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Low-Dose Naltrexone (LDN) for Women’s Health

Although Women’s Health Month is over, we are continuing to focus on compounded preparations for women’s health in the second of our three-part blog series on women’s health. The first blog post about hormone replacement therapy can be found here.

Naltrexone is an FDA-approved opioid antagonist used to manage alcohol use or opioid use disorder at a dose of 50 mg, but at lower doses (typically ≤ 4.5 mg), it elicits different therapeutic effects in various patient populations. Although naltrexone has been used for decades, the indications of LDN have only begun to emerge, especially in the past several years. 

In our most recent blog post, we discussed some of these off-label indications, including the use of low-dose naltrexone (LDN) eye drop for treating a variety of ophthalmic conditions. This month, we’ll be focusing on indications related to women’s health, including conditions that affect only women and conditions that affect predominantly women. 

Vulvodynia

At some point during their life, as many as eight percent of women may suffer from vulvodynia (chronic pain or discomfort around the vulva), with one-third to half never seeking treatment (1). Even if treatment is sought, there is no guarantee that a proper diagnosis will be made, with half of women failing to receive a diagnosis. It has been suggested that LDN can treat vulvodynia by reducing pro-inflammatory cytokines that worsen the symptoms of vulvodynia (2), indicating that LDN has the potential to treat this underdiagnosed condition (3). The LDN Research Trust lists various reports of LDN being used to treat vulvodynia, with a suggested titration schedule from 0.1 mg/day to 0.5 mg/day. In fact, it has shown such promising results that investigators have registered a clinical trial for the use of LDN to treat vulvodynia, with an expected completion date in 2026.

Irritable bowel syndrome (IBS)

IBS is more common in women than men, and its symptoms often overlap with those of chronic pain disorders, such as fibromyalgia, chronic pelvic pain, and migraines. Moreover, its symptoms are often worse during menstruation (4). LDN improved the number of pain-free days and overall symptom relief in 76 percent of IBS patients in a small pilot study (5). In another study to determine side effects of LDN for gastrointestinal disorders (diarrhea, constipation, and inflammatory bowel disease), the authors administered LDN in the range of 2.5 mg/day to 4.5 mg/day and concluded that LDN had mostly tolerable side effects and appeared to help patients with gastrointestinal disorders (6).  

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Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome (PCOS) affects women of reproductive age, who may present obesity, infertility, or androgenic features. Weight gain is a common PCOS symptom, and it has been suggested that a weight loss of just five percent can help improve PCOS symptoms

For more than 30 years, naltrexone has been investigated for managing PCOS and associated symptoms (7). Previous research has shown that naltrexone decreased BMI and improved menstrual cycles in 80 percent of women with PCOS after six months of treatment (8). Now, there are several case reports on the LDN Research Trust website in which prescribers have used LDN to treat patients with PCOS. 

Weight loss

Naltrexone may help reduce appetite and modulate the release of insulin (9), with one study showing that naltrexone was more effective in helping women lose more weight than men (10). In other studies, naltrexone significantly reduced BMI in patients with PCOS (8), with another study from Yale reporting that naltrexone helped suppress appetite and sustain weight loss.

Fibromyalgia

It has been estimated that 75–90 percent of all patients diagnosed with fibromyalgia are women (11). Fibromyalgia patients may fail to respond to FDA-approved drugs for treating fibromyalgia such as pregabalin, milnacipran, and duloxetine. Several studies have shown that LDN may be used as an effective, safe, and inexpensive adjunctive therapy for treating fibromyalgia pain (12–14).  

Premenstrual syndrome (PMS)

LDN has been suggested to improve the menstrual cycle, including significant improvements in period pain, as many as 80 percent of women reporting dramatic improvements in premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), in line with previous clinical trials that have shown the benefits of naltrexone for treating these conditions (15).

Menopause symptoms

Chronic pain

During menopause, women’s bodies undergo numerous changes that can manifest as localized or systemic pain. Women experiencing menopause may also experience musculoskeletal pain that affects different parts of their body (muscles, ligaments, tendons, and bones). Oftentimes, this pain is chronic and may last for years and may begin due to a decline in estrogen. Although hormone replacement therapy can help address some of these challenges, it’s no cure. LDN has been shown to address a variety of chronic pains, many of which are experienced by women undergoing menopause (16,17).

Insomnia

Sleep disturbances are a common occurrence for women during perimenopause and post-menopause, with as many as 60 percent of women experiencing sleep disturbances after menopause. As we’ve discussed previously, LDN has been prescribed in doses ranging from 3 mg/day to 12 mg/day to help improve sleep in various patient populations (18,19).

Burning mouth syndrome

Burning mouth syndrome causes chronic pain that manifests as a burning sensation of the oral mucosa in the absence of injury. Perimenopausal and postmenopausal women are the populations most affected by this syndrome, which may not respond to other treatments. Two recent case studies have reported the use of LDN to treat this condition in two elderly women. 

In both cases, the LDN doses were titrated up from 1.5 mg/day to 4.5 mg/day (20,21). In both cases, the patients experienced clinically meaningful reductions in pain associated with burning mouth syndrome, as well as reductions in systemic pain associated with other concurrent conditions such as fibromyalgia, irritable bowel syndrome, and interstitial cystitis.

Potential Future Indications

The off-label indications of LDN for women’s health are continually expanding. A clinical trial has been registered by researchers at Stanford University to investigate the use of LDN to treat bladder pain syndrome, which is estimated to be completed later this year.

Other studies have suggested that LDN can be used to treat other chronic pains experienced by women, including pelvic pain syndrome (22). LDN research has been gaining momentum in recent years, so we’ll be keeping a close eye and will report any emerging indications.

Why Choose VLS Pharmacy and New Drug Loft for Compounded LDN?

Accurate LDN Dosing

Because naltrexone is currently only commercially available as 50 mg tablets, patients may try to create their own LDN dosages by cutting up these tablets. Some patients may rely on Internet sources that explain how to do this or create a solution and then divide the liquid doses (23). As accurate dosing is critical to the success of any therapy, this will almost certainly lead to inaccurate day-to-day dosing. VLS Pharmacy & New Drug Loft can create LDN formulations with patient-specific dosing and administration routes, helping ensure that patients are receiving accurate doses. 

Accurate LDN Dose Titration Schedule

There is no agreed upon effective dose of LDN, so prescribers will likely have to titrate the dose to determine the maximally effective dose for their individual patients.16 LDN is typically titrated up from 1.5 mg/day to up to 4.5 mg/day over the course of at least one month. Regardless of which titration schedule is prescribed, our pharmacists will tailor it to meet each individual patient’s specific needs. 

As a 503A compounding pharmacy specializing in sterile and non-sterile compounding, we will support you and your patients by creating safe, individualized, and effective pharmaceutical therapies. All formulations are compounded with high-quality pharmaceutical-grade APIs sourced directly from PCCA, the leader of superior-quality APIs.

 

Please comment below with any thoughts or questions!

Reach out to our team to learn about best practices and to partner with our experts on custom compounded medications for your patients. All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.

 

References

  1. Harlow BL, Kunitz CG, Nguyen RHN, Rydell SA, Turner RM, Maclehose RF. Prevalence of symptoms consistent with a diagnosis of vulvodynia: Population-based estimates from 2 geographic regions. American Journal of Obstetrics and Gynecology. 2014;210(1):40.e1-40.e8. doi:10.1016/j.ajog.2013.09.033
  2. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia – PubMed. Accessed June 4, 2024. https://pubmed.ncbi.nlm.nih.gov/28536359/
  3. Vieira-Baptista P, Lima-Silva J, Pérez-López FR, Preti M, Bornstein J. Vulvodynia: A disease commonly hidden in plain sight. Case Rep Womens Health. 2018;20:e00079. doi:10.1016/j.crwh.2018.e00079
  4. Kim YS, Kim N. Sex-Gender Differences in Irritable Bowel Syndrome. J Neurogastroenterol Motil. 2018;24(4):544-558. doi:10.5056/jnm18082
  5. Kariv R, Tiomny E, Grenshpon R, et al. Low-dose naltreoxone for the treatment of irritable bowel syndrome: a pilot study. Dig Dis Sci. 2006;51(12):2128-2133. doi:10.1007/s10620-006-9289-8
  6. Ploesser J, Weinstock LB, Thomas E. Low dose naltrexone: side effects and efficacy in gastrointestinal disorders. Int J Pharm Compd. 2010;14(2):171-173.
  7. Lanzone A, Apa R, Fulghesu AM, Cutillo G, Caruso A, Mancuso S. Long-term naltrexone* treatment normalizes the pituitary response to gonadotropin-releasing hormone in polycystic ovarian syndrome†. Fertility and Sterility. 1993;59(4):734-737. doi:10.1016/S0015-0282(16)55851-8
  8. 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. Fertility and Sterility. 2002;77(5):936-944. doi:10.1016/S0015-0282(02)02955-2
  9. Duleba AJ. Medical management of metabolic dysfunction in PCOS. Steroids. 2012;77(4):306-311. doi:10.1016/j.steroids.2011.11.014
  10. Atkinson RL, Berke LK, Drake CR, Bibbs ML, Williams FL, Kaiser DL. Effects of long-term therapy with naltrexone on body weight in obesity. Clinical Pharmacology & Therapeutics. 1985;38(4):419-422. doi:10.1038/clpt.1985.197
  11. Arout CA, Sofuoglu M, Bastian LA, Rosenheck RA. Gender Differences in the Prevalence of Fibromyalgia and in Concomitant Medical and Psychiatric Disorders: A National Veterans Health Administration Study. J Womens Health (Larchmt). 2018;27(8):1035-1044. doi:10.1089/jwh.2017.6622
  12. Metyas S, Chen CL, Yeter K, Solyman J, Arkfeld DG. Low Dose Naltrexone in the Treatment of Fibromyalgia. Curr Rheumatol Rev. 2018;14(2):177-180. doi:10.2174/1573397113666170321120329
  13. Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013;65(2):529-538. doi:10.1002/art.37734
  14. Ramanathan S, Panksepp J, Johnson B. Is fibromyalgia an endocrine/endorphin deficit disorder? Is low dose naltrexone a new treatment option? Psychosomatics. 2012;53(6):591-594. doi:10.1016/j.psym.2011.11.006
  15. Chuong CJ, Coulam CB, Bergstralh EJ, O’Fallon WM, Steinmetz GI. Clinical trial of naltrexone in premenstrual syndrome. Obstet Gynecol. 1988;72(3 Pt 1):332-336.
  16. Marcus NJ, Robbins L, Araki A, Gracely EJ, Theoharides TC. Effective Doses of Low-Dose Naltrexone for Chronic Pain – An Observational Study. J Pain Res. 2024;17:1273-1284. doi:10.2147/JPR.S451183
  17. McKenzie-Brown AM, Boorman DW, Ibanez KR, Agwu E, Singh V. Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series. J Pain Res. 2023;16:1993-1998. doi:10.2147/JPR.S389957
  18. Cote B, Ross B, Fortner J, Rao D. The Use and Utility of Low-dose Naltrexone Capsules for Patients with Fibromyalgia. Int J Pharm Compd. 2018;22(3):252-256.
  19. Bolton MJ, Chapman BP, Van Marwijk H. Low-dose naltrexone as a treatment for chronic fatigue syndrome. BMJ Case Rep. 2020;13(1):e232502. doi:10.1136/bcr-2019-232502
  20. Sangalli L, Miller CS. Low-dose naltrexone for treatment of burning mouth syndrome. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2023;135(4):e83-e88. doi:10.1016/j.oooo.2022.04.048
  21. Neuman DL, Chadwick AL. Utilization of Low-Dose Naltrexone for Burning Mouth Syndrome: A Case Report. A A Pract. 2021;15(5):e01475. doi:10.1213/XAA.0000000000001475
  22. Poliwoda S, Noss B, Truong GTD, et al. The Utilization of Low Dose Naltrexone for Chronic Pain. CNS Drugs. 2023;37(8):663-670. doi:10.1007/s40263-023-01018-3
  23. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014;33(4):451-459. doi:10.1007/s10067-014-2517-2

 

 


 

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