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. Similar content being viewed by others Data availability This structured narrative review synthesizes evidence from previously published studies. No new data were generated, and all information used in this review is available in the cited literature. Code availability No datasets were generated or analysed during the current study.

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Anuja Pant is a recipient of a junior research fellowship from the Indian Council of Medical Research (ICMR) Government of India (5/10/FR/03/2021-RBMCH). Funding The Indian Council of Medical Research (ICMR), Government of India, is gratefully acknowledged by Pawan Kumar Maurya for giving financial assistance (5/10/FR/03/2021-RBMCH). Author information Authors and Affiliations Contributions The authors confirm that no paper mill and artificial intelligence was used. Anuja Pant conceptualized and wrote the main manuscript. Formal Analysis and investigation was done by Anuja Pant, Pawan Kumar Maurya. Editing was done by Kareena Moar. Anuja Pant, Kareena Moar, Reetu Hooda, Pawan Kumar Maurya reviewed the manuscript. Pawan Kumar Maurya validated and supervised the whole manuscript. Pawan Kumar Maurya received funding from ICMR for the manuscript. Corresponding author Ethics declarations Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Conflict of interest The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Glossary - Annexin V - A cellular protein that binds to phosphatidylserine (a phospholipid) residues present on the outer leaflet of theplasma membrane during early apoptosis. It is commonly used as a marker for detecting apoptotic cells. - Dysmenorrhea - Common gynecological problem associated with conditions like endometriosis characterized by painfulmenstrual cramps originating from the uterus, typically occurring just before or during menstruation. - Levonorgestrel - It is an emergency hormonal contraceptive (a synthetic progestin) used to prevent pregnancy, manageendometriosis-related symptoms, and reduce endometrial proliferation. - Lignans - Plant-derived natural compounds found in seeds, whole grains, and vegetables, known for their anti-oxidant, anticancerousand weak estrogenic activity. - Menorrhagia - Abnormally heavy or prolonged menstrual bleeding, often associated with gynecological disorders such asfibroids, endometriosis, or hormonal imbalances. - Neovascularization - The formation of new blood vessels, often seen in pathological conditions like endometriosis, tumors,or ischemic tissue, supporting lesion growth and survival. - NSAIDs (Non-Steroidal Anti-Inflammatory Drugs - Non-steroidal drug commonly used to manage endometriosisassociatedpain, inflammation, and headaches by inhibiting cyclooxygenase (COX) enzymes. - Piceatannol - A naturally occurring metabolite of resveratrol studied for potential therapeutic effects in cancer andendometriosis exhibiting anti-inflammatory, anti-oxidant, and anti-proliferative properties. - Survivin - It belongs to a member of the inhibitor of apoptosis (IAP)vs protein family (anti-apoptotic protein) that regulatescell division and inhibits programmed cell death, often overexpressed in cancers and endometriotic tissues. - Xanthones - A class of polyphenolic compounds (tricyclic structures with two benzene rings connected by a carbonyl groupand an oxygen atom) found in certain fruits and medicinal plants, known for their anti-oxidant properties. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Pant, A., Moar, K., Hooda, R. et al. Revisiting endometriosis management: Polyphenols as alternative therapeutic candidates. Naunyn-Schmiedeberg's Arch Pharmacol (2026). https://doi.org/10.1007/s00210-026-05615-z Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00210-026-05615-z