Risk factors for lower urinary tract symptom progression among older men

描述（由申请人提供）：下尿路症状（LUTS）是一组慢性泌尿系统疾病，每年影响美国和国外数百万男性。LUTS是良性前列腺增生的临床表现，是前列腺生长不受调节的一种情况。LUTS的患病率随着年龄的增长而增加，许多男性的症状随着时间的推移而恶化。与这一模式一致的是，我们在男性骨质疏松性骨折（MrOS）队列中65岁及以上男性的初步数据表明，约20%的患者报告了临床相关的症状进展，定义为症状评分至少改变4分。尽管LUTS给男性健康带来了负担，但令人惊讶的是，人们对影响这些症状进展的因素知之甚少。一个障碍是认为LUTS是不可避免的衰老过程，由不可改变的刺激，如性类固醇激素驱动。然而，主要来自横断面研究的令人兴奋的新数据表明，可改变的因素，特别是代谢来源的因素，可能影响LUTS的发病机制。因此，我们的目标是进一步阐明LUTS的病因，以扩大预防的选择和改善患者预后的临床工具。本提案的主要目标是：1)确定老年男性LUTS进展的危险因素；2)利用所得的流行病学数据建立临床有用的风险预测模型。为了实现这些目标，我们提出了一项前瞻性研究，使用在mrs队列中收集的5,995名年龄在65-100岁的美国男性的综合数据。在5年的随访中，使用美国泌尿协会症状指数（AUA-SI）对LUTS进行了三次评估，这是一种经过验证且广泛使用的7项工具。在随访中，主要的进展指标将被定义为AUA评分增加4分，这是临床公认的相关症状进展指标。将进行详细的风险因素评估，重点是代谢和生活方式因素。与这些评估相关的测量包括全身和躯干脂肪分布（直接通过双能x线吸收仪[DXA]量化），准确测定的空腹血清胰岛素、葡萄糖、脂质和维生素D，以及经过验证的仪器测量的身体活动和饮食。我们将测试这样的假设，即进展的风险与肥胖和高脂血症等因素有关，显著增加，与体育锻炼或水果和蔬菜摄入较多等因素有关，显著降低。分析将根据初始症状水平（无/轻度、中度/严重）进一步分层，以确定任何观察到的与症状严重程度相关的适用性。利用前瞻性分析的结果，我们将应用一种新的统计技术组合来预测经历LUTS结果的个体风险。这项研究将进一步了解老年男性LUTS进展的自然历史与代谢和生活方式因素的关系。通过这样做，我们期望为预防和治疗LUTS确定各种新的选择。

DESCRIPTION (provided by applicant): Lower urinary tract symptoms, or LUTS, represent a cluster of chronic urinary disorders that affect millions of men in the U.S. and abroad each year. LUTS is the clinical manifestation of benign prostatic hyperplasia, a condition of unregulated growth in the prostate gland. The prevalence of LUTS increases with age, and many men experience a worsening of their symptoms over time. Consistent with this pattern, our preliminary data among men ages 65 years or older in the Osteoporotic Fractures in Men (MrOS) cohort indicates that about 20% reported clinically relevant progression of symptoms, defined as a change of at least 4 points in symptom score. Despite the burden that LUTS imposes on men's health, surprisingly little is known about factors that affect progression of these symptoms. One barrier has been the view that LUTS are in inevitable process of aging driven by non-modifiable stimuli such as sex steroid hormones. However, exciting new data primarily from cross-sectional studies suggests that modifiable factors, especially those of metabolic origin, could influence LUTS pathogenesis. Thus, our goal is to further elucidate LUTS etiology in order to expand the options for prevention and improve clinical tools for patient prognosis. The primary objectives of this proposal are to 1) determine the risk factors for progression of LUTS among older men and 2) to use the resulting epidemiologic data to develop clinically useful risk prediction models. To accomplish these objectives, we propose a prospective study using comprehensive data already collected among 5,995 US men ages 65-100 years in the MrOS cohort. LUTS have been assessed three times during 5 years of follow-up with the American Urologic Association Symptom Index (AUA-SI), a validated and widely used 7-item instrument. During follow-up, the primary measure of progression will be defined as an increase in AUA score of 4 points, a clinically accepted indicator of relevant symptom progression. Detailed risk factor assessments with a focus on metabolic and lifestyle factors will be performed. Measures relevant to these assessments include total body and trunk fat distribution (quantified directly from dual energy x-ray absorptiometry[DXA]), fasting serum insulin, glucose, lipids, and vitamin D from accurate assays, and physical activity and diet from validated instruments. We will test hypotheses that risk of progression is significantly increased in relation to factors such as greater adiposity and hyperlipidemia, and is significantly reduced in relation to factors such as greater physical activity or higher fruit and vegetable consumption. Analyses will be further stratified by initial symptom level (none/mild, moderate/severe) in order to determine the applicability of any observed associations to symptom severity. Using results of the prospective analysis, we will apply a novel combination of statistical techniques to predict individual risk of experiencing a LUTS outcome. This study will advance knowledge about the natural history of LUTS progression among older men in relation to metabolic and lifestyle factors. By so doing, we expect to identify a variety of new options for the prevention and treatment of LUTS. PUBLIC HEALTH RELEVANCE: Chronic lower urinary tract symptoms, known as LUTS, affect millions of men in the U.S. each year and cost billions of dollars to diagnose and treat. Defining possible causes of and methods for preventing these symptoms remains an understudied area. Results of the proposed research will help determine the clinically relevant characteristics of older men at greatest risk of developing LUTS and uncover potential ways of preventing these bothersome and costly symptoms.