Current approaches to overcome the side effects of GnRH analogs in the treatment of patients with uterine fibroids

Expert Opin Drug Saf. 2022 Apr;21(4):477-486. doi: 10.1080/14740338.2022.1989409. Epub 2021 Oct 20.

Abstract

Introduction: Uterine fibroids (UFs) are the most prevalent benign neoplastic threat originating from myometria of reproductive age women, with a profound financial load valued in hundreds of billions of dollars. Unfortunately, there is no curative treatment so far except surgery and available pharmacological treatments are restricted for short-term treatment options. Thus, there is a large unmet need in the UF space for noninvasive therapeutics.

Areas covered: The authors reviewed the literature available for the utility of gonadotropin-releasing hormone (GnRH) analogs in women with UFs. We also focused on clinical studies exploring the therapeutic benefits of novel oral non-peptide GnRH antagonists that were recently approved by the U.S. Food and Drug Administration (FDA) in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with UFs in premenopausal women.

Expert opinion: The results regarding the efficacy of new-generation oral GnRH-antagonists, such as elagolix, relugolix and linzagolix, are promising and offer potential prospect for the future therapy of UFs. However, these antagonists must be combined with hormonal add-back therapy to minimize the resultant hypoestrogenic side effects such as bone loss.

Keywords: GnRH analogs; add-back therapy; hypoestrogenic side effects; leiomyoma; safety; uterine fibroids.

Publication types

  • Review

MeSH terms

  • Carboxylic Acids / therapeutic use
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Humans
  • Leiomyoma* / drug therapy
  • Pyrimidines
  • Uterine Neoplasms* / drug therapy

Substances

  • Carboxylic Acids
  • Pyrimidines
  • Gonadotropin-Releasing Hormone
  • linzagolix