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

J Clin Endocrinol Metab. 2000 Sep;85(9):3161-8. doi: 10.1210/jcem.85.9.6792.


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 1,000 mg x 2 daily for 3 months) or to ethinyl estradiol (35 microg)-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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgen Antagonists / therapeutic use*
  • Area Under Curve
  • Blood Glucose / metabolism
  • Calorimetry
  • Cyproterone Acetate / therapeutic use*
  • Estradiol Congeners / therapeutic use*
  • Ethinyl Estradiol / therapeutic use*
  • Fats / metabolism
  • Female
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Hormones / blood
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Insulin Resistance / physiology
  • Metformin / therapeutic use*
  • Obesity / blood
  • Obesity / drug therapy*
  • Obesity / etiology
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / drug therapy*


  • Androgen Antagonists
  • Blood Glucose
  • Estradiol Congeners
  • Fats
  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Ethinyl Estradiol
  • Cyproterone Acetate
  • Metformin