MELATONIN AS A THERAPEUTIC OPTION FOR ENDOMETRIOSIS: A NARRATIVE REVIEW

MELATONIN AS A THERAPEUTIC OPTION FOR ENDOMETRIOSIS: A NARRATIVE REVIEW DOI: https://doi.org/10.31435/ijitss.4(52).2026.6316Keywords: Melatonin, Endometriosis, Oxidative Stress, Chronic Pelvic Pain, Anti-inflammatory AgentsAbstract Endometriosis is a chronic condition in which conventional hormonal suppression and surgical excision are frequently accompanied by high recurrence and risks to ovarian reserve (Q. Li et al., 2024; Y. Li et al., 2024). Melatonin, a pleiotropic neuroendocrine hormone with antioxidant, anti-inflammatory, and antinociceptive properties, has emerged as an adjunctive candidate that targets the oxidative-inflammatory-angiogenic axis without suppressing reproductive function (Li et al., 2022; Mosher et al., 2019). This narrative review synthesizes the available preclinical and clinical evidence, retrieved through a structured search of PubMed, Scopus, and Web of Science (January 2005–May 2025), examining melatonin's therapeutic role across seven mechanistic domains: lesion size, histological characteristics, oxidative stress, inflammatory modulation, matrix metalloproteinase regulation, angiogenesis, and chronic pelvic pain. Across more than a dozen rodent studies at 10–50 mg/kg/day, melatonin consistently reduced lesion volume and weight, restored superoxide dismutase and catalase activity while lowering malondialdehyde and COX-2, downregulated proMMP-9 and elevated TIMP-1/TIMP-2, and suppressed VEGF/VEGFR-2 signaling (Mosher et al., 2019; Yılmaz et al., 2014). Clinically, two randomized controlled trials — Schwertner et al. (n = 40, 10 mg nightly, 8 weeks) (Schwertner et al., 2013) and Esmaeilzadeh et al. (n = 80) (Esmaeilzadeh et al., 2025) — documented analgesic benefit, with the former reducing daily pain by 39.80% and the latter yielding a VAS change of −1.56 (P < 0.001). Melatonin is therefore a mechanistically distinctive, fertility-preserving adjunctive candidate for endometriosis. However, the evidence base remains weighted toward preclinical rodent models and rests on a small number of short-duration randomized trials. Larger Phase III studies with imaging-based endpoints, dose-finding designs, active-comparator arms, and extended follow-up are required before its clinical role can be considered definitive. References Anderson, G. (2019). Endometriosis Pathoetiology and Pathophysiology: Roles of Vitamin A, Estrogen, Immunity, Adipocytes, Gut Microbiome and Melatonergic Pathway on Mitochondria Regulation. BioMolecular Concepts, 10(1), 133–149. https://doi.org/10.1515/bmc-2019-0017 Çetinkaya, N., Attar, R., Yıldırım, G., Fıçıcıoğlu, C., Özkan, F., Yılmaz, B., & Yeşildağlar, N. 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