Effects of a 1-year treatment with a low-dose combined oral contraceptive containing ethinyl estradiol and cyproterone acetate on glucose and insulin metabolism

To study the effects of the slightly estrogen-dominant monophasic low-dose oral contraceptive (OC) Diane-35 (Schering AG, Berlin, Germany) (35 μg ethinyl estradiol [EE2] + 2 mg cyproterone acetate, a 17α-hydroxyprogesterone derivative [17-OHP]) on glucose and insulin metabolism. Seven healthy young women were investigated by using the euglycemic hyperinsulinemic glucose clamp technique (insulin delivery rate = 100 mU/kg per hour for 120 minutes). This test was performed, after an overnight fast, during the last 7 days of a spontaneous cycle and within the last 5 days of pill intake during the sixth and twelfth cycle of a continuous treatment with Diane-35 in each subject. The three indexes measuring the insulin-induced glucose disposal during the clamp (glucose infusion rate, glucose metabolic clearance rate, and glucose infusion rate divided by plasma insulin plateau levels) were not significantly affected by Diane-35. In contrast, the metabolic clearance rate of the exogenous insulin infused during the clamp tended to be slightly increased with Diane-35 (significant after 6 but not after 12 cycles). These results suggest that a 1-year treatment with the OC Diane-35, which contains EE2 + a 17-OHP rather than a 19-nortestosterone derivative as the progestogen compound, does not significantly alter peripheral (presumably muscular) insulin sensitivity but slightly increases insulin (presumably hepatic) clearance.