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

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 normoin¬sulinemic 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 /3-cell function, the chronic administration of naltrexone appears to reduce the hyperinsulinemia in those women with an exaggerated insulin response to the OGTT. (by American Society for Reproductive Medicine.).