Is GH replacement recommended for the healthy elderly?
Although GH therapy in younger GH-deficient patients improves body composition, bone mineral density, exercise capacity, cardiac function, cholesterol levels, and quality of life, and may decrease mortality, the efficacy and safety of therapy for the otherwise “healthy” elderly is controversial. A 2007 systematic review of clinical trials of GH in the healthy elderly concluded that GH therapy does increase serum IGF-1 concentrations, although women may require higher doses of GH for longer periods compared with men to achieve physiologic replacement levels. Despite higher GH doses per kilogram of body weight, women do not consistently demonstrate the increase in lean body mass or decrease in fat mass that occur in men. Furthermore, translation into clinically significant changes in strength, function, bone mineral density, and improved metabolic parameters has been difficult to demonstrate in either gender. GH treatment is associated with several important adverse events, such as a significantly increased incidence compared with placebo of soft tissue edema (42%), carpal tunnel syndrome (18%), arthralgias (16%), gynecomastia (6%), impaired glucose tolerance (13%), and new-onset diabetes (4%).
The scant clinical experience with GH treatment for the healthy elderly suggests that although GH may minimally improve body composition, it does not improve other clinically relevant outcomes, such as strength or function, and it is associated with high rates of adverse events. Furthermore, studies in invertebrate and rodent models have suggested that lower GH axis activity may be protective for longevity. On the basis of available evidence, GH cannot be recommended for routine use in the healthy elderly. Large RCTs would be needed to determine the safety and efficacy of GH combined with exercise, sex hormones, and other replacement strategies, such as GHRH, IGF-1, and ghrelin-mimetic GHS.