Treating PCOS and Infertility with Low Dose Naltrexone
Infertility is a heartbreaking problem that haunts millions of women; a large number of them, PCOS sufferers. Nearly $2 billion is spent each year by couples struggling with a confusing group of health factors in an effort to have a child. Because of this persistent issue there is a real commitment on the part of researchers worldwide to unravel the exceedingly complex mechanisms of the endocrine system hoping to develop new techniques and protocols for reversing infertility. One such effort has resulted in the "off-label" adaptation of the drug, Naltrexone also known as "LDN."
How Does Naltrexone Work?
Naltrexone is not a new drug. It was originally approved by the FDA (U.S. Food and Drug Administration) in 1984 as a treatment for alcohol and narcotic addiction. These days however, it is also finding new applications in lower dosages, hence "Low Dose Naltrexone" or "LDN" to differentiate it from the original drug, Naltrexone.
The term "off label" refers to its use in a different capacity and dosage than what was originally intended or "labeled." Classified as an "opiate antagonist," it works by blocking the opiate (narcotic) receptors which contributes to a build-up of endorphins that have not been able to bind. Using an "opiate antagonist" as a medicinal therapy is referred to as "Opioid" Therapy. LDN is such a therapy and has shown promise in a variety of health issues including the reversal of infertility and other symptoms associated with PCOS.
LDN boosts the immune system, the mechanisms of which we do not entirely understand. Science is still looking for answers to the many immune-deficiency diseases such as HIV/Aids, Multiple Sclerosis, Rheumatoid Arthritis, Crohn's Disease and even many cancers. There is, however, a growing body of research which indicates that our own endorphin secretions are important to the functioning of the immune system. Endorphins are "feel-good" neurotransmitters in our brains typically associated with "runner's high." They are only one of a whole class of neurotransmitters that have recently been found to have far reaching connections throughout the body, especially affecting the immune system. (1)
According to the New England Journal of Medicine article, "Opioid-Induced Immune Modulation," preclinical evidence indicates that opioids alter the development, differentiation and function of immune cells..." (2). In essence, LDN makes the immune system begin working at optimum levels again which includes the correction of the many imbalances which plague the body.
LDN therapy requires taking the medication, typically around 3-5 mg of Naltrexone, at bedtime. This causes a blockage of the endorphin receptors throughout the body between 2 a.m. and 4 a.m. The body, sensing that proper binding has not happened, makes even more endorphins. With no place to bind and with increasing production, endorphins accumulate, causing a higher concentration in the system, which, in turn, stimulates and/or alters the different cells and components of the immune system. This brief blockage every night seems to be enough to effect a prolonged change in many aspects of the immune system.
A typical prescription ranges from $30-$40/month. That's good news for all of us who need it but bad news for research because of the lack of financial incentive for the big pharmaceutical companies. It is currently available through compounding pharmacies, pharmacies that do their own formulations, with a doctor's prescription. The challenge is to find a doctor who is educated about LDN and who will prescribe it.
LDN therapy was pioneered by New York doctor, Bernard Bihari, who in 1985 used it with his own HIV patients and found it affective in strengthening their responses to infection. In the 90's he had good results with cancer patients. Subsequently, it was supported by animal studies conducted by Dr. Ian Zagon, researcher at the Milton S. Hershey Medical Center at Pennsylvania State University who has spent over two decades developing an extensive body of research into endorphins and their remarkable effects on the body. (3)
Naltrexone, Insulin Resistance and Infertility
Infertility is an endorphin-deficient state so it would seem reasonable to expect that Naltrexone would have an effect. The most promising studies in this area and the ones that have sparked so much interest, however, were not Low-Dose studies; they used higher levels of Naltrexone. Nonetheless, the results are extremely promising and clearly indicate that the use of endorphins and possibly other neurotransmitters to increase the body's ability to heal itself could not only help us conquer some of these difficult autoimmune problems, but also significantly change the way we approach healing.
The studies that are most publicized were done outside the U.S. A 2002 Egyptian research study focused on determining if Naltrexone could restore fertility in Clomiphene Citrate-resistant women. Clomiphene Citrate, also known as Clomid, is used to stimulate ovulation and many women develop a resistance to it after several months of use. The study showed that, administering a six-month regimen of Naltrexone, modified after 12 weeks with the addition of Clomiphene Citrate, to infertile, obese, insulin resistant and hyperandrogenic PCOS sufferers --- who had also developed a resistance to Clomiphene Citrate -- was very effective.
Results revealed that the Opioid Therapy actually reduced androgen levels, enabled significant weight loss - reductions in BMI (Body Mass Index), and had a positive effect on menstrual cycling and insulin resistance. Further, out of thirty PCOS women tested with a combination of Naltrexone plus Clomiphene Citrate, nine conceived and eight delivered. (4)
Just as noteworthy is an Italian study that suggests that Naltrexone can affect Insulin Resistance and potentially the onset of serious diseases that it precipitates. This study, cited in The Journal of Clinical Endocrinology and Metabolism, concerning the effect of ovarian-generated hormones on insulin disorders in PCOS patients, showed that Naltrexone significantly reduced the insulin response to Glucose Tolerance Tests. There is evidence that it can affect pancreatic function and the removal of insulin from the blood, (5) which directly influences the problem of insulin resistance, a foundational culprit in PCOS.
These, along with other studies, have helped uncover some extremely important relationships between the immune system, the hormonal balance of the body and the problems of women with PCOS.
As mentioned earlier, Naltrexone was initially designed to lessen the problems of addiction by binding to the narcotic receptors to reduce the effect of the narcotic on the brain. And, although LDN is touted as being side-effect-free because it stimulates the body's own mechanisms, there are patients for whom it is not well-suited - especially those already being treated for addictions.
As with all drugs, LDN needs careful observation. Although the dosages are very much lower in Opioid Therapy than in Addictive Therapy, there are a variety of issues a health care provider needs to carefully consider when prescribing it. Toxicity, side-effects such as increased pain sensitivity, and loss of effectiveness with prolonged use require careful attention so dosages can be adjusted.
With each new breakthrough and with each new drug, the promise of health seems closer, yet, the associated risks can be serious. One thing is clear and consistently makes the top of the list whenever new studies are done; the better our lifestyle choices and the more consistent our exercise, the greater support we provide our natural immune system. The hope is that as we each educate ourselves and start to understand our particular situation, our lifestyle choices will be based on healthier priorities.
(1) Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor; Zagon IS, Kreiner S, Heslop JJ, Conway AB, Morgan CR, McLaughlin PJ.; Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. Int J Oncol. 2008 Aug;33(2):317-23, PMID: 18636152
(2) Effects of Opioids on the Immune System. Neurochem Res 1996;21:1375-1386; Roy S, Loh HH. Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18 PMID: 8947928
(3) Ian S. Zagon, Pennsylvania State University Faculty Research Expertise Database,
(4) Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome; M.I. Ahmed, A.J. Duleba, O. El Shahat, M.E. Ibrahim and A. Salem , 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 ; Hum. Reprod., July 18, 2008; den273v1.
(5) Involvement of Ovarian Steroids in the Opioid-Mediated Reduction of Insulin Secretion in Hyperinsulinemic Patients with Polycystic Ovary Syndrome; Maurizio Guido, et al. The Journal of Clinical Endocrinology & Metabolism, Vol. 83, No. 5 1742-1745, Copyright © 1998 by The Endocrine Society
(6) Opioids for Chronic Nonterminal Pain, Jane C. Ballantyne, MD, FRCA, Division of Pain Medicine, Massachusetts General Hospital, Department of Anesthesia and Critical Care, Harvard Medical School, Boston, MA 02114, USA. South Med J. 2006 Nov;99(11):1245-55, PMID: 17195420.