TY - JOUR
T1 - Obesity is associated with increased prostate growth and attenuated prostate volume reduction by dutasteride
AU - Muller, Roberto L.
AU - Gerber, Leah
AU - Moreira, Daniel M.
AU - Andriole, Gerald
AU - Hamilton, Robert J.
AU - Fleshner, Neil
AU - Parsons, J. Kellogg
AU - Freedland, Stephen J.
PY - 2013/6
Y1 - 2013/6
N2 - 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. Design, setting, and participants: 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. Intervention: Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. Outcome measurements and statistical analysis: 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/m2 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. Results and limitations: 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/m2 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/m2 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. ClinicalTrials.gov identifier: NCT00056407.
AB - 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. Design, setting, and participants: 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. Intervention: Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. Outcome measurements and statistical analysis: 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/m2 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. Results and limitations: 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/m2 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/m2 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. ClinicalTrials.gov identifier: NCT00056407.
KW - 5α-reductase inhibitors
KW - Dutasteride
KW - Growth and development
KW - Obesity
KW - Prostate
KW - Prostatic hyperplasia
KW - Ultrasonography
UR - http://www.scopus.com/inward/record.url?scp=84876478193&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2013.02.038
DO - 10.1016/j.eururo.2013.02.038
M3 - Article
C2 - 23541458
AN - SCOPUS:84876478193
SN - 0302-2838
VL - 63
SP - 1115
EP - 1121
JO - European Urology
JF - European Urology
IS - 6
ER -