Advertisement

AGE

, 37:5 | Cite as

Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies

  • Walter Krause Neto
  • Eliane Florencio Gama
  • Leandro Yanase Rocha
  • Carla Cristina Ramos
  • Wagner Taets
  • Katia Bilhar Scapini
  • Janaina B. Ferreira
  • Bruno Rodrigues
  • Érico Caperuto
Article

Abstract

The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61–1.69) to 6.20 (95 % CI, 5.22–7.18) kg, although it was heterogeneous (I 2 = 98 %). Effect estimate was 3.59 [2.38–4.81]. Androgen therapy decreased fat mass; effect estimate was −1.78 [−2.57, −0.99] that analysis had also a high level of heterogeneity (I 2 = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.

Keywords

Androgen therapy Testosterone Fat free mass Elderly men 

Notes

Conflict of interest

The authors declare that there is no conflict of interests.

References

  1. Abbasi AA, Drinka PJ, Mattson DE, Rudman D (1993) Low circulating levels of insulin-like growth factors and testosterone in chronically institutionalized elderly men. J Am Geriatr Soc 41(9):975–982PubMedGoogle Scholar
  2. Allan CA, Forbes EA, Strauss BJ, McLachlan RI (2008) Testosterone therapy increases sexual desire in ageing men with low-normal testosterone levels and symptoms of androgen deficiency. Int J Impot Res 20(4):396–401Google Scholar
  3. Aya K, Alhawagri M, Hagen-Stapleton A, et al (2005) NF-(kappa)B-inducing kinase controls lymphocyte and osteoclast activities in inflammatory arthritis. J Clin Invest 115:1848–54Google Scholar
  4. Blackman MR, Sorkin JD, Munzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O’Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell Em St Clair C, Pabst KM, Harman SM (2002) Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 288 (18): 2282–92Google Scholar
  5. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW (2005) 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 90(2):678–688CrossRefPubMedGoogle Scholar
  6. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM (2010) Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95(6):2536–2559CrossRefPubMedGoogle Scholar
  7. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60(11):1451–1457CrossRefPubMedGoogle Scholar
  8. Demchenko YN, Glebov OK, Zingone A, et al (2010) Classical and/or alternative NFkappaB pathway activation in multiple myeloma. Blood 115:3541–52Google Scholar
  9. Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, Bosch JL, Grobbee DE, van der Schouw YT (2008) Effect of testosterone replacement therapy on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299(1):39–52. doi: 10.1001/jama.2007.51, Erratum in: JAMA. 2008 Feb 13;299(6):634CrossRefPubMedGoogle Scholar
  10. Ferrando AA, Sheffield-Moore M, Paddon-Jones D, Wolfe RR, Urban RJ (2003) Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88(1):358–62CrossRefPubMedGoogle Scholar
  11. Iannuzzi-Sucich M, Prestwood KM, Kenny AM (2002) Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol: Med Sci 57A(12):M772–M777CrossRefGoogle Scholar
  12. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A (2005) Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf) 63(3):280–293, ReviewCrossRefGoogle Scholar
  13. Kenny AM, Prestwood KM, Raisz LG (2000) Short-term effects of intramuscular and transdermal testosterone on bone turnover, prostate symptoms, cholesterol, and hematocrit in men over age 70 with low testosterone levels. Endocr Res 26(2):153–168CrossRefPubMedGoogle Scholar
  14. Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG (2001) Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 56(5):M266–M272CrossRefPubMedGoogle Scholar
  15. Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, McGee D (2010) 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 58(6):1134–1143. doi: 10.1111/j.1532-5415.2010.02865.x CrossRefPubMedCentralPubMedGoogle Scholar
  16. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700CrossRefPubMedCentralPubMedGoogle Scholar
  17. Liverman C, Blazer D (2005) Testosterone in aging: directions for clinical research. National Academy Press, Washington, DCGoogle Scholar
  18. McGill JJ, Shoskes DA, Sabanegh ES (2012) Androgen deficiency in older men: indications, advantages, and pitfalls of testosterone replacement therapy. Cleve Clin J Med 79(11):797–806CrossRefPubMedGoogle Scholar
  19. Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS (1998) The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf) 49(4):421–432CrossRefGoogle Scholar
  20. Morley JS, Bridson J, Nash TP, Miles JB, White S, Makin MK (2003) Low-dose methadone has an analgesic effect in neuropathic pain: a double-blind randomized controlled crossover trial. Palliat Med 17(7):576–587CrossRefPubMedGoogle Scholar
  21. Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, Acha AA, Ostir GV (2006) Androgen treatment and muscle strength in elderly men: a meta-analysis. J Am Geriatr Soc 54(11):1666–1673CrossRefPubMedCentralPubMedGoogle Scholar
  22. Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL (2005) Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 90(3):1502–1510CrossRefPubMedGoogle Scholar
  23. Qin W, Pan J, Wu Y et al (2010) Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1alpha. Biochem Biophys Res Commun 403:473–478CrossRefPubMedGoogle Scholar
  24. Sattler FR, Castaneda-Sceppa C, Binder EF, Schroeder ET, Wang Y, Bhasin S, Kawakubo M, Stewart Y, Yarasheski KE, Ulloor J, Colletti P, Roubenoff R, Azen SP (2009) Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab 94(6):1991–2001. doi: 10.1210/jc.2008-2338 CrossRefPubMedCentralPubMedGoogle Scholar
  25. Schroeder ET, Terk M, Sattler FR (2003a) Androgen therapy improves muscle mass and strength but not muscle quality: results from two studies. Am J Physiol Endocrinol Metab 285(1):E16–E24CrossRefPubMedGoogle Scholar
  26. Schroeder ET, Singh A, Bhasin S, Storer TW, Azen C, Davidson T, Martinez C, Sinha-Hikim I, Jaque SV, Terk M, Sattler FR (2003b) Effects of an oral androgen on muscle and metabolism in older, community-dwelling men. Am J Physiol Endocrinol Metab 284(1):E120–E128CrossRefPubMedGoogle Scholar
  27. Schroeder ET, Zheng L, Yarasheski KE, Qian D, Stewart Y, Flores C, Martinez C, Terk M, Sattler FR (2004) Treatment with oxandrolone and the durability of effects in older men. J Appl Physiol (1985) 96(3):1055–1062CrossRefGoogle Scholar
  28. Schroeder ET, Vallejo AF, Zheng L, Stewart Y, Flores C, Nakao S, Martinez C, Sattler FR (2005) Six-week improvements in muscle mass and strength during androgen therapy in older men. J Gerontol A Biol Sci Med Sci 60(12):1586–92Google Scholar
  29. Sculthorpe N, Solomon AM, Sinanan AC et al (2012) Androgens affect myogenesis in vitro and increase local IGF-1 expression. Med Sci Sports Exercise 44:610–615CrossRefGoogle Scholar
  30. Sheffield-Moore M, Dillon EL, Casperson SL, Gilkison CR, Paddon-Jones D, Durham WJ, Grady JJ, Urban RJ (2011) A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. J Clin Endocrinol Metab 96(11):E1831–E1837. doi: 10.1210/jc.2011-1262 CrossRefPubMedCentralPubMedGoogle Scholar
  31. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999) Effect of testosterone replacement therapy on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84(8):2647–53PubMedGoogle Scholar
  32. Starkey JM, Haidacher SJ, LeJeune WS, et al (2006) Diabetes-induced activation of canonical and noncanonical nuclear factor-kappaB pathways in renal cortex. Diabetes 55:1252–9Google Scholar
  33. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R, North American AA2500 T Gel Study Group (2003) AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 88(6):2673–2681CrossRefPubMedGoogle Scholar
  34. Tenover JL (1998) Male hormone replacement therapy including "andropause". Endocrinol Metab Clin North Am 27(4):969–87, x. ReviewCrossRefPubMedGoogle Scholar
  35. Urban RJ, Dillon EL, Choudhary S, Zhao Y, Horstman AM, Tilton RG, Sheffield-Moore M (2014) Translational studies in older men using testosterone to treat sarcopenia. Trans Am Clin Climatol Assoc 125:27–44PubMedCentralPubMedGoogle Scholar
  36. Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE (2003) Oral testosterone treatment increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 58(7):618–625CrossRefPubMedGoogle Scholar
  37. Wu Y, Bauman WA, Blitzer RD et al (2010) Testosterone-induced hypertrophy of L6 myoblasts is dependent upon Erk and mTOR. Biochem Biophys Res Commun 400:679–683CrossRefPubMedGoogle Scholar
  38. Xu L, Freeman G, Cowling BJ, Schooling CM (2013) Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 11:108CrossRefPubMedCentralPubMedGoogle Scholar
  39. Yang D, Li J, Yuan Z, Liu X (2013) Effect of hormone replacement therapy on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLoS One 8(5):e62329. doi: 10.1371/journal.pone.0062329, Print 2013CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© American Aging Association 2015

Authors and Affiliations

  • Walter Krause Neto
    • 1
  • Eliane Florencio Gama
    • 1
  • Leandro Yanase Rocha
    • 2
  • Carla Cristina Ramos
    • 2
  • Wagner Taets
    • 2
  • Katia Bilhar Scapini
    • 3
  • Janaina B. Ferreira
    • 3
  • Bruno Rodrigues
    • 2
  • Érico Caperuto
    • 2
    • 4
  1. 1.Laboratory of Morphoquantitative Studies and Immunohistochemistry, Department of Physical EducationSão Judas Tadeu UniversitySão PauloBrazil
  2. 2.Laboratory of Human Movement, Department of Physical EducationSão Judas Tadeu UniversitySão PauloBrazil
  3. 3.LaboratoryINCORSão PauloBrazil
  4. 4.Laboratory of Exercise and Movement SciencesMackenzie Presbiterian UniversitySão PauloBrazil

Personalised recommendations