NALTREXONE EFFECTS ON INSULIN SENSITIVITY AND INSULIN-SECRETION IN HYPERANDROGENIC WOMEN

A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 kg/m(2)) with hyperandrogenism (HA) and with normal glucose tolerance test wer e studied to evaluate the involvement of endogenous opioids in the pat hophysiology of insulin secretion and insulin sensitivity in HA by adm inistering naltrexone, an oral opioid receptor antagonist. Six patient s received naltrexone orally (75 mg daily) and another six received pl acebo for 12 weeks (double-blind study). Before and after therapy a fr equently sampled intravenous glucose tolerance test (FSIVGTT) was perf ormed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plas ma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samp les, before and after therapy. Treatment with naltrexone in hyperandro genic patients resulted in a decrease in fasting insulin concentration s of 40% and C-peptide concentrations of 50% (p < 0.05). Insulin and C -peptide from the FSIVGTT displayed a similar pattern with a fall in t he area under the curve under naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltre xone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or plac ebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administ ration. However, glucose effectiveness increased significantly with na ltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucos e (fasting and area under the curve) was not modified significantly af ter naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment wit h naltrexone or placebo. In conclusion, these results support the hypo thesis of elevated opioid tonus and increased insulin secretion as a p ossible mechanism of hyperinsulinism in a group of hyperandrogenic wom en of ovarian origin. This alteration could act as an additional facto r in the pathogenesis of insulin resistance found in an important prop ortion of these patients.