Does melatonin reduce endometriotic lesions? A systematic review and meta-analysis of preclinical evidence

Ensiyeh Kordparijaei, Fatemeh Alibabaei-Omran, Parvaneh Mirabi
In: Advances in Redox Research · 2026 · vol. 20 , pp. 100176 · doi:10.1016/j.arres.2026.100176 · W7165635327
Systematic review / meta-analysis OA: gold CC0
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This systematic review and meta-analysis found melatonin significantly increased antioxidant enzymes in animal models but showed inconsistent effects on endometriotic lesion size, necessitating further research.

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Abstract

Background Endometriosis is a chronic, estrogen-dependent inflammatory disorder linked to pelvic pain, infertility, and reduced quality of life. Melatonin, a potent antioxidant and anti-inflammatory agent, has shown preclinical promise. This systematic review and meta-analysis evaluated its effects on endometriotic lesion regression and oxidative stress in animal models. Methods Following PRISMA guidelines and registered with PROSPERO under identifier CRD420251180598, we conducted a comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar from January 1994 to July 2025. Animal studies reporting quantitative lesion size as the primary outcome and oxidative stress markers as secondary outcomes were included. A random-effects model using restricted maximum likelihood estimation pooled the data. Heterogeneity was assessed via I² and τ² statistics. Risk of bias was evaluated using the SYRCLE tool. Sensitivity analyses included the Knapp–Hartung correction. Results Eleven studies were included in qualitative synthesis, and six studies comprising seven comparisons were included in the meta-analysis. Melatonin was associated with a statistically significant but non-robust reduction in endometriotic lesion size (SMD 1.26, 95% CI 0.28–2.23; p = 0.01), an effect that did not remain significant following sensitivity analysis using the Knapp–Hartung correction. Melatonin significantly increased antioxidant enzyme activity, including superoxide dismutase (SMD 1.98, 95% CI 0.55–3.41; p = 0.01) and catalase (SMD 3.49, 95% CI 1.31–5.67; p < 0.001), whereas no significant effect was observed for malondialdehyde levels (SMD −0.64, 95% CI −4.36 to 3.07; p = 0.73). Conclusions Melatonin may exert disease-modifying effects in experimental endometriosis, but evidence for lesion regression remains inconsistent and sensitive to statistical assumptions. Further rigorously designed clinical studies are required to establish its therapeutic relevance in women with endometriosis

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