A Lifelong Impact on Endometriosis: Pathophysiology and Pharmacological Treatment

Abstract

Endometriosis is a chronic inflammatory disease associated with bothersome symptoms in premenopausal women and is complicated with long-term systemic impacts in the post-menopausal stage. It is generally defined by the presence of endometrial-like tissue outside the uterine cavity, which causes menstrual disorders, chronic pelvic pain, and infertility. Endometriotic lesions can also spread and grow in extra-pelvic sites; the chronic inflammatory status can cause systemic effects, including metabolic disorder, immune dysregulation, and cardiovascular diseases. The uncertain etiologies of endometriosis and their diverse presentations limit the treatment efficacy. High recurrence risk and intolerable side effects result in poor compliance. Current studies for endometriosis have paid attention to the advances in hormonal, neurological, and immunological approaches to the pathophysiology and their potential pharmacological intervention. Here we provide an overview of the lifelong impacts of endometriosis and summarize the updated consensus on therapeutic strategies.

Keywords: angiogenesis; endometriosis; inflammation; medical therapy; pathogenesis; pharmacological inhibitors.

Figure 1

Theories of endometriosis pathogenesis. The potential origins of endometriotic lesions include traveling of endometrial tissue through retrograde menstruation and in situ by coelomic metaplasia of the peritoneal lining or from Müllerian remnants. Lymphovascular dissemination contributes to extra-pelvic lesions. Bone marrow-derived stem cells (BMDSCs) can directly differentiate into endometrial cells at ectopic locations in the peritoneal cavity and distant sites, further expanding the hypothesis of retrograde menstruation and lymphovascular dissemination. Invagination theory is characterized by altered endometrial basalis cells invading the uterine myometrium through disruption of the endometrial-myometrial interface (EMI), resulting in endometriosis of uterus. Epigenomic and genomic alterations further explain the aberrant gene expression in endometriotic lesions.

Figure 2

Pathophysiological processes of endometriosis. Endometriotic lesions are established through interacting molecular mechanisms in a micro-environment of hyperestrogenism and progesterone resistance that promote cell survival and invasion, systemic and localized steroidogenesis, inflammatory response, immune dysregulation, and neuro-angiogenesis. The upward arrows represent overexpression; the downward arrows represent down-regulation.

Figure 3

Endometriosis across the life course. Summary of the symptoms associated with endometriosis, including pain, infertility, and systemic effects. They have a wide range of spectrum and can overlap with these other conditions. The upward arrows represent an increase, and the downward arrows represent a decrease.

Figure 4

Medical treatments for endometriosis [155].

Figure 5

Treatment algorithm of endometriosis.

Figure 6

Assisted reproductive technology for endometriosis.