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: 8211993
• 负责人: HARRISON G POPE
• 金额: $ 53.04万
• 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/8211993
• 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; public health relevance; 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(申请人提供)：合成代谢-雄激素(AAS)是一类激素，包括睾酮及其合成衍生物。几十年来，精英运动员一直在使用AAS来提高成绩，但直到20世纪80年代，非法使用AAS才从精英运动员蔓延到普通民众。现在，大约有200万美国人使用了原子吸收光谱，有时累积了多年的高超生理剂量的总暴露。初步证据表明，长期使用AAS可能会导致严重的医学后果，特别是对心血管的影响。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，随着第一大批非法AAS用户--那些在20世纪80年代年轻时首次使用AAS的人--进入中年，这种情况即将改变。在目前正在进行的一项先导性研究中，我们小组使用心电图和超声心动图对12名32-46岁的长期使用AAS的人和7名年龄匹配的举重运动员进行了比较，他们报告的运动水平相似，但没有使用AAS。与非使用者相比，AAS使用者表现出明显的心肌去极化延迟，同时心脏收缩和松弛(收缩和舒张功能)显著和非常显著的损害，类似于在已有的心肌病类型中看到的。虽然我们在初步研究中没有评估动脉粥样硬化性疾病，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的效果，我们建议对80名长期使用AAS的人、55名没有AAS使用史的举重运动员和55名非举重男性进行详细的医学和心脏评估。将招募男子，并使用过去10年来由国际刑警组织开发的行之有效的方法进行筛查，这些方法旨在最大限度地减少在研究非法药物使用者时的选择和信息偏见。我们的主要目标是验证这样一种假设：长期使用AAS会导致1)心脏电传导异常，特征是心肌除极延迟，增加心律失常的风险；2)心肌功能受损，特别是左心室舒缩功能障碍，增加心力衰竭的风险；3)加速动脉粥样硬化形成，增加心肌梗死和其他动脉粥样硬化性疾病的风险。我们的次要目标是通过比较3组的医学和实验室测试来评估其他可能的AAS效应，特别是1)肝和肾脏，2)下丘脑-垂体-性腺轴。在任何主要形式的药物滥用中，长期滥用AAS的医疗影响可能是最不被了解的；到目前为止，还没有一项比较研究对一大批长期使用AAS的人进行全面的医学评估。这代表着科学知识的严重匮乏，因为即使是保守的估计，也有数十万美国人经历过长期接触AAS，而这一群体中的老年成员刚刚步入中年。因此，拟议的研究将对公众健康产生重大影响。 与公共健康相关：至少有200万美国人使用了非法的合成代谢-雄激素类固醇(AAS；睾酮及其亲属等药物)，用于运动目的或仅仅是为了改善个人形象-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，特别是对心血管系统。我们实验室最近的一项初步研究增加了这一证据，该研究显示，12名长期使用AAS的人心脏收缩和松弛明显受损，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发现，我们建议对80名长期使用AAS的非法使用者、55名没有AAS使用史的配对举重运动员和55名非举重对照男子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项大型研究，它解决了我们目前对药物滥用危险的认识的一个重大缺陷。