The scientific side of steroid use and abuseAndrogens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to anabolic steroids brain damage muscle growth by manipulating testosterone levels or assuming sustanon 250 hinta anabolic steroids AAS. These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is anabolic steroids brain damage wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common.
The scientific side of steroid use and abuse -- ScienceDaily
Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids AAS. These substances were originally synthesized to obtain anabolic effects greater than testosterone.
Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia.
Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system.
Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. Anabolic-androgenic steroids AAS are synthetic compounds derived from testosterone, which is the main male hormone. The binding of testosterone to androgen receptors has anabolic and androgenic effects.
During puberty, the increase in testosterone levels contributes to linear growth augmentation, as well as muscle mass accumulation Bhasin et al. Testosterone also acts by increasing the number of muscle progenitor cells Sinha-Hikim et al. Testosterone promotes mitochondrial biogenesis, improves net oxygen delivery to the tissue by increasing red cell mass and tissue capillarity, and facilitates oxygen unloading from oxyhemoglobin Coviello et al.
The idea of designing and developing steroids with anabolic properties arose during the s soon after the identification and isolation of the hormone androsterone by the German investigator Butenandt, who collected this compound from thousands of liters of pooled human urine derived from a number of military service volunteers. Most of the AAS used before the s were pharmacological agents approved for medicinal or veterinary use.
By the s, various androgen precursors became nutritional supplements. Androgen precursors are either inactive or weak androgens that the body converts into potent androgens. These include naturally occurring precursors to testosterone, such as 4-androstenediol, 5-androstenediol, 4-androstenedione, and dehydroepiandrosterone, as well as precursors to synthetic AAS including 4-norandrostenedione, 4-norandrostenediol, and 5-norandrostenediol, which the body converts to nandrolone Pope et al.
Other synthetic AAS, such as desmethylstanozolol, methylclostebol, and methyltrienolone have been recently introduced into the market as dietary supplements. Thus, they potentially represent an even more serious health risk than the more traditionally used AAS. From a clinical standpoint, AAS are commonly prescribed to treat several disorders, such as the androgen deficiency syndromes Conway et al.
Less common medical uses of AAS deal with heart and renal failure Basaria et al. Contrasting data exists in the literature regarding the use of AAS in the treatment of androgen deficiency in aging males, infertility, sexual dysfunctions or impotence, as well as post-menopausal syndrome in women. Thus, while a review of Morley points toward therapeutic effects on libido and menopause-induced sarcopenia, Conway et al. Hence, according to the state of the art presented in their review, they reported no indication for androgen therapy in male infertility because of its suppressing effect on spermatogenesis.
Importantly, there is no evidence in available literature that AAS abuse or dependence might develop from the legitimate medical use of AAS. The use of AAS for non-medical intentions can easily determine abuse and lead to dependence. When used by athletes, AAS can improve performance to levels obtainable by virtually any other combination of non-chemical solutions provided by modern sport techniques Noakes, Generally, supra-pharmacological doses of AAS act either by a direct mechanism, promoting an increase in mass, force, speed of muscular contraction, and recovery after intense physical exercise Tremblay et al.
Consumption of high doses of AAS typically consists in 6—12 week cycles, followed by a 6—12 week period of wash-out. These patterns of AAS use may easily precipitate in periods of continuous consumption without any AAS-free intervals due to the fact that abusers try to assure their muscle gains while avoiding withdrawal symptoms Brower, ; Kuhn, Several other drugs are frequently associated with the use of supra-pharmacological doses of AAS by abusers that are designed to increase their effects, diminish side effects or avoid detection by urine testing Wichstrom and Pedersen, The abuse of other illicit drugs, such as amphetamines and opioids, has also been shown to be strengthened by AAS use Arvary and Pope, Moreover, such abuse might reinforce the occurrence of adverse substance interactions.
In particular, in the case of AAS and amphetamine association, the overdose potential appears to be increased, due to cardiotoxicity Thiblin et al.
The contemporary consumption of AAS and bromocriptine, used to rapidly reduce body fat and total weight, has been described as the cause of a syndrome characterized by syncopal episodes and atrial fibrillation Manoharan et al. Populations of adolescents and young adults have been the subject of several clinical studies that explore the prevalence of AAS misuse and abuse. They observed that steroid use was more common in non-Caucasian males and in middle school students as compared to high school.
In males, steroid use was associated with poor self-esteem, higher rates of depressed mood and attempted suicide, poor knowledge and attitudes about health, greater participation in sports emphasizing weight and shape, greater parental concern about weight, and higher rates of eating disorders and substance abuse. In a study by Wichstrom and Pedersen , a representative sample of Norwegian youths 15—22 years of age was surveyed. Results showed that AAS use did not vary according to sport involvement or demographics.
Moreover, AAS use was associated mainly with the abuse of marijuana, aggressive-type conduct problems and eating disorders. The severity and impact of side effects induced by AAS abuse depend on a wide range of factors, such as dose, duration of administration, possible consumption of a combination of AAS, as well as gender and age of the abusers. Data on the impact of sustained administration, failed to show any documented adverse events associated to a single episode of acute consumption of supra-pharmacological doses of AAS.
Their abuse has been shown to be associated to greater effects on physical performance in younger individuals and women, together with increased incidence and risk of developing serious side events Kindlundh et al.
Few data exist on the risk of side effects linked to long-term use of high-dose of AAS for non-therapeutic purposes Parssinen and Seppala, Cardiovascular complications have been widely described in AAS abusers, including the occurrence of arrhythmic events Furlanello et al. In a recent post-mortem study that compared 87 deceased men positive for AAS with control subjects Far et al.
In another clinical investigation, ventricular hypertrophy, associated with fibrosis and myocytolysis, was detected after cardiac death in four AAS users Montisci et al. Also, controlled studies realized by echocardiography Krieg et al. Pathological effects on urogenital and reproductive systems have been reported.
In particular, hypogonadotropic hypogonadism with consequent testicular atrophy in men and development of inhibitory mechanisms for FSH and LH production in women have been described in selected populations of AAS abusers Anderson and Wu, ; Dohle et al.
Increased virility and lowering of voice tone, irregular menstruation with infertility, decreased breast size, hypertrophic clitoris, and increased sexual desire have also been described in a population of female AAS abusers Franke and Berendonk, ; Kutscher et al. Other complications include liver damage and hepatitis Tanaka et al. Although several studies point toward a reversibility of undesirable AAS-induced effects following suspension, they can become irreversible complications with prolonged AAS abuse Kutscher et al.
AAS are universally recognized to have psychoactive effects Yates, Although some spared studies have reported their therapeutic use in depression to improve mood and anergia Rabkin et al. Indeed, suicide and homicide have been shown to be the main cause of premature deaths among steroid users and, in particular, in the teen population Thiblin et al. Although this does not imply that all steroid users will suffer crippling depression or homicidal rage, steroids appear to strongly contribute to psychiatric dysfunctions in susceptible individuals.
Globally, the prevalence of AAS-induced psychiatric disorders has been hard to evaluate and determine, because of sampling biases in clinical case reports.
In a review of Pope et al. However, this estimated percentage appears to be influenced by the fact that in most controlled trials, it is not possible to completely mimic the extreme doses and combinations of AAS taken by abusers for ethical reasons. Thus, estimated rates of AAS-induced psychiatric alterations are probably even higher. This is also due to the fact that other factors can increase the likelihood of psychiatric consequences of AAS abuse, such as the presence of a positive psychiatric anamnesis, alcohol, or other drug use Dean, as well as other medical comorbidities.
For example, in a case-report of Morton et al. Psychological motivations contributing to anabolic steroid use and abuse have received little attention in psychiatric literature. Clinical studies demonstrate that steroids are used in part to deal with an earlier trauma, such as childhood physical or sexual abuse Porcerelli and Sandler, The data in the literature show no documented cases of dependence induced by AAS use at therapeutic doses. This suggests that dependence is likely associated to the use of higher doses of AAS Long et al.
However, molecular mechanisms leading to AAS-induced dependence are still unclear. In a review of the scientific literature published between and Brower, , AAS dependence was defined as a diagnosable mental disorder. Between and , two more diagnostic studies of AAS dependence were published Midgley et al.
In the s, Tennant et al. The initial phase of the AAS-induced withdrawal lasting for about 1 week seemed to be comparable to opioid-induced withdrawal, while the second phase was mostly characterized by clear depressive symptoms and craving Tennant et al.
Considerable evidence suggests that AAS dependence might share crucial mechanisms of opioid dependence in humans. In , Kashkin and Kleber posited that AAS dependence might partly arise via an opioidergic mechanism, through which AAS might enhance the activity of central endogenous opioids, and AAS withdrawal would lead to a decrease in this activity and a subsequent acute hyperadrenergic syndrome Kashkin and Kleber, This posited link between AAS and opioids was later confirmed by a large number of observations indicating that AAS users seem to be particularly at risk for developing opioid abuse or dependence McBride et al.
Additional clinical studies provided evidence that AAS might decrease the analgesic action of both metamizol and morphine Philipova et al. In , a study by Kanayama et al. In the population included in that study, opioid abuse or dependence began either before or after the onset of AAS use, suggesting the possibility that these forms of substance abuse might arise from a common molecular pathway Kanayama et al.
However, in a study of Negus et al. AAS seem to act through a more modest reinforcement mechanism compared to cocaine or heroin and resembles the reinforcement mechanism described for caffeine, nicotine, and benzodiazepines. In , Brower proposed a 2-stage model of steroid dependence. Stage 2 deals with consequent chronic use, following which physiological and psychological dependence may develop, thereby making it increasingly difficult for users to quit. Psychoactive effects, such as mood changes and increases in aggressive behavior, characterize this stage of dependence.
In Stage 2, addiction treatment may be required, especially when AAS abuse is associated with other substance dependence, such as alcohol, opioids, or amphetamine abuse Brower, Arvary and Pope investigated this phenomenon in a clinical study, including patients admitted to a private facility for dependence on heroin or other opioids.
Results of this study strongly suggested that these patients were introduced to opioids through AAS use and bodybuilding physical activity. A second model, explaining mechanisms leading to AAS dependence, has also been proposed Bahrke and Yesalis, This model holds that AAS-dependence development occurs specifically in socio-cultural contexts that are likely to motivate certain individuals, particularly men, to attain large and strong muscles by frequent and intensive training sessions.
These training sessions also improve mood and self-esteem and are generally associated with very strict and controlled dietary regimens. Thus, AAS-induced muscle-active effects might underlie the reinforcing actions of these compounds Midgley et al. Studies to elucidate mechanisms leading to AAS dependence have also included surveys of current and former AAS users, recruited from gyms, websites, and physicians. Specific dysfunctions of the various components of the brain reward system have been described in clinical studies.
For example, alterations in levels of monoamine metabolites, neurohormones, and neuropeptides, which play a crucial role in the reward mechanism, have been investigated in the cerebrospinal fluid of subjects who received methyltestosterone MT with respect to placebo-treatment Daly et al.
In particular, changes in cerebrospinal fluid 5-HIAA significantly correlated with the activation of specific psychiatric symptom cluster scores.