DESCRIPTION (provided by applicant): Benign prostatic hyperplasia (BPH) is an extremely common clinical syndrome in aging men that is characterized by a constellation of signs and lower urinary tract symptoms which can have a dramatic negative impact on quality of life and serious long-term sequelae. Once considered a normal concomitant of aging, with surgical treatment the only option, new minimally invasive and pharmacologic therapies permit earlier intervention and have led to a critical need to better understand its development and progression. To this end, we have been performing biennial examinations, with standardized instruments and protocols, on a cohort of over 2000 randomly selected Olmsted County Minnesota men since 1990. These population- based data permit inferences that are not subject to the selection biases present in most previous studies. These efforts have allowed us to, in many ways, define the epidemiology of BPH with respect to the rate of onset and progression of BPH in community-dwelling men, its impact on long-term outcomes (e.g., acute urinary retention, chronic kidney disease) and quantified its impact on quality of life. These insights have proven extremely valuable in designing intervention studies, and putting their results in the community context. Nonetheless, with each new insight, important new questions arise. In this next funding period, we will build on our findings of cross-sectional associations between BPH and circulating sex steroid levels as well as polymorphisms in genes encoding proteins involved in steroid metabolism and action. Based on our extensive longitudinal phenotypic information, banked DNA and serum samples and genotype information, we are ideally poised to now determine how changes in hormone levels are related to changes in measures of BPH and how these genetic polymorphisms modify these associations. We will also investigate the population distributions of Prostate Specific Antigen(PSA) species (e.g. BPSA and pro-PSA), which may improve our ability to differentiate between men with cancer, BPH and normal prostates. And, by adding three new sonographic measurements (i.e. estimated total bladder weight and intravesical prostatic protrusion and presumed circle area ratio) to our protocol we will be able to evaluate their prognostic value from a population perspective, that will help us understand how they should be used in new large-scale clinical trials. Finally, through continued passive followup of this cohort, and a population-based cohort of men newly-diagnosed with BPH, through their community medical records, we will inform a major controversy about the risks and outcomes associated with acute urinary retention. Thus, with the completion of these aims, our multi-disciplinary team will build on our fifteen years of experience, unparalleled clinical data and cutting edge laboratory measurements to further our understanding of this chronic, progressive and important disease, from a population perspective that is free from many of the biases inherent in studies conducted in referral or other clinical practices. Public Health Relevance: We will use state-of-the-art clinical and laboratory methods to address important questions about how genes, hormones and other factors play a role in the development and progression of BPH, with a goal of understanding how this common and extremely bothersome condition might be avoided.
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