Opigolix

The aim of this systematic review is to summarize the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on hormonal therapeutic options for endometriosis-associated pelvic pain (EAPP), excluding studies focusing on fertility.

We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 219 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, 11 primary articles met the inclusion criteria. A systematic review of the data was conducted.

This review included several emerging drug therapies for EAPP. Randomized control trials showed promising results with several oral gonadotropin-releasing hormone antagonists (elagolix, relugolix, ASP1707, linzagolix). However, studies of other hormonal agents such as aromatase inhibitors and selective progesterone receptor modulators have not yielded significant or new advantages. Selective estrogen receptor modulators have not been represented in randomized control trials and have failed to demonstrate clinical efficacy.

Although numerous novel agents are being investigated for the treatment of endometriosis, there is still no significant progress in the development of curative rather than suppressive drugs. Therefore, further efforts are needed to develop an effective and hopefully curative treatment for this chronic, costly, and overwhelming disease.

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short- and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.