Objective: To investigate the association of body mass index (BMI) and BMI change with change in prostate-specific antigen (PSA) level and to assess the possible roles of PSA hemodilution and prostate volume in explaining the obesity and PSA association. Methods: In 1990, a randomly selected cohort of Caucasian men, aged 40 to 79 years, from Olmsted County, Minnesota, completed questionnaires ascertaining demographic characteristics, current medical conditions, and medications biennially, with a subset undergoing blood draws and clinical examinations. Linear mixed models were used to predict annual changes and intercepts of individual changes in BMI, PSA, prostate volume, plasma volume, and PSA mass, adjusting for age in 545 men with at least 2 serial PSA, BMI, and prostate volume measurements. Results: Baseline BMI was inversely associated with the annual percent change in PSA, adjusting for age, baseline PSA, and prostate volume and for the rates of change in BMI and prostate volume (β =-0.003, 95% CI: -0.006 to -0.0003). Baseline obesity was positively associated with mean baseline levels and the rate of change in prostate volume (P = 0.002) and plasma volume (both P < 0.001) but was not associated with either the mean baseline values or the rate of change in PSA mass. Conclusions: Baseline obesity was associated with baseline PSA and prostate volume and with the rate of change in PSA over 15 years of follow-up. Impact: The inverse association of obesity with prostate cancer diagnosis may be at least partly due to detection bias, which is due to larger prostate volumes and PSA hemodilution in obese men.
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