Objective: To compare the effects of combined oral contraceptives (OCs) containing cyproterone acetate or desogestrel on insulin sensitivity in adolescents with polycystic ovary syndrome (PCOS). Design: A prospective randomized clinical trial. Setting: Outpatient gynecological clinic of Aretaieion University Hospital. Patient(s): Thirty- six adolescent girls with hyperandrogenismand six or less menses in the preceding 12 months. Intervention(s): Patients were separated in two groups: group A (n = 18) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl E2 daily; and group B (n = 18) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl E2 daily, for 21 days followed by a 7- day rest, for 12 months. Main Outcome Measure(s): Hirsutism score, lipid, androgen, and sex hormone- binding globulin (SHBG) levels were evaluated at baseline. An oral glucose tolerance test (OGTT)was performed and metabolism indices, based on previously studied mathematical formulas, were assessed at baseline and at 12 months. Result(s): After 12 months of treatment, the homeostasis model assessment index of insulin resistance increased significantly in both groups. The fasting glucose- to- insulin ratio and predicted insulin sensitivity index decreased in group B. The delta of the area under the OGTT curve for insulin and predicted first and second phase insulin secretion indices increased significantly only in group B. Conclusion(s): We conclude that treatment of adolescent girls with PCOS with the two combined OCs administered, results in unfavorable changes of insulin sensitivity. In addition, cyproterone acetate is associated with an increase of insulin secretion and hyperinsulinemia. Objective: To compare the effects of combined oral contraceptives (OCs) containing cyproterone acetate or desogestrel on insulin sensitivity in adolescents with polycystic ovary syndrome (PCOS). Design: A prospective randomized clinical trial. Setting: Outpatient gynecological clinic of Aretaieion University Hospital. Patient (s): Thirty-six adolescent girls with hyperandrogenismand six or less menses in the preceding 12 months. Intervention (s): Patients were separated in two groups: group A (n = 18) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl E2 daily; and group B (n = 18) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl E2 daily for 21 days followed by a 7- day rest, for 12 months. Main Outcome Measure (s): Hirsutism score, lipid, androgen, and sex hormone-binding globulin (SHBG) levels were evaluated at baseline. An oral glucose tolerance test (OGTT) was performed and metabolism indices, based on previously studied mathematical formulas, were assessed at ba seline and at 12 months. Result (s): After 12 months of treatment, the homeostasis model assessment index of insulin resistance increased significantly in both groups. The fasting glucose-to- insulin ratio and predicted insulin sensitivity index decreased in group B. The delta of the area under the OGTT curve for insulin and predicted first and second phase insulin secretion indices increased significantly only in group B. Conclusion (s): We conclude that treatment of adolescent girls with PCOS with the two combined OCs administered, results in unfavorable changes of insulin sensitivity. In addition, cyproterone acetate is associated with an increase of insulin secretion and hyperinsulinemia.