Insulin Resistance and Metformin Treatment in Women with Polycystic Ovary Syndrome

Abstract

Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). Obesity, visceral fat accumulation and excessive serine phosphorylation of the insulin receptor are factors responsible for insulin resistance in PCOS. Insulin resistance induces compensatory hyperinsulinemia, which stimulates androgen synthesis in the theca cells of the PCOS ovary. Therefore, hyperinsulinemia results in hyperandrogenemia in PCOS patients who tend to have androgen-producing ovaries. In Japanese PCOS, 25% of patients are obese and 30% of patients have insulin resistance. Improvement of insulin resistance by weight loss, exercise and insulin sensitizing drugs such as metformin can recover reproductive function. Meformin has the potential to induce ovulation in PCOS, and 58% of clomiphene resistant Japanese PCOS patients resume ovulation after combined clomiphene metformin treatment. Clomiphene-metformin therapy is simple and has low risks of multiple pregnancy and ovarian hyperstimulation syndrome. Metformin use should be considered fertility treatment, especially as a second line therapy for the clomiphene resistant PCOS.