Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels
Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels
复制标题
DOI：
10.1093/gerona/56.5.m266
复制
发表时间：
2001-05-01
影响因子：
5.1
通讯作者：
Raisz, LG
中科院分区：
文献类型：
--
作者：
Kenny, AM;Prestwood, KM;Raisz, LG
背景。很大一部分65岁以上男性的生物可利用睾酮水平低于年轻成年男性的参考范围。这对肌肉骨骼健康的影响以及补充睾酮对这一群体功能改善的潜力需要调查。67名生物可利用睾酮水平低于4.44 nmol/l（成人正常范围下限）的男性（平均年龄76±4岁，范围65-87）随机接受透皮睾酮（每天2个2.5 mg贴片）或安慰剂贴片，为期1年。结果测量包括性激素（睾酮、生物可利用睾酮、性激素结合球蛋白[SHBG]、雌二醇和雌酮）、骨密度（骨密度、股骨颈、沃德三角区、粗隆、腰椎和全身）、骨转换标志物、下肢肌肉力量、体脂百分比、瘦体重、血红蛋白、红细胞压积、前列腺症状和前列腺特异性抗原（PSA）水平。23名男性（34%）退出研究；44名男性完成了试验。在这些男性中，睾酮组的生物可利用睾酮水平在12个月时从3.2 +/- 1.2 nmol/l （SD）增加到5.6 +/- 3.5 nmol/l (p < 0.002)，而对照组没有发生变化。尽管两组的雌二醇水平都没有变化，但睾酮组的雌二醇水平升高（103 +/- 26 pmol/l至117 +/- 33 pmol/l； p < 0.017）。睾酮组股骨颈骨密度增加0.3%，而对照组在12个月内下降1.6% （p = 0.015）。两组的骨转换指标均未见明显变化。与基线评分相比，两组患者在12个月时肌肉力量均有所改善。睾酮组肌力增加38% (p = 0.017)，对照组肌力增加27% (p = 0.06)，两组间差异无统计学意义。在睾酮组，体脂从26.3 +/- 5.8%下降到24.6 +/- 6.5% (p = .001)，瘦体重从56.2 +/- 5.3 kg增加到57.2 +/- 5.1 kg (p = .001)，而体重没有变化。接受睾酮治疗的男性PSA从2.0 +/- 1.4马克杯/升增加到2.6 +/- 1.8马克杯/升（p = 0.04），而接受安慰剂治疗的男性PSA从1.9 +/- 1.0马克杯/升增加到2.2 +/- 1.5马克杯/升（p = 0.09）。两组间血红蛋白、红细胞压积、良性前列腺增生的症状或体征或PSA水平均无显著差异。经皮睾酮（5mg /d）可防止股骨颈骨质流失，减少体脂，增加65岁以上生物可利用睾酮水平低的健康男性的瘦体重。此外，睾酮组和安慰剂组都表现出下肢肌肉力量的增加，可能是由于维生素d的有益作用。睾酮确实导致PSA水平适度增加，但没有导致前列腺增生的体征或症状改变。
Background. A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men. The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation.Methods. Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 4.44 nmol/l (Lower limit for adult normal range) were randomized to receive transdermal testosterone (two 2.5-mg patches per day) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex-hormone binding globulin [SHBG], estradiol, and estrone), bone mineral density (BMD; femoral neck, Ward's triangle, trochanter, lumbar spine, and total body), bone turnover markers, lower extremity muscle strength, percent body fat, lean body mass, hemoglobin, hematocrit, prostate symptoms, and prostate specific antigen (PSA) levels.Results. Twenty-three men (34%) withdrew from the study; 44 men completed the trial. In these men, bioavailable testosterone levels increased from 3.2 +/- 1.2 nmol/l (SD) to 5.6 +/- 3.5 nmol/l (p < .002) at 12 months in the testosterone group, whereas no change occurred in the control group. Although there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (103 +/- 26 pmol/l to 117 +/- 33 pmol/l; p < .017). The testosterone group had a 0.3% gain in femoral neck BMD, whereas the control group lost 1.6% over 12 months (p = .015). No significant changes were seen in markers of bone turnover in either group. Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores. Strength increased 38% (p = .017) in the testosterone group and 27% in the control group (p = .06), with no statistical difference between the groups. In the testosterone group, body fat decreased from 26.3 +/- 5.8% to 24.6 +/- 6.5% (p = .001), and lean body mass increased from 56.2 +/- 5.3 kg to 57.2 +/- 5.1 kg (p = .001), whereas body mass did not change. Men receiving testosterone had an increase in PSA from 2.0 +/- 1.4 mug/l to 2.6 +/- 1.8 mug/l (p = .04), whereas men receiving placebo had an increase in PSA from 1.9 +/- 1.0 mug/l to 2.2 +/- 1.5 mug/l(p = .09). No significant differences between groups were seen in hemoglobin, hematocrit, symptoms or signs of benign prostate hyperplasia, or PSA levels.Conclusions. Transdermal testosterone (5 mg/d) prevented bone loss at the femoral neck, decreased body fat, and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels. In addition, both testosterone and placebo groups demonstrated gains in lower extremity muscle strength, possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but resulted in no change in signs or symptoms of prostate hyperplasia.