Novel pharmacological therapies for the treatment of endometriosis

ABSTRACT

Introduction

Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease.

Areas covered

This narrative review aims to present the latest advances in the pharmacological management of endometriosis. In particular, the potential role of GnRH antagonists, selective progesterone receptor modulators (SPRMs), and selective estrogen receptors modulators (SERMs) will be discussed. We performed a literature search in PubMed and Embase, and selected the best quality evidence, giving preference to the most recent and definitive original articles and reviews.

Expert opinion

Medical therapy represents the cornerstone of endometriosis management, although few advances have been made in the last decade. Most studies have focused on the evaluation of the efficacy and safety of GnRH antagonists (plus add-back therapy in cases of prolonged treatment), which should be used as second-line treatment options in selected cases (i.e. non-responders to first-line treatments). Further studies are needed to identify the ideal treatment for women with endometriosis.

KEYWORDS:

• elagolix
• endometriosis
• GnRH antagonist
• linzagolix
• relugolix
• SPRM
• SERM

Article highlights

• According to major international guidelines, standard first-line treatments for symptomatic endometriosis include low-dose combined hormonal contraceptives and progestogens, which are effective in about two-thirds of symptomatic women.

• The principal advantages of GnRH antagonists include dose-dependent estrogen suppression, fast reversibility of hormone secretion after the end of the treatment, avoidance of the flare-up effect and oral delivery.

• Oral GnRH antagonists induce dose-dependent symptom amelioration in patients with endometriosis.

• SPRMs have shown promising results in ameliorating endometriosis-associated pain; however, their safety profile regarding potential liver toxicity and progesterone receptor modulator-associated endometrial changes (PAEC) in the endometriotic foci has not been proven with a sufficient level of evidence. The evidence on the potential role of SERMs in treating endometriosis is scarce and of low quality.

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

A reviewer on this manuscript has disclosed being the VP and Head GMA Fertility at Merck KGaA, based in Darmstadt, Germany. Merck does not have marketed products to treat endometriosis. This reviewer has spent 25 years of research in endometriosis biomarkers and new drugs evaluation when they were in academia full time before joining Merck KGaA. Another reviewer has disclosed study participation in Elaris and Edelweiss. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

L Buggio: manuscript writing/editing and data collection; D Dridi: data collection and manuscript editing; G Barbara: manuscript editing; CEM Merli: manuscript editing; GE Cetera: manuscript editing; P Vercellini: manuscript editing; all authors read and approved the final manuscript.

Additional information

Funding

This paper was not funded.