Muniyappa R, Sorkin JD, Veldhuis JD, Harman SM, Mü nzer T, Bhasin S, Blackman MR. Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men. Am J Physiol Endocrinol Metab 293: E769-E775, 2007. First published June 5, 2007; doi:10.1152/ajpendo.00709.2006.-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 ϭ 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, Q 20 min sampling, analyzed by multiparameter deconvolution and approximate entropy (ApEn) algorithms]. The results were that T administration increased serum total T by 33% (P ϭ 0.004) and E 2 by 31% (P ϭ 0.009) and decreased SHBG by 17% (P ϭ 0.002) vs. placebo. T supplementation increased nocturnal integrated GH concentrations by 60% (P ϭ 0.02) and pulsatile GH secretion by 79% (P ϭ 0.05), primarily due to a twofold increase in GH secretory burst mass (P ϭ 0.02) and a 1.9-fold increase in basal GH secretion rate (P ϭ 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 ϭ 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 AGING IN HEALTHY MEN is associated with progressive declines in circulating concentrations of total testosterone (T) and free T and in growth hormone (GH) secretion and IGF-I levels (8,17). Concomitant with these hormonal changes, there are decrements in skeletal muscle mass and strength (sarcopenia) and bone mass (osteopenia), increases in visceral adiposity, and reductions in physical fitness (18,19,31,35,36). These undesirable changes in body composition and function may be precursors of major health problems for the older population, including musculoskeletal frailty, bone fractures, insulin resistance, and dyslipidemia, with consequent increased risk of type 2 diabetes and cardiovascular disease (16,19,23). Age-related reductions in serum T concentrations are associated with declines in spontaneous GH secretion in men (14,21,46). In addition, T administration increases GH-IGF-I axis activity in hypogonadal, but not eugonadal, men (5, 10, 13, 24 -26, 40, 47). Thus, it has been proposed that the age-related decline in T secretion in healthy men contributes to the observed reduction in GH secretion and that the hyposomatotropism acco...