Endometriosis: where are we and where are we going?

Abstract

Endometriosis currently affects ∼5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed.

Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility

“…Endometriosis is a heterogenous disease with diverse symptoms, visual appearance, and long-term outcome (25). Infertility is one of the most common symptoms of endometriosis, often in combination with pelvic pain.…”

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

“…The interaction between immune and hormonal systems considerably impacts endometriosis pathogenesis and development (14). Hormonal signaling differentially regulates immune response; P4 is known by its anti-inflammatory capacity, mediated mainly through PR-B, which overcomes nuclear factor kappa-light-chain-enhancer of active B cells (NF-κB) signaling (54).…”

“…Hormonal treatment consists of suppression of growth lesions and pain reduction by abolishing ovulation and menstruation through the administration of progestins, oral contraceptives, and gonadotropin-releasing hormone agonists (13). Surgical elimination is frequently made by laparoscopy, the gold standard for diagnosis and treatment, by which peritoneal implants, deep nodules, and ovarian cysts are removed; moreover, this technique is also performed for more radical proceedings as hysterectomy (1,14). However, there is not an actual cure for the disease, and lesions and pain tend to reappear after treatments (15); therefore, it is important to continue the development of cuttingedge research focused on studying the underlying mechanisms involved in endometriosis pathophysiology.…”

“…The more accepted theory is the origin of lesions from retrograde menstruation, which establishes that during menstruation, residual endometrial tissue reaches the pelvic cavity, by traveling through fallopian tubes, due to uterine contraction disorders (3). This phenomenon is observed in 90% of women in reproductive age; however, it does not explain why only 10% of them develop endometriosis or the presence of lesions in more distal locations (14). Among other proposed theories are the coelomic metaplasia and the theory of Müllerian remnant; the first one involves the transformation of healthy peritoneal tissue into ectopic endometrial tissue; this theory is based on the fact that peritoneal and endometrial cells have a common origin from coelomic epithelium.…”

Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain

“…[4][5][6][7][8][9][10][11] However, excision of endometriotic lesions and/or anti-inflammatory drugs cannot relieve pain symptoms completely. What is more, a high probability of recurrence and serious side effects might occur, 1,[12][13][14][15] thereby leading to the dilemma in its clinical treatment.…”