Medication Summary
In the United States, adult growth hormone (GH) replacement is approved for acquired pituitary hormone deficiency, proven prior childhood-onset GHD, and for the treatment of muscle wasting in HIV-infected adults. Guidelines recommend GH replacement therapy only be offered to those patients diagnosed as being GH-deficient with an established etiology for the disorder. [14, 15]
According to a 2011 systematic review, GH replacement [21] 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:
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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
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Reduction in total cholesterol level by 4-8% and low-density lipoprotein cholesterol (LDL) by 11-16% but no change in HDL and triglycerides
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Improvement in quality of life
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No consistent improvement in blood pressure or bone mineral density; additionally, no data are available on GH-deficient patients older than 80 years
GH is used in antiaging medicine in an attempt to reverse the decrease of GH levels with age. [22] The American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults make a strong recommendation against the use of GH in older adults because "the impact on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia and impaired fasting glucose." The only exception is its use as hormone replacement after pituitary gland removal. [16]
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. [23] GH reduced serum leptin and LDL-C and increased triglycerides, with no effect on HDL. [24] 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. [25, 26]
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. [7]
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. Five months of treatment with daily subcutaneous injections of tesamorelin, an analog of human GHRH (1 mg/d), improved executive function in adults with mild cognitive impairment as well as in healthy older adults. [27] It is postulated that the positive effect was mediated by an increase of IGF-1, which can cross the blood-brain barrier. However, longer trials are needed before GHRH can be recommended to improve cognitive function. An orally active GH secretagogue, MK-0677, was studied in older adults with recent hip fractures. [28] Although it increased serum IGF-1, it did not significantly improve functional performance measures. [29]
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. [30] 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.
Because of potential adverse effects, experts do not recommend GH replacement to rejuvenate older persons. [31, 16]
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. It should not be used for hyposomatotropism of aging.
