Endometriosis

Sedighe Esmaeilzadeh et al. (2025) · Reproductive biology and endocrinology : RB&E

This systematic review and meta-analysis combined 17 randomized controlled trials (15 pooled, 996 women) to ask whether antioxidant supplements ease the pain of endometriosis, a chronic inflammatory condition in which tissue like the uterine lining grows outside the uterus. Oxidative stress (damage from unstable oxygen molecules called free radicals) is thought to feed the inflammation and pain, so antioxidants such as melatonin, vitamins C, D, and E, curcumin (from turmeric), garlic, silymarin (from milk thistle), and resveratrol have been tested. Results across individual trials have been inconsistent, and earlier reviews were narrower, so this one searched seven sources through January 2025 and graded the certainty of the evidence. Included trials enrolled women aged 18 to 49 with confirmed endometriosis, mostly in Iran, plus Egypt, Brazil, the United States, China, and Sweden. Women took an oral antioxidant or a comparator (placebo, standard care, or nothing) for 8 to 24 weeks. The review pooled three pain outcomes using standardized mean differences (a way to combine different pain scales into one measure): painful periods (dysmenorrhea), painful intercourse (dyspareunia), and chronic pelvic pain. Study quality was graded with Cochrane RoB 2, and evidence certainty with GRADE. For painful periods, 12 trials (706 women) showed lower pain with antioxidants (SMD -1.26; 95% CI -2.19 to -0.32, equal to about 3 points on a 0 to 10 scale), but results varied enormously between trials (I² = 90.1%), so the evidence was rated low certainty. Melatonin stood out (SMD -1.89; 95% CI -2.48 to -1.31), while vitamin D, vitamins C plus E, omega-3, resveratrol, and curcumin did not reach significance. Painful intercourse showed no significant effect (SMD -1.01; 95% CI -2.27 to 0.24). Chronic pelvic pain fell in the pooled analysis (SMD -1.07; 95% CI -1.71 to -0.42), but the evidence was very low certainty and the effect vanished when trials with conflicts of interest were removed. Single trials of garlic powder and silymarin reported lower pain, whereas curcumin did not. Only 7 of 17 trials had low risk of bias. The authors say the findings do not support routine antioxidant use for endometriosis pain, and describe melatonin as the most promising candidate for painful periods, pending confirmation. Limitations include very high heterogeneity, small trials, different antioxidants and doses, bigger effects in weaker studies, and little control of baseline vitamin levels or diet. The paper did not report adverse events. The garlic and silymarin findings come from single trials, and publication-bias testing found no small-study effects for chronic pelvic pain. The authors call for larger, standardized trials.

Sophia Tsokkou et al. (2026) · International journal of molecular sciences

This systematic review pulled together seven randomized controlled trials to ask whether vitamin D, vitamin C, and vitamin E supplements affect endometriosis, a long-term inflammatory condition in which tissue like the uterine lining grows outside the uterus and affects roughly 1 in 10 women of reproductive age. Common symptoms include painful periods (dysmenorrhea), chronic pelvic pain, pain during intercourse (dyspareunia), and difficulty conceiving. The vitamins were chosen because vitamin D helps regulate immune signaling, while vitamins C and E act as antioxidants that neutralize reactive oxygen species (unstable molecules that damage cells and add to inflammation). Both processes are central to how endometriosis develops and causes pain. The authors registered their protocol in PROSPERO and searched PubMed, Scopus, and ScienceDirect, screening 5,639 records down to seven eligible trials. Two reviewers screened independently, and trial quality was graded with the Jadad scale and the Cochrane RoB 2 tool. The trials varied widely: vitamin D doses ranged from 2000 IU daily to 50,000 IU weekly, vitamin C and E doses from 343 mg and 84 mg to 1000 mg and 800 IU daily, and treatment lasted from about 8 weeks to 6 months. Because of this variation, results were described narratively rather than pooled. High-dose vitamin D (50,000 IU every two weeks) cut pelvic pain scores by 1.12 points (95% CI -2.1 to -0.09; p = 0.03) and lowered hs-CRP, an inflammation marker, by 0.64 mg/L. A weekly 50,000 IU regimen lowered active β-catenin (a signaling protein linked to lesion invasion) in endometrial tissue. Lower daily doses did not clearly beat placebo, since both groups improved by similar amounts. Vitamin C plus E for eight weeks reduced oxidative stress markers, and one trial reported pain drops of 43% for daily pelvic pain, 37% for painful periods, and 24% for painful intercourse. Pregnancy rates did not rise in the trial that measured them. Side effects were generally minor, mostly occasional digestive upset. Three trials were rated low risk of bias and four had some concerns. The authors describe vitamins as a possible well-tolerated adjunct for pain and oxidative stress, though not for fertility. The evidence base is small, with only seven trials, English-language inclusion only, very different dosing across studies, and no trial using a publicly available preregistered protocol. Few trials checked participants' baseline vitamin levels, so it remains unclear whether any benefit depends on deficiency. The authors call for larger multicenter trials with standardized doses, longer follow-up, and fertility and lesion outcomes.

Angelika Bogusz et al. (2026) · Nutrients

This randomized controlled trial of 46 women with endometriosis explored whether a fish-derived lipid supplement (a mixture of marine omega-3 fats such as EPA and DHA, plus compounds called squalene and alkylglycerols) adds anything to a Healthy Eating Plate diet. Endometriosis is a long-term, estrogen-dependent condition in which tissue similar to the uterine lining grows outside the uterus. Researchers increasingly describe it as an inflammatory condition, in which signaling proteins called cytokines (messengers that coordinate immune cells) help drive pelvic pain. Omega-3 fats are known to influence these immune pathways, but evidence in endometriosis has been limited, so the team treated the work as exploratory. Women aged 22 to 48 with confirmed endometriosis were randomly assigned to one of two groups for 12 weeks. Both groups followed an individualized Healthy Eating Plate diet with meal plans from a dietitian. One group also took the fish-derived lipid product, dosed by body weight (0.5 mL per kilogram daily). Blood and stool samples were collected before and after to measure five cytokines and fecal calprotectin (a marker of gut inflammation). Pain was rated on a 0 to 10 visual analog scale, and quality of life was scored with the 30-item Endometriosis Health Profile. The clearest signal was in IL-10, a cytokine that restrains immune activation: levels rose in the supplement group and the adjusted difference between groups was significant (about 5-fold higher; 95% CI 1.32 to 19.48; p = 0.019). Other cytokines gave mixed results, with IL-1β, TNF-α, and IL-6 landing right at the edge of significance (p = 0.050 to 0.057) and fecal calprotectin unchanged. Average pain scores dropped within the supplement group (5.0 to 4.3; p = 0.011), yet the difference between groups was not significant. A pain drop of at least 1 point was more common with the supplement (73.9% versus 34.8%; adjusted risk ratio 2.11, meaning roughly twice the likelihood). Quality-of-life scores did not differ between groups, and the paper did not report safety outcomes. The authors describe the pain and IL-10 findings as hints worth testing rather than proof of benefit, since most outcomes showed no consistent advantage over diet alone. The study was small, lasted only 12 weeks, had no placebo, relied on self-reported food records, and ran many secondary analyses without statistical correction. The supplement was also a complex mixture, so the effects cannot be pinned on omega-3 fats alone. The authors call for larger, longer trials that measure fatty acid levels in blood and examine immune cells directly.

Ángel Rodríguez-Ruiz et al. (2024) · Medicina (Kaunas, Lithuania)

This randomized controlled trial with 44 women explored whether a four-week "HAMMAM" program -- combining hydrotherapy (therapeutic water bathing at varying temperatures) and Swedish massage (a full-body technique using kneading, stroking, and tapping to relax muscle tissue and improve circulation) -- could ease pain in women with endometriosis-related chronic pelvic pain that had not improved with standard medical treatment. Endometriosis is a condition where tissue similar to the uterine lining grows outside the uterus, commonly causing pain during menstruation (dysmenorrhea, governing cyclical cramping) and intercourse (dyspareunia) that standard analgesics and hormonal therapy fail to relieve in roughly a third to half of patients. Women aged 20-50 with confirmed endometriosis and pelvic pain rated at least 4 out of 10 were randomly assigned to the HAMMAM group (21 women) or a control group continuing usual care (23 women) at a hospital in Granada, Spain. The HAMMAM group attended three 90-minute sessions over four weeks at a bathhouse: a 60-75 minute circuit of warm, hot, and cold water baths plus a steam room, then a 15-minute Swedish massage with essential oils; the last session added a traditional exfoliating scrub. Pain was measured on a 0-10 scale, and pressure sensitivity with a handheld algometer. The HAMMAM group reported significantly less menstrual pain (p = 0.035, a large effect) and pain during intercourse (p = 0.020, a moderate-to-large effect) after the program compared with the control group. Pain interfering with sleep also dropped notably (p = 0.018), and pressure pain thresholds in the pelvic region rose (p = 0.029, meaning the area became less sensitive to pressure -- a sign of reduced pain sensitization), with the strongest change at the left groin ligament (p = 0.006). Everyone attended all sessions (100% adherence) and rated satisfaction at 9.71 out of 10, with no adverse events. However, overall pelvic pain ratings, catastrophic thinking about pain, general subjective well-being, and endometriosis-specific quality of life did not change significantly, showing the benefits were concentrated in specific pain measures rather than global wellness. For women whose endometriosis pain persists despite conventional treatment, this suggests a short, low-intensity spa-style program combining water therapy and massage may meaningfully ease menstrual and intercourse pain and pain-disrupted sleep, with high satisfaction and no safety concerns. Because hydrotherapy and massage were only tested together, it is not yet known which component -- or their combination -- drives the benefit, and the small, single-site sample limits how broadly these results apply. Larger trials testing each therapy alone are needed before firm clinical recommendations can be made.