The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men
The Effects of Injected Testosterone Dose and Age on the Conversion of Testosterone to Estradiol and Dihydrotestosterone in Young and Older Men
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DOI：
10.1210/jc.2010-0102
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Bhasin, Shalender
中科院分区：
文献类型：
--
作者：
Lakshman, Kishore M.;Kaplan, Beth;Bhasin, Shalender
背景：在睾酮（T）治疗期间，T部分转化为17 β-雌二醇（E-2）和5 α-双氢睾酮（DHT）。年龄、睾酮剂量和身体成分对总的和游离的E-2和DHT水平的影响尚不清楚。目的：我们评估了年轻和老年男性中E-2和DHT水平对分级剂量庚酸睾酮反应的年龄和剂量相关差异。五十一岁的年轻人（19-35岁）和52岁以上（年龄59-75岁）男性完成治疗，每月注射GnRH激动剂加随机分配的每周剂量的庚酸睾酮结果：在睾酮给药期间，无论是年轻男性还是老年男性，总E-2和游离E-2水平均呈剂量依赖性增加（剂量效应，P < 0.001）。总的和游离E-2水平和E-2：T比率在T给药期间，老年男性高于年轻男性，但在调整睾酮水平，脂肪质量百分比和SHBG后，游离E-2和游离E-2：T比率的年龄相关差异并不显著。双氢睾酮水平和双氢睾酮：T比率与剂量有关，但在年轻和老年男性之间没有差异。游离激素数据的机制建模显示，T到E-2和DHT的转化都符合饱和Michaelis-Menten动力学。估计芳香酶的体内Km值为1.83 nM，5 α-还原酶为3.35 nM，与年龄无关。E-2的V-max参数是40%以上，在老年男性比年轻男性，但V-max的DHT是没有显着不同年龄组之间。结论：在IM睾酮管理，E-2和DHT水平表现出饱和的增加与剂量。老年男性的全身芳香化率较高，部分与他们较高的脂肪量百分比，SHBG和睾酮水平有关。（临床内分泌代谢杂志95：3955-3964，2010）
Background: During testosterone (T) therapy, T is partly converted to 17 beta-estradiol (E-2) and 5 alpha-dihydrotestosterone (DHT). Effects of age, testosterone dose, and body composition on total and free E-2 and DHT levels are unknown.Objective: We evaluated age and dose-related differences in E-2 and DHT levels in response to graded doses of testosterone enanthate in young and older men.Methods: Fifty-one young (aged 19-35 yr) and 52 older (aged 59-75 yr) men completed treatment with monthly injections of a GnRH agonist plus randomly assigned weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg) for 5 months.Results: During testosterone administration, total and free E-2 levels increased dose-dependently (dose effect, P < 0.001) in both young and older men. Total and free E-2 levels and E-2: T ratios during T administration were higher in older than young men, but age-related differences in free E-2 and free E-2: T ratios were not significant after adjusting for testosterone levels, percentage fat mass, and SHBG. DHT levels and DHT: T ratios were dose-related but did not differ between young and older men. Mechanistic modeling of free hormone data revealed that the conversions of T to E-2 and DHT were both consistent with saturable Michaelis-Menten kinetics. The in vivo K-m values were estimated to be 1.83 nM for aromatase and 3.35 nM for 5 alpha-reductase, independent of age. The V-max parameter for E-2 was 40% higher in older men than younger men, but V-max for DHT was not significantly different between age groups.Conclusions: During im testosterone administration, E-2 and DHT levels exhibit saturable increases with dose. The rate of whole body aromatization is higher in older men, partly related to their higher percentage fat mass, SHBG, and testosterone levels. (J Clin Endocrinol Metab 95: 3955-3964, 2010)