Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome

Abstract

Endogenous opiates may affect various aspects of reproductive and metabolic function in patients with polycystic ovary syndrome (PCOS). This study evaluated long-term inhibition of the opioid system using naltrexone in clomiphene citrate (CC)-resistant women with PCOS. A group of 30 infertile females with PCOS were evaluated; all subjects were obese, hyperandrogenic and hyperinsulinemic; 16 patients were amenorrhic and 14 were oligomenorrhic. All subjects received natrexone (50 mg p.o. daily) for 6 months. Patients who did not ovulate after 12 weeks of naltrexone monotherapy, also received CC (starting at 50 mg/day for 5 days and, for non-responders, increasing it up to 150 mg/day). Of the 30 women, 3 ovulated during naltrexone monotherapy and 19 of the remaining 27 ovulated during naltrexone + CC therapy. There were no conceptions during naltrexone monotherapy, but 9 of 27 women (33.3%) conceived during naltrexone + CC; there was one missed abortion at 9 weeks, one preterm delivery at 34 weeks and seven term live births. Naltrexone therapy was also followed by significant reductions in BMI, fasting serum insulin, luteinizing hormone (LH), LH/follicle-stimulating hormone ratio and testosterone. In this preliminary trial, naltrexone improved endocrine and metabolic function in women with CC-resistant PCOS. Furthermore, naltrexone restored CC sensitivity in the majority of subjects, resulting in a significant number of pregnancies.