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Introduction: Use of high-dose androgens causes drastic changes in hormonal milieu and is associated with adverse medical, psychological, and cognitive effects. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors plays a critical role in neuroplasticity, with implications for cognitive function and mental health. The impact of long-term, high-dose androgen use on BDNF in a natural setting has not been investigated. This study examined the association between long-term androgen exposure and BDNF levels, and the links between BDNF, heavy resistance exercise, hormones, androgens and mental health. Methods: We measured serum levels of BDNF and sex steroid hormones in male weightlifters (N=141) with a history of current (n=59), past (n=29) or no (n=52) androgen use. All participants completed questionnaires assessing maximum strength and measures of anxiety and depression. Group differences in BDNF were tested using general linear models adjusting for age, and associations between BDNF and strength, anxiety and depression using Pearson’s or Kendall’s correlations. Results: Both current (mean: 44.1 ng/ml (SD:12.7)) and past (39.5 ng/ml (SD:13.9)) androgen users showed lower serum BDNF levels compared to non-using controls (51.5 (SD: 15.3), p<.001, ηp²=0.10). BDNF levels were negatively related to maximal strength, and with hormonal status in past androgen users, but no significant associations were found with measures of depression and anxiety. Conclusion: Lower circulating BDNF concentrations in current and past androgen users, suggest that high-dose androgen exposure triggers persistent changes in BDNF expression. Further studies are needed to verify the relationship and its’ potential clinical implications.

Purpose of review The purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use. Recent findings Supraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems. Summary Findings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.