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Background: Organochlorine pesticides are detectable in serum from most adults. Animal studies provide evidence of pesticide effects on sex hormones, suggesting that exposures may impact human reproductive function. Mounting evidence of sex differences in chronic diseases suggest that perturbations in endogenous sex hormones may influence disease risk. However, the association between organochlorine pesticide exposure and sex hormone levels in males across the lifespan is not well understood.Methods: We evaluated cross-sectional associations of lipid-adjusted serum concentrations of β-hexachlorocyclohexane, hexachlorobenzene, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethylene (DDE), p,p'-dichlorodiphenyltrichloroethane (DDT), trans-nonachlor, and mirex in relation to sex steroid hormone levels [testosterone (ng/dL), sex hormone binding globulin (SHBG; nmol/L), estradiol (pg/mL), and androstanediol glucuronide (ng/dL)] in a sample of 748 males aged 20 years and older from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression models were performed to estimate geometric means (GM) and their 95% confidence intervals (CIs) for quartiles of lipid-adjusted pesticide concentrations, adjusting for age, race, body mass index, serum lipids, smoking, education, and survey cycle.Results: Hexachlorobenzene concentration was positively associated with total estradiol (GM Q4 = 43.2 pg/mL (95% CI 36.5-51.1) vs. Q1 GM = 25.6 pg/mL (24.1-27.3), p-trend <0.0001) and free estradiol (GM Q4 = 0.77 pg/mL (95% CI 0.64-0.93) vs. Q1 GM = 0.47 pg/mL (0.44-0.51), p-trend = 0.002). Serum DDT concentration was positively associated with total estradiol (GM Q4 = 31.6 pg/mL (95% CI 25.9-38.5) vs. Q1 GM = 27.3 pg/mL (25.9-28.7), p-trend = 0.05) and free estradiol (GM Q4 = 0.60 pg/mL (95% CI 0.48-0.76) vs. Q1 GM = 0.50 pg/mL (0.47-0.53), p-trend 0.02). There was a suggestive inverse association of DDT and SHBG (GM Q4 = 29.2 nmol/L (95% CI 23.8-35.9) vs. Q1 GM = 33.9 nmol/L (32.3-35.5), p-trend 0.07). A positive association of β-hexachlorocyclohexane with total estradiol (GM Q4 = 30.3 pg/mL (95% CI 26.5-34.6) vs. Q1 GM = 26.7 pg/mL (24.5-29.0), p-trend = 0.09) was also suggestive but did not reach statistical significance. No distinct associations were observed for other hormone levels or other organochlorine pesticides.Conclusions: Our findings suggest that select organochlorine pesticides may alter male estradiol levels. The positive associations with estradiol may implicate sex hormones as a possible mechanism for disease risk among those with organochlorine pesticide exposure. [ABSTRACT FROM AUTHOR]