Background: Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk. Methods: The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race–ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium. Results: Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03–40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53–37.14); P trend ¼ 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92–1.01) vs. Q4, 0.90 (95% CI, 0.85–0.95); P trend ¼ 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (P interaction ¼ 0.073) and those with limited alcohol intake (P interaction ¼ 0.017). No associations were observed for the other sex steroid hormones studied. Conclusions: Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen. Impact: Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed.
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