Glycolytic Reprogramming in Endometriosis: Biological Basis and Emerging Targets for Disease-Modifying Therapy

Endometriosis is a chronic gynecological disease affecting approximately 10% of women of reproductive age and up to 40% of women with infertility, with a significant impact on quality of life due to pain and reproductive impairment. Its etiology remains unclear, although several mechanisms have been proposed, including retrograde menstruation and immune dysfunction. Increasing evidence highlights similarities between endometriosis and cancer, particularly regarding selected hallmarks such as sustained cell proliferation, angiogenesis, inflammation, invasion, and immune dysregulation. Notably, alterations in glucose metabolism have been identified, suggesting a metabolic reprogramming resembling the Warburg effect in cancer. This review examines clinical aspects, therapeutic challenges, and emerging evidence for Warburg-like glycolytic metabolism in endometriotic lesions, which favors aerobic glycolysis over oxidative phosphorylation to evade apoptosis and promote survival in hypoxic microenvironments. These cancer-like hallmarks—shared with malignancies—suggest repurposing glycolytic inhibitors as targeted therapies to disrupt disease progression beyond symptom palliation. However, most evidence remains preclinical, and important challenges regarding disease heterogeneity, target validation, and safety still need to be addressed.