Brill Kimberly T, Weltman Arthur L, Gentili Angela, Patrie James T, Fryburg David A, Hanks John B, Urban Randall J, Veldhuis Johannes D
Department of Internal Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
J Clin Endocrinol Metab. 2002 Dec;87(12):5649-57. doi: 10.1210/jc.2002-020098.
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.
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。