Metabolomic profiling of adolescent endometriosis

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ABSTRACT Endometriosis is a debilitating disease affecting 200 million women worldwide, causing severe pain and infertility. Although over 50% of adults with endometriosis report onset of pain during adolescence, most women with endometriosis experience a delayed diagnosis on average of seven years due to the current diagnostic standard of surgical visualization, resulting in prolonged pain and decreased quality of life. Thus, there is a critical need to identify novel, non-invasive biomarkers for endometriosis, which is one of the NICHD research goals related to endometriosis. Being able to diagnose endometriosis earlier in the life course, during adolescence and young adulthood, may lead to earlier intervention and improved clinical outcome. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed in adolescents. Adolescent endometriosis typically presents with severe pelvic pain and superficial peritoneal lesions, which is distinct from adult-diagnosed endometriosis which typically present with pain, infertility, and deep fibrotic lesions. Furthermore, our preliminary data shows that about 30% of adolescents with endometriosis suffer from persistent or recurring post-surgical pelvic pain despite being treated with post-surgical hormone therapy, leading to recurring surgeries. Recently, we reported that blood CA125, which is elevated in endometriosis diagnosed in adults, was not elevated in adolescents with endometriosis. Adolescent-diagnosed endometriosis may have distinct molecular phenotype compared to adult-diagnosed endometriosis, which may require different strategies for diagnosis and treatment. The objective of this application is to identify novel (1) blood metabolomic profiles associated with adolescent endometriosis and (2) peritoneal fluid metabolomic markers predictive of persistent post-surgical pain. Metabolites are the downstream products of cellular activities regulated by the genome and modified by environmental factors and have proven valuable in biomarker discovery for many chronic diseases. Based on our preliminary data, upregulation of prostaglandin synthesis could be an important pathway for adolescent endometriosis pathophysiology given its common presentation with pain. Using the detailed clinical information, pain measures, plus paired blood and peritoneal fluid samples from the well-annotated longitudinal cohort of the Women’s Health Study: From Adolescence to Adulthood cohort, we will apply a validated metabolomics platform which can simultaneously measure over 600 metabolites, allowing us identify metabolites and biologic pathways unique to adolescent endometriosis. The proposed aims will identify novel metabolomic biomarkers of adolescent endometriosis which may lead to advances in determining early diagnostic biomarkers and personalized treatment strategies for endometriosis. Importantly, elucidating molecular profiles of adolescent endometriosis will provide new information about the pathophysiology during the earlier course the disease trajectory, informing future R01 proposals to elucidate changes in metabolomic profiles as the disease progresses from adolescence to adulthood.