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 9472 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 adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys.
Highlights
Men have higher circulating levels of uric acid than women
Using data from a large representative US cohort, this study found that neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescents or adults from a general US population after full adjustment
It found that the sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys
Summary
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. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. All three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. If estradiol decreases uric acid levels under physiological conditions, estradiol is expected to be inversely associated with circulating uric acid in a general population. This study aimed to test this hypothesis using a representative US cohort of adolescents and adults who attended the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016
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