Age-related changes in growth hormone secretion: should the somatopause be treated?

Growth hormone (GH) secretion declines progressively with aging, and many age-related changes resemble those of the adult GH deficiency (GHD) syndrome, including a decrease in lean body mass; an increase in body fat, especially in the visceral/abdominal compartment; adverse changes in lipoproteins; and a reduction in aerobic capacity. The increase in central obesity can further inhibit GH secretion. GH replacement is effective in reversing many of these changes in adult GHD, and GH is now FDA approved for treatment of adults with documented GHD or hypopituitarism, although there is still only limited experience with its long-term benefits, side effects, and risks. This early experience with GHD has led to speculation that replacing GH or stimulating its secretion may also be beneficial in normal aging, and to widespread off-label use of GH in this context; however, there are still very few well controlled studies of the effects and side effects of GH or GH secretagogues in aging. All published studies are of 6 months or shorter treatment periods. From this limited experience there is a consensus that GH has effects on body composition, but reports disagree on effects on psychological or physical functional performance. Older adults are much more susceptible to the dose-related side effects of GH, including peripheral edema, carpal tunnel syndrome, and a variable decrease in insulin sensitivity; and it is not known whether chronic GH treatment affects the risk of malignancy or has other long-term risks. Thus while short-term results are somewhat encouraging, the evidence on risks and clinically pertinent benefits is still lacking to support the use of GH in normal aging outside of clinical studies. In evaluating patients with clinical features suggesting GHD, which can be quite nonspecific, it is important to assess the presence or absence of true GH deficiency by the context (pituitary disease or its treatment, childhood GHD) and by appropriate GH stimulation tests before considering GH replacement.