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

基本信息

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
项目类别：
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&apos s group middle age muscle form steroid dependence trend

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&apos s group middle age muscle form steroid dependence trend

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项目摘要

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 - 原源性类固醇（AAS）是包括睾丸激素及其合成衍生物的激素家族。几十年来，精英运动员一直使用AAS来提高性能，但是直到1980年代，AAS才能使用精英田径运动并进入普通人群。现在，约有200万美国人使用了AAS，有时会积累数年的全部暴露于高度生理学的剂量。初步证据表明，长期使用AA可能会导致严重的医疗后果，包括尤其是心血管影响。但是，这些知识仍然很糟糕，部分原因是直到最近，大多数AAS使用者还太年轻，无法进入风险年龄。现在，这种情况有望改变，因为第一批非法AAS使用者（1980年代首次使用AAS作为年轻人）进入了中年。在一项试点研究中，现在在新闻界中，我们的小组使用心电图和超声心动图来比较12个长期AAS使用者，年龄32-46岁，以及7个年龄匹配的举重运动员，报告了相似的运动水平，但没有使用AAS。与非使用者相比，AAS使用者表现出明显延迟的心肌去极化，以及与既定类型的心肌病类型的心脏收缩和放松（收缩和舒张功能）的惊人和严重的损害（收缩和舒张功能）相似。尽管我们没有在试点研究中评估动脉粥样硬化疾病，但我们小组的先前工作表明，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，我们建议在80个长期AAS使用者中执行详细的医疗和心脏评估，55名举重运动员报告没有使用AAS的历史，还有55名非授予男性。在过去10年中，PI开发的男性将被招募和筛选，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。我们的主要目的是检验以下假设：长期AA的使用导致1）心脏电导传导异常，其特征是心肌去极化延迟，增加了心律障碍的风险； 2）心肌功能受损，尤其是左心室舒张压和收缩功能障碍的特征，增加了心力衰竭的风险； 3）加速了动脉粥样硬化，增加了心肌梗塞和其他动脉粥样硬化疾病的风险。我们的次要特定目的是通过使用专注于1）肝脏和肾脏的医疗和实验室测试来评估其他可能的AAS效应，以及2）下丘脑 - 垂体 - 核 - 轴轴。长期AAS滥用的医学作用可能是任何主要形式的滥用药物的理解最少。迄今为止，还没有对大量慢性AAS使用者进行全面的医学评估。这代表了科学知识的严重赤字，因为即使是保守的估计，成千上万的美国人经历了长期的AAS暴露，并且该小组的年长成员现在刚刚达到中年。因此，拟议的研究将对公共卫生产生重大影响。公共卫生相关性：至少有200万美国人用于用于运动目的或仅仅是为了增强个人外表，否则越来越多的证据表明，这些人可能面临严重的医疗后果，尤其是对心血管系统的风险。我们的实验室最近的一项试点研究（如今在印刷中）通过显示12个长期AAS使用者的心脏收缩和放松的惊人障碍，与7个年龄匹配的举重运动员报告可比的运动历史但无AAS使用，但使用AAS，这增加了这一证据。基于这些不祥的初步发现，我们建议在80个长期非法AAS用户中进行详细的医学评估，包括全面的心脏测试，55名匹配的举重运动员报告没有使用AAS的历史，而55名非降低性比较的男性；据我们所知，这是对同类研究的第一个大型研究，它解决了我们目前对滥用毒品危险的严重赤字。