Long-term anabolic androgenic steroid use is associated with deviant brain aging

Abstract Background High-dose long-term use of anabolic-androgenic steroids (AAS) may cause a range of adverse effects, including brain and cognitive abnormalities. We performed age prediction based on brain scans to test whether prolonged AAS use is associated with accentuated brain aging. Methods T1-weighted MRI (3D MPRAGE) scans were obtained from male weightlifters with a history of prolonged (n=130) or no (n=99) AAS use. We trained machine learning models on combinations of regional brain volumes, cortical thickness and surface area in an independent training set of 1838 healthy males (18-92 years) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval 3.5 years, n=76) MRI data, we used linear mixed effects (LME) models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and tested for group differences in the rate of change in BAG. We tested for associations between apparent brain aging and AAS use duration, pattern of administration and dependence. Results AAS users had higher BAG compared to weightlifting controls, which was associated with dependency and longer history of use. Group differences in BAG could not be explained by other substance use, general cognitive abilities or depression. While longitudinal analysis revealed no evidence of increased brain aging in the overall AAS group, accelerated brain aging was seen with longer AAS exposure. Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to dependency and exaggerated use of AAS.