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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. 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. 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.

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