Off-label use of clomiphene citrate to treat anabolic androgenic steroid induced hypogonadism upon cessation among men (CloTASH) - A pilot study protocol.

Background: Non-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. Methods: In this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.

Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of Anabolic-Androgenic Steroids.

AIM: In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodeling and their association with hormones and echocardiographic myocardial pathology in weightlifters. METHODS: In a cross-sectional study, 93 weightlifting AAS-users, of which 62 were current and 31 were past users, with at least one-year cumulative AAS-use (mean 11±7 accumulated years of AAS-use), were compared to 54 non-using weightlifting controls (WLC) using clinical interview, blood pressure measurements, and echocardiography. RESULTS: Serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), interferon (IFN)γ, growth differentiation factor (GDF)-15 and matrix metalloproteinase (MMP-9), sex hormones and lipids were analyzed. Serum levels of IL-8, GDF-15 and MMP-9 were significantly increased in current AAS users compared to former users and WLC. MMP-9, but not IL-8, correlated consistently with sex-hormone levels, and sex-hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current versus former AAS users, in significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP9 also with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users. CONCLUSION: In conclusion, long-term AAS is associated with increased levels of markers of inflammation and extracellular matrix remodeling, which seems to have a hormone-dependent (MMP-9) and hormone-independent (IL-8) association with markers of myocardial dysfunction.

Long-term use of anabolic-androgenic steroids (AAS) can increase inflammation and mediators of extracellular matrix (ECM) remodeling which potentially could be involved in myocardial pathology seen in these individuals. AAS use increased levels of inflammatory marker IL-8 and marker of ECM remodeling MMP-9.IL-8 and MMP-9 were both associated with myocardial pathology in current, but not former users, suggesting that these markers are association with risk of myocardial damage during AAS use.

Treatment-seeking behavior and cardiovascular morbidity among men with anabolic-androgenic steroid use: A cross-sectional study.

AIMS: To determine associations between anabolic-androgenic steroid (AAS) use-related morbidity including cardiovascular disease (CVD) and engagement to health services. METHODS: In this cross-sectional study, 90 males with at least 12 months cumulative current or former use of AAS were included. The participants were divided into a treatment-seeking group (TSG) and a non-treatment seeking group (non-TSG) based on their responses to a self-report web questionnaire. All participants were screened for symptoms that could be indicative of CVD through a clinical interview, and examined with blood samples, blood pressure measurements and transthoracic echocardiography. RESULTS: In the total sample (n = 90), mean age was 39 ± 11 years with cumulative AAS use of 12 ± 9 years. Among men in the TSG with current use there were higher prevalence of dyspnoea (50% vs 7%) and reduced left ventricular ejection fraction (LVEF) in conjunction with left ventricular hypertrophy (LVH) (36 vs. 9%) and/or high blood pressure (55% vs. 19%) compared to men in the non-TSG. Among men with current AAS use and established LVEF <50% (n = 25) or LVH (n = 21), 44% (11) and 43% (9) respectively, had never engaged health services due to AAS-related adverse effects. Deviant liver- and kidney parameters were frequently observed in the total sample but without between-group differences. CONCLUSIONS: Treatment-seeking behavior among current AAS users may be associated with increased levels of dyspnoea and established CVD. Despite objective signs of severe CVD among a substantial amount of study participants, it is of great concern that the majority had never sought treatment for AAS-related concerns.

Sleep pathology and use of anabolic androgen steroids among male weightlifters in Norway.

Use of anabolic androgenic steroids (AAS) causes drastic changes in hormonal milieu and is associated with a range of medical and psychological consequences. Sleep pathology is a common side-effect of AAS use but few have studied these relations. This study examined the relationship between AAS use, psychological distress and sleep quality, and how phases of heavy use and abstinence influence sleep. The Pittsburgh-Sleep-Quality-Index (PSQI) and Jenkins Sleep Scale (JSS) were used to assess sleep quality, and psychological distress was measured with the Hopkins Symptoms Checklist (HSCL). Participants comprised men who have previous or current long-term use of AAS (n = 68) and non-using weightlifting controls (WLC) (n = 58), where a subgroup of participants (n = 22) was monitored over ~ 6 months during phases of AAS use and withdrawal. Group differences on PSQI and JSS were evaluated with Kruskal-Wallis H tests, and the mediating role of psychological distress was evaluated using structural equation modeling. Linear mixed models were used to assess the role of AAS use and withdrawal on sleep quality. Among the AAS group, 66% reported sleep problems as a side effect, and 38% had used sleep medication. PSQI scores showed significantly lower sleep quality in the AAS group compared to WLC (p < 0.001) on all subscales except "sleep latency". Furthermore, sleep quality was significantly poorer during withdrawal-phases than periods with AAS use (p < .001). Our findings provide key insight into sleep disturbances among men who use AAS, suggesting a link between sleep disturbances and hormone levels that deviate from physiologically normal levels in both directions.

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).

Prevalence and correlates of androgen dependence: a meta-analysis, meta-regression analysis and qualitative synthesis.

PURPOSE OF REVIEW: To investigate the prevalence and correlates of androgen dependence among users. A meta-analysis, meta-regression analysis, and qualitative synthesis were conducted based on a systematic literature search in Google Scholar, ISO Web of Science, PsycNET, and PubMed. RECENT FINDINGS: Twenty-six studies were included in the review and 18 studies ( N  = 1782) in the statistical analysis. The overall lifetime androgen dependence prevalence was 34.4% [95% confidence interval (CI): 27.8-41.7, Q  = 113.1, I2  = 85.0, P  < 0.001]. Although males (36.1%, P  < 0.001) and females (37.0%, P  = 0.188) did not differ ( Q  = 0.0, P  = 0.930) in dependence prevalence, controlling for other study characteristics, higher study male sample proportion was related to higher dependence prevalence. Combined interview and questionnaire assessments showed higher prevalence compared to interviews only. Publications from 1990-1999 generated higher prevalence compared to 2000-2009 and 2010-2023 publications. Dependents were associated with a wide array of demographic inequalities, and biophysical, cognitive, emotional, and psychosocial problems. SUMMARY: One of three persons who initiate androgen use experiences dependence along with various serious disorders. Androgen use and dependence should be considered an important public health issue requiring targeted health interventions.

Investigating anabolic-androgenic steroid dependence and muscle dysmorphia with network analysis among male weightlifters.

BACKGROUND: Anabolic-androgenic steroid (AAS) dependence has numerous adverse health consequences, and may be driven in part by body image concerns, primarily muscle dysmorphia. This study aims to further understand and identify potential clinical targets using network analyses of AAS dependence and muscle dysmorphia symptoms in males who used AAS and weightlifting controls. METHODS: A sample of 153 men who currently or previously used AAS and 88 weight-lifting controls were recruited through social media and relevant online forums, and via posters and flyers distributed in select gyms in Oslo, Norway. Symptoms of AAS dependence and muscle dysmorphia were assessed using clinical interviews and standardized questionnaires. Severity of muscle dysmorphia symptoms were compared between the groups using independent samples t-tests. The following symptom networks were computed using Gaussian graphical modeling or mixed graphical modeling: (1) AAS dependence symptoms among men with AAS use (2) muscle dysmorphia symptoms among men with AAS use and weight-lifting controls in two separate networks, which were compared using a network comparison test, and (3) AAS dependence and muscle dysmorphia symptoms among men with AAS use. RESULTS: In a network of AAS dependence symptoms, continuing use despite physical and mental side effects, using longer than planned, tolerance, and work/life interference were the most central symptoms. When comparing symptom structures of muscle dysmorphia between those who used AAS and controls, the most central symptoms in each group were exercise dependence and size/symmetry concerns, respectively. Men with AAS use demonstrated elevated muscle dysmorphia symptoms compared to controls, indicating that both the severity and structure of symptoms differ between these groups. In a network including both AAS dependence and muscle dysmorphia symptoms, no significant connections between symptom groups were identified. CONCLUSIONS: AAS dependence is complex, with correlated somatic and psychological challenges driving the symptom network, indicating that alleviating physical and mental health concerns during both AAS use and cessation is an important clinical target. Muscle dysmorphia symptoms related to taking action (diet, exercise, and supplement use) appear to cluster together more for those who use AAS than those who do not.

Clustering psychopathology in male anabolic-androgenic steroid users and nonusing weightlifters.

INTRODUCTION: Prior research has demonstrated that personality disorders and clinical psychiatric syndromes are common among users of anabolic-androgenic steroids (AAS). However, the prevalence, expression, and severity of psychopathology differ among AAS users and remain poorly understood. In this study, we examine the existence of potential clinically coherent psychopathology subgroups, using cluster procedures. METHODS: A sample of 118 male AAS users and 97 weightlifting nonusers was assessed using the Millon Clinical Multiaxial Inventory-III (MCMI-III), measuring personality disorders and clinical syndromes. Group differences in MCMI-III scales were assessed using Wilcoxon-Mann-Whitney tests and Fisher's exact test. Agglomerative hierarchical clustering was used to identify clusters based on MCMI-III scale scores from the whole sample. RESULTS: AAS users displayed significantly higher scores on all personality disorder (except narcissistic) and clinical syndrome scales compared to nonusing weightlifters. The clustering analysis found four separate clusters with different levels and patterns of psychopathology. The "no psychopathology" cluster was most common among nonusing weightlifters, while the three other clusters were more common among AAS users: "severe multipathology," "low multipathology," and "mild externalizing." The "severe multipathology" cluster was found almost exclusively among AAS users. AAS users also displayed the highest scores on drug and alcohol dependence syndromes. CONCLUSIONS: AAS users in our sample demonstrated greater psychopathology than the nonusing weightlifters, with many exhibiting multipathology. This may pose a significant challenge to clinical care for AAS users, particularly as there appears to be significant variation in psychopathology in this population. Individual psychiatric profiles should be taken into consideration when providing treatment to this group. SIGNIFICANT OUTCOMES: As a group, AAS users displayed markedly greater psychopathology than nonusing weightlifters. Multipathology was common among AAS users. Four different subgroups of personality profiles were identified with distinct patterns of pathology and severity. LIMITATIONS: The cross-sectional nature of the study precludes inferences about causality. The study is limited by possible selection bias, as participants choosing to be involved in research may not be entirely representative for the group as a whole. The study is vulnerable to information bias, as the results are based on self-report measures and interviews.

Health service engagement, side effects and concerns among men with anabolic-androgenic steroid use: a cross-sectional Norwegian study.

BACKGROUND: Recreational use of anabolic-androgenic steroids (AAS) is a public health concern world-wide associated with a range of physical and psychological side effects. Still, people who use AAS tend to be reluctant to seek treatment. This study aims to explore use characteristics, treatment-seeking behaviour, side effects and associated health concerns among men with AAS use. METHODS: The study includes cross-sectional self-report data from 90 men with a current or previous use of AAS exceeding 12 months, where 41 (45.6%) had sought treatment at least once during their lifetime, and 49 (54.4%) had not. Health service engagement was examined with descriptive statistics on reasons for contacting health services, transparency about AAS use, satisfaction with health services and reasons for not seeking treatment. Furthermore, experienced side effects and health concerns were compared between the treatment seeking and the non-treatment seeking group, using two-sample t-tests and Chi2 or Fisher exact tests for numerical and categorical variables, respectively. RESULTS: All 90 AAS-using men reported side effects from AAS use. Treatment seekers were significantly younger, experienced more side effects including gynecomastia, excessive sweating, fatigue, depression and anxiety, and expressed more concern for testosterone deficiency. Preventive health check-up was the most common reason for seeking treatment (n = 22, 53.7%), and 38 men (93%) were transparent about AAS use during consultations with health professionals. The main reported reasons for not seeking healthcare services were that the experienced side effects were not considered to be of treatment demanding nature (n = 39, 79.6%) and the belief that healthcare providers had scarce knowledge about AAS use and its health impacts (n = 12, 24.5%). CONCLUSIONS: Reluctance to seek treatment among people who use AAS, despite having associated side effects and health concerns, may contribute to continued health risks. It is important to fill the knowledge gap on how to reach and treat this new patient group, and policy makers and treatment providers need to be educated on how to meet their treatment needs.

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.

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.

ADHD symptoms and use of anabolic androgenic steroids among male weightlifters.

Use of anabolic androgenic steroids (AAS) is associated with adverse health effects. The factors that predispose to AAS use among athletes are poorly understood, but attention deficit/hyperactivity disorder (ADHD), which is known to occur among athletes more often than in the general population, is associated with risk behaviors, including substance abuse. We aimed to see if AAS use in male weightlifters was associated with ADHD symptoms, and test the link between ADHD symptoms and cognitive performance. Hundred and forty male weightlifters, 72 AAS users and 68 weightlifting controls (WLC), completed the Achenbach system of empirically based assessment (ASEBA) for ADHD symptoms and underwent cognitive examination. Self-reported ADHD symptom scores were significantly higher among AAS users compared to WLC, and scores in the range indicating clinically important ADHD was significantly more common in the AAS-using group. Age of onset of AAS use correlated inversely with ADHD scale score (r = - 0.35; p = 0.003). ADHD score correlated inversely with cognitive scores for working memory (r = - 0.25, p < 0.001), processing speed (r = - 0.24, p < 0.001), verbal learning and memory (r = - 0.19, p = 0.03), and problem solving (r = - 0.20, p = 0.02). AAS use among weightlifters is associated with ADHD symptoms and corresponding lower cognitive performance. Recognising a relationship between ADHD symptoms and AAS use may guide drug prevention strategies in sports.

Severity of anabolic steroid dependence, executive function, and personality traits in substance use disorder patients in Norway.

INTRODUCTION: Anabolic androgenic steroids (AAS), including testosterone and synthetic derivatives, are typically used to increase muscle mass. Many users develop a dependence on these substances, contributing to worsened physical and mental health outcomes. Aspects of personality and executive dysfunction may represent underlying vulnerabilities for developing dependence. OBJECTIVE: To identify levels of AAS dependence within substance use disorder (SUD) treatment patients and assess the relationship between dependence severity and personality traits and executive function (EF). METHODS: Data were collected from patients at 38 SUD treatment facilities in Norway. Questionnaires were completed for measures of personality and EF. Measures of symptoms of AAS dependence were used in latent class analysis to identify sub-groups of patients, which were evaluated for association with EF and personality traits, and compared with a group of non-AAS using SUD patients. RESULTS: Three classes were identified; largely reflecting low, moderate, and high symptoms of dependence. Multinomial regression analyses indicated that moderate and high symptoms were associated with several measures of EF and personality traits, particularly self-monitoring, antagonism, disinhibition, and rigid perfectionism while users with low symptoms exhibited higher capacities for emotional control and shift, and lower negative affectivity, relative to non-AAS using SUD patients. Backward stepwise regressions indicated antagonism, and decreased self-monitoring as key personality and cognitive characteristics of SUD patients with severe AAS dependence. CONCLUSION: Our findings indicate that specific executive dysfunctions and personality features, particularly those associated with poor emotional control, reduced empathy, and impulsivity are associated with more severe AAS dependence in the SUD population.

Androgen abuse and the brain.

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.

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.

Anabolic androgenic steroids, antisocial personality traits, aggression and violence.

BACKGROUND: Anabolic androgenic steroid (AAS) use is associated with a wide range of adverse physical, psychological and social effects. While some experience few side effects, others might experience severe consequences. Aggression and violence are among the often-cited side effects associated with high-dose AAS use; however, most of the knowledge is generated from subgroups, such as prison populations. A likely hypothesis is that AAS use is associated with aggression and violence, but that these associations are complex and may be mediated by several factors, such as substance use, AAS dependence and personality traits. METHODS: In the present study, we tested this hypothesis by examining the relations between long-term AAS use and AAS dependence, aggression, interpersonal violence and potential mediating factors in a sample of male AAS exposed and non-exposed weightlifting controls (WLC), using self-report questionnaires. Based upon AAS dependence criteria, a sample of male AAS users and WLC (N = 139) were stratified into three groups: WLC (n = 66), AAS dependents (n = 41) and AAS non-dependents (n = 32). RESULTS: The results demonstrate that AAS dependents reported significantly higher levels of aggression compared to WLC and AAS non-dependents. While interpersonal violence was reported in all three groups, the highest percentage was found in the AAS dependent group. CONCLUSION: In summary, our study confirms a link between AAS use, aggression and violence in a weightlifting population. However, the association is foremost seen in AAS dependent users and it seems that antisocial personality traits are an important mediator.

Anabolic-androgenic steroid use among women - A qualitative study on experiences of masculinizing, gonadal and sexual effects.

BACKGROUND: Female users of anabolic-androgenic steroids (AAS) are at risk of developing masculinizing side effects. This study explores how the development of masculinizing effects has been experienced and processed by women with current or previous AAS use. METHODS: Individual, semi-structured interviews were undertaken among 16 current or previous AAS-using women. The interviews were recorded, transcribed verbatim and thematically analyzed. RESULTS: Almost all of the women were introduced to AAS and advised about what substance(s) to use, how much to use and how to use it by a trusted male partner, friend or coach. For some, AAS initiation was an impulsive choice, while others wanted to overcome stagnation and/or prepare for fitness competitions. Many were unprepared for the unwanted masculinizing effects, but some experienced these to be outweighed by the desired effects. Masculinizing effects that could be mediated by hair removal or breast implants were easier to process than a deepened voice. As very few women were open with others about their AAS use, the voice change could disclose use and was often accompanied by feelings of shame and regret. Absence of menstruation and its return following cessation were used to monitor effect, normal function and safety when deciding when to start a new cycle. Clitoral enlargement gave rise to shame and reduced self-esteem, but negative emotions could be reduced by a positive partner response. Increased libido was common and gave rise to positive and negative experiences, depending on life situation, partner status, whether the partner used AAS simultaneously and whether genital changes had also been experienced. CONCLUSION: Women who use AAS are at risk of developing irreversible masculinizing effects that are difficult to process and that may negatively influence self-esteem, social life and sexual function, both during and after use. More gender-specific information about women and AAS use is needed.

Theory of mind in users of anabolic androgenic steroids.

RATIONALE: Anabolic androgenic steroids are used to improve physical performance or increase lean muscle mass. About one-third of users develop a dependency syndrome, which is characterized by elevated rates of psychopathology, cognitive impairments, and aggressive and antisocial behaviors. The mechanisms behind these intra- and interpersonal problems are not known. OBJECTIVE: To examine theory of mind (ToM), i.e., the ability to infer the mental state of others, in users of anabolic androgenic steroids. Reduced ToM may be one factor underlying the interpersonal problems that have been reported with prolonged use of anabolic androgenic steroids. METHODS: The Movie for the Assessment of Social Cognition (MASC) was used to assess ToM. Study participants were male/female weightlifters who used anabolic androgenic steroids (AAS, n = 34/9), who were dependent on anabolic androgenic steroids (AASdep, n = 44/7), and a non-using weightlifting comparison group (WLC, n = 69/16). RESULTS: Analyses of variance showed that the AASdep group performed significantly worse than the WLC group, for all MASC measures (total ToM, cognitive ToM, affective ToM, overmentalizing/undermentalizing errors). Sex and sex x group interaction effects were non-significant. CONCLUSIONS: Male and female weightlifters who were dependent on anabolic androgenic steroids had impaired ToM. Their reduced social cognition may be one contributing factor to the elevated rates of antisocial behavior reported in this population.