Erectile dysfunction (ED) poses a significant disease morbidity and contributor to male infertility, where an estimated 20-40% of men are affected annually. While several risk factors have been identified in the etiology of ED (e.g., aging, heart disease, diabetes, and obesity), the complete pathogenesis remains to be elucidated. Over the last few decades, the contribution of environmental exposures to the pathogenesis of ED has gained some attention, though population studies are limited and results are mixed. Among environmental contaminants, organophosphate (OP) insecticides represent one of the largest chemical classes, and chlorpyrifos is the most commonly used OP in the U.S. OP exposure has been implicated in driving biological processes, including inflammation, reactive oxygen species production, and endocrine and metabolism disruption, which have been demonstrated to adversely affect the hypothalamus and testes and may contribute to ED. Currently, studies evaluating the association between OPs and ED within the U.S. general population are sparse.
Data were leveraged from the National Health and Nutrition Examination Survey (NHANES), which is an annually conducted, population-based cross-sectional study. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of the most pervasive OP insecticide chlorpyrifos, were quantified as measures of OP exposure. ED was defined by responses to questionnaire data, where individuals who replied “sometimes able” or “never able” to achieve an erection were classified as ED. Chi-square, analysis of variance (ANOVA), and multivariable, weighted linear and logistic regression analyses were used to compare sociodemographic variables between quartiles of TCPy exposure, identify risk factors for TCPy exposure and ED, and to analyze the relationship between TCPy and ED.
A total of 671 adult men were included in final analyses, representing 28,949,379 adults after survey weighting. Approximately 37% of our cohort had ED. Smoking, diabetes, aging, Mexican-American self-identification, and physical inactivity were associated with higher ED prevalence. Analysis of TCPy modeled as a continuous variable revealed nonsignificant associations with ED (OR = 1.02 95% CI [0.95, 1.09]). Stratification of total TCPy into quartiles revealed increased odds of ED among adults in the second and fourth quartiles, using the first quartile as the reference (OR = 2.04 95% CI [1.11, 3.72], OR = 1.51 95% CI [0.58, 3.93], OR = 2.62 95% CI [1.18, 5.79], for quartiles 2, 3, and 4, respectively).
The results of our study suggest a potential role for chlorpyrifos and other OPs the pathogenesis of ED. Future studies are warranted to validate these findings, determine clinical significance, and to investigate potential mechanisms underlying these associations.

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