Gen Kanayama

Long-Term Psychiatric and Medical Consequences of Anabolic-Androgenic Steroid Abuse: A Looming Public Health Concern?

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.

Anabolic-androgenic steroid dependence: an emerging disorder.

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 self-administer 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.

Risk factors for anabolic-androgenic steroid use among weightlifters: a case-control study.

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.

Over-the-Counter Drug Use in Gymnasiums: An Underrecognized Substance Abuse Problem?

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.

Long Term Anabolic-Androgenic Steroid Use is Associated with Left Ventricular Dysfunction

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.

The lifetime prevalence of anabolic‐androgenic steroid use and dependence in Americans: Current best estimates

BACKGROUND AND OBJECTIVES Although various surveys have tracked the prevalence of anabolic-androgenic steroid (AAS) use in American teenagers and young adults, no recent surveys have assessed the lifetime prevalence of AAS use in Americans overall. We therefore analyzed serial youth-survey data to derive estimates of the lifetime prevalence of AAS use in the current American general population. METHODS We first determined the distribution of age of onset of AAS use, based on pooled data from nine studies. Using this distribution, we then developed equations to project the eventual lifetime prevalence of AAS use among young survey respondents, once they aged and completed the period of risk for initiating AAS. We similarly calculated the denominator of lifetimes of risk for AAS use in the total American population. We next applied these equations to four independent national youth datasets to derive current American general-population estimates for lifetime AAS use. Finally, using data from 10 pooled studies, we estimated the lifetime prevalence of AAS dependence among AAS users. RESULTS Age-of-onset studies consistently showed that AAS use begins later than most drugs, with only 22% of users (95% confidence interval: 19-25%) starting before age 20. Applying the age-of-onset findings to national youth datasets, we estimated that among Americans currently age 13-50 years, 2.9-4.0 million have used AAS. Within this group, roughly 1 million may have experienced AAS dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE Although subject to various limitations, our estimation techniques suggest a surprisinigly high prevalence of AAS use and dependence among Americans.

Risk factors for illicit anabolic-androgenic steroid use in male weightlifters: a cross-sectional cohort study.

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 < .001. 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.

Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment.

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.

Issues for DSM-V: Clarifying the Diagnostic Criteria for Anabolic-Androgenic Steroid Dependence

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)

Human Growth Hormone Abuse in Male Weightlifters

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.