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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 9 3161-3168
Copyright © 2000 by The Endocrine Society


Original Studies

Endocrine and Metabolic Effects of Metformin Versus Ethinyl Estradiol-Cyproterone Acetate in Obese Women with Polycystic Ovary Syndrome: A Randomized Study1

Laure C. Morin-Papunen, Ilkka Vauhkonen, Riitta M. Koivunen, Aimo Ruokonen, Hannu K. Martikainen and Juha S. Tapanainen

Departments of Obstetrics and Gynecology (L.C.M.-P., R.M.K., H.K.M., J.S.T.) and Clinical Chemistry (A.R.), University Hospital of Oulu, FIN-90220 Oulu; and Department of Medicine (I.V.), University Hospital of Kuopio, FIN-70210 Kuopio, Finland

Address correspondence and requests for reprints to: Dr. J. S. Tapanainen, Department of Obstetrics and Gynecology, University Hospital of Oulu, Kajaaninitie 52 A, FIN-90220 Oulu, Finland. E-mail: juha.tapanainen{at}oulu.fi

Metformin, a biguanide antihyperglycemic drug, has been shown to improve ovarian function and glucose metabolism in women with polycystic ovary syndrome (PCOS), but results concerning its effects on insulin sensitivity are controversial. Oral contraceptive pills are commonly used in the treatment of PCOS; but, like metformin, their influence on insulin sensitivity is not well known. We randomized 32 obese (body mass index > 27 kg/m2) women with PCOS, either to metformin (500 mg x 2 daily for 3 months, then 1000 mg x 2 daily for 3 months) or to ethinyl estradiol (35 µg)-cyproterone acetate (2 mg) oral contraceptive pills (Diane Nova) for 6 months. Metformin significantly decreased the waist-to-hip ratio, serum testosterone, fasting free fatty acid, and insulin concentrations and improved oxidative glucose utilization and menstrual cyclicity, with slight (but nonsignificant) improvements in insulin hepatic extraction and insulin sensitivity. Diane Nova significantly decreased serum testosterone and increased serum sex hormone-binding globulin concentrations and glucose area under the curve during oral glucose tolerance test. It is concluded that metformin, probably by way of its effect on adipose tissue, leads to reduction of hyperinsulinemia and concomitant improvement in the menstrual pattern; and therefore, it offers a useful alternative treatment for obese, anovulatory women with PCOS. Despite slight worsening of glucose tolerance, Diane Nova is an efficient treatment for women with hyperandrogenism and hirsutism.




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