A review of phase II and III drugs for the treatment and management of endometriosis

ABSTRACT

Introduction

Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy.

Areas Covered

The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis.

Expert Opinion

Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.

KEYWORDS:

• Endometriosis
• hormonal treatments
• gonadotropin-releasing hormone antagonists
• SERM
• SPRM
• progestins
• medical therapy
• aromatase inhibitors

Article highlights

• Standard first-line treatments for pain related to endometriosis involve the use of low-dose combined estro-progestins and progestins, which prove effective in approximately two-thirds of affected women.

• The current second-line therapy for endometriosis is centered around GnRH agonists. However, due to their undesirable tolerability profile resulting from induced sustained hypoestrogenism, their use should be limited to a specific period and combined with an appropriate add-back therapy.

• In recent years, there has been a growing interest in the use of GnRH antagonists for endometriosis therapy, with the majority of phase II and III trials being organized.

• The primary benefits of oral GnRH antagonists encompass estrogen suppression dependent on the dosage, rapid restoration of hormone secretion once treatment concludes, and prevention of the flare-up effect.

• Nevertheless, data on their efficacy and safety remain limited. Additionally, they are associated with considerable costs, and at higher dosages, the induced hypoestrogenism may necessitate the use of add-back therapy, akin to the approach with GnRH agonists.

• Current limited and low-quality evidence supports the use of SERMs and SPRMs for endometriosis treatment.

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.