Growth hormone-releasing hormone in normal aging: An update

Muscle mass, strength, and aerobic capacity all decline with aging, ultimately leading to an increased risk of falls and impaired ability to live independently. Several pharmacological approaches, including androgen and growth hormone (GH) therapy, have been suggested as offering promise in counteracting this decline in functional capacity. Recently, administration of a growth hormone secretagogue such as growth hormone-releasing hormone (GHRH) has been explored as a possible alternative to GH for use in this application. The aging pituitary remains responsive to GHRH, and GHRH treatment may be a more physiological approach to enhancing GH levels. There are still relatively few controlled prospective studies of the effects of GH or GH secretagogues in aging, but preliminary results of short-term studies demonstrate an increase in lean body mass, decreased fat mass, and modest increases in bone mineral density. GHRH(1-29)NH₂ (sermorelin acetate, Geref®), which is FDA-approved for the treatment of pediatric GH deficiency, has shown preliminary promise in several studies in healthy seniors. Follow-up studies currently underway are assessing the effects of once-daily dosing of subcutaneous sermorelin on hormonal and functional endpoints in normal older adults. Early results show that this treatment is well tolerated by aging subjects, and can increase 24-hour GH secretion, boost circulating levels of insulin-like growth factor-I, and improve body composition. However, much larger-scale prevention studies will be required to fully document the safety of chronic GH secretagogue therapy, and its efficacy in achieving such outcomes as reducing falls or fractures, or prolonging the capacity for independent living.