Maggio Marcello, Lauretani Fulvio, Ceda Gian Paolo, Bandinelli Stefania, Ling Shari M, Metter E Jeffrey, Artoni Andrea, Carassale Laura, Cazzato Anna, Ceresini Graziano, Guralnik Jack M, Basaria Shehzad, Valenti Giorgio, Ferrucci Luigi
National Institute on Aging, National Institutes of Health, NIA Clinical Research Branch at Harbor Hospital, 3001 S Hanover Street, Baltimore, MD 21225, USA.
Arch Intern Med. 2007 Nov 12;167(20):2249-54. doi: 10.1001/archinte.167.20.2249.
Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders.
Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 microg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis.
Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88-2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12-4.68), respectively (test for trend, P <.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P <.001).
Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons.
男性衰老的特征是合成代谢激素水平逐渐下降，如睾酮、胰岛素样生长因子1（IGF-1）和硫酸脱氢表雄酮（DHEA-S）。我们假设，在老年男性中，生物可利用睾酮、IGF-1和DHEA-S分泌随年龄增长而出现的平行下降与较高的死亡率相关，且不受潜在混杂因素影响。
在参与基安蒂地区衰老研究（InCHIANTI）的410名65岁及以上男性的代表性样本中，评估了睾酮、IGF-1、DHEA-S和人口统计学特征。在6年随访期间，共有126名男性死亡。生物可利用睾酮最低四分位数定义的阈值为70 ng/dL（换算为每升纳摩尔数，乘以0.0347），总IGF-1为63.� ng/mL（换算为每升纳摩尔数，乘以0.131），DHEA-S为50 μg/dL（换算为每升微摩尔数，乘以0.027）。男性被分为4组：最低四分位数中无激素（参照组）以及最低四分位数中有1种、2种和3种激素。分析中使用了经混杂因素调整的Kaplan-Meier生存曲线和Cox比例风险模型。
与3种激素水平均高于最低四分位数的男性相比，1种、2种和3种激素失调的男性的死亡风险比分别为1.47（95%置信区间[CI]，0.88 - 2.44）、1.85（95% CI，1.04 - 3.30）和2.29（95% CI，1.12 - 4.68）（趋势检验，P <.001）。在完全调整分析中，只有3种合成代谢激素缺乏的男性死亡率显著增加（风险比，2.44；95% CI，1.09 - 5.46（趋势检验，P <.001）。
合成代谢激素水平随年龄增长而下降是老年男性死亡率的一个强有力的独立预测因素。存在多种激素缺乏而非单一合成代谢激素缺乏是老年人健康状况的一个可靠生物标志物。
