BACKGROUND: Endometriosis (EMS) is an estrogen-dependent chronic inflammatory disorder for which metabolic reprogramming has emerged as a central pathological feature. Driven by genetic, epigenetic, and microenvironmental stressors, ectopic endometrial cells undergo extensive metabolic remodeling integrating energy production, redox homeostasis, and biosynthetic demands. These adaptations not only sustain cell survival under hypoxia and inflammation, but reshape epigenetic marks and the immune microenvironment, promoting lesion progression and impairing reproductive function. AIM OF REVIEW: This review systematically outlines the molecular mechanisms of metabolic reprogramming in EMS, examines its impact on lesion development and fertility, and evaluates the potential of targeting metabolic pathways for precision therapy. KEY SCIENTIFIC CONCEPTS: Ectopic endometrial cells display a phenotype with enhanced aerobic glycolysis, dysregulated fatty acid oxidation and phospholipid synthesis, and abnormal amino acid metabolism. These alterations support lesion survival and proliferation through epigenetic and immune modulation. Granulosa cell metabolic reprogramming-characterized by excessive glycolysis, mitochondrial dysfunction, lipid accumulation, and iron overload-disrupts oocyte energy and redox balance, reducing oocyte quality, and contributing to EMS-associated infertility. Preclinical studies suggest that targeting glucose, lipid, and amino acid pathways could mitigate disease phenotypes; however, metabolic plasticity, overlap with physiological metabolism, and safety concerns limit clinical translation. These challenges highlight the need for combinatorial interventions, precise delivery, and optimized therapeutic strategies to improve patient outcomes.
Guo et al. (Fri,) studied this question.