Efficacy and Safety of Oral GnRh Antagonists in Patients With Uterine Fibroids: A Systematic Review

J Obstet Gynaecol Can. 2022 Dec;44(12):1279-1288. doi: 10.1016/j.jogc.2022.10.012. Epub 2022 Nov 9.


Objective: This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids.

Data sources: A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov using the MeSH and Emtree terms "leiomyoma" and "gonadotropin-releasing hormone."

Study selection: All clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc.) were included. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question.

Data extraction and synthesis: Two authors extracted data from 9 clinical studies. The extracted data included the study's characteristics, participants' baseline characteristics, treatment drugs, efficacy measures, and toxicity.

Conclusion: Among oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with E2/NETA (estradiol/norethindrone acetate), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized, double-blind, multicentre clinical trials are needed to confirm these results and to see long-term benefits.

Keywords: drug therapy; gonadotropin-releasing hormone; systematic review; uterine fibroids.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Female
  • Gonadotropin-Releasing Hormone
  • Hormone Antagonists / therapeutic use
  • Humans
  • Leiomyoma* / drug therapy
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Uterine Neoplasms* / drug therapy


  • Gonadotropin-Releasing Hormone
  • Hormone Antagonists