Thursday, November 21, 2024
11/21/2024
ABSTRACT Uterine leiomyomata (UL), or fibroids, are neoplasms of the myometrium that are associated with heavy menstrual bleeding, anemia, pelvic pain, infertility, and complications of pregnancy and delivery. In the United States (U.S.), UL are diagnosed in 25%-30% of reproductive-aged females and they are the leading indication for hysterectomy. Black women are disproportionately affected by UL, experiencing greater incidence, earlier age at first diagnosis and surgery, and greater disease severity on average than White women. Factors associated with UL incidence, growth, and symptom severity are poorly understood. Not all UL patients experience the same symptoms, and the relation of UL characteristics (e.g., size, number, location) with symptom severity and quality of life has not been well studied. Since its inception in 2010, the NIEHS-funded Study of Environment, Lifestyle and Fibroids (SELF) has carried out nearly 8,000 clinic visits during a 10-year period among >1600 Black females living in the Detroit area with the goal of defining the natural history of UL and identifying risk factors for UL incidence and growth (R01ES028235: funding completed 8/2022). This cohort of minority participants who are underrepresented in scientific research has >85% retention during approximately 10 years of follow-up. Data from SELF participants have already produced 58 peer reviewed publications. The present R01 renewal application will extend the follow-up of the cohort for another 5 years (incident period: 15 years) with an additional (6th) clinic visit, which will again involve performing transvaginal ultrasounds to map and measure UL among new and existing cases, collect biospecimens, and gather detailed covariate data via interview. These new data, combined with data from both completed and soon to be completed analyses of biological samples from prior SELF study visits, will be used to achieve the following specific aims: 1) Describe changes in UL incidence and characteristics (size, number, location) during a 15-year period; 2) Determine the relationship between UL characteristics and UL symptom severity as ascertained by the UFS-QOL, a validated UL-specific quality of life questionnaire; and 3) Build on our previous work by evaluating a broader set of biomarkers of environmental chemicals and/or their metabolites in blood and urine from targeted panels (e.g., heavy metals, PCBs, PFAS, PBDEs, phthalates, phenols) and untargeted metabolomics to identify exposures associated with UL incidence and growth during a longer incident period (up to 15 years). We will use flexible approaches to evaluate non-linearity and assess interaction between exposures. As SELF participants were ages 23-35 years at enrollment and are nearing peak age of UL incidence (40-45 years), the ongoing study of cohort members is extremely valuable. With its prospective study design, serial ultrasounds, repeated collection of data on exposures and covariates, interdisciplinary research team, and inclusion of a highly-engaged study population, the SELF cohort is ideal for defining the natural history of UL and the environmental factors that influence it in a population disproportionately affected by the condition.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
