Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men

A. Gentili, T. Mulligan, M. Godschalk, J. Clore, J. Patrie, A. Iranmanesh, Johannes D Veldhuis

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

The present clinical study compares the impact of low- and high-dose parenteral testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I, IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40 yr) men. To this end, we administered three consecutive weekly injections of randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8 older) of androgen. To monitor somatotropic-axis responses, blood was sampled every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3 concentrations. Data were analyzed via a nested analysis of covariance statistical design. At baseline (saline injection), older, compared with young, men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I concentrations, namely, mean (±SEM) IGF-I 160 plus or minus 15 vs. 280 plus or minus 18 μg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 ± 0.09 vs. 1.2 ± 0.20 μg/liter, P = 0.031); 3) more disorderly GH release patterns (approximate entropy 0.501 ± 0.058 vs. 0.288 ± 0.021, P < 0.001); and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 ± 0.05 vs. 0.47 ± 0.08 μg/liter, P = 0.025). Serum T concentrations (ng/dl) did not differ in the two age groups supplemented with either a low dose [550 ± 50 (young) and 544 ± 128 (older)] and high [1320 ± 92 (young) and 1570 ± 140 (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on GH secretion in either age cohort but increased the serum IGF-I concentration in young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH production in young volunteers but in older men stimulated: 1) a 2.03-fold rise in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P = 0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4) a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a 1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40% increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate statistical analysis indicated that following high-dose T administration, the E2 increment significantly predicted the IGF-I increment in both age groups combined (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P = 0.0031); and age and T dose jointly determined serum LH concentrations (P = 0.031). In summary, neither a physiological nor a pharmacological dose of T administered parenterally for 3 wk augments daily GH secretion in eugonadal young men. In contrast, a high dose of aromatizable androgen significantly amplifies 24-h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and elevates the serum IGF-I concentration in older men. The mechanistic basis for the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not known.

Original languageEnglish (US)
Pages (from-to)825-834
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor I
Testosterone
Serum
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Androgens
Entropy
Assays
Age Groups
Chemiluminescence
Immunoradiometric Assay
Injections
Amplification
Luminescence
Statistical methods
Blood
Volunteers
Fasting
Multivariate Analysis
Scanning electron microscopy

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Gentili, A., Mulligan, T., Godschalk, M., Clore, J., Patrie, J., Iranmanesh, A., & Veldhuis, J. D. (2002). Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. Journal of Clinical Endocrinology and Metabolism, 87(2), 825-834. https://doi.org/10.1210/jc.87.2.825

Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. / Gentili, A.; Mulligan, T.; Godschalk, M.; Clore, J.; Patrie, J.; Iranmanesh, A.; Veldhuis, Johannes D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 2, 2002, p. 825-834.

Research output: Contribution to journalArticle

Gentili, A, Mulligan, T, Godschalk, M, Clore, J, Patrie, J, Iranmanesh, A & Veldhuis, JD 2002, 'Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men', Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 2, pp. 825-834. https://doi.org/10.1210/jc.87.2.825
Gentili, A. ; Mulligan, T. ; Godschalk, M. ; Clore, J. ; Patrie, J. ; Iranmanesh, A. ; Veldhuis, Johannes D. / Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 2. pp. 825-834.
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T1 - Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men

AU - Gentili, A.

AU - Mulligan, T.

AU - Godschalk, M.

AU - Clore, J.

AU - Patrie, J.

AU - Iranmanesh, A.

AU - Veldhuis, Johannes D

PY - 2002

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N2 - The present clinical study compares the impact of low- and high-dose parenteral testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I, IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40 yr) men. To this end, we administered three consecutive weekly injections of randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8 older) of androgen. To monitor somatotropic-axis responses, blood was sampled every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3 concentrations. Data were analyzed via a nested analysis of covariance statistical design. At baseline (saline injection), older, compared with young, men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I concentrations, namely, mean (±SEM) IGF-I 160 plus or minus 15 vs. 280 plus or minus 18 μg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 ± 0.09 vs. 1.2 ± 0.20 μg/liter, P = 0.031); 3) more disorderly GH release patterns (approximate entropy 0.501 ± 0.058 vs. 0.288 ± 0.021, P < 0.001); and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 ± 0.05 vs. 0.47 ± 0.08 μg/liter, P = 0.025). Serum T concentrations (ng/dl) did not differ in the two age groups supplemented with either a low dose [550 ± 50 (young) and 544 ± 128 (older)] and high [1320 ± 92 (young) and 1570 ± 140 (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on GH secretion in either age cohort but increased the serum IGF-I concentration in young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH production in young volunteers but in older men stimulated: 1) a 2.03-fold rise in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P = 0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4) a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a 1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40% increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate statistical analysis indicated that following high-dose T administration, the E2 increment significantly predicted the IGF-I increment in both age groups combined (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P = 0.0031); and age and T dose jointly determined serum LH concentrations (P = 0.031). In summary, neither a physiological nor a pharmacological dose of T administered parenterally for 3 wk augments daily GH secretion in eugonadal young men. In contrast, a high dose of aromatizable androgen significantly amplifies 24-h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and elevates the serum IGF-I concentration in older men. The mechanistic basis for the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not known.

AB - The present clinical study compares the impact of low- and high-dose parenteral testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I, IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40 yr) men. To this end, we administered three consecutive weekly injections of randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8 older) of androgen. To monitor somatotropic-axis responses, blood was sampled every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3 concentrations. Data were analyzed via a nested analysis of covariance statistical design. At baseline (saline injection), older, compared with young, men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I concentrations, namely, mean (±SEM) IGF-I 160 plus or minus 15 vs. 280 plus or minus 18 μg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 ± 0.09 vs. 1.2 ± 0.20 μg/liter, P = 0.031); 3) more disorderly GH release patterns (approximate entropy 0.501 ± 0.058 vs. 0.288 ± 0.021, P < 0.001); and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 ± 0.05 vs. 0.47 ± 0.08 μg/liter, P = 0.025). Serum T concentrations (ng/dl) did not differ in the two age groups supplemented with either a low dose [550 ± 50 (young) and 544 ± 128 (older)] and high [1320 ± 92 (young) and 1570 ± 140 (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on GH secretion in either age cohort but increased the serum IGF-I concentration in young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH production in young volunteers but in older men stimulated: 1) a 2.03-fold rise in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P = 0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4) a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a 1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40% increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate statistical analysis indicated that following high-dose T administration, the E2 increment significantly predicted the IGF-I increment in both age groups combined (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P = 0.0031); and age and T dose jointly determined serum LH concentrations (P = 0.031). In summary, neither a physiological nor a pharmacological dose of T administered parenterally for 3 wk augments daily GH secretion in eugonadal young men. In contrast, a high dose of aromatizable androgen significantly amplifies 24-h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and elevates the serum IGF-I concentration in older men. The mechanistic basis for the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not known.

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