Independent and combined associations of urinary heavy metals exposure and serum sex hormones among adults in NHANES 2013–2016

Accumulating evidences indicated that heavy metals may disrupt human sex hormones. However, the combined effects of heavy metals on sex hormones remain to be clarified. To explore the independent and combined associations between heavy metal exposure and serum sex hormones among adults, data of 2728 adults from the National Health and Nutrition Examination Survey (NHANES) was applied. We examined independent and combined associations of fourteen urinary heavy metals and three serum sex steroid hormones (total testosterone (TT), estradiol (E2) and sex hormone-binding globulin (SHBG)). Multivariate linear regression was used to evaluate the independent associations between metal exposure and sex hormone alterations. Principle component analysis -weighted quantile sum regression (PCA-WQSR) model was performed to estimate the combined associations in our individuals. In the co-exposure model, we determined that weighted quantile sum (WQS) index of industrial pollutants was negatively associated with E2 in females (WQS Percent change₈₋ₘₑₜₐₗ = -20.6%; 95% CI: -30.1%, -9.96%), while in males WQS index of water pollutants was negatively related to SHBG (WQS Percent change₈₋ₘₑₜₐₗ = -5.35%; 95% CI: -9.88%, -0.598%). Cadmium (Cd), tin (Sn) and lead (Pb) were the dominating metals of female E2-negative association while Ba was the leading contributor related to male SHBG reduction, which was consistent with the results of multivariate linear regression. Additionally, in postmenopausal women, the associations of E2 decrease with heavy metal co-exposure remained significant while Cd and monomethylarsonic acid (MMA) were identified as hazardous metals in the mixture. We concluded that the exposure to heavy metals was associated with human sex hormone alterations in independent or combined manners. Considering the design of NHANES study, further studies from other national-representative surveys are necessary.