Metformin was initially introduced in obese women with PCOS to help them lose weight. More recently metformin has been used in slim and amenorrhoeic (without menstrual periods) women with PCOS for cycle regulation and treatment of anovulatory infertility.
Initial anecdotal reports of pregnancies achieved with metformin in previously amenorrhoeic PCOS women were followed by numerous studies assessing the effectiveness of metformin alone or in combination with conventional induction of ovulation on ovulatory and pregnancy rates. Most of these studies are observational and predominantly in obese women with PCOS. In a number of studies ovulation rates increased with no change in weight which suggests that the effect is independent of weight loss. Indeed a direct effect of metformin on ovarian steroidogenesis (production of male hormones) has been demonstrated in several studies. Although no clear predictors of a positive response to metformin have been identified there seem to be inverse relationship between a body mass index (BMI) and the response to metformin. Anecdotal reports suggest that the best responders are slim and amenorrhoeic patients. Also decreased cravings for carbohydrates and a reduction in abdominal fat have been reported with metformin treatment.
Several studies have shown that continuing metformin throughout pregnancy in women with PCOS appears to safely reduce early pregnancy loss as well as the development of gestational (pregnancy induced) diabetes. All these studies also point to the safety of metformin throughout pregnancy as no adverse foetal outcomes were reported among women treated with metformin. Metformin is listed as category B drug which means that the safety in pregnancy has not been established but significant teratogenicity is not apparent. It is however still questionable whether metformin should be continued during pregnancy unless gestational diabetes is present.
The use of metformin as a chronic therapy in women with PCOS with the aim of preventing diabetes type 2 and cardiovascular disease is a controversial and critical issue. Long term metformin use is associated with decreased intestinal absorption of folic acid and vitamin B12 and therefore their supplementation is recommended.