Search

Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.

Purpose of review To summarize recent findings regarding the public health impact of androgen abuse. Recent findings Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease. Withdrawal from androgens after long-term use may produce prolonged and sometimes irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes cause irritability, aggressiveness, and violence, whereas androgen withdrawal may cause depression. However, these psychiatric effects are idiosyncratic, affecting only a minority of users. Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia. Several recent studies have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse musculoskeletal effects. Summary Recent studies have demonstrated marked adverse effects of long-term androgen abuse. As increasing numbers of androgen abusers reach middle age, these effects will likely represent an emerging public health problem.

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic–androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Out-patient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiological testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes [estimated difference, 95% confidence interval (CI) = 2.3 (0.1, 4.5) ml; P = 0.042] and lower serum testosterone levels [estimated difference: 95% CI = 131 (25, 227) dl; P = 0.009], with five users showing testosterone levels below 200 ng/dl despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF sexual desire subscale [estimated difference: 95% CI = 2.4 (1.3, 3.4) points on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus untreated former users, seven (29%) had experienced major depressive episodes during AAS withdrawal; four of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic–androgenic steroid misusers, anabolic–androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged and associated with substantial morbidity.

Background: Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Methods: Using a cross-sectional cohort design, we recruited 140 experienced male weightlifters 34 to 54 years of age, comprising 86 men reporting ≥2 years of cumulative lifetime AAS use and 54 nonusing men. Using transthoracic echocardiography and coronary computed tomography angiography, we assessed 3 primary outcome measures: left ventricular (LV) systolic function (left ventricular ejection fraction), LV diastolic function (early relaxation velocity), and coronary atherosclerosis (coronary artery plaque volume). Results: Compared with nonusers, AAS users demonstrated relatively reduced LV systolic function (mean±SD left ventricular ejection fraction = 52±11% versus 63±8%; P P P P =0.035) compared with users currently off-drug (N=28). In addition, AAS users demonstrated higher coronary artery plaque volume than nonusers (median [interquartile range] 3 [0, 174] mL 3 versus 0 [0, 69] mL 3 ; P =0.012). Lifetime AAS dose was strongly associated with coronary atherosclerotic burden (increase [95% confidence interval] in rank of plaque volume for each 10-year increase in cumulative duration of AAS use: 0.60 SD units [0.16–1.03 SD units]; P =0.008). Conclusions: Long-term AAS use appears to be associated with myocardial dysfunction and accelerated coronary atherosclerosis. These forms of AAS-associated adverse cardiovascular phenotypes may represent a previously underrecognized public-health problem.

The use of androgens, frequently referred to as anabolic-androgenic steroids (AAS), has grown into a worldwide substance abuse problem over the last several decades. Testosterone was isolated in the 1930s, and numerous synthetic androgens were quickly developed thereafter. Athletes soon discovered the dramatic anabolic effects of these hormones, and AAS spread rapidly through elite athletics and bodybuilding from the 1950s through the 1970s. However it was not until the 1980s that widespread AAS use emerged from the elite athletic world and into the general population. Today, the great majority of AAS users are not competitive athletes, but instead are typically young to middle-aged men who use these drugs primarily for personal appearance. AAS abuse has now become particularly prevalent in regions such as Scandinavia, the United States, Brazil, and British Commonwealth countries, but remains rare in countries such as China, Korea, and Japan - a pattern that reflects cultural differences in attitudes towards male muscularity.

To summarize recent advances in studies of illicit use of androgens and other hormones.Androgens and other appearance-enhancing and performance-enhancing substances are widely abused worldwide. Three notable clusters of findings have emerged in this field in recent years. First, studies almost unanimously find that androgen users engage in polypharmacy, often ingesting other hormones (e.g., human growth hormone, thyroid hormones, and insulin), ergo/thermogenic drugs (e.g., caffeine, ephedrine, and clenbuterol), and classical drugs of abuse (e.g., cannabis, opiates, and cocaine). Second, reports of long-term psychiatric and medical adverse effects of androgens continue to accumulate. In cardiovascular research particularly, controlled studies have begun to supersede anecdotal evidence, strengthening the case that androgens (possibly acting synergistically with other abused drugs) may cause significant morbidity and even mortality. Third, it is increasingly recognized that androgen use may lead to a dependence syndrome with both psychological and physiological origins. Androgen dependence likely affects some millions of individuals worldwide, and arguably represents the least studied major class of illicit drug dependence.Given mounting evidence of the adverse effects of androgens and associated polypharmacy, this topic will likely represent an expanding area of research and an issue of growing public health concern.

Patterns of illicit drug use vary widely around the world. For example, one recent survey [1] found lifetime cannabis use among 41.9% of respondents in New Zealand, but only 6.6% of respondents in Italy and 1.5% in Japan. Cocaine was reported by 16.2% of respondents in the USA, versus 4.1% in Spain and 0.0% in the People's Republic of China. Favored drugs of abuse may also rank differently within different countries. Japan, for instance, has experienced three major epidemics of methamphetamine abuse over the last 50 years [2, 3], but shows a low prevalence of many other forms of drug abuse that are widespread elsewhere [4]. Clearly, factors such as drug availability, government enforcement policies and national healthcare systems contribute to these figures, but one must also acknowledge the critical role of culture [5]. Culture influences not only attitudes towards illicit drug use in general, but also which particular drugs people choose to use; a drug effect sought by one population might have little appeal for another. As one example of this little-studied issue, we explore here a form of drug abuse that is strikingly asymmetric across cultures: the use of ‘body image drugs’ such as anabolic-androgenic steroids (AAS).

In a study of performance-enhancing substance use among 231 experienced young male weightlifters, we found that 27 (12%) reported illicit use of human growth hormone (HGH) or its bioactive derivative, insulin-like growth factor-1. All of these 27 men also reported use of anabolic-androgenic steroids (AAS) and 22 (81%) met criteria for current or past AAS dependence. Fifteen (56%) also reported current or past dependence on opioids, cocaine, and/or ecstasy. These findings suggest that among young male weightlifters, illicit HGH use has become a common form of substance abuse, frequently associated with both AAS dependence and classical substance dependence.

The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body-image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years, but remains little studied.

Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men. We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed, hypogonadal men. For this study, we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower. We randomized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen. The primary outcome measure was the Hamilton Depression Rating Scale (HDRS) score. Secondary measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression Scale, and the Quality of Life Scale. Our primary analysis, using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures, failed to show a significant difference between groups (mean [95% confidence interval] 6-week change in HDRS for testosterone vs placebo, -0.4 [-2.6 to 1.8]). However, in one exploratory analysis of treatment responders, we found a possible trend in favor of testosterone on the HDRS. Our findings, combined with the conflicting data from earlier smaller studies, suggest that testosterone is not generally effective for depressed men. The possibility remains that testosterone might benefit a particular subgroup of depressed men, but if so, the characteristics of this subgroup would still need to be established.

The syndrome of anabolic-androgenic steroid (AAS) dependence, though well recognized, remains poorly studied. In this preliminary psychometric study, American and British investigators separately administered a structured diagnostic interview module, based on recently proposed criteria for AAS dependence, to 42 male AAS users in Middlesbrough, England. Another investigator, blinded to the diagnostic interview findings, assessed self-reported symptoms of “muscle-dysmorphia”; effects of AAS on various aspects of functioning; and maximum proportion of annual income spent on AAS. We also assessed demographic measures, history of other substance use, and performance on a hypothetical AAS-purchasing task. The interview module yielded very good interrater reliability (kappa = 0.76 and overall intraclass correlation = 0.79) and strong internal consistency (Cronbach’s alpha = 0.77–0.87). Men diagnosed as AAS-dependent, when compared to nondependent men, reported significantly earlier onset of AAS use, longer duration and higher maximum doses of AAS used, more frequent use of other performance-enhancing drugs, and a somewhat larger maximum percentage of income spent on AAS. Dependent users also “bought” more AAS in the hypothetical purchase task, but rated significantly more negatively the effects of AAS on their mental health—findings all suggesting that the diagnosis of AAS dependence shows construct validity. As a group, AAS users showed high preoccupation with muscular appearance, but dependence per se was not significantly associated with this measure—suggesting that the diagnosis of AAS dependence shows some evidence of discriminant validity. Collectively, these findings suggest that AAS dependence may be diagnosed reliably, with preliminary evidence for construct and discriminant validity.

Illicit methamphetamine abuse represents a major problem in many countries worldwide, including the United States. Prolonged regular smoking or injection of methamphetamine can cause a psychosis, typically characterized by paranoid delusions and auditory hallucinations and often associated with disturbances in mood. These symptoms may persist long after methamphetamine is discontinued and may prove refractory to antipsychotic medications. The authors describe a patient who developed a typical methamphetamine psychosis that persisted despite months of abstinence from methamphetamine and weeks of treatment with antipsychotic medication but that responded promptly to electroconvulsive therapy (ECT) on two separate occasions: on initial presentation and again a year later when the patient relapsed into methamphetamine abuse and developed psychosis again. The authors review the large international literature on methamphetamine psychosis, much of which is from Japan and has not previously been summarized in English. Persistent methamphetamine psychosis has been widely reported in Japan for more than 50 years but is rarely discussed in the American literature, possibly because some such cases are misdiagnosed in the United States as primary psychotic disorders. Given the growing public health problem of methamphetamine abuse in the United States, the distinction between persistent methamphetamine psychosis and a primary psychotic disorder has grown increasingly important. Thus, American clinicians should be alert to the possibility of methamphetamine psychosis and may wish to consider ECT in refractory cases.

Aims Anabolic–androgenic steroids (AAS) are widely used illicitly to gain muscle and lose body fat. Here we review the accumulating human and animal evidence showing that AAS may cause a distinct dependence syndrome, often associated with adverse psychiatric and medical effects. Method We present an illustrative case of AAS dependence, followed by a summary of the human and animal literature on this topic, based on publications known to us or obtained by searching the PubMed database. Results About 30% of AAS users appear to develop a dependence syndrome, characterized by chronic AAS use despite adverse effects on physical, psychosocial or occupational functioning. AAS dependence shares many features with classical drug dependence. For example, hamsters will selfadminister AAS, even to the point of death, and both humans and animals exhibit a well-documented AAS withdrawal syndrome, mediated by neuroendocrine and cortical neurotransmitter systems. AAS dependence may particularly involve opioidergic mechanisms. However, AAS differ from classical drugs in that they produce little immediate reward of acute intoxication, but instead a delayed effect of muscle gains. Thus standard diagnostic criteria for substance dependence, usually crafted for acutely intoxicating drugs, must be adapted slightly for cumulatively acting drugs such as AAS. Conclusions AAS dependence is a valid diagnostic entity, and probably a growing public health problem. AAS dependence may share brain mechanisms with other forms of substance dependence, especially opioid dependence. Future studies are needed to characterize AAS dependence more clearly, identify risk factors for this syndrome and develop treatment strategies.

Illicit anabolic-androgenic steroid (AAS) use represents a growing worldwide public health problem (1, 2). Some AAS users consume only a few courses of these drugs in a lifetime, but others progress from discrete courses of use to a maladaptive pattern of almost continuous use, despite adverse medical, psychological, and social effects (3, 4). In the last 20 years, accumulating animal and human studies have documented and characterized this syndrome of AAS dependence. For example, rats and mice will select AAS in conditioned place preference models (5), and hamsters will self-administer testosterone even to the point of death (6). Unlike rodents, humans may initially develop a pattern of AAS dependence as a result of “muscle dysmorphia” – a form of body dysmorphic disorder where they become preoccupied that they do not look adequately muscular (7). In later stages, however, AAS dependence comes to resemble “classical” drug dependence, with a well-defined withdrawal syndrome mediated both by neuroendocrine factors and by a variety of cortical neurotransmitter systems, especially the opioidergic system (5, 8). AAS dependence may be associated with substantial medical and psychiatric morbidity, including hypertension, dyslipidemia, cardiomyopathy, persistent hypogonadism, major mood disorders, and progression to other forms of substance abuse and dependence, especially opioid dependence (2). The full magnitude of these risks is still unknown, because widespread AAS abuse did not spread from the athletic world to the general population until the 1980s (2), and only now are many AAS users becoming old enough to have established a dependence pattern and to have entered the age of risk for some of these adverse outcomes. Although AAS users historically have been reluctant to seek treatment (1, 9), these adverse outcomes may bring increasing numbers to clinical attention. Importantly, unlike classical drugs of abuse, AAS are not ingested to achieve an immediate “high” of acute intoxication, but instead are consumed over a preplanned course of many weeks to achieve a delayed reward of increased muscularity. Therefore, the existing DSM-IV criteria for substance dependence, which were designed primarily for acutely intoxicating drugs, do not apply precisely to AAS. For example, criteria such as “using the substance in larger amounts than was intended, ” or “giving up or reducing important activities because of substance use, ” apply more easily to alcohol or cocaine than to AAS. But these considerations should not obscure the fact that AAS have definite psychoactive effects, including a potential for addiction, that is likely underestimated because attention has focused on the drugs’ muscle-building properties (1). On the basis of the available literature (2–4, 10) and clinical experience with AAS-dependent individuals, we would suggest that the existing DSM criteria could be adapted for diagnosing AAS dependence with only small interpretive changes (Table 1). AAS are presently the only major class of drugs scheduled by the Drug Enforcement Administration for which DSM-IV does not explicitly recognize a dependence syndrome (11); this omission could be rectified in DSM-V by offering these proposed interpretations for AAS dependence in a small table or in the accompanying text of the substance dependence section. Alternatively, DSM-V could initially propose these criteria only for research purposes, pending further evidence of their reliability and validity. In either case, clarified criteria for AAS dependence will likely improve recognition of this diagnosis among clinicians and researchers encountering the syndrome, and stimulate increased attention to this emerging public health problem. TABLE 1 DSM Substance Dependence Criteria (Shown in Bold), Interpreted for Diagnosing AAS Dependence (Shown in Plain Text)

Anabolic-androgenic steroid (AAS) dependence has been a recognized syndrome for some 20 years, but remains poorly understood.We evaluated three groups of experienced male weightlifters: (1) men reporting no history of AAS use (N=72); (2) nondependent AAS users reporting no history of AAS dependence (N=42); and (3) men meeting adapted DSM-IV criteria for current or past AAS dependence (N=20). We assessed demographic indices, lifetime history of psychiatric disorders by the Structured Clinical Interview for DSM-IV, variables related to AAS use, and results from drug tests of urine and hair.Nondependent AAS users showed no significant differences from AAS nonusers on any variable assessed. Dependent AAS users, however, differed substantially from both other groups on many measures. Notably, they reported a more frequent history of conduct disorder than nondependent AAS users (odds ratio [95% CI]: 8.0 [1.7, 38.0]) or AAS nonusers (13.1 [2.8, 60.4]) and a much higher lifetime prevalence of opioid abuse and dependence than either comparison group (odds ratios 6.3 [1.2, 34.5] and 18.6 [3.0, 116.8], respectively).Men with AAS dependence, unlike nondependent AAS users or AAS nonusers, showed a distinctive pattern of comorbid psychopathology, overlapping with that of individuals with other forms of substance dependence. AAS dependence showed a particularly strong association with opioid dependence - an observation that recalls recent animal data suggesting similarities in AAS and opioid brain reward mechanisms. Individuals with AAS dependence and individuals with "classical" substance dependence may possibly harbor similar underlying biological and neuropsychological vulnerabilities.

Background The problem of anabolic–androgenic steroid (AAS) abuse has recently generated widespread public and media attention. Most AAS abusers, however, are not elite athletes like those portrayed in the media, and many are not competitive athletes at all. This larger but less visible population of ordinary AAS users began to emerge in about 1980. The senior members of this population are now entering middle age; they represent the leading wave of a new type of aging former substance abusers, with specific medical and psychiatric risks. Methods We reviewed the evolving literature on long-term psychiatric and medical consequences of AAS abuse. Results Long-term use of supraphysiologic doses of AAS may cause irreversible cardiovascular toxicity, especially atherosclerotic effects and cardiomyopathy. In other organ systems, evidence of persistent toxicity is more modest, and interestingly, there is little evidence for an increased risk of prostate cancer. High concentrations of AAS, comparable to those likely sustained by many AAS abusers, produce apoptotic effects on various cell types, including neuronal cells—raising the specter of possibly irreversible neuropsychiatric toxicity. Finally, AAS abuse appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood syndromes, and progression to other forms of substance abuse. However, the prevalence and severity of these various effects remains poorly understood. Conclusions As the first large wave of former AAS users now moves into middle age, it will be important to obtain more systematic data on the long-term psychiatric and medical consequences of this form of substance abuse.

Background Recent media reports have portrayed an alarming increase in apparent anabolic–androgenic steroid (AAS) use among American teenage girls; Congress even held hearings on the subject in June 2005. We questioned whether AAS use among teenage girls was as widespread as claimed. Methods We reviewed four large national surveys and many smaller surveys examining the prevalence of AAS use among teenage girls. Virtually all of these surveys used anonymous questionnaires. We asked particularly whether the language of survey questions might generate false-positive responses among girls who misinterpreted the term “steroid.” We also reviewed data from other countries, together with results from the only recent study (to our knowledge) in which investigators personally interviewed female AAS users. Results The surveys produced remarkably disparate findings, with the lifetime prevalence of AAS use estimated as high as 7.3% among ninth-grade girls in one study, but only 0.1% among teenage girls in several others. Upon examining the surveys reporting an elevated prevalence, it appeared that most used questions that failed to distinguish between anabolic steroids, corticosteroids, and over-the-counter supplements that respondents might confuse with “steroids.” Other features in the phrasing of certain questions also seemed likely to further bias results in favor of false-positive responses. Conclusions Many anonymous surveys, using imprecise questions, appear to have greatly overestimated the lifetime prevalence of AAS use among teenage girls; the true lifetime prevalence may well be as low as 0.1%. Future studies can test this impression by using a carefully phrased question regarding AAS use.

Background: Accumulating case reports have described tendon rupture in men who use anabolic-androgenic steroids (AAS). However, no controlled study has assessed the history of tendon rupture in a large cohort of AAS users and comparison nonusers. Hypothesis: Men reporting long-term AAS abuse would report an elevated lifetime incidence of tendon rupture compared with non–AAS-using bodybuilders. Study Design: Cohort study; Level of evidence, 3. Methods: Medical histories were obtained from 142 experienced male bodybuilders aged 35 to 55 years recruited in the course of 2 studies. Of these men, 88 reported at least 2 years of cumulative lifetime AAS use, and 54 reported no history of AAS use. In men reporting a history of tendon rupture, the circumstances of the injury, prodromal symptoms, concomitant drug or alcohol use, and details of current and lifetime AAS use (if applicable) were recorded. Surgical records were obtained for most participants. Results: Nineteen (22%) of the AAS users, but only 3 (6%) of the nonusers, reported at least 1 lifetime tendon rupture. The hazard ratio for a first ruptured tendon in AAS users versus nonusers was 9.0 (95% CI, 2.5-32.3; P < .001). Several men reported 2 or more independent lifetime tendon ruptures. Interestingly, upper-body tendon ruptures occurred exclusively in the AAS group (15 [17%] AAS users vs 0 nonusers; risk difference, 0.17 [95% CI, 0.09-0.25]; P < .001 [hazard ratio not estimable]), whereas there was no significant difference between users and nonusers in risk for lower-body ruptures (6 [7%] AAS users, 3 [6%] nonusers; hazard ratio, 3.1 [95% CI, 0.7-13.8]; P = .13). Of 31 individual tendon ruptures assessed, only 6 (19%) occurred while weightlifting, with the majority occurring during other sports activities. Eight (26%) ruptures followed prodromal symptoms of nonspecific pain in the region. Virtually all ruptures were treated surgically, with complete or near-complete ultimate restoration of function. Conclusion: AAS abusers, compared with otherwise similar bodybuilders, showed a markedly increased risk of tendon ruptures, particularly upper-body tendon rupture.

Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans.This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS).AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053).Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction.

The objective of this study was to identify the differences in cerebral activation between chronic cannabis smokers and controls in response to finger sequencing. We hypothesized that attentional areas related to motor function as well as primary and supplementary motor cortices would show diminished activation in chronic cannabis smokers. Nine cannabis smokers and 16 controls were included in these analyses. Scanning was performed on a GE 1.5 T scanner. Echo planar images and high-resolution MR images were acquired. The challenge paradigm included left and right finger sequencing. Group differences in cerebral activation were examined for Brodmann areas (BA) 4, 6, 24, and 32 using ROI analyses in SPM. Cannabis users, tested within 4–36 h of discontinuation, exhibited significantly less activation than controls in BA 24 and 32 bilaterally during right- and left-sided sequencing and for BA 6 in all tasks except for left-sided sequencing in the left hemisphere. There were no statistically significant differences for BA 4. None of these regional activations correlated with urinary cannabis concentration and verbal IQ for smokers. These results suggest that recently abstinent chronic cannabis smokers produce reduced activation in motor cortical areas in response to finger sequencing compared to controls.

Aims To assess anabolic-androgenic steroid (AAS) users’ trust in the knowledge and advice of physicians. Design Interviews of AAS users and non-users. Setting Research offices. Participants Eighty weight-lifters (43 AAS users, 37 non-users) recruited by advertisement in Massachusetts and Florida, USA. Measurements Personal interviews and questionnaire responses, including subjects’ ratings of physicians’ knowledge regarding various health- and drug-related topics. AAS users also rated their level of trust in various sources of information about AAS. Findings Both groups of subjects gave physicians high ratings on knowledge about general health, cigarette smoking, alcohol, and conventional illicit drugs, but gave physicians markedly and significantly lower ratings on knowledge about AAS. When rating sources of information on AAS, users scored physicians as no more reliable than their friends, Internet sites, or the person(s) who sold them the steroids. Forty percent of users trusted information on AAS from their drug dealers at least as much as information from any physician that they had seen, and 56% had never revealed their AAS use to any physician. Conclusion AAS users show little trust in physicians’ knowledge about AAS, and often do not disclose their AAS use to physicians. These attitudes compromise physicians’ ability to educate or treat AAS users. Physicians can respond to these problems by learning more about AAS and by maintaining a high index of suspicion when evaluating athletic male patients.

Anabolic-androgenic steroid (AAS) use represents a major public health problem in the United States, but the risk factors for this form of drug use are little studied. We evaluated 48 men who had used AAS for at least 2 months and 45 men who had never used AAS, using a verbal interview and a battery of questionnaires covering hypothesized demographic, familial, and psychosocial risk factors for AAS use. All subjects in both groups were experienced weightlifters; thus, differences between groups were likely to be associated specifically with AAS use, rather than with weightlifting in general. The AAS users and non-users generally described similar childhood and family experiences, but users reported significantly poorer relationships with their fathers and greater childhood conduct disorder than non-users. At the time that they first started lifting weights, AAS users and non-users were similar in their perceived physical, social, and sexual status, but users were significantly less confident about their body appearance. AAS users displayed much higher rates of other illicit substance use, abuse, or dependence than non-users, with use of other illicit substances almost always preceding first use of AAS. These findings suggest that AAS use may be most likely to occur in men with high levels of antisocial traits and low levels of body esteem.

Background: Recent reports suggest that anabolic-androgenic steroids (AAS) may cause mood disorders or dependence syndromes and may help to introduce some individuals to opioid abuse. At present, however, little is known about prior AAS use among men entering inpatient substance abuse treatment. Method: We assessed lifetime AAS use in 223 male substance abusers admitted to a substance abuse treatment unit primarily for treatment of alcohol, cocaine, and opioid dependence. Subjects reporting definite or possible AAS use were then asked to participate in a detailed semi-structured interview that covered demographics, drug use history, and symptoms experienced during AAS use and withdrawal, and whether AAS use had helped introduce the subject to other classes of drugs. Results: Twenty-nine men (13%) reported prior AAS use, but this history was documented on physicians' admission evaluations in only 4 cases. Among 88 men listing opioids as their drug of choice, 22 (25%) acknowledged AAS use, versus only 7 (5%) of the other 135 men (p

Prolonged use of high-dose anabolic-androgenic steroids (AAS) may induce a dependence syndrome, and emerging evidence suggests that AAS effects on endogenous opioid systems may contribute to AAS abuse. The present study tested the hypothesis that high dose AAS treatment enhances endogenous opioid activity in rhesus monkeys as revealed by 1) tolerance to the antinociceptive effects of the mu opioid agonist morphine and 2) physical dependence as indicated by evidence of opioid withdrawal following administration of the opioid antagonist naloxone. Three rhesus monkeys were treated for 14 days with 3.2 mg/kg/day testosterone propionate, and the effects of morphine (0.32-10 mg/kg) and naloxone (0.01-0.32 mg/kg) were examined both before and during treatment. Morphine antinociception was evaluated using a warm-water tail-withdrawal procedure, and naloxone-precipitated withdrawal was evaluated using checked behavioral signs and measures of ventilatory rate. Chronic testosterone administration for 14 days produced a 100-fold increase in mean plasma testosterone levels. However, testosterone treatment did not significantly alter the antinociceptive effects of morphine, and naloxone did not precipitate signs of opioid withdrawal either before or during testosterone treatment. These data do not support the hypothesis that high-dose AAS treatment enhances endogenous opioid activity in rhesus monkeys in a way that produces opioid tolerance or dependence.

To characterize the cytoskeletal aberration due to traumatic injury, temporal and regional profiles of changes in immunoreactivity of microtubule-associated protein 2 (MAP2), neurofilament heavy subunit protein (NFH) and heat shock protein 72 (HSP72) were investigated after different magnitudes of traumatic brain injury by fluid percussion. The experimental rat brain was perfusion-fixed at 1, 6 and 24 hours after traumatic brain injury. Conventional histological staining has demonstrated that the mildest traumatic brain injury (1.0 atm) induced no neuronal loss at the impact site and that neuron loss was apparent when traumatic brain injury was increased to 4.3 atm. The mildest traumatic brain injury, however, caused a significant increase in HSP72 immunoreactivity in the superficial cortical layers at the impact site as early as 1 hour after the injury. In the case of severe traumatic brain injury (4.3 atm), neuron loss was apparent in the area at the impact site, but the increase in HSP72 immunoreactivity was moderate, and it was observed only after 6 hours in the deep cortical layers under the necrotic area. The increased immunostaining of MAP2 was demonstrated in damaged axons and neuronal perikarya in the wider area surrounding the impact site at 6 and 24 hours after the injury. Six and 24 hours after the injury, perikaryal accumulation of neurofilament was observed, and the accumulated neurofilament was mostly phosphorylated. These results indicate that the severe traumatic brain injury of 4.3 atm triggers the abnormal accumulation of cytoskeletal proteins in neuronal perikarya, most probably due to an impairment of axonal transport. It is implied that the increased expression of HSP72 may be involved in the protective process of neurons after traumatic brain injury.

Objective This manuscript summarizes the best available scholarly evidence related to anabolic-androgenic steroids (AAS) as a reference for health care professionals, including athletic trainers, educators, and interested others. Background Health care professionals associated with sports or exercise should understand and be prepared to educate others about AAS. These synthetic, testosterone-based derivatives are widely abused by athletes and nonathletes to gain athletic performance advantages, develop their physiques, and improve their body image. Although AAS can be ergogenic, their abuse may lead to numerous negative health effects. Recommendations Abusers of AAS often rely on questionable information sources. Sports medicine professionals can therefore serve an important role by providing accurate, reliable information. The recommendations provide health care professionals with a current and accurate synopsis of the AAS-related research.

Millions of individuals worldwide have used anabolic-androgenic steroids (AAS) to gain muscle or improve athletic performance. Recently, in vitro investigations have suggested that supraphysiologic AAS doses cause apoptosis of neuronal cells. These findings raise the possibility, apparently still untested, that humans using high-dose AAS might eventually develop cognitive deficits.We administered five cognitive tests from the computerized CANTAB battery (Pattern Recognition Memory, Verbal Recognition Memory, Paired Associates Learning, Choice Reaction Time, and Rapid Visual Information Processing) to 31 male AAS users and 13 non-AAS-using weightlifters age 29-55, recruited and studied in May 2012 in Middlesbrough, UK. Testers were blinded to participants' AAS status and other historical data.Long-term AAS users showed no significant differences from nonusers on measures of response speed, sustained attention, and verbal memory. On visuospatial memory, however, AAS users performed significantly more poorly than nonusers, and within the user group, visuospatial performance showed a significant negative correlation with total lifetime AAS dose. These were large effects: on Pattern Recognition Memory, long-term AAS users underperformed nonusers by almost one standard deviation, based on normative population scores (adjusted mean difference in z-scores=0.89; p=0.036), and performance on this test declined markedly with increasing lifetime AAS dose (adjusted change in z-score=-0.13 per 100g of lifetime AAS dose; p=0.002). These results remained stable in sensitivity analyses addressing potential confounding factors.These preliminary findings raise the ominous possibility that long-term high-dose AAS exposure may cause cognitive deficits, notably in visuospatial memory.

The anabolic–androgenic steroids (AAS) are a family of hormones that includes the natural male hormone, testosterone, together with a group of synthetic derivatives of testosterone. These drugs are widely abused by men (and rarely, women) to gain muscle mass and lose body fat. Prior to about 1980, abuse of AAS was confined largely to elite competitive athletes, but in recent decades, AAS abuse has broken out of the athletic community and into the general population. Many modern AAS users have no specific athletic aspirations at all, but simply want to become bigger and more muscular. About 2–6% of men in many Western industrialized countries have used AAS, but AAS use is rare in Asian societies. Individuals with body image concerns, such as “muscle dysmorphia,” appear more prone to abuse AAS. Male muscularity is more strongly emphasized and rewarded in industrialized Western cultures than in Asia, and this difference likely explains the geographic distribution of AAS abuse. AAS cause few serious short-term medical effects, but over the long term may cause suppression of hypothalamic–pituitary–gonadal function, adverse effects on serum lipids, and cardiomyopathy. The most common psychiatric effects of AAS are mood disorders (typically hypomanic or manic syndromes during AAS exposure and depressive symptoms during AAS withdrawal); these are idiosyncratic, affecting a minority of AAS users, but are occasionally severe. A growing literature describes syndromes of AAS dependence, where individuals use AAS almost continuously despite adverse medical or psychiatric effects. Individuals displaying AAS abuse or dependence may also exhibit other forms of substance dependence. Unfortunately, AAS users rarely seek treatment, but this situation may change as the first large wave of illicit AAS users—those who first began AAS as youths in the 1980s—now reaches middle age and enters the age of risk for long-term cardiac, neuroendocrine, and psychiatric complications from these drugs.

Testosterone replacement is the most effective treatment for sexual dysfunction in hypogonadal men. Comorbid depression and antidepressant side effects may reduce its influence. The authors conducted a 6-week, double-blind, placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level. A total of 100 men were enrolled at 2 study sites (Boston, Massachusetts, USA, and Tel Aviv, Israel). The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function (IIEF). Complete pre- and posttrial IIEF data were available for 63 subjects. Men randomized to testosterone (n = 31) and placebo (n = 32) were similar in age, baseline testosterone levels, and baseline IIEF scores. At study termination, men randomized to placebo showed virtually no change from baseline in mean (95% CI) IIEF score (-0.7 [-6.5, 5.2]), whereas those receiving testosterone exhibited a substantial increase (15.8 [8.5, 23.1]). The estimated mean difference between groups was 16.8 [7.5, 26.1]; p = .001 by linear regression with adjustment for age and study site. There were also significant between-group differences in each of the 5 IIEF subscales, as well as on the single question involving ejaculatory ability (p ≤ .03 in all cases). Effect sizes in these comparisons remained little changed, and generally remained statistically significant, when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale. It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels, suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone. In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants, treatment with exogenous testosterone was associated with a significant improvement in sexual function, particularly including ejaculatory ability.

Psychiatric disorders are often profoundly modulated by culture; syndromes common in one society, or in one period of history, may be rare or nonexistent in another. Indeed, the latest Diagnostic a...

Background Illicit anabolic-androgenic steroid (AAS) abuse, though an important public health problem, remains inadequately studied. Almost all AAS abusers are male and lift weights, but the risk factors for AAS use among male weightlifters remain poorly understood. Methods We recruited 233 experienced male weightlifters, of whom 102 (44%) reported lifetime AAS use, and assessed their childhood and adolescent attributes retrospectively, using structured clinical interviews and computerized questionnaires. This cross-sectional cohort approach—a design that we have formally presented in the recent methodological literature—utilizes a study cohort, not selected for outcomes of interest, and assesses exposures and outcomes retrospectively. We hypothesized that conduct disorder and body-image concerns would be major risk factors for subsequent AAS use among male weightlifters. Results Within our study population, many attributes showed little association with AAS use, but conduct disorder and body-image concerns showed strong associations. For individuals with prior conduct disorder versus those without, the hazard ratio (95% confidence interval) for subsequent AAS use was 2.2 (1.5, 3.4). For individuals in the middle versus lowest tertile of scores on a retrospective adolescent muscle-dysmorphia scale, the hazard ratio was 1.5 (.84, 2.6); for the highest versus lowest tertile, the hazard ratio was 3.3 (2.0, 5.3); and for the linear trend of hazard ratios, p Conclusions Conduct disorder and body-image concerns represent important risk factors for AAS use among male weightlifters. Thus, assessment of these attributes may help to identify individuals most likely to require interventions to discourage this form of substance abuse.

Background— Although illicit anabolic-androgenic steroid (AAS) use is widespread, the cardiac effects of long-term AAS use remain inadequately characterized. We compared cardiac parameters in weightlifters reporting long-term AAS use to those in otherwise similar weightlifters without prior AAS exposure. Methods and Results— We performed 2D tissue-Doppler and speckle-tracking echocardiography to assess left ventricular (LV) ejection fraction, LV systolic strain, and conventional indices of diastolic function in long-term AAS users (n=12) and otherwise similar AAS nonusers (n=7). AAS users (median [quartile 1, quartile 3] cumulative lifetime AAS exposure, 468 [169, 520] weeks) closely resembled nonusers in age, prior duration of weightlifting, and current intensity of weight training. LV structural parameters were similar between the two groups; however, AAS users had significantly lower LV ejection fraction (50.6% [48.4, 53.6] versus 59.1% [58.0%, 61.7%]; P =0.003 by two-tailed Wilcoxon rank sum test), longitudinal strain (16.9% [14.0%, 19.0%] versus 21.0% [20.2%, 22.9%]; P =0.004), and radial strain (38.3% [28.5%, 43.7%] versus 50.1% [44.3%, 61.8%]; P =0.02). Ten of the 12 AAS users showed LV ejection fractions below the accepted limit of normal (≥55%). AAS users also demonstrated decreased diastolic function compared to nonusers as evidenced by a markedly lower early peak tissue velocity (7.4 [6.8, 7.9] cm/s versus 9.9 [8.3, 10.5] cm/s; P =0.005) and early-to-late diastolic filling ratio (0.93 [0.88, 1.39] versus 1.80 [1.48, 2.00]; P =0.003). Conclusions— Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.

Currently, few users of anabolic-androgenic steroids (AAS) seek substance abuse treatment. But this picture may soon change substantially, because illicit AAS use did not become widespread until the 1980s, and consequently the older members of this AAS-using population - those who initiated AAS as youths in the 1980s - are only now reaching middle age. Members of this group, especially those who have developed AAS dependence, may therefore be entering the age of risk for cardiac and psychoneuroendocrine complications sufficient to motivate them for substance abuse treatment. We suggest that this treatment should address at least three etiologic mechanisms by which AAS dependence might develop. First, individuals with body image disorders such as "muscle dysmorphia" may become dependent on AAS for their anabolic effects; these body image disorders may respond to psychological therapies or pharmacological treatments. Second, AAS suppress the male hypothalamic-pituitary-gonadal axis via their androgenic effects, potentially causing hypogonadism during AAS withdrawal. Men experiencing prolonged dysphoric effects or frank major depression from hypogonadism may desire to resume AAS, thus contributing to AAS dependence. AAS-induced hypogonadism may require treatment with human chorionic gonadotropin or clomiphene to reactivate neuroendocrine function, and may necessitate antidepressant treatments in cases of depression inadequately responsive to endocrine therapies alone. Third, human and animal evidence indicates that AAS also possess hedonic effects, which likely promote dependence via mechanisms shared with classical addictive drugs, especially opioids. Indeed, the opioid antagonist naltrexone blocks AAS dependence in animals. By inference, pharmacological and psychosocial treatments for human opioid dependence might also benefit AAS-dependent individuals.

Objective: Many individuals, attempting to gain muscle or lose fat, use ‘dietary supplements’. Though widely available over the counter or by mail order in America and Europe, some of these ‘supplements’ are actually potent drugs such as androstenedione and ephedrine. We sought to estimate the prevalence of these forms of drug use in American gymnasiums. Methods: We distributed anonymous questionnaires to 511 clients entering five gymnasiums, asking about use of both supplements and anabolic steroids. Results: Among men, 18% reported use of androstenedione and/or other adrenal hormones, 25% reported ephedrine use, and 5% reported anabolic steroid use within the last 3 years; among women these rates were 3, 13 and 0%. Extrapolating from these figures to the United States as a whole, we estimated that possibly 1.5 million American gymnasium clients have used adrenal hormones and 2.8 million have used ephedrine within the last 3 years. Conclusions: Millions of men and women are currently using potent drugs, widely sold over the counter as ‘supplements’, despite their known adverse effects, unknown long-term risks, and possible potential for causing abuse or dependence.

Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65 who had refractory depression and low or borderline testosterone levels.Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial.The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone.These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.

Change in calcium response was studied to clarify the pathological process of Alzheimer''s disease (AD). Cultured fibroblasts from patients with familial Alzheimer''s disease (FAD; n = 6), sporadic Alzheimer’s disease (SAD; n = 4), and age-matched healthy control subjects (n = 4) were studied with an ACAS Interactive Laser Cytometer (ACAS-470). Fibroblasts from two independent families with FAD (OS-1, and OS-2 families) showed a suppressed calcium response after stimulation by 100 nM bradykinin (BK) 100 nM Vasopressin (VP)or 10% FCS in Ca2+-free condition compared with control fibroblasts at 48 h after plating. However, on the 7th day after plating, the abnormal calcium response was no longer observed. The height of the calcium peak showed periodic variation, indicating a relationship of calcium response with the cell cycle. When fibroblasts from OS-1 and OS-2 families were arrested in S phase, they showed a significantly suppressed calcium peak after BK stimulation. However, when those fibroblasts were arrested in other phases, they showed the same calcium peak as the other cells. The suppression of calcium response in S phase was indistinguishable from the calcium suppression induced by A23187 administration. Since Hardy type mutation on amyIoid precursor protein gene is found in the OS-1 family, the observed abnormalities in calcium response might be related with pathological processing of amyloid precursor protein in AD. The reported abnormal calcium response, which is observed most obviously in fibroblasts in S phase, may indicate participation of the cell-cycle-dependent process in the pathology of AD.