Johannes D. Veldhuis, MD

Disclosures

March 15, 2000

In This Article

The Aging GH Axis

Gender markedly influences GH secretion in young adults. Premenopausal women exhibit a 2-fold less rapid decline than men in daily GH production with increasing age. Young women also manifest less vulnerability to the suppressive effects of increased total body fat and reduced physical fitness on GH secretion.[30] Withdrawal of estrogen at menopause appears to eliminate much of this gender difference.

An important ongoing clinical issue relates to the uncertain role of sex-hormone deficiency in the aging-related impoverishment of GH and IGF-I production in women and men.[31] Preliminary data from clinical studies raise the possibility that combined GH and androgen repletion in older men can have an additive effect on increasing muscle mass.[30]

Short-term Experimental Use of GHRH in Older Adults

New clinical studies are appraising the effect of stimulating endogenous GH secretion in a manner that approximates physiologic levels (pulsatile and feedback-preserved). This strategy involves administration of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP)-like analogues.[32] New data indicate that treatment with GHRH can restore plasma IGF-I to levels found in young adults and is associated with little evident toxicity.[33,34,35] Body composition also improves. However, to date this treatment has not enhanced strength and physical aerobic capacity. Ongoing investigations are being conducted to evaluate the effects of combining GH, gonadal steroids, and/or GH secretagogues in older individuals. However, it appears that the relatively brief trials conducted thus far (eg, 6 months duration) may be inadequate to unveil the true spectrum of responses.[36]

Experimental Administration of recombinant human GH (rhGH) in Older Adults

New prospective interventions corroborate the dose-dependent restoration of plasma IGF-I concentrations by GH injections in older volunteers. Estrogen replacement in older women limits, but does not abolish, the ability of GH to stimulate IGF-I secretion. Treatment with GH consistently reduces visceral adiposity and increases muscle mass in men. Physical performance and maximal aerobic capacity most often do not change.[14]

Recent studies have successfully used lower doses of rhGH (3-10 mcg/kg/day, daily at night), which elicit fewer adverse events (eg, less fluid retention, carpal tunnel syndrome, gynecomastia, headache, bloating, pedal edema, or myalgias). The issue of whether long-term GH supplementation will stimulate neoplasia of the breast, prostate, or other tissues at increased risk for neoplasia in the elderly remains unclear.

New GH Secretagogues

Various peptidyl and nonpeptidyl compounds stimulate pulsatile GH secretion and increase plasma IGF-I concentrations in the elderly both acutely and over intervals of days to months without producing a clinically significant downregulation of GH responsiveness.[34] These novel agents include rhGHRH-1,44-amide and various members of the GHRP family.[14]

Individual GH secretagogues are uniformly less effective in older men and women. However, in older individuals, the coadministration of either GHRH or GHRP with L-arginine (an effector believed to restrain hypothalamic somatostatin secretion) stimulates GH secretion to levels approximating those of young adults.[37] A preliminary intervention study in elderly Dutch patients (>75 years of age) undergoing surgical repair of acute hip fractures suggests that perioperative short-term (6 weeks) rhGH treatment can accelerate recovery to premorbid quality of life.[9] This beneficial effect will need to be confirmed by additional studies.

processing....