Associations between organochlorine pesticide mixtures and sex steroid hormones modified by age, gender and body mass index in the US 2011-2016: a quantile-based g-computation approach

BACKGROUND AND AIM: Toxicological studies have shown adverse effects of organochlorine pesticides on reproductive function in animals; however, human studies are limited and mostly on a single pesticide. This study, therefore, examined the combined effects of lipid-adjusted serum concentrations of organochlorine pesticides and sex hormones in the US and to what extent these associations vary by age, gender, and body mass index (BMI). METHODS: We have used six years of repeated cross-sectional data that consist of three consecutive National Health and Nutrition Examination Survey (NHANES) cycles from 2011 to 2016. Serum concentrations of seven organochlorine pesticides (β-hexachlorocyclohexane, hexachlorobenzene, oxychlordane, p,p'-dichlorodiphenyltrichloroethene, p,p'-dichlorodiphenyltrichlorethane, trans-Nonachlor, and Mirex) were used as mixtures. The sex hormones considered were testosterone in nmol/L (n=798), estradiol in pmol/L (n=528 in), sex hormone-binding globulin -SHBG in nmol/L (n=497), and testosterone/estradiol in pg/mL (n=528). Quantile-based g-computation method was used for mixture effects, adjusting for potential confounders, and survey design. RESULTS: Results showed that lipid-adjusted pesticide mixtures had an inverse association with testosterone (β=-1.02, 95% CI: -1.81, -0.23; p= 0.012), estradiol (β= -663.16, 95% CI: -1232.09, -94.23, p= 0.022), SHBG (β= -14.62, 95% CI: -32.00, 2.77, p=0.100) and testosterone/estradiol (β= -3.06, 95% CI: -17.41, 11.29, p= 0.676). These associations were modified by gender with higher precisions for testosterone (Male: -1.90, 95% CI: -3.46, -0.35, pint= 0.003; Female: -0.79, 95% CI: -1.60, 0.02, p= 0.003). Moreover, age and BMI also significantly modified the effects of pesticide mixtures on sex hormones with higher precision in testosterone and estradiol. CONCLUSIONS: Our study suggests that pesticide mixture is inversely associated with sex hormones in the US population aged 12-80 years old, and these associations are modified by age, gender, and BMI. Intervention should be focused on reducing pesticide mixture exposures focusing on vulnerable communities. KEYWORDS: Pesticides; Mixture; Testosterone; Hormones; Quantile g-computation