title: Obesity is associated with increased prostate growth and attenuated prostate volume reduction by dutasteride.
abstract: BACKGROUND
  Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors.
  
  
  OBJECTIVE
  To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements.
  
  
  METHODS
  We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy.
  
  
  METHODS
  Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr.
  
  
  METHODS
  Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25-29.9, and ≥ 30 kg/m(2) using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression.
  
  
  CONCLUSIONS
  Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥ 30 versus < 25 kg/m(2) had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p<0.001; at 4 yr: 29.4% vs 20.1%; p=0.001). Men on dutasteride with BMI ≥ 30 versus < 25 kg/m(2) had attenuated PV reduction from baseline (at 2 yr: -14.3% vs -18.5%; p=0.002; at 4 yr: -13.2% vs -19.3%; p=0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08-1.93; p=0.014; at 4 yr: OR: 1.62; 95% CI, 1.18-2.22; p=0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥ 0.36). No clinical outcomes or effects of weight change were assessed.
  
  
  CONCLUSIONS
  Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy.
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA. roberto.muller@doctor.com
authors.forename: Roberto L
authors.initials: RL
authors.lastname: Muller
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hamilton
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
authors.forename: J Kellogg
authors.initials: JK
authors.lastname: Parsons
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000368:Aged; D001378:Azasteroids / Q000627:therapeutic use*; D001706:Biopsy; D015992:Body Mass Index; D000068538:Dutasteride; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000150:complications*; D009929:Organ Size; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D000068538:Dutasteride