Toxic metals and trace elements, markers of inflammation, and hyperandrogenemia in women and testosterone deficiency in men: Associations and potential mediating factors

There is evidence suggesting that toxic metal and trace element exposure disrupts androgen levels. However, specific effects of such exposure on hyperandrogenemia (HA) in women and testosterone deficiency (TD) in men remain unclear. The study investigated associations between toxic metal and trace element exposure and HA in women and TD in men, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016, and included 2205 women and 2621 men. Single-exposure analyses found lead (Pb) (adjusted odds ratio [aOR] 1.19, 95 % confidence interval [CI] 1.04-1.36) and cadmium (Cd) (aOR 1.20, 95 % CI 1.03-1.39) were positively associated with HA, especially strong in women over the age of 35. Manganese (Mn) was positively associated with TD (aOR 1.15, 95 % CI 1.03-1.28), especially strong in men aged between 45 and 50 years and obese men. A grouped weighted quantile sum (GWQS) model was performed to assess the effects of combined exposure, and found toxic metal mixture was positively associated with HA, particularly Cd (0.59) and Pb (0.40), and trace element mixture was positively associated with TD, particularly Mn (0.78). Mediation analyses demonstrated inflammation, particularly monocyte count and alkaline phosphatase (ALP) mediated 7.5-11.76 % of the associations. These findings provide insights to inform interventions for reducing exposure.