EFFECTS OF THE DURATION OF THERAPY WITH THE LHRH AGONIST D-SER (BUT)6 AZGLY10-LHRH (ICI 118-630) ON THE STEROID-HORMONE CONTENT AND THE MORPHOLOGY OF HUMAN TESTICULAR TISSUE IN THE TREATMENT OF PATIENTS WITH ADVANCED PROSTATE-CANCER

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (chi-BAR = 0.586 mg/ml) and in group III (chi-BAR = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P < 0.000001) and follicle-stimulating hormone (P < 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy. In contrast, the functional endocrine changes achieved in the serum and testicular tissue after 2 months of treatment remained stable even if treatment with the depot LHRH agonist ICI 118-630 was continued for 3 years.