Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Aging Cell. 2012 Oct;11(5):876-84. doi: 10.1111/j.1474-9726.2012.00852.x. Epub 2012 Aug 1.
Serum dehydroepiandrosterone (DHEA) concentrations decrease approximately 80% between ages 25 and 75 year. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine whether DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) as indices of arterial stiffness. A randomized, double-blind trial was conducted to study the effects of 50 mg day(-1) DHEA replacement on AI (n = 92) and PWV (n = 51) in women and men aged 65-75 year. Inflammatory cytokines and sex hormones were measured in fasting serum. AI decreased in the DHEA group, but not in the placebo group (difference between groups, -6 ± 2 AI units, P = 0.002). Pulse wave velocity also decreased (difference between groups, -3.5 ± 1.0 m s(-1), P = 0.001); however, after adjusting for baseline values, the between-group comparison became nonsignificant (P = 0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (tumor necrosis factor α and IL-6, P < 0.05) and correlated with increases in serum DHEAS (r = -0.31 and -0.37, respectively, P < 0.05). The reductions in AI also correlated with free testosterone index (r = -0.23, P = 0.03). In conclusion, DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore, the improvements observed in this study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.
血清脱氢表雄酮 (DHEA) 浓度在 25 岁至 75 岁之间下降约 80%。衰老还会导致动脉僵硬增加，这是心血管疾病 (CVD) 风险和死亡率的独立预测因素。因此，可以想象在老年人中补充 DHEA 可以降低动脉僵硬度。我们旨在确定在老年人中补充 DHEA 治疗是否可以降低颈动脉增强指数 (AI) 和颈股脉搏波速度 (PWV)，作为动脉僵硬的指标。进行了一项随机、双盲试验，以研究 50mg/天 DHEA 替代治疗对 65-75 岁女性和男性 AI（n=92）和 PWV（n=51）的影响。在空腹血清中测量了炎症细胞因子和性激素。AI 在 DHEA 组中降低，但在安慰剂组中没有降低（组间差异，-6±2 AI 单位，P=0.002）。脉搏波速度也降低（组间差异，-3.5±1.0 m/s，P=0.001）；然而，在校正基线值后，组间比较变得无统计学意义（P=0.20）。AI 和 PWV 的降低伴随着炎症细胞因子的降低（肿瘤坏死因子-α和 IL-6，P<0.05），并与血清 DHEAS 的增加相关（分别为 r=-0.31 和-0.37，P<0.05）。AI 的降低也与游离睾酮指数相关（r=-0.23，P=0.03）。总之，在老年男性和女性中补充 DHEA 可改善动脉僵硬度指标。动脉僵硬度随年龄增长而增加，是 CVD 的独立危险因素。因此，本研究观察到的改善表明，DHEA 替代治疗可能部分逆转动脉老化并降低 CVD 风险。
