Skip to main content
Log in

Cardiovascular risk in aging and obesity: Is there a role for GH?

  • Review Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

GH has significant impact in adults. In fact, patients with the GH deficiency (GHD) syndrome are now recognized as having an increased cardiovascular risk. The effects of human aging on GH secretion have been evaluated by a number of researchers. Studies of 24 h secretion of GH have shown variable reductions in most 24-h GH secretory parameters in middle-aged and in older men and women, resulting in a decrease in plasma levels of its anabolic mediator IGF-I. Obesity is also associated with several endocrine and metabolic abnormalities. These include decreased serum GH concentrations, reduced GH half-life, frequency of GH secretory episodes and daily GH production rate. The mechanism of the low GH in obesity is not completely understood nor is it clear whether its relationship with visceral adiposity is causal. The aim of this article will be to review the available clinical data concerning the potential involvement of “subclinical” or perhaps better “functional” GHD, which is observed in aging and obesity, in the increase in cardiovascular risk which characterizes these two conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. De Boer H, Blok GJ, van der Veen VA. Clinical aspects of growth hormone deficiency in adults. Endocr Rev 1995, 16: 63–86.

    Article  PubMed  Google Scholar 

  2. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism: West Midlands Prospective Hypopituitary Study Group. Lancet 2001, 357: 425–31.

    Article  PubMed  CAS  Google Scholar 

  3. Giustina A, Veldhuis JD. Pathophysiology of the neuroregu-lation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998, 19: 717–97.

    PubMed  CAS  Google Scholar 

  4. Janssen JA, Stolk RP, Pols HA, Grobbee DE, Lamberts SW. Serum total IGF-1, free IGF-1 and IGFB-1 levels in an elderly population: relation to cardiovascular risk factors and disease. Arterioscler Thromb Vasc Biol 1998, 18: 277–82.

    Article  PubMed  CAS  Google Scholar 

  5. Walsh MF, Ali SS, Sowers JR. Vascular insulin/insulin-like growth factor-1 resistance in female obese Zucker rats. Metabolism 2001, 50: 607–12.

    Article  PubMed  CAS  Google Scholar 

  6. Wilson PW, Anderson KM, Kannel WB. Epidemiology of diabetes mellitus in the elderly. Am J Med 1986, 80: 3–9.

    Article  PubMed  CAS  Google Scholar 

  7. Rowe JW, Minaker KL, Pallotta JA, Flier JS. Characterization of the insulin resistance of aging. J Clin Invest 1983, 71: 1581–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Fink RI, Kolterman OG, Griffin J, Olefsky JM. Mechanisms of insulin resistance in aging. J Clin Invest 1983, 71: 1581–7.

    Article  Google Scholar 

  9. Jackson JA, Hawa MI, Roshania RD, Sim BM, Di Silvio L, Jaspan JB. Influence of aging on hepatic and peripheral glucose metabolism in humans. Diabetes 1988, 36: 119–29.

    Article  CAS  Google Scholar 

  10. Moller N, Gormens L, Fulgasang J, Gjedsted J. Effects of aging on insulin secretion and action. Horm Res 2003, 60: 102–4.

    PubMed  CAS  Google Scholar 

  11. Forbes GB, Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 1970, 19: 653–63.

    Article  PubMed  CAS  Google Scholar 

  12. Novack LP. Aging, total body potassium, fat free mass and cell mass in males and females between ages 18 and 85 years. J Gerontol 1972, 27: 438–43.

    Article  Google Scholar 

  13. Iranmanesh A, Lizzaralde G, Veldhuis JD. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991, 73: 1081–8.

    Article  PubMed  CAS  Google Scholar 

  14. Ruiz-Torres A, Soares de Melo Kirzner M. Ageing and longevity are related to growth hormone/insulin-like growth factor-1 secretion. Gerontology 2002, 48: 401–7.

    Article  PubMed  CAS  Google Scholar 

  15. Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D.The prospective association of serum insulin-like growth factor 1 (IGF-1) and IGF-Binding Protein-1 levels with all cause and cardiovascular disease mortality in older adults: The Rancho Bernardo Study. J Clin Endocrinol Med 2004, 89: 114–120.

    Article  CAS  Google Scholar 

  16. Volterrani M, Desenzani P, Lorusso R, d’Aloia A, Manelli F, Giustina A. Haemodynamic effects of intravenous growth hormone in congestive heart failure. Lancet 1997, 349: 1067–8.

    Article  PubMed  CAS  Google Scholar 

  17. Fazio S, Sabatini D, Capalbo B, et al. A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996, 334: 809–14.

    Article  PubMed  CAS  Google Scholar 

  18. Alpert MA, Hashimi MW. Obesity and the heart. Am J Med Sci 1993, 306: 117–23.

    Article  PubMed  CAS  Google Scholar 

  19. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001, 345: 790–7.

    Article  PubMed  CAS  Google Scholar 

  20. Olefsky JM, Kolterman OG, Scarlett JA. Insulin action and resistance in obesity and non-insulin dependent type 2 diabetes mellitus. Am J Physiol 1982, 243: E15–30

    PubMed  CAS  Google Scholar 

  21. De Fronzo RA. The triumvirate; B cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 1988, 37: 64447.

    Google Scholar 

  22. De Fronzo RA, Ferranini E. Insulin resistance a multifaceted syndrome responsible for NIDDM, obesity hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14: 173–94.

    Article  Google Scholar 

  23. Markovic TP, Campbell LV, Balasubramanian S, et al. Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with orwithouttype 2 diabetes. Diabetes Care 1998, 21: 695–700.

    Article  PubMed  CAS  Google Scholar 

  24. Zadik Z, Chalew SA, McCarter RJ, Meistas M, Kowarski AA. The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab 1985, 60: 513–6.

    Article  PubMed  CAS  Google Scholar 

  25. Giustina A, Desenzani P, Bossoni S, Perini P. Growth hormone treatment in aging: state of the art and perspectives. Aging (Milano) 1997, 9: 73–4.

    CAS  Google Scholar 

  26. Arvat E, Gianotti L, Grottoli S, et al. Arginine and growth hormone-releasing hormone restore the blunted growth hormone-releasing activity of hexarelin in elderly subject. J Clin Endocrinol Metab 1994, 79: 1440–3.

    PubMed  CAS  Google Scholar 

  27. Giustina A, Bossoni S, Bodini C, et al. Arginine normalizes the growth hormone (GH) in response to GH-releasing hormone in adult patients receiving chronic daily immunosop-pressive glucocorticoid therapy. J Clin Endocrinol Metab 1992, 74: 1301–5.

    PubMed  CAS  Google Scholar 

  28. Friend K, Iranmanesh A, Login IS, Veldhuis JD. Pyridostig-mine treatment selectively amplifies the mass of GH secreted per burst without altering the GH burst frequency, half-life, basal GH secretion or the orderliness of the GH release process. Eur J Endocrinol 1997, 137: 377–86.

    Article  PubMed  CAS  Google Scholar 

  29. Giustina A, Bussi A, Conti C, et al. Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subject. Horm Res 1992, 37: 165–70.

    Article  PubMed  CAS  Google Scholar 

  30. Iranmanesh A, South S, Liem AY, et al. Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men. Eur J Endocrinol 1998, 139. 59–71.

    Article  PubMed  CAS  Google Scholar 

  31. Evans WS, Anderson SM, Hull LT, Azimi PP, Bowers CY, Veldhuis JD. Continuous 24-h intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1,44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states. J Clin Endocrinol Metab 2001, 86: 700–12.

    PubMed  CAS  Google Scholar 

  32. Iovino M, Monteleone P, Steardo L. Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging. J Clin Endocrinol Metab 1989, 69: 910–3.

    Article  PubMed  CAS  Google Scholar 

  33. Veldhuis JD, Patrie JT, Frick K, Weltman JY, Weltman A. Sustained Growth Hormone (GH) and insulin-like Growth factor I responses to prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged and older men. J Clin Endocrinol Metab 2004, 89: 6325–30.

    Article  PubMed  CAS  Google Scholar 

  34. Ghigo E, Arvat E, Gianotti L, et al. Human aging and the GH-IGF-I axis. J Pediatr Endocrinol Metab 1996, 9: 271–8.

    PubMed  Google Scholar 

  35. van der Lely AJ, Tschop M, Heiman ML, Ghigo E. 2004 Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 2004, 25: 866–98.

    Article  Google Scholar 

  36. Conley LK, Teik JA, Deghenghi R, et al. Mechanism of action of hexarelin and GHRP-6: analysis of the involvement of GHRH and somatostatin in the rat. Neuroendocrinology 1995, 61: 44–50.

    Article  PubMed  CAS  Google Scholar 

  37. Giustina A, Bussi AR, Deghenghi R, et al. Comparison of the effects of growth hormone-releasing hormone and hexarelin, a novel growth hormone-releasing peptide-6 analog, on growth hormone secretion in humans with or without glucocorticoid excess. J Endocrinol 1995 146: 227–32.

    Article  PubMed  CAS  Google Scholar 

  38. Veldhuis JD, Patrie JT, Brill KT, et al. Ontributions 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 2004, 89: 6291–6.

    Article  PubMed  CAS  Google Scholar 

  39. Veldhuis JD, Weltman JY, Weltman A, Iranmanesh A, Mueller EE, Bowers CY. Age and secretagogue type jointly determine dynamic growth hormone responses to exogenous insulin-like growth factor-negative feedback in healthy men. J Clin Endocrinol Metab 2004, 89: 5542–8.

    Article  PubMed  CAS  Google Scholar 

  40. Veldhuis JD, Iranmanesh A, Ho KKY, Waters MJ, Johnson ML, Lizzaralde G. Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 1991, 72: 51–9.

    Article  PubMed  CAS  Google Scholar 

  41. Scacchi M, Pincelli AI, Cavagnini F. Growth Hormone in obesity. Int J Obes 1999, 23: 260–71.

    Article  CAS  Google Scholar 

  42. Kopelman PG, Noonan K, Goulton R, Forrest AJ. Impaired growth hormone response to growth hormone releasing factor and insulin-hypoglicemia in obesity. Clin Endocrinol (Oxf) 1985, 23: 87–94.

    Article  CAS  Google Scholar 

  43. Ghigo E, Procopio M, Maccario M, et al. Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity? Horm Metab Res 1993, 25: 305–8.

    Article  PubMed  CAS  Google Scholar 

  44. Cordido F, Casanueva FF, Dieguez C. Cholinergic receptor activation by pyridostigmine restores growth hormone responsiveness to Gh-releasing hormone administration in obese subject: evidence for hypothalamic somatostatiner-gic participation in the blunted GH release of obesity. J Clin Endocrinol Metab 1989, 68: 290–3.

    Article  PubMed  CAS  Google Scholar 

  45. Cordido F, Penalva A, Peino R, Casanueva FF, Dieguez C. Effect of combined administration of growth hormone (GH)- releasing hormone, GH-releasing peptide-6 and pyridostigmine in normal and obese subjects. Metabolism 1995, 44: 745–8.

    Article  PubMed  CAS  Google Scholar 

  46. Tassone F, Broglio S, Destefanis S, et al. Neuroendocrine and metabolic effects of acute ghrelin administration in human obesity. J Clin Endocrinol Metab 2003, 88: 5478–83.

    Article  PubMed  CAS  Google Scholar 

  47. Mauras N, O’Brien KO, Welch S, et al. Insulin-like growth factor I and growth hormone (GH) treatment in GH-deficient humans: differential effects on protein, glucose, lipid, and calcium metabolism. J Clin Endocrinol Metab 2000, 85: 1686–94

    PubMed  CAS  Google Scholar 

  48. Richelsen B, Pedersen SB, Kristensen K, et al. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. Metabolism 2000, 49: 906–11.

    Article  PubMed  CAS  Google Scholar 

  49. Cordido F, Peino R, Penalva A, Alvarez CV, Casanueva FF, Dieguez C. Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression. J Clin Endocrinol Metab 1996, 81: 914–8.

    PubMed  CAS  Google Scholar 

  50. Brunanti A, Invitti C, Dubini A, et al. Cerebrospinal fluid and plasma concentrations of SRIH, beta-endorphin, CRH, NPY and GHRH in obese and normalweight subjects. Int J Obes 1995, 19: 17–21.

    Google Scholar 

  51. Bonert VS, Elashoff JD, Barnett P, Melmed S. Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 2004, 89: 3397–401.

    Article  PubMed  CAS  Google Scholar 

  52. Biller BMK, Samuels MH, Zager A, Chipman JJ, Harman ML. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab 2002, 87: 2067–79.

    Article  PubMed  CAS  Google Scholar 

  53. Rudman D. GH, body composition, and aging. J Am Geriatr Soc 1985, 33: 800–72.

    PubMed  CAS  Google Scholar 

  54. Rudman D, Feller AG, Nagraj HS. Effects of human growth hormone in men over 60 years old. N Engl J Med 1990, 323: 1–6.

    Article  PubMed  CAS  Google Scholar 

  55. Papadakis MA, Grady D, Black D, et al. Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 1996, 124: 708–16.

    Article  PubMed  CAS  Google Scholar 

  56. Thompson JL, Butterfield GE, Marcus R, et al. The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. J Clin Endocrinol Metab 1995, 80: 1845–52.

    PubMed  CAS  Google Scholar 

  57. Holloway L, Butterfield G, Hintz L, Gesundheit N, Marcus R. Effects of recombinant human growth hormone on metabolic indices, body composition and bone turnover in healthy elderly women. J Clin Endocrinol Metab 1994, 79: 470–9.

    PubMed  CAS  Google Scholar 

  58. Munzer T, Harman SM, Hees P, et al. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 2001, 86: 3604–10.

    Article  PubMed  CAS  Google Scholar 

  59. Marcus R, Butterfield G, Holloway L, et al. Effects of short term administration of recombinant human growth hormone to elderly people. 1990, 70: 519–27.

    CAS  Google Scholar 

  60. Corpas E, Harman SM, Blackman MR. Human Growth Hormone and human aging. Endocr Rev 1993, 14: 20–39.

    Article  PubMed  CAS  Google Scholar 

  61. Khorram O, Laughlin GA, Yen SS. 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 1997, 82: 1472–9.

    PubMed  CAS  Google Scholar 

  62. Chapman IM, Bach MA, Van Cauter E, et al. Stimulation of the growth hormone (GH)-insulin-like-growth-factor I axis by daily oral administration of a GH secretagogue (MK677) in healthy elderly subjects. J Clin Endocrinol Metab 1996, 81: 4249–57.

    PubMed  CAS  Google Scholar 

  63. Johannsson G, Marin P, Lonn L, et al. Growth hormone treatment of abdominally obese men reduced abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab 1997, 82: 725–6.

    Google Scholar 

  64. Angelin B, Rudling M. Growth hormone and hepatic lipoprotein metabolism. Curr Opin Lipidol 1994, 5: 160–5.

    Article  PubMed  CAS  Google Scholar 

  65. Lucidi P, Parlanti N, Piccioni F, Santeusanio F, De Feo P. Short-term treatment with low doses of recombinant human GH stimulates lipolysis in visceral obese men. J Clin Endocrinol Metab 2002, 87: 3105–9.

    Article  PubMed  CAS  Google Scholar 

  66. Snyder DK, Underwood LE, Clemmons DR. Persistent lipolytic effect of exogenous growth hormone during caloric restriction. Am J Med 1995, 98: 129–34.

    Article  PubMed  CAS  Google Scholar 

  67. Copeland KC, Nair KS. Recombinant human insulin-like growth factor-I increases forearm blood flow. J Clin Endocrinol Metab 1994, 79: 230–2.

    PubMed  CAS  Google Scholar 

  68. Albert SG, Mooradian AD. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Metab 2004, 89: 695–701

    Article  PubMed  CAS  Google Scholar 

  69. Thompson JL, Butterfield GE, Gylfadottir UK, et al. Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. J Clin Endocrinol Metab 1998, 83: 1477–84.

    PubMed  CAS  Google Scholar 

  70. Kim KR, Nam SY, Song YD, Lim SK, Lee HC, Huh KB. Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults. Horm Res 1999, 51: 78–84.

    Article  PubMed  CAS  Google Scholar 

  71. Norrelund H, Borglum JD, Jorgensen JO, et al. Effects of growth hormone administration on protein dynamics and substrate metabolism during 4 weeks of dietary restriction in obese women. Clin Endocrinol (Oxf) 2000, 52: 305–12.

    Article  CAS  Google Scholar 

  72. Nam SY, Kim KR, Cha BS, et al. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Int J Obes Relat Metab Disord 2001, 25: 1101–7.

    Article  PubMed  CAS  Google Scholar 

  73. Gola M, Bonadonna S, Doga M, Giustina A. Growth hormone (GH) and cardiovascular risk factors. J Clin Endocrinol Metab 2005, 90: 1864–70.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Giustina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gola, M., Bonadonna, S., Doga, M. et al. Cardiovascular risk in aging and obesity: Is there a role for GH?. J Endocrinol Invest 28, 759–767 (2005). https://doi.org/10.1007/BF03347561

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347561

Keywords

Navigation