Experimental and new investigational drugs for the treatment of uterine fibroids

ABSTRACT

Introduction

Uterine fibroids, the most prevalent benign tumors among reproductive-age women, pose treatment challenges that range from surgical interventions to medical therapies for symptom control. Progestins and estroprogestins effectively manage uterine bleeding by suppressing dysfunctional endometrium over fibroids. While GnRH agonists represent a crucial milestone in symptom treatment, their prolonged use results in menopausal-like symptoms and irreversible bone mineral density loss. Advancements in understanding fibroid pathophysiology have prompted the exploration of new compounds to overcome current therapy limitations.

Areas covered

This manuscript offers an updated overview of investigational drugs for symptomatic uterine fibroids.

Expert opinion

Despite ulipristal acetate’s well-established efficacy as a selective progesterone receptor modulator (SPRM) in fibroid treatment, its prescription has declined due to the rare but severe risk of liver damage. Oral GnRH antagonists, like elagolix, relugolix, and linzagolix, with their novel pharmacodynamic properties, are gaining traction in fibroid management, inducing a dose-dependent reduction in circulating sex hormone levels. Ongoing research on natural compounds, such as vitamin D and epigallocatechin gallate (EGCG), presents emerging options for treating uterine fibroids. This evolving landscape reflects the ongoing efforts to improve therapeutic outcomes for individuals with symptomatic uterine fibroids.

KEYWORDS:

• Uterine fibroids
• GnRH-agonists
• elagolix
• relugolix
• linzagolix
• ulipristal acetate
• vitamin D
• epigallocatechin gallate

Article highlights

• Premenopausal individuals with symptomatic uterine fibroids (UFs) have various medical alternatives, offering temporary symptom relief and potentially postponing or avoiding surgery.

• GnRH-agonists are a traditional option for UF-related symptoms, but sustained estrogen deprivation with them leads to menopausal-like symptoms and irreversible bone density loss.

• Ulipristal acetate efficacy in UF treatment is established, but global prescription has declined due to rare but severe liver damage risk. Prophylactic measures, including contraindications and monitoring, have been implemented.

• Recent GnRH-antagonist advancements include linzagolix, an oral option with a safe profile even without add-back therapy (ABT), meeting the needs of patients for whom ABT is contraindicated.

• Exploration of natural compounds like vitamin D and epigallocatechin gallate (EGCG), along with consideration of genetic factors, offers potential avenues for long-term therapy and addressing ethnic-specific differences in UF development.

Declaration of Interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The preliminary analysis of literature research has been presented by F Barra at the ESHRE Campus organized by the ESHRE SIG Endometriosis & Endometrial Disorders, (Palermo, Italy; 16 -17 Feb 2023).

Additional information

Funding

This paper was not funded.