Anabolic-Androgenic Steroid Dependence: An Emerging DisorderTopical steroid androgenic steroids may be associated with early coronary artery disease, androgenic anabolic research to research presented at the Brazilian Congress of Cardiology SBC This study examined whether anabolic androgenic steroids could be associated with early coronary artery disease. It also tested whether reduced high-density lipoprotein HDL function could be a androgenic anabolic research leading to coronary artery disease in anabolic androgenic steroid users. The study included 51 men with an average age of 29 years range 23 to 43 years. Of those, 21 did weight lifting and had taken anabolic androgenic steroids for at least two years, what is the best way to take dbol androgenic anabolic research weight lifting but did not take steroids, and ten were healthy but sedentary. Participants underwent computed tomography coronary angiography a type of imaging used to visualise androgenic anabolic research arteries to assess the presence of atherosclerosis in the coronary arteries. A urine test was performed in all participants to confirm steroid use.
Effects of Long Term Supplementation of Anabolic Androgen Steroids on Human Skeletal Muscle
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. 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.
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 slightly adapted for cumulatively acting drugs such as AAS. AAS dependence is a valid diagnostic entity, and likely 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 better characterize AAS dependence, identify risk factors for this syndrome, and develop treatment strategies. The anabolic-androgenic steroids AAS are a family of lipophilic hormones derived from cholesterol that includes the natural male hormone, testosterone, together with numerous synthetic testosterone derivatives 1.
By ingesting supraphysiological doses of these hormones, in combination with intensive weight lifting and appropriate nutrition, AAS users can greatly increase their muscle mass, often well beyond the limits attainable by natural means 2.
For decades, elite athletes have used AAS to improve performance 3. Today, however, most AAS users are not competitive athletes, but simply individuals who want to look leaner and more muscular 1 , 4 — 8. As we have explained in detail elsewhere 9 , this much larger but less visible population of illicit AAS users began to emerge in the s — a trend stimulated in part by the appearance of progressively more sophisticated underground guides on how to self-administer AAS 10 — Western cultural developments also likely contributed to the increased prevalence of use of AAS, as media images increasingly focused on male muscularity 15 — Perhaps as a result of these trends, illicit AAS use has now grown into a widespread form of substance abuse throughout Western societies, including the United States 20 — 22 , British Commonwealth countries 23 — 25 , Scandinavian countries 26 — 28 , and others 25 , 29 — By contrast, AAS use in women is uncommon, since women are less likely to want to become very muscular, and are also vulnerable to the masculinizing effects of AAS, such as beard growth, deepening of the voice, and masculinized sexual characteristics 32 — AAS users generally self-administer their drugs for blocks of time, colloquially called "cycles.
Planned cycles of increasing and decreasing AAS doses "pyramiding" allow users to avoid plateauing developing tolerance , minimize withdrawal symptoms at the end of a cycle, and conserve drug supplies Perhaps the most important rationale for cycles, however, is the fact that exogenous AAS administration suppresses the hypothalamic-pituitary-testicular HPT axis, leading to decreased endogenous testosterone production in men 39 , If a man uses AAS in cycles, rather than continuously, then the HPT axis can rebound during the drug-free intervals between cycles, restoring normal endogenous testosterone production.
Many individuals use only a few cycles of AAS in their careers, with a cumulative lifetime exposure of less than 12 months 36 , Such individuals often report few, if any, adverse medical or psychological effects from AAS 41 , On the other hand, some individuals progress from discrete cycles of AAS into a pattern of nearly unbroken use, which may continue despite prominent adverse medical, psychological, and social effects This syndrome of AAS dependence has been recognized for more than 20 years; it appears to be common and possibly increasing in prevalence, as explained below, but much in need of further study 1.
Here we attempt to summarize current knowledge on AAS dependence. We begin with an illustrative case of AAS dependence, then review the accumulating human and animal literature on this topic, compare AAS dependence with classical drug dependence, and suggest avenues for future research. This review is based on publications known to us, a search of publications involving "anabolic steroids" in the PubMed database, and additional publications referenced in these articles.
A, currently 34 years old, grew up in an upper-middle-class professional family in South Florida. He reported no major social or academic problems prior to adolescence, but by age 17 developed alcohol and nicotine dependence, soon followed by polysubstance dependence involving marijuana, hallucinogens, alcohol, and cocaine, depending on which drugs were available.
During this period, however, he began regular weightlifting in the gym, acquired AAS-using friends, and soon began to use AAS himself, starting with cycles of 12—16 weeks in duration, separated by drug-free intervals of 4—8 weeks. Like his AAS-using friends, Mr. A became focused on his muscularity and often felt that he was still not big enough, despite his objective gains. He increased his doses of AAS over the next several years, reaching a maximum weekly dose of mg of injectable testosterone esters, combined with mg of injected nandrolone decanoate, plus 50 mg of oral methenolone per day — a total dose equivalent to more than 20 times normal male endogenous testosterone production He gained some 25 kg of muscle over the course of the first two years; during this time he reported increased self-confidence and mild irritability, but no major adverse psychiatric or medical effects.
At age 22, Mr. A relapsed into use of classical drugs, and developed opioid and cocaine dependence, reaching doses of mg of OxyContin long-acting oxycodone per day. He continued to take AAS intermittently during this period. He underwent three detoxification admissions for opioid dependence over the next four years, and successfully stopped using all classical drugs of abuse including alcohol by age By the age of 32, he also stopped smoking cigarettes.
However, he has continued to use AAS steadily from age 26 to the present. During the first part of this interval, Mr. A still discontinued AAS for several weeks between cycles, but since age 31, he has been taking AAS virtually without interruption. He reports that if he stops using AAS, he quickly develops prominent fatigue, loss of sex drive, and depressed mood. Therefore, he carefully maintains a sufficient supply of AAS to allow uninterrupted use.
A now uses lower doses of AAS than when younger, with an average weekly dose of about — mg of testosterone or equivalent. A expresses concern about these effects, but is reluctant to discontinue or reduce AAS because he fears "losing size. He has worked as a personal trainer for some time in a local health club, then at a store selling sports supplements such as protein powders and creatine.
His life remains centered around the gym and the weightlifting culture, often to the exclusion of other social or occupational opportunities. A's history above resembles that of other cases of AAS dependence previously reported. Interestingly, one of these individuals exhibited symptoms resembling opiate withdrawal when challenged with naloxone, although he had no apparent history of opiate use — an observation suggesting that AAS dependence might be associated with opioid-type features In the first published case series, Brower et al.
Of AAS users across these five studies, As in the case series above, withdrawal was the criterion most commonly met, whereas "frequent intoxication or withdrawal symptoms when expected to function" was rare, as might be expected. However, these latter two studies did not specify the number of AAS users meeting each individual DSM-IV substance dependence criterion in the manner of the studies summarized in Table 1.
It should be recognized that the above studies are naturalistic studies of AAS users recruited in the field from gymnasiums 37 , 50 — 53 , 57 or via the Internet Like all naturalistic studies of illicit substance abusers, these studies are potentially vulnerable to various forms of bias 58 , For example, dependent AAS users may have been either more or less likely to agree to participate in these studies than non-dependent AAS users or AAS nonusers, resulting in selection bias.
Information bias may have resulted if respondents failed to disclose that they have used AAS, or failed to report adverse or undesirable outcomes associated with AAS use. Confounding variables, such as premorbid attributes of AAS users or concomitant use of other substances, may have also influenced observed associations.
However, since human AAS dependence cannot ethically be studied prospectively under laboratory conditions, these field studies presently represent our best available evidence regarding this syndrome. For example, individuals who had experimented only briefly with AAS might be underrepresented in samples recruited from gymnasiums, causing the studies to overestimate the prevalence of AAS dependence.
In any event, however, there is reason to suspect that the prevalence of clinically significant AAS dependence may be increasing.
This impression is based on the observation that the mean age of onset of AAS dependence in the above studies appears to be in the late 20s. Therefore, adverse psychiatric and medical effects of prolonged AAS dependence would likely not surface until age 30 or later 1 , 9. When it is considered that illicit AAS use did not become widespread until the s, as discussed above, it follows that within the subgroup of AAS users who have developed chronic use, many are only now growing old enough to show clinically significant AAS dependence.
Therefore, as new waves of recent younger AAS users reach their 30s and 40s, the prevalence of AAS dependence may continue to rise. We can illustrate the above considerations using prevalence data on male AAS users in the United States. Furthermore, since the median age of onset of initial AAS use in the United States appears to be considerably older than age 19 35 , 36 , one must add to this figure at least another million American men in the last two decades who first initiated AAS use after the age of About half of this year cohort of American AAS users is still under age 30 today.
Chronologically, most other Western countries probably lag the United States in the onset of widespread AAS use — placing them earlier on this possible curve of rising AAS dependence. Despite the substantial prevalence of AAS dependence, little is known about the features of AAS-dependent individuals.
Several studies have noted that dependent users consumed significantly more AAS than non-dependent users, as measured by total dose 50 , number of different AAS taken simultaneously 53 , total number or length of AAS cycles 50 , 51 , 54 , or cumulative duration of AAS use When demographic correlates of dependent use were assessed 50 , 51 , however, no differences between dependent and non-dependent users were found.
However, none of the studies in Table 1 systematically assessed lifetime psychiatric disorders in user groups. In this study, nondependent AAS users exhibited virtually no significant differences from nonusers on any of a wide range of demographic variables or lifetime psychiatric diagnoses, whereas the dependent AAS users differed markedly from both comparison groups on a number of measures. Specifically, dependent AAS users were significantly older and more muscular than the other groups; more likely to have had a single parent by age 13; more likely to report a first-degree relative with a substance use disorder; and less well educated.
Dependent AAS users also reported a much more frequent history of conduct disorder than nondependent AAS users and a much higher lifetime prevalence of non-alcohol substance dependence than either comparison group; the latter differences were driven largely by a strikingly higher prevalence of opioid abuse and dependence — an important finding that we discuss in more detail in the following paragraphs.
Several reports have suggested that AAS dependence might share features with opioid dependence in humans.
As early as , Kashkin and Kleber hypothesized that AAS dependence might arise in part via an opioidergic mechanism, in which AAS might potentiate central endogenous opioid activity, and where AAS withdrawal would lead to a decrease in this activity and a subsequent acute hyperadrenergic syndrome This hypothesized link between AAS and opioids would seem consistent with a number of human observations including 1 the "opioid-type features" described in the case report of AAS dependence cited above 45 ; 2 the observation that AAS users seem to be particularly at risk for developing opioid abuse or dependence 66 — 68 ; 3 the converse finding that men with opioid dependence were more likely to report prior AAS use than men with other forms of substance dependence 69 ; and 4 a post-mortem study of Swedish AAS users, reporting that AAS appeared to reduce the threshold for heroin overdose The recent field study described above adds further evidence for a relationship between AAS and opioids 8.
Among the various men with AAS dependence, opioid abuse or dependence began both before and after the onset of AAS use, suggesting the possibility that these forms of substance use might arise from a common diathesis. Animal studies offer extensive additional evidence that AAS can induce dependence, and further support a link between the actions of AAS and opioids In humans, it is difficult to separate the direct rewarding effects of AAS from the secondary rewards of increased muscularity and fitness.
However, using conditioned place preference and self-administration models of reward, studies in animals have demonstrated that AAS are rewarding in a context where athletic performance is irrelevant. Rats and mice will choose to spend time in an environment where they have previously received AAS 72 , Hamsters will self-administer testosterone, including direct intracranial injections to the point of death, and they develop a syndrome of high-dose testosterone intoxication with opioid-like features Moreover, this syndrome is antagonized by naltrexone, and naltrexone pretreatment will prevent testosterone self-administration Not all animal species, however, appear to self-administer AAS Animal studies also suggest that AAS modify brain opioid systems.
For example, chronic nandrolone treatment in rats increased levels of endogenous opioids and their receptors in select limbic regions, including a fold increase in beta-endorphin in the ventral tegmental area 77 , as well as a selective reduction in dynorphin b in the nucleus accumbens Other studies in rats 79 and mice 80 have also shown that AAS may act by altering levels of opioid receptors. Treatment with kappa receptor antagonists in the nucleus accumbens produces anxiolytic and antidepressant effects 81 , 82 , similar to the effects of AAS The AAS-induced reduction in nucleus accumbens dynorphin might also facilitate dopaminergic activity However it is notable that, unlike many other drugs of abuse, AAS do not acutely stimulate dopamine release in the nucleus accumbens This is consistent with the relatively slow time-course of AAS action, and may account for the absence of acute intoxicating effects.