Papadakis and colleagues [1] reported that a cohort of healthy, active men older than 70 years of age with low insulin-like growth factor 1 (IGF-1) levels had increased lean body mass and decreased fat mass after receiving human growth hormone for 6 months. This finding confirmed our observations after 6 months [2] and 12 months [3] of human growth hormone treatment in a similar group of healthy older men. Papadakis and colleagues noted no significant functional improvement, as measured by muscle strength and physical endurance. In contrast, Jorgensen and associates [4] studied growth hormone-deficient younger adults after long-term human growth hormone treatment and found significant improvement in physical performance. Thus, this issue remains unresolved and as such raises another question. What would be the effect of human growth hormone supplementation in frail, functionally impaired elderly persons who have age-related growth hormone deficiency?

Other potential benefits of improved body composition need to be considered. We showed significant increases in liver and spleen volumes [3]. Whether these changes contribute to improved function (for example, drug metabolizing capacity and enhanced immune function) remains to be determined.

On the other hand, during an observation period of 18 to 21 months, our control patients with low IGF-1 levels lost lean body mass at a much faster rate than expected [3, 5]. Thus, it is possible that in some persons, the age-related decline in growth hormone secretion contributes to a more rapid deterioration of body composition. This finding might not be apparent in studies of shorter duration [1, 2].

We reported [5] that during treatment with human growth hormone, the maximum improvement in body composition and minimum of adverse side effects in elderly men occurred at doses that elevate IGF-1 levels between 0.5 to 1.0 U/mL (the lower normal IGF-1 level in younger persons). When IGF-1 levels increased between 1.0 and 1.5 U/mL (the higher normal IGF-1 level in younger persons), side effects were frequent and changes in body composition were attenuated. Given the frequency of side effects observed by Papadakis and colleagues, it is possible that the growth hormone dose was not optimal for an adequate balance between beneficial and adverse effects.

Future trials of human growth hormone should study the effects of short periods of supplementation alone and combined with exercise in the frail elderly and in immobilized persons (such as those with stroke or hip fracture) as a means of preventing loss of lean body mass and enhancing rehabilitation.