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 bring a range of health consequences, 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 brain MRI data were obtained from male weightlifters with a history of prolonged (n=133) or no (n=105) 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 aged 18-92 years and predicted brain age for each participant in our study. We used linear models to compare the gap between chronological age and predicted brain age (the brain age gap, BAG) between the two groups, and, in a subsample with longitudinal data (mean interval 3.5 years), tested for group differences in the change rate of BAG. Moreover, we tested for associations between apparent brain aging and AAS use duration, administration pattern and dependence. Results AAS users had higher BAG compared to weightlifting controls with strongest effects for frontal and insular regions. Higher BAG was associated with current AAS use, dependency, and longer history of AAS use. Group differences in BAG could not be explained by substance use, general cognitive abilities or depression. Longitudinal data revealed no group difference in the rate of BAG change. Conclusions The findings suggest that long-term high dose AAS use may have adverse effects on brain aging, potentially linked to current and exaggerated use of AAS.

Use of High-Dose Androgens Is Associated with Reduced Brain-Derived Neurotrophic Factor in Male Weightlifters

“…Accumulating evidence suggests that long-term steroid use may have harmful consequences for the brain, cognition [26,30,[35][36][37], and mental health [38]. These effects are thought to be mediated through reduced neurotrophic support to specific brain regions.…”

“…The present study consisted of 141 adult male weightlifters, including current ( n = 59) and past ( n = 30) androgen users and weightlifting controls (WLC, n = 52). Data were derived from a longitudinal study of the brain, medical and mental health consequences of long-term androgen use [26] at Oslo University Hospital. Inclusion criteria for androgen users were previous or current androgen use corresponding to at least 1 year of cumulative androgen use (summarizing on-cycle periods).…”

“…Urine samples were collected and analyzed for external use of androgens using gas and liquid chromatography coupled to mass spectrometry at the WADA-accredited Norwegian Doping Laboratory at Oslo University Hospital [29]. The criteria used to determine external androgen use were (1) urine samples positive for synthetic testosterone compounds (2) a testosterone to epitestosterone ratio (T/E) >15 equivalent to previous work [26, 29, 30].…”

Use of high-dose androgens is associated with reduced brain derived neurotrophic factor in male weightlifters

“…Accumulating evidence suggests that long-term steroid use may have harmful consequences for brain, cognition [35,30,36,26,37] and mental health [38]. These effects are thought to be mediated through reduced neurotrophic support to specific brain regions.…”

“…Urine samples were collected and analyzed for external use of androgens using gas and liquid chromatography coupled to mass spectrometry at the WADA accredited Norwegian Doping Laboratory at Oslo University Hospital [29]. The criteria used to determine external androgen use were: 1) urine samples positive for synthetic testosterone compounds 2) a testosterone to epitestosterone ration (T/E) > 15 equivalent to previous work [29,30,26].…”