Introduction: We have recently described relationships between environmental contaminants (ECs) and sex-hormones in the elderly. The present study investigates whether blood concentrations of four classes of ECs also associated with concentrations of five adrenal steroids (AS), cortisol and its four precursors.

Methods: Plasma samples from participants of the cross-sectional population-based Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 70-year-old men and women, n = 950) were analyzed using validated mass spectrometry-based methods for four AS: pregnenolone (Pregn), 17 hydroxy Pregn (17OH-Pregn), 17 hydroxy progesterone (17OH-Prog), 11 deoxycortisol; 21 persistent organic pollutants (POP); 8 perfluoroalkyl substances (PFAS); 4 phthalates and 10 metals. Cortisol was analyzed using competitive ELISA.

Results: Results of this study provide evidence that ECs of all evaluated classes were related to AS concentrations in a complex manner, suggesting structure-activity relationships influencing AS biosynthesis. Among the steroids analyzed, Pregn exhibited the strongest associations with ECs concentrations, while cortisol was the least affected. The most pronounced relationships with Pregn, 17OH-Prog, and 17OH-Pregn were observed with highly chlorinated PCBs, all analyzed phthalates, and metals, aluminum, cadmium, copper, mercury and nickel. These associations were generally consistent between men and women, although stronger associations between the ECs and Pregn, 17OH-Pregn, and 17OH-Prog were observed in women. Multivariable regression models further revealed several non-linear relationships between ECs and AS concentrations.

Conclusions: Our data suggest that in elderly, concentrations of many ECs are associated with concentrations of AS of cortisol pathway. The impact of such relationships on diseases associated with AS biosynthesis remains to be established.