Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys

Abstract Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9 472 participants (weighted sample size of 184 342 210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in males or females or adolescents or adults or females around menopausal age (47–56 years). Log-transformed free testosterone was positively associated with serum uric acid in adolescent boys (β = 0.250, P < 0.001), girls (β = 0.159, P < 0.001), adult women (β = 0.131, P < 0.001) and women around menopausal age (β = 0.143, P < 0.001) after adjustment for all tested confounders. The results from bioavailable testosterone were similar to those from free testosterone. In addition, log-transformed sex hormone-binding globulin was inversely associated with serum uric acid in males (β=- 0.171, P < 0.001) and females (β=-0.181, P < 0.001) after adjustment for all tested confounders and the inverse association remained in all sub-cohorts. Moreover, sex difference in circulating uric acid was established during adolescence and this establishment coincided with a dramatic increase in testosterone and a dramatic decrease in sex hormone-binding globulin in boys. These results suggest that estradiol is not inversely associated with circulating uric acid and the establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys.