Bhasin Shalender, Woodhouse Linda, Casaburi Richard, Singh Atam B, Mac Ricky Phong, Lee Martin, Yarasheski Kevin E, Sinha-Hikim Indrani, Dzekov Connie, Dzekov Jeanne, Magliano Lynne, Storer Thomas W
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, University of California, Los Angeles, CA 90059, USA.
J Clin Endocrinol Metab. 2005 Feb;90(2):678-88. doi: 10.1210/jc.2004-1184. Epub 2004 Nov 23.
Although testosterone levels and muscle mass decline with age, many older men have serum testosterone level in the normal range, leading to speculation about whether older men are less sensitive to testosterone. We determined the responsiveness of androgen-dependent outcomes to graded testosterone doses in older men and compared it to that in young men. The participants in this randomized, double-blind trial were 60 ambulatory, healthy, older men, 60-75 yr of age, who had normal serum testosterone levels. Their responses to graded doses of testosterone were compared with previous data in 61 men, 19-35 yr old. The participants received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate weekly for 20 wk. Fat-free mass, fat mass, muscle strength, sexual function, mood, visuospatial cognition, hormone levels, and safety measures were evaluated before, during, and after treatment. Of 60 older men who were randomized, 52 completed the study. After adjusting for testosterone dose, changes in serum total testosterone (change, -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, -3.6, +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) levels were dose-related in older men and significantly greater in older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2, +5.6, and +7.3 kg, respectively, in five ascending dose groups) and muscle strength in older men were correlated with testosterone dose and concentrations and were not significantly different in young and older men. Changes in fat mass correlated inversely with testosterone dose (r = -0.54; P < 0.001) and were significantly different in young vs. older men (P < 0.0001); young men receiving 25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and visuospatial cognition did not change significantly in either group. Frequency of hematocrit greater than 54%, leg edema, and prostate events were numerically higher in older men than in young men. Older men are as responsive as young men to testosterone's anabolic effects; however, older men have lower testosterone clearance rates, higher increments in hemoglobin, and a higher frequency of adverse effects. Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events, and significant gains in fat-free mass and muscle strength.
尽管睾酮水平和肌肉量会随着年龄增长而下降,但许多老年男性的血清睾酮水平仍在正常范围内,这引发了关于老年男性对睾酮是否不太敏感的猜测。我们测定了老年男性雄激素依赖结果对不同剂量睾酮的反应性,并将其与年轻男性进行比较。这项随机、双盲试验的参与者为60名60至75岁能自由活动的健康老年男性,他们的血清睾酮水平正常。将他们对不同剂量睾酮的反应与61名19至35岁男性的先前数据进行比较。参与者接受长效促性腺激素释放激素(GnRH)激动剂以抑制内源性睾酮的产生,并每周分别接受25、50、125、300或600毫克庚酸睾酮,共20周。在治疗前、治疗期间和治疗后评估无脂肪量、脂肪量、肌肉力量、性功能、情绪、视觉空间认知、激素水平和安全指标。在随机分组的60名老年男性中,52名完成了研究。在调整睾酮剂量后,老年男性血清总睾酮水平的变化(每周25、50、125、300和600毫克时,变化分别为-6.8、-1.9、+16.1、+49.5和+101.9纳摩尔/升)和血红蛋白水平的变化(每周25、50、125、300和600毫克时,变化分别为-3.6、+9.9、+20.9、+12.6和+29.4克/升)与剂量相关,且老年男性的变化显著大于年轻男性(均P<0.0001)。老年男性无脂肪量的变化(五个递增剂量组分别为-0.3、+1.7、+4.2、+5.6和+7.3千克)和肌肉力量与睾酮剂量和浓度相关,在年轻男性和老年男性中无显著差异。脂肪量的变化与睾酮剂量呈负相关(r=-0.54;P<0.001),在年轻男性和老年男性中差异显著(P<0.0001);接受25毫克和50毫克剂量的年轻男性比老年男性增加的脂肪量更多(P<0.0001)。两组的情绪和视觉空间认知均无显著变化。老年男性血细胞比容大于54%、腿部水肿和前列腺事件的发生率在数值上高于年轻男性。老年男性对睾酮的合成代谢作用与年轻男性一样敏感;然而,老年男性的睾酮清除率较低,血红蛋白升高幅度较大,不良反应发生率较高。尽管给予超生理剂量的睾酮可使老年男性的肌肉量和力量显著增加,但这些高剂量与高不良反应发生率相关。给予与高正常睾酮水平、低不良事件发生率以及无脂肪量和肌肉力量显著增加相关的睾酮剂量(125毫克)可实现最佳权衡。