Dias Jenny Pena, Veldhuis Johannes D, Carlson Olga, Shardell Michelle, Chia Chee W, Melvin Denise, Egan Josephine M, Basaria Shehzad
Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 21225.
Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, MN, United States.
Metabolism. 2017 Apr;69:143-147. doi: 10.1016/j.metabol.2017.01.025. Epub 2017 Jan 19.
Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men.
This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone.
Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months.
At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059).
In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels.
生长激素是生长和身体成分的主要调节因子。生长激素的脉冲式分泌随年龄呈指数下降。越来越多的老年男性因年龄相关的低睾酮水平而接受睾酮替代治疗。已证明给予睾酮可刺激生长激素分泌。然而，关于睾酮芳香化转化为雌二醇对老年男性生长激素脉冲性及其对胰岛素样生长因子-1（IGF-1）的影响知之甚少。
这项随机对照概念验证试验研究了睾酮和雌二醇对低睾酮老年男性生长激素脉冲性和IGF-1的相对影响。
37名年龄≥65岁、总睾酮<350ng/dL的男性被随机分为三组，分别每日使用5g经皮睾酮凝胶（TT）、1mg口服芳香化酶抑制剂（AI）或安慰剂，持续12个月。主要结局是在基线和3个月时对包括基础分泌模式和熵分泌模式在内的脉冲性进行去卷积和近似熵分析。次要结局包括在基线、3个月和6个月时评估的IGF-1。
3个月时，三组的平均生长激素和IGF-1水平相似。6个月时，与安慰剂组相比，TT组的IGF-1显著增加，增量为15.3±10.3ng/ml（P=0.03）。与安慰剂组相比，两个干预组的生长激素脉冲频率均显著增加（TT组，P=0.04；AI组，P=0.05）。与安慰剂组相比，TT组的生长激素分泌爆发模式（持续时间）显著缩短（P=0.0018），而AI组保持不变（P=0.059）。
在老年男性中，睾酮增加生长激素脉冲频率，而芳香化转化为雌二醇参与IGF-1水平的升高。
