Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome

Objective: To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). Patients and methods: Twenty-four women with PCOS, aged 25.4 +/- 4.3 (mean+/-S.D.) years, body mass index 24.5 +/- 3.9 kg/m(2) were randomly assigned to receive either transdermal oestradiol plus CPA (n = 12) or a peroral oestradiol-CPA combination (n = 12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. Results: After peroral oestradiol-CPA, insulin sensitivity (P < 0.004) and the disposition index as the function of insulin sensitivity and secretion (P < 0.0001) decreased significantly. Fasting insulin (P < 0.05), cholesterol (P < 0.05), high-density lipoprotein cholesterol (P < 0.05) and sex-hormone binding globulin (P < 0.0001) increased significantly. Dehydroepiandrosterone (P < 0.05) and 17-OH progesterone (P < 0.01) decreased significantly. After transdermal oestradiol + CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. Conclusions: In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity.