{"paper_id":"72f1c57d-7f09-474d-b847-f9b3b5637455","body_text":"Abstract\nAccurate pre-operative discrimination between ovarian endometriomas (EMs) and other benign ovarian tumors is crucial for surgical planning and fertility counseling. This study aimed to evaluate the diagnostic performance of serum CA125, CA19-9, and HE4 in differentiating endometriomas from non-endometriotic benign ovarian cysts. This retrospective cohort study included 654 patients with histologically confirmed benign ovarian cysts (343 endometriomas and 311 other benign ovarian tumors) from January 2024 to March 2025. Serum CA125, CA19-9, and HE4 levels were compared between groups. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic accuracy, with stratified analyses by age, dysmenorrhea, cyst laterality, and parity. Patients with endometriomas had significantly elevated CA125 (median: 56.40 vs. 17.30 U/mL, P<0.001) and HE4 (31.50 vs. 14.94 pmol/L, P<0.001), whereas CA19-9 showed no significant difference. ROC analysis revealed that CA125 had excellent diagnostic performance (AUC=0.895; sensitivity=85.7% (95% CI: 81.6-89.2%); specificity=80.6% (95% CI: 75.8-84.9%) at cutoff=27.45 U/mL), consistently superior across all subgroups. HE4 demonstrated moderate utility (AUC=0.683), while CA19-9 lacked discriminatory value. Serum CA125 reliably distinguishes endometriomas from other benign ovarian tumors across diverse clinical scenarios. CA125 should be routinely integrated as a biochemical adjunct to ultrasonography, whereas HE4 and CA19-9 have limited clinical utility in this context. The retrospective design of this study should be considered when interpreting the findings.\nSimilar content being viewed by others\nReferences\nBaumler M, Heiss N, Druckmann R. 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J Clin Lab Anal. 2021;35(9):e23947.\nFunding\nThere was no external funding for this study.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nHuman Ethics\nThis study was conducted as a retrospective analysis and has received ethical approval from the Third Affiliated Hospital of Sun Yat-sen University (No.II2025-179-01).\nConflict of interest\nOn behalf of all authors, the corresponding author states that there is no conflict of interest.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nHe, H., Yang, X., Li, Y. et al. CA125 Outperforms HE4 and CA19-9 as a Serum Biomarker for Preoperative Diagnosis of Ovarian Endometriomas: A Retrospective Cohort Study. Reprod. Sci. (2026). https://doi.org/10.1007/s43032-026-02115-6\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s43032-026-02115-6","source_license":"CC0","license_restricted":false}