Polycystic ovary syndrome (PCOS) is associated with about 75% of all cases of anovulatory infertility. Insulin resistance is frequently associated with PCOS, occurring in 80% of women with PCOS and central obesity, but also in 30–40% of lean women with PCOS. As a result of the reduction in insulin sensitivity, high levels of insulin (hyperinsulinaemia) are invoked as a compensatory mechanism and this is of prime importance in the severity of symptoms of PCOS as hyperinsulinaemia, which is significantly exacerbated by obesity, is a key factor in the production of male hormones from the ovary (hyperandrogenism), the root problem in PCOS.
Weight loss often seems to be an unsurmountable object for the obese patient with PCOS and the alternative possibility of using insulin lowering drugs, particularly metformin, is theoretically attractive. Although metformin as a single agent is capable of improving menstrual frequency and restoring regular ovulation in patients who ovulate infrequently, when used as first line therapy and compared to clomifene (CC), it fairs very poorly.
In a large North American randomised controlled trial, CC was found to be superior to metformin as there was a significant difference in the number of clinical pregnancies and live full-term singleton births (22.6% vs 7.2%) using CC and metformin respectively. Insulin sensitizers should not be used as first-choice agents for induction of ovulation in women with PCOS and their administration does not appear to decrease the incidence of early pregnancy losses. The combination of metformin and CC is no better than CC alone except perhaps in CC resistant patients. Evidence for a possible role for long-term metformin treatment for the prevention of the long-term consequences of PCOS (mainly diabetes and heart disease) is awaited.