Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH).
We compared the effect of a variety of drug regimens to lower prostate DHT concentration. Patients with BPH were treated for one week prior to surgery with either tamoxifen, flutamide, megestrol acetate, megestrol acetate plus tamoxifen and megestrol acetate plus DES or ketoconazole. DHT concentration in the surgically resected tissue was compared with tissues obtained from untreated patients. We also obtained prostate tissue at the time of relapse in patients with prostate cancer who had been treated with orchiectomy with or without estrogen therapy. Megestrol acetate plus the mini-dose of DES (0.1 mg) and megestrol acetate plus ketoconazole both decreased DHT concentrations in prostate tissue to levels (0.79 ng/g) significantly below those noted with orchiectomy (1.16 ng/g). The difference between the DHT concentration in the two groups (orchiectomy vs. total androgen blockade) represents the contribution of adrenal androgens to prostate tissue DHT. This small amount of DHT (approximately 0.4 ng/g) may be biologically important in stimulating prostate epithelial cell growth.
D000726:Androgen Antagonists / Q000494:pharmacology*; D002369:Castration; D003131:Combined Modality Therapy; D004054:Diethylstilbestrol / Q000627:therapeutic use; D013196:Dihydrotestosterone / Q000032:analysis / Q000378:metabolism*; D004338:Drug Combinations; D006801:Humans; D006965:Hyperplasia / Q000628:therapy*; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D008535:Megestrol / Q000031:analogs & derivatives / Q000627:therapeutic use; D019290:Megestrol Acetate; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D014018:Tissue Distribution
D000726:Androgen Antagonists; D004338:Drug Combinations; D013196:Dihydrotestosterone; D004054:Diethylstilbestrol; D008535:Megestrol; D007654:Ketoconazole; D019290:Megestrol Acetate