Harnessing biomarker and phenotypic diversity among adolescents and women with endometriosis to advance personalized medicine for diagnosis and pain remediation

项目总结/文摘

Project Summary/Abstract Endometriosis is a common disease among reproductive aged adolescents and women and can lead to debilitating pelvic pain, infertility, reduced quality of life and significant health care costs. Currently laparoscopic surgery is the only means for providing a definitive diagnosis of endometriosis. The average delay to diagnosis from symptom onset is 7 years, potentially leading to unchecked endometriotic lesion progression and increased risk and severity of morbidity later in adulthood. While numerous studies have investigated non- invasive screening tests for diagnosing endometriosis, none have proven to have sufficient specificity and/or sensitivity to replace laparoscopic surgery. Further, once an adolescent or woman has been diagnosed with endometriosis she often faces a struggle to find the most effective treatment modality to relieve endometriosis- related symptoms. While the revised American Society for Reproductive Medicine endometriosis staging and the Endometriosis Fertility Index have been used to predict prognosis after endometriosis diagnosis; neither is specific to predicting if adolescents and women will experience pain remediation. Additionally, a subset of endometriosis patients will develop central sensitization leading to treatment refractory chronic pelvic pain. The lack of discovery for a non-invasive screening test for endometriosis diagnosis and for monitoring disease progression may be due to considering endometriosis as a single entity and not including the full heterogeneity in symptom profiles and patient characteristics to assess diagnosis and pain remediation after treatment. Our proposal fills this scientific gap by (1) investigating a non-invasive diagnostic for endometriosis combining patient symptoms and characteristics with inflammatory, oxidative stress and central sensitization biomarkers; (2) assessing changes in inflammatory, oxidative stress and central sensitization biomarkers before and after surgery; and (3) determining the optimal set of patient symptoms and characteristics in addition to inflammatory, oxidative stress and central sensitization biomarkers to advance personalized treatment selection. We will assess inflammatory and oxidative stress biomarkers as an aberrant immune response and increased oxidative stress have been implicated in endometriosis etiology and progression. Collectively, these aims have the potential to advance our understanding of phenotypic diversity among adolescents and women with endometriosis; diversity that will be the foundation for successful personalized, precision medicine to shorten diagnostic delay and maximize pain remediation. Success will reduce health care costs and increase long-term health and quality of life for adolescents and women with endometriosis.