Castration-like effects on the human prostate of a 5 alpha-reductase inhibitor, finasteride.
Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BPH) and prostate cancer. 5 alpha-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 5 alpha-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trials 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 from 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Geller
J
J
Department of Medical Education, Mercy Hospital and Medical Center, San Diego, California 92103-2180.
Sionit
L
L
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes / Q000494:pharmacology*; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000378:metabolism; D018120:Finasteride; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride