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Involvement of Ovarian Steroids in the Opioid-Mediated Reduction of Insulin Secretion in Hyperinsulinemic Patients with Polycystic Ovary Syndrome

Institute of Obstetrics and Gynecology, Catholic University of Sacred Heart (M.G., V.P., M.C., F.M., A.M.F., R.A., A.C., S.M.), Rome; OASI Institute for Research (A.L.), Troina, Italy

Address all correspondence and requests for reprints to: Antonio Lanzone, M.D., Institute of Obstetrics and Gynecology, Catholic University of Sacred Heart, L.go A. Gemelli 8, 00168 Rome, Italy.

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol.

Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization.

Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

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				M.I. Ahmed, A.J. Duleba, O. El Shahat, M.E. Ibrahim, and A. Salem Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome Hum. Reprod., November 1, 2008; 23(11): 2564 - 2569. [Abstract] [Full Text] [PDF]