Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations

Abstract

Endometriosis is a common estrogen‐dependent disorder wherein uterine lining tissue (endometrium) is found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, and infertility. Recent evidence also supports a systemic inflammatory component that underlies associated co‐morbidities, e.g., migraines and cardiovascular and autoimmune diseases. Genetics and environment contribute significantly to disease risk, and with the explosion of omics technologies, underlying mechanisms of symptoms are increasingly being elucidated, although novel and effective therapeutics for pain and infertility have lagged behind these advances. Moreover, there are stark disparities in diagnosis, access to care, and treatment among persons of color and transgender/nonbinary identity, socioeconomically disadvantaged populations, and adolescents, and a disturbing low awareness among health care providers, policymakers, and the lay public about endometriosis, which, if left undiagnosed and under‐treated can lead to significant fibrosis, infertility, depression, and markedly diminished quality of life. This review summarizes endometriosis epidemiology, compelling evidence for its pathogenesis, mechanisms underlying its pathophysiology in the age of precision medicine, recent biomarker discovery, novel therapeutic approaches, and issues around reproductive justice for marginalized populations with this disorder spanning the past 100 years. As we enter the next revolution in health care and biomedical research, with rich molecular and clinical datasets, single‐cell omics, and population‐level data, endometriosis is well positioned to benefit from data‐driven research leveraging computational and artificial intelligence approaches integrating data and predicting disease risk, diagnosis, response to medical and surgical therapies, and prognosis for recurrence.

An overview and comprehensive analysis of interdisciplinary clinical research in endometriosis based on trial registry

“…Despite the systemic approach taken in addressing endometriosis, there is still a notable scarcity of studies employing a multi-omics approach to investigate the disease. 54 It will continue to necessitate further interdisciplinary collaboration and technological innovation to address this gap in current research.…”

Time for global health policy and research leaders to prioritize endometriosis

“…Reliance on surgery and marginal advances in medical therapies for symptom relief maintain delayed diagnosis and insufficient care for many 1 . Moreover, menstrual stigma, pain in women, sexism, and racism are impediments globally for life-improving care 3 , 4 . Lack of awareness and/or discomfort regarding menstrual health remains surprisingly prevalent among healthcare providers 3 , 4 .…”

“…Moreover, menstrual stigma, pain in women, sexism, and racism are impediments globally for life-improving care 3 , 4 . Lack of awareness and/or discomfort regarding menstrual health remains surprisingly prevalent among healthcare providers 3 , 4 .…”

“…Siloed structures also negatively impact awareness and applying cutting-edge technologies to multidisciplinary scientific discovery of causes, diagnostics, and treatments for endometriosis 3 – 5 . Impediments to determining aetiology and pathophysiology, classifying clinically-relevant subphenotypes, diagnosing, and treating endometriosis include socio-cultural factors that continue its obscurity among practitioners and the public 1 , 3 , 4 . Here we summarize challenges in endometriosis care and advancing research in this space.…”

“…Also, in the central nervous system, brain volume and regional biochemical alterations accompany chronic endometriosis-related pain 7 . Endometriosis is also associated with infertility—attributed to scarred Fallopian tubes, diminished egg quality, and/or disrupted hormone signaling within the uterus 1 , 3 , 4 . Improved understanding of endometriosis pathogenesis and its complex and heterogenous manifestations and physiologic impacts are essential to develop improved diagnostics and patient-centred therapies.…”