Menstruation Dysregulation and Endometriosis Development

Abstract

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

“…Although the relationship between the cellular components of menstrual flow and the etiopathogenesis of endometriosis is undeniable [ 55 ], as well as the immunoregulatory roles of MenSCs as actors of endometriosis [ 8 ], the origin of ectopic tissue remains unclear. In this scenario, more outstanding efforts have been devoted to unraveling molecular changes in progenitor cells in the endometrium (eMSC) [ 27 , 28 , 29 , 30 ] than those in menstrual blood (MenSCs) [ 7 , 31 ].…”

Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort

“…Furthermore, we found that hypothalamic amenorrhea, another etiology of irregular cycles, 33 , 51 , 52 , 53 , 54 , 55 may contribute to a higher prevalence of arrhythmia, which may be explained by low estrogen levels and stress. 33 , 56 , 57 Abnormal menstrual patterns may be indicative of a proinflammatory process 58 that may result in elevated CVD risk. In summary, irregular cycles may serve as an early vital sign to initiate earlier screening, counseling, and lifestyle interventions for cardiometabolic conditions.…”

Noninvasive electrophysiological imaging identifies 4D uterine peristalsis patterns in subjects with normal menstrual cycles and patients with endometriosis

“…Endometriosis has long been hypothesized to be caused by retrograde menstruation 13,[41][42][43][44][45][46] . However, as all reproductive-age women have some amount of retrograde menstruation, it is unclear why only 10-15% of females would develop endometriosis 42,45,[47][48][49] .…”