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Hum. Reprod. Advance Access originally published online on July 18, 2008
Human Reproduction 2008 23(11):2564-2569; doi:10.1093/humrep/den273
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome

M.I. Ahmed1, A.J. Duleba2,3, O. El Shahat1, M.E. Ibrahim1 and A. Salem1

1 Department of Obstetrics and Gynecology, Benha School of Medicine, Benha, Egypt 2 Reproductive Endocrinology Unit, Department of Obstetrics and Gynecology, University of California, 4869 Y Street, Suite 2500, Sacramento, Davis, CA 95817, USA

3 Correspondence address. Tel: +1-916-734-6900; Fax: +1-916-734-6980; E-mail: ajduleba{at}ucdavis.edu or antoni.duleba{at}yale.edu

BACKGROUND: 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.

METHODS: 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).

RESULTS: 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.

CONCLUSIONS: 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.

Key words: naltrexone/PCOS/infertility/clomiphene resistance

Submitted on February 12, 2008; resubmitted on June 6, 2008; accepted on June 11, 2008.


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