The purpose of this phase I dose-finding randomized controlled trial was to evaluate the safe and effective dose of
isoflavones to be used in future clinical trials for
prostate cancer prevention. Forty-five eligible men were supplemented with 40, 60, and 80 mg of purified
isoflavones or no supplement from biopsy to
prostatectomy. Compliance with the study agent, toxicity, and changes in plasma
isoflavones, serum
steroid hormones,
prostate-specific antigen (PSA), and tissue Ki-67 were analyzed from baseline to completion of the study. Forty-four subjects completed the study with a duration of intervention of 30 (+/- 3) days. We observed significant increases in plasma
isoflavones with treatment for all doses compared with controls without producing any toxicity. Significant increases in serum total
estradiol were observed in the 40 and 60 mg
isoflavone-treated arms. However, a significant increase in serum free
testosterone was observed in the 60 mg
isoflavone-treated arm. Changes in serum
sex hormone-binding globulin, PSA, and percentage of tissue Ki-67 were not statistically significant with treatment for this sample size and duration of intervention. Our results identify a safe dose of purified
isoflavones for future clinical trials and establish the need for further definitive, well-powered trials to examine the role of
isoflavones in prostate
carcinogenesis.