Agledahl Ingvild, Brodin Ellen, Svartberg Johan, Hansen John-Bjarne
Center for Atherothrombotic Research in Tromsø (CART), Department of Medicine, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway.
Thromb Haemost. 2009 Mar;101(3):471-7.
Low testosterone levels in men have been associated with cardiovascular risk factors, some prothrombotic factors, and lately also an increased risk of both cardiovascular disease and all-cause mortality. Experimental studies have shown increased synthesis and release of tissue factor pathway inhibitor (TFPI) by physiological levels of testosterone in endothelial cells. Our hypothesis was that elderly men with low testosterone levels would have lower plasma levels of plasma free TFPI with subsequent increased thrombin generation. Elderly men with low (n = 37) and normal (n = 41) testosterone levels were recruited from a general population, and tissue factor (TF)-induced thrombin generation ex vivo and plasma free TFPI Ag were measured. Elderly men with low testosterone levels had lower plasma free TFPI Ag (10.9 +/- 2.3 ng/ml vs. 12.3 +/- 3.0 ng/ml, p = 0.027) and shorter initiation phase of TF-induced coagulation assessed by lag-time (5.1 +/- 1.0 min vs. 5.7 +/- 1.3, p = 0.039). The differences between groups remained significant and were strengthened after adjustment for waist circumference and other cardiovascular risk factors. Lag-time increased linearly across quartiles of plasma free TFPI Ag (p<0.001). Multiple regression analysis revealed that total and free testosterone were independent predictors of plasma free TFPI Ag. Our findings suggest that low testosterone levels in elderly men is associated with low plasma free TFPI Ag and subsequent shortened initiation phase of TF-induced coagulation.
男性睾酮水平低与心血管危险因素、一些促血栓形成因素有关，最近还与心血管疾病和全因死亡率风险增加有关。实验研究表明，内皮细胞中生理水平的睾酮可增加组织因子途径抑制剂（TFPI）的合成和释放。我们的假设是，睾酮水平低的老年男性血浆游离TFPI水平会更低，随后凝血酶生成增加。从普通人群中招募了睾酮水平低（n = 37）和正常（n = 41）的老年男性，测量了体外组织因子（TF）诱导的凝血酶生成和血浆游离TFPI抗原。睾酮水平低的老年男性血浆游离TFPI抗原水平更低（10.9±2.3 ng/ml对12.3±3.0 ng/ml，p = 0.027），通过滞后时间评估的TF诱导凝血的起始阶段更短（5.1±1.0分钟对5.7±1.3，p = 0.039）。调整腰围和其他心血管危险因素后，两组之间的差异仍然显著且有所增强。滞后时间随血浆游离TFPI抗原四分位数呈线性增加（p<0.001）。多元回归分析显示，总睾酮和游离睾酮是血浆游离TFPI抗原的独立预测因子。我们的研究结果表明，老年男性睾酮水平低与血浆游离TFPI抗原水平低以及随后TF诱导凝血的起始阶段缩短有关。
