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生长激素和睾酮给药对健康老年男性身体成分、身体机能、情绪、性功能、骨转换和肌肉基因表达指标的单一及联合作用。

Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men.

作者信息

Brill Kimberly T, Weltman Arthur L, Gentili Angela, Patrie James T, Fryburg David A, Hanks John B, Urban Randall J, Veldhuis Johannes D

机构信息

Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.

出版信息

J Clin Endocrinol Metab. 2002 Dec;87(12):5649-57. doi: 10.1210/jc.2002-020098.

Abstract

We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after a baseline (B) study in randomized order with an intervening 3-month washout: transdermal T patch (5.0 mg/daily); recombinant human GH (6.25 micro g/kg sc daily); and combined hormones (GHT). ANOVA with repeated measures was used to evaluate interventional effects. Integrated serum GH concentrations [mean (SEM)] were elevated comparably by GH and GHT: [B = 363 (55), GH = 1107 (120), T = 459 (131), and GHT = 1189 (46) micro g/liter.min; P < 0.0001]. Serum IGF-I concentrations also increased commensurately after GH and GHT: [B = 168 (14), GH = 285 (16), T = 192 (25), and GHT = 294 (25) micro g/liter; P < 0.0001]. GHT administration increased total estradiol: [B = 110 (20), GH = 106 (13), T = 129 (13), and GHT = 153 (17) pmol/liter; P < 0.02], and both T and GHT elevated free T: [B = 12 (2.1), GH = 11 (1.5), T = 22 (2.8), and GHT = 24 (2.5) pg/ml; P < 0.0001]. No significant changes occurred in strength, flexibility, percentage body fat, or sexual function and mood. However, fat-free mass increased under combined GHT exposure: [B = 55 (1.3), GH = 56 (1.1), T = 55 (1.5), GHT = 57 (1.7) kg; P < 0.03]. Balance improved in response to GH intervention (P < 0.05), as did 30-m walk time during T and GHT interventions [B = 6.6 (0.3), GH = 6.2 (0.7), T = 5.9 (0.3), GHT = 5.5 (0.3) sec; P = 0.04] and stair climb time for all three interventions [B = 32.2 (1.4), GH = 29.8 (1.2), T = 30.5 (1.4), and GHT = 29.9 (1.2) sec (P = 0.0034), wherein the effects of GH, T, and GHT were different from that of B]. Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration (P < 0.05, compared with B). Myostatin and androgen receptor gene expression were not affected. Serum osteocalcin increased in response to the GH and GHT interventions: [B = 4.8 (0.52), GH = 5.7 (0.54), T = 4.7 (0.33), and GHT = 5.5 (0.39); P <0.009]. There were no significant adverse events during 30 patient-months of intervention. We conclude that 1 month of GH and/or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression.

摘要

我们研究了生长激素(GH)和/或睾酮(T)给药对健康老年男性身体成分、运动能力、情绪、性功能、骨转换和肌肉基因表达的影响。10名男性[平均(标准误)年龄68(2.5)岁;身高171.5(2.4)厘米;体重80(3.0)千克]在完成基线(B)研究后,以随机顺序接受以下每项为期1个月的双盲干预,并间隔3个月洗脱期:经皮T贴片(每日5.0毫克);重组人生长激素(皮下注射每日6.25微克/千克);以及联合激素(GHT)。采用重复测量方差分析来评估干预效果。GH和GHT使血清GH综合浓度[平均(标准误)]同等升高:[B = 363(55),GH = 1107(120),T = 459(131),GHT = 1189(46)微克/升·分钟;P < 0.0001]。GH和GHT给药后血清IGF - I浓度也相应增加:[B = 168(14),GH = 285(16),T = 192(25),GHT = 294(25)微克/升;P < 0.0001]。GHT给药使总雌二醇增加:[B = 110(20),GH = 106(13),T = 129(13),GHT = 153(17)皮摩尔/升;P < 0.02],T和GHT均使游离T升高:[B = 12(2.1),GH = 11(1.5),T = 22(2.8),GHT = 24(2.5)皮克/毫升;P < 0.0001]。力量、柔韧性、体脂百分比、性功能和情绪均无显著变化。然而,在联合GHT暴露下无脂肪量增加:[B = 55(1.3),GH = 56(1.1),T = 55(1.5),GHT = 57(1.7)千克;P < 0.03]。GH干预后平衡能力改善(P < 0.05),T和GHT干预期间30米步行时间也改善[B = 6.6(0.3),GH = 6.2(0.7),T = 5.9(0.3),GHT = 5.5(0.3)秒;P = 0.04],所有三种干预的爬楼梯时间均改善[B = 32.2(1.4),GH = 29.8(1.2),T = 30.5(1.4),GHT = 29.9(1.2)秒(P = 0.0034),其中GH、T和GHT的效果与B不同]。GH给药期间肌肉IGF - I基因表达增加1.9倍,GHT给药期间增加2.3倍(与B相比,P < 0.05)。肌生成抑制素和雄激素受体基因表达未受影响。GH和GHT干预后血清骨钙素增加:[B = 4.8(0.52),GH = 5.7(0.54),T = 4.7(0.33),GHT = 5.5(0.39);P < 0.009]。在30个患者月的干预期间无显著不良事件。我们得出结论,为期1个月的GH和/或T给药可改善老年男性的某些平衡和身体运动能力指标,并增加肌肉IGF - I基因表达。

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