{"paper_id":"62a02495-57d2-4621-b143-c959160e05ea","body_text":"Abstract\nEndometriosis is a chronic gynecological disorder characterized by ectopic tissue growth and significant morbidity, yet current hormonal and surgical treatments often fail to prevent recurrence or entail severe side effects. Increasing evidence highlights metabolic reprogramming, specifically aerobic glycolysis (the Warburg effect), as a fundamental driver of endometriotic lesion pathogenesis. This narrative review synthesizes current research on the regulatory mechanisms and therapeutic potential of targeting glycolytic dysregulation in endometriosis. We examine the aberrant upregulation of rate-limiting enzymes, including hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), and pyruvate kinase M2 (PKM2), driven by signaling axes such as ALKBH5–HK2, PAK5–PKM2, and S1PR4/mTOR. The review further elucidates how enhanced glycolytic flux and lactate accumulation promote cell proliferation, invasion, and epithelial–mesenchymal transition (EMT) while orchestrating an immunosuppressive microenvironment via M2 macrophage polarization and histone lactylation. Furthermore, we evaluate emerging non-hormonal therapeutic strategies, including specific glycolysis inhibitors and natural compounds, and discuss the utility of immune-metabolic gene signatures for non-invasive diagnosis. Highlighting these metabolic vulnerabilities offers promising avenues for precision medicine to improve clinical management and patient outcomes in endometriosis.\nSimilar content being viewed by others\nAbbreviations\n- 2-DG:\n-\n2-Deoxy-D-glucose\n- ALKBH5:\n-\nAlkB Homolog 5\n- AURKA:\n-\nAurora Kinase A\n- CD47:\n-\nCluster of Differentiation 47\n- CHIP:\n-\nSTIP1 Homology and U-box Containing Protein 1\n- CGRP:\n-\nCalcitonin Gene-Related Peptide\n- EMT:\n-\nEpithelial–Mesenchymal Transition\n- ERβ:\n-\nEstrogen Receptorβ\n- HIF-1α:\n-\nHypoxia-Inducible Factor-1α\n- HK2:\n-\nHexokinase 2\n- HMGB1:\n-\nHigh Mobility Group Box 1\n- LDHA:\n-\nLactate Dehydrogenase A\n- m6A:\n-\nN6-methyladenosine\n- MCT1:\n-\nMonocarboxylate Transporter 1\n- MDSC:\n-\nMyeloid-Derived Suppressor Cells\n- mTOR:\n-\nMammalian Target of Rapamycin\n- PAK5:\n-\nP21-Activated Kinase 5\n- PDCD1:\n-\nProgrammed Cell Death Protein 1\n- PDPK1:\n-\n3-Phosphoinositide-Dependent Protein Kinase 1\n- PFKFB3/4:\n-\n6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 3/4\n- PIM2:\n-\nProviral Integration Site for Moloney Murine Leukemia Virus 2\n- PKM2:\n-\nPyruvate Kinase M2\n- RAMP1:\n-\nReceptor Activity-Modifying Protein 1\n- ROS:\n-\nReactive Oxygen Species\n- S1PR4:\n-\nSphingosine-1-Phosphate Receptor 4\n- STAT1:\n-\nSignal Transducer and Activator of Transcription 1\nAcknowledgements\nThe authors thank Figdraw platform for providing graphics-related help.\nFunding\nThis work was supported by Wuxi Taihu Talent Medical Team, Wuxi Medical Development Discipline (FZXK2021008), and Elite Talent Project of Wuxi Maternity and Child Care Healthy Hospital of Jiangnan University (LY2023004).\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nEthics approval and consent to participate\nNot applicable.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\nAbout this article\nCite this article\nGuo, L., Liu, L., Geng, Y. et al. Glycolytic reprogramming in endometriosis: molecular mechanisms, immune modulation, and non-hormonal therapeutic opportunities. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04570-4\nReceived:\nAccepted:\nPublished:\nDOI: https://doi.org/10.1186/s12905-026-04570-4","source_license":"CC0","license_restricted":false}