Malkin Chris J, Pugh Peter J, West John N, van Beek Edwin J R, Jones T Hugh, Channer Kevin S
Department of Cardiology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
Eur Heart J. 2006 Jan;27(1):57-64. doi: 10.1093/eurheartj/ehi443. Epub 2005 Aug 10.
Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism, vasodilator incapacity, and loss of skeletal muscle bulk and function. In men, androgens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties.
We conducted a randomized, double-blind, placebo-controlled parallel trial of testosterone replacement therapy (5 mg Androderm) at physiological doses in 76 men (mean+/-SD, age 64+/-9.9) with heart failure (ejection fraction 32.5+/-11%) over a maximum follow-up period of 12 months. The primary endpoint was functional capacity as assessed by the incremental shuttle walk test (ISWT). At baseline, 18 (24%) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT (r=0.3, P=0.01). Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period (mean change +25+/-15 m) corresponding to a 15+/-11% improvement from baseline (P=0.006 ANOVA). Symptoms improved by at least one functional class on testosterone in 13 (35%) vs. 3 (8%) on placebo (P=0.01). No significant changes were found in handgrip strength, skeletal muscle bulk by cross-sectional computed tomography, or in tumour necrosis factor levels. Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients.
Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure.
慢性心力衰竭与适应不良且持续的神经激素和促炎细胞因子激活有关，会导致有利于分解代谢的代谢转变、血管舒张功能丧失以及骨骼肌量和功能的丧失。在男性中，雄激素是合成代谢功能和体力的重要决定因素，还具有抗炎和血管舒张特性。
我们对76名心力衰竭（射血分数32.5±11%）男性（平均±标准差，年龄64±9.9岁）进行了一项随机、双盲、安慰剂对照平行试验，给予生理剂量的睾酮替代疗法（5mg安特尔），最长随访期为12个月。主要终点是通过递增往返步行试验（ISWT）评估的功能能力。基线时，18名（24%）患者的血清睾酮低于正常范围，且生物可利用睾酮与初始ISWT步行距离相关（r=0.3，P=0.01）。与安慰剂相比，在整个研究期间，睾酮治疗使运动能力显著提高（平均变化+25±15m），相对于基线提高了15±11%（方差分析，P=0.006）。接受睾酮治疗的患者中有13名（35%）症状改善至少一个功能级别，而接受安慰剂治疗的为3名（8%）（P=0.01）。握力、横断面计算机断层扫描测量的骨骼肌量或肿瘤坏死因子水平均未发现显著变化。睾酮治疗是安全的，没有过多不良事件，尽管研究患者对贴片制剂耐受性不佳。
睾酮替代疗法可改善中度严重心力衰竭男性的功能能力和症状。
