Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lancet Diabetes Endocrinol. 2018 Nov;6(11):879-890. doi: 10.1016/S2213-8587(18)30171-2.
The Physical Function Trial (PFT) was one of seven Testosterone Trials (TTrials), the aim of which was to assess the effect of testosterone on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) in older men with low testosterone concentrations, self-reported mobility limitation, and walking speed of less than 1·2 m/s. Using data from the PFT and the overall TTrials study population, we also aimed to identify whether the effect of testosterone on mobility differed according to baseline walking speed, mobility limitation, or other participant-level factors.
The TTrials included 790 men aged 65 years or older and with an average of two total testosterone concentrations below 275 ng/dL (9·5 nmol/L), of whom 390 had mobility limitation and a walking speed below 1·2 m/s and were enrolled in the PFT. Participants were assigned (by minimisation method) to 1% testosterone gel or placebo gel daily for 12 months, with participants and study staff masked to intervention allocation. The primary outcome of the PFT was an increase in 6 min walk test (6MWT) distance of 50 m or more. Here we report data for absolute change in 6MWT distance and physical component of Short Form-36 (PF10), and for PGIC and falls. Data are reported for men enrolled in the PFT and those who were not, and for all men in TTrials; data are also reported according to baseline walking speed and mobility limitation. Analyses were done in a modified intention-to-treat population in all patients who were allocated to treatment, had a baseline assessment, and at least one post-intervention assessment. The TTrials are registered with ClinicalTrials.gov, number NCT00799617.
The TTrials took place between April 28, 2011 and June 16, 2014. Of 790 TTrials participants, 395 were allocated to testosterone and 395 to placebo; of the 390 participants enrolled in the PFT, 193 were allocated to testosterone and 197 to placebo. As reported previously, 6MWT distance improved significantly more in the testosterone than in the placebo group among all men in the TTrials, but not in those who were enrolled in the PFT; among TTrials participants not enrolled in the PFT, 6MWT distance improved with a treatment effect of 8·9 m (95% CI 2·2-15·6; p=0·010). As reported previously, PF10 improved more in the testosterone group than in the placebo group in all men in TTrials and in men enrolled in the PFT; among those not enrolled in the PFT, PF10 improved with an effect size of 4·0 (1·5-6·5; p=0·0019). Testosterone-treated men with baseline walking speed of 1·2 m/s or higher had significantly greater improvements in 6MWT distance (treatment effect 14·2 m, 6·5-21·9; p=0·0004) and PF10 (4·9, 2·2-7·7; p=0·0005) than placebo-treated men. Testosterone-treated men reporting mobility limitation showed significantly more improvement in 6MWT distance (7·6 m, 1·0-14·1; p=0·0237) and PF10 (3·6, 1·3-5·9; p=0·0018) than placebo-treated men. Men in the testosterone group were more likely to perceive improvement in their walking ability (PGIC) than men in the placebo group, both for men enrolled in the PFT (effect size 2·21, 1·35-3·63; p=0·0018) and those not enrolled in the PFT (3·01, 1·61-5·63; p=0·0006). Changes in 6MWT distance were significantly associated with changes in testosterone, free testosterone, dihydrotestosterone, and haemoglobin concentrations. Fall frequency during the intervention period was identical in the two treatment groups of the TTrials (103 [27%] of 380 analysed in both groups had at least one fall).
Testosterone therapy consistently improved self-reported walking ability, modestly improved 6MWT distance (across all TTtrials participants), but did not affect falls. The effect of testosterone on mobility measures were related to baseline gait speed and self-reported mobility limitation, and changes in testosterone and haemoglobin concentrations.
US National Institute on Aging and AbbVie.
体能试验（PFT）是 Testosterone Trials（TTrials）的七个试验之一，其目的是评估睾酮对移动能力、自我报告的身体功能、跌倒和患者整体印象变化（PGIC）的影响，对象是睾酮浓度低、自我报告的移动能力受限且行走速度低于 1.2 m/s 的老年男性。使用 PFT 和整个 TTrials 研究人群的数据，我们还旨在确定睾酮对移动能力的影响是否因基线行走速度、移动能力受限或其他参与者水平因素而不同。
TTrials 纳入了 790 名年龄在 65 岁及以上、平均总睾酮浓度低于 275ng/dL（9.5nmol/L）的男性，其中 390 名有移动能力受限和行走速度低于 1.2 m/s，并且被纳入 PFT。参与者（通过最小化方法）被分配到每天接受 1%睾酮凝胶或安慰剂凝胶治疗 12 个月，参与者和研究人员对干预分配情况不知情。PFT 的主要结局是 6 分钟步行测试（6MWT）距离增加 50 米或更多。这里我们报告了 6MWT 距离和简短表格-36（PF10）的身体成分的绝对变化，以及 PGIC 和跌倒的情况。报告了参加 PFT 和未参加 PFT 的男性的数据，以及 TTrials 中的所有男性的数据；还根据基线行走速度和移动能力受限报告了数据。在所有接受治疗、进行基线评估和至少一次干预后评估的患者中，按照改良意向治疗人群进行了分析。TTrials 在 ClinicalTrials.gov 上注册，编号为 NCT00799617。
TTrials 于 2011 年 4 月 28 日至 2014 年 6 月 16 日进行。790 名 TTrials 参与者中，395 名被分配到睾酮组，395 名被分配到安慰剂组；在被纳入 PFT 的 390 名参与者中，193 名被分配到睾酮组，197 名被分配到安慰剂组。正如之前报道的那样，在所有 TTrials 男性中，6MWT 距离在睾酮组显著优于安慰剂组，但在参加 PFT 的男性中没有；在未参加 PFT 的 TTrials 参与者中，6MWT 距离改善，治疗效果为 8.9 m（95%CI 2.2-15.6；p=0.010）。正如之前报道的那样，在所有 TTrials 男性和参加 PFT 的男性中，PF10 在睾酮组的改善显著优于安慰剂组；在未参加 PFT 的参与者中，PF10 的改善效果为 4.0（1.5-6.5；p=0.0019）。基线行走速度为 1.2 m/s 或更高的睾酮治疗男性在 6MWT 距离（治疗效果 14.2 m，6.5-21.9；p=0.0004）和 PF10（4.9，2.2-7.7；p=0.0005）方面的改善显著大于安慰剂治疗男性。报告有移动能力受限的睾酮治疗男性在 6MWT 距离（7.6 m，1.0-14.1；p=0.0237）和 PF10（3.6，1.3-5.9；p=0.0018）方面的改善显著大于安慰剂治疗男性。与安慰剂组相比，睾酮组的男性更有可能认为自己的行走能力有所改善（PGIC），这既适用于参加 PFT 的男性（效应大小为 2.21，1.35-3.63；p=0.0018），也适用于未参加 PFT 的男性（3.01，1.61-5.63；p=0.0006）。6MWT 距离的变化与睾酮、游离睾酮、二氢睾酮和血红蛋白浓度的变化显著相关。在干预期间，两组的跌倒频率相同（两组各有 103 人[27%]至少发生了一次跌倒）。
睾酮治疗持续改善自我报告的行走能力，适度改善 6MWT 距离（所有 TTrials 参与者），但不影响跌倒。睾酮对移动能力测量的影响与基线步态速度和自我报告的移动能力受限有关，以及睾酮和血红蛋白浓度的变化有关。
美国国家老龄化研究所和 AbbVie。
