Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance

Insulin resistance (IR) has been reported in as many as 50% of women with polycystic ovary syndrome (PCOS) and in up to 95% of those who are obese. Today, insulin sensitizers are given to many of these affected women. This study examined the comparative effectiveness of rosiglitazone, a thiazolidinedione, and an oral contraceptive combining ethinyl estradiol (EE) with cyproterone acetate (CPA). Participants were 28 obese women ranging in age from 18 to 45 years who met criteria for PCOS and who still had high insulin levels despite 4 months of dietary treatment. They were randomly assigned to 6 months of treatment with either 4 mg rosiglitazone daily or a combination of 35 μg EE and 2 mg CPA given on 21 days per 28-day cycle. Each group then received both treatments for 6 months longer. Women in both treatment groups had normal blood glucose levels throughout the study. Rosiglitazone decreased insulin levels, indices of IR (homeostasis model assessment, quantitative sensitivity check index, and the area under the curve for insulin in response to an oral glucose tolerance test [OGTT]). Drug effects on lipids, androgens, and hirsutism were limited. Treatment with EE/CPA did not alter insulin levels or the response to an OGTT. It did increase levels of high-density lipoprotein cholesterol and triglycerides while decreasing androgen levels and hirsutism. Similar findings were obtained when both treatments were given for 6 months. Only EE/CPA significantly lowered hirsutism scores, as shown in Figure 1 in which patients in group A were those randomized to receive rosiglitazone initially and patients in group B began treatment by taking EE/CPA. There were no serious side effects. This approach to obese women with PCOS and insulin resistance might be particularly appropriate for women who request an oral contraceptive.