Occupation Associated with Altered Steroid Hormone Metabolism in Men: A Cross-Sectional Metabolome-Wide Association Study

Objectives. This exploratory study aims to characterize metabolic distinctions among men in crafts and labor occupations hypothesized to underlie the shared risk of chronic diseases observed among occupational groups historically referred to as blue collar. Methods. Using high-resolution mass spectrometry, we characterized the serum metabolome of 220 men (n = 98 vs. 122, craftsmen and laborers vs. others) enrolled in the founding generation (1959–1967) of the Child Health and Development Studies. Metabolic changes associated with occupation were identified using Student’s t-tests and multivariable linear regression models, followed by pathway enrichment analysis. Results. Alterations in steroid hormone metabolism were consistently found among craftsmen and laborers. The abundance of C21-steroids, such as tetrahydrocorticosterone, were increased in craftsmen and laborers, whereas C19-steroids, including androstenedione, testosterone, and 5-dihydrotestosterone, were reduced. Alteration of energy metabolism was also evidenced by reductions in acylcarnitines. In addition, several metabolic pathways such as androgen synthesis, carnitine shuttle, and bile acid synthesis showed BMI-dependent differences. Conclusion . Alterations in steroidogenesis and energy metabolism observed in serum samples from male craftsmen and laborers offer insights into the biological pathways that may contribute to increased health risks in both these workers and their offspring. These findings provide a framework for elucidating shared metabolic responses associated with a suite of occupational conditions characteristic of craftsmen and laborers.