Research priorities for endometriosis

**Background:** Endometriosis is a hormone-dependent chronic inflammatory disease affecting an estimated 6–10% of women of reproductive age, approximately 176 million women worldwide. It causes symptoms including dysmenorrhea, nonmenstrual pelvic pain, and painful deep intercourse, significantly impacting quality of life, work, social relationships, and sexual function. Conventional pharmacological and surgical treatments are not completely effective and carry considerable side effects such as menopausal symptoms, osteoporosis, and cardiovascular risks. This overview aimed to explore the effect of complementary medicine on treating or mitigating the risk of endometriosis.

**Methods:** This overview was conducted in Iran. Two independent researchers systematically searched three databases (Medline, Scopus, and Cochrane Central Register of Trials) until September 2020. Search terms included exercise, tobacco, coffee, diet, complementary medicine, acupuncture, and endometriosis. Inclusion criteria were: population (women with endometriosis), intervention (all complementary medicine), results (effect on treating or mitigating risk), and methods (meta-analysis). Six meta-analyses were included. The methodological quality of each systematic review was assessed using the 11-item AMSTAR tool. A predesigned form was used to extract data including type of review, year, first author, study populations, sample size, and main outcomes.

**Key Results:** Six meta-analyses were included. (1) Physical activity: Based on 6 case-control and 3 cohort studies (3,355 recent activity cases, 4,600 past activity cases), the summary OR for endometriosis with recent physical activity was 0.85 (95% CI: 0.67–1.07). ORs for low and moderate/high physical activity were 1.00 (95% CI: 0.68–1.28) and 0.75 (95% CI: 0.53–1.07), respectively. Physical activity did not significantly reduce risk. (2) Tobacco smoking: Summary RRs compared to never-smokers were 0.96 (95% CI: 0.86–1.08) for ever smokers, 0.95 (95% CI: 0.81–1.11) for former smokers, 0.92 (95% CI: 0.82–1.04) for current smokers, 0.87 (95% CI: 0.70–1.07) for moderate smokers, and 0.93 (95% CI: 0.69–1.26) for heavy smokers. No association was found. (3) Diet: Calcium (OR: 0.99, 95% CI: 0.83–1.18), milk (OR: 0.90, 95% CI: 0.65–1.23), eggs (OR: 1.01, 95% CI: 0.81–1.28), bacon (OR: 1.26, 95% CI: 0.60–2.65), and red meat (OR: 1.26, 95% CI: 0.73–2.18) showed no statistically significant associations. (4) Coffee/caffeine: Summary RR for caffeine intake vs. nonintake was 1.26 (95% CI: 0.95–1.66) and for coffee 1.13 (95% CI: 0.46–2.76). Overall estimate was 1.18 (95% CI: 0.92–1.49). No evidence of association. (5) Acupuncture: Mean difference in pain reduction between acupuncture and control was 1.36 (95% CI: 1.01–1.72, p < 0.0001) on a 0–10 scale. Acupuncture significantly reduced serum CA-125 levels (MD = 5.9, 95% CI: 1.56–10.25, p = 0.008) and improved clinical effective rate (OR = 2.07, 95% CI: 1.24–3.44, p = 0.005). (6) Other complementary treatments (exercise, electrotherapy, yoga) showed inconclusive outcomes.

**Clinical Implications:** Among the complementary medicine approaches evaluated, only acupuncture demonstrated statistically significant benefits for pain reduction and improvement in serum CA-125 levels in women with endometriosis. Physical activity, dietary modifications, tobacco smoking cessation, and reduced coffee/caffeine intake were not supported by evidence as effective strategies for reducing endometriosis risk. The authors note that most included studies had methodological limitations including small sample sizes (ranging from 8 to 36 patients per arm in acupuncture studies), lack of blinding, and inadequate reporting of randomization and attrition. Future research should adopt CONSORT criteria to improve quality. Acupuncture may be considered as an adjunctive therapy for endometriosis-related pain, but higher-quality blinded randomized controlled trials with adequate sample sizes are needed to confirm these findings.