Abstract：
OBJECTIVE: Studies are needed to examine the effects of testosterone replacement therapy on ambulatory blood pressure (BP) parameters. This study assessed a testosterone transdermal system (TTS) using 24-hour ambulatory BP monitoring.
METHODS: In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.2 years) with hypogonadism not receiving testosterone replacement therapy in the past 6 months were enrolled and received ≥1 study drug dose. Nightly TTS treatment was administered for 16 weeks (starting dose: 4 mg/d; min, max dose: 2, 6 mg/d) to achieve testosterone concentration of 400-930 ng/dL. The primary endpoint was mean change from baseline to week 16 in 24-hour systolic BP (SBP). Noninferiority was determined based on the upper bound of the 2-sided 95% CI <3.0 mmHg.
RESULTS: Sixty-two men had ≥85% study drug compliance and a valid week 16 ambulatory BP monitoring session. Mean change from baseline to week 16 in 24-hour average SBP was 3.5 mmHg (95% CI, 1.2-5.8 mmHg; n = 62). Since the upper limit of the CI was >3 mmHg, an effect of TTS could not be ruled out. Mean changes were larger at daytime vs nighttime and in subgroups of men with vs without hypertension. Cardiovascular adverse events were rare (<2%) and nonserious; no major cardiovascular adverse events were reported.
CONCLUSIONS: A meaningful effect of 16-week TTS treatment on 24-hour average SBP among men with hypogonadism could not be ruled out based on the study\'s noninferiority criterion. The magnitude of mean changes observed may not be clinically meaningful regarding cardiovascular events.
METHODS: In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.2 years) with hypogonadism not receiving testosterone replacement therapy in the past 6 months were enrolled and received ≥1 study drug dose. Nightly TTS treatment was administered for 16 weeks (starting dose: 4 mg/d; min, max dose: 2, 6 mg/d) to achieve testosterone concentration of 400-930 ng/dL. The primary endpoint was mean change from baseline to week 16 in 24-hour systolic BP (SBP). Noninferiority was determined based on the upper bound of the 2-sided 95% CI <3.0 mmHg.
RESULTS: Sixty-two men had ≥85% study drug compliance and a valid week 16 ambulatory BP monitoring session. Mean change from baseline to week 16 in 24-hour average SBP was 3.5 mmHg (95% CI, 1.2-5.8 mmHg; n = 62). Since the upper limit of the CI was >3 mmHg, an effect of TTS could not be ruled out. Mean changes were larger at daytime vs nighttime and in subgroups of men with vs without hypertension. Cardiovascular adverse events were rare (<2%) and nonserious; no major cardiovascular adverse events were reported.
CONCLUSIONS: A meaningful effect of 16-week TTS treatment on 24-hour average SBP among men with hypogonadism could not be ruled out based on the study\'s noninferiority criterion. The magnitude of mean changes observed may not be clinically meaningful regarding cardiovascular events.
摘要：
目的：需要研究睾酮替代疗法（TRT）对动态血压（BP）参数的影响。这项研究使用24小时动态BP监测（ABPM）评估了睾丸激素透皮系统（TTS）。
方法：在单臂中，在41个美国地点进行的非劣效性试验，168名男性（平均年龄：56.2岁）在过去6个月内未接受TRT的性腺机能减退患者纳入研究，并接受≥1次研究药物剂量。每晚TTS治疗16周（起始剂量：4mg/d;min，最大剂量：2,6mg/d）以达到400-930ng/dL的睾酮浓度。主要终点是24小时收缩压（SBP）从基线到第16周的平均变化。根据双侧95%CI<3.0mmHg的上限确定非劣效性。
结果：62名男性有≥85%的研究药物依从性和有效的16周ABPM疗程。从基线到第16周24小时平均SBP的平均变化为3.5mmHg（95％CI，1.2-5.8mmHg；n=62）。由于CI的上限>3mmHg，不能排除TTS的影响。白天和夜间以及有高血压和无高血压的男性亚组的平均变化更大。心血管不良事件（AEs）罕见（<2%）且非严重；未报告重大心血管不良事件。
结论：根据研究的非劣效性标准，不能排除16周TTS治疗对性腺机能减退男性24小时平均SBP有意义的影响。观察到的平均变化幅度对于心血管事件可能没有临床意义。
方法：在单臂中，在41个美国地点进行的非劣效性试验，168名男性（平均年龄：56.2岁）在过去6个月内未接受TRT的性腺机能减退患者纳入研究，并接受≥1次研究药物剂量。每晚TTS治疗16周（起始剂量：4mg/d;min，最大剂量：2,6mg/d）以达到400-930ng/dL的睾酮浓度。主要终点是24小时收缩压（SBP）从基线到第16周的平均变化。根据双侧95%CI<3.0mmHg的上限确定非劣效性。
结果：62名男性有≥85%的研究药物依从性和有效的16周ABPM疗程。从基线到第16周24小时平均SBP的平均变化为3.5mmHg（95％CI，1.2-5.8mmHg；n=62）。由于CI的上限>3mmHg，不能排除TTS的影响。白天和夜间以及有高血压和无高血压的男性亚组的平均变化更大。心血管不良事件（AEs）罕见（<2%）且非严重；未报告重大心血管不良事件。
结论：根据研究的非劣效性标准，不能排除16周TTS治疗对性腺机能减退男性24小时平均SBP有意义的影响。观察到的平均变化幅度对于心血管事件可能没有临床意义。
