Naltrexone for PCOS

By Amy Medling, founder of PCOS Diva

Years ago, I heard of the drug Naltrexone being used as a therapy for PCOS, particularly in Ireland. Now low-dose Naltrexone (LDN) is often used for autoimmune disorders. Since many women with PCOS also struggle with multiple autoimmune disorders, LDN may be a helpful option. This is not a drug that I have ever used or necessarily recommend, but as a PCOS Diva, it is my responsibility to educate myself and share what I have learned. I encourage you to do the same.

What is Naltrexone?

Naltrexone Hydrochloride, or simply Naltrexone, is a licensed drug commonly utilized as treatment for alcohol and drug dependency. It is the proposed treatment for heroin addiction.

Naltrexone functions as an opioid receptor blocker in the brain and affects the brain’s response to narcotic medication and alcohol.

Blocking these receptors also triggers a chain reaction that affects immune system in multiple, complex ways. While Naltrexone is still primarily used to treat alcohol and drug addiction, recent research has shown Naltrexone in low doses (often referred to as low-dose – typically 4.5 mg) on the body’s immune system. ) might also help treat certain chronic diseases such as Crohn’s disease, ulcerative colitis, and PCOS.

PCOS, Opioids, and the Immune system

You must be wondering: How could a drug used to treat drug and alcohol dependency be useful for a PCOS patient like me?

Multiple studies have indicated Naltrexone has PCOS benefits. More than PCOS, Naltrexone has been found to treat premenstrual syndrome (PMS) and endometriosis. Other studies suggest its potential benefits for “tail end brown bleeding,” anxiety, sleep disturbance, and low mood.

How It Works

Opioids

Generally speaking, opioids are substances found in your brain support pain and pleasure regulation. They also interact with sex hormones.

Opioids in other parts of your body serve to regulate function of the pancreas and liver. These same opioids also regulate glucose metabolism and insulin balance, two internal processes critical to women with PCOS. According to a 2009 study, we are more likely to suffer from opioid system dysregulation both in the brain and elsewhere in the body, with obesity as a complicating factor.

The research showed positive results when using the drug, and researchers concluded that “naltrexone has been demonstrated to successfully augment traditional ovulation induction regimens.” Which means naltrexone’s opioid regulating benefit can possibly help alleviate PCOS symptoms and even improve fertility.

Immune system

PCOS and immune system dysregulation, a condition where the function of the immune system is altered in a way that causes harm, are often linked.

• One aspect of this dysregulation is the occurrence of autoimmune diseases such as autoimmune thyroiditis or Hashimoto’s Disease. In autoimmunity, there is breakdown of mechanisms responsible for self-tolerance and the immune system begins to fight itself.
• Another aspect is the high levels of androgen (male hormones) in many women with PCOS leads components of the immune system to become hypersensitive to certain stimuli. Unfortunately, there is barely any discussion with regards to the immune system and its links to PCOS, so immune dysregulation becomes an overlooked aspect of this disease.

Recent studies show low-dose naltrexone to be capable of modulating the immune system and brain neurochemistry. It’s basically making sure your immune system doesn’t malfunction when you have a disease that is actively trying to make it go haywire.

“It is proposed that low-dose naltrexone can be used effectively as a buffer for a large variety of bodily and mental ailments through its ability to beneficially modulate both the immune system and the brain neurochemistries that regulate positive affect.”

A compound capable of making the immune system run smoothly can only be beneficial for PCOS patients. Regardless, asking your physician on whether low dose naltrexone is helpful or not is the first step.

Dosage and Side Effects

Recommended Dosage:

Naltrexone is typically used orally at a dose of 25–50 mg daily. Low-dose Naltrexone is typically dosed at 4.5 mg.

Known Side effects:

Adverse effects may include:

• Abdominal pain
• Nausea
• Vomiting
• Anorexia
• Diarrhea
• Headaches
• Chest and muscle pains
• Thrombocytopenia

Naltrexone should not be given to patients using opioids chronically, as well as those who have hepatitis or hepatic failure. Since Naltrexone is excreted primarily in the urine, using the drug should be avoided if the patient has a history or is afflicted with renal impairment.

Naltrexone should be administered with caution in the presence of concomitant use of drugs such as acetaminophen and disulfiram, as these drugs are associated with potential liver toxicity. It is listed as a pregnancy category C medication, or a medication that show adverse effects on the fetus but also offer potential health benefits in pregnant women.

Recent studies

Due to its rather novel status as PCOS treatment, researchers were compelled to dive in and see just how effective Naltrexone is. Here are some studies that demonstrate the efficacy of naltrexone when it comes to treating PCOS and its symptoms.

1. Study: Medical management of metabolic dysfunction in PCOS

About: The review presented multiple available medical treatments of selected features of metabolic dysfunction and discussed the benefits and drawbacks of their use in PCOS. Medications reviewed were Metformin, acarbose, thiazolidinediones, vitamin D, orlistat, statins and naltrexone.

Use of Naltrexone in treatment of PCOS is based on the evidence that PCOS is characterized by increased activity of sympathetic nervous system, altered central opioid tone and elevated beta-endorphin release. There is also a growing body of evidence demonstrating that beta-endorphins exert profound effects on insulin release.

Results/Conclusion: Oral administration of Naltrexone in PCOS patients resulted in a significant reduction of fasting insulin level following glucose load without adversely affecting glucose levels.

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

About: This clinical study seeks to evaluate the clinical and endocrine effects of prescribing naltrexone in obese women with PCOS. The women were treated with 50 mg naltrexone per day for six months.

Results/Conclusion: BMI decreased significantly from an average of 30 to 26 during treatment. The menstrual cycle improved in 80% of PCOS women. Plasma levels of free testosterone, dehydroepiandrosterone sulfate, cortisol, and androstenedione decreased significantly. Fasting glucose-to-insulin ratio improved in those with insulin resistance.

3. Study: Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome

About: 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 PCOS patients were evaluated; all of them were obese, hyperandrogenic and hyperinsulinemic; 16 subjects were amenorrhic (absence of menstruation) while 14 were oligomenorrhic (infrequent menstrual periods). All patients received natrexone (50 mg daily) for 6 months.

Those who did not ovulate after 12 weeks of naltrexone monotherapy were also given CC. The dose started at 50 mg per day for the first five days, non responders increased the dosage all the way to 150 mg per day.

Results/Conclusion: Naltrexone improved endocrine and metabolic function in women with CC-resistant PCOS. Taking naltrexone also brought back CC sensitivity in the majority of subjects, resulting in a significant number of pregnancies.

*Before trying any new treatment or drug, I encourage you to discuss it with your medical provider.

Amy Medling,author of Healing PCOS and certified health coach, specializes in working with women with Polycystic Ovary Syndrome, (PCOS), who are frustrated and have lost all hope when the only solution their doctors offer is to lose weight, take a pill, and live with their symptoms. In response, Amy founded PCOS Diva and developed a proven protocol of supplements, diet, and lifestyle programs that offer women tools to help gain control of their PCOS and regain their fertility, femininity, health, and happiness.  

References:

1. Eyvazzadeh AD, Pennington KP, Pop-busui R, Sowers M, Zubieta JK, Smith YR. The role of the endogenous opioid system in polycystic ovary syndrome. Fertil Steril. 2009;92(1):1-12.
2. Sinha U, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK. Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India. Indian Journal of Endocrinology and Metabolism. 2013;17(2):304-309. doi:10.4103/2230-8210.109714.
3. Brown N, Panksepp J. Low-dose naltrexone for disease prevention and quality of life. Med Hypotheses. 2009;72(3):333-7.
4. Duleba AJ. Medical management of metabolic dysfunction in PCOS. Steroids. 2012;77(4):306-311. doi:10.1016/j.steroids.2011.11.014.
5. Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani AR. Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome. Fertil Steril. 2002;77(5):936-44.
6. Ahmed MI, Duleba AJ, El shahat O, Ibrahim ME, Salem A. Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome. Hum Reprod. 2008;23(11):2564-9.