Abstract 3227: Getting rid of obesity in middle-to-late adulthood relates to lower prostate cancer risk: Another piece of evidence supporting the “rapid testosterone reduction theory”
Authors: Kai Wang, Xinguang Chen, Travis A. Gerke, Victoria Y. Bird, Mattia Prosperi
Journal: Cancer Research (2018)

Abstract Background: Previously we demonstrated that a smoothed age-related decline in testosterone was associated with decreased risk of prostate cancer (PCa) (“rapid testosterone reduction theory”). Obesity relates to low testosterone, so body weight pattern reflecting smoothed testosterone decline should be related to lower PCa risk. This study aimed to validate the “rapid testosterone reduction theory” from the perspective of body mass index (BMI) pattern and risk of PCa. Methods: We conducted a nested case-control study in a retrospective hospital cohort with median follow-up of 5.0 years from a tertiary-level hospital in the Southeastern US. Electronic medical records of 18168 patients with prostate-related disease diagnosed between November 4, 1995 and January 10, 2016 were screened. The outcome was newly diagnosed PCa. Only patients with BMI measured at ≥3 differing calendar years before PCa diagnosis or the latest follow-up (for non-PCa patients) were included, resulting in a sample of 1571, among which 128 were PCa patients. BMI was analyzed in cross-section value, change, and developmental trajectories in relation to PCa risk. Results: Participant ages spanned a range of 40 to 90 years, with mean age at baseline was 57 years (standard deviation = 9.6). Baseline BMI was inversely associated with PCa risk (adjusted odds ratio [AOR], 0.76; 95% confidence interval [CI], 0.63-0.91 for every 5-unite increase in BMI). When analyzed in change between baseline and the latest follow-up, BMI increment was associated with increased PCa risk (AOR, 1.26; 95% CI, 1.05-1.51 for every 5-unite increase in BMI change). When analyzed in latent-class trajectory, a downward BMI trajectory of being obese in the 4th, 5th, and 6th decade then progressing to be non-obese since the 7th decade of age was associated with decreased PCa risk (AOR, 0.66; 95% CI, 0.45-0.98), compared to those with consistently normal BMI. When analyzed by strata of PCa diagnosis age, the same associations were more evident for PCa diagnosed after age 65. Conclusions: Weight loss and getting rid of obesity during middle-to-late adulthood is related to a decreased PCa risk, supporting the “rapid testosterone reduction theory” in explaining PCa risk. If this finding can be verified with more rigorous study, provision of testosterone replacement therapy as a weight control measure for men in middle-to-later adulthood has potentials in PCa prevention. Citation Format: Kai Wang, Xinguang Chen, Travis A. Gerke, Victoria Y. Bird, Mattia Prosperi. Getting rid of obesity in middle-to-late adulthood relates to lower prostate cancer risk: Another piece of evidence supporting the “rapid testosterone reduction theory” [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3227.