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

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. Th...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2004-07, Vol.89 (7), p.3255-3260
Main Authors: Orrego, John J, Dimaraki, Eleni, Symons, Kathy, Barkan, Ariel L
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Adult
Aged
Aging
Biological and medical sciences
Endocrinopathies
Fundamental and applied biological sciences. Psychology
Gonadal Steroid Hormones - blood
Growth Hormone-Releasing Hormone - antagonists & inhibitors
Hormone Antagonists - pharmacology
Human Growth Hormone - secretion
Humans
Hypogonadism - etiology
Hypogonadism - metabolism
Male
Medical sciences
Reference Values
Testosterone - administration & dosage
Testosterone - blood
Testosterone - pharmacology
Vertebrates: endocrinology
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Summary: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2003-031530