Medical Consequences of Long-Term Anabolic-Androgenic Steroid Abuse

长期滥用合成代谢雄激素类固醇的医疗后果

• 批准号: 8039576
• 负责人: HARRISON G POPE
• 金额: $ 54.62万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039576
• 关键词: 7 year old; Address; Adverse effects; Affect; Age; Aging; American; Anabolic steroids; Androgens; Appearance; Athletic; Cardiac; Cardiomyopathies; Cardiovascular system; Chronic; Clinical; Communities; Comparative Study; Congenital Heart Defects; Congresses; Country; Disease; Dose; Drug abuse; Echocardiography; Electrocardiogram; Employee Strikes; Evaluation; Exercise; Exposure to; Family; Functional disorder; General Population; Heart failure; Hormones; Hypogonadism; Hysteria; Impairment; Individual; Influentials; Investigation; Kidney; Knowledge; Laboratories; Left; Light; Literature; Liver; Long-Term Effects; Measures; Medical; Methods; Myocardial; Myocardial Infarction; Pathology; Peer Review; Performance; Pharmaceutical Preparations; Pilot Projects; Population; Prevalence; Production; Public Health; Publications; Recording of previous events; Recruitment Activity; Relative (related person); Relaxation; Renal function; Reporting; Research; Risk; Scientist; Steroids; Substance abuse problem; Testing; Testosterone; Time; Toxic effect; United States; Ventricular; Withdrawal; Work; Youth; aged; atherogenesis; base; body system; cost; design; disorder risk; experience; heart rhythm; hypothalamic pituitary gonadal axis; improved; liver function; male; member; men; men' s group; middle age; muscle form; steroid dependence; trend

DESCRIPTION (provided by applicant): The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its synthetic derivatives. For decades, elite athletes have used AAS to improve performance, but it was not until the 1980s that illicit AAS use spread out of elite athletics and into the general population. Now, some 2 million Americans have used AAS, sometimes accumulating years of total exposure to highly supraphysiologic doses. Preliminary evidence suggests that long-term AAS use may cause serious medical consequences, including especially cardiovascular effects. However, these remain poorly understood, in part because until recently, most AAS users were still too young to have entered the age of risk. Now, this situation is poised to change, as the first large wave of illicit AAS users - those who first used AAS as youths in the 1980s - enters middle age. In a pilot study, now in press, our group used electrocardiography and echocardiography to compare 12 long- term AAS users, aged 32-46 years, and 7 age-matched weightlifters reporting similar exercise levels but no AAS use. Compared with nonusers, the AAS users showed significantly delayed myocardial depolarization, together with striking and highly significant impairments of cardiac contraction and relaxation (systolic and diastolic function), similar to those seen in established types of cardiomyopathy. Although we did not assess atherosclerotic disease in the pilot study, prior work by our group and others suggests that this too may be a consequence of AAS use. To further assess the effects of long-term AAS use, we propose to perform detailed medical and cardiac assessments in 80 long-term AAS users, 55 weightlifters reporting no history of AAS use, and 55 non-weightlifting men. Men will be recruited and screened using proven methods, developed by the PI over the last 10 years, designed to minimize selection and information bias to the maximum extent possible when studying illicit substance users. Our primary specific aim is to test the hypothesis that long-term AAS use causes 1) abnormalities of cardiac electrical conduction, characterized by delayed myocardial depolarization, increasing the risk for cardiac rhythm disturbances; 2) impaired myocardial function, characterized particularly by left ventricular diastolic and systolic dysfunction, increasing the risk for heart failure; and 3) accelerated atherogenesis, increasing the risk for myocardial infarction and other atherosclerotic disease. Our secondary specific aim is to assess other possible AAS effects by comparing the 3 groups using medical and laboratory tests focused especially on 1) the liver and kidney and 2) the hypothalamic-pituitary-gonadal axis. The medical effects of long-term AAS abuse are probably the least understood of any major form of drug abuse; no comparative study to date has performed full medical evaluations on a large group of chronic AAS users. This represents a serious deficit in scientific knowledge since, even by conservative estimates, hundreds of thousands of Americans have experienced long-term AAS exposure, and the older members of this group are just now reaching middle age. Thus the proposed study will have major public health impact. PUBLIC HEALTH RELEVANCE: At least 2 million Americans have used illicit anabolic-androgenic steroids (AAS; drugs such as testosterone and its relatives), either for athletic purposes or simply to enhance personal appearance - and growing evidence now suggests that these individuals may be at risk for serious medical consequences, especially on the cardiovascular system. A recent pilot study from our laboratory, now in press, adds to this evidence by showing striking impairments of cardiac contraction and relaxation in 12 long-term AAS users as compared to 7 age-matched weightlifters reporting comparable exercise history but no AAS use. Based on these ominous preliminary findings, we propose to perform detailed medical evaluations, including a comprehensive battery of cardiac tests, in 80 long-term illicit AAS users, 55 matched weightlifters reporting no history of AAS use, and 55 non-weightlifting comparison men; to our knowledge, this the first large study of its kind, and it addresses a major deficit in our current knowledge of the dangers of substance abuse.

描述（由申请人提供）：合成代谢雄激素类固醇（AAS）是一类激素，包括睾酮及其合成衍生物。几十年来，精英运动员一直使用 AAS 来提高成绩，但直到 20 世纪 80 年代，非法 AAS 的使用才从精英运动员中蔓延到普通人群。现在，大约有 200 万美国人使用过原子吸收光谱法，有时累积多年总暴露于高超生理剂量。初步证据表明，长期使用 AAS 可能会导致严重的医疗后果，尤其是心血管影响。然而，人们对这些仍然知之甚少，部分原因是直到最近，大多数 AAS 用户还太年轻，还没有进入风险年龄。现在，这种情况即将发生改变，因为第一批非法 AAS 用户（在 20 世纪 80 年代首次使用 AAS 的年轻人）已进入中年。在一项现已出版的试点研究中，我们的小组使用心电图和超声心动图比较了 12 名年龄在 32-46 岁之间的长期 AAS 用户和 7 名年龄匹配的举重运动员，他们报告了相似的运动水平，但没有使用 AAS。与非用户相比，AAS 用户表现出明显的心肌去极化延迟，以及心脏收缩和舒张（收缩和舒张功能）的显着和高度显着的损害，类似于已确定类型的心肌病中所见的情况。尽管我们在试点研究中没有评估动脉粥样硬化疾病，但我们小组和其他人之前的工作表明，这也可能是使用 AAS 的结果。为了进一步评估长期使用 AAS 的影响，我们建议对 80 名长期 AAS 用户、55 名没有使用 AAS 历史的举重运动员和 55 名非举重男性进行详细的医疗和心脏评估。将使用 PI 在过去 10 年中开发的行之有效的方法来招募和筛选男性，旨在在研究非法药物使用者时最大程度地减少选择和信息偏见。我们的主要具体目标是检验以下假设：长期使用 AAS 会导致 1) 心脏电传导异常，其特征是心肌去极化延迟，增加心律紊乱的风险； 2）心肌功能受损，特别是左心室舒张和收缩功能障碍，增加心力衰竭的风险； 3）加速动脉粥样硬化形成，增加心肌梗塞和其他动脉粥样硬化疾病的风险。我们的次要具体目标是通过使用医学和实验室测试比较 3 组来评估其他可能的 AAS 效应，特别关注 1) 肝脏和肾脏以及 2) 下丘脑-垂体-性腺轴。 长期滥用 AAS 的医疗影响可能是所有主要形式的药物滥用中最不为人所知的。迄今为止，还没有比较研究对一大群长期使用 AAS 的人进行全面的医学评估。这代表了科学知识的严重缺乏，因为即使按照保守估计，也有数十万美国人经历过长期的 AAS 暴露，而这个群体的老年成员现在刚刚步入中年。因此，拟议的研究将对公共卫生产生重大影响。 公共健康相关性：至少有 200 万美国人使用非法合成代谢雄激素类固醇（AAS；睾酮及其相关药物等药物），无论是出于运动目的还是仅仅为了增强个人外观 - 现在越来越多的证据表明，这些人可能面临严重医疗后果的风险，尤其是对心血管系统的影响。我们实验室最近进行的一项初步研究（现已出版）补充了这一证据，显示 12 名长期 AAS 用户的心脏收缩和舒张功能明显受损，而 7 名年龄匹配的举重运动员报告了类似的运动史，但没有使用 AAS。基于这些不祥的初步结果，我们建议对 80 名长期非法 AAS 用户、55 名没有使用 AAS 历史的匹配举重运动员以及 55 名非举重对照男性进行详细的医学评估，包括全面的心脏测试；据我们所知，这是此类研究中的第一个大型研究，它解决了我们目前对药物滥用危险的认识中的一个重大缺陷。