Castration-like effects on the human prostate of a 5α-reductase inhibitor, finasteride

Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BHP) and prostate cancer. 5α-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5α-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trails in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue form surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates. If the acute effects of finasteride on tissue T and DHT persist during chronic therapy, prostatic hormone concentrations could be said to closely resemble those found following surgical castration; such changes might prevent the occurrence of prostate cancer, similar to the effects noted after surgical castration in younger males. © 1992 Wiley-Liss, Inc.