The influence of anabolic steroids on physiologic processes and exercise: Difference between revisions

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= '''Introduction'''    =
= '''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 esthetic purposes, as well as for improvement of their endurance and performances<ref>Bertozzi G, Sessa F, Albano GD, Sani G, Maglietta F, Roshan MH, Volti GL, Bernardini R, Avola R, Pomara C, Salerno M. [https://link.springer.com/article/10.1007/s12035-017-0774-1 The role of anabolic androgenic steroids in disruption of the physiological function in discrete areas of the central nervous system]. Molecular neurobiology. 2018 Jul 1;55(7):5548-56. Available from: https://link.springer.com/article/10.1007/s12035-017-0774-1 (last accessed 20.12.2019)</ref>. 


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, and 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:&nbsp;androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics; 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.<br>  
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, and 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:&nbsp;androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics; 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.<br>  
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{{#ev:youtube|https://www.youtube.com/watch?v=v5Rv8XWmvoQ|width}}<ref>BBC Earth lab What happens when you take steroids Available from: https://www.youtube.com/watch?v=v5Rv8XWmvoQ (last accessed 20.12.2019)</ref>  
{{#ev:youtube|https://www.youtube.com/watch?v=v5Rv8XWmvoQ|width}}<ref>BBC Earth lab What happens when you take steroids Available from: https://www.youtube.com/watch?v=v5Rv8XWmvoQ (last accessed 20.12.2019)</ref>  


= '''Cardiovascular Effects'''  =
=== '''Important Issues'''  ===
 
* AAS increases protein synthesis and lean muscle mass.<ref name="Haupt" /><ref name="Modlinski" /><ref name="Tamaki" /> AAS promotes muscle hypertrophy in Type I and Type IIa fibers.<ref name="Tamaki" /><ref name="stanozolol" /><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> AAS may increase exercise capacity, muscle endurance, and aerobic performance.<ref name="Tamaki" /><ref name="Van" /> AAS can lead to increases in strength without resistance training.<ref name="BStorer" />
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>.&nbsp;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 decreased 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>.&nbsp;Reduced parasympathetic activity in the heart slows the recovery of the heart rate post exercise<ref name="Maior" /><span style="line-height: 1.5em; font-size: 13.28px;">. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood</span><ref name="Akçakoyun">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><span style="line-height: 1.5em; font-size: 13.28px;">. Evidence has shown a relationship between long-term AAS</span><span style="line-height: 1.5em;">&nbsp;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&nbsp;<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>.&nbsp;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" />.
* AAS use may improve recovery from hip surgery and TKA.<ref name="Farooqi">Farooqi V, Van Den Berg M, Cameron I. Anabolic steroids for rehabilitation after hip fracture in older people. The Cochran Collaboration. 2013:</ref><ref name="Metcalfe">Metcalfe D., Watts E., Masters JP., Smith N. Anabolic steroids in patients undergoing total knee arthroplasty. BMJ Open. 2011; 2(5): Doi: 10.1136/bmjopen-2012-001435</ref> It may help elderly adult males to improve quality of life.<ref name="fraility">Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MDL, Adams JE, Oldham JA, Wu FCW. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: A randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010;95(2):639-50. http://press.endocrine.org/doi/full/10.1210/jc.2009-1251</ref>
</span>  
* AAS may lead to euphoria and increased endorphin levels, which may promote increased motivation to exercise and continuation of exercise.<ref name="Haupt" /><ref name="Hildebrandt" /><br><br>'''Potential Risk Factors:''' <br>


= '''Muscular Effects'''  =
* The cardiovascular effects include hypertension, myocardial infarction, cardiomyopathy, increased risk of thrombosis, ventricular arrhythmia, atrial fibrillation, and reduced parasympathetic activity. <ref name="Modlinski" /><ref name="Achar" /><ref name="Kuipers H" /><ref name="Laroche GP" /><ref name="Maior" /><ref name="Hedman" /><ref name="Akçakoyun" /><ref name="refst" /><br>
* AAS may cause an increased risk of tendon rupture, and increased tendon stiffness.<ref name="Kanayama" /><ref name="Horn" /><ref name="Seynnes" /><br>
* May lead to over-exertion and increase the risk of rhabdomyolysis.<ref name="deltoid" /><ref name="british" /><ref name="german" /><ref name="necrotising" /><br>
* 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.<ref name="Modlinski" /><br>
* AAS can exacerbate or lead to many psychological disorders including depression, increased anger, increased aggression, anxiety disorders, schizophrenia, and eating disorders.<ref name="Piacentino" />


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&nbsp;<ref name="deltoid">Farkash U., Shabshin N., Pritsch M. Rhabdomyolysis of the Deltoid Muscle in a Bodybuilder Using Anabolic-Androgenic Steroids: A Case Report. Journal of Athletic Training. 2009; 44(1): 98–100.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629047/</ref><ref name="british">Adamson R, Rambaran C, D'Cruz D. Anabolic steroid-induced rhabdomyolysis. British Journal of Hospital Medicine (2005). 2005;66(6):362. http://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2005.66.6.18414</ref><ref name="european">Braseth N, Allison Jr E, Gough J. Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. European Journal of Emergency Medicine. 2001;8(2):155-7. http://journals.lww.com/euro-emergencymed/Abstract/2001/06000/Exertional_rhabdomyolysis_in_a_body_builder.15.aspx</ref><ref name="german">Daniels JM, van Westerloo DJ, de Hon OM, Frissen PH. Rhabdomyolysis in a bodybuilder using steroids. [Abstract]. Nederlands tijdschrift voor geneeskunde. 2006;150(19):1077-80. http://europepmc.org/abstract/med/16733985</ref><ref name="necrotising">Hughes M., Ahmed S. Anabolic androgenic steroid induced necrotising myopathy. Rheumatology International. 2001; 31(7): 915-917. https://hal.archives-ouvertes.fr/hal-00615341/document</ref>.&nbsp;
=== '''Cardiovascular Effects'''  ===


Athletes use AAS to improve performance. AAS causes muscle hypertrophy and protein synthesis, especially when combined&nbsp;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>.&nbsp;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&nbsp;<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&nbsp;<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&nbsp;<ref name="BStorer" />.  
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>.  


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&nbsp;<ref name="Tamaki" />. The study found&nbsp;that AAS treatment before a single bout of exhaustive weight-lifting exercise enhances the fatigue resistance in involved muscles and increases protein synthesis&nbsp;<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&nbsp;<ref name="Van">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>.<br>  
AAS abuse in body builders has been linked with
* myocardial infarction,  
* cardiomyopathy,  
* sudden death
* 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>.&nbsp;
* 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>.
* 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.
* decreased 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>.&nbsp;Reduced parasympathetic activity in the heart slows the recovery of the heart rate post exercise<ref name="Maior" /><span style="line-height: 1.5em; font-size: 13.28px;">. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood</span><ref name="Akçakoyun">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><span style="line-height: 1.5em; font-size: 13.28px;">.</span>
* <span style="line-height: 1.5em;">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&nbsp;<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>.&nbsp;</span>
* <span style="line-height: 1.5em;">Hypertension, </span>
* <span style="line-height: 1.5em;">ventricular remodeling, and </span>
* <span style="line-height: 1.5em;">myocardial ischemia <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>. </span>
<span style="line-height: 1.5em;">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" />.
</span>  


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&nbsp;<ref name="Kanayama">Kanayama G, DeLuca J, Meehan WP, Hudson JI, Isaacs S, Baggish A, et al. Ruptured Tendons in Anabolic-Androgenic Steroid Users. 2015;43(11):2638-44. http://ajs.sagepub.com/content/43/11/2638.short</ref> . No significant difference was found between the two groups concerning lower extremity tendon ruptures&nbsp;<ref name="Kanayama" /> . 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 <ref name="Kanayama" />. One study found ultrastructural changes in tendons of mice treated with AAS <ref name="Michna">Michna H. Tendon injuries induced by exercise and anabolic steroids in experimental mice. Int Orthop 1987;11(2):157-62. http://link.springer.com/article/10.1007/BF00266702</ref>, but strong evidence of structural changes in human tendons has not been demonstrated <ref name="Kanayama" />. 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&nbsp;<ref name="Seynnes">Seynnes OR, Kamandulis S, Kairaitis R, Helland C, Campbell E-L, Brazaitis M, et al. Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties. J Appl Physiol 2013;115(1):84-9. http://jap.physiology.org/content/115/1/84.short</ref>. 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 <ref name="Kanayama" />. 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 <ref name="Horn">Horn S, Gregory P, Guskiewicz KM. Self-reported anabolic-androgenic steroids use and musculoskeletal injuries: findings from the center for the study of retired athletes health survey of retired NFL players. Am J Phys Med Rehab 2009;88(3):192-200. http://www.ncbi.nlm.nih.gov/pubmed/19847128</ref>.
= '''Muscular Effects'''  =


AAS can promote muscular development and strength in older populations. AAS use may benefit those recovering from hip surgery <ref name="Farooqi">Farooqi V, Van Den Berg M, Cameron I. Anabolic steroids for rehabilitation after hip fracture in older people. The Cochran Collaboration. 2013:</ref>. 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. <ref name="fraility">Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MDL, Adams JE, Oldham JA, Wu FCW. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: A randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010;95(2):639-50. http://press.endocrine.org/doi/full/10.1210/jc.2009-1251</ref>&nbsp; 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.<ref name="Metcalfe">Metcalfe D., Watts E., Masters JP., Smith N. Anabolic steroids in patients undergoing total knee arthroplasty. BMJ Open. 2011; 2(5): Doi: 10.1136/bmjopen-2012-001435</ref> The evidence to support AAS use following TKA is insignificant, but there are some implications that AAS use may benefit those following surgery.<ref name="Metcalfe" />
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&nbsp;<ref name="deltoid">Farkash U., Shabshin N., Pritsch M. Rhabdomyolysis of the Deltoid Muscle in a Bodybuilder Using Anabolic-Androgenic Steroids: A Case Report. Journal of Athletic Training. 2009; 44(1): 98–100.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629047/</ref><ref name="british">Adamson R, Rambaran C, D'Cruz D. Anabolic steroid-induced rhabdomyolysis. British Journal of Hospital Medicine (2005). 2005;66(6):362. http://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2005.66.6.18414</ref><ref name="european">Braseth N, Allison Jr E, Gough J. Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. European Journal of Emergency Medicine. 2001;8(2):155-7. http://journals.lww.com/euro-emergencymed/Abstract/2001/06000/Exertional_rhabdomyolysis_in_a_body_builder.15.aspx</ref><ref name="german">Daniels JM, van Westerloo DJ, de Hon OM, Frissen PH. Rhabdomyolysis in a bodybuilder using steroids. [Abstract]. Nederlands tijdschrift voor geneeskunde. 2006;150(19):1077-80. http://europepmc.org/abstract/med/16733985</ref><ref name="necrotising">Hughes M., Ahmed S. Anabolic androgenic steroid induced necrotising myopathy. Rheumatology International. 2001; 31(7): 915-917. https://hal.archives-ouvertes.fr/hal-00615341/document</ref>.&nbsp;
Athletes use AAS to improve performance as AAS cause muscle hypertrophy and protein synthesis [especially when combined&nbsp;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>.
* 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>, hypothetically hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy <ref name="stanozolol" />.  
* Steroids have not been shown to increase creatine concentrations in the muscle&nbsp;<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&nbsp;<ref name="BStorer" />.
* 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&nbsp;<ref name="Tamaki" />. The study found&nbsp;that AAS treatment before a single bout of exhaustive weight-lifting exercise enhances the fatigue resistance in involved muscles and increases protein synthesis&nbsp;<ref name="Tamaki" />.
* AAS treatment in combination with exercise delays fatigue during sub-maximal exercise, possibly due to AAS induced muscle fiber transformations&nbsp;<ref name="Van">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>.
* AAS can promote muscular development and strength in older populations. AAS use may benefit those recovering from hip surgery <ref name="Farooqi" />. 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. <ref name="fraility" />&nbsp; 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.<ref name="Metcalfe" /> The evidence to support AAS use following TKA is insignificant, but there are some implications that AAS use may benefit those following surgery.<ref name="Metcalfe" />
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&nbsp;<ref name="Kanayama">Kanayama G, DeLuca J, Meehan WP, Hudson JI, Isaacs S, Baggish A, et al. Ruptured Tendons in Anabolic-Androgenic Steroid Users. 2015;43(11):2638-44. http://ajs.sagepub.com/content/43/11/2638.short</ref> . No significant difference was found between the two groups concerning lower extremity tendon ruptures&nbsp;<ref name="Kanayama" /> . 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 <ref name="Kanayama" />. One study found ultrastructural changes in tendons of mice treated with AAS <ref name="Michna">Michna H. Tendon injuries induced by exercise and anabolic steroids in experimental mice. Int Orthop 1987;11(2):157-62. http://link.springer.com/article/10.1007/BF00266702</ref>, but strong evidence of structural changes in human tendons has not been demonstrated <ref name="Kanayama" />. 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&nbsp;<ref name="Seynnes">Seynnes OR, Kamandulis S, Kairaitis R, Helland C, Campbell E-L, Brazaitis M, et al. Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties. J Appl Physiol 2013;115(1):84-9. http://jap.physiology.org/content/115/1/84.short</ref>. 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 <ref name="Kanayama" />. 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 <ref name="Horn">Horn S, Gregory P, Guskiewicz KM. Self-reported anabolic-androgenic steroids use and musculoskeletal injuries: findings from the center for the study of retired athletes health survey of retired NFL players. Am J Phys Med Rehab 2009;88(3):192-200. http://www.ncbi.nlm.nih.gov/pubmed/19847128</ref>.


= '''Neurological Effects'''  =
= '''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<ref name="Hildebrandt">Hildebrandt T, Shope S, Varangis E, Klein D, Pfaff DW, Yehuda R. Exercise reinforcement, stress, and β-endorphins: An initial examination of exercise in anabolic–androgenic steroid dependence. Drug and alcohol dependence. 2014;139:86-92.http://www.drugandalcoholdependence.com/article/S0376-8716%2814%2900784-4/abstract</ref>.&nbsp; The increase in endorphin levels and exercise reinforcement may contribute to AAS dependence and abuse<ref name="Hildebrandt" />. AAS dependence is characterized by increases in AAS cycles, higher doses, and increases in psychological disorders, such as increased aggression<ref name="Piacentino">Piacentino D, D Kotzalidis G, del Casale A, Rosaria Aromatario M, Pomara C, Girardi P, et al. Anabolic-androgenic steroid use and psychopathology in athletes. A systematic review. Current Neuropharmacology. 2015;13(1):101-21. http://www.ingentaconnect.com/content/ben/cn/2015/00000013/00000001/art00011</ref>. Depression and suicide can be caused by off-cycles of AAS or withdrawal from AAS use.&nbsp; 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<ref name="Piacentino" />.&nbsp; 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<ref name="Piacentino" />. 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.<br>
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.  
 
= '''Conclusion'''  =
 
AAS increases protein synthesis and lean muscle mass.<ref name="Haupt" /><ref name="Modlinski" /><ref name="Tamaki" /> AAS promotes muscle hypertrophy in Type I and Type IIa fibers.<ref name="Tamaki" /><ref name="stanozolol" /><ref name="powerlifters" /> AAS may increase exercise capacity, muscle endurance, and aerobic performance.<ref name="Tamaki" /><ref name="Van" /> AAS can lead to increases in strength without resistance training.<ref name="BStorer" /><br><br>AAS use may improve recovery from hip surgery and TKA.<ref name="Farooqi" /><ref name="Metcalfe" /> It may help elderly adult males to improve quality of life.<ref name="fraility" /><br><br>AAS may lead to euphoria and increased endorphin levels, which may promote increased motivation to exercise and continuation of exercise.<ref name="Haupt" /><ref name="Hildebrandt" /><br><br>'''Potential Risk Factors:''' <br>
 
The cardiovascular effects include hypertension, myocardial infarction, cardiomyopathy, increased risk of thrombosis, ventricular arrhythmia, atrial fibrillation, and reduced parasympathetic activity. <ref name="Modlinski" /><ref name="Achar" /><ref name="Kuipers H" /><ref name="Laroche GP" /><ref name="Maior" /><ref name="Hedman" /><ref name="Akçakoyun" /><ref name="refst" /><br>
 
AAS may cause an increased risk of tendon rupture, and increased tendon stiffness.<ref name="Kanayama" /><ref name="Horn" /><ref name="Seynnes" /><br>
 
May lead to over-exertion and increase the risk of rhabdomyolysis.<ref name="deltoid" /><ref name="british" /><ref name="german" /><ref name="necrotising" /><br>


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.<ref name="Modlinski" /><br>
AAS may increase beta-endorphin levels, decrease cortisol levels, and increase ACTH levels, which may lead to an increase in positive associations with exercise<ref name="Hildebrandt">Hildebrandt T, Shope S, Varangis E, Klein D, Pfaff DW, Yehuda R. Exercise reinforcement, stress, and β-endorphins: An initial examination of exercise in anabolic–androgenic steroid dependence. Drug and alcohol dependence. 2014;139:86-92.http://www.drugandalcoholdependence.com/article/S0376-8716%2814%2900784-4/abstract</ref>.&nbsp; The increase in endorphin levels and exercise reinforcement may contribute to AAS dependence and abuse<ref name="Hildebrandt" />.


AAS can exacerbate or lead to many psychological disorders including depression, increased anger, increased aggression, anxiety disorders, schizophrenia, and eating disorders.<ref name="Piacentino" />  
AAS dependence is characterized by increases in AAS cycles, higher doses, and increases in psychological disorders, such as increased aggression<ref name="Piacentino">Piacentino D, D Kotzalidis G, del Casale A, Rosaria Aromatario M, Pomara C, Girardi P, et al. Anabolic-androgenic steroid use and psychopathology in athletes. A systematic review. Current Neuropharmacology. 2015;13(1):101-21. http://www.ingentaconnect.com/content/ben/cn/2015/00000013/00000001/art00011</ref>. Depression and suicide can be caused by off-cycles of AAS or withdrawal from AAS use.&nbsp; 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<ref name="Piacentino" />.&nbsp; 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<ref name="Piacentino" />. 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.<br>  


=== Conclusions  ===
= '''References'''  =
= '''References'''  =


<references />
<references />

Revision as of 07:26, 20 December 2019

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

Introduction  [edit | edit source]

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 esthetic purposes, as well as for improvement of their endurance and performances[1]. 

Anabolic-androgenic steroids (AAS) are a group of synthetic compounds that mimic the effects of testosterone in the body[2]. AAS abuse can have profound effects on the cardiovascular system, hepatic function, and adrenal and renal function [3]. As its name refers, AAS has two major effects: androgenic and anabolic. Androgenic effects increase secondary masculine sexual characteristics; anabolic effects increase protein synthesis [3]. 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

[4]

Important Issues[edit | edit source]

  • AAS increases protein synthesis and lean muscle mass.[5][3][6] AAS promotes muscle hypertrophy in Type I and Type IIa fibers.[6][7][8] AAS may increase exercise capacity, muscle endurance, and aerobic performance.[6][9] AAS can lead to increases in strength without resistance training.[10]
  • AAS use may improve recovery from hip surgery and TKA.[11][12] It may help elderly adult males to improve quality of life.[13]
  • AAS may lead to euphoria and increased endorphin levels, which may promote increased motivation to exercise and continuation of exercise.[5][14]

    Potential Risk Factors:
  • The cardiovascular effects include hypertension, myocardial infarction, cardiomyopathy, increased risk of thrombosis, ventricular arrhythmia, atrial fibrillation, and reduced parasympathetic activity. [3][15][16][17][18][19][20][21]
  • AAS may cause an increased risk of tendon rupture, and increased tendon stiffness.[22][23][24]
  • May lead to over-exertion and increase the risk of rhabdomyolysis.[25][26][27][28]
  • 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.[3]
  • AAS can exacerbate or lead to many psychological disorders including depression, increased anger, increased aggression, anxiety disorders, schizophrenia, and eating disorders.[29]

Cardiovascular Effects[edit | edit source]

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 [15].

AAS abuse in body builders has been linked with

  • myocardial infarction,
  • cardiomyopathy,
  • sudden death
  • elevated blood pressure and increased risk of thrombosis[16][17]. 
  • lower amount of heart rate variability (HRV) than non-users, putting them at an increased risk of autonomic cardiovascular dysfunction and ventricular arrhythmia [18].
  • atrial fibrillation (AF) [30]. This may be due to inter- and intra-atrial electromechanical delay.
  • decreased vagal and parasympathetic activity in the heart[18][19]. Reduced parasympathetic activity in the heart slows the recovery of the heart rate post exercise[18]. However, the exact mechanism of how AAS abuse contributes to atrial electromechanical delay is poorly understood[20].
  • 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 [31]. 
  • Hypertension,
  • ventricular remodeling, and
  • myocardial ischemia [21].

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[21]. These effects persist long after use has been discontinued and have significant impact on subsequent morbidity and mortality[21].

Muscular Effects[edit | edit source]

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 [5].
  • AAS disallows glucocorticoids from binding to their receptors. This is important because glucocorticoids produce catabolic effects by depressing protein synthesis [5].
  • AAS psychologically impacts users by producing euphoria, encouraging users to work harder during workouts [5]. In turn, AAS use may lead to rhabdomyolysis by promoting over exertion [25][26][32][27][28]. 

Athletes use AAS to improve performance as AAS cause muscle hypertrophy and protein synthesis [especially when combined with resistance exercise][6].

  • stanozolol significantly increased type I muscle fiber size [7], hypothetically hypertrophy of type I fibers allows athletes to exercise longer, in turn causing type II fiber hypertrophy [7].
  • Steroids have not been shown to increase creatine concentrations in the muscle [10].
  • 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 [10].
  • 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 [6]. Rats in the steroid group performed 47%, 12%, 22%, and 81% better in these areas respectively [6]. 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 [6].
  • AAS treatment in combination with exercise delays fatigue during sub-maximal exercise, possibly due to AAS induced muscle fiber transformations [9].
  • AAS can promote muscular development and strength in older populations. AAS use may benefit those recovering from hip surgery [11]. 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. [13]  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.[12] The evidence to support AAS use following TKA is insignificant, but there are some implications that AAS use may benefit those following surgery.[12]

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 [22] . No significant difference was found between the two groups concerning lower extremity tendon ruptures [22] . 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 [22]. One study found ultrastructural changes in tendons of mice treated with AAS [33], but strong evidence of structural changes in human tendons has not been demonstrated [22]. 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 [24]. 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 [22]. 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 [23].

Neurological Effects[edit | edit source]

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[14].  The increase in endorphin levels and exercise reinforcement may contribute to AAS dependence and abuse[14].

AAS dependence is characterized by increases in AAS cycles, higher doses, and increases in psychological disorders, such as increased aggression[29]. 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[29].  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[29]. 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.

Conclusions[edit | edit source]

References[edit | edit source]

  1. ↑ Bertozzi G, Sessa F, Albano GD, Sani G, Maglietta F, Roshan MH, Volti GL, Bernardini R, Avola R, Pomara C, Salerno M. The role of anabolic androgenic steroids in disruption of the physiological function in discrete areas of the central nervous system. Molecular neurobiology. 2018 Jul 1;55(7):5548-56. Available from: https://link.springer.com/article/10.1007/s12035-017-0774-1 (last accessed 20.12.2019)
  2. ↑ National Institute on Drug Abuse. Anabolic Steroids. http://www.drugabuse.gov/publications/drugfacts/anabolic-steroids (accessed November 10, 2015)
  3. ↑ 3.0 3.1 3.2 3.3 3.4 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
  4. ↑ BBC Earth lab What happens when you take steroids Available from: https://www.youtube.com/watch?v=v5Rv8XWmvoQ (last accessed 20.12.2019)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 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
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 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
  7. ↑ 7.0 7.1 7.2 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
  8. ↑ 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
  9. ↑ 9.0 9.1 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
  10. ↑ 10.0 10.1 10.2 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).
  11. ↑ 11.0 11.1 Farooqi V, Van Den Berg M, Cameron I. Anabolic steroids for rehabilitation after hip fracture in older people. The Cochran Collaboration. 2013:
  12. ↑ 12.0 12.1 12.2 Metcalfe D., Watts E., Masters JP., Smith N. Anabolic steroids in patients undergoing total knee arthroplasty. BMJ Open. 2011; 2(5): Doi: 10.1136/bmjopen-2012-001435
  13. ↑ 13.0 13.1 Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MDL, Adams JE, Oldham JA, Wu FCW. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: A randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010;95(2):639-50. http://press.endocrine.org/doi/full/10.1210/jc.2009-1251
  14. ↑ 14.0 14.1 14.2 Hildebrandt T, Shope S, Varangis E, Klein D, Pfaff DW, Yehuda R. Exercise reinforcement, stress, and β-endorphins: An initial examination of exercise in anabolic–androgenic steroid dependence. Drug and alcohol dependence. 2014;139:86-92.http://www.drugandalcoholdependence.com/article/S0376-8716%2814%2900784-4/abstract
  15. ↑ 15.0 15.1 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/
  16. ↑ 16.0 16.1 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
  17. ↑ 17.0 17.1 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
  18. ↑ 18.0 18.1 18.2 18.3 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
  19. ↑ 19.0 19.1 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
  20. ↑ 20.0 20.1 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/
  21. ↑ 21.0 21.1 21.2 21.3 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
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 Kanayama G, DeLuca J, Meehan WP, Hudson JI, Isaacs S, Baggish A, et al. Ruptured Tendons in Anabolic-Androgenic Steroid Users. 2015;43(11):2638-44. http://ajs.sagepub.com/content/43/11/2638.short
  23. ↑ 23.0 23.1 Horn S, Gregory P, Guskiewicz KM. Self-reported anabolic-androgenic steroids use and musculoskeletal injuries: findings from the center for the study of retired athletes health survey of retired NFL players. Am J Phys Med Rehab 2009;88(3):192-200. http://www.ncbi.nlm.nih.gov/pubmed/19847128
  24. ↑ 24.0 24.1 Seynnes OR, Kamandulis S, Kairaitis R, Helland C, Campbell E-L, Brazaitis M, et al. Effect of androgenic-anabolic steroids and heavy strength training on patellar tendon morphological and mechanical properties. J Appl Physiol 2013;115(1):84-9. http://jap.physiology.org/content/115/1/84.short
  25. ↑ 25.0 25.1 Farkash U., Shabshin N., Pritsch M. Rhabdomyolysis of the Deltoid Muscle in a Bodybuilder Using Anabolic-Androgenic Steroids: A Case Report. Journal of Athletic Training. 2009; 44(1): 98–100.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629047/
  26. ↑ 26.0 26.1 Adamson R, Rambaran C, D'Cruz D. Anabolic steroid-induced rhabdomyolysis. British Journal of Hospital Medicine (2005). 2005;66(6):362. http://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2005.66.6.18414
  27. ↑ 27.0 27.1 Daniels JM, van Westerloo DJ, de Hon OM, Frissen PH. Rhabdomyolysis in a bodybuilder using steroids. [Abstract]. Nederlands tijdschrift voor geneeskunde. 2006;150(19):1077-80. http://europepmc.org/abstract/med/16733985
  28. ↑ 28.0 28.1 Hughes M., Ahmed S. Anabolic androgenic steroid induced necrotising myopathy. Rheumatology International. 2001; 31(7): 915-917. https://hal.archives-ouvertes.fr/hal-00615341/document
  29. ↑ 29.0 29.1 29.2 29.3 Piacentino D, D Kotzalidis G, del Casale A, Rosaria Aromatario M, Pomara C, Girardi P, et al. Anabolic-androgenic steroid use and psychopathology in athletes. A systematic review. Current Neuropharmacology. 2015;13(1):101-21. http://www.ingentaconnect.com/content/ben/cn/2015/00000013/00000001/art00011
  30. ↑ 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
  31. ↑ 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/
  32. ↑ Braseth N, Allison Jr E, Gough J. Exertional rhabdomyolysis in a body builder abusing anabolic androgenic steroids. European Journal of Emergency Medicine. 2001;8(2):155-7. http://journals.lww.com/euro-emergencymed/Abstract/2001/06000/Exertional_rhabdomyolysis_in_a_body_builder.15.aspx
  33. ↑ Michna H. Tendon injuries induced by exercise and anabolic steroids in experimental mice. Int Orthop 1987;11(2):157-62. http://link.springer.com/article/10.1007/BF00266702
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