Long-acting testosterone injections improved exercise capacity and insulin sensitivity in elderly men with heart failure, Dr. Giuseppe Caminiti of the Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana in Rome, and colleagues reported in an article published online Aug. 24 in the Journal of the American College of Cardiology.
“The increase in functional capacity and muscle strength is related to the increase in plasma levels of testosterone and not related to changes in left ventricular function,” noted the authors (J. Am. Coll. Cardiol. 2009 Aug. 24 [doi:10.1016/j.jacc.2009.04.078]).
“Testosterone deficiency, decreased insulin sensitivity, and impaired muscle performance might represent a pathogenic loop” in the progression of heart failure as a syndrome which involves not only the heart and circulation but also encompasses “other organs and organ systems such as the skeletal muscle, the lungs, and the brain,” Dr. Pål Aukrust of Oslo University Hospital, wrote in an accompanying editorial.
The study randomized 70 elderly patients, median age 70 years, with stable chronic heart failure (CHF) to either long-acting testosterone undecanoate (1,000 mg), or placebo intramuscular injections given at baseline, 6, and 12 weeks, in addition to optimal medical therapy.
Echocardiographic examination, muscle strength assessment, and cardiopulmonary exercise testing, as well as a 6-minute walk test (6MWT) were performed at the same three time points. Blood samples were taken at these time points to measure testosterone and insulin, among other parameters. Baroreceptor cardiac reflex sensitivity (BRS) was assessed at the start and end of the study.
At baseline, 21 patients in the testosterone group and 9 in the placebo group had total and free testosterone levels below the normal range—a phenomenon that has been well documented in CHF patients. Baseline testosterone levels correlated with peak oxygen consumption (VO2), distance reached in the 6MWT, and isometric strength.
As expected, testosterone levels normalized in the treatment group but not the placebo group, and improved testosterone levels correlated with improved VO2 and quadriceps maximal voluntary contraction. Insulin resistance, as estimated by the homeostasis model assessment, was significantly reduced in the treated group, from 2.6 to 1.8, but not in the placebo group (from 2.5 to 2.6). BRS improved with treatment but not with placebo. There were no significant changes in left ventricular function in either group.
The authors suggested that testosterone’s ability to improve such extra-cardiac problems of muscle performance and glucose metabolism might not only improve the symptoms but possibly the pathophysiology and worsening of heart failure syndrome.
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意大利罗马圣拉斐尔皮萨纳住院病人治疗科学研究所(IRCCS)Giuseppe Caminiti博士及其同事在8月24日《美国心脏病学会杂志》(Journal of the American College of Cardiology)网络版刊出的一篇文章指出：注射长效睾酮可改善老年男性心衰患者的运动耐量和胰岛素敏感性。
作者指出：“心脏功能容量和心肌肌力的增加与血浆睾酮水平提高相关，而与左心室功能改变无关。”(J. Am. Coll. Cardiol. 2009 Aug. 24 [doi:10.1016/j.jacc.2009.04.078])
挪威奥斯陆大学医院Pål Aukrust博士在所附的编者按中写到，心衰进展中发生的“睾酮缺乏、胰岛素敏感性降低和肌肉损伤可能互为病因，”心衰进展作为一种综合征不仅包括心脏和血液循环，还包括“其他器官和器官系统如骨骼肌、肺和大脑。”
该研究将70例平均年龄在70岁的稳定性慢性心力衰竭(CHF)老年患者随机分到肌注长效十一烷酸睾酮组(1,000 mg)或安慰剂组，除采用最佳药物治疗的患者外，其余患者分别在0、6、12周给药。
在上述的3个时相点，进行超声心动图检查、肌力评估、运动心肺功能测试以及6 min步行试验(6MWT)，并抽血检查睾酮和胰岛素水平等部分指标。在研究开始和结束时，对心脏压力反射敏感性(baroreceptor cardiac reflex sensitivity，BRS)进行评估。
睾酮组和安慰剂组各有21例和9例患者的基线总睾酮和游离睾酮水平低于正常范围，已证明CHF患者同样存在类似情况。基线睾酮水平与峰值氧消耗(VO2)、6MWT步行距离及等速肌力相关。
正如所预期的，治疗组的睾酮水平恢复正常，而安慰剂组并未恢复，而且睾酮水平的改善与VO2升高及股四头肌最大随意等长收缩(MVC)相关。正如稳态模型评估法(HOMA)所预计的那样，治疗组的胰岛素抵抗(从2.6降为1.8)较安慰剂组(从2.5到2.6)显着下降。治疗组BSR得到改善，而安慰剂组并无改变。两组的左心室功能均无显著变化。
作者认为，睾酮具有改善肌力和糖代谢等心外症状的功效，不但能改善症状，还可能扭转心衰综合征的恶化趋势和病理生理学过程。
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