Condition
Endometriosis
Endometriosis is a chronic condition in which tissue like the uterine lining grows outside the uterus, causing inflammation, scarring, and pelvic pain. The strongest evidence is for the hormone-lowering medicines leuprolide and nafarelin: trials found leuprolide eased pelvic pain better than placebo, and most people on nafarelin had less visible endometriosis on laparoscopy. Evidence for nutrients such as omega-3s and vitamin D is only moderate.
Sources: PMID 7533699; PMID 2963213
- Supplements studied
- 4
- Medicines and peptides
- 2
- Graded outcomes
- 10
- Trials
- 6
- People studied
- 820
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Dysmenorrhea Symptoms Moderate Improvement | Improves (the measure goes down) | Moderate effect | 1 study | 102 people | ||
Studies that measured dysmenorrhea symptoms | ||||||
| Dyspareunia | Improves (the measure goes up) | 102 people | ||||
| Pain | Improves (the measure goes down) | 102 people | ||||
Melatonin
- Dyschezia: improves
- Dysmenorrhea Symptoms: improves
- Serum BDNF: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Dyschezia Moderate Improvement | Improves (the measure goes up) | Moderate effect | 40 people | |||
| Dysmenorrhea Symptoms | Improves (the measure goes down) | 1 study | 40 people | |||
Studies that measured dysmenorrhea symptoms | ||||||
| Serum BDNF | Improves (the measure goes up) | 1 study | 40 people | |||
| Dyspareunia | Improves (the measure goes up) | 40 people | ||||
| Dysuria | Improves (the measure goes up) | 40 people | ||||
| Endometriosis-associated pelvic pain | Improves (the measure goes down) | 40 people | ||||
| Sleep Quality | Improves (the measure goes up) | 40 people | ||||
Fish Oil
- Endometriosis-associated pelvic pain: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Endometriosis-associated pelvic pain | Improves (the measure goes down) | 1 study | 69 people | |||
Studies that measured endometriosis-associated pelvic pain | ||||||
Prescription medicines and peptides studied, for context
Nafarelin (Synarel)
- Post-Treatment Fertility: improves
- Endometriosis Reduction: improves
- Pain Reduction: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Post-Treatment Fertility 39% (58/149) achieved pregnancy after treatment completion. Comparable to danazol pregnancy rates. | Improves (the measure goes up) | Moderate effect | 24 studies | |||
| Endometriosis Reduction Double-blind trial: >80% of patients had laparoscopic reduction in endometriosis. AFS scores significantly improved vs baseline. | Improves (the measure goes down) | Large effect | 23 studies | |||
| Pain Reduction Severe painful symptoms decreased from 40% to 5-10%. 3-month course provides effective symptom relief with continued benefit at 1 year. | Improves (the measure goes down) | Large effect | 23 studies | |||
| Post-Surgical Efficacy 6 months nafarelin after laparoscopic surgery significantly delays symptom return vs placebo. | Improves (the measure goes up) | Moderate effect | 23 studies |
Leuprolide (Lupron)
- Pelvic Pain (Endometriosis): improves
- Endometriotic Lesions: improves
- Dysmenorrhea: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Pelvic Pain (Endometriosis) Superior to placebo, comparable to danazol for pelvic pain reduction. Significant improvement in dysmenorrhea and dyspareunia. | Improves (the measure goes down) | Large effect | 12 studies | |||
| Endometriotic Lesions Reduces size and number of endometriotic lesions. Objective improvement confirmed by laparoscopy in clinical trials. | Improves (the measure goes down) | Large effect | 12 studies | |||
| Dysmenorrhea Significant reduction in menstrual pain. Comparable efficacy to intranasal buserelin 900 mcg/day. | Improves (the measure goes down) | Large effect | 12 studies |
Key findings
- Blood glucoseImproves (the measure goes down)
- Dysmenorrhea SymptomsImproves (the measure goes down)
- DyscheziaImproves (the measure goes up)
The Endometriosis Supportive Care protocol
2 primary supplements · 7 supporting supplements
- Omega-3 Fatty Acids2–3 g EPA+DHA daily
- Vitamin D2,000–4,000 IU daily (target 40–60 ng/mL)
Shop the evidence-backed picks
Support alongside medical care. These supplements are not a treatment for Endometriosis. If you are being treated for it, talk to your clinician before adding one: supplements can interact with medicines.
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Studies cited
56 studies from PubMed
- Leuprolide
- Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty.
- Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status
- Follicular mucinosis and mycosis-fungoides-like drug eruption due to leuprolide acetate: a case report and review.
- Leuprolide acetate: a drug of diverse clinical applications
- Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature.
- Treatment of endometriosis with a decreasing dosage of a gonadotropin-releasing hormone agonist (nafarelin): a pilot study with low-dose agonist therapy ("draw-back" therapy)
- Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis
- Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian hyperstimulation before in vitro fertilization: a prospective clinical trial.
- Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain
- Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis
- Efficacy and safety of nafarelin in the treatment of endometriosis
- Leuprorelin. A review of its pharmacology and therapeutic use in prostatic cancer, endometriosis and other sex hormone-related disorders
- Leuprolide (TAP-144)--a general review.
- Clinical experience treating endometriosis with nafarelin
- Role of nafarelin in the management of endometriosis
- Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial
- Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin)
- A randomized controlled trial of zinc as adjuvant therapy for severe pneumonia in young children
- A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal
- Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial
- A randomized controlled trial of oral zinc in acute pneumonia in children aged between 2 months to 5 years
- Role of zinc in severe pneumonia: a randomized double bind placebo controlled study
- Two weeks of zinc administration to Nepalese children with pneumonia does not reduce the incidence of pneumonia or diarrhea during the next six months
- Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2-24 mo of age: a randomized, double-blind, placebo-controlled trial
- The efficacy of zinc supplementation on outcome of children with severe pneumonia. A randomized double-blind placebo-controlled clinical trial
- The impact of vitamin D supplementation on glycemic control and lipid metabolism in polycystic ovary syndrome: a systematic review of randomized controlled trials.
- Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial
- Effect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial.
- Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose
- Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.
- The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients
- Vitamin D Supplementation for Premenstrual Syndrome-Related inflammation and antioxidant markers in students with vitamin D deficient: a randomized clinical trial
- Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial
- Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial.
- A randomized, placebo-controlled trial of vitamin D supplementation to improve glycaemia in overweight and obese African Americans
- Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults
- Vitamin D supplementation for severe pneumonia--a randomized controlled trial
- Effects of vitamin D supplementation to children diagnosed with pneumonia in Kabul: a randomised controlled trial
- Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers
- Vitamin D for primary dysmenorrhea and endometriosis-related pain - A systematic review of registered RCTs.
- The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis
- Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial
- Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis.
- The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis.
- Spirulina did not ameliorate idiopathic chronic fatigue in four N-of-1 randomized controlled trials
- Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial
- Efficacy of Korean red ginseng (Panax ginseng) for middle-aged and moderate level of chronic fatigue patients: A randomized, double-blind, placebo-controlled trial
- Effects of melatonin supplementation on BDNF concentrations and depression: A systematic review and meta-analysis of randomized controlled trials.
- Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial
- Ginger extract reduces delayed gastric emptying and nosocomial pneumonia in adult respiratory distress syndrome patients hospitalized in an intensive care unit
- The Effects of Chamomile and Flaxseed on Pelvic Pain, Dyspareunia, and Dysmenorrhea in Endometriosis: A Controlled Randomized Clinical Trial.
- The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA
- Supplementation with vitamin D or ω-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial
- Effects of Citric Acid and l-Carnitine on Physical Fatigue
- Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome