{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:05:15Z","timestamp":1784880315458,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Endometriosis is a chronic inflammatory and estrogen-dependent disease in which oxidative stress, immune dysregulation, and lesion-supportive microenvironmental signaling contribute to lesion development. N-acetylcysteine (NAC), a glutathione-replenishing and redox-modulating agent, has been studied as a possible non-hormonal intervention. Methods: Following preregistration in the Open Science Framework (OSF), we performed a PRISMA-compliant systematic review of studies evaluating NAC in endometriosis-related clinical, in vivo, ex vivo, or in vitro settings. We searched PubMed\/MEDLINE, EBSCOhost, and the Bielefeld Academic Search Engine (BASE) from inception to 24 May 2026. Risk of bias was assessed with design-specific instruments. Results: Twenty-two studies were included. Clinical evidence comprised six studies and suggested that the findings vary by clinical context. In non-postoperative settings, NAC was associated with reduced pain, decreased NSAID use, and endometrioma shrinkage or stabilization. In contrast, the only postoperative randomized comparison found no added benefit of NAC over continuous oral contraceptive therapy for recurrence or pain. Fertility-related clinical findings were suggestive but preliminary. Across nonclinical models, NAC reduced proliferation, lesion burden, oxidative stress, inflammatory mediators, and, in selected systems, migration-related behavior. Mechanistic studies linked NAC to modulation of ROS-dependent proliferation, TNF-\u03b1, COX-2, MMP-2\/-9, autophagy-related signaling, oxidation-sensitive nociception, and partial protection of oocyte and embryo competence under endometriosis-associated oxidative conditions. Conclusions: NAC shows biological plausibility and preclinical activity in endometriosis, but clinical evidence is heterogeneous and methodologically limited.<\/jats:p>","DOI":"10.3390\/antiox15070880","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N-Acetylcysteine in Endometriosis: A Systematic Review of Biological Rationale and Clinical Evidence"],"prefix":"10.3390","volume":"15","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6123-1628","authenticated-orcid":false,"given":"Roberto","family":"Tozzi","sequence":"additional","affiliation":[{"name":"Unit of Gynecology and Obstetrics, Department of Women and Children\u2019s Health, University of Padua, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-8576","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"Kupec","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital of the RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany"}],"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\/0000-0001-7482-3833","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, 10126Turin, Italy"}],"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\/0000-0003-0515-1951","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"}]},{"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"}]},{"given":"Salvatore Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit, \u201cGaspare Rodolico\u201d University Hospital, Department of General Surgery and Medical Surgical Specialties, University of Catania, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Alkatout","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(21)00389-5","article-title":"Endometriosis Is a Chronic Systemic Disease: Clinical Challenges and Novel Innovations","volume":"397","author":"Taylor","year":"2021","journal-title":"Lancet"},{"key":"ref_2","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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