Epidemiology, Risk Factors, Diagnosis, and Comorbidities of Endometriosis: An Umbrella Review

Background: Endometriosis is a chronic estrogen-dependent inflammatory disease estimated to affect up to 190 million women of reproductive age worldwide based on clinical and population-based estimates, although only 22.3 million prevalent cases were formally documented-a gap that itself reflects substantial under-diagnosis. Despite an exponential increase in systematic reviews (SRs) and meta-analyses (MAs), the evidence base remains fragmented across clinical domains. An umbrella review provides the methodologically highest level of evidence synthesis and allows critical appraisal and hierarchical classification of published SRs and MAs. Objective: The aim of this study was to conduct a comprehensive critical synthesis of published SRs and MAs on the epidemiology, pathogenesis, diagnosis, treatment, and long-term consequences of endometriosis and to assess their methodological quality using AMSTAR-2. Methods: Systematic searches were conducted in PubMed, Embase, Cochrane Library, and Scopus (2016-2026). Eligibility: SRs with or without MA covering any clinical aspect of endometriosis in women were considered eligible. Quality was assessed using AMSTAR-2. Association strength was classified as convincing (Class I), highly suggestive (Class II), suggestive (Class III), weak (Class IV), or non-significant (NS). Results: Fifty-two SRs and MAs were included (total sample > 6,000,000 participants). AMSTAR-2 quality: high 25% (n = 13), moderate 40% (n = 21), low 29% (n = 15), critically low 6% (n = 3). Class I evidence: short menstrual cycle (<27 days) associated with endometriosis risk (OR 1.68; 95% CI 1.48-1.89). Class II: post-operative dienogest reduces recurrence by 70% (OR 0.30; 95% CI 0.18-0.53); the risks of anxiety (RR 2.82; 95% CI 1.69-4.68) and depression (RR 2.78; 95% CI 1.63-5.25) are markedly elevated. Diagnostic delay persists at 4-12 years globally. Multi-biomarker platforms and AI-assisted imaging (e.g., PromarkerEndo and IMAGENDO) have shown promising preliminary diagnostic performance (reported AUCs of 0.997 and 0.906, respectively) in initial validation studies, although external validation in larger and more diverse cohorts is required before clinical implementation can be recommended. Conclusions: Endometriosis is a systemic, chronically under-diagnosed disease requiring a multidisciplinary approach. The available evidence supports dienogest as one of the preferred options for post-operative maintenance therapy, identifies multi-biomarker platforms as a promising-though not yet clinically validated-avenue for non-invasive diagnosis, and underscores the importance of incorporating psychological assessment into multidisciplinary management.