Among new highly potent antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), containing neutral hydrophilic D-ureidoalkyl amino acids such as D-Cit and D-Hci at position 6 and free of edematogenic and anaphylactoid reactions, Ac-D-Nal(2)1, D-Ph(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10 (LH-RH) (SB-75; Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 micrograms SB-75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6 prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of SB-75 administration. This improvement continued during the course of treatment. Before therapy with SB-75, the serum levels of prostate-specific antigen (PSA) (6.73 +/- 1.46 ng/ml), acid phosphatases, total (12.67 +/- 1.15 U/l), and prostatic (2.27 +/- 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 +/- 0.59 ng/ml; P < 0.01), (7.68 +/- 0.89 U/l; P < 0.01), and (1.39 +/- 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 +/- 8.86 to 37.92 +/- 8.52 cm3; P < 0.01, which represents a reduction of 44%. In patients with prostate cancer, after the first week of therapy with SB-75, we observed a significant decrease in bone pain, relief in urinary outflow obstruction, and reversal of the signs of prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed analgesics. PSA, acid, and alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum testosterone levels in BPH and prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog SB-75, fell to castration values. A major fall in free testosterone levels was observed after the first dose; the maximal inhibition was seen after 6-12 hr, with a simultaneous decrease in levels of both gonadotropins. Our results show that antagonist SB-75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of prostatism obtained with antagonistic analog SB-75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a therapeutic alternative in men who are considered poor surgical risks.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma zinc (Zn), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and androgens concentrations were determined in 15 male patients with chronic renal failure who were successful recipients of kidney transplant. After 25 +/- 8.5 months of the renal transplant, Zn levels were (88 +/- 4 g/dl) lower than in the control group (116 +/- 5 micrograms/dl). Normal concentrations for androstenedione (A) (0.63 +/- 0.05 ng/ml) and testosterone (T) (3.31 +/- 0.15 ng/ml) were found. Dihydrotestosterone (DHT) levels (0.38 +/- 0.01 ng/ml) were lower than normal (1.11 +/- 0.09 ng/ml), suggesting a blockade in the conversion of T to DHT. Eleven of the 15 patients showed higher PRL levels (9.5 +/- 0.8 ng/ml) in contrast with the normal group (3.6 +/- 0.3 ng/ml). Ten patients received orally 2-alpha-bromoergocriptine (BEC) 2.5 mg/day for ten days. Plasma PRL decreased to 2.6 +/- 1.0 ng/ml (p less than 0.001), but A and T levels did not significantly change; however, DHT increased from 0.38 +/- 0.02 ng/ml to 0.72 +/- 0.04 ng/ml (p less than 0.01). All patients showed an increase in both gonadotropins before BEC without significant changes after treatment. The high PRL levels may be responsible for the impaired conversion of T to DHT, possibly by interference with the enzyme 5 alpha-reductase.