Association of blood metals with serum sex hormones in adults: A cross-sectional study

Heavy metals such as lead, mercury, and cadmium have been identified to have negative impacts on human health. Although the individual effects of these metals have been extensively researched, the present study aims to explore their combined effects and their association with serum sex hormones among adults. Data for this study were obtained from the general adult population of the 2013-2016 National Health and Nutrition Survey (NHANES) and included five metal (mercury, cadmium, manganese, lead, and selenium) exposures and three sex hormones (total testosterone [TT], estradiol [E2], and sex hormone-binding globulin [SHBG]) levels. The free androgen index (FAI) and TT/E2 ratio were also calculated. The relationships between blood metals and serum sex hormones were analysed using linear regression and restricted cubic spline regression. The effect of blood metal mixtures on sex hormone levels was examined using the quantile g-computation (qgcomp) model. There were 3,499 participants in this study, including 1,940 males and 1,559 females. In males, positive relationships between blood cadmium and serum SHBG (β=0.049 [0.006, 0.093]), lead and SHBG (β=0.040 [0.002, 0.079]), manganese and FAI (β=0.080 [0.016, 0.144]), and selenium and FAI (β=0.278 [0.054, 0.502]) were observed. In contrast, manganese and SHBG (β=-0.137 [-0.237, -0.037]), selenium and SHBG (β=-0.281 [-0.533, -0.028]), and manganese and TT/E2 ratio (β=-0.094 [-0.158, -0.029]) were negative associations. In females, blood cadmium and serum TT (β=0.082 [0.023, 0.141]), manganese and E2 (β=0.282 [0.072, 0.493]), cadmium and SHBG (β=0.146 [0.089, 0.203]), lead and SHBG (β=0.163 [0.095, 0.231]), and lead and TT/E2 ratio (β=0.174 [0.056, 0.292]) were positive relationships, while lead and E2 (β=-0.168 [-0.315, -0.021]) and FAI (β=-0.157 [-0.228, -0.086]) were negative associations. This correlation was stronger among elderly women (>50 years old). The qgcomp analysis revealed that the positive effect of mixed metals on SHBG was mainly driven by cadmium, while the negative effect of mixed metals on FAI was mainly driven by lead. Our findings indicate that exposure to heavy metals may disrupt hormonal homeostasis in adults, particularly in older women.