Indmedica Home | About Indmedica | Medical Jobs | Advertise On Indmedica
Search Indmedica Web
Indmedica - India's premier medical portal

Indian Journal for the Practising Doctor

Growth Hormone Supplementation in Elderly People

Author(s): Kalra S

Vol. 5, No. 6 (2009-01 - 2009-02)

Kalra S

Dr. Sanjay Kalra,
Bharti Hospital, Karnal, India 132001
[E mail: bhartihospital(at)]

ISSN: 0973-516X

The rapid increase in the number of elderly people, secondary to a prolonged life expectancy due to improved medical care, has led to heightened interest in the geriatric medicine. During the last half-century, the average life span has increased by 20 years, and is expected to rise another 10 years by 20501. The global population ≥65 years in age will grow from 420 million to 973 million between 2000 and 20302.

The average individual is more concerned than before about his health, and geriatric citizens demand independence, mobility and activity. Discussion about ‘healthy aging’ and about the utility of hormonal supplementation to ensure a youthful old age is needed. This review deals with the role, advantages and limitations of growth hormone supplementation in the elderly population.

Clinical features of growth hormone deficiency in the elderly Growth hormone deficiency (GHD) is a clinical, metabolic syndrome with many nonendocrine manifestations. These include:3–13

  1. Change in body composition
    • increased total fat mass
    • central obesity
    • decreased lean body mass
  2. Change in bone metabolism
    • decreased bone mass
    • increased fraction rate
  3. Insulin resistance
    • increased fat mass
    • dyslipidemia
    • premature atherosclerosis
  4. Cardiac dysfunction
    • impaired diastolic function
    • impaired systolic function(controversial)
  5. Change in quality of life
    • decreased well being
    • increased social isolation
    • decreased energy

Elderly patients present with similar symptoms, especially reduced quality of life and asthenia. Growth hormone deficiency should be suspected in patients with catabolic symptoms or those in whom one feels anabolic therapy is required.

Growth hormone physiology in the elderly Growth hormone secretion declines with aging by 15-70%14,15. This decline is associated with an increase in total body fat of 9-18% in men and 12-13% in women,16,17 localized to the intra-abdominal compartment, rather than subcutaneous fat.18 An actual reduction in subcutaneous fat in the thigh occurs with aging.19

A gradual, age-dependent reduction in bone mineral density and lean body mass also occurs with age17,19,20. When expressed as ‘relative’ muscle mass, the decline in skeletal muscle mass occurs from third decade onwards, but when reported as ‘absolute’ muscle mass, the fall is evident only after age 45. At this time, changes begin occurring in muscle fibre crosssectional area, body cell mass and strength21.

By age 80, an average male will lose about 7 kg of muscle mass, while an average female will lose 3.8 kg21. This is associated with a reduction in the lower extremity strength of up to 50% by this age24.

This loss of muscle mass and function (sarcopenia) leads to physical frailty, weakness and decreased physical activity. The resultant decreased mobility causes disability and loss of independence25.

The reasons for sarcopenia include a large number of contributory factors26-33, such as loss of alpha-motor neurons; dietary protein deficiency; reduced physical activity; increase in interleukin-6, tumor necrosis factor-α, interleukin-15, and ciliary neutrotrophic factor-1; decrease in insulin-like growth factor-1 (1GF-1); and changes in voltage-gated Ca2 and K+ ion channels.

Sacropenia, therefore, may be a potential target for those wishing to improve quality of life in the aged patients. Similarly, the changes in body composition and physiology that occur with aging may be targeted to improve ability and independence in geriatric patients.

Growth hormone therapy in the elderly: the rationale14,16

  1. There is an age-dependent decline in growth hormone and IGF-1.
  2. The age-dependent changes in body composition/physiology are similar to those noted in adult growth hormone deficiency (AGHD)
  3. Growth hormone supplementation in patients with AGHD improves body composition, body physiology and quality of life.
  4. Hence, growth hormone therapy should be effective in otherwise healthy, elderly subjects.

Effect of growth hormone supplementation Growth hormone replacement in patients with AGHD improves quality of life, as documented in many studies34,35. Withdrawal of the hormone therapy also results in negative psychologic effects35.

Positive effects on memory have been found in animals treated with growth hormone. These effects are mediated through an increase in endogenous glutathione, which reduces oxidative stress in the hippocampus, where GH receptors are present.36

Growth hormone supplementation in healthy older male adults aged >60 years over 6 months with 0.03mg/kg/wk given SC, 3 times a week, increased lean body mass, bone density at the spine, and decreased the fat mass.37 Similar results were found in a group of 52 men older than 69 years, treated for the same duration with the same dose.

A shorter (10 week long) study in 18 healthy elderly men demonstrated positive effects on body composition when GH treatment (0.02mg/kg/day) was combined with muscle strength training.38

Beneficial effects have been noted in postmenopausal women given a combination of growth hormone, diet and exercise therapy. An enhanced loss of truncal fat rather than peripheral fat was achieved, as compared to the placebo group.39

Growth hormone, given in combination with testosterone, has synergistic anabolic action. Total body strength, VO2 max, and protein synthesis increased in men older than 65 years, who received the two hormones for 26 weeks42. However, similar results were not achieved in women given growth hormone and estrogen together.

In another study, growth hormone and testosterone combination therapy was compared with both hormones given as monotherapy, in healthy men aged 65 to 80 years. The lean body mass and strength of knee extension increased with the combination therapy.43

Potential risks of growth hormone One potential risk of the exogenous growth hormone therapy is malignancy. The antiapoptotic effect of growth hormone/1GF-1, coupled with the proliferative effects of 1GF-1, in the presence of genetically-damaged cells, could increase the risk of cancer.

However, no increase in de novo neoplasia or re-growth of primary pituitary tumours has been seen in children or adults. Review of current data emphatically shows that the growth hormone is safe and does not lead to tumorigenesis in the growth hormone- deficient adults44-46.

Another potential risk is diabetes mellitus, as growth hormone is counter regulatory to insulin. However, only two cases of reversible diabetes have been reported in a series of 400 adults treated with growth hormone. It has been documented that growth hormone has beneficial effect at 1 year, and no effect at 7 years, on insulin sensitivity.46,47

Other side effects such as edema, carpal tunnel syndrome and joint pains are dose dependent, and reverse on dose reduction. No major side effects, therefore, limit the utility of growth hormone in the elderly.

Clinical investigations

Concomitant pituitary hormone deficiencies should be investigated for, identified and corrected before initiating growth hormone in the elderly. Incipient adrenal insufficiency and central or secondary hypothyroidism should be ruled out, or corrected prior to the therapy. Baseline estimation of lipid, glucose and other metabolic parameters is necessary. Ideally, this assessment should include investigations for osteoporosis and psychological well being. Body composition can be checked by determining weight, body mass index, waist and hip circumferences, and skin fold thickness. If available, bio-impedance assessment (BIA) or dual energy x-ray absorptiometry (DEXA) can be performed to assess lean mass and fat distribution.48

Dose selection

Older, more obese patients with adult onset growth hormone deficiency are more sensitive to growth hormone than younger, leaner patients, or those with childhood-onset deficiency.49 Men are more sensitive to the effects of growth hormone, with regards to body composition, lipid profile, and bone turnover markers, than women.50 Women receiving oral estrogens are more resistant to growth hormone in serum insulin-like growth factor-1 response, and develop less edema or fluid retention.51 Dose selection thus depends on clinical and biological response markers, and should be individualized

Dose titration

The initial dose in elderly patients is 0.1 mg/day, but speed of titration will vary from person to person. Response can be assessed clinically, by quality of life, or serum IGF-1. This is a more sensitive marker of the growth hormone, and is more appropriate as a dose titration tool than serum GF binding prtein-3 (1GFBP-3) and acid-labile subunit (ALS). IGF-1 response to growth hormone reflects the hepatic effect of the drug, and mediates many of the anabolic and metabolic effects.53 It cannot be used as a surrogate marker for other efficacy variables, Other parameters to monitor efficacy of growth hormone include BIA, which can measure changes in extra cellular water (ECW) compartment.54

In the absence of these parameters, one can monitor therapy by watching for side effects such as fluid retention, weight gain or edema.

The mean dose of growth hormone at 1 year was 0.45 mg/d when titrated vis-ŕ-vis an individualized dose regime based on serum IGF- 1, body composition and clinical response.

When dose titration was weight-based, the mean dose was 0.55 mg/day, but the incidence of side effects was 70%, as compared to only 30% in the individualized dose-titration group.55

In another study, median maintenance doses were 0.27mg/day in men and 0.4mg/day in women when titration was done against serum 1GF-1 levels, aiming for an 1GF-1 level in the upper half of age specific reference ranges.56

The optimal approach is to commence treatment at a low dose, and titrate upward depending on a response of growth hormonedependent variables.

Quality of life can be used as an endpoint to titrate growth hormone doses, but no studies have been done to confirm this. It has been documented, however, that many beneficial effect of the treatment are noted only after 6 months. The onset of effects may be delayed in patient receiving low initial doses of the drug.57

This means that therapy should be continued for an adequate period of time before making judgements on the effects on quality of life or psychological well being.

Long term replacement of growth hormone has been carried out for up to 10 years.58 These studies show improvement in bone mineral content59 (9%), bone mineral density, muscle strength and muscle function.60 It reduces intima media thickness, a marker for atherosclerosis.61


As of today, no strong data exists to recommend growth hormone supplementation in healthy elderly subjects. However, the data available does permit use of this hormone, in low doses, under controlled conditions, in individual geriatric patients, where sacropenia seems to be a major factor for frequent falls, fractures, disability and loss of independence.


Low dose growth hormone, used cautiously, can improve the metabolic health and quality of life of elderly people. This field of medicine needs to be studied in greater detail, as our growing geriatric population expects better care and a healthier, more independent old age.

The future should see more frequent utilization of this, as well as other anabolic treatment modalities, in elderly persons wishing to enjoy better, more active and productive lives.


  1. United Nation Report of the Second World Assembly on Ageing. Madrid, Spain. April8-12, 2002. Available at: http/ Accessed December6, 2006.
  2. CDC Public Health and Aging. Trends in aging- United States and worldwide. J Am Med Assoc 2003; 289:1371-3.
  3. Toogood AA, Adams JE, O’Neill PA, et al. Body composition in growth hormone deficient adults over the age of 60years. Clin Endocrinol (Oxf) 1996;45(4):399-405
  4. Barreto-Filho JA, Alcantara MR, Salvatori R, et al. Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia. J Clin Endocrinol Metab 2002;87(5):2018-23.
  5. Snel YE, Brummer RJ, Doerga ME, et al. Adipose tissue assessed by magnetic resonance imaging in growth hormone-deficient adults: the effect of growth hormone replacement and a comparison with control subjects. Am J Clin Nutr 1995;61 (6):1290-4
  6. Bex M, Abs R, Maiter d, et al. The effect of growth hormone replacement therapy on bone metabolism in adults-onset growth hormone deficiency: a 2-year open randomized controlled multicentre trial. J Bone Miner Res 2002;17 (6):1081-94.
  7. Johansson JO, Fowelin J, Landin K, et al. Growth hormone-deficiency adults are insulin-resistant. Metabolism 1995; 44(9):1126-9.
  8. Bates AS, Van’t Hoff W, Jones PJ, et al. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996;81(3):1169-72.
  9. Colao A, Cuocolo A, Di Somma C, et al. Impaired cardiac performance in elderly patients growth hormone deficiency. J Clin Endocrinol Metab 1999;84(11):3950-5.
  10. Attanasio AF, Bates PC, Ho KK, et al. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status -3-year results from the HypoCCS Database. J Clin Endocrinol Metab 2002; 87(4):1600-6.
  11. Shahi M, Beshyah SA, Hackett D, et al. Myocardial dysfunction in treated adult hypopituitarism: a possible explanation for increased cardiovascular mortality. Br Heart J 1992;67(1):92-6.
  12. Rosen T, JohannsonS G , Hallgren P, et al. beneficial effect of 12 months replacement therapy with recombinant human growth hormone deficient adults. J Clin Endocrinol Metab 1994; 1:55-66.
  13. Mahajan T, Crown A, Checkley S, et al. Atypical depression in growth hormone deficient adults, and the beneficial effects of the growth hormone treatment of depression and quality of life. Eur J Endorcinol 2004; 151(3):325-32.
  14. Finkelstein JW, Roffwarg HP, Boyar RM, et al. Age-related change in the twenty –four –hour spontaneous secretion of growth hormone. J Clin Endocrinol Metab 1972; 35(5):665-70.
  15. Zadik Z, Chalew SA , McCarter RJ Jr , et al. The influence of the age on the 24-hour integrated concentration of growth hormone in human individuals. J Clin Endocrinol Metab 1985; 60(3):513 -6.
  16. Novack L. 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.
  17. Rudman D. Growth hormone, body composition, and aging. J Am Geriatr Soc 1985; 33(11):800-7.
  18. DeNino WF, Tchernol A, Dionne IJ, et al. contribution of abdominal adiposity to agerelated differences in insulin sensitivity and plasma lipids in healthy nonobese woman. Diabetes Care 2001; 24(5):925-32.
  19. Delbono O. Molecular mechanisms and therapeutics of the deficit in specific force in ageing skeletal muscle. Biogerontol 2002;3(5):265-70.
  20. Hannan M, Felson D, Anderson J. Bone mineral density in elderly men and woman: results from the Framingham Osteoporosis Study. J Bone Miner Res 1992; 7:547-53.
  21. Forbes G, Reina J. Adult lean body mass decline with age: some longitudinal observations. Metabolism 1970; 19: 653-63.
  22. Janssen I, Heymsfield SB, Wang ZM , et al. Skeletal muscle mass and distribution in 468 men and woman aged 18-88 yr. J Appl Physiol 2000; 89(1):81-8.
  23. Clement FJ. Longitudinal and cross sectional assessments of age changes in physical strength as related to sex, social class, and mental ability. J Gerontol 1974; 29(4):423-9.
  24. Hurley BF. Age gender and muscular strength. J Gerontol Biol Sci Med Sci 1995; 50:41-4.
  25. Doherty TJ. Invited review: aging and sarcopeina. J Appl Physiol 2003; 95(4):1717-27.
  26. Walston J, Hadley ec, Ferrucci L, et al. Research agenda for frailty in older adults: towards a better understanding of physiology and etiology : summary from the American Geriatrics Society / National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 2006; 54(6):991-1001.
  27. Brown WF. A method for estimating the number of motor units in thenar muscles and the changes in motor unit count with ageing. J Neurol Neurosurg psych 1972; 35(6):845-52.
  28. Young VR. Amino acids and protein in relation to the nutrition of elderly people. Age Ageing 1990; 19(4): 239-42.
  29. Westerterp KR. Daily physical activity, aging and body composition. J Nutr Health Aging 2000; 4 (4):S10-24.
  30. Roubenoff R, Harris TB, Abad LW, et al. Monocyte cytokine production in elderly population : effect of age and inflammation. J Gerontol A Biol Sci Med Sci 1998; 53(1):M20-6.
  31. Argiles JM, Busquets S Felipe A, et al. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia. Int J Biochem Cell Biol 2005;37(5):1084-104.
  32. Gamper N, Fillon S, Huber SM, et al. IGF-1 up regulates K + channels via P13-kinase, PDK1 and SGK1. Pflugers Arch 2002;443(4):625-34.
  33. Labrie F, Belanger A,Luu- The V, et al. DHEA and the intracrine formation of androgen and estrogens in peripheral target tissues: its role during aging. Steroids 1998; 63(5-6):322-8.
  34. Blum WF, Shavrikova EP, Edwards DJ, et al. Decreased quality of life in adults patients with growth hormone deficiency compared with general population using the new, validated, elfweighted questionnaire, questions on life satisfaction hypopituitarism module. J Clin Endocrinol Metab 2003; 88(9):4158-67.
  35. McMillan CV, Bradley C, Gibney J, et al. Psychological effect of withdrawal of growth hormone therapy from adult with growth hormone deficiency. Clin Endocrinol (Oxf) 2003; 59(4):467-75.
  36. Donahue CP, Kosik KS, Shors TJ. Growth hormone I produced within the hippocampus where it responds to age, sex, and tress. Proc Natl Acad Sci USA 2006; 103(15):6031-6.
  37. Rudman D, Feller A. 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(8):708-16.
  38. Taaffe DR, Pruitt L, Reim J, et al. Effect of recombinant human growth hormone, on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 1994; 79(5):1361-6.
  39. Taaffe DR, Thompson JL, Butterfield GE,et al. Recombinant human growth hormone, but not insulin-like growth factor-1, enhance central fat loss in postmenopausal woman under-going a diet and exercise program. Horm Metab Res 2001; 33(3):156-62.
  40. Muenzer T Harman S, Hees P, et al. Effect of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged woman and men. J Clin Endocrinol Metab2001; 86:3604-10.
  41. Lange KH, Isaksson F, Rasmussen MH, et al. GH administration and discontinuation in healthy elderly men: effect on body composition, GHrelated serum markers, resting heart rate and resting oxygen uptake. Clin Endocrinol (Oxf) 2001; 55(1):77-86.
  42. Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex steroid administration in healthy aged woman and men a randomized controlled trial. J Am Med Assoc 2002; 288(18):2282-92.
  43. Giannoulis MG, Sonksen PH, Umpleby M, et al. The Effects of growth hormone and /or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab 2006; 91 (2):477-84. 72 Indian Journal for the Practising Doctor, 2009, Vol V, No. 6 (Jan-Feb)
  44. Orme SM, McNally RJ, Cartwright RA, et al. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 1998; 83(8):2730-4.
  45. GHR Society Consensus. Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society. J Clin Endocrinol Metab 2001; 86: 1868-70.
  46. Chipman JJ, Attanasio AF, Birkett MA, et al. The safety profile of GH replacement therapy in adults. Clin Endocrinol (Oxf) 1997; 46(4):473-81.
  47. Svensson J, Fowelin J, Landin K, et al. Effects of seven years of GH-replacement therapy on insulin sensitivity in G-deficient adults. J Clin Endocrinol Metab 2002; 87(5):2121-7.
  48. Jonnhsson G. Management of adults growth hormone deficiency. In: Ho KKY, Le Roith D, eds-Endo Metab Clin North. Am, 2007; 36(1):203-20.
  49. Holnes SJ, Shalet SM. Which adults develop side-effects of growth hormone replacement? Clin Endocrinol [Oxf]1995;43:143-9.
  50. Burman P, Johanson AG, Siegbahn A,et al. Growh hormone (GH)-deficient men are more responsive to GH replacement therapy than woman. J Clin Endocrinol Metab 1997;82:550-5.
  51. Janssen YJ, Helmerhorst F, Frolich M, et al. A switch from oral(2mg/day) to transdermal (50microg/day)17 beta-etradiol therapy increases serum insulin-like growth factor-I levels in recombinant human growth hormone (GH)- subsituted woman with GH deficiency. J Clin Endocrinol Metab 2000;85:464-7.
  52. de Boer H, Blok GJ, Popp-Snijers C,et al. Monitoring of growth hormone replacement therapy in adult, based on measurement of serum marker. J Clin Endocrinol Metab 1996;81:1371-7.
  53. Sjogren K, Liu JL, Blad K,et al. Liver-derived insulin-like growth hormone factor I (IGF-I) is he principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 1999;96:7088-92.
  54. de Boer H, Blok GJ, Voerman B, et al. The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis. J Clin Endocrinol Metab 1995; 80:2069-76.
  55. Johannson G, Roen T, Bengtsson B-A. Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults. Clin Endocrinol [Oxf] 1997;47:571-81.
  56. Drake WM, Coyte D, Camacho-Hubner C,et al. Opimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998;83:3913-9.
  57. Wiren L, Bengesson B-A,Johananson G.Benefical effects of long term GH replacement therapy on quality of life in adults with GH deficiency. Clin Endocrinol [Oxf] 1998;48:613-20.
  58. Gibney J,Wallace JD, Spinks T, et al. The effects of 10 years of recombinant human growth hormone (GH)in adults GH-deficent patients. J Clin Endocrinol Metab 1999;84: 2596-602.
  59. Johannsson G, Rosen T ,Bosaeus I, et al. Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adults –on set GH deficiency. J Clin Endocrinol Metab 1996;81:2865-73.
  60. C uneo RC , Salomon F,Wiles CM et al. Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl physiol 1991;70:688-94.
  61. Pfeifer M, Verhovec M, Zi Zek B, et al. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999;84:453-7.
Access free medical resources from Wiley-Blackwell now!

About Indmedica - Conditions of Usage - Advertise On Indmedica - Contact Us

Copyright © 2005 Indmedica