Fluoride mediated disruption of sex steroid hormones has been demonstrated in animals. However, evidence from humans was limited and contradictory, especially for children and adolescents. Based on data of the National Health and Nutrition Survey (NHANES) 2013-2016, a total of 3392 subjects aged 6-19 years were analyzed in this cross-sectional study. Both plasma and water fluoride levels were quantified electrometrically using the ion-specific electrode. Sex steroid hormones of total testosterone, estradiol and sex hormone-binding globulin (SHBG) were tested in serum. Percent changes and 95% confidence intervals (CIs) in sex steroid hormones associated with tertiles of fluoride levels (setting the first as reference) were estimated using adjusted linear regression models by stratification of gender and age. Compared with subjects at the first tertile of plasma fluoride, percent changes (95% CIs) in testosterone were -8.08% (-17.36%, 2.25%) and -21.65% (-30.44%, -11.75%) for the second and third tertiles, respectively (P <0.001). Male adolescents at the third tertile of plasma fluoride had decreased levels of testosterone (percent change = -21.09%, 95% CIs = -36.61% to -1.77%). Similar inverse associations were also found when investigating the relationships between plasma fluoride and estradiol. Besides, the data indicated decreased levels of SHBG associated with water and plasma fluoride among the male adolescents (percent change of the third tertile = -9.39%, 95% CIs = -17.25% to -0.78%) and female children (percent change of the second tertile = -10.78%, 95% CIs = -17.55% to -3.45%), respectively. The data indicated gender- and age-specific inverse associations of fluoride in plasma and water with sex steroid hormones of total testosterone, estradiol and SHBG in U.S. children and adolescents. Prospective cohort studies are warranted to confirm the causality.
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