A comprehensive review of hormonal and biological therapies for endometriosis: latest developments

ABSTRACT

Introduction: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis.

Areas covered: This review aims to give to the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research.

Expert opinion: Among the new drugs investigated, late clinical trials on gonadotropin-releasing hormone (GnRH) antagonists and aromatase inhibitors (AIs) have demonstrated the most promising results. For this reason, elagolix, a new GnRH-antagonist, recently received the approval by the Food and Drug Administration (FDA) for treating pain associated to endometriosis. Other drugs with innovative targets have been identified, but the majority of these compounds have only been evaluated in pre-clinical studies or early clinical trials. Thus, a further extensive clinical research is necessary to better elucidate their pharmacologic characteristics, their efficacy, and safety for the treatment of this benign chronic disease.

KEYWORDS:

• Elagolix
• aromatase inhibitors
• gonadotropin-releasing hormone antagonists
• hormonal treatments
• biological therapy

Article highlights

• Combined hormonal contraceptives and progestins are commonly employed therapies for initially treating the majority of women with endometriosis;

• Among second-line therapies for endometriosis, gonadotropin-releasing hormone (GnRH)-agonists have been largely used in the last decades. However, they cause relevant estrogen deprivation-related adverse events;

• The administration of aromatase inhibitors (AIs) for endometriosis is off-label and, therefore, they should be considered only in patients with symptoms resistant to other conventional therapies;

• In the last few years, great attention has been given to the emerging use of GnRH-antagonists; recently, elagolix has been approved by the USA Food and Drug Administration (FDA) for the treatment of pain associated to endometriosis;

• Among new early hormonal targets, drugs blocking steroid sulfatase and 17βhydroxysteroid dehydrogenase type 1 are currently under pre-clinical and early clinical assessment;

• New alternative biological therapies are emerging with intriguing findings from latest pre-clinical trials: anti-angiogenic, anti-inflammatory and immunomodulatory drugs have been investigated in a pre-clinical setting.

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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 relationships or otherwise to disclose.

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Funding

This paper was not funded.