Cannabis consumption is associated with altered steroid metabolism in young men

BACKGROUND: Cannabis use has been hypothesized to alter endocrine function. We aimed at investigating this hypothesis through extended steroid profiling in young men. METHODS: Using liquid chromatography - tandem mass spectrometry (LC-MS/MS), 70 endogenous steroids were reliably identified in serum samples from 47 cannabis consumers and 47 controls. Seven major steroids were subject to absolute quantification, while the others were considered as relative concentrations. RESULTS: This cross-sectional study shows a global increase in androgen levels among cannabis consumers. Androstenedione (A4), testosterone (T), and dihydrotestosterone (DHT) are among the most significantly increased steroids. In contrast, C11-oxy androgens show no significant change upon cannabis use. This pattern suggests that phytocannabinoids might selectively affect gonadal androgen synthesis without altering adrenal or peripheral pathways, possibly via direct effects on the testes, or disruption of the hypothalamic-pituitary-gonadal (HPG) axis function. Additionally, two progesterone metabolites, 11β-hydroxyprogesterone (11β-OHP4) and 5β-dihydroprogesterone (5β-DHP4), are markedly elevated in cannabis consumers. When the cannabis user group is stratified according to the corresponding usage biomarkers, 11β-OHP4 proves to be a biomarker of general exposure, whereas 5β-DHP4 displays a dose-dependent relationship. CONCLUSIONS: These findings highlight the value of extended steroid profiling for investigating hormonal variations and evidence a possible link between cannabis consumption and altered male endocrine function.