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

Abstract

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. 1.2+/-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 (GIR) required to maintain euglycaemia was lower in PCOS compared to controls (33.6+/-2.7 vs. 45.1+/-3.5 micromol/kg/min, p<0.05) but similar in PCOS before and after treatment (33.6+/-2.8 vs. 33.6+/-2.7 micromol/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.

Clinical and metabolic features of polycystic ovary syndrome

“…Legro et al [7] reported a higher prevalence of insulin resistance in obese (64%) than in nonobese (20%) women with PCOS. Results of euglycemic hyperinsulinemic clamps have showed obese women with PCOS to have a higher insulin resistance [5,27–32]. In this study, the prevalence of insulin resistance was significantly higher in overweight patients than in patients of normal weight.…”

Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome

“…Plasma insulin concentrations were constant in both of these studies indicating that the decrease in glucose tolerance was again due to a decrease in insulin sensitivity rather than a change in insulin levels/production. However, other studies performed in non-obese women showed no change in glucose tolerance and insulin sensitivity (Armstrong et al 2001; Cibula et al 2002; Elter et al 2002; Morin-Papunen et al 2003). This variation in results may suggest that metabolic consequences from COC treatment of PCOS depend on body type (Vrbikova and Cibula 2005).…”

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“…Apart from these positive effects on PCOS, OCPs are believed to slightly worsen insulin sensitivity 88-90, and for this reason, their use may aggravate the already impaired glucose metabolism of women with PCOS. However, studies estimating the role of OCPs on glucose tolerance 91 or insulin sensitivity [92][93][94][95][96][97][98] in women with PCOS have obtained conflicting results, and either no effect or a negative modification 91,94,96,97 was reported. There may be some negative influence on lipids also, and a low dose COCP may be preferable 99,100 .…”