ENERGY BALANCE AND RISK OF BPH-RELATED OUTCOMES AND LUTS: A PROSPECTIVE STUDY

描述（由申请人提供）：良性前列腺增生（BPH）是一种良性前列腺疾病，组织学上以尿道周围和前列腺过渡区增生结节为特征，临床表现为前列腺增大和下尿路症状（LUTS）。BPH相关的结果和LUTS，我们称之为BPH/LUTS，在老年男性中非常常见，导致相当大的麻烦和生活质量下降，以及严重的并发症，如急性尿潴留，在最严重的情况下，死亡。这种常见疾病的管理和治疗费用是巨大的。仅2000年一年，BPH/LUTS的管理和治疗费用在美国就超过11亿美元。因此，鉴于BPH/LUTS对老年男性生活质量的巨大成本和负面影响，确定BPH/LUTS发展的可改变风险因素及其行动时机对于有效的一级预防策略至关重要。以体型和体力活动（PA）衡量的能量平衡有望成为BPH/LUTS的可改变原因。一些关于晚年体型和PA的研究发现体型与BPH/LUTS呈正相关，而PA与BPH/LUTS呈负相关，这表明能量平衡可能有助于BPH/LUTS。然而，这些研究大多局限于流行的BPH/LUTS，使他们的研究结果容易受到反向因果关系和回忆偏差的影响。很少有研究调查了体型和/或PA与BPH/LUTS事件的关系，在这些少数研究中，大多数研究没有观察到任何关联，这引起了对普遍发现的质疑。其他悬而未决的问题包括可能的时机的影响身体大小和PA BPH /附近地区发展和这两个因素的共同影响。因此，为了解决这些重要的研究空白，我们建议在大型前列腺、肺癌、结直肠癌和卵巢癌筛查试验中，调查基线时的体型和PA与BPH/LUTS事件的关系，以及生命早期、整个成年期的PA。拟议的分析具有创新性，因为它们将是调查体型和PA与BPH/LUTS事件之间关系的少数研究之一；这是仅有的几项研究之一，研究了早期和成年期体型和前列腺癌与BPH/LUTS的关系，也是据我们所知的第一个研究体型和前列腺癌对BPH/LUTS风险的共同影响。提出的分析具有重要意义，因为它们有望为BPH/LUTS的发展提供新颖、有效和量身定制的初级预防策略，包括可能干预措施的性质，例如，在“肥胖和健康”的男性中，PA维持还是体型减小对压力更重要；以及干预的必要时机，即是否需要在生命早期强调体型减小和/或PA增加，或者在生命后期体型和PA的变化是否仍然可以降低BPH/LUTS的风险。BPH/LUTS的新型预防策略对于减少这种极其常见和令人烦恼的疾病的发病率，减轻其巨大的经济和健康负担至关重要。

DESCRIPTION (provided by applicant): Benign prostatic hyperplasia (BPH) is a benign prostate condition characterized histologically by hyperplastic nodules in the periurethral region and transition zone of the prostate, and clinically by an enlarged prostate and lower urinary tract symptoms (LUTS). BPH-related outcomes and LUTS, which we refer to as BPH/LUTS, are extremely common among older men, leading to considerable bother and decreased quality of life, as well as severe complications, such as acute urinary retention and, in the most severe cases, death. Costs associated with management and treatment of this common condition are tremendous. In the year 2000 alone, BPH/LUTS management and treatment cost over $1.1 billion in the U.S. Therefore, given the considerable costs and negative impact of BPH/LUTS on older men's quality of life, identification of modifiable risk factors for BPH/LUTS development and their timing of action is crucial to inform effective primary prevention strategies. Energy balance, measured as body size and physical activity (PA), shows promise as a modifiable cause of BPH/LUTS. Several studies of later-life body size and PA have observed positive associations for body size, and inverse associations for PA with BPH/ LUTS, suggesting that energy balance may contribute to BPH/LUTS. However, most of these studies were limited to prevalent BPH/LUTS, making their findings susceptible to reverse causation and recall bias. Very few studies have investigated body size and/or PA in relation to incident BPH/LUTS and, of these few studies, most have observed null associations, drawing into question prevalent findings. Other unanswered questions include the possible timing of influence of body size and PA on BPH/LUTS development and the joint influence of these two factors. Therefore, to address these important research gaps, we propose to investigate body size and PA at baseline, as well as earlier in life, across adulthood, and jointly in relation to incident BPH/LUTS in the large Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The proposed analyses are innovative because they will be one of only a few studies to investigate body size and PA in relation to incident BPH/LUTS; one of only a few to examine body size and PA earlier in life and across adulthood in relation to BPH/LUTS, and the first, to our knowledge, to investigate the joint influence of body size and PA on BPH/LUTS risk. The proposed analyses are significant because they hold the promise to inform novel, effective and tailored primary prevention strategies for BPH/LUTS development, including both the nature of possible interventions, e.g., whether PA maintenance or body size reduction is more important to stress in a "fat and fit" man; as well as the necessary timing of interventions, i.e., whether body size reduction and/or increase in PA need to be stressed earlier in life, or whether changes in body size and PA later in life may still reduce BPH/LUTS risk. Novel prevention strategies for BPH/LUTS are critical to reduce the incidence of this extremely common and bothersome condition, and ease its substantial economic and health burden. PUBLIC HEALTH RELEVANCE: The proposed secondary data analyses are relevant to public health because they will determine whether large body size (e.g., overweight and obesity) and lesser physical activity contribute to the development of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in middle- and older-aged men. If our findings are promising, these could guide the development of novel, effective, and tailored primary prevention strategies for BPH/LUTS based on reduction or maintenance of body size and increase or maintenance of physical activity in men. Novel primary prevention strategies for BPH/LUTS are crucial to reduce the incidence of this extremely common and bothersome condition, and ease its tremendous financial and health toll.