Medical management of adenomyosis: current and future therapies

The current issue of Journal of Fertility and Sterility has focused exclusively on etiology, pathophysiology, and medical and surgical treatment of adenomyosis. Adenomyosis has long been the source of controversy and its only with the recent advent of Transvaginal sonography (TVS) and MRI that its etiology and pathophysiology been better understood.

Adenomyosis is a uterine pathology in which the endometrial glands and stroma invaginate within the uterine myometrium. This ectopic endometrium induces hypertrophy and hyperplasia of the myometrium resulting in the typical ‘globular” enlargement of the uterus.

It is also now known that endometriosis and adenomyosis are two different phenotypes of the disorder characterized by impaired cellular response to ovarian hormone. This concept has to lead to the use of common treatment modalities for both the diseases.

Transvaginal sonography (TVS) and MRI are now the gold standards for diagnosing adenomyosis. Adenomyosis requires a lifelong treatment plan that depends upon patient’s age, desire for children and symptoms. Medical management is the treatment of choice for women who want to preserve fertility, while hysterectomy is preferable in older women who have completed the childbearing.

No new drug has been developed in recent years for the treatment of adenomyosis although many new drugs are under development and undergoing clinical trials.  

Medical management includes minimally invasive procedures as well as medication to treat the symptoms.

Minimally invasive surgical procedures help preserve fertility as well as reduce the pain and abnormal uterine bleeding (AUB) and include endometrial ablation and resection, laparoscopic as well as open excision of adenomyosis and MRI-guided focused ultrasound. They are offered to patients who have not responded to medical drug treatments. 

The medical treatment is mainly aimed at easing the symptoms, improving quality of life and promote fertility. The rationale behind using these drugs is based on the pathophysiology of the disease which includes aberrant response to the ovarian hormone, inflammation, and impaired apoptosis.

http://journals.sagepub.com/doi/full/10.5301/je.5000261

The class of drugs includes:

Current Medical Treatments: 

GnRH agonist: These group of drugs cause a downregulation of GnRH activity and induce a reversible state of medical menopause. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice before fertility treatments to improve the chances of pregnancy in infertile women with adenomyosis.

Progestins: Drugs such as danazol, norethindrone acetate (NETA), Levonorgestrel-releasing intrauterine system (LNG-IUS), and Dienogest are mainly used because of anti-inflammatory properties to relieve pain and reduce the amount of abnormal uterine bleeding.

The Levonorgestrel-releasing intrauterine system (LNG-IUS) has been found extremely effective in reducing menorrhagia and decrease the uterine volume over a period of 12 months use.

Combined oral contraceptives (COC): They are effectively used to reduce pain and control bleeding with the additional advantage of long-term use with minimal side effects.

Future Medical treatments:

Selective estrogen receptor modulators (SERMs)

Aromatase inhibitors (AIs)

Selective progesterone receptor modulators (SPRMs)

Valproic acid

Anti-platelets therapy

NSAIDs

Thus, the medical treatment of adenomyosis comprises many current and future drugs. No double-blind, RCTs have yet been conducted in the management of adenomyosis and the drugs are solely used based on results of observational studies.

Abstract

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