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Physiological Testosterone Replenishment in Healthy Elderly Men Does Not Normalize Pituitary Growth Hormone Output: Evidence against the Connection between Senile Hypogonadism and Somatopause

Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Michigan Medical Center (J.J.O., E.D., A.L.B.), and Department of Veterans Affairs Medical Center (K.S., A.L.B.), Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Ariel L. Barkan, M.D., Division of Endocrinology and Metabolism, 3920 Taubman Center, Room 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109. E-mail: abarkan{at}umich.edu.

Normal aging in men is accompanied by lower serum testosterone (T), GH, and IGF-I concentrations. The mechanisms of the age-related diminution in the activity of the somatotropic axis (somatopause) are uncertain. Several explanations have been proposed, including a lower hypothalamic GHRH output. The aim of the present study was to test the hypothesis that the physiological hypogonadism that accompanies normal aging is responsible for GHRH deficiency. We assessed the suppressibility of spontaneous and GHRH-stimulated GH secretion by a specific competitive GHRH receptor antagonist in seven elderly (61–76 yr old) and six young (20–23 yr old) healthy nonobese men. Elderly men then received transdermal T (5 mg/d) for 5–6 wk and had the same experiment repeated. Mean final total T, free T, and dihydrotestosterone increased in elderly men [521.5 ± 56.3 vs. 395.4 ± 57.2 ng/dl (P = 0.021), 13.8 ± 1.3 vs. 10.1 ± 1.7 pg/ml (P = 0.017), and 71.4 ± 8.9 vs. 41 ± 8.1 ng/dl (P = 0.004), respectively] to the levels found in their younger controls, but estradiol did not change (19.1 ± 2.5 vs. 18.5 ± 2.9 pg/ml; P = 0.67). GH pulse frequency or amplitude and maximum GH were not altered, and the integrated GH concentrations actually decreased. The percent suppression of GH output in the elderly did not change during GHRH antagonist infusion (35.8 ± 2.6% vs. 27.7 ± 6.5%; P = 0.29). We conclude that the T deficiency of old age is unlikely to be the proximate cause of the somatopause.

This work was supported by NIH Grants RO-1-DK-38449 (to A.L.B.), MO-1-RR-00042 (General Clinical Research Center), and P30-AG-08808 (Claude D. Pepper Older Americans Independence Center) and by the Department of Veterans Affairs Medical Research Service (A.L.B.).

Abbreviations: BMI, Body mass index; CV, coefficient of variation; DHT, dihydrotestosterone; IGHC, integrated GH concentration; T, testosterone; WHR, waist to hip ratio.

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