Effects of graded doses of testosterone on erythropoiesis in healthy young and older men
Effects of graded doses of testosterone on erythropoiesis in healthy young and older men
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DOI：
10.1210/jc.2007-1692
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发表时间：
2008-03-01
影响因子：
5.8
通讯作者：
Bhasin, Shalender
中科院分区：
文献类型：
--
作者：
Coviello, Andrea D.;Kaplan, Beth;Bhasin, Shalender
背景：红细胞增多症是睾酮治疗的一种剂量限制性的不良反应，尤其是在老年男性中。目的：我们的目标是比较年轻和老年男性中与剂量相关的血红蛋白和红细胞压积的变化，并确定是否可以用促红细胞生成素和可溶性转铁蛋白受体(STfR)水平的变化来解释与年龄相关的红细胞生成反应的差异。设计：我们对每月接受长效GnRH激动剂和每周五剂睾酮(25，50,125,300,300,100)的睾酮原酸酯(25，50,125,300,300)的年轻和老年男性进行二次分析。参与者：60名60-75岁的老年男性和61名19-35岁的年轻男性。结果：结果测量包括红细胞压积和血红蛋白、血清促红细胞生成素和sTfR水平。结果：年轻和老年男性的血红蛋白和红细胞压积显著增加，呈线性，呈剂量依赖关系，对分级剂量的睾酮(P<；0.0001)。在老年男性中，血红蛋白和红细胞压积的增加明显大于年轻男性。无论是年轻男性还是老年男性，不同组别的促红细胞生成素或sTfR水平与基线相比没有显著差异。促红细胞生成素或sTfR水平的变化与总或游离睾酮水平的变化没有显著相关性。结论：睾酮对男性红细胞生成的刺激作用具有剂量依赖性，在老年男性中更为明显。睾酮诱导的血红蛋白和红细胞压积的升高以及与年龄相关的对睾酮治疗反应的差异可能是由促红细胞生成素和sTfR以外的因素介导的。
Context: Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men.Objective: Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels.Design: We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate ( 25, 50, 125, 300, or 600 mg im) for 20 wk.Setting: The study took place at a General Clinical Research Center.Participants: Participants included 60 older men aged 60-75 yr and 61 young men aged 19-35 yr.Outcome Measures: Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels.Results: Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P < 0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels.Conclusions: Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.