An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women

ABSTRACT

Introduction

Uterine Fibroids (UFs) are the most predominant benign tumor in women who are coming of reproductive age, and causes intense economic load priced in billions of US dollars. Historically, surgery has been the main definitive treatment, albeit less attractive nowadays, especially for women with future fertility plans. Therefore, studies to explore the pharmacological treatment options are increasing especially as those that are currently available are limited for short-term use only.

Areas covered

This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs.

Expert opinion

The combination of relugolix/E2/NETA is an encouraging, well-tolerated and noninvasive pharmacological option for UFs patients. Relugolix induced a concentration-dependent decrease in HMB. However, it should be used with hormonal add-back therapy (E2+ NETA) to avoid induced hypoestrogenic side effects, importantly bone mineral density loss. Moreover, symptoms will likely resume shortly after the termination of the relugolix combination administration.

KEYWORDS:

• Oral GnRH antagonists
• relugolix
• add-back therapy
• leiomyoma
• Uterine Fibroids
• heavy menstrual bleeding

Declaration of interest

A Al-Hendy is a consultant for Allergan, Bayer, Repros and Myovant Sciences, as well as AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer discloses that they serve occasionally on the advisory boards of Gedeon Richter and Bayer and have planned and lectured at educational events organized by these companies. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Drug summary box

Additional information

Funding

This study was supported in part by the National Institutes of Health grants: R01 HD094378-04, R01 ES 028615–02, R01 HD100367-01, U54 MD007602, and R01 HD094380-02.