Androgen Replacement to Improve Patient-Important Outcomes in Men with Opioid-Induced Hypogonadism

项目总结 有大量证据表明，女性和男性体验痛苦的方式并不相同。与男人相比，女人 在大多数临床疼痛情况下都有过多的表现，而且对 实验性疼痛。同样，在女性中使用止痛剂的情况是男性的两倍。 与之相当的严重性。这些数据表明，睾丸激素具有抗伤害性。然而，这 当给男性开阿片类镇痛剂时，睾丸激素提供的止痛垫就会丢失 有效地抑制睾丸素的产生。事实上，约70%-100%的长期服用阿片类药物的男性性腺功能低下。在……里面 近年来，持续作用阿片类药物在慢性非癌症疼痛治疗中的使用有所增加 许多男性服用多种阿片类镇痛剂。阿片类药物所致性腺功能减退的进展 这些男性具有抗伤害性的睾丸激素，并导致恶性循环，导致 尽管服用阿片类药物，但慢性疼痛仍持续存在，使患者不得不长期服用 高剂量的鸦片类药物。男性阿片类药物诱导的睾酮替代治疗的初步试验 性腺功能减退症在临床和实验疼痛方面都有改善，在 生活质量的某些方面。然而，睾丸素替代疗法对痛觉的疗效尚未得到证实。 在动力充足的试验中进行了研究。这项提案的总体目标是评估 生理性睾酮替代疗法改善临床和实验性疼痛的双盲试验， 在接受阿片类药物治疗的慢性背痛患者中进行的随机、安慰剂对照试验 止痛药至少6个月，并有阿片类药物诱导的性腺功能减退。我们还计划在 定量感觉测试以表征支撑疼痛变化的中枢机制 这些性腺功能低下的男性在睾丸激素替代过程中发生的过程。我们还将 评估睾酮替代治疗对生活质量、情绪和抑郁的疗效。我们提议一个大的，双倍的- 随机、随机、安慰剂对照、为期6个月的盲法试验，我们将比较生理学疗法的疗效 每周肌肉注射(最可靠的睾丸素形式)来替代睾丸素 18岁及以上男性慢性背痛和阿片类药物诱导的安慰剂注射的对比研究 性腺功能减退。以下结果将被测量：1)临床疼痛，2)定量感觉测试 3)生活质量、情绪和抑郁。因为慢性疼痛是一个主要的公共卫生问题， 如果这项试验证实了睾丸素的益处，那么现有的治疗方法并不理想，只能提供部分缓解。 治疗，患者将拥有一种廉价、相对安全和易于管理的药物，这种药物具有 改变这些患者护理的潜力。

PROJECT SUMMARY There is abundant evidence that women and men do not experience pain equally. Compared to men, women are overrepresented in the majority of clinical pain conditions and also exhibit greater sensitivity to experimental pain. Similarly, use of analgesics is twice as common in women, compared to men, for conditions of comparable severities. These data suggest that testosterone has anti-nociceptive properties. However; this analgesic cushion provided by testosterone is lost when men are prescribed opioid-analgesics as opioids potently suppress testosterone production. Indeed, ~70-100% of men on chronic opioids are hypogonadal. In recent years, the use of sustained-action opioids in the management of chronic non-cancer pain has grown with many men taking multiple opioid analgesics. The development of opioid-induced hypogonadism deprives these men of the anti-nociceptive properties of testosterone and leads to a vicious cycle resulting in perpetuation of chronic pain despite being on opioids, subjecting patients to long-term requirement of even higher doses of opiates. Preliminary trials of testosterone replacement in men with opioid-induced hypogonadism have shown improvement in both clinical and experimental pain, and also improvement in certain aspects of QOL. However, the efficacy of testosterone replacement on pain perception has not been studied in adequately-powered trials. The overall goal of this proposal is to evaluate the efficacy of physiologic testosterone replacement therapy in improving clinical and experimental pain in a double-blind, randomized, placebo-controlled trial in men with chronic back pain who are being treated with opioid- analgesics for at least 6 months and have opioid-induced hypogonadism. We also plan to perform fMRI during quantitative sensory testing to characterize the central mechanisms underpinning the changes in pain processing that occur over the course of testosterone replacement in these hypogonadal men. We will also assess the efficacy of testosterone replacement on QOL, mood and depression. We propose a large, double- blind, randomized, placebo-controlled, 6-month trial in which we will compare the efficacy of physiologic testosterone replacement with weekly intramuscular injections (the most reliable form of testosterone replacement) versus placebo injections in men age 18 and older with chronic back pain and opioid-induced hypogonadism. The following outcomes will be measured: 1) clinical pain, 2) quantitative sensory testing along with fMRI, and 3) QOL, mood and depression. Because chronic pain is a major public health problem for which existing therapies are suboptimal and only provide partial relief, if this trial confirms benefits of testosterone therapy, patients will have an inexpensive, relatively safe and easy to administer medication available that has the potential to transform the care of these patients.