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: 10118343
• 负责人: Shehzad Basaria
• 金额: $ 75.28万
• 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/10118343
• 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; 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.

项目概要 有大量证据表明，女性和男性所经历的疼痛并不相同。与男性相比，女性 在大多数临床疼痛病症中所占比例过高，并且对 实验性疼痛。同样，由于病情原因，女性使用镇痛药的比例是男性的两倍 具有可比的严重性。这些数据表明睾酮具有抗伤害特性。然而;这 当男性服用阿片类镇痛药作为阿片类药物时，睾酮提供的镇痛缓冲作用就会消失 有效抑制睾酮的产生。事实上，约 70-100% 长期服用阿片类药物的男性患有性腺功能减退症。在 近年来，持续作用阿片类药物在治疗慢性非癌症疼痛中的使用有所增加 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症的发展剥夺 这些人缺乏睾酮的抗伤害特性，导致恶性循环 尽管服用阿片类药物，但慢性疼痛仍持续存在，使患者长期需要甚至 更高剂量的阿片类药物。睾酮替代治疗男性阿片类药物引起的初步试验 性腺功能减退症已显示出临床和实验疼痛的改善，以及 生活质量的某些方面。然而，睾酮替代疗法对疼痛感知的功效尚未得到证实。 在足够有力的试验中进行了研究。该提案的总体目标是评估 双盲生理睾酮替代疗法可改善临床和实验疼痛， 对正在接受阿片类药物治疗的慢性背痛男性进行的随机、安慰剂对照试验 服用镇痛药至少 6 个月且患有阿片类药物引起的性腺功能减退症。我们还计划在期间进行功能磁共振成像 定量感觉测试来表征支撑疼痛变化的中心机制 这些性腺功能减退男性在睾酮替代过程中发生的处理。我们也会 评估睾酮替代疗法对生活质量、情绪和抑郁症的疗效。我们建议一个大型的、双 盲法、随机、安慰剂对照、为期 6 个月的试验，我们将比较生理学的疗效 每周肌内注射睾酮替代（最可靠的睾酮形式） 对于 18 岁及以上患有慢性背痛和阿片类药物引起的男性来说，注射替代疗法与安慰剂注射比较 性腺功能减退症。将测量以下结果：1）临床疼痛，2）定量感觉测试 功能磁共振成像，以及 3) 生活质量、情绪和抑郁。因为慢性疼痛是一个重大的公共卫生问题 如果该试验证实睾酮的益处，现有疗法并不理想，只能提供部分缓解 治疗时，患者将获得一种廉价、相对安全且易于使用的药物， 改变这些患者护理的潜力。