New perspectives in managing chronic pelvic pain in endometriosis: the role of GnRH antagonists versus dienogest

INTRODUCTION: Endometriosis 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. AREAS COVERED: We 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. EXPERT OPINION: Dienogest 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.