Elagolix - a novel drug for management of endometriosis and uterine fibroids

Farha Khan, Farzana Alam Khan
In: International Journal of Reproduction, Contraception, Obstetrics and Gynecology · 2025 · vol. 14(8) , pp. 2836–2839 · doi:10.18203/2320-1770.ijrcog20252375 · W4412768919
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⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Elagolix, an oral GnRH receptor antagonist, effectively reduces menstrual bleeding and pelvic pain in endometriosis and uterine fibroids by reversibly suppressing gonadotropin secretion and allowing dose-adjusted hormonal suppression.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 · read from full text ⓘ

The paper describes elagolix, an oral non-peptide GnRH receptor antagonist, as a hormone-dependent treatment strategy for endometriosis and uterine fibroids, focusing on its mechanism of rapidly and reversibly suppressing pituitary LH/FSH without the GnRH-agonist hormone flare. It summarizes findings from clinical trials reporting that elagolix significantly reduces fibroid-associated heavy menstrual bleeding and alleviates endometriosis-related pelvic pain, with dosing used to adjust the degree of estradiol suppression. A key limitation noted is the hypoestrogenic adverse-effect risk (including bone mineral density loss and vasomotor symptoms), motivating adjustable dosing rather than uninterrupted profound suppression. This paper is centrally about endometriosis — it focuses on elagolix as an oral GnRH antagonist that suppresses ovarian estrogen/progesterone and reduces endometriosis-related pelvic pain.

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Abstract

Endometriosis and uterine fibroids are two hormone-dependent gynecological disorders that significantly impact women’s health impairing their quality of life. Traditional medical therapies used to control symptoms have side effects such as initial symptom flare and hypoestrogenic complications which limit their use. Elagolix is an oral non-peptide gonadotropin releasing hormone receptor (GnRH) antagonist. It is a new therapeutic approach which acts by directly and reversibly suppressing pituitary gonadotropin secretion. It acts by binding competitively to GnRH receptors in pituitary gland which leads to a rapid dose dependent suppression of LH and FSH leading to reduction in production of ovarian sex hormones (estrogen and progesterone). Alternative medications like GnRH agonists cause a transient hormone flare which is complete and long lasting before down regulation. Elagolix immediately inhibits GnRH receptor signaling, avoiding this flare phenomenon. The degree of hormonal suppression can be adjusted by dosing, allowing partial or near-complete suppression of estradiol levels, which is beneficial for tailoring therapy to minimize hypoestrogenic side effects. Elagolix, offers a safe and effective approach in the management of uterine fibroids and endometriosis. Clinical trials have demonstrated that Elagolix significantly reduces fibroid-associated heavy menstrual bleeding and alleviates endometriosis-related pelvic pain. Its rapid onset of action and adjustable dosing regimen allow individualized therapy aimed at balancing efficacy and minimizing hypoestrogenic adverse effects such as bone mineral density loss and vasomotor symptoms.
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Elagolix - a novel drug for management of endometriosis and uterine fibroids DOI: https://doi.org/10.18203/2320-1770.ijrcog20252375Keywords: Elagolix, Endometriosis, Fibroid, GnRH antagonist, Estrogen, ProgesteroneAbstract Endometriosis and uterine fibroids are two hormone-dependent gynecological disorders that significantly impact women’s health impairing their quality of life. Traditional medical therapies used to control symptoms have side effects such as initial symptom flare and hypoestrogenic complications which limit their use. Elagolix is an oral non-peptide gonadotropin releasing hormone receptor (GnRH) antagonist. It is a new therapeutic approach which acts by directly and reversibly suppressing pituitary gonadotropin secretion. It acts by binding competitively to GnRH receptors in pituitary gland which leads to a rapid dose dependent suppression of LH and FSH leading to reduction in production of ovarian sex hormones (estrogen and progesterone). Alternative medications like GnRH agonists cause a transient hormone flare which is complete and long lasting before down regulation. Elagolix immediately inhibits GnRH receptor signaling, avoiding this flare phenomenon. The degree of hormonal suppression can be adjusted by dosing, allowing partial or near-complete suppression of estradiol levels, which is beneficial for tailoring therapy to minimize hypoestrogenic side effects. Elagolix, offers a safe and effective approach in the management of uterine fibroids and endometriosis. Clinical trials have demonstrated that Elagolix significantly reduces fibroid-associated heavy menstrual bleeding and alleviates endometriosis-related pelvic pain. Its rapid onset of action and adjustable dosing regimen allow individualized therapy aimed at balancing efficacy and minimizing hypoestrogenic adverse effects such as bone mineral density loss and vasomotor symptoms. Metrics References Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382(4):328-40. DOI: https://doi.org/10.1056/NEJMoa1904351 Ng J, Chwalisz K, Carter DC, Klein CE. Dose-dependent suppression of gonadotropins and ovarian hormones by Elagolix in healthy premenopausal women. J Clin Endocrinol Metab. 2017;102:1683-91. DOI: https://doi.org/10.1210/jc.2016-3845 Lamb YN. Elagolix: First Global Approval. Drugs. 2018;78(14):1501-8. DOI: https://doi.org/10.1007/s40265-018-0977-4 AbbVie Inc. Prescribing information for OrilissaTM (Elagolix) tablets, for oral use. 2018. Available at: http://www.accessdata.fda.gov/. Accessed on 14 April 2025. Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, et al. Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist Elagolix. J Clin Endocrinol Metab. 2009;94(2):545-51. DOI: https://doi.org/10.1210/jc.2008-1695 Donnez J, Dolmans MM. Uterine fibroid management: from the present to the future. Hum Reprod Update. 2016;22:665-86. DOI: https://doi.org/10.1093/humupd/dmw023 Allaire C, Bedaiwy MA, Yong PJ. Diagnosis and management of endometriosis. CMAJ. 2023;195(10):E363-71. DOI: https://doi.org/10.1503/cmaj.220637 Gurusamy KS, Vaughan J, Fraser IS, Best LM, Richards T. Medical therapies for uterine fibroids — a systematic review and network meta-analysis of randomised controlled trials. PLoS One. 2016;11(2):e0149631. DOI: https://doi.org/10.1371/journal.pone.0149631 Ali M, Sara AR, Al Hendy A. Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. Expert Rev Clin Pharmacol. 2021;14(4):427-37. DOI: https://doi.org/10.1080/17512433.2021.1900726 Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with Elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377(1):28-40. DOI: https://doi.org/10.1056/NEJMoa1700089 Wegienka G, Baird DD, Hertz-Picciotto I, Harlow SD, Steege JF, Hill MC, et al. Self-reported heavy bleeding associated with uterine leiomyomata. Obstet Gynecol. 2003;101:431-7. DOI: https://doi.org/10.1097/00006250-200303000-00005

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