Growth Hormone

Levels of growth hormone (GH) decrease with aging, as do levels of insulin-like growth factor I (IGF-I), which mediates many of the effects of GH in adults. The decrease in GH levels is probably one of many factors that contribute to sarcopenia (age-related loss of muscle mass). Many of the symptoms and signs of GH deficiency (eg, decreased muscle mass, weakness, fatigue) are similar to those that occur with normal aging.

Causes of the age-related decrease in GH are multifactorial. Secretion of somatostatin, a neuropeptide that inhibits GH release, increases with aging. Secretion of growth hormone-releasing hormone (GHRH) decreases with aging; as a result, circulating GH levels decrease, there are fewer daily peaks of GH secretion, and sleep may become fragmented (because GHRH affects slow-wave sleep). The age-related decrease in estrogen and testosterone (which is converted to estrogen through aromatization) may also reduce GH secretion.

GH supplementation should be used only for patients with a documented deficiency (as GH replacement therapy) or for patients with muscle atrophy due to AIDS. GH is sometimes used to stimulate appetite in undernourished patients when other treatments are ineffective (most likely because the treatments cause fluid retention); however, in such cases, GH is often ineffective. Its use to reverse age-related effects on body composition is experimental. Overall, little evidence supports routine use of GH supplementation in the elderly.

GH replacement therapy appears to increase muscle mass and decrease fat mass. However, muscle strength increases little, if at all, unless GH is accompanied by weight-training or is given with testosterone replacement therapy in hypogonadal men. GH replacement therapy affects cardiovascular risk factors; it reduces total cholesterol, low density lipoprotein cholesterol, and diastolic BP, but it significantly increases fasting plasma glucose and insulin. Clinical cardiovascular effects are not yet known. GH replacement therapy increases skin thickness and has minor effects on the immune system (eg, increases natural killer cell activity), but it does not increase bone density. Effects on cognitive function are unknown.

GH is given sc. The elderly are more sensitive to GH, so the initial dose should be low (such doses are usually still supraphysiologic). Whether use of more physiologic doses of GH would have positive effects with fewer adverse effects is unknown. Long-term effects are unclear; middle-aged people with high levels of GH and IGF-I have higher mortality rates than do those with lower levels of GH and IGF-I.

Adverse effects of GH supplementation include carpal tunnel syndrome, arthralgias, glucose intolerance, headaches, lethargy, fluid retention, and gynecomastia.

Contraindications to use of GH in the elderly include hypersensitivity to the drug, an acute critical disorder, acute respiratory failure, cancer, and intracranial lesions. GH replacement therapy must be used cautiously in patients with hypopituitarism and diabetes. Systemic corticosteroids reduce the efficacy of GH.

As an alternative to GH supplementation, IGF-I administration decreases body fat mass and increases muscle mass in the elderly. However, its use is limited because the incidence of adverse effects (eg, carpal tunnel syndrome) is high. Use of GHRH increases GH and IGF-I levels in the elderly. Oral GH secretagogues (small peptide molecules) given once/day for 28 days increase GH, IGF-I, and IGF-binding protein-3 levels. Treatment is well tolerated; however, in some patients, appetite is stimulated, possibly causing weight gain.

This topic was last updated March 2006.