What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment

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Endometriosis is a debilitating and often incurable condition characterized by the presence of endometrial- like glands and stroma thriving outside of the uterine cavity. The condition affects approximately 10–15% of all women of reproductive age. The most common symptom of endometriosis is pain, with endometriosis diagnosed in approximately 83% of all chronic pelvic pain (CPP) cases in the US. Current classification and staging systems for endometriosis have not found clinically useful associations with the level or chronicity of pain. Approximately 30% of women with endometriosis-associated pain (EAP) continue to experience persistent pain after surgery to treat the condition, possibly explained by central sensitization (CS). The parent grant, “What is Endometriosis? Deep Phenotyping to Advance Diagnosis and Treatment (WisE),” (PI: Missmer; R01 HD094842; Project dates 08/01/18 to 04/30/23) aims to identify unique classifications of patients with endometriosis that will inform non-invasive diagnostics, prognosis given current treatments, and novel treatment pathways. This Research Supplement to Promote Diversity in Health-Related Research application is requested to formally add Ms. Claire Lunde to the WisE team and support her research time during her final nine months as a doctoral student at the University of Oxford. The proposed mentoring team also includes Professor Vincent and Dr. Sieberg; both are Co-Is on the parent award and are Ms. Lunde’s current Ph.D. supervisors. As the parent R01 aims to discover informative subtypes of endometriosis and disease classifications, the candidate will supplement this research by analyzing existing sensory data (n=108) conducted on the same sample to further subdivide endometriosis participants by low and high CS. The most relevant aims of the parent award are Aims 3 and 4, which entail characterizing disease phenotypes by symptom presentation and heterogeneity of phenomics data for patients with endometriosis. The parent R01 uses harmonized medical records, participant data, blood, urine, and tissue samples for a diverse cohort of adolescents and adult females (n~2600). Integrating Quantitative Sensory Testing and phenomics data will further identify differences in functional pain characteristics between endometriosis participants and pain- free controls and provide a comprehensive set of objective patient phenotypes complementing the rich self- reported phenotype data. These results will elucidate the pain profiles in the clinical presentations (including pain thresholds and psychological variables) and if there is an association with outcomes after interventions (e.g., surgery). This will also allow for defining strategies for patient selection for future trials of novel therapeutics targeting these mechanisms. This critical research will expand upon our current collaborative research by enhancing our understanding of the impact of centralized pain on patients with endometriosis through establishing characteristics of patient subgroups using a mixed-method approach.