Benign prostatic hyperplasia: Role of metabolic abnormalities and association with prostate cancer risk

This dissertation examines the role of obesity related metabolic abnormalities in the development of symptomatic benign prostatic hyperplasia (BPH), and investigates the association between symptomatic BPH and prostate cancer. Data are from the Prostate Cancer Prevention Trial (PCPT), a 7-year randomized, double-blinded, placebo-controlled trial of the drug finasteride (ProscarRTM) for the primary prevention of prostate cancer. Analyses are restricted to the approximate 9,000 men in the placebo control group. This dissertation begins by examining whether blood concentrations of two adipokines, adiponectin and leptin, and C-peptide, an indirect measure of insulin secretion and insulin resistance affect the risk of symptomatic BPH. This analysis shows that high adiponectin concentrations were associated with a reduced risk of symptomatic BPH however, only for men who were moderately/very active. The second analysis examines whether blood concentrations of pro-inflammatory cytokines known to be elevated in obesity are associated with risk of symptomatic BPH. This analysis shows that low soluble tumor necrosis factor receptor 2 and high interleukin 6 concentrations increased BPH risk however, only among men aged < 65 years. Together, these results suggest that obesity related metabolic abnormalities in glucose uptake and insulin sensitivity and systemic inflammation increase the risk of symptomatic BPH however, these abnormalities explain only a moderate amount of the relationship between obesity and BPH. Finally, I explore the association between symptomatic BPH and risk of prostate cancer in a study population where diagnostic surveillance of both BPH and prostate cancer was rigorous and complete. In this analysis there were no associations of prevalent BPH or prevalent plus incident BPH with prostate cancer risk. This lack of association was also consistent across subgroups defined by type of BPH defining event (treatment, symptoms or physician diagnosis), prompt or reason of prostate cancer diagnosis ('For-cause' or 'Not-for-cause') and prostate cancer grade (Gleason score 2-7(3+4) vs. 7(4+3)-10). This study provides the strongest evidence to date that BPH does not increase the risk of prostate cancer.