, Volume 7, Issue 2, pp 133–139 | Cite as

Growth hormone treatment in human ageing: benefits and risks

  • Roberta Giordano
  • Lorenza Bonelli
  • Elisa Marinazzo
  • Ezio GhigoEmail author
  • Emanuela Arvat


This paper will focus on the rationale of using Growth Hormone (GH) as an anti-ageing therapy in the healthy elderly with age-related decline in the activity of the GH/IGF-I axis, the so called “somatopause”. Although the age-related decline in the activity of the GH/IGF-I axis is considered to contribute to age-related changes similar to those observed in Growth Hormone Deficient (GHD) adults, GH/IGF-I deficiency or resistance is also known to result in prolonged life expectancy, at least in animals. These data raise the question whether or not GH deficiency constitutes a beneficial adaptation to ageing and therefore requires no therapy. Moreover, although GH therapy has been shown to exert positive effects in GHD patients, its safety, efficacy and role in healthy elderly individuals is highly controversial. This review provides a comprehensive account of the implications of GH therapy in the ageing subject.

Key words



Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Corpas E, Harman SM, Blackman MR, 1993 Human growth hormone and human ageing. Endocr Rev 14: 20–39.CrossRefPubMedGoogle Scholar
  2. 2.
    Muller EE, Cella SG, Parenti M, et al, 1995 Somatotropic dysregulation in old mammals. Horm Res 43: 39–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Ghigo E, Arvat E, Gianotti L, et al, 1996 Human ageing and the GH-IGF-I axis. J Ped Endocrinol Metab 9: 271–278.Google Scholar
  4. 4.
    Arvat E, Giordano R, Gianotti L, Broglio F, Camanni F, Ghigo E, 1999 Neuroendocrinology of the human growth hormone-insulin-like growth factor I axis during ageing. Growth Horm IGF Res 9: 111–115.CrossRefPubMedGoogle Scholar
  5. 5.
    Ghigo E, Arvat E, Gianotti L, Maccario M, Camanni F 1999 The regulation of growth hormone secretion. In: Jenkins RC, Ross RJM (eds) The endocrine response to acute illness, Front Horm Res, Basel Karger; pp, 152–175.CrossRefGoogle Scholar
  6. 6.
    Giustina A, Veldhuis JD, 1998 Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 19: 717–797.PubMedGoogle Scholar
  7. 7.
    Zadik Z, Chalew SA, McCarter RJ Jr, Meistas M, Kowarski AA, 1985 The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 60: 513–516.CrossRefPubMedGoogle Scholar
  8. 8.
    Veldhuis JD, Liem AY, South S, et al, 1995 Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 80: 3209–3222.PubMedGoogle Scholar
  9. 9.
    de Boer H, Blok GJ, Van der Veen EA, 1995 Clinical aspects of growth hormone deficiency in adults. Endocr Rev 16: 63–86.CrossRefPubMedGoogle Scholar
  10. 10.
    Kojima M, Hosoda H, Date Y, et al, 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656–660.CrossRefPubMedGoogle Scholar
  11. 11.
    van der Lely AJ, Tschop M, Heiman ML, Ghigo E, 2004 Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25: 426–457.CrossRefPubMedGoogle Scholar
  12. 12.
    Arvat E, Giordano R, Broglio F, et al, 2000 GH Secre-tagogues in Ageing. J Anti-ageing Med 3: 149–158.CrossRefGoogle Scholar
  13. 13.
    Toogod AA, Shalet SM, 1998 Ageing and growth hormone status. Baillieres Clin Endocrinol Metab 12: 281–296.CrossRefGoogle Scholar
  14. 14.
    Rudman D, Feller AG, Nagraj HS, et al, 1990 Effects of human growth hormone in men over 60 years old. N Engl J Med 323: 1–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Sartorio A, Conti A, Molinari E, et al, 1996 Growth, growth hormone and cognitive functions. Horm Res 45: 23–29.CrossRefPubMedGoogle Scholar
  16. 16.
    van Cauter E, Leproult R, Plat L, 2000 Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 284: 861–868.CrossRefPubMedGoogle Scholar
  17. 17.
    Aleman A, de Vries WR, de Haan EH, et al, 2000 Age-sensitive cognitive function, growth hormone and insulinlike growth factor 1 plasma levels in healthy older men. Neuropsychobiol 41: 73–78.CrossRefGoogle Scholar
  18. 18.
    Compton DM, Bachman LD, Brand D, 2000 Age-associated changes in cognitive function in highly educated adults: emerging myths and realities. Int J Geriatr Psychiatry 15: 75–85.CrossRefPubMedGoogle Scholar
  19. 19.
    van Dam PS, Aleman A, de Vries WR, et al, 2000 Growth hormone, insulin-like growth factor I and cognitive function in adults. Growth Horm IGF Res 10: S69–73.CrossRefPubMedGoogle Scholar
  20. 20.
    Schneider HJ, Pagotto U, Stalla GK, 2003 Central effects of the somatotropic system. Eur J Endocrinol 149: 377–392.CrossRefPubMedGoogle Scholar
  21. 21.
    Liu H, Bravata DM, Olkin I, et al, 2007 Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med 146: 104–115.CrossRefPubMedGoogle Scholar
  22. 22.
    Holloway L, Butterfield G, Hintz RL, et al, 1994 Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women. J Clin Endocrinol Metab 79: 470–479.PubMedGoogle Scholar
  23. 23.
    Papadakis MA, Grady D, Black D, 1996 Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 124: 708–716.CrossRefPubMedGoogle Scholar
  24. 24.
    Johannsson G, Mårin P, Lönn L, et al, 1997 Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 82: 727–734.PubMedGoogle Scholar
  25. 25.
    Franco C, Brandberg J, Lönn L, et al, 2005 Growth hormone treatment reduces abdominal visceral fat in postmenopausal women with abdominal obesity: a 12-month placebo-controlled trial. J Clin Endocrinol Metab 90: 1466–1474.CrossRefPubMedGoogle Scholar
  26. 26.
    Lange KH, Andersen JL, Beyer N, et al, 2002 GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab 87: 513–523.CrossRefPubMedGoogle Scholar
  27. 27.
    Hameed M, Lange KH, Andersen JL, et al, 2004 The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol 555: 231–240.CrossRefPubMedGoogle Scholar
  28. 28.
    Weissberger AJ, Anastasiadis AD, Sturgess I, et al, 2003 Recombinant human growth hormone treatment in elderly patients undergoing elective total hip replacement. Clin Endocrinol 58: 99–107.CrossRefGoogle Scholar
  29. 29.
    Johannsson G, Bengtsson BA, Ahlmen J, 1999 Doubleblind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement. Am J Kidney Dis 33: 709–717.CrossRefPubMedGoogle Scholar
  30. 30.
    Nyberg F, Burman P, 1996 Growth hormone and its receptors in the central nervous system-location and functional significance. Horm Res 45: 18–22.CrossRefPubMedGoogle Scholar
  31. 31.
    Jones JI, Clemmons DR, 1995 Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16: 3–34.PubMedGoogle Scholar
  32. 32.
    Morley JE, Kaiser F, Raum WJ, 1997 Potentially predictive and manipulable blood serum correlates of ageing in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA 94: 7537–7542.CrossRefPubMedGoogle Scholar
  33. 33.
    Kalmijn S, Janssen JA, Pols HA, et al, 2000 A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. J Clin Endocrinol Metab 85: 4551–4555.CrossRefPubMedGoogle Scholar
  34. 34.
    Papadakis MA, Grady D, Tierney MJ, et al, 1995 Insulin-like growth factor 1 and functional status in healthy older men. J Am Geriatr Soc 43: 1350–1355.CrossRefPubMedGoogle Scholar
  35. 35.
    Paolisso G, Ammendola S, Del Buono A, 1997 Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab 82: 2204–2209.CrossRefPubMedGoogle Scholar
  36. 36.
    Rollero A, Murialdo G, Fonzi S, et al, 1998 Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects. Neuropsychobiology 38: 73–79.CrossRefPubMedGoogle Scholar
  37. 37.
    Friedlander AL, Butterfield GE, Moynihan S, 2001 One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women. J Clin Endocrinol Metab 86: 1496–1503.PubMedGoogle Scholar
  38. 38.
    Cummings DE, Merriam GR, 2003 Growth hormone therapy in adults. Annu Rev Med 54: 513–533.CrossRefPubMedGoogle Scholar
  39. 39.
    Moller J, Moller N, Frandsen E, Wolthers T, Jorgensen JO, Christiansen JS, 1997 Blockade of the renin-angiotensin-aldosterone system prevents growth hormone-induced fluid retention in humans. Am J Physiol 272: E803–808.PubMedGoogle Scholar
  40. 40.
    Yuen K, Warehan N, Frystyk J, et al, 2004 Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance. Eur J Endocrinol 151: 39–45.CrossRefPubMedGoogle Scholar
  41. 41.
    Chan JM, Stampfer MJ, Giovannucci E, et al, 1998 Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279: 563–566.CrossRefPubMedGoogle Scholar
  42. 42.
    Shim M, Cohen P, 1999 IGFs and human cancer: implications regarding the risk of growth hormone therapy. Horm Res 51: Suppl 3: 42–51.PubMedGoogle Scholar
  43. 43.
    Laban C, Bustin SA, Jenkins PJ, 2003 The GH-IGF-I axis and breast cancer. Trends Endocrinol Metab 14: 28–34.CrossRefPubMedGoogle Scholar
  44. 44.
    Banerjee I, Clayton PE, 2007 Growth hormone treatment and cancer risk. Endocrinol Metab Clin North Am 36: 247–263.CrossRefPubMedGoogle Scholar
  45. 45.
    Webb SM, Casanueva F, Wass JA, 2002 Oncological complications of excess GH in acromegaly. Pituitary 5: 21–25.CrossRefPubMedGoogle Scholar
  46. 46.
    Colao A, Ferone D, Marzullo P, Lombardi G, 2004 Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25: 102–152.CrossRefPubMedGoogle Scholar
  47. 47.
    Corpas E, Harman SM, Pineyro MA, Roberson R, Blackman MR, 1992 Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab 75: 530–535.PubMedGoogle Scholar
  48. 48.
    Ghigo E, Ceda GP, Valcavi R, et al, 1995 Effect of 15-day treatment with growth-hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal ageing. Eur J Endocrinol 132: 32–36.CrossRefPubMedGoogle Scholar
  49. 49.
    Khorram O, Laughlin GA, Yen SS, 1997 Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab 82: 1472–1479.PubMedGoogle Scholar
  50. 50.
    Vittone J, Blackman MR, Busby-Whitehead J, et al, 1997 Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism 46: 89–96.CrossRefPubMedGoogle Scholar
  51. 51.
    Veldhuis JD, Patrie JT, Brill KT, et al, 2004 Contributions of gender and systemic estradiol and testosterone concentrations to maximal secretagogue drive of burst-like growth hormone secretion in healthy middle-aged and older adults. J Clin Endocrinol Metab 89: 6291–6296.CrossRefPubMedGoogle Scholar
  52. 52.
    Borst SE, 2004 Interventions for sarcopenia and muscle weakness in older people. Age Ageing 33: 548–555.CrossRefPubMedGoogle Scholar
  53. 53.
    Ghigo E, Arvat E, Muccioli G, Camanni F, 1997 Growth Hormone-releasing peptides. Eur J Endocrinol 136: 445–460.CrossRefPubMedGoogle Scholar
  54. 54.
    Ghigo E, Arvat E, Broglio F, et al, 1999 Endocrine and non-endocrine activities of growth hormone secretagogues in humans. Horm Res 51: Suppl 3: 9–15.PubMedGoogle Scholar
  55. 55.
    Rahim A, O’Neill PA, Shalet SM, 1998 Growth hormone status during long-term hexarelin therapy. J Clin Endocrinol Metab 83: 1644–1649.CrossRefPubMedGoogle Scholar
  56. 56.
    Chapman IM, Bach MA, Van Cauter E, et al, 1996 Stimulation of the GH / IGF-I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects. J Clin Endocrinol Metab 81: 4249–4257.PubMedGoogle Scholar
  57. 57.
    Aloi JA, Gertz BJ, Hartman ML, et al, 1994 Neuroendo-crine responses to a novel growth hormone secretagogue, L-692,429, in healthy older subjects. J Clin Endocrinol Metab 79: 943–949.PubMedGoogle Scholar
  58. 58.
    Murphy MG, Weiss S, McClung M, et al, 2001 Effect of alendronate and MK-677 (a growth hormone secreta-gogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 86: 1116–1125PubMedGoogle Scholar
  59. 59.
    Bartke A, Coshigano K, Kopchick J, et al, 2001 Genes that prolong life: relationships of growth hormone and growth to ageing and life span. J Gerontol A Biol Sci Med Sci 56: B340–349.CrossRefPubMedGoogle Scholar
  60. 60.
    Holzenberger M, Dupont J, Ducos B, et al, 2003 IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–187.CrossRefPubMedGoogle Scholar
  61. 61.
    Bartke A, 2003 Is growth hormone deficiency a beneficial adaptation to ageing? Evidence from experimental animals. Trends Endocrinol Metab 14: 340–344.CrossRefPubMedGoogle Scholar
  62. 62.
    Blum-Degen D, Frolich L, Hoyer S, Riederer P, 1995 Altered regulation of brain glucose metabolism as a cause of neurodegenerative disorders? J Neural Transm 46: Suppl: 139–147.Google Scholar

Copyright information

© Hellenic Endocrine Society 2008

Authors and Affiliations

  • Roberta Giordano
    • 1
  • Lorenza Bonelli
    • 1
  • Elisa Marinazzo
    • 1
  • Ezio Ghigo
    • 1
    Email author
  • Emanuela Arvat
    • 1
  1. 1.Division of Endocrinology and Metabolism, Department of Internal MedicineUniversity of TurinTorinoItaly

Personalised recommendations