{"paper_id":"f51871f3-ff06-4e5c-9cdd-529514178954","body_text":"PATHOGENESIS OF ENDOMETRIOSIS: AN UMBRELLA REVIEW OF RECENT SYSTEMATIC REVIEWS AND META-ANALYSES\nDOI:\nhttps://doi.org/10.31435/ijitss.1(49).2026.4983Keywords:\nEndometriosis, Adenomyosis, Dysbiosis, Autoimmunity, InflammatoryAbstract\nEndometriosis is a chronic, estrogen-dependent inflammatory disease affecting approximately 10% of women of reproductive age and remains a major cause of pelvic pain and infertility. Despite its high prevalence and substantial clinical burden, the biological mechanisms underlying endometriosis are still incompletely understood. Although numerous systematic reviews and meta-analyses have addressed individual pathogenic domains, their findings are often fragmented, methodologically heterogeneous, and partially overlapping. This umbrella review aimed to provide a comprehensive synthesis of recent evidence on the pathogenesis of endometriosis while critically appraising methodological quality and overlap of primary studies.\nAn umbrella review was conducted in accordance with the PRISMA 2020 guidelines. PubMed was searched for systematic reviews and meta-analyses published between January 2019 and January 2026. Methodological quality was assessed using the AMSTAR 2 tool, and overlap of primary studies was evaluated using the corrected covered area (CCA). Evidence was synthesized narratively using a predefined domain-based framework.\nEighteen systematic reviews and meta-analyses were included, covering seven major pathogenic domains, including genetic and epigenetic susceptibility, immunological dysregulation, oxidative stress, tissue remodeling, microbiota dysbiosis, and systems-level molecular networks. Most reviews demonstrated moderate methodological quality, with limited overlap across most domains, except for microbiota-related evidence (CCA = 20%). Overall, the findings support a multifactorial, network-based model of endometriosis pathogenesis involving interactions between genetic susceptibility, immune dysfunction, hormonal signaling, and environmental modifiers. This umbrella review highlights key pathogenic domains, identifies areas of evidentiary fragility, and underscores the need for integrative, systems-level research to inform future mechanistic studies and targeted clinical interventions.\nReferences\nParasar, P., Ozcan, P., & Terry, K. L. (2017). Endometriosis: Epidemiology, diagnosis and clinical management. Current Obstetrics and Gynecology Reports, 6(1), 34–41. https://doi.org/10.1007/s13669-017-0187-1\nViscardi, M. F., Piacenti, I., Musella, A., Cacciamani, L., Piccioni, M. G., Manganaro, L., Muzii, L., & Porpora, M. G. (2025). 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Journal of Assisted Reproduction and Genetics, 38(10), 2543–2557. https://doi.org/10.1007/s10815-021-02265-3\nAzeze, G. G., Wu, L., Alemu, B. K., Lee, W. F., Fung, L. W. Y., Cheung, E. C. W., Zhang, T., & Wang, C. C. (2024). Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: A systematic review and meta-analysis. Journal of Translational Medicine, 22(1), 685. https://doi.org/10.1186/s12967-024-05474-3\nDownloads\nPublished\nIssue\nSection\nLicense\nAll articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.\nCC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.","source_license":"CC0","license_restricted":false}