ORAL GnRH RECEPTOR ANTAGONISTS IN THE TREATMENT OF ENDOMETRIOSIS: CURRENT EVIDENCE AND FUTURE THERAPEUTIC PERSPECTIVES

ORAL GnRH RECEPTOR ANTAGONISTS IN THE TREATMENT OF ENDOMETRIOSIS: CURRENT EVIDENCE AND FUTURE THERAPEUTIC PERSPECTIVES DOI: https://doi.org/10.31435/ijitss.4(52).2026.6455Keywords: Endometriosis, GnRH Antagonists, Relugolix, Linzagolix, Elagolix, Pain TreatmentAbstract Endometriosis is a chronic, estrogen-dependent systemic disease that significantly impairs women's quality of life and remains a major therapeutic challenge due to frequent symptom recurrence and the limitations of currently available treatments. This review aimed to summarize current evidence regarding the efficacy, safety, and clinical role of oral gonadotropin-releasing hormone (GnRH) antagonists in the management of endometriosis-associated pain. A literature search was conducted using the PubMed and Cochrane Library databases with the terms “endometriosis,” “GnRH antagonists,” “elagolix,” “relugolix,” and “linzagolix.” Relevant prospective and retrospective studies, systematic reviews, meta-analyses, and landmark publications providing essential background on the pathophysiology of endometriosis and the mechanism of action of GnRH antagonists were included. Current evidence indicates that oral GnRH antagonists provide rapid, reversible, and dose-dependent suppression of ovarian estrogen production without the initial flare effect observed with GnRH agonists. Clinical trials have demonstrated significant reductions in dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, accompanied by improvements in health-related quality of life and reductions in analgesic use. The availability of different dosing strategies and add-back therapy enables individualized treatment while minimizing hypoestrogenic adverse effects, including bone mineral density loss. Despite their favorable efficacy and safety profile, treatment remains limited by high costs, the need for long-term monitoring, and the lack of direct comparisons with standard hormonal therapies. Oral GnRH antagonists represent an important advancement in the pharmacological management of endometriosis and offer a promising option for long-term individualized treatment, particularly in women with persistent symptoms or resistance to conventional hormonal therapy. References Eskenazi, B., & Warner, M. L. (1997). Epidemiology of endometriosis. Obstetrics and gynecology clinics of North America, 24(2), 235–258. https://doi.org/10.1016/s0889-8545(05)70302-8 Meuleman, C., Vandenabeele, B., Fieuws, S., Spiessens, C., Timmerman, D., & D’Hooghe, T. (2009). 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