IN middle and late adulthood all people experience a series of progressive alterations in body composition.1 The lean body mass shrinks and the mass of adipose tissue expands. The contraction in lean body mass reflects atrophic processes in skeletal muscle, liver, kidney, spleen, skin, and bone.
These structural changes have been considered unavoidable results of aging.1 It has recently been proposed, however, that reduced availability of growth hormone in late adulthood may contribute to such changes.1, 2 This proposal is based on two lines of evidence. First, after about the age of 30, the secretion of growth hormone by the pituitary gland tends to decline.1, 3, 4 Since growth hormone is secreted in pulses, mostly during the early hours of sleep, it is difficult to measure the 24-hour secretion of the substance directly. Growth hormone secretion can be measured indirectly, however, by measuring the plasma concentration of insulin-like growth factor I (IGF-I, also known as somatomedin C), which is produced and released by the liver and perhaps other tissues in response to growth hormone.5 There is little diurnal variation in the plasma IGF-I concentration, and measurements of it are therefore a convenient indicator of growth hormone secretion.5 Plasma IFG-I concentrations decline with advancing age in healthy adults.1, 4, 6 Less than 5 percent of the healthy men 20 to 40 years old have plasma IGF-1 values of less than 350 U per liter, but the values are below this figure in 30 percent of the healthy men over 60.4 Likewise, the nocturnal pulses of growth hormone secretion become smaller or disappear with advanced age. If the plasma concentration of IGF-I falls below 350 U per liter in older adults, no spontaneous circulating pulses of growth hormone can be detected by currently available radioimmunoassay methods.4 The concomitant decline in plasma concentrations of both hormones supports the view that the decrease in IGF-I results from diminished growth hormone secretion.4, 6 Second, diminished secretion of growth hormone is accompanied not only by a fall in the plasma IGF-I concentration, but also by atrophy of the lean body mass and expansion of the mass of adipose tissue.1 These alterations in body composition caused by growth hormone deficiency can be reversed by replacement doses of the hormone, as experiments in rodents,7 children,8, 9 and adults 20 to 50 years old10 11 12 13 have shown. These findings suggest that the atrophy of the lean body mass and its component organs and the enlargement of the mass of adipose tissue that are characteristic of the elderly result at least in part from diminished secretion of growth hormone.1, 2If so, the age-related changes in body composition should be correctable in part by the administration of human growth hormone, now readily available as a biosynthetic product.14
In this study we administered biosynthetic human growth hormone for six months to 12 healthy men from 61 to 81 years old whose plasma IGF-I concentrations were below 350 U per liter, and we measured the effects on plasma IGF-I concentration, lean body mass, adipose-tissue mass, skin (dermal plus epidermal) thickness, regional bone density, and mandibular-height ratio (the height of the alveolar ridge divided by the total height of the mandible). The measurement of the mandible was included to test the hypothesis that the age-related involution of dental bone results in part from the loss of stimulation by growth hormone.1 In addition, the men were monitored for possible adverse effects of the hormone by means of interviews, physical examinations, and standard laboratory tests. Nine men matched for age and with similar plasma IGF-I concentrations served as controls.