Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content.
The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3 alpha-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 0.01 for DHT and P less than 0.05 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (0.10 greater than P greater than 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 +/- 1.79 (SD) ng/mL (16.5 +/- 6.2 nmol/L) to 0.27 +/- 0.42 ng/mL (0.9 +/- 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.
Forti
G
G
Department of Clinical Physiopathology, University of Florence, Italy.
Salerno
R
R
Moneti
G
G
Zoppi
S
S
Fiorelli
G
G
Marinoni
T
T
Natali
A
A
Costantini
A
A
Serio
M
M
Martini
L
L
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000032:analysis*; D003692:Delayed-Action Preparations; D013196:Dihydrotestosterone / Q000032:analysis; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D007668:Kidney / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000032:analysis*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D011944:Receptors, Androgen / Q000032:analysis*; D013739:Testosterone / Q000032:analysis; D014599:Uterus / Q000032:analysis
D000728:Androgens; D003692:Delayed-Action Preparations; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase