Axel G. Feller

Effects of Human Growth Hormone in Men over 60 Years Old

BACKGROUND The declining activity of the growth hormone--insulin-like growth factor I (IGF-I) axis with advancing age may contribute to the decrease in lean body mass and the increase in mass of adipose tissue that occur with aging. METHODS To test this hypothesis, we studied 21 healthy men from 61 to 81 years old who had plasma IGF-I concentrations of less than 350 U per liter during a six-month base-line period and a six-month treatment period that followed. During the treatment period, 12 men (group 1) received approximately 0.03 mg of biosynthetic human growth hormone per kilogram of body weight subcutaneously three times a week, and 9 men (group 2) received no treatment. Plasma IGF-I levels were measured monthly. At the end of each period we measured lean body mass, the mass of adipose tissue, skin thickness (epidermis plus dermis), and bone density at nine skeletal sites. RESULTS In group 1, the mean plasma IGF-I level rose into the youthful range of 500 to 1500 U per liter during treatment, whereas in group 2 it remained below 350 U per liter. The administration of human growth hormone for six months in group 1 was accompanied by an 8.8 percent increase in lean body mass, a 14.4 percent decrease in adipose-tissue mass, and a 1.6 percent increase in average lumbar vertebral bone density (P less than 0.05 in each instance). Skin thickness increased 7.1 percent (P = 0.07). There was no significant change in the bone density of the radius or proximal femur. In group 2 there was no significant change in lean body mass, the mass of adipose tissue, skin thickness, or bone density during treatment. CONCLUSIONS Diminished secretion of growth hormone is responsible in part for the decrease of lean body mass, the expansion of adipose-tissue mass, and the thinning of the skin that occur in old age.

Effects of Human Growth Hormone on Body Composition in Elderly Men

Body composition changes progressively in mid and late adulthood. Lean body mass in men over 50 years old contracts at an average rate of -0.6% per year. Body weight tends to remain stable because of a reciprocal expansion of adipose mass. The shrinkage of the lean body mass reflects the atrophy of skeletal muscles, skin and visceral organs. Because growth hormone causes expansion of the lean body mass and contraction of the adipose mass, and because growth hormone secretion tends to diminish in late adulthood, it has been postulated that geriatric hyposomatotropism is a contributory cause to the body composition changes described above. The authors have tested this hypothesis by recruiting 45 independent men over 61 years old with plasma somatomedin C level below 0.35 U/ml, indicating little or no detectable growth hormone secretion. The 21-month protocol was as follows: baseline period 0-6 months, experimental period 6-18 months and post-experimental period 18-21 months. During the experimental period, 26 men (group I) received approximately 0.03 mg/kg of biosynthetic human growth hormone (hGH) subcutaneously 3 times a week, while 19 men (group II) received no treatment. Plasma somatomedin C was measured monthly. The following outcome variables were measured at 0, 6, 12 and 18 months: lean body mass, adipose mass, skin thickness (dermis plus epidermis), sizes of the liver, spleen and kidneys, the cross sectional areas of ten muscle groups, and bone density at 9 skeletal sites. Lean body mass and adipose mass were also measured at 21 months. In group I, hGH treatment raised the plasma somatomedin C level and maintained it in the range 0.5-1.5 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF‐I concentrations

OBJECTIVE We studied the relationship between plasma level of insulin‐like growth hormone I (IGF‐I), changes in lean body mass and in adipose mass, and adverse side‐effects during human growth hormone (hGH) treatment of elderly men who had low IGF‐I levels.

Prognostic significance of serum cholesterol in nursing home men

Serum cholesterol was measured in 129 men (average age 70.6; range 41-96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base. Serum cholesterol was less than 150 mg/dl in 13% of the subjects, and was less than 160 mg/dl in 18%. Cholesterol greater than 280 mg/dl occurred in 8%. Serum cholesterol varied directly (p less than 0.02) with: body weight, serum albumin, serum total protein, serum sodium, ability to walk, and ability to feed oneself; and indirectly (p less than 0.02) with death rate, degree of functional dependence, and serum SGOT and LDH. Nursing home men with cholesterol less than 150 mg/dl had a death rate of 63% during the 14 months after the cholesterol analysis, compared to a death rate of 9% in men with cholesterol greater than 150 mg/dl (p less than 0.05). Death rate during the year after the analysis was 52% if cholesterol was below 160 mg/dl, compared to 7% if it was above this threshold (p less than 0.05).

Relation of Serum Albumin Concentration to Death Rate in Nursing Home Men

Serum albumin was measured in 126 men (average age 70.6; range 40 to 96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base, including death or survival during the year after the analysis. The reason for institutionalization was chronic neurologic disease or other disabling physical condition in 63 men (group A), and psychiatric disorder in 63 men (group B). In group A, the proportions of men with albumin less than 3.5, 3.5-4.0, and greater than 4.0 g/dl were 6%, 37%, and 57%, respectively. In this group, the serum albumin level was significantly (p less than 0.05) correlated with death rate, hemoglobin, hematocrit, serum cholesterol, and serum lactic dehydrogenase. The death rate in group A during the year after the albumin analysis was 25%. For the patients with albumin level less than 3.5, 3.5-4.0, and greater than 4.0 g/dl, the death rates were 50%, 43%, and 11% respectively (p less than 0.01 for comparison of the former two groups with the latter). The subgroup with albumin 3.5-4.0 g/dl represented only 37% of the men in group A, but accounted for 63% of the groups deaths. In group B, serum albumin level was not significantly correlated with any other clinical variable. Death rate during the year after the albumin analysis was only 2% in group B, and did not correlate with the albumin level. These data indicate that, in nonpsychiatric Nursing Home men, the desirable level for the serum albumin concentration is higher than 3.5 g/dl.

Effects of Three Liquid Diets on Nutrition-Sensitive Plasma Proteins of Tube-Fed Elderly Men

The effects on three nutrition‐sensitive plasma proteins of isocaloric feedings with three enteral formulas were compared in 10 tube‐fed male nursing home residents. The enteral products were Isocal (based on whole protein), Peptamen (based on a mixture of oligopeptides), and Vivonex T.E.N. (based on free amino acids). The nutrition‐sensitive plasma proteins were albumin, transferrin, and retinol‐binding protein. After observation during four weeks of feeding with Isocal, each subject was then monitored during four weeks of Peptamen and four weeks of Vivonex T.E.N. The latter two products were alternated in a crossover design.

Growth Hormone and Function in Elderly Persons

TO THE EDITOR: Papadakis and colleagues [1] reported that a cohort of healthy, active men older than 70 years of age with low insulin-like growth factor 1 (IGF-1) levels had increased lean body mass and decreased fat mass after receiving human growth hormone for 6 months. This finding confirmed our observations after 6 months [2] and 12 months [3] of human growth hormone treatment in a similar group of healthy older men. Papadakis and colleagues noted no significant functional improvement, as measured by muscle strength and physical endurance. In contrast, Jorgensen and associates [4] studied growth hormone-deficient younger adults after long-term human growth hormone treatment and found significant improvement in physical performance. Thus, this issue remains unresolved and as such raises another question. What would be the effect of human growth hormone supplementation in frail, functionally impaired elderly persons who have age-related growth hormone deficiency? Other potential benefits of improved body composition need to be considered. We showed significant increases in liver and spleen volumes [3]. Whether these changes contribute to improved function (for example, drug metabolizing capacity and enhanced immune function) remains to be determined. On the other hand, during an observation period of 18 to 21 months, our control patients with low IGF-1 levels lost lean body mass at a much faster rate than expected [3, 5]. Thus, it is possible that in some persons, the age-related decline in growth hormone secretion contributes to a more rapid deterioration of body composition. This finding might not be apparent in studies of shorter duration [1, 2]. We reported [5] that during treatment with human growth hormone, the maximum improvement in body composition and minimum of adverse side effects in elderly men occurred at doses that elevate IGF-1 levels between 0.5 to 1.0 U/mL (the lower normal IGF-1 level in younger persons). When IGF-1 levels increased between 1.0 and 1.5 U/mL (the higher normal IGF-1 level in younger persons), side effects were frequent and changes in body composition were attenuated. Given the frequency of side effects observed by Papadakis and colleagues, it is possible that the growth hormone dose was not optimal for an adequate balance between beneficial and adverse effects. Future trials of human growth hormone should study the effects of short periods of supplementation alone and combined with exercise in the frail elderly and in immobilized persons (such as those with stroke or hip fracture) as a means of preventing loss of lean body mass and enhancing rehabilitation.

Further Observations on the Effects of Human Growth Hormone in Elderly Hyposomatomedinemic Men

In 1990 the authors described the effects of human growth hormone (hGH) in 12 hyposomatomedinemic healthy men over 60 years of age (1). A significant increase in lean body mass and a decrease in adipose tissue mass were observed during a 6-month treatment period. The hGH doses were chosen in order to elevate the plasma level of insulin-like growth factor I (IGF-I, also termed somatomedin C) to a youthful range of 0.5–1.5 units/ml. Early adverse side effects were not observed. The present chapter extends the earlier report by describing a larger group of hyposomatomedinemic men over 60 years old, initially numbering 42, who were treated for up to 12 months. Complications of hGH treatment were encountered and a relation to the plasma level of IGF-I was identified.