ABSTRACT Uterine leiomyomata (UL), endometriosis, and polycystic ovarian syndrome (PCOS) are debilitating gynecologic conditions diagnosed in up to 30% of North American women. These conditions are associated with infertility, pain, menorrhagia, and other sequelae that can profoundly affect quality of life. In the United States (US), annual health care costs for treating these conditions exceed $3 billion. Childhood sexual abuse (CSA) is reported by up to 25% of US women, but there has been limited study of its effects on gynecologic health. CSA has been associated with altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic stress response, demonstrating long-term effects on health that can persist into adulthood. Emerging research suggests that exposure to CSA influences risk of gynecologic conditions. MPIs of the present application, Drs. Boynton-Jarrett and Wise, have published studies from two US cohorts showing that early life abuse victimization, particularly CSA, was associated with greater UL incidence and that resilience factors may mitigate the adverse effects of CSA. Given the dearth of research in this area, and the potential role of moderators and mediators, greater study of the effects of CSA on the occurrence of gynecological diseases is critical. With ongoing NIH funding since 2013 (R01-HD086742), Pregnancy Study Online (PRESTO) has enrolled and followed more than 17,200 female-identified participants—including more than 3,200 participants who identify as Black, Indigenous, and People of Color (BIPOC)—residing in the US and Canada. Comprehensive data are collected on socio-demographics, diet, behaviors, medical history, medication use, mental health, and stress, including data on social determinants of health such as adverse childhood experiences, abuse, financial hardship, and discrimination, as well as measures of resilience, social and emotional support, and coping. This application will leverage the existing PRESTO infrastructure to assess the following hypotheses: CSA will be associated with a greater risk of UL, endometriosis, and PCOS. Greater social and emotional support, resilience, coping skills, and neighborhood cohesion will buffer these associations. Mental health conditions—depression, anxiety, post-traumatic stress disorder (PTSD)—that develop after abuse initiation but before onset of gynecologic conditions will mediate these associations. This study will be one of the largest investigations of CSA and gynecologic disease. Added strengths include the comprehensive collection of data on abuse and other adversities across the life course; proposed validation of gynecologic diseases using medical records; collection of extensive data on potential moderators, mediators, and confounders; geographically dispersed and racially diverse study population; and interdisciplinary research team. Preliminary data from PRESTO indicate wide variability in exposure to CSA. Future research could build on th...