PROJECT SUMMARY Uterine fibroids are the most common pelvic tumors in women of reproductive age, coming to clinical attention in one in four women. Fibroids are 2-3 times as common among Black women compared to White women. Each year, fibroids result in $2.2 billion in health care costs and account for over 200,000 hysterectomies. Despite significant quality of life and health care costs associated with fibroids, few modifiable, factors have been identified, and it is unknown why Black women are disproportionately affected. A major barrier to understanding the relative contributions of established and yet-to-be identified risk factors that may contribute to the fibroid disparity is that no single study has adequate numbers of both Black and White women to apply advanced epidemiologic methods (e.g., mediation analyses, population attribute risks) to evaluate these differences. Further, while an association between perceived interpersonal racism and fibroids has been shown, no studies have examined the role of structural racism in fibroid incidence. We propose to study women from two prospective U.S. cohorts — Black women from the Black Women’s Health Study (BWHS) and White women from the Nurses’ Health Study II (NHSII) — to identify factors that explain the differences in fibroid incidence between Black and White women. Among 59,000 participants (6,200+ newly diagnosed cases) in the BWHS and 116,429 (8,100+ newly diagnosed cases) in the NHSII, we will examine the following specific aims: Aim 1. Determine if established fibroid risk factors (e.g., parity, age at menarche, smoking, body size), which differ in prevalence or timing between Black and White women, contribute to racial disparities in the risk of uterine fibroids. We will calculate race-specific population attributable fractions to identify the proportion of fibroids cases that are attributable to each risk factor and summarize the impact of differences in the distribution of fibroids risk factors by race on fibroids incidence using a novel average odds ratio method. Aim 2. Determine if environmental and neighborhood-level factors, including structural racism, contribute to the racial disparities in the risk of uterine fibroids. Aim 3. Estimate the contribution of multiple factors simultaneously to the fibroids incidence disparity between Black and White women using multiple mediation analysis. Factors to be considered for inclusion into the mediation models include reproductive, lifestyle, psychosocial, and environmental factors, and measures of structural racism. Given that more than 25% of women experience fibroids, the potential health and economic impact of this novel study is substantial. Black women suffer disproportionately from fibroids, but the reasons for this disparity are not understood. The identification factors that contribute to the racial disparity in fibroid incidence could lay the groundwork for identifying strategies that would reduce fibroid incidence, particula...