Intra-Subject Hormone Variation

描述：(申请人提供)在男性生殖内分泌学领域，缺乏可靠的数据来估计男性激素在一段时间内(短期和长期)的内部变异性是一个明显的缺陷。我们马萨诸塞州男性老龄化研究(MMAS)的数据表明，随着时间的推移，性腺功能减退可能不是一种稳定的综合征。此外，受试者内部可变性的数据对于设计任何科学可信的男性雄激素替代试验是必不可少的。这些数据在患者护理水平上也很重要--特别是单个清晨血清样本是否足够用于诊断目的。 这项研究有三个主要目的：(1)获得成年男性激素水平短期(每日)和长期(6个月)内变化的可靠估计。虽然主要关注的是睾酮(总的、游离的、生物可利用的和游离的雄激素指数)，但其他主要激素(DHT、SHBG、黄体生成素、催乳素、DHEA、DHEAS、皮质醇、雄烯二酮、雄烯二醇(3-α-二醇G)和雌酮)也包括在内，因为人们对它们的作用越来越感兴趣，而且在一项单独的研究中收集这些数据也具有成本效益；(2)确定受试者内激素水平的变化是否随着年龄的变化而变化(一些研究集中在相对年轻的男性)；(3)检查任何季节性变化的大小(这可能会影响临床对结果的解释和临床试验中的功率计算)。估计化验变异和生物变异对受试者内部总变异的相对贡献也很重要。 这项拟议的研究建立在近20年来对MMA的工作基础上，结果将在几个层面产生影响--男性内分泌变化的流行病学、临床试验设计和雄激素缺乏患者的临床管理。

DESCRIPTION: (provided by applicant) The dearth of reliable data to permit estimation of intra-subject variability in male hormones over time (both short and longer-term) is a glaring deficiency in the field of male reproductive endocrinology. Data from our Massachusetts Male Aging Study (MMAS) suggests that hypogonadism may not be a stable syndrome over time. Moreover, data on intra-subject variability is essential to the design of any scientifically credible trial of androgen replacement in men. These data are also important at the level of patient care- especially the adequacy of a single early morning serum sample for diagnostic purposes. This study has three primary aims: (1) To obtain reliable estimates of short term (day-to-day) and longer-term (six months) intra-subject variation in hormone levels in adult men. While the main focus is on testosterone (total, free, bioavailable and the free androgen index), other major hormones (DHT, SHBG, LH, prolactin, DHEA, DHEAS, cortisol, androstenedione, androstanediol glucoronide (3-alpha-diol G) and estrone) are included because of rapidly growing interest in their actions, and because it's cost-efficient also to gather these data in a single study; (2) To determine if the intra-subject variation in hormone levels changes with age (a few studies have focused on relatively young men); (3)To examine the magnitude of any seasonal variability (this could affect clinical interpretation of results and power calculations in clinical trials). It is also important to estimate the relative contribution of assay variation and biological variation to total intra-subject variation. The proposed research builds on nearly 20 years of work on the MMAS and results will have an impact at several levels- the epidemiology of male endocrine change, clinical trials design and the clinical management of individual patients with androgen deficiency.