Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/cyproterone acetate

Polycystic ovary syndrome (PCOS) is associated with abnormalities of insulin action and insulin secretion. Ethinyl oestradiol/cyproterone acetate is a common agent used to treat the symptoms of PCOS, but its effects on insulin action and insulin pulsatility have not been examined. We investigated the relationship between insulin action and insulin secretion in 11 patients with PCOS, at diagnosis and after 3 months of treatment with ethinyl oestradiol/cyproterone acetate, and in 13 controls. Insulin action was assessed using the euglycaemic hyperinsulinaemic clamp (2 mU/kg/min for 2 h). Insulin pulsatility was examined over 90 min by 2 min sampling. Short-term insulin pulses were identified using PULSAR. Treatment with ethinyl oestradiol/cyproterone acetate resulted in significant reductions in testosterone (3.3 +/- 0.7 vs. 1.9 +/- 0.2 nmol/l, p < 0.05), free androgen index (10.2 +/- 0.7 vs. 1.21 +/- 0.2, p < 0.05) and LH/FSH ratio (2.6 +/- 0.5 vs. 1.0 +/- 0.2, p < 0.05). During hyperinsulinaemic clamps, the glucose infusion rate (CIR) required to maintain euglycaemia was lower in PCOS compared to controls (33.6 +/- 2.7 vs. 45.1 +/- 3.5 mol/kg/min, p < 0.05) but similar in PCOS before and after treatment (33.6 +/- 2.8 vs. 33.6 +/- 2.7 mol/kg/min, p = 0.9). Numbers of pulses identified in PCOS and controls were similar and unaltered by ethinyl oestradiol/cyproterone acetate. There was no correlation between GIR and frequency of insulin pulses in PCOS before or after treatment (r = 0.2, p = 0.6; post r = -0.5, p = 0.1) unlike controls (r = -0.6, p = 0.04). Despite considerable improvement in androgen profile, treatment with ethinyl oestradiol/cyproterone acetate did not alter insulin action in PCOS, and this insulin resistance does not appear to be determined by insulin pulse frequency.