Use of naltrexone in postmenopausal women with exaggerated insulin secretion: a pilot study

Abstract

Objective To determine the effect of naltrexone (an opiate receptor blocker) on insulin metabolism in postmenopausal women with different insulinemic patterns. Design Randomized placebo-controlled study. Setting Academic research environment. Patient(s) Forty-one healthy normoinsulinemic or hyperinsulinemic postmenopausal women. Intervention(s) Oral glucose tolerance test (OGTT) before and after 5 weeks of the opioid antagonist (naltrexone, 50 mg/d orally) or the placebo administration; euglycemic–hyperinsulinemic glucose clamp. Main outcome measure(s) Glucose, insulin, and C-peptide plasma levels assessed in fasting condition and during the OGTT. Insulin sensitivity was calculated as total body glucose utilization. Result(s) Naltrexone reduced fasting and stimulated insulin response to the glucose load while inducing a significant improvement of the hepatic extraction, only in the hyperinsulinemic patients. No differences were found in the C-peptide pancreatic secretion and in the peripheral insulin sensitivity. No net change in the glycoinsulinemic metabolism was observed in normoinsulinemic patients or in placebo-controlled normoinsulinemic and hyperinsulinemic subjects. Conclusion(s) Similar to that reported in premenopausal women, endogenous opioid peptides are involved in the modulation of glycoinsulinemic metabolism in postmenopause. Through a prevalent action on liver insulin metabolism, without any clear improvement of insulin resistance and pancreatic β-cell function, the chronic administration of naltrexone appears to reduce the hyperinsulinemia in those women with an exaggerated insulin response to the OGTT.