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

雄激素替代疗法可改善阿片类药物引起的性腺功能减退症男性患者的重要预后

• 批准号: 10266840
• 负责人: Shehzad Basaria
• 金额: $ 71.3万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10266840
• 关键词: Absence of pain sensation; Acute; Age; Analgesics; Androgens; Animal Experimentation; Back Pain; Brief Pain Inventory; Caring; Chronic; Clinical; Cohort Studies; Data; Development; Dose; Double-Blind Method; Exhibits; Goals; Gonadal structure; Gonadotropin Hormone Releasing Hormone; Human; Hypogonadism; Hypothalamic structure; Inflammatory; Injections; Insula of Reil; Intramuscular; Intramuscular Injections; Luteinizing Hormone; Magnetic Resonance Imaging; Measures; Mental Depression; Moods; Opioid; Opioid Analgesics; Outcome; Pain; Pain interference; Patient Care; Patients; Pharmaceutical Preparations; Physiological; Pituitary Gland; Placebos; Postoperative Period; Prevalence; Production; Property; Public Health; Quality of life; Questionnaires; Randomized; Reference Values; Reporting; Rodent; SF-36; Sensory; Serum; Severities; Stimulus; Testing; Testosterone; Woman; arm; base; brain circuitry; chronic back pain; chronic pain; clinical pain; comparative efficacy; cytokine; double-blind placebo controlled trial; efficacy evaluation; endogenous opioids; health related quality of life; improved; instrument; male; mechanical pressure; men; mortality; non-cancer chronic pain; pain perception; pain processing; pain reduction; pain sensitivity; patient population; population based; prescription opioid; randomized placebo controlled trial; randomized trial; response; testosterone replacement therapy

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.

项目摘要 有大量的证据表明，女性和男性并不平等地经历疼痛。与男性相比，女性 在大多数临床疼痛病症中过度表现，并且还表现出对 实验性疼痛同样，女性使用止痛药的比例是男性的两倍， 严重程度相当这些数据表明，睾酮具有抗伤害性。然而，这 当男性被处方阿片类镇痛药作为阿片类药物时，睾酮提供的镇痛垫丧失 能有效抑制睾丸激素的产生事实上，约70-100%的慢性阿片类药物男性性腺功能减退。在 近年来，持续作用阿片类药物在慢性非癌性疼痛治疗中的应用有所增加 许多男性服用多种阿片类镇痛药。阿片类药物引起的性腺功能减退的发展 这些人的抗伤害性的睾丸激素，并导致恶性循环， 尽管服用阿片类药物，但慢性疼痛持续存在，使患者长期需要甚至 更高剂量的鸦片阿片类药物诱导的男性睾酮替代治疗的初步试验 性腺机能减退症在临床和实验疼痛方面都显示出改善， QOL的某些方面。然而，睾酮替代对疼痛感知的功效尚未得到证实。 在有足够把握度的试验中进行研究。本提案的总体目标是评估以下方面的功效： 生理性睾酮替代疗法在改善临床和实验性疼痛中的双盲， 在接受阿片类药物治疗的慢性背痛男性中进行的随机、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。我们还计划在手术期间进行功能性磁共振成像 定量感觉测试，以表征支撑疼痛变化的中枢机制 在这些性腺功能减退的男性中睾酮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。我们提出一个大的，双- 一项为期6个月的盲法、随机、安慰剂对照试验，我们将比较生理性 每周肌肉注射睾酮替代（最可靠的睾酮形式 在18岁及以上患有慢性背痛和阿片类药物诱导的男性中， 性腺机能减退将测量以下结局：1）临床疼痛，2）定量感觉测试沿着 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酮的益处，现有的治疗方法是次优的，只能提供部分缓解， 治疗，患者将有一个便宜的，相对安全和易于管理的药物， 改变对这些病人的护理的潜力。