ORAL GNRH ANTAGONISTS IN THE TREATMENT OF ENDOMETRIOSIS: EFFICACY, SAFETY, AND IMPACT ON QUALITY OF LIFE

ORAL GNRH ANTAGONISTS IN THE TREATMENT OF ENDOMETRIOSIS: EFFICACY, SAFETY, AND IMPACT ON QUALITY OF LIFE DOI: https://doi.org/10.36557/2674-9432.2026v5n1p1216-1224Palavras-chave: Endometriosis; GnRH antagonists; Hormonal therapy; Quality of lifeResumo Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the presence of endometrial-like tissue outside the uterine cavity and is frequently associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility, leading to substantial impairment in quality of life. Although traditional hormonal therapies are widely used for symptom control, they are often limited by adverse effects, incomplete clinical response, and reduced long-term adherence. In this context, oral gonadotropin-releasing hormone (GnRH) antagonists have emerged as a promising therapeutic alternative, as they provide rapid, reversible, and dose-dependent hormonal suppression with the potential for individualized treatment. This narrative literature review aims to analyze the efficacy, safety, and impact on quality of life of oral GnRH antagonists in the treatment of endometriosis. The literature was examined using the PICo strategy, including studies published between 2017 and 2025. The evidence indicates that oral GnRH antagonists are effective in reducing endometriosis-associated pain, present a favorable safety profile when appropriately dosed, and contribute to meaningful improvements in patients’ quality of life. Despite these benefits, concerns remain regarding long-term safety, bone health, and accessibility, underscoring the need for continued research. Downloads Referências AS-SANIE, S. et al. Impact of relugolix combination therapy on functioning and quality of life in women with endometriosis-associated pain. Fertility and Sterility, v. 122, n. 4, p. 687–695, Oct. 2024. DOI: https://doi.org/10.1016/j.fertnstert.2024.06.009. Available at: https://www.fertstert.org. Accessed on: 10 Jan. 2026. BARRETTA, M. et al. The oral GnRH antagonists, a new class of drugs in gynecology: from pharmacokinetics to possible clinical applications. Expert Opinion on Drug Metabolism & Toxicology, p. 1–13, Dec. 17, 2024.DOI: https://doi.org/10.1080/17425255.2024.2441981. Available at: https://www.tandfonline.com. Accessed on: 31 Jan. 2026. BECKER, C. M. et al. Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. Human Reproduction, v. 39, n. 3, p. 526–537, Mar. 2024. DOI: https://doi.org/10.1093/humrep/dead263. Available at: https://academic.oup.com/humrep. Accessed on: 10 Jan. 2026. CARBALLO GARCÍA, A. et al. Relugolix in monotherapy and combined therapy for the treatment of uterine diseases and its effects on bones: a systematic review. Biomedicines, v. 13, n. 8, art. 1851, July 2025. DOI: https://doi.org/10.3390/biomedicines13081851. Available at: https://www.mdpi.com/journal/biomedicines. Accessed on: 2 Feb. 2026. DONNEZ, J. et al. Linzagolix therapy versus a placebo in patients with endometriosis-associated pain: a prospective, randomized, double-blind, Phase 3 study (EDELWEISS 3). Human Reproduction, v. 39, n. 6, p. 1208–1221, June 2024. DOI: https://doi.org/10.1093/humrep/deae076. Available at: https://academic.oup.com/humrep. Accessed on: 14 Jan. 2026. DONNEZ, J.; DOLMANS, M.-M. Endometriosis and medical therapy: from progestogens to progesterone resistance to GnRH antagonists: a review. Journal of Clinical Medicine, v. 10, p. 1085, 2021. DOI: https://doi.org/10.3390/jcm10051085. Available at: https://www.mdpi.com/journal/jcm. Accessed on: 15 Jan. 2026. FERNANDEZ, H. et al. Update on the management of endometriosis-associated pain in France. Journal of Gynecology Obstetrics and Human Reproduction, v. 52, n. 9, art. 102664, Nov. 2023. DOI: https://doi.org/10.1016/j.jogoh.2023.102664. Available at: https://www.sciencedirect.com/journal/journal-of-gynecology-obstetrics-and-human-reproduction. Accessed on: 18 Jan. 2026. GIUDICE, L. C. et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). The Lancet, v. 399, n. 10343, p. 2267–2279, June 18, 2022. DOI: https://doi.org/10.1016/S0140-6736(22)00793-1. Available at: https://www.thelancet.com . Accessed on: 20 Jan. 2026. KALAITZOPOULOS, D. R. et al. Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Women’s Health, v. 21, n. 1, art. 397, Nov. 2021. DOI: https://doi.org/10.1186/s12905-021-01545-5 . Available at: https://bmcwomenshealth.biomedcentral.com . Accessed on: 20 Jan. 2026. MILLER, C. E. et al. Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: twelve months of an ongoing randomized phase 3 trial. American Journal of Obstetrics and Gynecology, v. 231, n. 6, p. 630.e1–630.e13, Dec. 2024. DOI: https://doi.org/10.1016/j.ajog.2024.07.021. Available at: https://www.ajog.org. Accessed on: 28 Jan. 2026. NICE. Relugolix–estradiol–norethisterone for treating symptoms of endometriosis in adults of reproductive age (Technology Appraisal Guidance). 2025. TAYLOR, H. S. et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. The New England Journal of Medicine, v. 377, n. 1, p. 28–40, July 6, 2017. DOI: https://doi.org/10.1056/NEJMoa1700089. Available at: https://www.nejm.org. Accessed on: 22 Jan. 2026. XIE, J. et al. Relugolix’s impact on endometriosis-associated pain and quality of life: a meta-analysis of EHP-30 outcomes. Frontiers in Endocrinology, v. 16, art. 1650579, Sept. 28, 2025. DOI: https://doi.org/10.3389/fendo.2025.1650579 . Available at: https://www.frontiersin.org/journals/endocrinology. Accessed on: 31 Jan. 2026. WORLD HEALTH ORGANIZATION. Endometriosis (Fact sheet). 2025. Available at: https://www.who.int/news-room/fact-sheets/detail/endometriosis. Accessed on: 22 Jan. 2026. Downloads Publicado Como Citar Edição Seção Licença Copyright (c) 2026 Melissa Antunes, Rodolfo de Oliveira Medeiros, Kellen de Pícoli Alexandre, Sabrina Becari Couto, Felipe Colatto Alves, Hacise Colatto, Gabriela Florentino dos Santos, Durcelina Schiavoni Bortoloti, José Antonio Pizzolato Neto, Pedro Henrique Lima Domingues, Camila Menon Oliveros, Cristiano Machado Galhardi Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License. Você tem o direito de: - Compartilhar — copiar e redistribuir o material em qualquer suporte ou formato para qualquer fim, mesmo que comercial. - Adaptar — remixar, transformar, e criar a partir do material para qualquer fim, mesmo que comercial. - O licenciante não pode revogar estes direitos desde que você respeite os termos da licença. De acordo com os termos seguintes: - Atribuição — Você deve dar o crédito apropriado , prover um link para a licença e indicar se mudanças foram feitas . Você deve fazê-lo em qualquer circunstância razoável, mas de nenhuma maneira que sugira que o licenciante apoia você ou o seu uso. - Sem restrições adicionais — Você não pode aplicar termos jurídicos ou medidas de caráter tecnológico que restrinjam legalmente outros de fazerem algo que a licença permita.