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The influence of anabolic steroids on physiologic processes and exercise

2015-12-04

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= '''Introduction''' =

= '''Introduction''' =

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Anabolic-androgenic steroids (AAS) are a group of synthetic compounds that mimic the effects of testosterone in the body<ref name="NIH DEF">National Institute on Drug Abuse. Anabolic Steroids. http://www.drugabuse.gov/publications/drugfacts/anabolic-steroids (accessed November 10, 2015)</ref>. AAS abuse can have profound effects on the cardiovascular system, hepatic function, adrenal and renal function <ref name="Modlinski">Modlinski R, Fields KB. The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands. Current Sports Medicine Reports. 2006; 5: 104-
109
</ref>. As its name refers, AAS has two major effects: androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics, and anabolic effects increase protein synthesis <ref name="Modlinski" />. The latter effect is why many individuals abuse AAS, with the intent of increasing lean muscle mass. 

+

Anabolic-androgenic steroids (AAS) are a group of synthetic compounds that mimic the effects of testosterone in the body<ref name="NIH DEF">National Institute on Drug Abuse. Anabolic Steroids. http://www.drugabuse.gov/publications/drugfacts/anabolic-steroids (accessed November 10, 2015)</ref>. AAS abuse can have profound effects on the cardiovascular system, hepatic function, adrenal and renal function <ref name="Modlinski">Modlinski R, Fields KB. The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands. Current Sports Medicine Reports. 2006;5
(2)
:104-
9.

+

http://link.springer.com/article/10.1007/s11932-006-0039-7
</ref>. As its name refers, AAS has two major effects: androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics, and anabolic effects increase protein synthesis <ref name="Modlinski" />. The latter effect is why many individuals abuse AAS, with the intent of increasing lean muscle mass. 

= '''Cardiovascular Effects''' =

= '''Cardiovascular Effects''' =

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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 <ref name="Achar">Achar S, Rostamian A, Narayan SM. Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. The American journal of cardiology. 2010;106(6):893-901. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111565/</ref>. AAS abuse in body builders has been linked with elevated blood pressure and increased risk of thrombosis<ref name="Kuipers H">Kuipers H, Wijnen JA, Hartgens F, Willems SM.Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders. Int J Sports Med 1991;12(4):413-8.</ref><ref name="Laroche GP">Laroche GP. Steroid anabolic drugs and arterial complications in an athlete-a case history. Angiology 1990;41(11):964-9.</ref>. 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 <ref name="Maior">Maior A, Carvalho A, Marques-Neto S, Menezes P, Soares P, Nascimento J. Cardiac autonomic dysfunction in anabolic steroid users. Scandinavian journal of Medicine and Science in Sports. 2013;23(5):548-55. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0838.2011.01436.x/full</ref>. Some evidence suggests a causal link between power athletes, body builders, and supraphysiological AAS use with atrial fibrillation (AF) <ref>Lau DH, Stiles MK, John B, Young GD, Sanders P. Atrial fibrillation and anabolic steroid abuse. International journal of cardiology. 2007;117(2):e86-e7. http://www.researchgate.net/profile/Martin_Stiles/publication/6469883_Atrial_fibrillation_and_anabolic_steroid_abuse/links/00b49528eb236dea49000000.pdf</ref>. 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 decresed vagal and parasympathetic activity in the heart<ref name="Maior" /><ref name="Hedman">Hedman A, Hartikainen J, Tahvanainen K, Hakumäki M. The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic ‘tone’. Acta Physiologica Scandinavica. 1995;155(3):267-73. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+8619324</ref>. Reduced parasympathetic activity in the heart slows the recovery of heart rate post exercise<ref name="Maior" />. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood<ref>Akçakoyun M, Alizade E, Gündoğdu R, Bulut M, Tabakcı MM, Açar G, et al. Long-term anabolic androgenic steroid use is associated with increased atrial electromechanical delay in male bodybuilders. Biomed Res Int. 2014;2014:8. http://www.hindawi.com/journals/bmri/2014/451520/abs/</ref>. 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 <ref name="D'Andrea et al">D’Andrea A, Caso P, Salerno G, Scarafile R, De Corato G, Mita C, et al. Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis. British journal of sports medicine. 2007;41(3):149-55. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2465218/</ref>. Hypertension, ventricular remodeling, and myocardial ischemia have also been associated with anabolic steroid use<ref name="refst">Sullivan M, Martinez C, Gennis P, Gallagher E. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41(1). doi:10.1016/S0033-0620(98)80019-4</ref>. 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<ref name="refst" />. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality<ref name="refst" />.

+

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 <ref name="Achar">Achar S, Rostamian A, Narayan SM. Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. The American journal of cardiology. 2010;106(6):893-901. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111565/</ref>. AAS abuse in body builders has been linked with elevated blood pressure and increased risk of thrombosis<ref name="Kuipers H">Kuipers H, Wijnen JA, Hartgens F, Willems SM.Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders. Int J Sports Med 1991;12(4):413-8.
http://europepmc.org/abstract/med/1917227
</ref><ref name="Laroche GP">Laroche GP. Steroid anabolic drugs and arterial complications in an athlete-a case history. Angiology 1990;41(11):964-9.
http://ang.sagepub.com/content/41/11/964.short
</ref>. 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 <ref name="Maior">Maior A, Carvalho A, Marques-Neto S, Menezes P, Soares P, Nascimento J. Cardiac autonomic dysfunction in anabolic steroid users. Scandinavian journal of Medicine and Science in Sports. 2013;23(5):548-55. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0838.2011.01436.x/full</ref>. Some evidence suggests a causal link between power athletes, body builders, and supraphysiological AAS use with atrial fibrillation (AF) <ref>Lau DH, Stiles MK, John B, Young GD, Sanders P. Atrial fibrillation and anabolic steroid abuse. International journal of cardiology. 2007;117(2):e86-e7. http://www.researchgate.net/profile/Martin_Stiles/publication/6469883_Atrial_fibrillation_and_anabolic_steroid_abuse/links/00b49528eb236dea49000000.pdf</ref>. 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 decresed vagal and parasympathetic activity in the heart<ref name="Maior" /><ref name="Hedman">Hedman A, Hartikainen J, Tahvanainen K, Hakumäki M. The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic ‘tone’. Acta Physiologica Scandinavica. 1995;155(3):267-73. http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+8619324</ref>. Reduced parasympathetic activity in the heart slows the recovery of heart rate post exercise<ref name="Maior" />. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood<ref>Akçakoyun M, Alizade E, Gündoğdu R, Bulut M, Tabakcı MM, Açar G, et al. Long-term anabolic androgenic steroid use is associated with increased atrial electromechanical delay in male bodybuilders. Biomed Res Int. 2014;2014:8. http://www.hindawi.com/journals/bmri/2014/451520/abs/</ref>. 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 <ref name="D'Andrea et al">D’Andrea A, Caso P, Salerno G, Scarafile R, De Corato G, Mita C, et al. Left ventricular early myocardial dysfunction after chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain imaging analysis. British journal of sports medicine. 2007;41(3):149-55. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2465218/</ref>. Hypertension, ventricular remodeling, and myocardial ischemia have also been associated with anabolic steroid use<ref name="refst">Sullivan M, Martinez C, Gennis P, Gallagher E. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998;41(1). doi:10.1016/S0033-0620(98)80019-4</ref>. 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<ref name="refst" />. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality<ref name="refst" />.





= '''Muscular System Effects''' =

= '''Muscular System 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 <ref name="Haupt">Haupt HA, Rovere GD. Anabolic steroids: a review of the literature. Am J Sport Med 1984;12:469-84 http://europepmc.org/abstract/med/6391216</ref>. AAS disallows glucocorticoids from binding to their receptors. This is important because glucocorticoids produce catabolic effects by depressing protein synthesis <ref name="Haupt" />. AAS psychologically impacts users by producing euphoria, encouraging users to work harder during workouts <ref name="Haupt" />. In turn, AAS use may lead to rhabdomyolysis by promoting over exertion <ref name="deltoid">Farkash, U., Shabshin, N., &amp;amp;amp;amp;amp;amp; Pritsch (Perry), M. (2009). Rhabdomyolysis of the Deltoid Muscle in a Bodybuilder Using Anabolic-Androgenic Steroids: A Case Report. Journal of Athletic Training, 44(1), 98–100.</ref><ref name="british">Adamson, R., Rambaran, C., &amp;amp;amp;amp;amp;amp; D'Cruz, D. P. (2005). Anabolic steroid-induced rhabdomyolysis. [Abstract]. British Journal of Hospital Medicine, 66(6), 362. doi:10.12968/hmed.2005.66.6.18414</ref><ref name="european">Braseth, N. R., Allison, E. J., Jr., &amp;amp;amp;amp;amp;amp; Gough, J. E. (2001). Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. European Journal of Emergency Medicine, 8(2), 155-157.</ref><ref name="german">Daniels, J. M., van Westerloo, D. J., de Hon, O. M., &amp;amp;amp;amp;amp;amp; Frissen, P. H. (2006). Rhabdomyolysis in a bodybuilder using steroids. [Abstract]. Ned Tijdschr Geneeskd, 150(19), 1077-1080.</ref><ref name="necrotising">Hughes, M., &amp;amp;amp;amp;amp;amp; Ahmed, S. (2011). Anabolic androgenic steroid induced necrotising myopathy. Rheumatology International, 31(7), 915-917. doi:10.1007/s00296-009-1235-6</ref>.

+

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 <ref name="Haupt">Haupt HA, Rovere GD. Anabolic steroids: a review of the literature. Am J Sport Med 1984;12:469-84 http://europepmc.org/abstract/med/6391216</ref>. AAS disallows glucocorticoids from binding to their receptors. This is important because glucocorticoids produce catabolic effects by depressing protein synthesis <ref name="Haupt" />. AAS psychologically impacts users by producing euphoria, encouraging users to work harder during workouts <ref name="Haupt" />. In turn, AAS use may lead to rhabdomyolysis by promoting over exertion <ref name="deltoid">Farkash, U., Shabshin, N., &
amp;
amp;amp;amp;amp;amp;amp;amp;amp; Pritsch (Perry), M. (2009). Rhabdomyolysis of the Deltoid Muscle in a Bodybuilder Using Anabolic-Androgenic Steroids: A Case Report. Journal of Athletic Training, 44(1), 98–100.</ref><ref name="british">Adamson, R., Rambaran, C., &
amp;
amp;amp;amp;amp;amp;amp;amp;amp; D'Cruz, D. P. (2005). Anabolic steroid-induced rhabdomyolysis. [Abstract]. British Journal of Hospital Medicine, 66(6), 362. doi:10.12968/hmed.2005.66.6.18414</ref><ref name="european">Braseth, N. R., Allison, E. J., Jr., &
amp;
amp;amp;amp;amp;amp;amp;amp;amp; Gough, J. E. (2001). Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. European Journal of Emergency Medicine, 8(2), 155-157.</ref><ref name="german">Daniels, J. M., van Westerloo, D. J., de Hon, O. M., &
amp;
amp;amp;amp;amp;amp;amp;amp;amp; Frissen, P. H. (2006). Rhabdomyolysis in a bodybuilder using steroids. [Abstract]. Ned Tijdschr Geneeskd, 150(19), 1077-1080.</ref><ref name="necrotising">Hughes, M., &
amp;
amp;amp;amp;amp;amp;amp;amp;amp; Ahmed, S. (2011). Anabolic androgenic steroid induced necrotising myopathy. Rheumatology International, 31(7), 915-917. doi:10.1007/s00296-009-1235-6</ref>.

-

Athletes use AAS to improve performance. AAS causes muscle hypertrophy and protein synthesis, especially when combined with resistance exercise <ref name="Tamaki">Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Roy RR, Edgerton VR. Anabolic steroids increase exercise tolerance. American Journal of Physiology-Endocrinology And Metabolism. 2001;280(6):E973-E81.
fckLRhttp
://ajpendo.physiology.org/content/280/6/E973.short</ref>. A 1988 study found that stanozolol significantly increased type I muscle fiber size <ref name="stanozolol">Hosegood JL, Franks AJ. Response of human skeletal muscle to the anabolic steroid stanozolol. BMJ. 1988;297(6655):1028-9.
fckLRhttp
://www.ncbi.nlm.nih.gov/pmc/articles/PMC1834821/pdf/bmj00308-0040.pdf</ref>. The authors hypothesized that hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy <ref name="stanozolol" />. 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 <ref name="powerlifters">Kadi F, Eriksson A, Holmner S, Thornell L-E. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Medicine and science in sports and exercise. 1999;31(11):1528-34. http://europepmc.org/abstract/med/10589853</ref>. Steroids have not been shown to increase creatine concentrations in the muscle <ref name="BStorer">Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The Effects of supraphysiologic doses of testosterone on muscle size and strength in normal men.Abridged version: NEJM 1996;335:1–7.Full version: http://www.nejm.org/doi/pdf/10.1056/nejm199607043350101 (accessed 28 Oct 2015).</ref>. 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 <ref name="BStorer" />.

+

Athletes use AAS to improve performance. AAS causes muscle hypertrophy and protein synthesis, especially when combined with resistance exercise <ref name="Tamaki">Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Roy RR, Edgerton VR. Anabolic steroids increase exercise tolerance. American Journal of Physiology-Endocrinology And Metabolism. 2001;280(6):E973-E81.
http
://ajpendo.physiology.org/content/280/6/E973.short</ref>. A 1988 study found that stanozolol significantly increased type I muscle fiber size <ref name="stanozolol">Hosegood JL, Franks AJ. Response of human skeletal muscle to the anabolic steroid stanozolol. BMJ. 1988;297(6655):1028-9.
http
://www.ncbi.nlm.nih.gov/pmc/articles/PMC1834821/pdf/bmj00308-0040.pdf</ref>. The authors hypothesized that hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy <ref name="stanozolol" />. 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 <ref name="powerlifters">Kadi F, Eriksson A, Holmner S, Thornell L-E. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Medicine and science in sports and exercise. 1999;31(11):1528-34. http://europepmc.org/abstract/med/10589853</ref>. Steroids have not been shown to increase creatine concentrations in the muscle <ref name="BStorer">Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The Effects of supraphysiologic doses of testosterone on muscle size and strength in normal men.Abridged version: NEJM 1996;335:1–7.Full version: http://www.nejm.org/doi/pdf/10.1056/nejm199607043350101 (accessed 28 Oct 2015).</ref>. 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 <ref name="BStorer" />.

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 <ref name="Tamaki" />. Rats in the steroid group performed 47%, 12%, 22%, and 81% better in these areas respectively <ref name="Tamaki" />. 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 <ref name="Tamaki" />. 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 <ref>Van Zyl CG, Noakes TD, Lambert MI. Anabolic-androgenic steroid increases running endurance in rats. Med Sci Sport Exer, 1995;27(10):1385-9. http://europepmc.org/abstract/med/8531609</ref>. 

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 <ref name="Tamaki" />. Rats in the steroid group performed 47%, 12%, 22%, and 81% better in these areas respectively <ref name="Tamaki" />. 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 <ref name="Tamaki" />. 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 <ref>Van Zyl CG, Noakes TD, Lambert MI. Anabolic-androgenic steroid increases running endurance in rats. Med Sci Sport Exer, 1995;27(10):1385-9. http://europepmc.org/abstract/med/8531609</ref>.