{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:27:54Z","timestamp":1784233674577,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: The individual and social burden of endometriosis is high, and the diagnosis is usually delayed by 7\u201310 years. Menstrual effluent (ME) represents an accessible and uniquely informative biofluid. This systematic review evaluated the pathophysiological relevance and diagnostic potential of ME in endometriosis. Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed\/MEDLINE, EBSCOhost (Academic Search Premier, APA PsycArticles, APA PsycInfo, CINAHL, and MEDLINE), Semantic Scholar, and Google Scholar from inception to 30 November 2025. Original studies analyzing human ME or ME-derived cells in women with endometriosis versus controls were eligible. We extracted study design, analytic methods, diagnostic accuracy metrics (AUC, sensitivity, and specificity), mechanistic pathways, and risk of bias (QUADAS-2 for diagnostic, and NIH tools for mechanistic studies). Results: Thirty-five studies were included. ME consistently captured key pathophysiological mechanisms of endometriosis, including impaired decidualization and progesterone resistance, immune dysregulation with diminished cytotoxic clearance, pro-angiogenic and invasive phenotypes, heightened stem\/progenitor cell survival, cellular senescence and DNA damage, and altered extracellular-vesicle signaling. Diagnostic accuracy was reported in nine studies. Aromatase mRNA showed the highest performance (AUC 0.977), followed by TGF-\u03b21 (AUC 0.973) and IGFBP1 (AUC 0.92). A lipidomic two-marker model achieved an AUC of 0.87. All diagnostic assessments were based on case\u2013control studies; none conducted prospective validation. Conclusions: ME is a biologically relevant, non-invasive, and patient-acceptable biospecimen reflecting core endometriosis mechanisms and yielding promising diagnostic accuracy. The highest diagnostic performance was achieved for assays reflecting steroidogenic and growth-factor pathways (e.g., aromatase and TGF-\u03b21). Standardization and prospective validation are needed before clinical adoption.<\/jats:p>","DOI":"10.3390\/diagnostics16050677","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T11:23:45Z","timestamp":1772105025000},"page":"677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Menstrual Effluent in the Pathogenesis and Diagnosis of Endometriosis\u2014A Systematic Review"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6828-1887","authenticated-orcid":false,"given":"Rafa\u0142","family":"Watrowski","sequence":"first","affiliation":[{"name":"Department of Gynecology, Helios Hospital M\u00fcllheim, Heliosweg 1, 79379 M\u00fcllheim, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-3095","authenticated-orcid":false,"given":"Stoyan","family":"Kostov","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Hospital \u201cSaint Anna\u201d, 9002 Varna, Bulgaria"},{"name":"Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Tsoneva","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University Pleven, 5800 Pleven, Bulgaria"},{"name":"Department of Reproductive Medicine, Specialized Hospital for Active Treatment of Obstetrics and Gynaecology Dr Shterev, 1330 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8010-1463","authenticated-orcid":false,"given":"Sebastian D.","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Clemenshospital M\u00fcnster, 48153 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-1951","authenticated-orcid":false,"given":"Radmila","family":"Spari\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, Dr Suboti\u0107a 8, 11000 Belgrade, Serbia"},{"name":"Clinic for Gynecology and Obstetrics, University Clinical Centre of Serbia, Dr Koste Todorovi\u0107a 26, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Public Health, School of Medicine, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospitals Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slavica","family":"Ak\u0161am","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, Dr Suboti\u0107a 8, 11000 Belgrade, Serbia"},{"name":"Clinic for Gynecology and Obstetrics, University Clinical Centre of Serbia, Dr Koste Todorovi\u0107a 26, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7719-382X","authenticated-orcid":false,"given":"Angel","family":"Yordanov","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Medical University Pleven, 5800 Pleven, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-3833","authenticated-orcid":false,"given":"Pierluigi","family":"Chieppa","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Gynecology and Obstetrics 1, A.O.U. City of Health and Science of Turin, S. Anna Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-6490","authenticated-orcid":false,"given":"Ingolf","family":"Juhasz-B\u00f6ss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Center\u2014University Hospital Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-6097","authenticated-orcid":false,"given":"Salvatore Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, Department of General Surgery and Medical Surgical Specialties, \u201cGaspare Rodolico\u201d University Hospital, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-6034","authenticated-orcid":false,"given":"Ibrahim","family":"Alkatout","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospitals Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. 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