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: 8401169
• 负责人: HARRISON G POPE
• 金额: $ 50.78万
• 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/8401169
• 关键词: 7 year old; Address; Adverse effects; Affect; Age; Aging; American; Anabolic steroids; Androgens; Appearance; Athletic; Cardiac; Cardiomyopathies; Cardiovascular system; Chronic; 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; clinical risk; 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.

描述（由申请人提供）：合成代谢雄激素类固醇（AAS）是一个激素家族，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，非法使用AAS才从精英运动员中蔓延到普通人群中。现在，大约有200万美国人使用AAS，有时累积多年的高度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疗后果，特别是心血管影响。然而，这些仍然知之甚少，部分原因是直到最近，大多数AAS用户仍然太年轻，尚未进入风险年龄。现在，这种情况即将改变，因为第一波非法AAS使用者-那些在20世纪80年代首次使用AAS的年轻人-进入中年。在一项初步研究中，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岁的长期AAS使用者和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。与非使用者相比，AAS使用者表现出显著延迟的心肌去极化，以及心脏收缩和舒张功能（收缩和舒张功能）的显著和高度显著的损害，与已确定类型的心肌病相似。虽然我们在初步研究中没有评估动脉粥样硬化疾病，但我们小组和其他人先前的工作表明，这也可能是AAS使用的结果。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名非举重运动员进行详细的医疗和心脏评估。将使用PI在过去10年中开发的经过验证的方法招募和筛选男性，旨在最大限度地减少研究非法药物使用者时的选择和信息偏差。我们的主要具体目的是检验以下假设：长期使用AAS会导致1）心脏电传导异常，其特征在于延迟心肌去极化，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;和3）加速动脉粥样硬化形成，增加心肌梗塞和其它动脉粥样硬化疾病的风险。我们的第二个具体目标是通过使用医学和实验室检查比较3组来评估其他可能的AAS效应，特别是1）肝脏和肾脏和2）下丘脑-垂体-性腺轴。 长期AAS滥用的医学影响可能是任何主要形式的药物滥用中最不了解的;迄今为止，没有比较研究对一大群长期AAS使用者进行全面的医学评价。这代表了科学知识的严重不足，因为即使保守估计，也有数十万美国人经历了长期的AAS暴露，而这一群体中的老年人刚刚步入中年。因此，拟议的研究将对公共卫生产生重大影响。