Low Dose Naltrexone (LDN) for Endometriosis: A Comprehensive Naturopathic Guide

For years, many women with endometriosis have been told their only options are hormonal birth control, pain medications, or surgery. While excision surgery remains the gold standard for removing endometrial lesions, LDN has emerged as a powerful complementary therapy that addresses the underlying inflammation, immune dysfunction, and pain that characterize this complex condition.

If you're living with endometriosis, you know the reality: debilitating pelvic pain, fatigue that steals your energy, digestive symptoms that disrupt daily life, and the emotional toll of a condition that's often dismissed or minimized. LDN offers hope—not as a cure, but as a tool that can significantly improve quality of life while addressing root causes.

In this guide, we'll explore:

• What LDN is and how it works for endometriosis

• The science behind LDN's effects on pain and inflammation

• How to safely titrate and use LDN

• What to expect: benefits, timeline, and side effects

• Integrating LDN into a comprehensive naturopathic treatment plan

Understanding Low Dose Naltrexone: From Addiction Medicine to Endometriosis Treatment

Naltrexone has a fascinating history. Originally developed in the 1960s and FDA-approved in 1984, naltrexone was designed as an opioid receptor antagonist to treat addiction. At standard doses of 50-100 mg daily, it blocks opioid receptors in the brain, preventing substances like heroin and morphine from producing their euphoric effects.

But here's where the story gets interesting: In the 1980s, Dr. Bernard Bihari, an HIV researcher, discovered something unexpected. When his patients took naltrexone at much lower doses—just 1.5 to 4.5 mg—they experienced significant immune system benefits. This serendipitous finding sparked decades of research into what we now call Low Dose Naltrexone (LDN).

Today, LDN is being used off-label for over 100 conditions, with growing evidence for its effectiveness in autoimmune diseases, chronic pain conditions, and inflammatory disorders—including endometriosis. While LDN isn't FDA-approved for endometriosis specifically, clinical experience and emerging research suggest it may be one of the most promising complementary therapies available.

Why Endometriosis Responds to LDN: The Science Behind the Benefits

Endometriosis is far more than just "bad periods." It's a complex, systemic inflammatory condition characterized by:

• Immune system dysfunction with elevated inflammatory cytokines

• Chronic neuroinflammation and central sensitization

• Endorphin deficiency linked to pain and mood dysregulation

• Oxidative stress and impaired cellular function

  
  

LDN addresses these underlying mechanisms through three primary pathways:

1. Endorphin Modulation: Boosting Your Body's Natural Painkillers

At low doses, LDN temporarily blocks opioid receptors for approximately 4-6 hours. This brief blockade triggers a rebound effect: your body responds by upregulating opioid receptors and producing more endogenous endorphins (your body's natural opioids) over the following 18-20 hours.

This is crucial for endometriosis because research shows that women with endometriosis often have endorphin deficiency. Endorphins don't just reduce pain—they also:

• Regulate immune function

• Improve mood and reduce anxiety

• Support hormonal balance

• Enhance sleep quality

• Reduce inflammation

By taking LDN at night, you're essentially "tricking" your body into producing more of these beneficial compounds throughout the day.

2. Immune System Modulation: Calming the Inflammatory Response

Endometriosis is increasingly recognized as having significant immune system involvement. Women with endometriosis show:

• Elevated pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha)

• Dysfunctional natural killer (NK) cell activity

• Increased macrophage activation

• Autoimmune features in many cases

  
  

LDN works by binding to Toll-like Receptor 4 (TLR4) on immune cells, particularly microglia in the nervous system. This binding reduces the production of inflammatory cytokines and helps rebalance immune function. Studies have shown that LDN can:

• Decrease levels of inflammatory markers

• Reduce oxidative stress

• Modulate the overactive immune response seen in endometriosis

• Support healthier immune surveillance

3. Central Sensitization and Neuroinflammation: Breaking the Pain Cycle

Many women with endometriosis develop central sensitization—a condition where the nervous system becomes hypersensitive to pain signals. This explains why pain often persists even after surgical removal of endometrial lesions, and why pain may spread beyond the pelvis.

LDN's action on microglial cells in the central nervous system helps reduce neuroinflammation, potentially "resetting" the pain response and breaking the cycle of chronic pain amplification.

Image source: ResearchGate, 'Low dose naltrexone's mechanism of action' from Impact of Opioid Use in Hematological Malignancies

The Clinical Evidence: What Research and Experience Tell Us

While large-scale randomized controlled trials for LDN in endometriosis are still limited (partly because LDN is off-patent and not promoted by pharmaceutical companies), the existing evidence is compelling:

Clinical Experience: Dr. Phil Boyle, a pioneer in using LDN for women's health conditions, reports that approximately 80% of his endometriosis patients experience significant pain relief with nightly LDN use. Over two decades, he has treated thousands of women with endometriosis using LDN as part of a comprehensive approach.

Research Findings:

• Studies on LDN for chronic pain conditions, including fibromyalgia (which shares many features with endometriosis), show significant pain reduction and improved quality of life

• Research on multiple sclerosis and Crohn's disease—both inflammatory conditions—demonstrates LDN's anti-inflammatory and immune-modulating effects

• Preliminary studies suggest LDN may improve fertility outcomes in women with endometriosis and PCOS

• Patient surveys consistently show high satisfaction rates, with many reporting it as "life-changing"

  
  

Patient-Reported Outcomes: Clinical reports and patient surveys indicate that many women who try LDN for endometriosis experience significant improvements within weeks to months. While individual responses vary considerably, commonly reported benefits include:

• Substantial reduction in pelvic pain severity

• Decreased reliance on NSAIDs and other pain medications

• Improvements in fatigue and energy levels

• Better mood stability and reduced anxiety

• Improved digestive function and reduced bloating

• Enhanced ability to exercise and engage in daily activities

• Better sleep quality

Who Should Consider LDN for Endometriosis?

LDN may be particularly beneficial if you experience:

• Chronic pelvic pain despite medical management

• Widespread pain or central sensitization

• Significant fatigue and low energy

• Mood dysregulation, anxiety, or depression

• Inflammatory bowel symptoms

• Suspected or confirmed immune dysfunction

• Desire to reduce reliance on NSAIDs or opioid medications

• Post-surgical pain that persists

• Concurrent autoimmune conditions (Hashimoto's, rheumatoid arthritis, etc.)

  
  

LDN is not appropriate if you:

• Are currently taking opioid medications (must wait 7-14 days after discontinuation)

• Have active liver disease (monitoring required)

• Are pregnant or breastfeeding (unless under direct medical supervision)

• Have a history of severe psychiatric conditions (use caution and close monitoring)

The Naturopathic Approach: How to Start and Titrate LDN Safely

The "Start Low and Go Slow" Principle

Unlike many medications, LDN requires patience and individualized titration. This slow approach is essential for three reasons:

1. Minimizing side effects: Starting low reduces the likelihood of vivid dreams, temporary insomnia, headaches, or initial fatigue

2. Finding your optimal dose: Every woman's "sweet spot" is different—typically between 3.0-4.5 mg, but some women do best on as little as 1.5 mg or as much as 6 mg

3. Supporting physiological adaptation: LDN triggers significant changes in endorphin production and immune function—your body needs time to adjust

   
   

Standard Titration Protocol

Starting Dose: Most women begin at 0.5 mg to 1.5 mg nightly, taken at bedtime (aligning with the body's natural endorphin cycle).

Important Notes:

• Increase by 0.5 mg every 1-2 weeks, guided by your response

• If side effects emerge, stay at your current dose for an extra week or two before increasing

• Some women, especially those with thyroid conditions, mast cell activation syndrome, or high sensitivity, may need to start even lower (0.25 mg) and increase more slowly

• Typical maintenance dose is 3.0-4.5 mg, but this is individual

  
  

Special Considerations for Endometriosis

Timing with Your Cycle: Some women find that starting LDN during the follicular phase (days 1-14 of the cycle) results in better tolerance. Others prefer to start after ovulation when progesterone is higher, which may provide additional anti-inflammatory support.

Consider Your Thyroid: Many women with endometriosis also have thyroid issues, particularly Hashimoto's thyroiditis. If this is you, start at 0.5 mg or lower and titrate very slowly. LDN can be particularly beneficial for thyroid autoimmunity, but initial immune modulation may temporarily affect thyroid function.

Mast Cell Activation: If you have mast cell activation syndrome (MCAS)—common in endometriosis patients—you may be more sensitive to new supplements and medications. Start at 0.25 mg if needed, and ensure your LDN is compounded without common fillers that trigger mast cell degranulation.

Practical Tips for Success

1. Take at the same time each night: Consistency helps maintain stable endorphin cycling

2. Take on an empty stomach when possible: For best absorption, take 2 hours after eating

3. If you miss a dose: Simply skip it and resume your normal schedule the next night—don't double up

4. Keep a symptom journal: Track pain levels (1-10 scale), mood, energy, sleep quality, and any side effects

5. Be patient: While some women notice improvements within 2-4 weeks, full benefits often take 2-3 months

6. Communicate with your provider: Regular check-ins help optimize your dose and address concerns

What to Expect: Benefits, Timeline, and Potential Side Effects

Positive Outcomes Reported by Patients

Pain Reduction (2-8 weeks): Most women report noticeable decreases in pelvic pain, with continued improvement over months. Pain may not disappear entirely, but many report 50-80% reductions, allowing them to reduce or eliminate NSAIDs.

Energy and Fatigue (4-12 weeks): Improved energy is often one of the most appreciated benefits. Women describe feeling like they can "finally function again" and engage in activities that were previously impossible.

Mood Stabilization (2-8 weeks): Many women experience significant improvements in mood, reduced anxiety, and better emotional regulation. This makes sense given endorphin's role in mood modulation.

Reduced Inflammation and Bloating (4-12 weeks): Digestive symptoms, "endo belly," and overall inflammation often decrease significantly.

Better Sleep Quality (2-6 weeks): After initial potential sleep disturbances, many women report deeper, more restorative sleep.

Improved Exercise Tolerance: With reduced pain and increased energy, women find they can return to exercise and movement they love.

Common Side Effects (Usually Temporary)

Vivid Dreams or Altered Sleep (First 2-4 weeks): This is the most commonly reported side effect. Dreams may be unusually vivid or intense. For most women, this normalizes within 2-4 weeks. If it persists:

• Try taking LDN earlier in the evening (6-8 PM instead of bedtime)

• Reduce your dose slightly

• Take magnesium glycinate before bed for sleep support

  
  

Mild Headaches (First 1-2 weeks): Usually transient and related to detoxification effects. Stay well-hydrated and ensure adequate electrolytes.

Initial Fatigue or Energy Fluctuations (First 2-4 weeks): Some women experience temporary fatigue as their body adjusts. This typically resolves as endorphin production stabilizes.

Mild Digestive Changes (First 1-3 weeks): Some women report temporary nausea or digestive changes. Taking LDN with a small piece of fruit or in the evening after dinner can help.

Rare Immune Reactions (First 4-8 weeks): Occasionally, women may experience temporary worsening of inflammatory symptoms as the immune system recalibrates. This usually resolves with continued use, but should be discussed with your provider.

When to Pause or Adjust

If you experience:

• Worsening symptoms that don't improve after 1-2 weeks at the same dose

• Significant sleep disturbance that affects daily function after 4 weeks

• Persistent headaches or nausea

• Any concerning symptoms

  
  

Pause your increase and consult with your naturopathic doctor or healthcare provider. Sometimes a slower titration or lower maintenance dose is more appropriate.

Critical Safety Considerations

Absolute Contraindications

Opioid Medications: You cannot take LDN while using opioid pain medications (codeine, oxycodone, hydrocodone, morphine, tramadol, etc.). LDN blocks opioid receptors and can precipitate withdrawal symptoms. You must be off all opioids for at least 7-14 days before starting LDN.

Alcohol Interaction: LDN may increase sensitivity to alcohol. Many women find they tolerate alcohol poorly while on LDN. Limit intake and monitor your response carefully.

Monitoring and Precautions

Liver Function: Although LDN is used at doses far below those that typically affect the liver, baseline and periodic liver function testing is recommended, especially if you have any history of liver issues.

Pregnancy and Breastfeeding: LDN has been used successfully by some practitioners throughout pregnancy and breastfeeding, but this should only be done under direct medical supervision. Dr. Phil Boyle has treated over 2,000 pregnancies with LDN through 37 weeks gestation with reported safety, but individual assessment is essential.

Thyroid Monitoring: If you have thyroid disease, monitor thyroid function more frequently when starting LDN, as immune modulation may affect thyroid hormone levels.

Sourcing High-Quality LDN: What You Need to Know

LDN is not available as a commercial product—it must be compounded by a specialized pharmacy. Here's what you need to know:

Finding a Compounding Pharmacy

At Tang Naturopathic, we work with trusted compounding pharmacies that specialize in high-quality LDN formulations. We ensure our patients receive pharmaceutical-grade naltrexone from experienced compounders who understand proper dosing and formulation.

When sourcing LDN, it's essential to work with a pharmacy that:

• Specializes in LDN compounding with extensive experience

• Uses high-quality, pharmaceutical-grade naltrexone

• Offers multiple formulation options (capsules, sublingual, transdermal)

• Avoids common fillers that may cause reactions

• Provides consistent, reliable dosing

  
  

Formulation Options

Capsules (Most Common): Standard LDN capsules are most commonly prescribed. Request fillers like microcrystalline cellulose or acidophilus rather than lactose if you have sensitivities.

Sublingual/Liquid: May provide more consistent absorption for some women, particularly those with digestive issues. Can be easier to titrate in very small increments.

Transdermal Cream: An option for women who cannot tolerate oral formulations, though absorption may be less predictable.

Cost Considerations

LDN is typically affordable, ranging from $30-60 per month depending on your pharmacy and dose. It's often not covered by insurance when used off-label for endometriosis, but the out-of-pocket cost remains reasonable for most patients.

Integrating LDN into a Comprehensive Naturopathic Treatment Plan

LDN is powerful, but it's not a standalone solution. As a naturopathic doctor, I view LDN as one tool in a comprehensive, root-cause approach to endometriosis. For optimal results, LDN should be combined with:

1. Anti-Inflammatory Nutrition

Focus on:

• Eliminating or significantly reducing inflammatory foods: processed sugars, refined grains, conventional dairy, gluten (for many women), industrial seed oils

• Emphasizing anti-inflammatory foods: wild-caught fish, leafy greens, colorful vegetables, berries, healthy fats (olive oil, avocado, coconut)

• Supporting blood sugar balance: adequate protein, healthy fats, and fiber at each meal

• Considering an elimination diet to identify personal food triggers

  
  

Key supplements to consider alongside LDN:

• Omega-3 fatty acids (EPA/DHA): 2,000-3,000 mg daily for anti-inflammatory support

• Curcumin: 1,000-2,000 mg daily for powerful anti-inflammatory effects

• Vitamin D3: Optimize levels to 50-80 ng/mL for immune and hormonal support

• N-Acetyl Cysteine (NAC): 1,800-2,400 mg daily for antioxidant support and endometriosis-specific benefits

• Resveratrol: 200-500 mg daily for anti-inflammatory and estrogen-modulating effects

2. Hormone Balancing

Endometriosis is estrogen-dependent and often involves progesterone resistance. Support healthy hormone metabolism through:

• DIM (Diindolylmethane) or I3C: 200-400 mg daily to support healthy estrogen metabolism

• Bioidentical progesterone: Consider cyclic or continuous progesterone support (discuss with your ND)

• Liver support: Milk thistle, glutathione, B-vitamins for enhanced estrogen detoxification

• Regular bowel movements: Essential for estrogen elimination (fiber, magnesium, hydration)

3. Gut Health Optimization

The gut-endometriosis connection is profound. Many women with endometriosis have:

• SIBO (Small Intestinal Bacterial Overgrowth)

• Leaky gut/intestinal permeability

• Dysbiosis

• Food sensitivities

Address through:

• Comprehensive stool testing to identify imbalances

• Targeted probiotic support: strains like Lactobacillus plantarum and Bifidobacterium species

• L-glutamine for gut lining repair: 5-10 grams daily

• Digestive enzyme support with meals

• Addressing SIBO if present with herbal antimicrobials or antibiotics

4. Stress Management and Nervous System Regulation

Chronic stress perpetuates inflammation and pain. Essential practices include:

• Neural therapy: At Tang Naturopathic, we offer neural therapy—a specialized injection technique that helps reset the autonomic nervous system, reduce pain signals, and address interference fields that may be contributing to chronic pelvic pain

• Daily nervous system regulation: vagal toning exercises, breathwork, meditation

• Adaptogenic herbs: ashwagandha, rhodiola, holy basil for HPA axis support

• Adequate sleep: 7-9 hours nightly in a dark, cool room

• Movement that feels good: gentle yoga, walking, swimming (avoid overexercise)

• Connection and support: therapy, support groups, meaningful relationships

5. Detoxification Support

Environmental toxins (endocrine disruptors) contribute to endometriosis development and progression:

• Reduce exposure: switch to clean personal care products, avoid plastics, choose organic when possible

• Support liver detoxification: cruciferous vegetables, sulfur-rich foods, adequate hydration

• Consider periodic gentle detoxification protocols under supervision

• Infrared sauna for toxin elimination through sweat

• Castor oil packs over the abdomen: 3-5x weekly for local detoxification and inflammation reduction

6. Pelvic Floor Physical Therapy

Many women with endometriosis develop pelvic floor dysfunction—tight, painful muscles that perpetuate pain. Working with a pelvic floor physical therapist who specializes in endometriosis can:

• Release trigger points and tension

• Improve pelvic blood flow

• Reduce pain with intercourse

• Support overall pain reduction

7. Consideration of Excision Surgery

LDN is not a replacement for surgical treatment of endometriosis. If you have significant disease burden, finding an excision specialist for proper surgical removal of endometrial lesions is crucial. LDN can be used before surgery to improve symptoms and after surgery to manage inflammation and prevent recurrence.

Monitoring Your Progress: What Success Looks Like

Short-Term Markers (4-8 Weeks)

• Reduced pain intensity and frequency

• Decreased need for pain medications

• Improved energy levels

• Better mood and stress resilience

• Enhanced sleep quality

  
  

Medium-Term Markers (3-6 Months)

• Sustained pain reduction

• Ability to engage in activities previously limited by pain

• Improved quality of life scores

• Reduced inflammatory markers (if testing)

• Possible improvement in fertility markers

Long-Term Markers (6-12+ Months)

• Stabilized symptoms with maintained lower pain levels

• Improved overall health and vitality

• Better hormonal balance

• Enhanced immune function

• Greater resilience to stress

Keep a Journal

Track the following weekly:

• Pain levels (scale 1-10) at different times in your cycle

• Energy levels

• Mood quality

• Sleep quality

• Digestive symptoms

• Any other relevant symptoms

This data helps you and your provider optimize your dose and overall treatment plan.

Frequently Asked Questions

Q: How long will I need to take LDN? A: This is highly individual. Some women use LDN for 1-2 years while making lifestyle changes, then successfully taper off. Others find it beneficial to continue long-term. Work with your provider to reassess every 6-12 months.

Q: Can I take LDN if I'm trying to conceive? A: Yes, and it may actually improve fertility outcomes. Dr. Phil Boyle has helped thousands of couples achieve pregnancy using LDN. However, discuss with your provider, as some prefer to discontinue after conception while others continue through pregnancy.

Q: Will LDN cure my endometriosis? A: No. LDN is not a cure for endometriosis. It's a tool that addresses inflammation, immune dysfunction, and pain—but it doesn't remove endometrial lesions. Proper excision surgery remains the gold standard for disease removal.

Q: What if LDN doesn't work for me? A: While many women benefit significantly, LDN doesn't work for everyone. If you've titrated to 4.5 mg and used it consistently for 3-6 months without benefit, it may not be the right tool for you. Work with your provider to explore other options.

Q: Can I take LDN with hormonal birth control or other medications? A: Generally yes, with the exception of opioids. LDN can be used alongside birth control pills, IUDs, thyroid medication, antidepressants, and most other medications. Always inform your prescriber of all medications and supplements.

Q: Is LDN safe long-term? A: Research and clinical experience suggest LDN is safe for long-term use at low doses. Regular monitoring of liver function is recommended, especially in the first year.

Why Isn't LDN More Widely Used?

If LDN is so effective, why haven't you heard about it from your conventional gynecologist? Several factors contribute to LDN's relative obscurity:

1. Off-label use: LDN is not FDA-approved for endometriosis, limiting its promotion and insurance coverage

2. No pharmaceutical profit: Naltrexone is off-patent; no company profits from promoting low-dose use

3. Limited large-scale research: Without pharmaceutical funding, large randomized controlled trials are difficult to conduct

4. Compounding required: LDN must be specially compounded, creating a barrier compared to commercial medications

5. Lack of awareness: Many conventional doctors simply haven't heard of LDN for endometriosis

   
   

The good news? Awareness is growing. As more women share their success stories and more practitioners see remarkable results, LDN is becoming an increasingly accepted option in integrative and naturopathic approaches to endometriosis.

The Bottom Line: Is LDN Right for You?

Low Dose Naltrexone represents a paradigm shift in endometriosis management—moving from symptom suppression to addressing root causes like inflammation and immune dysfunction. While not a cure, LDN offers many women significant relief from pain, fatigue, and reduced quality of life.

Consider LDN if you:

• Have exhausted conventional options without adequate relief

• Want to address underlying inflammation and immune dysfunction

• Are seeking alternatives to long-term NSAID or opioid use

• Are willing to be patient with a slow titration process

• Are committed to a comprehensive, integrative treatment approach

Work with a knowledgeable provider who:

• Understands LDN dosing and titration

• Can prescribe and monitor appropriately

• Takes a holistic, root-cause approach

• Helps you integrate LDN into a comprehensive treatment plan

Your Next Steps

If you're interested in exploring LDN for your endometriosis:

1. Find a knowledgeable provider: Look for a naturopathic doctor, functional medicine practitioner, or integrative gynecologist familiar with LDN

2. Educate yourself: Review resources from the LDN Research Trust (ldnresearchtrust.org)

3. Prepare for your appointment: Bring your symptom history, previous treatments, and questions

4. Be patient: Remember that LDN requires slow titration and time to see full benefits

5. Commit to the bigger picture: Optimize nutrition, stress management, gut health, and other foundations alongside LDN

Additional Resources

• LDN Research Trust: www.ldnresearchtrust.org - Comprehensive information on LDN for various conditions

• Dr. Phil Boyle's Presentations: Search YouTube for his talks on LDN for women's health

  
  

A Message of Hope

Living with endometriosis can feel isolating and hopeless, especially when you've been told "there's nothing more we can do" or "you'll just have to live with it." But you don't have to accept that narrative.

LDN is just one tool—but for many women, it's a tool that has been truly transformative. Combined with proper surgical treatment, anti-inflammatory nutrition, hormone balancing, gut healing, and nervous system support, many women find they can reclaim their lives from endometriosis.

You deserve comprehensive, compassionate care that addresses the root causes of your condition. You deserve to feel better. And you deserve providers who believe you and are willing to explore innovative therapies alongside conventional approaches.

If LDN sounds like it might be right for you, I encourage you to explore it with a qualified provider. Your healing journey is unique—and LDN might be one important piece of your path to feeling better.

Medical Disclaimer

This article is intended for educational purposes only and does not constitute medical advice. Low Dose Naltrexone should only be taken under the supervision of a qualified healthcare provider. The information presented here is based on current research, clinical experience, and patient reports, but individual results may vary. Always consult your naturopathic doctor, physician, or healthcare provider before starting, stopping, or adjusting any medication or supplement regimen. This is especially important if you are pregnant, breastfeeding, taking other medications, or have underlying health conditions. LDN is used off-label for endometriosis and is not FDA-approved for this indication. The author and publisher are not responsible for any adverse effects or consequences resulting from the use of any suggestions, preparations, or procedures discussed in this article.

About the Author: My Tang, ND, specializes in naturopathic women's health with a focus gut and hormone balancing. She practices comprehensive, root-cause medicine that integrates evidence-based natural therapies with conventional medical approaches when appropriate.

Ready to explore whether LDN is right for your endometriosis? Schedule a consultation to discuss your symptoms, treatment history, and create a personalized integrative treatment plan. Contact our office here.