The influence of anabolic steroids on physiologic processes and exercise

Introduction  

Anabolic-androgenic steroids (AAS) are a group of synthetic compounds that mimic the effects of testosterone in the body[1]. AAS abuse can have profound effects on the cardiovascular system, hepatic function, and adrenal and renal function [2]. As its name refers, AAS has two major effects: androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics; anabolic effects increase protein synthesis [2]. The latter effect is why many individuals abuse AAS, with the intent of increasing lean muscle mass.

Cardiovascular Effects

Long-term use of supraphysiological doses of AAS has been associated with the development of pathological changes in the cardiovascular system. AAS users are at an increased risk of myocardial infarction, cardiomyopathy, sudden death, cardiovascular morbidity, and mortality when compared to non-users [3]. AAS abuse in body builders has been linked with elevated blood pressure and increased risk of thrombosis[4][5]. AAS users have been shown to have a lower amount of heart rate variability (HRV) than non-users, putting them at an increased risk of autonomic cardiovascular dysfunction and ventricular arrhythmia [6]. Some evidence suggests a causal link between power athletes, body builders, and supraphysiological AAS use with atrial fibrillation (AF) [7]. This may be due to inter- and intra-atrial electromechanical delay. AAS users have been found to have a lower measurement of high frequency power, which is indicative of decreased vagal and parasympathetic activity in the heart[6][8]. Reduced parasympathetic activity in the heart slows the recovery of the heart rate post exercise[6]. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood[9]. Evidence has shown a relationship between long-term AAS abuse and left ventricular dysfunction. A 2007 study published by the British Journal of Sports Medicine used Doppler myocardial and strain imaging analysis and found that chronic AAS abuse produced a much lower early diastolic peak velocity at the levels of the lateral wall of the left ventricle and the interventricular septum [10]. Hypertension, ventricular remodeling, and myocardial ischemia have also been associated with anabolic steroid use[11]. The normal adaptive mechanisms of the heart in response to exercise are negatively affected by both exogenous and endogenous steroids, leading to cellular alterations that are similar to those exhibited with heart failure and cardiomyopathy[11]. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality[11].

Muscular Effects

AAS utilize three physiological mechanisms on the muscular system to produce its effects. At the cellular level, AAS increases protein synthesis via gene transcription after binding to androgenic receptors [12]. AAS disallows glucocorticoids from binding to their receptors. This is important because glucocorticoids produce catabolic effects by depressing protein synthesis [12]. AAS psychologically impacts users by producing euphoria, encouraging users to work harder during workouts [12]. In turn, AAS use may lead to rhabdomyolysis by promoting over exertion [13][14][15][16][17]

Athletes use AAS to improve performance. AAS causes muscle hypertrophy and protein synthesis, especially when combined with resistance exercise [18]. A 1988 study found that stanozolol significantly increased type I muscle fiber size [19]. The authors hypothesized that hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy [19]. A study of 19 power lifters explained that the proportion of type I and type IIA fibers were similar regardless of steroid use, but steroid users’ fibers had significantly larger areas [20]. Steroids have not been shown to increase creatine concentrations in the muscle [21]. Injection of 600 mg of testosterone in adult males who did not exercise resulted in a greater increase in strength and fat free mass than in individuals who incorporated resistance training but only took a placebo [21].

Two separate studies found that use of AAS increases exercise capacity, muscle endurance, and running endurance in rats. A 2001 study measured total amount of weight lifted, the total number of sets, 10RM, and the number of complete sets at 10RM [18]. Rats in the steroid group performed 47%, 12%, 22%, and 81% better in these areas respectively [18]. The study found that AAS treatment before a single bout of exhaustive weight-lifting exercise enhances the fatigue resistance in involved muscles and increases protein synthesis [18]. A separate 1995 study showed that AAS treatment in combination with exercise delays fatigue during sub-maximal exercise, possibly due to AAS induced muscle fiber transformations [22].

Correlations between AAS use and upper extremity tendon rupture exist. Out of 88 AAS users in one study, 17% had confirmed triceps or biceps tendon ruptures, compared to none of the non AAS users [23] . No significant difference was found between the two groups concerning lower extremity tendon ruptures [23] . The mechanism of AAS-associated tendon rupture is not well understood. One hypothesis is that AAS use combined with intense exercise may cause structural tendon damage. Most evidence supporting this hypothesis comes from animal studies [23]. One study found ultrastructural changes in tendons of mice treated with AAS [24], but strong evidence of structural changes in human tendons has not been demonstrated [23]. A case-control study compared collagen ultrastructure, metabolism, and mechanical properties of patella tendons in 24 individuals assigned to three groups: resistance-trained AAS users (RTS), resistance-trained non-AAS users (RT), and a control group that neither used AAS nor resistance-trained (CTRL). Higher patellar stiffness and tensile modulus was found in the RTS group, but there was no significant difference in mechanical and material properties of the tendons between the RTS and RT groups [25]. A competing hypothesis suggests that AAS use causes hypertrophy in the muscle without causing corresponding changes in the tendon tissue. Sudden or maximal stress can cause tendon injury [23]. Lastly, a study on retired National Football League (NFL) players found an association between AAS use and an increased likelihood of musculoskeletal injury, specifically ligamentous injuries [26].

AAS can promote muscular development and strength in older populations. AAS use may benefit those recovering from hip surgery [27]. A randomized controlled study of 274 elderly men with frailty concluded that administering testosterone may improve quality of life by improving strength, physical function, and body composition. [28]  AAS may increase quadricep strength following total knee athroplasty (TKA) but there were no changes in outcomes related to activities of daily living such as hamstring strength, sit-to-stand test, or walking speed.[29] The evidence to support AAS use following TKA is insignificant, but there are some implications that AAS use may benefit those following surgery.[29]

Neurological Effects

AAS use is associated with both positive and negative psychological effects. AAS abuse and dependence is a potential problem among AAS users, especially those using it for performance or aesthetic purposes. AAS may increase beta-endorphin levels, decrease cortisol levels, and increase ACTH levels, which may lead to an increase in positive associations with exercise[30].  The increase in endorphin levels and exercise reinforcement may contribute to AAS dependence and abuse[30]. AAS dependence is characterized by increases in AAS cycles, higher doses, and increases in psychological disorders, such as increased aggression[31]. Depression and suicide can be caused by off-cycles of AAS or withdrawal from AAS use.  The risk for depression and suicide may be caused by the decrease in endorphin levels and changes in the reward systems of the brain. AAS can cause or exaccerbate anxiety disorders, schizophrenia, and eating disorders[31].  The psychopathology of AAS is theorized to be caused by direct or indirect changes in the central nervous system, including changes to intracellular receptors and neruotransmitter receptors. These changes may influence hormone and neurotransmitter levels, such as serotonin or GABA, and lead to changes in depression, anger, or stress[31]. AAS use may contribute to motivation and positive experiences with exercise, but it can lead to negative effects that are long-lasting and decreases in motivation to exercise.

Conclusion

AAS increases protein synthesis and lean muscle mass.[12][2][18] AAS promotes muscle hypertrophy in Type I and Type IIa fibers.[18][19][20] AAS may increase exercise capacity, muscle endurance, and aerobic performance.[18][22] AAS can lead to increases in strength without resistance training.[21]

AAS use may improve recovery from hip surgery and TKA.[27][29] It may help elderly adult males to improve quality of life.[28]

AAS may lead to euphoria and increased endorphin levels, which may promote increased motivation to exercise and continuation of exercise.[12][30]

Potential Risk Factors:

The cardiovascular effects include hypertension, myocardial infarction, cardiomyopathy, increased risk of thrombosis, ventricular arrhythmia, atrial fibrillation, and reduced parasympathetic activity. [2][3][4][5][6][8][9][11]

AAS may cause an increased risk of tendon rupture, and increased tendon stiffness.[23][26][25]

May lead to over-exertion and increase the risk of rhabdomyolysis.[13][14][16][17]

AAS use can lead to changes in hormone levels. The increase in androgens can lead to masculization in females and altered production of sex hormones in males.[2]

AAS can exacerbate or lead to many psychological disorders including depression, increased anger, increased aggression, anxiety disorders, schizophrenia, and eating disorders.[31]

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