Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia.
OBJECTIVE
The 5 alpha-reductase inhibitor, finasteride, provides a logical medical treatment for benign prostatic hyperplasia (BPH). However, the effects of chronic finasteride treatment on prostatic androgen levels, 5 alpha-reductase activity and tissue prostatic specific antigen (PSA) have not been studied. We have examined prostate tissue androgen concentrations and 5 alpha-reductase activity of the gland in men with BPH treated with the drug for 3 months.


METHODS
Twenty-eight patients with clinically diagnosed BPH, awaiting transurethral resection of the prostate, were entered in a double-blind placebo controlled study. Nineteen patients were randomly allocated to treatment with finasteride (5 mg daily) and 9 received placebo for 3 months.


METHODS
Prostate specimens were collected immediately following surgery and analysed for testosterone, dihydrotestosterone (DHT), androstenedione, 5 alpha-reductase activity and PSA. Blood specimens obtained before the start and immediately following treatment were also tested for steroid hormone concentrations and PSA levels.


RESULTS
There was no significant difference in the median levels of intraprostatic testosterone (P = 0.77), DHT (P = 0.46) and androstenedione (P = 0.09) between the finasteride and placebo groups. However, the 5 alpha-reductase activity of the placebo group (237.9 pmol DHT/g tissue/30 min) was approximately 10 times that of the finasteride group (21.5 pmol DHT/g tissue/30 min; P = 0.0008). Although we were unable to detect any differences in the PSA concentrations of the prostate glands, there was a significant difference (P = 0.0002) in the median percentage change of serum PSA concentrations for the two patient groups. Serum DHT levels were also depleted (P = 0.038) whilst serum testosterone was increased (P = 0.054) in the finasteride patients when compared to the placebo group. Furthermore our study demonstrated no correlation between the in vitro 5 alpha-reductase activity of the gland and tissue DHT concentrations.


CONCLUSIONS
Whilst finasteride treatment induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentrations, the impact of the drug on tissue androgen concentrations varied considerably from one patient to another. The differential effect of the drug on tissue androgen concentrations suggests that in the human prostate there are possibly more than one isoform of 5 alpha-reductase responsible for the accumulation of DHT in the gland.
Habib
F K
FK
University Department of Surgery (WGH), Western General Hospital, Edinburgh, Scotland.
Ross
M
M
Tate
R
R
Chisholm
G D
GD
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D013196:Dihydrotestosterone / Q000097:blood / Q000378:metabolism; D004311:Double-Blind Method; D018120:Finasteride / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000201:enzymology / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D017430:Prostate-Specific Antigen