Dale E. Mattson

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.

Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men.

OBJECTIVES It has been proposed that declining activities of the somatotrophic or gonadotrophic axes, or sedentary life style, are partial causes for geriatric losses of bone mineral density (BMD) and of lean body mass (LBM). The present study tested these hypotheses by determining, in both free‐living and institutionalized elderly men, the correlations of bone mineral density (BMD), total body bone mineral content (TBBMC) and lean body mass (LBM) with the following predictor variables: age, body mass index, body weight, serum insulin‐like growth factor I (IGF‐I), serum testosterone, habitual physical activity and mobility.

Low Circulating Levels of Insulin-Like Growth Factors and Testosterone in Chronically Institutionalized Elderly Men

Objective: To determine the prevalences of and the associations between hyposomatomedinemia and hypogonadism in healthy young men, healthy old men, and chronically institutionalized old men.

Association of Dehydroepiandrosterone Sulfate, Body Composition, and Physical Fitness in Independent Community-Dwelling Older Men and Women

OBJECTIVES: To determine the association of dehydroepiandrosterone sulfate (DHEAS), body composition, and physical fitness in independent community‐dwelling men and women aged 60 to 80 years.

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).

Antecedents of Death in the Men of a Veterans Administration Nursing Home

This study aims to learn whether the annual clinical and laboratory screening of nursing home residents provides significant information about their chance of dying during the following year.

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.

Serum Insulin‐Like Growth Factor I in Healthy Older Men in Relation to Physical Activity

Objective: The serum level of insulin‐like growth factor‐I (IGF‐I) is lower in old men than in young men. It has been theorized that this change may result in part from the lower level of physical activity in the elderly. The objective of the present study was to test this theory.

Predictors of Lean Body Mass and Total Adipose Mass in Community-Dwelling Elderly Men and Women

As part of an ongoing longitudinal study, we analyzed cross-sectional data to identify the predictors of lean body mass (LBM) and total adipose mass (TAM) in community-dwelling elderly men and women. Body composition analysis was done using dual energy x-ray absorptiometry. A total 262 subjects (118 women and 144 men), 60 to 80 years of age, from the urban and suburban communities of southeastern Wisconsin were studied. In women, the age (r = -.18), body mass index (BMI) (r = .43), and waist-to-hip ratio (WHR) (r = .30), and in men, BMI (r = .45) and insulin-like growth factor-1 (IGF-1) (r = .32) were identified as predictors (P < .05) of LBM. In women, the BMI (r = .87), WHR (r = .21), and functional work capacity (VO2 max) (r = -.47), and in men, the BMI (r = .83), WHR (r = .52), dehydroepiandrosterone sulfate (DHEAS) (r = -.27), total testosterone (TT) (r = -.35), free testosterone (FT) (r = -.23), physical activity (LTE) (r = -.32), and VO2 peak (r = -.59) were identified as predictors of TAM. After partialling out age in addition to the predictors identified earlier, the VO2 peak was identified as a predictor (P < .05) of LBM in both women and men, and TT, FT, and LTE as predictors (P < .05) of LBM in men. We conclude that the BMI, WHR, and VO2 peak influences LBM and TAM in both women and men. Additionally, in men LBM and TAM is influenced by hormone profile.

Hyposomatomedinemia in Quadriplegic Men

Many studies have shown that vigorous exercise acutely stimulates growth hormone (GH) release but the relative contribution of daily physical activity to maintaining the GH/somatomedin C (SmC) axis is not known. It has been reported that basal and post-exercise plasma SmC values are higher in physically conditioned young men than in sedentary men of similar age. To assess the effect of severe inactivity on the plasma SmC level, basal concentrations of this hormone were measured in patients with quadriplegia (QP) resulting from spinal cord injury (SCI). Venous blood samples were obtained after overnight fast in 41 QP men, ages 24-66, and compared with 119 healthy men of similar ages. Nonparametric analysis of variance showed SmC to be significantly lower in QP than in healthy men (p < .007). Plasma SmC below 0.35 U/ml in adults usually indicates little or no GH secretion by the pituitary gland. In QP, 46% of plasma SmC values were < 0.35 U/ml compared to 24% in the healthy group (p < .02). In both groups, an inverse relationship of SmC and increasing age was observed (p < .01). The data suggest that severe inactivity or SCI tend to cause hyposomatomedinemia. The latter endocrine alteration may contribute to the decrease in lean body mass and muscle atrophy of QP patients, and add further functional impairment to the original neurologic deficit. In addition, hyposomatomedinemia could increase the tendency for pressure sore formation and osteoporosis in SCI patients.