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

描述(申请人提供)：良性前列腺增生症(BPH)是一种良性前列腺疾病，在组织学上以尿道周围和前列腺移行区的增生性结节为特征，临床上以前列腺肥大和下尿路症状(LUTS)为特征。与BPH相关的结局和LUT，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。与这种常见疾病的管理和治疗相关的成本是巨大的。仅在2000年，美国的BPH/LUTS管理和治疗费用就超过11亿美元。因此，考虑到BPH/LUTS对老年男性生活质量的巨大成本和负面影响，识别BPH/LUTS发生的可改变的风险因素及其行动的时机对于制定有效的初级预防策略至关重要。能量平衡，以身体大小和体力活动(PA)衡量，显示出作为BPH/LUTS的可修改原因的前景。一些关于晚年身体大小和PA的研究已经观察到身体大小与PA正相关，而PA与BPH/LUTS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，使得他们的发现容易受到反向因果关系和回忆偏差的影响。很少有研究调查身体大小和/或PA与BPH/LUTS事件的关系，在这些少数研究中，大多数研究观察到无效的相关性，这对普遍存在的发现提出了质疑。其他悬而未决的问题包括身体大小和PA对BPH/LUTS发生影响的可能时机，以及这两个因素的共同影响。因此，为了解决这些重要的研究差距，我们建议在大型前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验中，调查基线和生命早期、成年期的体型和PA，并联合调查BPH/LUTS事件。拟议的分析是创新的，因为它们将是少数几项研究之一，调查身体尺寸和PA与BPH/LUTS事件的关系；少数几项研究生命早期和成年期与BPH/LUTS的关系的研究之一；以及第一，据我们所知，调查身体尺寸和PA对BPH/LUTS风险的联合影响。拟议的分析具有重要意义，因为它们有望为BPH/LUTS的发展提供新的、有效的和量身定制的一级预防策略，包括可能干预的性质，例如，保持PA或缩小身体尺寸对“肥胖和健康”的男性来说更重要；以及必要的干预时机，即是否需要在生活的早期强调身体尺寸的缩小和/或PA的增加，或者是否在生活的后期改变身体尺寸和PA是否仍然可以降低BPH/LUTS的风险。针对BPH/LUTS的新的预防策略对于减少这种极其常见和令人烦恼的疾病的发生率以及减轻其巨大的经济和健康负担至关重要。 公共健康相关性：拟议的二级数据分析与公共健康相关，因为它们将确定较大的身体尺寸(例如，超重和肥胖)和较少的体力活动是否会导致中老年男性发生良性前列腺增生症(BPH)/下尿路症状(LUTS)。如果我们的发现是有希望的，这些可以指导开发新的、有效的和量身定制的BPH/LUTS初级预防策略，基于减少或保持男性的身体尺寸和增加或保持体力活动。针对BPH/LUTS的新的初级预防策略对于减少这种极其常见和令人烦恼的疾病的发生率以及减轻其巨大的经济和健康损失至关重要。

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.