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Can conditions of skeletal muscle loss be improved by combining exercise with anabolic–androgenic steroids? A systematic review and meta-analysis of testosterone-based interventions

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Abstract

Sarcopenia, cachexia, and atrophy due to inactivity and disease states are characterized by a loss of skeletal muscle mass, often accompanied by reduced levels of anabolic hormones (e.g. testosterone). These conditions are associated with an increase in mortality, hospitalization and worsening in quality of life. Both physical exercise (EX) and anabolic–androgenic steroid (AAS) administration can improve the prognosis of patients as they increase physical functionality. However, there is a gap in the literature as to the impact of these therapies on the gains in strength and muscle mass and their implications for patient safety. Accordingly, we performed a random-effects meta-analysis to elucidate the effects of AAS and/or EX interventions on lean body mass (LBM) and muscle strength in conditions involving muscle loss. A systematic search for relevant clinical trials was conducted in MEDLINE, EMBASE, SCOPUS, Web of Science, and SPORTDiscus. Comparisons included AAS vs. Control, EX vs. Control, AAS vs. EX, AAS + EX vs. AAS and AAS + EX vs. EX. A total of 1114 individuals were analyzed. AAS increased LBM (effect size [ES]: 0.46; 95% CI: 0.25, 0.68, P = 0.00) and muscle strength (ES: 0.31; 95% CI: 0.08, 0.53, P = 0.01) when compared to a control group. EX promoted an increase in muscular strength (ES: 0.89; 95% CI: 0.53, 1.25, P = 0.00), with no effect on LBM when compared to the control group (ES: 0.15; 95% CI: -0.07, 0.38, P = 0.17). AAS did not demonstrate statistically significant differences when compared to EX for LBM and muscle strength. The combination of EX + AAS promoted a greater increase in LBM and muscular strength when compared to AAS or EX in isolation. Qualitatively, AAS administration had relatively few side effects. Significant heterogeneity was found in some analyses, which may be explained by the use of different AAS types and EX protocols. Our findings suggest that AAS administration in cachectic and sarcopenic conditions may be a viable interventional strategy to enhance muscle function when exercise is not a possible approach. Moreover, combining AAS with exercise may enhance positive outcomes in this population.

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Abbreviations

1RM:

One maximal repetition

AAS:

Anabolic–androgenic steroid

AIDS:

Acquired Immunodeficiency Syndrome

ALB:

Albumin

ALT:

Alanine transaminase

AST:

Aspartate transaminase

COPD:

Chronic Obstructive Pulmonary Disease

DHEA:

Dehydroepiandrosterone

EAA:

European Academy of Andrology

ES:

Effect size

EX:

Exercise

GGT:

Gamma-glutamyltransferase

HDL:

High-density lipoprotein

HF:

Heart Failure

HIIT:

High-intensity intermittent exercise

HIV:

Human Immunodeficiency Virus

LBM:

Lean body mass

LDL:

Low-density lipoprotein

PRISMA:

Preferred Reporting Items of Systematic Reviews and Meta‐Analysis

Q:

Cochran's Q test

RCTs:

Randomized Controlled Trials (RCTs)

PSA:

Prostate specific antigen

SCI:

Spinal Cord Injury

TG:

Triglycerides

TRT:

Testosterone replacement therapy

VLDL:

Very low-density lipoprotein

References

  1. Scicchitano BM, Dobrowolny G, Sica G, Musarò A. Molecular Insights into Muscle Homeostasis. Atrophy and Wasting Curr Genomics. 2018;19:356–69.

    Article  CAS  PubMed  Google Scholar 

  2. de Santana FM, Domiciano DS, Gonçalves MA, Machado LG, Figueiredo CP, Lopes JB, et al. Association of Appendicular Lean Mass, and Subcutaneous and Visceral Adipose Tissue With Mortality in Older Brazilians: The São Paulo Ageing & Health Study. J Bone Miner Res. 2019;34:1264–74.

    Article  PubMed  Google Scholar 

  3. Otten L, Stobäus N, Franz K, Genton L, Müller-Werdan U, Wirth R, et al. Impact of sarcopenia on 1-year mortality in older patients with cancer. Age Ageing. 2019;48:413–8.

    Article  PubMed  Google Scholar 

  4. Legrand D, Vaes B, Matheï C, Adriaensen W, Van Pottelbergh G, Degryse J-M. Muscle strength and physical performance as predictors of mortality, hospitalization, and disability in the oldest old. J Am Geriatr Soc. 2014;62:1030–8.

    Article  PubMed  Google Scholar 

  5. Giglio J, Kamimura MA, Lamarca F, Rodrigues J, Santin F, Avesani CM. Association of Sarcopenia With Nutritional Parameters, Quality of Life, Hospitalization, and Mortality Rates of Elderly Patients on Hemodialysis. J Ren Nutr. 2018;28:197–207.

    Article  PubMed  Google Scholar 

  6. Shachar SS, Deal AM, Weinberg M, Nyrop KA, Williams GR, Nishijima TF, et al. Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy. Clin Cancer Res. 2017;23:658–65.

    Article  CAS  PubMed  Google Scholar 

  7. Bye A, Sjøblom B, Wentzel-Larsen T, Grønberg BH, Baracos VE, Hjermstad MJ, et al. Muscle mass and association to quality of life in non-small cell lung cancer patients. J Cachexia Sarcopenia Muscle. 2017;8:759–67.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Trombetti A, Reid KF, Hars M, Herrmann FR, Pasha E, Phillips EM, et al. Age-associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life. Osteoporos Int. 2016;27:463–71.

    Article  CAS  PubMed  Google Scholar 

  9. Mijnarends DM, Luiking YC, Halfens RJG, Evers SMAA, Lenaerts ELA, Verlaan S, et al. Muscle, Health and Costs: A Glance at their Relationship. J Nutr Health Aging. 2018;22:766–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Santilli V, Bernetti A, Mangone M, Paoloni M. Clinical definition of sarcopenia. Clin Cases Miner Bone Metab. 2014;11:177–80.

    PubMed  PubMed Central  Google Scholar 

  11. Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol. 2000;88:1321–6.

    Article  CAS  PubMed  Google Scholar 

  12. Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 2006;61:72–7.

    Article  PubMed  Google Scholar 

  13. Chen L, Nelson DR, Zhao Y, Cui Z, Johnston JA. Relationship between muscle mass and muscle strength, and the impact of comorbidities: a population-based, cross-sectional study of older adults in the United States. BMC Geriatr. 2013;13:74.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Falcon LJ, Harris-Love MO. Sarcopenia and the New ICD-10-CM Code: Screening, Staging, and Diagnosis Considerations. Fed Pract. 2017;34:24–32.

    PubMed  PubMed Central  Google Scholar 

  15. Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr Edinb Scotl. 2008;27:793–9.

    Article  CAS  Google Scholar 

  16. Schols AMWJ, Broekhuizen R, Weling-Scheepers CA, Wouters EF. Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr. 2005;82:53–9.

    Article  CAS  PubMed  Google Scholar 

  17. Habedank D, Ewert R, Hetzer R, Anker SD. Reversibility of cachexia after bilateral lung transplantation. Int J Cardiol. 2009;133:46–50.

    Article  PubMed  Google Scholar 

  18. Anker SD, Negassa A, Coats AJS, Afzal R, Poole-Wilson PA, Cohn JN, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet. 2003;361:1077–83.

    Article  CAS  PubMed  Google Scholar 

  19. Hurley BF, Hanson ED, Sheaff AK. Strength training as a countermeasure to aging muscle and chronic disease. Sports Med. 2011;41:289–306.

    Article  PubMed  Google Scholar 

  20. Zinna EM, Yarasheski KE. Exercise treatment to counteract protein wasting of chronic diseases. Curr Opin Clin Nutr Metab Care. 2003;6:87–93.

    Article  PubMed  Google Scholar 

  21. Jones TE, Stephenson KW, King JG, Knight KR, Marshall TL, Scott WB. Sarcopenia–mechanisms and treatments. J Geriatr Phys Ther. 2001;2009(32):83–9.

    Google Scholar 

  22. Seynnes O, Fiatarone Singh MA, Hue O, Pras P, Legros P, Bernard PL. Physiological and functional responses to low-moderate versus high-intensity progressive resistance training in frail elders. J Gerontol A Biol Sci Med Sci. 2004;59:503–9.

    Article  PubMed  Google Scholar 

  23. Barcellos FC, Santos IS, Umpierre D, Bohlke M, Hallal PC. Effects of exercise in the whole spectrum of chronic kidney disease: a systematic review. Clin Kidney J. 2015;8:753–65.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lalande S, Cross TJ, Keller-Ross ML, Morris NR, Johnson BD, Taylor BJ. Exercise Intolerance in Heart Failure: Central Role for the Pulmonary System. Exerc Sport Sci Rev. 2020;48:11–9.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wilund KR, Viana JL, Perez LM. A Critical Review of Exercise Training in Hemodialysis Patients: Personalized Activity Prescriptions Are Needed. Exerc Sport Sci Rev. 2020;48:28–39.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem. 2006;75:19–37.

    Article  CAS  PubMed  Google Scholar 

  27. Storer TW, Magliano L, Woodhouse L, Lee ML, Dzekov C, Dzekov J, et al. Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. J Clin Endocrinol Metab. 2003;88:1478–85.

    Article  CAS  PubMed  Google Scholar 

  28. Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, et al. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol Dial Transplant. 2011;26:184–90.

    Article  CAS  PubMed  Google Scholar 

  29. Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol. 2015;30:244–51.

    Article  PubMed  Google Scholar 

  30. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:210.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gharahdaghi N, Rudrappa S, Brook MS, Idris I, Crossland H, Hamrock C, et al. Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. J Cachexia Sarcopenia Muscle. 2019;10:1276–94.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Glintborg D, Christensen LL, Kvorning T, Larsen R, Brixen K, Hougaard DM, et al. Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men. Mediators Inflamm. 2013;2013:539156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Glintborg D, Christensen LL, Kvorning T, Larsen R, Højlund K, Brixen K, et al. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition. Scand J Clin Lab Invest. 2015;75:659–66.

    PubMed  Google Scholar 

  35. Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Phillips J, et al. Testosterone Replacement and Resistance Exercise in HIV-Infected Men With Weight Loss and Low Testosterone Levels. JAMA. 2000;283:763–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Grinspoon S, Corcoran C, Parlman K, Costello M, Rosenthal D, Anderson E, et al. Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Ann Intern Med. 2000;133:348–55.

  37. Sattler FR, Jaque SV, Schroeder ET, Olson C, Dube MP, Martinez C, et al. Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus. J Clin Endocrinol Metab. 1999;84:1268–76.

    CAS  PubMed  Google Scholar 

  38. Shevitz AH, Wilson IB, McDermott AY, Spiegelman D, Skinner SC, Antonsson K, et al. A comparison of the clinical and cost-effectiveness of 3 intervention strategies for AIDS wasting. J Acquir Immune Defic Syndr. 2005;38:399–406.

    Article  PubMed  Google Scholar 

  39. Strawford A, Barbieri T, Loan MV, Parks E, Catlin D, Barton N, et al. Resistance Exercise and Supraphysiologic Androgen Therapy in Eugonadal Men With HIV-Related Weight Loss: A Randomized Controlled Trial. JAMA. 1999;281:1282–90.

    Article  CAS  PubMed  Google Scholar 

  40. Schroeder ET, Terk M, Sattler FR. Androgen therapy improves muscle mass and strength but not muscle quality: results from two studies. Am J Physiol Endocrinol Metab. 2003;285:E16-24.

    Article  CAS  PubMed  Google Scholar 

  41. Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis MI, et al. Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170:870–8.

    Article  PubMed  Google Scholar 

  42. Ferreira IM, Verreschi IT, Nery LE, Goldstein RS, Zamel N, Brooks D, et al. The influence of 6 months of oral anabolic steroids on body mass and respiratory muscles in undernourished COPD patients. Chest. 1998;114:19–28.

    Article  CAS  PubMed  Google Scholar 

  43. Stout M, Tew GA, Doll H, Zwierska I, Woodroofe N, Channer KS, et al. Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Am Heart J. 2012;164:893–901.

    Article  CAS  PubMed  Google Scholar 

  44. Dos Santos MR, Sayegh ALC, Bacurau AVN, Arap MA, Brum PC, Pereira RMR, et al. Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency. Mayo Clin Proc. 2016;91:575–86.

    Article  PubMed  CAS  Google Scholar 

  45. Gorgey AS, Khalil RE, Gill R, Gater DR, Lavis TD, Cardozo CP, et al. Low-Dose Testosterone and Evoked Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial. J Neurotrauma. 2019;36:2631–45.

    Article  PubMed  Google Scholar 

  46. Johansen KL, Painter PL, Sakkas GK, Gordon P, Doyle J, Shubert T. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial. J Am Soc Nephrol. 2006;17:2307–14.

    Article  CAS  PubMed  Google Scholar 

  47. Przkora R, Herndon DN, Suman OE. The effects of oxandrolone and exercise on muscle mass and function in children with severe burns. Pediatrics. 2007;119:e109-116.

    Article  PubMed  Google Scholar 

  48. Sartorio A, Maffiuletti NA, Agosti F, Marinone PG, Ottolini S, Lafortuna CL. Body mass reduction markedly improves muscle performance and body composition in obese females aged 61–75 years: comparison between the effects exerted by energy-restricted diet plus moderate aerobic-strength training alone or associated with rGH or nandrolone undecanoate. Eur J Endocrinol. 2004;150:511–5.

    Article  CAS  PubMed  Google Scholar 

  49. Shimodozono M, Kawahira K, Ogata A, Etoh S, Tanaka N. Addition of an anabolic steroid to strength training promotes muscle strength in the nonparetic lower limb of poststroke hemiplegia patients. Int J Neurosci. 2010;120:617–24.

    Article  CAS  PubMed  Google Scholar 

  50. Bacevičienė R, Valonytė L, Ceponis J. The effect of physiotherapy in addition to testosterone replacement therapy on the efficiency of the motor system in men with hypogonadism. Med Kaunas. 2013;49:71–7.

    Google Scholar 

  51. Hildreth KL, Barry DW, Moreau KL, Vande Griend J, Meacham RB, Nakamura T, et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab. 2013;98:1891–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Katznelson L, Robinson MW, Coyle CL, Lee H, Farrell CE. Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men. Eur J Endocrinol. 2006;155:867–75.

    Article  CAS  PubMed  Google Scholar 

  53. Kvorning T, Christensen LL, Madsen K, Nielsen JL, Gejl KD, Brixen K, et al. Mechanical muscle function and lean body mass during supervised strength training and testosterone therapy in aging men with low-normal testosterone levels. J Am Geriatr Soc. 2013;61:957–62.

    Article  PubMed  Google Scholar 

  54. Mavros Y, O’Neill E, Connerty M, Bean JF, Broe K, Kiel DP, et al. Oxandrolone Augmentation of Resistance Training in Older Women: A Randomized Trial. Med Sci Sports Exerc. 2015;47:2257–67.

    Article  CAS  PubMed  Google Scholar 

  55. Sullivan DH, Roberson PK, Johnson LE, Bishara O, Evans WJ, Smith ES, et al. Effects of muscle strength training and testosterone in frail elderly males. Med Sci Sports Exerc. 2005;37:1664–72.

    Article  CAS  PubMed  Google Scholar 

  56. Dillon EL, Sheffield-Moore M, Durham WJ, Ploutz-Snyder LL, Ryder JW, Danesi CP, et al. Efficacy of Testosterone plus NASA Exercise Countermeasures during Head-Down Bed Rest. Med Sci Sports Exerc. 2018;50:1929–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Igwebuike A, Irving BA, Bigelow ML, Short KR, McConnell JP, Nair KS. Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women. J Clin Endocrinol Metab. 2008;93:534–8.

    Article  CAS  PubMed  Google Scholar 

  58. Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab. 2006;291:E1003–8.

    Article  CAS  PubMed  Google Scholar 

  59. Morris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organ Res Methods. 2008;11:364–86.

    Article  Google Scholar 

  60. Bornstein M, Hedges L, Higgins J, Rothstein H. Introduction to Meta-Analysis. United Kingdom: A John Wiley & Sons; 2009.

    Book  Google Scholar 

  61. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111.

    Article  PubMed  Google Scholar 

  62. Cohen J. Statistical power analysis. Curr Dir Psychol Sci. 1992;1:98–101.

    Article  Google Scholar 

  63. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–63.

    Article  CAS  PubMed  Google Scholar 

  66. Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package. J Stat Softw. 2010;36:1–48.

    Article  Google Scholar 

  67. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154:502–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe. J Clin Endocrinol Metab. 2017;102:1161–73.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Haring R, Hannemann A, John U, Radke D, Nauck M, Wallaschofski H, et al. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2012;97:408–15.

    Article  CAS  PubMed  Google Scholar 

  70. Görgens SW, Eckardt K, Jensen J, Drevon CA, Eckel J. Exercise and Regulation of Adipokine and Myokine Production. Prog Mol Biol Transl Sci. 2015;135:313–36.

    Article  PubMed  Google Scholar 

  71. Atkins JL, Whincup PH, Morris RW, Lennon LT, Papacosta O, Wannamethee SG. Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men. J Am Geriatr Soc. 2014;62:253–60.

    Article  PubMed  Google Scholar 

  72. Batsis JA, Mackenzie TA, Barre LK, Lopez-Jimenez F, Bartels SJ. Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III. Eur J Clin Nutr. 2014;68:1001–7.

    Article  CAS  PubMed  Google Scholar 

  73. Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med. 2014;127:547–53.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Wannamethee SG, Shaper AG, Lennon L, Whincup PH. Decreased muscle mass and increased central adiposity are independently related to mortality in older men. Am J Clin Nutr. 2007;86:1339–46.

    Article  CAS  PubMed  Google Scholar 

  75. Andrews MA, Magee CD, Combest TM, Allard RJ, Douglas KM. Physical Effects of Anabolic-androgenic Steroids in Healthy Exercising Adults: A Systematic Review and Meta-analysis. Curr Sports Med Rep. 2018;17:232–41.

    Article  PubMed  Google Scholar 

  76. Wangxiao Bao YS, Wangxiao Bao YS. Exercise Programs for Muscle Mass, Muscle Strength and Physical Performance in Older Adults with Sarcopenia: A Systematic Review and Meta-Analysis. Aging Dis. 2020;11:863–73.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hsu K-J, Liao C-D, Tsai M-W, Chen C-N. Effects of Exercise and Nutritional Intervention on Body Composition, Metabolic Health, and Physical Performance in Adults with Sarcopenic Obesity: A Meta-Analysis. Nutrients. 2019;11:2163.

    Article  CAS  PubMed Central  Google Scholar 

  78. Pacifico J, Geerlings MAJ, Reijnierse EM, Phassouliotis C, Lim WK, Maier AB. Prevalence of sarcopenia as a comorbid disease: A systematic review and meta-analysis. Exp Gerontol. 2020;131:110801.

    Article  PubMed  Google Scholar 

  79. Tan BHL, Fearon KCH. Cachexia: prevalence and impact in medicine. Curr Opin Clin Nutr Metab Care. 2008;11:400–7.

    Article  PubMed  Google Scholar 

  80. Akashi YJ, Springer J, Anker SD. Cachexia in chronic heart failure: prognostic implications and novel therapeutic approaches. Curr Heart Fail Rep. 2005;2:198–203.

    Article  PubMed  Google Scholar 

  81. Kwan HY, Maddocks M, Nolan CM, Jones SE, Patel S, Barker RE, et al. The prognostic significance of weight loss in chronic obstructive pulmonary disease-related cachexia: a prospective cohort study. J Cachexia Sarcopenia Muscle. 2019;10:1330–8.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Skinner JW, Otzel DM, Bowser A, Nargi D, Agarwal S, Peterson MD, et al. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2018;9:465–81.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Gittings PM, Grisbrook TL, Edgar DW, Wood FM, Wand BM, O’Connell NE. Resistance training for rehabilitation after burn injury: A systematic literature review & meta-analysis. Burns. 2018;44:731–51.

    Article  PubMed  Google Scholar 

  84. Sinclair M, Grossmann M, Hoermann R, Angus PW, Gow PJ. Testosterone therapy increases muscle mass in men with cirrhosis and low testosterone: A randomised controlled trial. J Hepatol. 2016;65:906–13.

    Article  CAS  PubMed  Google Scholar 

  85. Wright TJ, Dillon EL, Durham WJ, Chamberlain A, Randolph KM, Danesi C, et al. A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women. J Cachexia Sarcopenia Muscle. 2018;9:482–96.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Storer TW, Basaria S, Traustadottir T, Harman SM, Pencina K, Li Z, et al. Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men. J Clin Endocrinol Metab. 2017;102:583–93.

    PubMed  Google Scholar 

  87. Baillargeon J, Deer RR, Kuo Y-F, Zhang D, Goodwin JS, Volpi E. Androgen Therapy and Rehospitalization in Older Men with Testosterone Deficiency. Mayo Clin Proc. 2016;91:587–95.

    Article  CAS  PubMed  Google Scholar 

  88. Chapman IM, Visvanathan R, Hammond AJ, Morley JE, Field JBF, Tai K, et al. Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women. Am J Clin Nutr. 2009;89:880–9.

    Article  CAS  PubMed  Google Scholar 

  89. Zhou T, Hu Z-Y, Zhang H-P, Zhao K, Zhang Y, Li Y, et al. Effects of Testosterone Supplementation on Body Composition in HIV Patients: A Meta-analysis of Double-blinded Randomized Controlled Trials. Curr Med Sci. 2018;38:191–8.

    Article  CAS  PubMed  Google Scholar 

  90. Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, et al. Testosterone supplementation in heart failure: a meta-analysis. Circ Heart Fail. 2012;5:315–21.

    Article  CAS  PubMed  Google Scholar 

  91. Jasuja GK, Ameli O, Reisman JI, Rose AJ, Miller DR, Berlowitz DR, et al. Health Outcomes Among Long-term Opioid Users With Testosterone Prescription in the Veterans Health Administration. JAMA Netw Open. 2019;2:e1917141.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Haider KS, Haider A, Saad F, Doros G, Hanefeld M, Dhindsa S, et al. Remission of type 2 diabetes following long-term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11-year data from a real-world registry study. Diabetes Obes Metab. 2020;22:2055–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Angell P, Chester N, Green D, Somauroo J, Whyte G, George K. Anabolic steroids and cardiovascular risk. Sports Med. 2012;42:119–34.

    Article  PubMed  Google Scholar 

  94. Solimini R, Rotolo MC, Mastrobattista L, Mortali C, Minutillo A, Pichini S, et al. Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping. Eur Rev Med Pharmacol Sci. 2017;21:7–16.

    CAS  PubMed  Google Scholar 

  95. Hoffman JR, Ratamess NA. Medical Issues Associated with Anabolic Steroid Use: Are They Exaggerated? J Sports Sci Med. 2006;5:182–93.

    PubMed  PubMed Central  Google Scholar 

  96. 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. N Engl J Med. 1996;335:1–7.

    Article  CAS  PubMed  Google Scholar 

  97. Gagliano-Jucá T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nat Rev Cardiol. 2019;16:555–74.

    Article  PubMed  Google Scholar 

  98. Fiuza-Luces C, Santos-Lozano A, Joyner M, Carrera-Bastos P, Picazo O, Zugaza JL, et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat Rev Cardiol. 2018;15:731–43.

    Article  CAS  PubMed  Google Scholar 

  99. Nystoriak MA, Bhatnagar A. Cardiovascular Effects and Benefits of Exercise. Front Cardiovasc Med. 2018;5:135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gordon B, Chen S, Durstine JL. The effects of exercise training on the traditional lipid profile and beyond. Curr Sports Med Rep. 2014;13:253–9.

    Article  PubMed  Google Scholar 

  101. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103:1715–44.

    Article  PubMed  Google Scholar 

  102. Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology. Andrology. 2020;8:970–87.

    Article  PubMed  Google Scholar 

  103. Chen Z, Zhang Y, Lu C, Zeng H, Schumann M, Cheng S. Supervised Physical Training Enhances Muscle Strength but Not Muscle Mass in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis. Front Physiol. 2019;10:843.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Chen L-K, Woo J, Assantachai P, Auyeung T-W, Chou M-Y, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020;21(300–307):e2.

    Google Scholar 

  105. von Haehling S, Anker SD. Treatment of cachexia: an overview of recent developments. J Am Med Dir Assoc. 2014;15:866–72.

    Article  Google Scholar 

  106. Mobley CB, Haun CT, Roberson PA, Mumford PW, Kephart WC, Romero MA, et al. Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training. PLoS ONE. 2018;13:e0195203.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Morton RW, Sato K, Gallaugher MPB, Oikawa SY, McNicholas PD, Fujita S, et al. Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy. Young Men Front Physiol. 2018;9:1373.

    Article  PubMed  Google Scholar 

  108. Hooper DR, Kraemer WJ, Focht BC, Volek JS, DuPont WH, Caldwell LK, et al. Endocrinological Roles for Testosterone in Resistance Exercise Responses and Adaptations. Sports Med. 2017;47:1709–20.

    Article  PubMed  Google Scholar 

  109. Hackney AC. Hypogonadism in Exercising Males: Dysfunction or Adaptive-Regulatory Adjustment? Front Endocrinol. 2020;11:11.

    Article  Google Scholar 

  110. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281:E1172-1181.

    Article  CAS  PubMed  Google Scholar 

  111. Srinivas-Shankar U, Wu FCW. Drug insight: testosterone preparations. Nat Clin Pract Urol. 2006;3:653–65.

    Article  CAS  PubMed  Google Scholar 

  112. Schoenfeld BJ, Grgic J, Ogborn D, Krieger JW. Strength and Hypertrophy Adaptations Between Low- vs. High-Load Resistance Training: A Systematic Review and Meta-analysis. J Strength Cond Res. 2017;31:3508–23.

  113. Grgic J, Lazinica B, Mikulic P, Krieger JW, Schoenfeld BJ. The effects of short versus long inter-set rest intervals in resistance training on measures of muscle hypertrophy: A systematic review. Eur J Sport Sci. 2017;17:983–93.

    Article  PubMed  Google Scholar 

  114. Schoenfeld BJ, Grgic J, Krieger J. How many times per week should a muscle be trained to maximize muscle hypertrophy? A systematic review and meta-analysis of studies examining the effects of resistance training frequency. J Sports Sci. 2019;37:1286–95.

    Article  PubMed  Google Scholar 

  115. Schoenfeld BJ, Ogborn D, Krieger JW. Dose-response relationship between weekly resistance training volume and increases in muscle mass: A systematic review and meta-analysis. J Sports Sci. 2017;35:1073–82.

    Article  PubMed  Google Scholar 

  116. Morey MC, Pieper CF, Crowley GM, Rnc‐Bsn, Sullivan RJ, Puglisi CM. Exercise Adherence and 10-Year Mortality in Chronically Ill Older Adults. J Am Geriatr Soc. 2002;50:1929–33.

  117. Friedenreich CM, Stone CR, Cheung WY, Hayes SC. Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis. JNCI Cancer Spectr. 2020;4:pkz080.

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Authors and Affiliations

  1. Medical School, Federal University of Fronteira Sul, SC 484 - Km 02, Chapecó, Santa Catarina, Brazil

    Hugo Falqueto, Mauro N. O. Silvério, Juliano C. H. Farias & Leandro H. Manfredi

  2. Graduate Program in Biomedical Sciences, UFFS, Chapecó, Santa Catarina, Brazil

    Hugo Falqueto & Leandro H. Manfredi

  3. Laboratory of Sport Biomechanics, Sports Department, School of Physical Education, Physiotherapy and Occupational Therapy, Federal University of Minas Gerais, Minas Gerais, Brazil

    Jorge L. R. Júnior

  4. Department of Health Sciences, CUNY Lehman College, Bronx, NY, USA

    Brad J. Schoenfeld

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All authors had a substantial contribution to conception and design, acquisition of data, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content, and final approval of the version to be published.

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Falqueto, H., Júnior, J.L.R., Silvério, M.N.O. et al. Can conditions of skeletal muscle loss be improved by combining exercise with anabolic–androgenic steroids? A systematic review and meta-analysis of testosterone-based interventions. Rev Endocr Metab Disord 22, 161–178 (2021). https://doi.org/10.1007/s11154-021-09634-4

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