. Metformin was also associated with increased gastrointestinal symptoms such as nausea and diarrhoea.
