GnRH antagonists for the treatment of fibroids and adenomyosis, current evidence and future perspectives

Introduction: Uterine fibroids and adenomyosis are common estrogen- and progesterone-dependent disorders associated with heavy menstrual bleeding, pelvic pain, anemia, and impaired quality of life. Although surgery remains widely used, there is an increasing demand for effective uterus-preserving medical therapies. Oral gonadotropin-releasing hormone (GnRH) antagonists have recently emerged as a novel therapeutic option, allowing rapid, reversible, and dose-dependent suppression of ovarian steroidogenesis. Areas covered: This narrative, based on a targeted PubMed/MEDLINE literature search and review of major guideline documents published up to May 2026, summarizes the pharmacological properties, mechanisms of action, and clinical evidence regarding GnRH antagonists (elagolix, relugolix and linzagolix) in uterine fibroids and adenomyosis. Evidence from randomized controlled, extension studies, and emerging literature was critically reviewed, focusing on control of heavy menstrual bleeding, pain reduction, quality of life, safety, and the role of add-back therapy. Expert opinion: GnRH antagonists represent a major advance in the medical treatment of uterine fibroids and are highly effective in controlling heavy menstrual bleeding. Their role in adenomyosis appears promising, although evidence remains limited. These agents should currently be considered suppressive rather than curative therapies, as symptoms often recur after discontinuation. Long-term integration into individualized treatment strategies will require further safety and comparative effectiveness data.