Environmental risk factors for uterine fibroids: a prospective ultrasound study

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Uterine leiomyomata (UL), or fibroids, are the most common neoplasms of the uterus and are a major source of gynecologic morbidity. In the United States (U.S.), the lifetime risk of symptomatic UL is approximately 25- 30%. UL are the leading indication for hysterectomy, and UL-related costs exceed $34.4 billion annually. Black women are disproportionately affected by UL, with a 3-fold greater risk of diagnosis, earlier age at diagnosis and surgery, and more symptomatic tumors on average than white women. Despite the large public health burden of UL, little is known about its natural history or pathogenesis. Animal data and cross-sectional human studies have provided compelling preliminary evidence of a role for vitamin D in UL development and growth. Exposure to heavy metals such as lead, mercury, and cadmium is widespread, with reproductive-aged women, African Americans, and those of lower socioeconomic status having higher exposure levels than other groups. Funded by the National Institute of Environmental Health Sciences (NIEHS), the Study of Environment, Lifestyle and Fibroids (SELF) is a multi-year prospective cohort study of UL determinants in black women from the Detroit area. In 2011-2012, SELF enrolled 1,696 black women aged 23-34 years who had never been diagnosed with UL. At baseline and every 20 months for a total of 5 years (4 total clinic visits), SELF participants complete interviews, have blood collected for biological measurements, and undergo transvaginal ultrasounds for precise identification and mapping of UL at each visit facilitating accurate determination of UL development and growth (cohort retention >85%). The final planned clinic visits are underway. In this application, we propose to extend follow-up of SELF for an additional five years. One more clinic visit with transvaginal ultrasound, biospecimen collection and detailed exposure assessments via interview will be conducted to achieve the following specific aims: 1) Describe the natural history of UL initiation and growth; calculate age-specific UL incidence; and evaluate changes in tumor characteristics (size, number, and location) over a 10-year period; 2) Assess whether vitamin D status influences UL incidence and growth over a 10-year period; and 3) Evaluate the influence of selected environmental toxicants on UL incidence and growth. Specifically, we will examine the influence of active and passive cigarette smoking on UL incidence and growth; assess exposure to a panel of 13 metals and metalloids (and their mixtures) measured in whole blood and UL incidence and growth over a 10-year period; and determine whether vitamin D status modifies the associations between environmental toxicants and UL incidence. With its prospective design, population of young black women, serial ultrasounds, repeated collection of data on exposures and covariates, and careful analysis of chemical mixtures, SELF is ideal for identifying environmental risk factors for UL. Using methods that overcome the limitations of prior studies, this will be the most definitive study of modifiable environmental risk factors of UL and is likely to have high impact on science, clinical care, and public health policy.