Our previous case-control study suggested that
equol, a metabolite of
isoflavone, has a preventive effect on
prostate cancer. To examine the
prostate cancer risk based on
isoflavone intake and
equol production, we carried out a phase II, randomized, double-blind, placebo-controlled trial of oral
isoflavone (60 mg/day) for 12 months. The inclusion criteria were Japanese men between 50 and 75 years of age, a serum
prostate-specific antigen level of 2.5-10.0 ng/mL, and a single, negative prostate biopsy within 12 months prior to enrollment. The study included 158 men in eight Japanese centers. Their median age was 66.0 years, and the numbers of
equol producers and non-producers were 76 (48%) and 82 (52%), respectively. The majority of adverse events were mild or moderate in severity, and the scheduled intake of
tablets was completed by 153 patients (96.8%). The
prostate-specific antigen value showed no significant difference before and
after treatment. Of the 89 patients evaluated by central pathological review, the incidence of biopsy-detectable
prostate cancer in the
isoflavone and placebo groups showed no significant difference (21.4%vs 34.0%, P = 0.140). However, for the 53 patients aged 65 years or more, the incidence of
cancer in the
isoflavone group was significantly lower than that in the placebo group (28.0%vs 57.1%, P = 0.031). These results support the value of
isoflavone for
prostate cancer risk reduction. A large-scale phase III randomized study of
isoflavone tablets in men with different hereditary factors and living environments is warranted. Registered with the UMIN Clinical Trials Registry (UMIN-CTR) for clinical trials in Japan (C000000446).