Successes and failures of uterine leiomyoma drug discovery

ABSTRACT

Introduction: To-date, the only cure for symptomatic uterine fibroids (UFs) is surgical intervention. However, surgery may eliminate the hope of future pregnancies; moreover, the intrinsic risks of surgery make it a less favorable to women with UFs. Because of this, conservative medical therapies have become an attractive and prior option for those women. Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) agonist, is the only pharmacological agent currently approved for the short-term and pre-operative management of symptomatic UFs in the USA.

Areas covered: This systematic review covers the successes and failures of prominent drugs that have been researched for UFs in the past and agents that have shown promise in recent clinical trials. The most recent clinical trials and advances in drug therapy are presented in a comprehensive overview outlining the direction UF drug discovery is heading.

Expert opinion: Experts in the field are already on the forefront leading the responsibility to uncover potential drugs as long term fertility friendly viable options for non-invasive treatment/prevention of UFs. Indeed, a shift in the UF management is expected in the future.

KEYWORDS:

• Uterine fibroids
• leiomyoma
• SPRMs
• GnRH agonist
• GnRH antagonist
• vitamin D analogs
• medical myomectomy
• fertility preservation
• treatment
• prevention

Article highlights

• Traditional hormonal medical therapies carry intrinsic risks of their own and frequently fail in long-term control symptoms.

• Novel drugs are essential to be the future of long-term fertility friendly medical management for UFs.

• SPRMs as Ulipristal acetate and oral GnRH antagonist as Elagolix are promising oral anti-UF medications, yet more safety data regarding long-term use are required.

• Lack of ethnic/racial diversity is unfortunately common in many clinical trials of UF treatment.

• A definite shift in the UF management is expected in future years from invasive treatment to orally administrated options, and this potential shift will require new drug discoveries and additional intense large scale clinical research.

This box summarizes key points contained in the article.

Declaration of interest

One author 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. One referee is a consultant for Gedeon Richter.

Additional information

Funding

The authors are funded by National Institutes of Health grants NIH R01DO89553-01 and NIH R01-ESO28615-01