The influence of anabolic steroids on physiologic processes and exercise

Original Editor - Lester Ryan Top Contributors - Kylie Volk, Matthew Wolfe, Christine Beavers, Marilyn Kozlowski, Ryan Lester, Maddisen Coleman, Emily North, Robert Long, Chelsea Miller, Landon Andrews, Lucinda hampton, Kyle Culver, Brandi Kindiger, Wanda van Niekerk, Samantha McGraw, Graham McIntyre, Taylor Ledford and Katie Sanders

Introduction  

Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for aesthetic purposes, as well as for improvement of their endurance and performance. 

Anabolic-androgenic steroids (AAS) are a group of synthetic compounds that mimic the effects of testosterone in the body. AAS abuse can have profound effects on the cardiovascular system, hepatic function, and adrenal and renal function . As its name refers, AAS has two major effects: androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics whereas anabolic effects increase protein synthesis . The latter effect is why many individuals abuse AAS, with the intent of increasing lean muscle mass.
This interesting 7 minute video summarises the topic

Complications

• Androgens have various side effects. Complications include:
  • Cardiac hypertrophy
  • Decreased serum HDL cholesterol
  • Hypogonadism after discontinuation of exogenous androgens
  • Neuropsychiatric concerns

Many studies show an association between the non-medical use of androgens and increases in risky and criminal behavior among the androgen intake abusers. In a survey of 10 000 to 15 000 college students, use of androgens correlated highly with drinking and driving, cigarette smoking, illicit drug use, and alcohol abuse.

• Anabolic steroids are completely prohibited in sports whether in- or out-of-competition. The following organizations prohibit anabolic steroids intake in sports:
  • National Collegiate Athletic Association (NCAA)
  • International Olympic Committee (IOC)
  • U.S. Anti-Doping Agency (USADA)
  • World Anti-Doping Agency (WADA)
• Anabolic steroid abuse occurs at sports competitions and gyms; one can buy these drugs on the street or purchase them via mail order. Most of the illegal use of androgens is due to anabolic steroids that get smuggled into the USA.

Cardiovascular Effects

Long-term use of supra-physiological 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 .

AAS abuse in body builders has been linked with:

• myocardial infarction
• cardiomyopathy
• sudden death
• elevated blood pressure and increased risk of thrombosis. 
• lower amount of heart rate variability (HRV) than non-users, putting them at an increased risk of autonomic cardiovascular dysfunction and ventricular arrhythmia .
• atrial fibrillation (AF) - This may be due to inter- and intra-atrial electromechanical delay.
• decreased vagal and parasympathetic activity in the heart. Reduced parasympathetic activity in the heart slows the recovery of the heart rate post exercise. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood
• 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 . 
• Hypertension
• ventricular remodeling, and
• myocardial ischemia .

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. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality.

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 .
• AAS disallows glucocorticoids from binding to their receptors. This is important because glucocorticoids produce catabolic effects by depressing protein synthesis .
• AAS psychologically impacts users by producing euphoria, encouraging users to work harder during workouts. In turn, AAS use may lead to rhabdomyolysis by promoting over exertion. 

Athletes use AAS to improve performance as AAS cause muscle hypertrophy and protein synthesis [especially when combined with resistance exercise].

• Stanozolol significantly increased type I muscle fiber size, hypothetically hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy.
• Steroids have not been shown to increase creatine concentrations in the muscle.
• 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.
• 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, 10 Repetition Max (RM), and the number of complete sets at 10RM. Rats in the steroid group performed 47%, 12%, 22%, and 81% better in these areas respectively. 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.
• AAS treatment in combination with exercise delays fatigue during sub-maximal exercise, possibly due to AAS induced muscle fiber transformations.
• AAS can promote muscular development and strength in older populations. AAS use may benefit those recovering from hip surgery. 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.  AAS may increase quadriceps 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. The evidence to support AAS use following TKA is insignificant, but there are some implications that AAS use may benefit those following surgery.

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 . No significant difference was found between the two groups concerning lower extremity tendon ruptures . 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 studie . One study found ultra-structural changes in tendons of mice treated with AAS, but strong evidence of structural changes in human tendons has not been demonstrated. A case-control study compared collagen ultra-structure, 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. 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. 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 .

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.  The increase in endorphin levels and exercise reinforcement may contribute to AAS dependence and abuse.

AAS dependence is characterized by increases in AAS cycles, higher doses, and increases in psychological disorders, such as increased aggression. 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 exacerbate anxiety disorders, schizophrenia, and eating disorders.  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 neurotransmitter receptors. These changes may influence hormone and neurotransmitter levels, such as serotonin or GABA, and lead to changes in depression, anger, or stress. 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.

Deterrence and Patient Education

The potential adverse cardiovascular effects from long-term anabolic steroid use are significant, and health care providers need to bring awareness among patients and implement protocols to help detect patients at risk.