World J Mens Health.  2018 Sep;36(3):192-198. 10.5534/wjmh.180001.

Testosterone and Sarcopenia

• Shin MJ
• Jeon YK
• Kim IJ

• KMID: 2419320
• DOI: http://doi.org/10.5534/wjmh.180001

Abstract

Aging affects metabolism, leading to physiological and functional impairments, and is also related to changes in body composition, including reduced skeletal muscle mass and increased body fat. These changes are correlated with the pathophysiology of sarcopenia, which is defined as age-related loss of skeletal muscle mass and strength. Low testosterone levels are associated with unfavorable body composition changes, and sex hormones decrease with aging. Androgen deficiency, along with lack of exercise and poor nutrition, may be among the modifiable contributors to sarcopenia. Testosterone treatment has been reported to have beneficial effects on muscle mass and function, but the results have been inconsistent. Here, we discuss the correlation between testosterone and muscle mass and function, the impact of testosterone on sarcopenia, and the probable mechanisms underlying these effects.

Keyword

Aging; Body composition; Muscles; Sarcopenia; Testosterone

MeSH Terms

Adipose Tissue
Aging
Body Composition
Gonadal Steroid Hormones
Metabolism
Muscle, Skeletal
Muscles
Sarcopenia*
Testosterone*
Gonadal Steroid Hormones
Testosterone

Figure

• 

  Fig. 1 The European Working Group on Sarcopenia in Older People (EWGSOP) suggested algorithm for sarcopenia case ascertainment in older individuals [13]. Data from Cruz-Jentoft et al (Age Ageing 2010;39:412-23) [13] with original copyright holder's permission.

Reference

1. Song MY, Ruts E, Kim J, Janumala I, Heymsfield S, Gallagher D. Sarcopenia and increased adipose tissue infiltration of muscle in elderly African American women. Am J Clin Nutr. 2004; 79:874–880. PMID: 15113728.

2. Harris T. Muscle mass and strength: relation to function in population studies. J Nutr. 1997; 127:1004S–1006S. PMID: 9164284.

3. Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997; 127:990S–991S. PMID: 9164280.

4. Araujo AB, Travison TG, Bhasin S, Esche GR, Williams RE, Clark RV, et al. Association between testosterone and estradiol and age-related decline in physical function in a diverse sample of men. J Am Geriatr Soc. 2008; 56:2000–2008. PMID: 19016935.

5. Hyde Z, Flicker L, Almeida OP, Hankey GJ, McCaul KA, Chubb SA, et al. Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metab. 2010; 95:3165–3172. PMID: 20410223.

6. Krasnoff JB, Basaria S, Pencina MJ, Jasuja GK, Vasan RS, Ulloor J, et al. Free testosterone levels are associated with mobility limitation and physical performance in communitydwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab. 2010; 95:2790–2799. PMID: 20382680.

7. Schaap LA, Pluijm SM, Deeg DJ, Penninx BW, Nicklas BJ, Lips P, et al. Low testosterone levels and decline in physical performance and muscle strength in older men: findings from two prospective cohort studies. Clin Endocrinol (Oxf). 2008; 68:42–50. PMID: 17666086.

8. Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R. Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol (1985). 2000; 88:1321–1326. PMID: 10749826.

9. Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006; 61:1059–1064. PMID: 17077199.

10. Deschenes MR. Effects of aging on muscle fibre type and size. Sports Med. 2004; 34:809–824. PMID: 15462613.

11. Evans WJ, Campbell WW. Sarcopenia and age-related changes in body composition and functional capacity. J Nutr. 1993; 123(2 Suppl):465–468. PMID: 8429405.

12. von Haehling S, Morley JE, Anker SD. An overview of sarcopenia: facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle. 2010; 1:129–133. PMID: 21475695.

13. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010; 39:412–423. PMID: 20392703.

14. Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011; 12:249–256. PMID: 21527165.

15. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc. 2014; 15:95–101. PMID: 24461239.

16. Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci. 2014; 69:547–558. PMID: 24737557.

17. Berger MJ, Doherty TJ. Sarcopenia: prevalence, mechanisms, and functional consequences. Interdiscip Top Gerontol. 2010; 37:94–114. PMID: 20703058.

18. Morley JE. Pharmacologic options for the treatment of sarcopenia. Calcif Tissue Int. 2016; 98:319–333. PMID: 26100650.

19. Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Morley PM, Stauber PM, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997; 46:410–413. PMID: 9109845.

20. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Int J Androl. 2009; 32:1–10. PMID: 18798761.

21. Carnegie C. Diagnosis of hypogonadism: clinical assessments and laboratory tests. Rev Urol. 2004; 6(Suppl 6):S3–S8.

22. Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011; 34:1669–1675. PMID: 21709300.

23. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991; 73:1016–1025. PMID: 1719016.

24. Simon D, Preziosi P, Barrett-Connor E, Roger M, Saint-Paul M, Nahoul K, et al. The influence of aging on plasma sex hormones in men: the Telecom Study. Am J Epidemiol. 1992; 135:783–791. PMID: 1595678.

25. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev. 1999; 107:123–136. PMID: 10220041.

26. Häkkinen K, Pakarinen A. Muscle strength and serum testosterone, cortisol and SHBG concentrations in middle-aged and elderly men and women. Acta Physiol Scand. 1993; 148:199–207. PMID: 8352031.

27. Kadi F. Adaptation of human skeletal muscle to training and anabolic steroids. Acta Physiol Scand Suppl. 2000; 646:1–52. PMID: 10717767.

28. Kadi F, Eriksson A, Holmner S, Thornell LE. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc. 1999; 31:1528–1534. PMID: 10589853.

29. Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR. Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol. 1998; 275:E864–E871. PMID: 9815007.

30. Powers ML, Florini JR. A direct effect of testosterone on muscle cells in tissue culture. Endocrinology. 1975; 97:1043–1047. PMID: 172315.

31. Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. Anat Rec. 1971; 170:421–435. PMID: 5118594.

32. Estrada M, Espinosa A, Müller M, Jaimovich E. Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells. Endocrinology. 2003; 144:3586–3597. PMID: 12865341.

33. Sculthorpe N, Solomon AM, Sinanan AC, Bouloux PM, Grace F, Lewis MP. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Med Sci Sports Exerc. 2012; 44:610–615. PMID: 21946153.

34. Wu Y, Bauman WA, Blitzer RD, Cardozo C. Testosteroneinduced hypertrophy of L6 myoblasts is dependent upon Erk and mTOR. Biochem Biophys Res Commun. 2010; 400:679–683. PMID: 20816664.

35. Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997; 82:1661–1667. PMID: 9177359.

36. Srinivas-Shankar U, Roberts SA, Connolly MJ, O';Connell MD, Adams JE, Oldham JA, et al. 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; 95:639–650. PMID: 20061435.

37. Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with lownormal gonadal status. J Gerontol A Biol Sci Med Sci. 2003; 58:618–625. PMID: 12865477.

38. 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; 102:583–593. PMID: 27754805.

39. Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc. 2010; 58:1134–1143. PMID: 20722847.

40. Travison TG, Basaria S, Storer TW, Jette AM, Miciek R, Farwell WR, et al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2011; 66:1090–1099. PMID: 21697501.

41. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005; 90:678–688. PMID: 15562020.

42. 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. PMID: 8637535.

43. Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, Acha AA, Ostir GV. Androgen treatment and muscle strength in elderly men: a meta-analysis. J Am Geriatr Soc. 2006; 54:1666–1673. PMID: 17087692.

44. Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study. J Clin Endocrinol Metab. 1996; 81:3469–3475. PMID: 8855787.