Association of Intrauterine and Early-Life Exposures with Diagnosis of Uterine Leiomyomata by 35 Years of Age in the Sister Study

BACKGROUND: Early-life exposures to hormonally active compounds and other factors may affect later response to estrogen or progesterone and hence may influence development of uterine leiomyomata (fibroids). OBJECTIVES: We evaluated associations of in utero and early-life exposures, including soy formula, with self-report of physician-diagnosed fibroids by 35 years of age. METHODS: Our study included 19,972 non-Hispanic white women who were 35–59 years of age when they enrolled in the Sister Study in 2003–2007. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using log-binomial regression models for fibroid associations with adjustment for participant’s age and education, maternal age at participant’s birth, birth order, and childhood family income. RESULTS: Greater risk of early fibroid diagnosis was associated with soy formula during infancy (RR = 1.25; 95% CI, 0.97–1.61), maternal prepregnancy diabetes (RR = 2.05; 95% CI, 1.16–3.63), low childhood socioeconomic status (RR = 1.28; 95% CI, 1.01–1.63), and gestational age at birth (RR = 1.64; 95% CI, 1.27–2.13, for being born at least 1 month early). In utero diethylstilbestrol (DES) exposure was also associated with early fibroid diagnosis (RR = 1.42; 95% CI, 1.13–1.80), but this association was driven by women reporting probable rather than definite exposure. CONCLUSIONS: There are plausible biological pathways by which these early-life factors could promote fibroid pathogenesis. This is the first epidemiologic study to evaluate such exposures, with the exception of in utero DES, in relation to fibroid risk, and replication of findings in other populations is needed.