The role of pharmacotherapy in the treatment of endometriosis across the lifespan

ABSTRACT

Introduction

Endometriosis is estimated to affect 10% of reproductive-aged women. The gold standard for treatment is surgery; however, surgery carries a significant morbidity and cost burden. There is an ongoing need for safe, effective medical therapies for endometriosis patients, both in conjunction with and independent of surgical interventions. Most conventional therapies for endometriosis work by a similar mechanism, and efficacy is variable. In recent years, there has been increased interest in the development and testing of novel pharmacotherapies for endometriosis.

Areas covered

This review discusses both conventional and emerging treatments for endometriosis. The authors present the application of these drugs in different presentations of endometriosis across the lifespan and discuss how emerging therapies might fit into future medical management of endometriosis. Conventional therapies include nonsteroidal anti–inflammatory drugs, combined oral contraceptives, progestins, GnRH agonists/antagonists, and aromatase inhibitors. Emerging therapies are focused on disease-specific targets such as endothelial growth factor receptors.

Expert opinion

The field of endometriosis therapy is moving toward modifying the immune and inflammatory milieu surrounding endometrial implants. If these drugs show efficacy in clinical trials, combining them with current medical treatment is expected to result in a profound impact on symptom and disease burden for patients who suffer from endometriosis worldwide.

KEYWORDS:

• Endometriosis
• estrogen
• gonadotropin releasing hormone analogues
• infertility
• medical therapy
• progestin

Article Highlights

• With rare exceptions (such as NSAIDs and dydrogesterone), pharmacologic agents used to treat endometriosis-related symptoms inhibit ovulation and are not useful in women actively trying to conceive. There are no pharmacologic agents that improve fertility outcomes in the setting of endometriosis.

• For those patients with pelvic pain and suspected endometriosis without surgical diagnosis, COCs or progestins, alone or in combination with NSAIDs, can be used as first-line empiric therapy.

• There are no data to support the use of the GnRH antagonist elagolix over COCs or progestins, as there no direct comparison studies. As these drugs have both significant side effects and cost, they should be considered as secondary or tertiary treatment options.

• Postoperative treatment with progestins or COCs for a period of 18–24 months results in reduced cyclic pelvic pain and endometrioma recurrence. The 2013 ESHRE guidelines recommend post-operative use of either a levonorgestrel IUS or COCs for the prevention of postoperative endometriosis recurrence.

• COCs taken continuously result in greater reductions in endometriosis-related pain compared to COCs taken cyclically.

• Second-line therapies include GnRH agonists, GnRH antagonists, and aromatase inhibitors.

• The utility of oral androgens is limited by androgenic side effects; however, there may be a role for vaginal and intrauterine administration of danazol for refractory symptoms.

• Emerging therapies that target molecular pathways, including immune modulators and anti-VEG-F agents, are under active investigation with promising preliminary data in animal models.

This box summarizes key points contained in the article.

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 manuscript was not funded.