Human Reproduction, Vol. 15, No. 1, 21-23,
January 2000
© 2000 European Society of Human Reproduction and Embryology
Metformin treatment reduces ovarian cytochrome P-450c17
response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome
1 Department Obstetrics and Gynaecology, University of Siena, Policlinico Le Scotte, 53100 Siena, 2 Hospital General de Douala, Cameroun and 3 University of Catania, Italy
It has recently been proposed that hyperinsulinaemic insulin resistance and increased ovarian cytochrome P-450c17
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 linkage between hyperinsulinaemia and supranormal activity of cytochrome P-450c17 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 2h, 75g 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-450c17 activity in women with polycystic ovary syndrome.
Key words: androgens/HCG/insulin/metformin/17OHP/PCOS
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