Polycystic ovary syndrome: metformin in women not planning pregnancy

Key points from the evidence

Metformin is licensed in the UK for the control of blood glucose in people with type 2 diabetes. It has also been used to treat polycystic ovary syndrome (PCOS). Metformin is not licensed in the UK for this indication so its use in PCOS is off-label.

This evidence summary relates to metformin for PCOS in women who are not planning pregnancy. The use of metformin for treating infertility in women with PCOS is not covered by this evidence summary.

Five small randomised controlled trials (RCTs) included in a Cochrane systematic review, and 4 RCTs published after the Cochrane review, provide the evidence for this summary.

There is no good evidence that regimens containing metformin are statistically significantly different from co-cyprindiol in controlling hirsutism in women with PCOS. Two small studies found no statistically significant difference between metformin and co-cyprindiol in effects on acne but the assessment methods were unclear. Metformin was less effective at improving menstrual regularity than co-cyprindiol. There was no or insufficient data in the studies included in this evidence summary from which to draw conclusions on the effectiveness of metformin for long-term outcomes such as preventing type 2 diabetes, cardiovascular events or endometrial cancer in women with PCOS.

Metformin use is associated with gastrointestinal adverse effects (nausea, vomiting and diarrhoea), which can be severe. The Cochrane review found that metformin caused a significantly higher incidence of gastrointestinal adverse effects that were severe (leading to treatment discontinuation) compared with co-cyprindiol, and a significantly lower incidence of other severe adverse effects (weight gain, high blood pressure, depression, chest pain and headache). Among all 9 trials there was significant heterogeneity in the rates of treatment discontinuation, which was not always because of adverse effects.

The annual cost of metformin at 1.5–2 g per day ranges from £30.03 to £83.20, depending on whether standard or modified-release tablets are prescribed.

Alternative commonly used treatments for hirsutism, acne and menstrual irregularity in PCOS in women not planning pregnancy are: