Cognitive Consequences of Endocrine Dysfunction in IDU

描述(申请人提供)：性类固醇受体在大脑中无处不在的分布表明性腺激素是认知功能的重要调节器。注射吸毒者(IDU)的下丘脑-垂体-性腺轴的内分泌异常已经被记录在案，可能是由于直接的药物效应和相关的共病的组合。我们的总体假设是，IDU患者存在认知功能障碍，原因是与IDU相关的性腺功能减退症继发的中枢神经系统改变，并且在标准化认知测试中表现不佳的情况可以通过使用性类固醇替代来改善。为了验证我们的假设，我们提出了以下具体目标：(1)记录IDU人群中的性腺激素环境，并了解该环境与认知表现和生活质量(QOL)的关系。(#2)使用标准化认知测试，在基于IDU和HLV状态的特定人群中表征认知表现和生活质量的模式。(3)评价性激素替代疗法(男性使用睾酮或女性使用雌激素)对性腺功能减退IDU患者认知功能和生活质量的安全性和有效性。我们提出了两项研究：IDU的横断面研究，以评估认知表现与其性腺激素环境的关系；以及一项随机、安慰剂对照的临床试验，在该临床试验中，性腺功能低下的IDU将接受性激素替代，以确定其对认知表现和生活质量的影响。我们已经组建了一个多学科团队，在研究IDU人群、内分泌异常和受性类固醇影响的认知任务表现方面拥有丰富的经验。我们将更好地了解药物使用和认知之间的关系，并在一个未被研究的人群中扩大我们对性类固醇对认知表现影响的理解。

DESCRIPTION (provided by applicant): The ubiquitous distribution of sex steroid receptors throughout the brain suggests that gonadal hormones are important modulators of cognitive function. Endocrine abnormalities in the hypothalamic-pituitary-gonadal axis have been documented in injection drug users (IDU) and are likely due to a combination of direct drug effects and associated co-morbidities. Our overall hypothesis is that there is cognitive dysfunction in IDU due to CNS alterations secondary to hypogonadism associated with IDU, and that poor performance on standardized cognitive tests can be improved by administering sex steroid replacement. To test our hypothesis we propose the following specific aims: (#1) To document the gonadal hormonal milieu in a population of IDU, and to understand the relationship of that milieu to cognitive performance and quality of life (QOL). (#2) To characterize patterns of cognitive performance and QOL in a defined population based on IDU and HlV status using standardized cognitive testing. (#3) To evaluate the safety and efficacy of sex hormone replacement therapy (either testosterone in men or estrogen in women) on cognitive performance and QOL in a subgroup of hypogonadal IDU. We propose two studies: a cross-sectional study of IDU to evaluate patterns of cognitive performance in relation to their gonadal hormone milieu and, a randomized, placebo-controlled, clinical trial in which hypogonadal IDU will be administered sex hormone replacement to determine the effects on cognitive performance and QOL. We have assembled a multidisciplinary team with extensive experience in studying IDU populations, endocrine abnormalities, and performance on cognitive tasks influenced by sex steroids. We will obtain a better understanding of the relationship between drug use and cognition, and also expand our understanding of the effects of sex steroids on cognitive performance, in an under-studied population.