ABSTRACT
Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to hormonal imbalance, including estrogen synthesis, metabolism and responsiveness and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed.
Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.
Financial and competing interests disclosure
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.
Hormonal imbalance characterizes the development of endometriosis lesions
Estrogen dependence involves increased steroid synthesis, metabolism, and modified responsiveness of nuclear and membrane ER. These features are also the main therapeutic targets currently under investigation.
In vivo and in vitro studies blocking ERs and estrogen local synthesis are promising but clinical data are lacking or hampered by important side effects.
Progesterone resistance involves PRA/B ratio and receptor signal transduction.
Targeting PR by SPRMs is promising, but still limited due to the higher doses needed and long-term safety concerns.
Endometriosis is a multifaceted disease, encompassing hormonal alterations, neuroinflammation, and epigenetic modifications. The concomitant targeting of these features will represent the next step for improving medical management.