Revisiting endometriosis management: Polyphenols as alternative therapeutic candidates

Endometriosis (EM) is a common gynecological disorder imposing a considerable burden on the quality of life of women through chronic pain, infertility, and other clinical manifestations. The effectiveness of management options for EM is limited by substantial side effects associated with current treatment options, including hormonal therapies and surgery, increasing the need for an alternative approach associated with fewer adverse effects. Polyphenols, a wide class of naturally occurring bioactive compounds, have generated considerable attention due to their antioxidant, anti-inflammatory, and anti-proliferative properties. This structured narrative review highlights the therapeutic potential of polyphenols, focusing on their ethnopharmacological relevance and providing valuable insights into these natural compounds to be used as an alternative therapeutic approach for managing endometriosis. A comprehensive literature search was conducted across databases, including PubMed, Web of Science, and Scopus, with studies on polyphenol interventions in EM models. Data were analyzed for mechanisms such as antioxidant, anti-proliferative, anti-inflammatory, apoptotic effects, and others associated with endometriosis pathology. The existing evidence indicates that polyphenols can mitigate endometriosis-related outcomes, including inflammation, pain, lesion growth, and invasion in experimental models of endometriosis. However, the majority of the evidence available comes from rodent models, high-dose in vitro research, and immortalized cell lines, all of which have significant translational constraints and might not accurately represent the complexity of human disease. Additionally, there are very few clinical trials assessing the safety and effectiveness of polyphenols in endometriosis patients. In our opinion, polyphenols hold significant promise as adjunct therapies for EM. However, further large-scale clinical trials are essential to validate efficacy, optimize dosing, and establish safety profiles in diverse patient populations.