Comparing the pharmacokinetic and pharmacodynamic qualities of current and future therapies for uterine fibroids

ABSTRACT

Introduction

Uterine fibroids are the most common benign gynecological tumors affecting women of reproductive ages. Although surgery is the definitive treatment choice, several medical approaches have been investigated to control their symptoms. The main issue of currently employed drugs for uterine fibroids is the long-term safety and tolerability profile. Today, new emerging options represent hopeful alternatives that could potentially overcome these limitations.

Areas covered

This manuscript aims to give an updated overview of the pharmacodynamic and pharmacokinetic properties of current and new investigational medical drugs for the treatment of symptomatic uterine fibroids. The bibliographic research was conducted by searching alone or combined keywords on the following electronic databases: Medline, PubMed, Embase, Science Citation Index via Web of Science.

Expert opinion

The most recent therapeutic strategies for uterine fibroids are represented by gonadotropin-releasing hormone antagonists (GnRH-ants; elagolix and relugolix) and selective progesterone receptor modulators (SPRM; ulipristal acetate). After early promising results, studies on innovative drugs, such as linzagolix (GnRH-ant) and vilaprisan (SPRM) are demanding. In the near future, a deeper knowledge of biological mechanisms at the basis of the genesis and growth of uterine fibroids could pave the way for the development of innovative targeted therapies.

KEYWORDS:

• Drug pharmacology
• elagolix
• levonorgestrel releasing intrauterine device
• linzagolix
• relugolix
• ulipristal acetate
• uterine fibroid
• vilaprisan
• GnRH-agonists
• leuprolide
• aromatase inhibitors

Article highlights

• Modulation of the hormonal microenvironment is the main target of medical therapy for uterine fibroids (UFs);

• Levonorgestrel releasing intrauterine device is a viable alternative to oral progestins for treating symptoms related to UFs. This device ensures effective control of uterine abnormal bleeding thanks to the direct localized progestin action on endometrium, offering also the additional benefit of long-term contraception.

• Gonadotropin-releasing hormone agonists have been widely employed to treat symptoms related to UFs. However, a drop in circulating estrogen might lead to the development of menopausal-like symptoms, which tend to limit their long-term use.

• More than 10 years ago, ulipristal acetate, a selective progesterone receptor modulator, has been effectively introduced in the clinical practice for treating UFs. However, reported cases of liver toxicity led the European Medicine Agency to review and limit its clinical indications.

• Gonadotropin-releasing hormone antagonists are new therapeutic options for UFs, characterized by rapid onset of action and dose-dependent effect, not causing a complete suppression of circulating estrogens. New studies on these drugs are demanding.

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.

Additional information

Funding

This paper was not funded.