Association between insulin resistance and prostate volume: A 4-year analysis from the Reduction by Dutasteride of Prostate Cancer (REDUCE) Trial.

Objectives: Most, but not all studies, suggest insulin resistance is associated with benign prostatic hyperplasia, but its impact on prostate volume (PV) changes over time remains unclear. We examined whether higher insulin resistance, measured by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), is associated with larger PV and greater prostate growth over a 4-year period. Materials and Methods: We analysed data from the 4-year, randomized, double-blind, placebo-controlled REDUCE trial testing whether dutasteride could prevent prostate cancer. Patients underwent transrectal ultrasound measuring PV at baseline, year 2 and year 4. We calculated HOMA-IR from baseline fasting glucose and insulin, then stratified patients into quartiles within each arm (placebo vs. dutasteride). Using multivariable models, we estimated PV changes over time. We conducted a sensitivity analysis excluding patients with diabetes. Results: Higher HOMA-IR quartiles were associated with larger PV at baseline, year 2 and year 4 in both placebo and dutasteride arms (all p < 0.001), though absolute differences were modest. PV increased in the placebo arm over 4 years, whereas it decreased in the dutasteride arm. However, there was no significant association between HOMA-IR and PV change in either arm. Results remained unchanged after excluding patients with diabetes. Conclusion: Patients with higher HOMA-IR had modestly larger PVs at baseline, year 2 and year 4, but insulin resistance was unrelated to PV change over four years. These findings suggest that insulin resistance may be a modifiable risk factor contributing to benign prostatic enlargement, though further research is needed to determine its clinical relevance.