School of Medicine and Pharmacology (B.B.Y., S.A.P.C., G.J.H., L.F.), University of Western Australia, Perth, Western Australia 6009, Australia; Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle, Western Australia 6160, Australia; Western Australian Centre for Health and Ageing (H.A., O.P.A., L.F.), Centre for Medical Research, University of Western Australia, Perth, Western Australia 6009, Australia; PathWest Laboratory Medicine (S.A.P.C.), Fremantle and Royal Perth Hospitals, Perth, Western Australia 6009, Australia; ANZAC Research Institute (D.J.H.), University of Sydney, Sydney, New South Wales 2139, Australia; School of Psychiatry and Clinical Neurosciences (O.P.A.), University of Western Australia, Perth, Western Australia 6009, Australia; Vascular Biology Unit (J.G.), Queensland Research Centre for Peripheral Vascular Disease, School of Medicine, James Cook University, Townsville, Queensland 4811, Australia; and School of Surgery (P.E.N.), University of Western Australia, Perth, Western Australia 6009, Australia.
J Clin Endocrinol Metab. 2014 Jan;99(1):E9-18. doi: 10.1210/jc.2013-3272. Epub 2013 Dec 20.
Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined.
We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men.
Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia.
Plasma total T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage.
There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8±5.1 vs 13.2±4.8 nmol/L [mean±SD], P=.013), DHT (1.4±0.7 vs 1.5±0.7 nmol/L, P=.002), and E2 (71.6±29.3 vs 74.0±29.0 pmol/L, P=.022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR]=0.82, P=.033; Q3:Q1, HR=0.78, P=.010; Q4:Q1, HR=0.86, P>.05; DHT: Q3:Q1, HR=0.76, P=.003; Q4:Q1, HR=0.84, P>.05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR=0.58, P=.002; Q4:Q1, HR=0.69, P=.026). E2 was not associated with either all-cause or IHD mortality.
Optimal androgen levels are a biomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed.
随着年龄的增长，睾丸激素（T）水平下降，较低的 T 与老年男性死亡率的增加有关。然而，其代谢物二氢睾酮（DHT）和雌二醇（E2）与死亡率的关系还没有明确界定。
我们评估了 T、DHT 和 E2 与老年人全因和缺血性心脏病（IHD）死亡率的关系。
参与者为居住在澳大利亚珀斯的 70 至 89 岁的社区居民。
使用液相色谱-串联质谱法于 2001 年至 2004 年清晨采集的 3690 名男性的血浆总 T、DHT 和 E2 进行检测。通过数据链接确定 2010 年 12 月前的死亡情况。
共发生 974 例死亡（26.4%），其中 325 例死于 IHD。死亡的男性基线 T（12.8±5.1 与 13.2±4.8 nmol/L [均值±SD]，P=.013）、DHT（1.4±0.7 与 1.5±0.7 nmol/L，P=.002）和 E2（71.6±29.3 与 74.0±29.0 pmol/L，P=.022）水平较低。在考虑其他危险因素后，T 和 DHT 与全因死亡率相关（T：四分位数 [Q] Q2：Q1，调整后的危险比[HR]=0.82，P=.033；Q3：Q1，HR=0.78，P=.010；Q4：Q1，HR=0.86，P>.05；DHT：Q3：Q1，HR=0.76，P=.003；Q4：Q1，HR=0.84，P>.05）。较高的 DHT 与较低的 IHD 死亡率相关（Q3：Q1，HR=0.58，P=.002；Q4：Q1，HR=0.69，P=.026）。E2 与全因或 IHD 死亡率均无关。
最佳雄激素水平是生存的生物标志物，因为 T 和 DHT 水平处于中间范围的老年男性的全因死亡率最低，而 DHT 较高的男性的 IHD 死亡率较低。需要进一步研究这些关联的生物学基础，包括 T 补充的随机试验。
