Anabolic-Androgenic Steroids

Introduction

Anabolic-androgenic steroids (AASs) refer to the male hormone, testosterone, and many of its natural and synthetic derivatives. All AASs have androgenic (masculinizing) and muscle-specific (anabolic) effects, but some are relatively more anabolic or androgenic than others. Oxandrolone, for example, has greater anabolic activity and less androgenic activity than testosterone. All AASs share a cholesterol-like and -derived chemical structure in common with other classes of steroid compounds, such as corticosteroids, mineralocorticoids, and estrogens. Synthetic selective androgen receptor modulators are nonsteroidal anabolic-androgenic drugs, but little is known about the addiction potential of these premarketed substances.

Although AAS use is widely focused on the illicit uses to increase muscle growth and strength, several established medical uses exist for these substances. The US Food and Drug Administration (FDA)–approved medical uses of AASs include male hypogonadism (androgen deficiency), hereditary angioedema (a dermatological disorder), treatment of weight loss associated with AIDS, burns, and other catabolic states, and relatively rare types of anemias including Fanconi and those related to bone marrow suppression (aplastic anemia). Other uses of AASs, including experimental ones, have included male contraception, postmenopausal hormonal therapy, and treatment of depression and sexual disorders.

AASs are rarely used in isolation. Typical appearance and performance enhancing drug (APED) use involves several synthetic androgens and some combination of legal stimulants, illegal stimulants/thermogenic drugs, illicit nonsteroidal anabolics, and legal supplement use. Within the international sports community, APEDs are commonly referred to as “doping agents” and subject to detection by the World Anti-Doping Agency. The use of APEDs by athletes to increase performance constitutes only a small subset of APED users, and the secrecy of this form of drug use prevents any substantial literature on specific patterns of use among athletes. Unlike recreational users, fear of detection leads athletes to use a range of evasion strategies including use of masking agents, altered drug use schedules, and designer drug use.

AASs have some superficial similarities to so-called classical addictive drugs, such as alcohol, cocaine, nicotine, and opioids. A major difference is that AASs are not taken to induce euphoria and have little interoceptive detectability. Rather, APEDs are often taken in the context of a fitness-focused lifestyle that prohibits use of classical drugs of abuse. Although not part of the motivating salience of APEDS, many of these substances have known psychoactive effects. For instance, the psychoactive influence of testosterone on mood has historically been a source of investigation in medicine that persists. Recent advances in the neurobiology of AASs have further increased overall attention to the neurobiology androgen effects on reward. There is now general consensus that AASs are reinforcing and have important psychiatric effects, including the potential for addiction-like pattern of use.

Epidemiology

AASs first entered the mainstream athletic spotlight with the 1956 World Games. The Russian team was discovered to be using AASs at the Vienna weightlifting championships, leading other teams to introduce this seemingly miraculous drug to their athletes. As elite sports athletes continued to misuse these substances, AASs became banned drugs by the International Olympic Committee in 1975. During the Montreal Olympic Games in 1976, eleven athletes were disqualified as a result of urine steroid screening tests that were instituted.

Since then, AAS use has become more commonplace within the population. A meta-analysis of 271 studies yielded a global lifetime prevalence rate of 3.3%, with males significantly more likely than females to have used (6.4% vs. 1.6%). The highest rates were found in “recreational sportspeople” (18.4%) and athletes (13.4%), followed by prisoners and arrestees (12.4%). In the United States., between 2.9 million and 4 million people have tried AAS. In 1990, Congress passed the Anabolic Steroid Control Act, in an effort to reduce use, and anabolic steroids became a Schedule III controlled substance. Anabolic steroid use had spread from professional athletes and body builders to high school athletes and non-athletes striving to improve strength and physical appearance. According to the National Youth Risk Behavior Survey, the percentage of all high school students who ever took steroids without a doctor’s prescription is 3.5. The prevalence of taking steroids without a prescription was higher among male (4.0%) than female (2.7%) students. According to the results from this survey, the prevalence of having ever taken steroids without a doctor’s prescription increased from 1991 to 2001 (2.7%–5.0%) and then decreased somewhat from 2001 to 2015 (5.0%–3.5%). In addition, the University of Michigan Monitoring the Future study, which conducts an annual survey on substance use among high school students, has collected data on steroid use in 8th, 10th, and 12th grade students since 1989. These data show a fairly stable rate of increase from 1991 to 1998 across these groups in overall annual prevalence rate and a gradual decline in use from 1999 to 2016. Lifetime prevalence of AAS use in 12th graders significantly decreased from 2.3% in 2015 to 1.6% in 2016. A consistent finding is that males outnumber females in prevalence of AAS use, ^a

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with onset commonly occurring in one’s early 20s, and risk persisting into middle age.

Overall, men who train extensively by lifting weights for athletic or aesthetic purposes are at highest risk to use AASs. Most studies also support a correlation with alcohol and other drug abuse, with some exceptions (e.g., Striegel et al. ). Conduct disorder during childhood and adolescence and adolescent body image and muscularity concerns are predictive of AAS use in male weightlifters. Body dissatisfaction commonly co-occurs with AAS use, but this finding is not consistent. A severe form of body dissatisfaction among male AAS users has been called muscle dysmorphia (MD), although women may also have it. Individuals with muscle dysmorphia exhibit a persistent belief that they are too weak or small and whose daily behavior is severely impacted by a preoccupation with increasing muscle mass. This syndrome has been compared to eating disorders—thus historically referred to as reverse anorexia nervosa or bigorexia . Individuals with MD may share patterns of cognitive functioning that are similar to individuals with eating and body image disturbances. Specifically, set-shifting difficulties and weak central coherence are positively associated with the drive for muscularity, a symptom of MD. MD also has features of obsessive-compulsive disorder.

Pharmacology

Patterns of Illicit Use

Users often take AAS with the very specific goals of improving physical appearance and athletic abilities. Thus they tend to take these substances in strategic doses and combinations for varying durations. Multiple substances are often combined (“stacked”) to maximize effects and to achieve supraphysiological dosages. These substances are self-administered during the drug cycles that typically last between 4 and 12 weeks. AAS use is sometimes started at low doses and increased to a peak, and then gradually reduced, a pattern referred to as “pyramid” dosing. The polypharmacy of the APED cycle can be complex and relies on recipes passed via expert user circles of an individual trial and error knowledge based in self experimentation. Often ignored, APED users use specific exercise and dietary practices in conjunction with the cycle and postcycle recovery period. Many surveys suggest that AAS users are more likely than nonusers to misuse other addictive drugs. In this regard, it is of interest that AASs can increase sensitivity to alcohol, amphetamine, and opioids. This sensitivity is likely part of a larger adaptation of the central nervous system to rewards of all types.

AASs are readily available through social networks associated with weightlifting gyms. Although classified as Schedule III controlled substances in the Unites States, AASs are available on the Internet, although the real contents may be suspect.

Adverse Medical Effects

Adverse medical effects of AASs have been well reviewed. Adverse medical effects may be transient, relatively reversible, and limited to periods of use and acute withdrawal; or long-term, relatively irreversible, and persistent during periods of sustained abstinence. The short-term effects generate less disagreement among experts than do the long-term effects, because good epidemiological studies of the latter are lacking. The major organ systems that are adversely affected by AASs are endocrine, hepatic, and cardiovascular.