Aromatase inhibitors for the treatment of endometriosis: a systematic review about efficacy, safety and early clinical development

ABSTRACT

Introduction

Pharmacotherapy has a key role in endometriosis treatment and management, however, a significant proportion of patients have only intermittent or limited benefits with current treatment options. Therefore, novel therapeutic approaches are necessary.

Areas covered

This systematic review provides an overview of the efficacy and safety of aromatase inhibitors (AIs) as monotherapies and combination therapies for endometriosis. A systematic literature search was performed from January 1990 to April 2020 in the electronic database MEDLINE, EMBASE, The Cochrane Library, and Web of Science.

Expert opinion

Based on the critical role of estrogens and the rate-limiting step in the production of the estrogens represented by the aromatase enzyme, AIs are a potential therapeutic option for women affected by endometriosis. Nevertheless, further research is needed to clarify the efficacy of AIs in this setting. Adverse effects need to be investigated to clarify the preventive role of add-back therapy. On that basis, AIs should be adopted only as second-line therapy in patients who are refractory to standard treatments in the setting of scientific research. Further studies should define best dosages, appropriate add-back therapies, administration routes, treatment length, and which patients may benefit more from AIs.

KEYWORDS:

• Endometriosis
• estrogen
• aromatase
• aromatase inhibitors
• dysmenorrhea
• dyschezia
• chronic pelvic pain
• adverse effects

Article highlights

• Pharmacotherapy has a key role in the treatment of endometriosis; however, a significant proportion of patients have only intermittent or limited benefit with progestins/estroprogestins and GnRH analogs. Therefore, the development of other therapeutic options is necessary.

• Estrogens have a key role in the pathophysiology of endometriosis. Aromatase inhibitors (AIs) have been proposed to treat endometriosis, reducing ovarian, systemic, and local estrogen production.

• Fifteen clinical trials have investigated anastrozole and letrozole (third-generation aromatase inhibitors) to treat endometriosis; however, the evidence related to their use is limited.

• Hormone add-back therapy during AI administration seems to prevent the reduction of bone mineral density and the development of functional cysts. However, the addition of AIs to hormone therapy has been associated with a higher rate of menopausal symptoms.

• Recent trials investigated the vaginal route of AI administration. Further research should define best dosages, appropriate add-back therapies, new administration routes, treatment length and those patients that may benefit most from AIs.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

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.

Additional information

Funding

This manuscript was not funded.