As the proportion of aging people continues to rapidly rise, reducing the burden of age-related diseases becomes increasingly important in primary care. A controversial hormone that is center stage in the debate over the use of hormone therapies in prevention and wellness is growth hormone.

Growth hormone, a single-chain polypeptide produced in the pituitary gland, has a wide range of metabolic and cellular effects. Growth hormone plays an important role in the regulation of body composition, lipid profiles, tissue repair, cardiac and neuronal functioning, and maintenance of bone mineral density. Growth hormone is secreted in pulsatile fashion, especially during stage III and IV deep sleep. It acts on liver and other tissues to stimulate the production of insulin like growth factors.

While there is considerable variation in growth hormone production among individuals of the same age, there is a progressive decline in average growth-hormone production and IFG-1 levels after age 20, with average levels declining by 30% to 60% by age 40 to 60, and by 50% to 80% after age 60.

A large number of peer-reviewed studies, including long-term randomized controlled trial data, has demonstrated that growth hormone replacement improves

• energy
• strength
• cardiac function
• blood pressure
• cholesterol levels
• insulin sensitivity
• cognitive function
• immunity
• psychologic well-being
• decreases body fat
• increases lean muscle
• prevents and reverses heart disease
• prevents and improves osteoporosis
• improves quality of life

Controversy

Controversial issues regarding growth hormone supplementation include the use of growth hormone as a therapeutic modality for age-related deficiency; the accuracy and necessity of commonly used stimulation testing when considering growth hormone usage in well patients; the need for guidelines for safe and effective treatment; and potential side effects of treatment.

Clinical Diagnosis

The adult age-related clinical syndrome of growth hormone deficiency includes increased fat mass, decreased muscle mass and strength, decreased bone density, elevated lipids, insulin resistance, decreased psychosocial well-being and depression, fatigue, increased social isolation, inability to handle stress, cardiovascular disease, memory decline, overall deterioration in quality of life, frailty, thin dry skin, increased wrinkles, and diminished exercise tolerance.

Clinicians commonly encounter these clinical symptoms in the aging patient. If considered appropriate by physician and patient, a 6-month therapeutic trial with growth hormone could be considered. Patients should be evaluated for symptomatic and metabolic improvements at a minimum at 3 and 6 months to decide if treatment should be continued.

Treatment

The treatment of age-related adult growth-hormone deficiency remains controversial even though the literature reports significant benefits from growth hormone supplementation. The main sources of concern associated with growth hormone replacement in somatopause include, in no particular order, significant cost of therapy from $250 to $1500 per month (depending on dose and manufacturer), side effects of water retention resulting in joint pain and carpal tunnel syndrome, temporary reduction in insulin sensitivity, and theoretic risk of cancer. Most short-term side effects are diminished with reduction in dose. While there is a long-held theoretic belief of an increased risk of cancer, based on the growth hormone’s antiapoptotic and mitogenic effects, neither long-term nor short-term data support this theory.

Conclusion

In conclusion, aging adults have a relative deficiency of growth hormone and supplementation with growth hormone may be of significant benefit. Although no long-term studies have assessed side effects with low physiologic doses of growth hormone supplementation in somatopause, the studies we reviewed above have confirmed that low doses are safe, well tolerated, and associated with a plethora of clinical benefits.

Treatment with growth hormone is presently limited to an affluent and highly motivated population. Cost and risk/benefit ratio over time must be taken into consideration. As our patients age, the challenge of maintaining quality of life for them becomes more difficult and must be considered in the design of future studies. For supplementation with growth hormone to become a first-line therapeutic option in the aging population, additional and more extensive randomized trials that evaluate results of growth hormone treatment in age-related deficiency must be undertaken, and cost factors must be addressed.