Improving Patient-Important Outcomes with Testosterone Replacement in Hypogonadal Men with a Prior History of Cancer

项目总结/摘要 本提案的总体目标是评估睾酮替代疗法在改善 疲劳和其他结果，如性功能，生活质量，身体成分，肌肉力量和 一项在年轻癌症幸存者中进行的双盲、随机、安慰剂对照试验中， 疲劳和睾丸激素缺乏。疲劳是最普遍和衰弱的症状之一， 癌症影响70-100%的患者，无论他们的年龄。癌症相关的疲劳是经历 不仅在积极的癌症治疗期间，而且在表现出癌症症状的癌症幸存者中也非常普遍。 治疗结束后数月至数年持续疲劳，患病率最高的是 化疗和/或放疗的接受者。除了疲劳，性功能障碍也是 在男性癌症幸存者中非常普遍。男性癌症幸存者也有增加的脂肪量， 瘦体重减少，这是一种易使他们肌肉力量降低的表型。这种表型 疲劳，性功能障碍和不良身体成分是常见的非癌症患者 睾酮缺乏的人群，这种情况在癌症中也很普遍（50-90%） 幸存者在非癌症患者人群中进行的睾酮替代疗法的临床试验显示， 随机接受睾酮治疗男性的疲劳、性功能和身体成分的改善， 安慰剂。然而，睾酮替代疗法对癌症相关性疲劳的疗效尚未得到证实。 本文研究了我们提出了一个大的，9个月，双盲，随机，安慰剂对照试验，其中：1）我们 将比较每周注射睾酮与安慰剂在改善癌症患者疲劳评分方面的疗效 幸存者谁报告疲劳，也有睾丸激素缺乏症，2）我们将比较的影响， 睾酮替代与安慰剂对性功能，幸福感，情绪和生活质量的影响，以及3）我们 将确定睾酮管理对身体成分，肌肉力量和身体素质的影响。 与安慰剂相比。随着癌症幸存者寿命的延长， 认识到症状控制在这些患者生活中的重要性，拟议的试验可能会 对患者报告结局的管理具有显著的临床影响。如果睾丸激素疗法 发现有效缓解这些症状，临床医生将为他们提供一种治疗方法， 这种选择相对便宜，使用方便，在年轻男性中具有良好的安全记录。

PROJECT SUMMARY/ABSTRACT The overall goal of this proposal is to evaluate the efficacy of testosterone replacement therapy in improving fatigue and other outcomes such as sexual function, quality of life, body composition, muscle strength and physical activity in a double-blind, randomized, placebo-controlled trial in young cancer survivors who report fatigue and have testosterone deficiency. Fatigue is one of the most prevalent and debilitating symptoms in men with cancer affecting 70-100% of patients irrespective of their age. Cancer-related fatigue is experienced by patients not only during active cancer treatment, but is also highly prevalent in cancer survivors who exhibit persistent fatigue months to years after the end of their treatment with the highest prevalence being in recipients of chemotherapy and/or radiation therapy. In addition to fatigue, sexual dysfunction is also highly prevalent in male cancer survivors. Male cancer survivors also have increased fat mass and decreased lean body mass, a phenotype that predisposes them to reduced muscle strength. This phenotype of fatigue, sexual dysfunction and adverse body composition is commonly encountered in non-cancer patient populations with testosterone deficiency, a condition which is also highly prevalent (50-90%) in cancer survivors. Pivotal trials of testosterone replacement therapy in non-cancer patient populations have shown an improvement in fatigue, sexual function and body composition in men randomized to testosterone compared with placebo. However, the efficacy of testosterone replacement therapy on cancer-related fatigue has not been studied. We propose a large, 9-month, double-blind, randomized, placebo-controlled trial in which: 1) we will compare the efficacy of weekly testosterone injections versus placebo in improving fatigue scores in cancer survivors who report fatigue and also have testosterone deficiency, 2) we will compare the effects of testosterone replacement versus placebo on sexual function, well-being, mood and quality of life, and 3) we will determine the effect of testosterone administration on body composition, muscle strength and physical activity compared with placebo. With an increase in longevity among cancer survivors and the growing recognition of the importance of symptom control in the lives of these patients, the proposed trial is likely to have a significant clinical impact in the management of patient-reported outcomes. If testosterone therapy is found to be efficacious in alleviating these symptoms, the clinicians will have available to them a therapeutic option that is relatively inexpensive, convenient to use and has a good safety record in young men.