Urinary cadmium excretion is associated with increased synthesis of cortico-And sex steroids in a population study

Abstract

Context: Urinary cadmium (Cd) excretion is associated with cancer and cardiovascular morbidity. A potential mechanism could be disturbance of steroidogenesis in gonads and adrenal glands. Objective: We tested whether urinary excretion of Cd is correlated with that of cortico-And sex steroid metabolites in the general adult population. Setting: The Swiss Kidney Project on Genes in Hypertension is a multicentric, family-based population study. Measures: Urinary excretions of steroid hormone metabolites and Cd were measured with separate day and night collections. Associations were analyzed by mixed linear models. Results: Urinary Cd and testosterone excretions in men were significantly correlated (respective day and night b values [standard error (SE)], 1.378 [0.242], P<0.0005; and 1.440 [0.333], P<0.0005), but not in women [0.333(0.257), P = 0.2; and 0.674 (0.361), P = 0.06]. Urinary Cd and cortisol excretions were positively associated in both sexes [day: b = 0.475 (SE, 0.157), P = 0.0025, and 0.877 (SE, 0.194), P , 0.0005, respectively; night: b = 0.875 (SE, 0.253), P < 0.0005 and 1.183 (SE, 0.277), P = 0.00002, respectively]. Cd excretion was correlated with mineralocorticoid metabolites excretion, except tetrahydroaldosterone, in both sexes (P < 0.01). There was an independent effect of Cd on sex hormone and corticosteroid synthesis and an interdependent effect on gluco-And mineralcorticoid production. Conclusion: Our findings provide evidence for a global stimulating effect on steroid synthesis already at low-dose Cd exposure. These findings might explain the association of Cd with diseases such as steroid-sensitive cancers or metabolic disorders.