{"paper_id":"3b495700-cff7-401f-ad2c-fc72cfb4ca9b","body_text":"ABSTRACT\nIntroduction\nEndometriosis is a chronic, estrogen-dependent inflammatory disease affecting about 10% of reproductive-age women. Chronic pelvic pain is its most disabling symptom, and available therapies often show limited long-term efficacy and tolerability. This review examines novel pharmacological strategies to improve outcomes.\nAreas covered\nWe compare the pharmacological, pharmacokinetic, and safety profiles of dienogest and oral GnRH antagonists (elagolix, relugolix, linzagolix). Mechanisms of action, levels of estrogen suppression, adverse events, particularly bone mineral density loss and hypoestrogenic symptoms, and regulatory aspects are discussed. Literature selection followed SANRA guidelines, with a comprehensive search of PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library up to 2026. Eligible studies included randomized and observational trials reporting clinical or pharmacological outcomes. Emerging biomarkers such as progesterone receptor expression, epigenetic modifications, and pain phenotyping are also highlighted as potential tools for treatment personalization.\nExpert opinion\nDienogest and oral GnRH antagonists share anti-inflammatory and anti-proliferative effects but differ in pharmacodynamics and safety. Dienogest remains a well-tolerated long-term option in estrogen-sensitive patients, whereas GnRH antagonists are better suited for severe or refractory cases requiring rapid control. Integrating molecular and clinical profiling will be crucial to optimize individualized therapy and long-term outcomes.\nArticle highlights\nDienogest and oral GnRH antagonists are key therapeutic options for endometriosis-associated pelvic pain, with distinct mechanisms and tolerability profiles.\nDienogest ensures long-term symptom relief with minimal hypoestrogenic side effects and preservation of bone mineral density.\nOral GnRH antagonists (elagolix, relugolix, linzagolix) provide rapid, reversible estrogen suppression with flexible dosing and add-back therapy options.\nEmerging biomarkers, including progesterone receptor expression, epigenetic alterations, and pain phenotyping, may guide personalized treatment strategies.\nShared decision-making and precision medicine are crucial to optimize outcomes and avoid unnecessary exposure to ineffective or poorly tolerated therapies.\nDeclaration of interests\nThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.\nReviewer disclosures\nPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.","source_license":"public-domain-us","license_restricted":false}