 Growth Hormone Releasing Hormone
Treatment in Normal Aging
Journal of Anti-Aging Medicine
Dec 2001, Vol. 4, No. 4: 331-343
George
R. Merriam Veterans Affairs (VA) Puget Sound Health Care System, and
Department of Medicine, University of Washington School of Medicine, Seattle,
Washington
Suzanne Barsness Department of Psychiatry and
Behavioral Sciences, University of Washington School of Medicine, Seattle,
Washington
David Buchner Veterans Affairs (VA) Puget Sound Health
Care System, and Department of Medicine, University of Washington School of
Medicine, Seattle, Washington
Monica Kletke Veterans Affairs (VA)
Puget Sound Health Care System, and Departments of Medicine, and Psychiatry and
Behavioral Sciences, University of Washington School of Medicine, Seattle,
Washington
Lawrence H. Larsen Department of Psychiatry and
Behavioral Sciences, University of Washington School of Medicine, Seattle,
Washington
Karen E. Moe Department of Psychiatry and Behavioral
Sciences, University of Washington School of Medicine, Seattle,
Washington
Robert S. Schwartz Department of Medicine, University
of Washington School of Medicine, Seattle, Washington
Michael V.
Vitiello Department of Psychiatry and Behavioral Sciences, University of
Washington School of Medicine, Seattle, Washington
Because the aging
pituitary remains responsive to stimulation by growth hormone (GH) secretagogues
- GHRH, ghrelin, and their mimetics - these compounds could potentially be used
instead of GH itself to increase GH secretion in aging.
The factors contributing
to the age-related decline in GH secretion are largely extrapituitary, and with
repeated or continuous administration GHS\'s can significantly increase GH
secretion and elevate levels of insulin-like growth factor-I (IGF-I) to the
young adult normal range.
Treatment with GHS\'s has both theoretical and
practical potential advantages over GH - preserving feedback regulation by IGF-I
to buffer against overtreatment, and yielding a more physiologic pulsatile
pattern of GH secretion. Nonpeptide GHS\'s can also be administered orally.
This review focuses primarily on results using GHRH; studies with ghrelin
agonists are reviewed in detail in other articles from this symposium. We and
others have shown that GHRH stimulates the brisk release of GH in healthy
seniors, and that repeated administration of GHRH elevates IGF-I in a
dose-dependent manner.
In two 6-month treatment studies in healthy older
women and men, subcutaneous injections of GHRH(1-29)NH2, self-administered once
nightly, chronically increased nighttime GH secretion and produced sustained
elevations of IGF-I levels. IGF-I increases were greatest in men, averaging 30%.
Women not taking estrogen showed somewhat lesser increases (23%), and women
taking oral estrogen replacement had no significant increase despite the
greatest increments in GH secretion. Lean body mass increased; body fat was
reduced by an average of 5-8%, with greatest effect on abdominal visceral fat;
and again this effect was blunted in estrogenized women.
Effects on physical
function varied by group. In nonestrogenized women, physical function
deteriorated in those receiving placebo; some measures were stabilized in women
receiving GHRH. These changes were not significant in estrogenized subjects.
GHRH appeared to improve cognitive function, especially in domains sensitive to
changes in processing speed. The formulation of GHRH used in these studies is
short-acting, with effects ending within a few hours. Perhaps for this reason,
late-night GH secretion decreased after the initial GHRH-stimulated surge, and
sleep quality was not improved. Side effects were those of fluid retention and
were generally mild.
The duration of these studies do not allow inferences to be
drawn on prevention of the onset of clinical features of frailty. Thus,
6-month treatment with once-daily GHRH can elevate GH secretion and IGF-I, and
improve body composition in a manner similar to the effects of GH. Effects
on physical function are equivocal. Effects on cognition are encouraging but
preliminary.
The current GHRH formulation is too short-acting to provide optimal
effects.
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