Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome

Abstract Objective: Evaluation of clinical and endocrine effects of naltrexone administration in obese women with PCOS. Design: Open, controlled, clinical study. Setting: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. Patient(s): Ten PCOS women were studied. Intervention(s): Women were treated with naltrexone (50 mg/day) for 6 months. Main Outcome Measure(s): Body mass index and the menstrual cyclicity during naltrexone treatment were assessed. Basal levels of LH, FSH, 17β-estradiol (E 2 ), 17-hydroxyprogesterone, total and free T, androstenedione, dehydroepiandrosterone sulfate, cortisol, sex hormone-binding globulin were evaluated before treatment and every 3 months. Progesterone levels were measured in the luteal phase during the sixth month. Gonadotropin response to GnRH administration (10 μg) and a 75-g oral glucose tolerance test were performed before and every 3 months. Result(s): Body mass index significantly decreased from 29.94 ± 1.04 to 26.07 ± 0.81 during treatment. The menstrual cyclicity improved in 80% of PCOS women: the mean cycle length was 40–360 days before treatment and ranged between 25 and 120 days and 28–120 days after 3 and 6 months of treatment. Plasma levels of free T, androstenedione, dehydroepiandrosterone sulfate, and cortisol significantly decreased. Fasting glucose-to-insulin ratio improved in women with insulin resistance. Conclusion(s): Naltrexone may have a beneficial effect on the clinical and endocrine-metabolic disturbances of obese PCOS women. Whether these effects are the consequences of weight loss or are due to changes in opioidergic tone is debatable.