Polyphenols as Modulators of Oxidative Stress and Inflammation in Endometriosis: Molecular Mechanisms and Clinical Perspectives.

Endometriosis, a chronic inflammatory condition affecting up to 10% of reproductive-age individuals, is characterized by the presence of endometrial-like tissue outside the uterine cavity. Current treatments are based primarily on hormonal therapy, analgesia, and surgery, while additional biologically targeted approaches remain under investigation. This review examines polyphenols in relation to endometriosis-associated redox dysregulation and inflammation. Rather than acting simply as antioxidants, individual polyphenols may function as context-dependent redox and signaling modulators. Preclinical studies suggest effects on NF-κB and MAPK signaling, Nrf2-related stress responses, angiogenesis, apoptosis, immune-cell activity, and hormone-related pathways, but the direction and magnitude of these effects differ substantially among compounds, doses, metabolites, and experimental models. Resveratrol and quercetin have generated the greatest clinical interest; however, human evidence remains sparse and heterogeneous, quercetin has been evaluated mainly in multicomponent formulations, and the only double-blind placebo-controlled randomized trial of resveratrol did not demonstrate superiority over placebo for pain reduction. Low and variable bioavailability, compound-specific metabolism, phytoestrogenic and pro-oxidant effects at some exposures, heterogeneous formulations, and limited long-term safety data remain major translational barriers. Polyphenols should therefore be regarded as potential adjunctive approaches whose clinical efficacy in endometriosis remains to be established.