The effects of cyproterone acetate and ethinyl oestradiol on carbohydrate metabolism

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as anti-androgen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and women were studied in two groups: the first when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13 to 22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to intravenous tolbutamide was increased by 50% but there was no accompanying change in the glucose nadir as compared with controls. These results show that the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. This shows that the observed hyperinsulinaemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. We propose that these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide but this was not significant. We conclude that these results are explained by a reduced but persisting effect of CA.