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

Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH

Published Online:

November 10, 2010

Polycystic ovary syndrome affects menstruation, prevents ovulation and causes hirsutism. Women with PCOS are also at risk of developing metabolic syndrome and have an increased rate of insulin resistance compared with women of similar body weight with normal ovaries. Insulin resistance is a key contributing factor in the pathogenesis of PCOS and worsens with increasing obesity. However, our analysis showed that the benefit of using therapy to lower insulin levels such as metformin is limited in terms of improvement in reproductive outcomes and metabolic parameters. In particular the use of metformin either alone or in combination with drugs to induce ovulation such as clomiphene citrate does not increase the chance of having a livebirth. Furthermore the long term use of metformin in reducing the risk of developing metabolic syndrome is questionable.

Abstract (click to read)

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 = 1.05, 95% C.I. 0.75 to 1.47). 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 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.

This record should be cited as:

Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD003053. DOI: 10.1002/14651858.CD003053.pub4

Assessed as up to date:

August 13, 2009

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Primary Review Group:

Menstrual Disorders and Subfertility Group

Health topics:

Gynaecology > Menstrual cycle disorders/oligo-amenorrhoea > Polycystic ovary syndrome

Gynaecology > Subfertility > Female: associated with other medical conditions

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

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

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