The association between 2,4-D and serum testosterone levels: NHANES 2013–2014

Background: Previous studies have investigated associations between herbicides such as 2,4-Dichlorophenoxyacetic acid (2,4-D) and dyshormonogenesis, specifically low testosterone, in human, rodent, and cell models, but results have been conflicting and inconclusive. Methods: Using data from a cross-sectional study of 456 adult men in the 2013–2014 NHANES survey cycle, we examined the relationship between urinary concentrations of 2,4-D and serum testosterone levels. Results: Multivariable regression models adjusting for potential confounders revealed a significant, negative association between urinary 2,4-D and mean serum testosterone among U.S. adult males (β = − 11.4 ng/dL, p = 0.02). Multivariable logistic regression models using a cutoff defining abnormally low testosterone (i.e., serum testosterone < 300 ng/dL) revealed no significant associations between 2,4-D and the odds of low testosterone. Conclusion: These findings expand on previous literature implicating a role for 2,4-D in the etiology of low testosterone and dyshormonogenesis. Future studies are warranted to corroborate these findings, determine clinical significance, and to investigate the proposed potential biological mechanisms underlying this association.