Can naltrexone (opioid receptor antagonist) be used to treat endometriosis and is a dose of 1 milligram (mg) twice daily (bid) appropriate?

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Last updated: June 25, 2025View editorial policy

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From the Guidelines

Naltrexone can be used as an off-label treatment option for endometriosis, and a dose of 1 mg twice daily is within the typical low-dose range used for this condition. The provided evidence does not directly address the use of naltrexone for endometriosis, but it discusses various treatment options for managing endometriosis-related pain, including GnRH agonists, danazol, oral contraceptives, and nonsteroidal anti-inflammatory drugs 1. However, based on the general understanding of low-dose naltrexone (LDN) and its application in chronic pain conditions, it is reasonable to consider its use in endometriosis. LDN is thought to work by temporarily blocking opioid receptors, leading to increased endorphin production and reduced inflammatory cytokines, which may help reduce pain and inflammation in endometriosis.

Key Considerations

  • The standard LDN dosing for chronic pain conditions and autoimmune disorders generally ranges from 1-4.5 mg daily, often starting at lower doses and gradually increasing.
  • Patients should be aware that this is an off-label use, and response varies between individuals.
  • Side effects are generally mild and may include temporary sleep disturbances, vivid dreams, headaches, or gastrointestinal upset, which typically resolve within the first few weeks of treatment.
  • LDN should be used as part of a comprehensive treatment approach for endometriosis, potentially alongside other therapies, and patients should work closely with their healthcare provider to monitor effectiveness and adjust dosing as needed.

Given the lack of direct evidence from the provided studies, the decision to use naltrexone for endometriosis should be based on the most recent and highest quality studies available, even if not listed here, and should prioritize the patient's overall morbidity, mortality, and quality of life outcomes. However, since no recent or high-quality studies are cited here regarding naltrexone's use in endometriosis, clinical judgment and patient-specific factors should guide the treatment decision.

From the Research

Naltrexone for Endometriosis

  • There is no direct evidence in the provided studies to support the use of naltrexone for endometriosis treatment 2, 3, 4, 5, 6.
  • The studies focus on hormonal treatments such as gonadotropin-releasing hormone (GnRH) agonists and antagonists, aromatase inhibitors, progestogens, and oral contraceptives for managing endometriosis symptoms 2, 3, 4, 5, 6.
  • Naltrexone, an opioid receptor antagonist, is not mentioned as a treatment option for endometriosis in the provided studies.

Dosage of 1 mg Bid

  • Without evidence supporting the use of naltrexone for endometriosis, it is unclear whether a dose of 1 milligram twice daily (bid) would be appropriate 2, 3, 4, 5, 6.
  • The provided studies discuss various dosing regimens for approved endometriosis treatments, but none pertain to naltrexone 2, 3, 4, 5, 6.

Alternative Treatments

  • Current medical treatments for endometriosis aim to reduce estrogen levels, inhibit ovulation, and suppress uterine blood flow 2, 3, 4, 5, 6.
  • Options include oral contraceptives, progestogens, GnRH agonists and antagonists, and aromatase inhibitors, each with varying efficacy, safety, and cost profiles 2, 3, 4, 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Advances in pharmacotherapy for treating endometriosis.

Expert opinion on pharmacotherapy, 2015

Research

Medical treatment of endometriosis-related pain.

Best practice & research. Clinical obstetrics & gynaecology, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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