Prior studies testing the association between insulin resistance (IR) and prostate cancer (PC) risk are inconsistent. We examined the association between Homeostatic Assessment of Insulin Resistance (HOMA-IR; calculated from fasting baseline insulin and glucose) and PC in REDUCE, a 4-year randomized trial of dutasteride vs. placebo for PC prevention.

All patients had prestudy negative biopsies and underwent study mandated biopsies at 2 and 4 years regardless of prostate-specific antigen. Multivariable logistic regression models were used to investigate the associations between log-transformed or categorized HOMA-IR scores and PC risk. Multinominal regression was used to assess associations between HOMA-IR scores and tumor grade (low grade [grade group 1]; high-grade [grade groups 2-5]).

Among 5430 REDUCE participants (1212 with PC; 856 low- and 356 high-grade), higher HOMA-IR was associated with lower PC risk (log-HOMA-IR: OR, 0.89; 95% CI, 0.80-0.99; p = .03; categorized HOMA-IR: p-trend = .04). When stratified by grade, HOMA-IR was significantly associated with reduced low-grade PC risk (log-HOMA-IR: OR, 0.84; 95% CI , 0.74-0.94; p = .003; categorized HOMA-IR: p-trend = .002) but was unrelated to high-grade PC (log-HOMA-IR: OR, 1.02; 95% CI, 0.86-1.21; p = .81; categorized HOMA-IR: p-trend = .26). Results were similar in placebo and treatment arms.

In summary, higher HOMA-IR was associated with a reduced risk of low-grade PC but was not associated with high-grade disease. The mechanisms to explain these findings are unclear.