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Am J Physiol Endocrinol Metab 293: E769-E775, 2007. First published June 5, 2007; doi:10.1152/ajpendo.00709.2006
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Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men

Ranganath Muniyappa,1 John D. Sorkin,3,4 Johannes D. Veldhuis,5 S. Mitchell Harman,2,6 Thomas Münzer,2,7 Shalender Bhasin,8 and Marc R. Blackman1,2

1Endocrine Section, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland; 2Endocrine and 3Metabolism Sections, National Institute on Aging, National Institutes of Health; 4Division of Geriatrics and Gerontology, Department of Medicine, Department of Veterans Affairs and Veterans Affairs Medical Center, Baltimore Geriatric Research, Education, and Clinical Center, and the University of Maryland School of Medicine, Division of Gerontology, Baltimore, Maryland; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinical Research Center, Rochester, Minnesota; 6Kronos Longevity Research Institute, Phoenix, Arizona; 7Geriatric Medicine and Rehabilitation, Bürgerspital, St. Gallen, Switzerland; and 8Endocrine, Diabetes, and Nutrition Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

Submitted 22 December 2006 ; accepted in final form 30 May 2007

Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men. Short-term administration of high doses of T augments GH secretion in older men. However, effects of long-term, low-dose T supplementation on GH secretion are unknown. Our objective was to evaluate effects of long-term, low-dose T administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I and IGFBP-3 in healthy older men (65–88 yr, n = 34) with low-normal T and IGF-I. In a double-masked, placebo-controlled, randomized study we assessed effects of low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH secretory dynamics [8 PM to 8 AM, Q20 min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% (P = 0.004) and E2 by 31% (P = 0.009) and decreased SHBG by 17% (P = 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% (P = 0.02) and pulsatile GH secretion by 79% (P = 0.05), primarily due to a twofold increase in GH secretory burst mass (P = 0.02) and a 1.9-fold increase in basal GH secretion rate (P = 0.05) vs. placebo. There were no significant changes in GH burst frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% (P = 0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We conclude that low-dose T supplementation for 26 wk increases spontaneous nocturnal GH secretion and morning serum IGF-I concentrations in healthy older men.

pulsatility; testosterone replacement; aging



Address for reprint requests and other correspondence: M. R. Blackman, Washington DC VAMC, Research Service (151), 50 Irving St., Washington, DC 20422 (e-mail: Marc.Blackman{at}va.gov)







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