title: Naltrexone effects on insulin sensitivity and insulin secretion in hyperandrogenic women.
abstract: A total of 12 women (24.2 +/- 1.6 years old, BMI 36.7 +/- 1.5 Kg/m2) with hyperandrogenism (HA) and with normal glucose tolerance test were studied to evaluate the involvement of endogenous opioids in the pathophysiology of insulin secretion and insulin sensitivity in HA by administering naltrexone, an oral opioid receptor antagonist. Six patients received naltrexone orally (75 mg daily) and another six received placebo for 12 weeks (double-blind study). Before and after therapy a frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. The insulin sensitivity index (SI) was determined by Bergman's program. SHBG, DHEAS, testosterone, free androgen index (FAI) and plasma concentrations of IGF-I and IGFBP-1 were determined in 3 basal samples, before and after therapy. Treatment with naltrexone in hyperandrogenic patients resulted in a decrease in fasting insulin concentrations 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 the area under the curve under naltrexone treatment of 34% for insulin and 35% for C-peptide. Insulin sensitivity did not change under naltrexone (1.26 +/- 0.19 vs 1.32 +/- 0.32 10(-4) x min(-1)/(uU/ml)) or placebo (0.95 +/- 0.19 vs 1.12 +/- 0.28 10(-4) x min(-1)/(uU/ml)) administration. However, glucose effectiveness increased significantly with naltrexone (2.231 +/- 0.002 vs 3.354 +/- 0.006 x 10(-2) min(-1)). Glucose (fasting and area under the curve) was not modified significantly after naltrexone administration. Baseline hormone levels were similar in the two groups, and they did not change after long-term treatment with naltrexone or placebo. In conclusion, these results support the hypothesis of elevated opioid tonus and increased insulin secretion as a possible mechanism of hyperinsulinism in a group of hyperandrogenic women of ovarian origin. This alteration could act as an additional factor in the pathogenesis of insulin resistance found in an important proportion of these patients.
authors.affiliation: Dept of Medicine West Division, School of Medicine Universidad de Chile, Santiago.
authors.forename: T
authors.initials: T
authors.lastname: Sir-Petermann
authors.forename: G
authors.initials: G
authors.lastname: López
authors.forename: T
authors.initials: T
authors.lastname: Castillo
authors.forename: M
authors.initials: M
authors.lastname: Calvillán
authors.forename: B
authors.initials: B
authors.lastname: Rabenbauer
authors.forename: L
authors.initials: L
authors.lastname: Wildt
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D017588:Hyperandrogenism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D010919:Placebos; D013739:Testosterone / Q000097:blood
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010919:Placebos; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D009271:Naltrexone; D007334:Insulin-Like Growth Factor I