Summary
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 (x=0.586 mg/ml) and in group III (x=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.
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Ahmed SR, Grant J, Shalet SM, Howell AL, Chowdhury SD, Weatherson T, Blacklock HJ (1985) Preliminary report on use of depot formulation of LHRH analogue ICI 118–630 (Zoladex) in patients with prostate cancer. Br Med J 290:185
Arimura A, Serafini P, Talbot S (1979) Reduction of testicular luteinizing hormone human chorionic gonadotropin receptors ba (D-Trp6) — luteinizing hormone-releasing hormone in hypophysectomized rats. Biochem Biophys Res Commun 90:687
Auclair C, Kelly PA, Coy DH (1977) Potent inhibitory activity of (D-Leu6 des-Gly-NH 102 )-LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat. Endocrinology 101:1890
Auclair C, Kelly PA, Labrie F (1977) Inhibition of testicular LH/hCG receptor level by treatment with a potent LHRH agonist or hCG. Biochem Biophys Res Commun 76:855
Auclair C, Ferland S, Cusan L (1978) Effect inhibiteur de la LHRH sur le recepteurs de la LH dans le testicule chez le rat. C R Acad Sci (D) (Paris) 1305
Badger TM, Longhlin JS, Nadaft PG (1983) The luteinizing hormone-releasing hormone (LHRH) desensitized rat pituitary: luteinizing hormone responsiveness to LHRH in vitro. Endocrinology 112:793
Bélanger A, Auclair C, Séguin C (1979) Down-regulation of testicular androgen biosynthesis and LH receptor levels by an LHRH agonist. Role of prolactin. Mol Cell Endocrinol 13:47
Bélanger A, Labrie F, Lemay A (1980) Inhibitory effects of a single intranasal administration of (D-Ser (TBU)6, des Gly-NH 102 )-LHRH agonist, on serum steroid levels in normal adult men. Steroid Biochem 13:123
Bergquist C, Nillius SJ, Bergh T (1979) Inhibitory effects of gonadotropin secretion and gonadal function in men during chronic treatment with a potent stimulatory luteinizing hormone-releasing hormone analogue. Acta Endocrinol 91:601
Coppage WS, Cooner AE (1965) Testosterone in human plasma. N Engl J Med 273:902
Faure N, Labrie F, Lemay A, Bélanger A, Gourgeau Y, Laroche B, Robert G (1982) Inhibition of serum androgen levels by chronic intranasal and subcutaneous administration of a potent luteinizing hormone-releasing hormone (LHRH) agonist in adult men. Fertil Steril 37:416
Grant JBF, Ahmed SR, Shalet SM (1986) Testosterone and gonadotropin prontes in patients on daily or monthly LHRH analogue ICI 118–630 (ZoladexR) compared with orchidectomy. Br J Urol 58:539
Hsueh AJW, Erickson GF (1979) Extrapituitary inhibition of testicular function by luteinizing hormone-releasing hormone. Nature 281:66
Labhart A (1978) The testis. In: Labhart A (ed) Clinical endocrinology. Springer, Berlin Heidelberg New York
Labrie F, Bélanger A, Cusan L (1980) Antifertility effects of LHRH agonists in the male. J Androl 1:209
Labrie F, Godbout M, Bélanger A (1981) Mechanisms of the antifertility effects of LHRH agonists in the male rat. In: Zatuchini GI, Shelton JD, Sciarra JJ (eds) LHRH peptides as female and male contraceptives. Harper & Row, Philadelphia
Lunglmayr G, Bieglmayer C, Stitch SR (1985) The endocrine response to a biodegradable depot formulation of Zoladex (ICI 118–630) in patients with advanced prostatic cancer. In: Jarding A (ed) Proceedings of the International Congress of Urology, p 309
Robinson MRG, Denis I, Mahler C (1985) An LHRH analogue (Zoladex) in the management of carcinoma of the prostate: a preliminary report comparing daily subcutaneous injection with monthly depot injection. Eur J Surg Oncol 11:159
Sandow J (1982) Inhibition of pituitary and testicular function by LHRH analogues. In: Jeffcoate SL, Sandler M (eds) Progress towards a male contraceptive. Wiley & Sons, London, p 19
Sandow J, Von Rechenberg WV, Jerzabek G (1978) Pituitary gonadotropin inhibition by highly active analogue of luteinizing hormone-releasing hormone. Fertil Steril 30:205
Sandow J, Von Rechenberg WV, König W (1978) Physiologic studies with highly active analogues of LHRH. In: Gupta D, Voelter W (eds) Hypothalamic hormones — chemistry, physiology and clinical applications. Verlag Chemie, Weinheim New York, p 307
Smith JA Jr (1984) Androgen suppression by a gonadotropin releasing hormone analogue in patients with metastatic carcinoma of the prostate. J Urol 131:1110
Smith R, Donald RA, Espiner EA (1979) Normal adults and subjects with hypogonadotrophic hypogonadism respond differently to (D-Ser (TBU)6, des Gly-NH 102 )-LHRH-EA. J Clin Endocrinol Metab 48:167
Van Chang PJ, Opsomer R. Treatment of advanced carcinoma of the prostate with a depot luteinizing hormone-releasing hormone analogue (ICI 118–630). J Urol 137:66
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Kuber, W., Viehberger, G., Zeillinger, R. et al. 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. Urol. Res. 19, 19–24 (1991). https://doi.org/10.1007/BF00294016
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DOI: https://doi.org/10.1007/BF00294016