Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case-control study

Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06-2.15; for estradiol, OR = 1.50, 95% CI = 1.03-2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk. Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation.