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 | 16 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 | 16 studies | |||
| Dysmenorrhea Significant reduction in menstrual pain. Comparable efficacy to intranasal buserelin 900 mcg/day. | Improves (the measure goes down) | Large effect | 16 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
100 studies from PubMed
- Effect of vitamin D supplementation for major adverse cardiovascular events: a meta-analysis based on randomised controlled trials.
- Leuprolide
- Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination.
- Relugolix: A Review in Advanced Prostate Cancer.
- Effects of Lupron and surgical castration on fecal androgen metabolite concentrations and intermale aggression in capybaras (Hydrochoerus hydrochaeris).
- Patient preferences for elagolix and leuprolide for treating endometriosis-related pain in the United States.
- Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty.
- Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.
- Optimal Vitamin D Status: Evidence and Guidelines
- Vitamin D and Cancer Prevention: A Comprehensive Review
- Pharmacokinetic-Pharmacodynamic Model for the Testosterone-Suppressive Effect of Leuprolide in Normal and Prostate Cancer Rats.
- Efficacy of Different Leuprolide Administration Schedules in Premenopausal Breast Cancer: A Retrospective Review.
- Elagolix (Orilissa)--an oral GnRH antagonist for endometriosis pain.
- Prolonged injectable formulation of Nafarelin using in situ gel combination delivery system.
- Effects of Vitamin D Supplementation on Musculoskeletal Health: A Systematic Review and Meta-Analysis
- Vitamin D and Prevention of Respiratory Tract Infections: A Systematic Review and Meta-Analysis
- Effects of Vitamin D Supplementation on Depression: A Systematic Review and Meta-Analysis
- Vitamin D and Immune Function: A Review
- Vitamin D Supplementation for Prevention of Mortality: A Meta-Analysis
- Vitamin D Supplementation During Pregnancy: Safety and Efficacy Review
- Androgen deprivation therapy with Leuprolide acetate for treatment of advanced prostate cancer.
- Vitamin D Supplementation: A Comprehensive Review of Efficacy for Various Health Outcomes
- Vitamin D Deficiency: Global Health Perspective
- Vitamin D and Cardiovascular Disease: A Review of Evidence
- Vitamin D and Bone Health in Adults: A Systematic Review
- Extended release, 6-month formulations of leuprolide acetate for the treatment of advanced prostate cancer: achieving testosterone levels below 20 ng/dl.
- 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.
- Association of A1C levels with vitamin D status in U.S. adults: data from the National Health and Nutrition Examination Survey
- GnRH agonists and antagonists in prostate cancer
- Leuprolide acetate: a drug of diverse clinical applications
- Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey
- GnRH agonist Lupron (leuprolide acetate) pre-treatments prevent ovulation in response to gonadotropin stimulation in the clouded leopard (Neofelis nebulosa).
- Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain?
- A randomized, parallel, comparative study of the efficacy and safety of nafarelin versus danazol in the treatment of endometriosis in Taiwan.
- Leuprolide acetate 6-month depot formulation: safety and efficacy in advanced prostate cancer
- Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis.
- The case of the elusive androgen.
- GnRH agonists in the treatment of endometriosis: the role of add-back therapy
- Long-term survival and metastatic disease-free survival in patients with prostate cancer treated with leuprolide acetate
- Lupron depot prevention of antispermatogenic/antifertility activity of the indenopyridine, CDB-4022, in the rat.
- Managing advanced prostate cancer with Viadur (leuprolide acetate implant).
- Chronic (60-week) toxicity study of DUROS leuprolide implants in dogs.
- Efficacy of nafarelin in assisted reproductive technology: a meta-analysis.
- Leuprolide implant approved for once-yearly palliative treatment of advanced prostate cancer.
- 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)
- Treatment with nafarelin for endometriosis in young women. Efficacy, safety and lipid metabolism. Niigata Nafarelin Study Group.
- [Conservative treatment of interstitial ectopic pregnancy and endometriosis with laparoscopic methotrexate and potassium chloride and complementary management with nasal nafarelin. Report of a case and review of the literature].
- Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature.
- Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study.
- PSA levels and the rate of positive surgical margins in radical prostatectomy specimens preceded by androgen blockade in clinical B2 (T2bNxMo) prostate cancer. The Lupron Depot Neoadjuvant Study Group.
- Leuprolide in the treatment of endometrial cancer.
- Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis
- Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy, safety, and bone mineral density.
- Nafarelin vs. leuprolide acetate depot for endometriosis. Changes in bone mineral density and vasomotor symptoms. Nafarelin Study Group.
- Therapeutic efficacy and bone mineral density response during and following a three-month re-treatment of endometriosis with nafarelin (Synarel).
- Intranasal nafarelin versus buserelin (short protocol) for controlled ovarian hyperstimulation before in vitro fertilization: a prospective clinical trial.
- Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study Group.
- Unexpected pregnancies exposed to leuprolide acetate administered after the mid-luteal phase for ovarian stimulation.
- Prospective randomized double-blind trial of 3 versus 6 months of nafarelin therapy for endometriosis associated pelvic pain
- Nafarelin therapy in endometriosis: long-term effects on bone mineral density.
- Leuprolide depot in the treatment of endometriosis
- Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and lupron: the first controlled and randomized trial.
- Insulin resistance improves in hyperandrogenic women treated with Lupron.
- Depot leuprolide acetate versus danazol in the treatment of women with symptomatic endometriosis: a multicenter, double-blind randomized clinical trial. II. Assessment of safety. The Lupron Endometriosis Study Group.
- Gonadotropin-releasing hormone agonist as a probe for the pathogenesis and diagnosis of ovarian hyperandrogenism.
- Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET)
- Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. The Nafarelin European Endometriosis Trial Group (NEET).
- Nafarelin versus leuprolide in ovulation induction for in vitro fertilization: a randomized clinical trial.
- Hyperandrogenism--what is normal?
- Leuprolide with flutamide for complete androgen ablation: therapeutic alternative for advanced prostatic cancer (stage D2).
- Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium.
- Drug induced polymyositis secondary to leuprolide acetate (Lupron) therapy for prostate carcinoma.
- Medical treatment of endometriosis: a comparison of the suppressive effects of danazol and nafarelin on reproductive hormones.
- Leuprorelin. A review of its pharmacology and therapeutic use in prostatic cancer, endometriosis and other sex hormone-related disorders
- Efficacy and safety of nafarelin in the treatment of endometriosis
- Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis
- Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist
- Nafarelin in the treatment of infertility caused by endometriosis.
- Nafarelin in the treatment of pelvic pain caused by endometriosis.
- Effects of nafarelin versus danazol on lipids and calcium metabolism.
- Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions.
- Leuprolide (TAP-144)--a general review.
- Role of nafarelin in the management of endometriosis
- A new test of combined pituitary-testicular function using the gonadotropin-releasing hormone agonist nafarelin in the differentiation of gonadotropin deficiency from delayed puberty
- Clinical experience treating endometriosis with nafarelin
- Treatment of advanced prostatic cancer with leuprolide acetate depot
- Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist
- Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial
- Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer.
- Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone (nafarelin)
- Ovulation inhibition with nafarelin acetate nasal administration for six months.
- Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The Leuprolide Study Group
- Leuprolide versus diethylstilbestrol for metastatic prostate cancer.
- A comparison of the effects of n-3 fatty acids from linseed oil and fish oil in well-controlled type II diabetes
- Effect of omega 3 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients
- Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y
- Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome
- DHA-rich oil modulates the cerebral haemodynamic response to cognitive tasks in healthy young adults: a near IR spectroscopy pilot study
- Effects of a Small Quantity of omega-3 Fatty Acids on Cardiovascular Risk Factors in NIDDM. A Randomized, Prospective, Double-Blind, Controlled Study