Changes in the Growth Hormone Axis with
The rate of HGH secretion from the anterior pituitary is highest
around puberty, and declines progressively thereafter. This
age-related decline in HGH secretion involves a number of changes
in the HGH axis, including decreased serum levels of insulin-like
growth factor-1 (IGF-1) and decreased secretion of growth
hormone-releasing HGH from the hypothalamus. The cause of the
normal age-related decrease in this secretion is not well
understood, but is thought to result, in part, from increased
secretion of somatostatin, the GH-inhibiting hormone.
Normal aging is accompanied by a number of catabolic effects,
including a decrease in lean mass, increase in fat mass, and
decrease in bone density. Associated with these physiologic
changes is a clinical picture often referred to as the
somatopause: frailty, muscle atrophy, relative obesity, increased
frequency of fractures and disordered sleep. These clinical signs
of aging are, without doubt, the manifestation of a very complex
set of changes which involve, at least in part, the GH-axis.
Naturally, this has spurred considerable interest in
administering supplemental HGH as a "treatment" for aging in
humans, and the availability of recombinant HGH has made
such studies feasible.
In contrast to the view that growth hormone deficiency contributes to the
aging phenomenon, there is information suggesting that normal or
high levels of growth hormone may accelerate aging. Mice with genetic
dwarfism due to deficiency in human growth hormone, prolactin and
thyroid-stimulating hormone live considerably longer than normal
mice, and the increased levels seen with acromegaly in
humans are associated with reduced life expectancy. Both of these
findings are likely due to metabolic effects of human growth hormone.
HGH Replacement Therapy in HGH-deficient Adults for
Adult-onset HGH deficiency in humans is almost always due to
pituitary disease, usually from a tumor or therapeutic efforts to
treat a tumor. Such patients have increased risk of death from
cardiovascular disease, and, relative to age-matched controls,
show increased fat mass, reduced muscle mass and strength, lower
bone density, and higher serum lipid concentrations.
Additionally, they suffer from reduced vigor, sexual dysfunction
and emotional problems.
More than a dozen clinical trials have sought to evaluate human growth hormone
replacement in patients with adult-onset deficiency. The goal has
usually been to normalize serum IGF-1 concentrations by daily
injections. In essentially all cases, several months of replacement therapy led to increased lean mass and decreased
adiposity (especially in visceral fat). The effects of HGH on bone density and hyperlipidemia has been
inconsistent or minor, as have been the effects on strength and
mental abilities. Common side effects observed in these trials
included edema and joint/muscle pain, which appeared related to
dose of growth hormone. Since the first of these trials was conducted in
1988, long term risks are not yet known.
HGH Therapy in the Elderly
Long before Ponce de Leon went in search of the legendary
fountain of youth, people sought treatments to prevent or reverse
the effects of aging. In 1990, considerable interest was
generated from a report by Rudman and colleagues which described
wonderful effects of HGH in a small group of elderly
males. These volunteers, who ranged in age from 61 to 81 years,
showed increased lean body and bone mass, decreased fat mass and,
perhaps most dramatically, restoration of skin thickness to that
typical of a 50-year-old.
The study cited above and a handful of others have provided an
initial understanding of the benefits, limitations and risks of
sustained (6 to 12 month) supplementation in elderly males and females. A consistent finding in these investigations was a high
incidence of adverse side effects - edema, fluid retention and
carpal tunnel syndrome - which necessitated reductions in dosage or cessation of treatment. HGH consistently induced an
increase in serum IGF-1, a decrease in fat mass and increase in
The effects on fat and lean masses may be viewed as positive
effects, but, at the end of the day, it has to be asked whether
the therapy improved functioning in the elderly. In the studies
in which function was objectively assessed, the therapy did not
improve cognitive function, and, despite the effects on lean body
mass, was not any more effective than exercise alone in promoting
strength. Long-term HGH therapy in elderly postmenopausal females
lead to significant increases in bone mineral density, but these
increases were less than what is routinely achieved with estrogen
replacement. While it must be acknowledged that a relatively
small number of elderly patients have been treated for prolonged
periods, the controlled trials conducted thus far do not
support is efficacy in alleviating age-related deficits in
cognitive or somatic function.
Another indication of potentially serious side effects of HGH
therapy in adults, including the elderly, has been provided by
controlled clinical trials that assessed the utility of human growth hormone
treatment in critical illness, where endogenous secretion is
typically suppressed. Therapy was anticipated to attenuate the
catabolic effects of illness and thereby decrease duration of
hospitalization. The results of several clinical trials involving
hundreds of patients, demonstrated a significant increase in
mortality associated with high doses. Additionally, those
patients treated that survived had longer periods of
intensive care and hospitalization than those receiving
References and Reviews
Borst SE and Lowenthal DT: Role of IGF-1 in
muscular atrophy of aging. Endocrine 7:61-63, 1997.
Cummings DE and Merriam GR: HGH therapy in adults.
Annu Rev Med 54:513-533, 2003.
Holloway L, Butterfield G, Hintz RL, et al.: Effect of
recombinant human growth hormone on metabolic indices, body
composition, and bone turnover in healthy elderly females. J Clin
Endocrinol Metab 79:470-479, 1994.
Marcus R and Hoffman AR: Growth hormone as therapy for older males and females. Annu Rev Pharmacol Toxicol 38:45-61, 1998.
Papadakis MA, Grady D, Black D, et al.: HGH
replacement in healthy older males improves body composition but
not functional ability. Ann Int Med 124:708-716, 1996.
Rudman D, Feller AG, Nagraj HS, et al.: Effects of human growth
hormone in males over 60 years old. New Eng J Med 323:1-6,
Taaffe DR, Pruitt L, Reim J, et al.: Effects of recombinant human
growth hormone on the muscle strength response to resistance
exercise in elderly males. J Clin Endocrinol Metab 79:1361-1366,
Takala J, Ruokonen E, Webster NR, et al.: Increased mortality
associated with HGH in critically ill
adults. New Eng J Med 341:785-792, 1999.
Vance ML and Mauras N: Drug therapy: Growth hormone therapy in
adults and children. New Eng J Med 341:1206-1216,