Growth Hormone Replacement in Older Men Medication
- Author: Angela Gentili, MD; Chief Editor: George T Griffing, MD more...
Medication Summary
According to a 2011 systematic review, GH replacement[14] is effective in reversing some of the changes that occur in older adults (aged >60 y) with GH deficiency secondary to hypopituitarism. The effects of GH replacement in these patients include the following:
- Decreased waist circumference (by about 3 cm) and waist-to-hip ratio without changing BMI; GH increased lean body mass and decreased total fat mass in 4 studies but not in another 2.
- Reduction in total cholesterol level by 4-8% and low-density lipoprotein cholesterol (LDL) by 11-16% but no change in HDL and triglycerides
- Improvement in quality of life
- No consistent improvement in blood pressure or bone mineral density; additionally, no data are available on GH-deficient patients older than 80 years
Growth hormones
Class Summary
Most studies of GH supplementation in healthy older people (not GH deficient) have shown that in both men and women, GH increases muscle mass and decreases body fat, but it does not improve strength. In a 6-month study, the combination of testosterone and GH also increased total body isotonic strength and aerobic capacity in older men.[15] GH reduced serum leptin and LDL-C and increased triglycerides, with no effect on HDL.[16] Common side effects were arthralgias and carpal tunnel syndrome.
One month of a small dose of GH (ie, 6.25 mcg/kg/d) alone or in combination with transdermal testosterone did not improve strength, flexibility, or percentage of body fat, but it improved certain measures of balance and physical performance in healthy older men. At such a small dose, there were no significant adverse events. In another study, GH did not enhance the positive effect of exercise on muscle strength.[17, 18]
A systematic review of randomized trials of GH therapy in 220 older men and women reported that GH therapy decreased fat mass and increased lean body mass without change in weight. Despite the improvement in body composition, persons treated with GH were significantly more likely to develop soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia. The authors concluded that GH cannot be recommended as antiaging therapy.[6]
GH secretagogues that would produce a more physiological increase in circulating GH levels are under investigation. These include GHRH and the growth hormone releasing peptides (GHRPs) and their analogs. Six months treatment with daily GHRH improved performance in cognitive tests compared to placebo in healthy older adults. An orally active GH secretagogue, MK-0677, was studied in older adults with recent hip fractures.[19] Although it increased serum IGF-1, it did not improve functional performance measures significantly.[20]
GH treatment in frail older people
In a placebo-controlled trial of patients aged 64-99 years who were malnourished, GH caused a rise in circulating IGF-1, an average weight gain of 2.2 kg, and an increase in nitrogen retention.[21] Older individuals are more sensitive to GH replacement than children and young adults; therefore, the dose of GH must be lower. Treating older adults with the amount of GH produced in healthy puberty (ie, 23-35 mcg/kg/d) can cause glucose intolerance, arthralgias, fluid retention, carpal tunnel syndrome, and, rarely, papilledema.
Growth hormone; somatropin (Genotropin, Humatrope, Norditropin)
Obtained by recombinant DNA technology. Amino acid sequence is identical to that of pituitary-derived hGH. Indicated in pediatrics to treat growth failure due to lack of adequate endogenous GH secretion, growth failure associated with chronic renal insufficiency up to the time of renal transplantation, and short stature associated with Turner syndrome. Indicated in adults to treat a biochemical diagnosis of adult GHD by means of a subnormal response to a standard GH stimulation test; patients who have adult GHD, either alone or with multiple hormone deficiencies (hypopituitarism) as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or patients who were GH deficient during childhood, confirmed as an adult before replacement therapy with somatropin is started.
Not FDA approved for older patients who do not meet the above criteria of adult GHD. Its use for hyposomatotropism of aging should be considered investigational.
Waters DL, Baumgartner RN, Garry PJ, Vellas B. Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update. Clin Interv Aging. 2010;5:259-70. [Medline].
Harman SM, Blackman MR. The Effects of Growth Hormone and Sex Steroid on Lean Body Mass, Fat Mass, Muscle Strength, Cardiovascular Endurance and Adverse Events in Healthy Elderly Women and Men. Horm Res. 2003;60:121-124. [Medline].
Harman SM, Blackman MR. Use of growth hormone for prevention or treatment of effects of aging. J Gerontol A Biol Sci Med Sci. 2004;59:652-8. [Medline].
Kiel DP, Puhl J, Rosen CJ, Berg K, Murphy JB, MacLean DB. Lack of an association between insulin-like growth factor-I and body composition, muscle strength, physical performance or self-reported mobility among older persons with functional limitations. J Am Geriatr Soc. Jul 1998;46(7):822-8. [Medline].
Sherlock M, Toogood AA. Aging and the growth hormone/insulin like growth factor-I axis. Pituitary. 2007;10(2):189-203. [Medline].
[Best Evidence] Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. Jan 16 2007;146(2):104-15. [Medline].
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. May 2006;91(5):1621-34. [Medline].
Lin L, Saha PK, Ma X, Henshaw IO, Shao L, Chang BH, et al. Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues. Aging Cell. Sep 5 2011;[Medline].
Holzenberger M. Igf-I signaling and effects on longevity. Nestle Nutr Workshop Ser Pediatr Program. 2011;68:237-49. [Medline].
Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing. 2004;33:548-555. [Medline].
Veldhuis JD, Iranmanesh A, Weltman A. Elements in the pathophysiology of diminished growth hormone (GH) secretion in aging humans. Endocrine. Aug 1997;7(1):41-8. [Medline].
[Guideline] Ho KK. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. Dec 2007;157(6):695-700. [Medline].
Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med. Jul 5 1990;323(1):1-6. [Medline].
Kokshoorn NE, Biermasz NR, Roelfsema F, Smit JW, Pereira AM, Romijn JA. GH replacement therapy in elderly GH-deficient patients: a systematic review. Eur J Endocrinol. May 2011;164(5):657-65. [Medline].
Urban RJ. Growth hormone and testosterone: anabolic effects on muscle. Horm Res Paediatr. 2011;76 Suppl 1:81-3. [Medline].
Brill KT, Weltman AL, Gentili A, Patrie JT, Fryburg DA, Hanks JB, et al. Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. J Clin Endocrinol Metab. Dec 2002;87(12):5649-57. [Medline].
Elgzyri T, Castenfors J, Hagg E, Backman C, Thoren M, Bramnert M. The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency. Clin Endocrinol (Oxf). Jul 2004;61(1):113-22. [Medline].
Haydar ZR, Blackman MR, Tobin JD, Wright JG, Fleg JL. The relationship between aerobic exercise capacity and circulating IGF-1 levels in healthy men and women. J Am Geriatr Soc. Feb 2000;48(2):139-45. [Medline].
Bach MA, Rockwood K, Zetterberg C, Thamsborg G, Hebert R, Devogelaer JP, et al. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. Apr 2004;52(4):516-23. [Medline].
Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, et al. Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med. Apr 15 1996;124(8):708-16. [Medline].
Kaiser FE, Silver AJ, Morley JE. The effect of recombinant human growth hormone on malnourished older individuals. J Am Geriatr Soc. Mar 1991;39(3):235-40. [Medline].
Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA. Nov 13 2002;288(18):2282-92. [Medline].
Genentech Inc. Nutropin (R) [somatropin (rDNA origin) for injection] prescribing information. Available at: http://www.genentech.com/gene/index.jsp. [Full Text].
Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. Feb 2006;27(2):318-23. [Medline].

