BACKGROUND: Ethylene oxide (EO) is an environmental chemical widely used in industry and has been related to various conditions such as dyslipidemia and metabolic syndrome. However, it is not clear what effect EO has on sex hormones. This paper aims to investigate the connection between EO exposure and sex hormones. METHODS: EO exposure was assessed by measuring blood levels of hemoglobin adducts of EO (HbEO). Based on the National Health and Nutrition Examination Survey (NHANES) 2013-2016 dataset, we assessed linear and nonlinear associations between HbEO and sex hormone levels using weighted multivariate linear regression analyses and weighted generalized additive modeling approaches. We further calculated the threshold effect using a two-piecewise linear regression model. In addition, we performed subgroup analyses. RESULTS: In men, HbEO levels showed a U-shaped relationship with total testosterone (TT) and sex hormone binding globulin (SHBG), with inflection points ln(HbEO) (natural logarithmic transformed value of HbEO) of 4.12 and 3.78 pmol/g Hb, respectively. HbEO levels in women showed an inverted U-shaped relationship with TT, with an inflection point ln(HbEO) of 4.54 pmol/g Hb. However, to the right of the inflection point, the relationship between HbEO and TT was not statistically significant (β = -0.09, 95%CI -0.21, 0.03). Female HbEO levels were negatively correlated with estradiol (β = -0.11, 95%CI -0.19, -0.03). In addition, we found a positive correlation between HbEO and SHBG in women with a body mass index (BMI) <
25 (β = 0.12, 95%CI 0.04, 0.20, P for interaction = 0.007). CONCLUSIONS: EO exposure leads to altered sex hormone levels in the general US population, and further research is required in the future to validate our findings.