Metformin treatment reduces ovarian cytochrome P-450c17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome

It has recently been proposed that hyperinsulinaemic insulin resistance and increased ovarian cytochrome P-450c17α activity, two features of the polycystic ovary syndrome (PCOS), are pathogenetically linked. The aim of the present study was to test the hypothesis of the hyperinsulinaemia and supranormal cytochrome P-450c17α using the human chorionic gonadotrophin (HCG) challenge, which is a more direct ovarian stimulus than gonadotrophin-releasing hormone (GnRH) in detecting modifications in ovarian steroidogenesis. Eleven women with insulin resistance-related PCOS were studied, HCG (10,000 IU) was given i.m., and blood samples were obtained 0, 8, 12, 16 and 24 h thereafter. Next day, metformin was given at a dose of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated. Two women ovulated after metformin treatment. The administration of metformin was associated with a decrease in area under the curve for insulin during a 2 h, 75 g oral glucose tolerance test, in plasma free testosterone concentrations and an increase in plasma sex hormone binding globulin concentration. The plasma 17-hydroxyprogesterone response to HCG was significantly lower after metformin treatment. The present study gives a direct demonstration that metformin leads to a reduction in stimulated ovarian cytochrome P-450c17α activity in women with polycystic ovary syndrome.