INVITED COMMENT
Possible Enhancement of Prostate Carcinogenesis by
Some Chemopreventive Agents
Some of the most promising agents for chemoprevention of prostatic cancer, i.e., 5a-reductase inhibitors and retinoids, may enhance rather than slow down the progression of prostatic cancer. I have summarized observations in the literature that form the basis for this troubling possibility below.
The proposition to use 5a-reductase inhibitors for chemoprevention of prostatic cancer is based on the assumption that these substances will prevent the predicted enhancing effect of endogenous androgens on progression of preneoplastic and early malignant lesions in the prostate. However, the studies summarized by Isaacs [ 11 indicate that theoppositeeffect may occur, perhaps due to a considerable increase of prostatic testosterone concentrations. Furthermore, it is possible that Sa-reductase inhibitors may actually select for androgen-independent cells by providing a selective growth advantage for these cells. A causal relation between androgens and prostate carcinoma development in man and animal models is very plausible. Male human populations that are at high risk for prostate cancer, for example African-Americans [2], often have slightly higher circulating testosterone levels than low risk populations [3,4]. Nevertheless, this may not be universally true in all high risk populations. Meikle andco-workers [ S ] found thatcirculating levels of testosterone and 5a-dihydrotestosterone were significantly lower in brothers (age 47-75) and