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

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 nonusing controls (51.5 [SD: 15.3], p < 0.001, 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.

Supraphysiological testosterone levels from anabolic steroid use and reduced sensitivity to negative facial expressions in men.

RATIONALE: Anabolic-androgenic steroids (AAS) are used to improve physical performance and appearance, but have been associated with deficits in social cognitive functioning. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects. OBJECTIVES: To assess the relationship between AAS use (current/previous), AAS dependence, and the ability to recognize emotional facial expressions, and investigate the potential mediating role of hormone levels. METHODS: In total 156 male weightlifters, including those with current (n = 45) or previous (n = 34) AAS use and never-using controls (n = 77), completed a facial Emotion Recognition Task (ERT). Participants were presented with faces expressing one out of six emotions (sadness, happiness, fear, anger, disgust, and surprise) and were instructed to indicate which of the six emotions each face displayed. ERT accuracy and response time were recorded and evaluated for association with AAS use status, AAS dependence, and serum reproductive hormone levels. Mediation models were used to evaluate the mediating role of androgens in the relationship between AAS use and ERT performance. RESULTS: Compared to never-using controls, men currently using AAS exhibited lower recognition accuracy for facial emotional expressions, particularly anger (Cohen's d = -0.57, pFDR = 0.03) and disgust (d = -0.51, pFDR = 0.05). Those with AAS dependence (n = 47) demonstrated worse recognition of fear relative to men without dependence (d = 0.58, p = 0.03). Recognition of disgust was negatively correlated with serum free testosterone index (FTI); however, FTI did not significantly mediate the association between AAS use and recognition of disgust. CONCLUSIONS: Our findings demonstrate impaired facial emotion recognition among men currently using AAS compared to controls. While further studies are needed to investigate potential mechanisms, our analysis did not support a simple mediation effect of serum FTI.

Severe biventricular cardiomyopathy in both current and former long-term users of anabolic-androgenic steroids.

AIMS: This study aims to explore the cardiovascular effects of long-term anabolic-androgenic steroid (AAS) use in both current and former weightlifting AAS users and estimate the occurrence of severe reduced myocardial function and the impact of duration and amount of AAS. METHODS AND RESULTS: In this cross-sectional study, 101 weightlifting AAS users with at least 1 year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use) were compared with 71 non-using weightlifting controls (WLC) using clinical data and echocardiography. Sixty-nine were current, 30 former (>1 year since quitted), and 2 AAS users were not available for this classification. Anabolic-androgenic users had higher left ventricular mass index (LVMI) (106 ± 26 vs. 80 ± 15 g/m2, P < 0.001), worse left ventricular ejection fraction (LVEF) (49 ±7 vs. 59 ± 5%, P < 0.001) and right ventricular global longitudinal strain (-17.3 ± 3.5 vs. -22.8 ± 2.0%, P < 0.001), and higher systolic blood pressure (141 ± 17 vs. 133 ± 11 mmHg, P < 0.001) compared with WLC. In current users, accumulated duration of AAS use was 12 ± 7 years and in former 9 ± 6 years (quitted 6 ± 6 years earlier). Compared with WLC, LVMI and LVEF were pathological in current and former users (P < 0.05) with equal distribution of severely reduced myocardial function (LVEF ≤40%) (11 vs. 10%, not significant (NS)). In current users, estimated lifetime AAS dose correlated with reduced LVEF and LVGLS, P < 0.05, but not with LVMI, P = 0.12. Regression analyses of the total population showed that the strongest determinant of reduced LVEF was not coexisting strength training or hypertension but history of AAS use (ß -0.53, P < 0.001). CONCLUSION: Long-term AAS users showed severely biventricular cardiomyopathy. The reduced systolic function was also found upon discontinued use.

In this, to date, largest cardiovascular study comparing 101 weightlifting long-term anabolic­androgenic steroid (AAS) users (11 ± 7 accumulated years of AAS use), with 71 weightlifting controls, we conclude that non-medical use of AAS is associated with adverse cardiovascular effects including enlarged heart muscle, seriously reduced heart function, and increased blood pressure. Both current and former users with accumulated years of AAS use of respectively 12 ± 7 years and 9 ± 6 years (former quitted 6 ± 6 years earlier) had biventricular cardiomyopathy with severely affected left and right myocardium. Of note, 11% of AAS users (10% of current and 11% of former) had severely reduced left ventricular systolic function with ejection fraction < 40%, consistent with heart failure.Regression analyses of the total population showed that the strongest determinant of reduced left ventricle ejection fraction was not coexisting strength training or hypertension but history of AAS use (ß −0.53, P < 0.001).

Psychopathology among anabolic-androgenic steroid using and non-using female athletes in Norway.

Anabolic-androgenic steroids (AAS) are primarily used to improve physical appearance and increase lean muscle mass. Due to their masculinizing properties, the majority of people using AAS are men; however, AAS use among females may increase with changing body ideals trending towards a more muscular appearance. AAS use among males have been associated with risk-taking behavior, and increased prevalence of personality disorders and psychopathology. As a result of low perceived prevalence and stigma among females who use AAS, the relationship between AAS use and psychopathology in this population is not well-known. AAS using women (n = 16) and weight-lifting controls (WLC) (n = 16) completed questionnaires regarding AAS use, health and training information. Psychopathology was evaluated using the Millon Clinical Multiaxial Inventory-III (MCMI-III). Group differences on demographic variables and scores on MCMI-III scales were evaluated with Mann-Whitney U tests. The clinical cut-off was then applied to all MCMI-III scales and groups were compared using Fisher's exact test. AAS consumers demonstrated significantly greater psychopathology than WLC on several scales. Externalizing personality disorder scales were elevated among those who use AAS relative to controls, such as borderline (p < 0.001), antisocial (p = 0.007) and sadistic (p = 0.002), and in addition depressive (p = 0.012), negativistic (p = 0.001) and masochistic (p = 0.029) personality disorders scales. Furthermore, all clinical syndromes were elevated among AAS consumers. AAS consumers thus demonstrated multi-pathology, and 56% (n = 9) of the group met the clinical criteria for six or more disorders. Females who use AAS experience in general increased levels of psychopathology compared to WLC. Clinicians should be aware of these traits and the challenges they present in providing care to this population.

Long-term Anabolic-Androgenic Steroid Use Is Associated With Deviant Brain Aging.

BACKGROUND: High-dose long-term use of anabolic-androgenic steroids (AASs) 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 magnetic resonance imaging (3D MPRAGE [magnetization-prepared rapid acquisition gradient-echo]) scans were obtained from male weightlifters with a history of prolonged AAS use (n = 130) or no AAS use (n = 99). We trained machine learning models on combinations of regional brain volumes, cortical thickness, and surface area in an independent training set of 1838 healthy male subjects (18-92 years of age) and predicted brain age for each participant in our study. Including cross-sectional and longitudinal (mean interval = 3.5 years, n = 76) magnetic resonance imaging data, we used linear mixed-effects models to compare the gap between chronological age and predicted brain age (the brain age gap [BAG]) for 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 with weightlifting control subjects, 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 AASs.

Inter-individual variation of the urinary steroid profiles in Swedish and Norwegian athletes.

The steroidal module of the Athlete Biological Passport (ABP) aims to detect doping with endogenous steroids, e.g. testosterone (T), by longitudinally monitoring several biomarkers. These biomarkers are ratios combined into urinary concentrations of testosterone and metabolically related steroids. However, it is evident after 5 years of monitoring steroid passports that there are large variations in the steroid ratios complicating its interpretation. In this study, we used over 11000 urinary steroid profiles from Swedish and Norwegian athletes to determine both the inter- and intra-individual variations of all steroids and ratios in the steroidal passport. Furthermore, we investigated if the inter-individual variations could be associated with factors such as gender, type of sport, age, time of day, time of year, and if the urine was collected in or out of competition. We show that there are factors reported in today's doping tests that significantly affect the steroid profiles. The factors with the largest influence on the steroid profile were the type of sport classification that the athlete belonged to as well as whether the urine was collected in or out of competition. There were also significant differences based on what time of day and time of year the urine sample was collected. Whether these significant changes are relevant when longitudinally monitoring athletes in the steroidal module of the ABP should be evaluated further.

Brain connectivity aberrations in anabolic-androgenic steroid users.

Sustained anabolic-androgenic steroid (AAS) use has adverse behavioral consequences, including aggression, violence and impulsivity. Candidate mechanisms include disruptions of brain networks with high concentrations of androgen receptors and critically involved in emotional and cognitive regulation. Here, we tested the effects of AAS on resting-state functional brain connectivity in the largest sample of AAS-users to date. We collected resting-state functional magnetic resonance imaging (fMRI) data from 151 males engaged in heavy resistance strength training. 50 users tested positive for AAS based on the testosterone to epitestosterone (T/E) ratio and doping substances in urine. 16 previous users and 59 controls tested negative. We estimated brain network nodes and their time-series using ICA and dual regression and defined connectivity matrices as the between-node partial correlations. In line with the emotional and behavioral consequences of AAS, current users exhibited reduced functional connectivity between key nodes involved in emotional and cognitive regulation, in particular reduced connectivity between the amygdala and default-mode network (DMN) and between the dorsal attention network (DAN) and a frontal node encompassing the superior and inferior frontal gyri (SFG/IFG) and the anterior cingulate cortex (ACC), with further reductions as a function of dependency, lifetime exposure, and cycle state (on/off).

Structural Brain Imaging of Long-Term Anabolic-Androgenic Steroid Users and Nonusing Weightlifters.

BACKGROUND: Prolonged high-dose anabolic-androgenic steroid (AAS) use has been associated with psychiatric symptoms and cognitive deficits, yet we have almost no knowledge of the long-term consequences of AAS use on the brain. The purpose of this study is to investigate the association between long-term AAS exposure and brain morphometry, including subcortical neuroanatomical volumes and regional cortical thickness. METHODS: Male AAS users and weightlifters with no experience with AASs or any other equivalent doping substances underwent structural magnetic resonance imaging scans of the brain. The current paper is based upon high-resolution structural T1-weighted images from 82 current or past AAS users exceeding 1 year of cumulative AAS use and 68 non-AAS-using weightlifters. Images were processed with the FreeSurfer software to compare neuroanatomical volumes and cerebral cortical thickness between the groups. RESULTS: Compared to non-AAS-using weightlifters, the AAS group had thinner cortex in widespread regions and significantly smaller neuroanatomical volumes, including total gray matter, cerebral cortex, and putamen. Both volumetric and thickness effects remained relatively stable across different AAS subsamples comprising various degrees of exposure to AASs and also when excluding participants with previous and current non-AAS drug abuse. The effects could not be explained by differences in verbal IQ, intracranial volume, anxiety/depression, or attention or behavioral problems. CONCLUSIONS: This large-scale systematic investigation of AAS use on brain structure shows negative correlations between AAS use and brain volume and cortical thickness. Although the findings are correlational, they may serve to raise concern about the long-term consequences of AAS use on structural features of the brain.

Black market products confiscated in Norway 2011-2014 compared to analytical findings in urine samples.

Doping agents are widely and illicitly distributed through the Internet. Analysis of these preparations is useful in order to monitor the availability of prohibited substances on the market, and more importantly to predict which substances are expected to be found in urine samples collected from athletes and to aid clinical and forensic investigations. Based on a close collaboration with the Norwegian police and the Norwegian custom authorities, the Norwegian Doping Control Laboratory has performed analyses of confiscated material suspected of containing doping agents. The analyses were performed using gas chromatography (GC) and liquid chromatography (LC) combined with mass spectrometry (MS). The majority (67%) of the analyzed black market products contained anabolic- androgenic steroids (AAS) as expected, whereas peptide- and protein-based doping substances were identified in 28% of the preparations. The Norwegian Doping Control Laboratory receives samples collected from recreational and elite athletes in addition to samples collected in clinical and forensic investigations. The findings in the seized material reflected the findings in the urine samples analyzed regarding the anabolic steroids. Thus, analyzing material seized in Norway may give a good indication of doping agents available on the local market.