The effects of melatonin on endometriosis-associated pain and regression of endometrioma; a triple blind randomized controlled trial

Sedighe Esmaeilzadeh, Mahdi Sepidarkish, Ayda Mortazavi, Zahra Basirat, Masoumeh Golsorkhtabaramiri, Neda Mahdinezhad Gorji, Parvaneh Mirabi
In: Heliyon · 2025 · vol. 12(1) , pp. e44262 · doi:10.1016/j.heliyon.2025.e44262 · W7111039397
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This randomized controlled trial found that 10 mg of melatonin daily for 8 weeks significantly reduced endometriosis-associated dysmenorrhea and analgesic use compared to placebo, without affecting endometrioma size.

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Abstract

AbstractBackground Current treatment options for endometriosis-associated symptoms are limited, prompting the exploration of alternative therapeutic approaches. Melatonin has been recognized as a significant analgesic, antioxidant, and anti-inflammatory agent. We aimed to investigate the effect of melatonin, on endometriosis-associated pain and regression of endometrioma. Methods Ninety-eight women with confirmed endometriosis and moderate-to-severe pain were randomized to receive 10 mg melatonin or placebo for 8 weeks. Primary outcomes included dysmenorrhea, with secondary endpoints such as chronic pelvic pain, analgesic use, and endometrioma size. A multivariable mixed-effects linear regression model was employed to evaluate the adjusted mean difference (aMD) in the primary outcomes, from baseline to week 8 across the two intervention groups. Results Dysmenorrhea, significantly improved in the melatonin group compared to placebo (aMD: 1.15, −1.74, −0.55; p < 0.001). The ‘moderate' and ‘severe' categories of Biberoglu and Behrman (B&B) pelvic pain symptoms (melatonin vs placebo: p = 0.216 at baseline, p = 0.406 at 8 weeks), dysmenorrhea (p = 0.702 at baseline, p = 0.562 at 8 weeks), and dyspareunia (p = 0.694 at baseline, p = 0.395 at 8 weeks) redistributed toward ‘mild' or ‘none' categories in both groups. Analgesic intake decreased significantly in the melatonin group (−1.04 ± 1.32 tablets/56 days) compared to the placebo group (−0.04 ± 0.45 tablets/56 days), with a statistically greater reduction in the melatonin group (aMD: 0.56, 95 % CI: 0.86, −0.26; p < 0.001). There was no significant difference between the groups in the size of right (aMD: 3.49, 95 % CI: 9.28, 2.28; p = 0.226) and left (aMD: 0.91, 95 % CI: 4.19, 2.36; p = 0.584) endometriomas. Conclusion Melatonin supplementation is an acceptable complementary option for pain control in endometriosis, showing benefits in the reduction of endometriosis-related pain, including dysmenorrhea, and reduced analgesic intake compared to placebo, without impacting endometrioma size.

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Outcome instruments

Biberoglu-Behrman

Condition tags

endometriosisendometriomachronic_pelvic_paindysmenorrheadyspareunia

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (26)

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