Use of Growth Hormone Secretagogues to Prevent or Treat the Effects of Aging: Not Yet Ready for Prime Time

Aging is associated with progressive and substantial decreases in growth hormone secretion and in circulating concentrations of insulin-like growth factor I (IGF-I) (1). Increasing evidence suggests that these hormonal changes, coupled with estrogen deficiency in menopausal women and reduced total and bioavailable testosterone in men, contribute to age-related decreases in skeletal muscle mass and strength (sarcopenia), increased total and intra-abdominal fat, loss of bone mass (osteopenia), insulin resistance, dyslipidemias, and enhanced risks for type 2 diabetes mellitus and cardiovascular disease (15). Taken together, these changes in body composition and function are precursors of musculoskeletal frailty, disability and reduced physical function, falls, bone fractures and subsequent nursing home admissions, and mortality (6).

Numerous reports indicate that growth hormone treatment improves body composition, muscle strength, metabolic and physical function, bone density, and quality of life in nonelderly adults with pathologic growth hormone deficiency (7). In contrast, relatively few randomized, controlled trials of recombinant human growth hormone have been conducted in older people, and the results of such studies have been equivocal or disappointing in terms of clinical benefits (8). In particular, administration of growth hormone to healthy older persons has consistently resulted in improvements in body composition (increases in lean body mass; decreases in total and abdominal fat mass; and, less frequently, augmented bone mineral density) and some metabolic parameters (lowering low-density lipoprotein cholesterol), without significantly affecting muscle strength, physical performance, or quality of life. Moreover, side effects of growth hormone treatment, such as peripheral edema, arthralgias, myalgias, glucose intolerance, and loss of insulin sensitivity, are especially common in older persons (8). Development of insulin resistance is of concern because it predisposes a patient to diabetes mellitus and vascular disease.

Injections or infusions of growth hormonereleasing hormone (GHRH) and parenteral or oral administration of a ghrelin-mimetic …