Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate

A new approach to the classical concept


Since the introduction of contrasexual treatment as the basic concept of palliation of prostatic carcinoma in the 1940's, orchiectomy, estrogens, and, in recent years, antiandrogens have become generally accepted treatment forms. Three facts: 1) estrogen treatment being at best palliative and at worst dangerous; 2) surgical castration having psychological impacts, at least in the younger age group; and 3) both being probably ineffective from the beginning, have led us to investigate an alternative of minimal toxicity and possible reversibility in the initial treatment of advanced prostatic carcinoma. 12 patients with far advanced carcinoma of the prostate were treated with the gonadotropin releasing hormone analogue [D-Ser(But)6]-LH-RH(1-9)-nonapeptide ethylamide (Buserelin, Hoe 766), which caused down-regulation of pituitary luteinizing hormone (LH) receptors and suppressed testosterone to castrate levels within four weeks. The production rate of testosterone (PR-T) was lowered to values comparable to those after bilateral orchiectomy within two weeks. Subjectively, patients responded favorably with a relief of metastatic bone pain in all cases and an improvement of the Karnofsky Performance Index to an average score of 75 in those patients who had had an initially low index averaging 45. Objective responses included reduction of local tumor mass with resolution of bilateral ureteral obstruction, regression of pulmonary and bone metastases, and decrease of initially elevated serum acid phosphatase concentration. On the basis of these preliminary data, it should be expected that treatment of far advanced prostatic adenocarcinoma with gonadotropin-releasing hormone analogues is a safe, nontoxic and effective form of palliation.

This is a preview of subscription content, access via your institution.


  1. 1.

    Badger TM, Beitius JZ, Ostrea T, Crisafulli JM, Little R, Saidel ME (1980) Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro. Endocrinology 106:1149–1153

    Google Scholar 

  2. 2.

    Bélanger A, Labrie F, Lemay A, Caron S, Raymond JP (1980) Inhibitory effects of a single intranasal administration of D-SER(TBU)6, des-Gly-NH210 LHRH ethylamide, a potent LHRH agonist, on serum steroid levels in normal adult men. J Steroid Biochem 13:123–126

    Google Scholar 

  3. 3.

    Berry WR, Laszlo J, Cox E, Walker A, Paulson D (1979) Prognostic factors in metastatic and hormonally unresponsive carcinoma of the prostate. Cancer 44: 763–775

    Google Scholar 

  4. 4.

    Borgmann V, Nagel R, Schmidt-Gollwitzer M, Hardt W (1982) Langzeitsuppression der gonadalen Testosteronproduktion durch den LH-RH-Agonisten (Buserelinacetat; Hoe 766) beim fortgeschrittenen Prostatakarzinom — eine neue Therapieform? Aktuel Urol 13:200–203

    Google Scholar 

  5. 5.

    Crowley WF, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB (1981) Therapeutic use of pituitary desensitization with a long acting LHRH agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab 52:370–372

    Google Scholar 

  6. 6.

    Cutt KJ, Harwood JP, Clayton RN, Davies TF, Chan V, Katikineni M, Nozu K, Dufau ML (1980) Regulation of peptide hormone receptors and gonadal steroidogenesis. Recent Prog Horm Res 36:557–622

    Google Scholar 

  7. 7.

    Ekman P, Snochowski M, Zetterberg A, Hogberg B, Gustafsson JA (1979) Steroid receptor content in human prostatic carcinoma and response to endocrine therapy. Cancer 44:1173–1181

    Google Scholar 

  8. 8.

    Happ J (1971) Therapie mit Gonadotropin-Releasing-Hormon, Untersuchungen zur Anwendung bei Hypogonadismus, Pubertas tarda und Kryptorchismus. Urban & Schwarzenberg, München

    Google Scholar 

  9. 9.

    Happ J, Hartmann V, Weber T, Cordes V, Beyer J (1978) Gonadotropin and testosterone secretion in normal human males after stimulation with gonadotropin-releasing hormone (GnRH) or potent GnRH analogs using different modes of application. Fertil Steril 30:666

    Google Scholar 

  10. 10.

    Hedlund PO, Gustafson H, Sjögren S (1980) Cardiovascular complications to treatment of prostatic cancer with estramustine phosphate (Estracyt) or conventional estrogen. A follow-up of 212 randomized patients. Scand J Urol Nephrol [Suppl] 55:103–105

    Google Scholar 

  11. 11.

    Huggins C, Stevens RE Jr, Hodges CV (1941) Studies on prostatic cancer. II. Effects of castration on advanced carcinoma of prostate gland. Arch Surg 43:209–223

    Google Scholar 

  12. 12.

    Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (1980) Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial. Br J Urol 52:208–215

    Google Scholar 

  13. 13.

    Jacobi GH, Ehrenthal W, Engelmann U, Grimm D, Riedmiller H, Prellwitz W, Hohenfellner R (1981) Immunological determination of serum acid phosphatase in patients with prostate cancer. II. Serum studies with the enzyme-immunoassay Enzygnost-PAP. Aktuel Urol 12:283–290

    Google Scholar 

  14. 14.

    Jacobi GH, Wenderoth UK (1982) Gonadotropin-releasing hormone analogues for prostate cancer: untoward side effects of high-dose regimens acquire a therapeutical dimension. Eur Urol 8:129–134

    Google Scholar 

  15. 15.

    Johnson DE, Scott WW, Gibbons RP, Prout GR, Schmidt JD, Ming chu T, Gaeta J, Savoff J, Murphy GP (1977) National randomized study of chemotherapeutic agents in advanced prostatic carcinoma. A progress report. Cancer Treat Rep 61:317–323

    Google Scholar 

  16. 16.

    Klein LA (1979) Prostatic carcinoma. N Engl J Med 300:824–833

    Google Scholar 

  17. 17.

    Linde R, Doelle CC, Alexander N, Kirchner F, Vale W, Rivier J, Rabin D (1981) Reversible inhibition of testicular steroid-genesis and spermatogenesis by a potent gonadotropin-releasing hormone agonist in normal men. N Engl J Med 305:663–667

    Google Scholar 

  18. 18.

    Lukkarinen O, Hammond GL, Kontturi M, Viktor R (1979) Testicular steroid secretion and peripheral serum steroid concentrations in patients with prostatic carcinoma after short-term estrogen treatment. Invest Urol 16:453–456

    Google Scholar 

  19. 19.

    Matsuo H, Nair RMG, Arimura A, Schally AV (1971) Structure of the porcine LH- and FSH-releasing hormone. I. The proposed aminoacid sequence. Biochem Biophys Res Commun 43:1334

    Google Scholar 

  20. 20.

    Nesbit RM, Baum WC (1950) Endocrine control of prostatic carcinoma. JAMA 143:1317–1320

    Google Scholar 

  21. 21.

    Prout GR Jr, Kliman B, Daly JJ, MacLaughlin RA, Griffin PD (1976) In vitro uptake of 3H-testosterone and its conversion to dihydrotestosterone by prostatic carcinoma and other tissues. J Urol 116:603–610

    Google Scholar 

  22. 22.

    Prout GR Jr, Kliman B, Daly JJ, MacLaughlin RA, Griffin PD, Young HH (1979) II. Endocrine changes after diethylstilbestrol therapy. Effects on prostate neoplasm and pituitary-gonadal axis. Urology 7:148–155

    Google Scholar 

  23. 23.

    Redding TW, Schally AV (1981) Inhibition of prostate tumor growth in two rat models by chronic administration of D-Trp6 analogue of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA 78:6509–6512

    Google Scholar 

  24. 24.

    Sandow J (1982) Gonadotropic and antigonadotropic actions of LHRH analogues. Neuroendocrine Perspectives 1:339–395

    Google Scholar 

  25. 25.

    Schally AV, Arimura A, Baba Y, Nair RMG, Matsuo H, Redding TW, Debeljuk L, White WF (1971) Isolation and properties of the FSH- and LH-releasing hormone. Biochem Biophys Res Commun 43:393–396

    Google Scholar 

  26. 26.

    Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, Nair RMG, Debeljuk L (1971) Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science 173:1036

    Google Scholar 

  27. 27.

    Scott WW (1953) Endocrine management of disseminated prostatic cancer, including bilateral adrenalectomy and hypophysectomy. Trans Am Assoc Genitourin Surg 44:101–104

    Google Scholar 

  28. 28.

    Scott WW, Menon M, Walsh PC (1980) Hormonal therapy of prostatic cancer. Cancer 45: 1929–1936

    Google Scholar 

  29. 29.

    Shearer RJ, Hendry WF, Sommerville IF, Fergusson JD (1973) Plasma testosterone: an accurate monitor of hormone treatment in prostatic cancer. Br J Urol 45:668–677

    Google Scholar 

  30. 30.

    Smith PH (1980) Oestrogen therapy in prostatic cancer. Scand J Urol Nephrol [Suppl] 55:91–94

    Google Scholar 

  31. 31.

    Smith RH (1980) The medical management of prostatic cancer. Some current questions. Eur Urol 6:65–68

    Google Scholar 

  32. 32.

    Tait F, Tait S, Little B, Laumas KR (1961) The disappearance of 7-3H-aldosterone in the plasma of normal subjects. J Clin Invest 40:72–74

    Google Scholar 

  33. 33.

    Tolis G, Mehra A, Comaru-Schally AM, Schally AV (1981) Suppression of androgen production by D-tryptophan-6-luteinizing hormone-releasing hormone in man. J Clin Invest 68:819–822

    Google Scholar 

  34. 34.

    Veterans Administration Cooperative Urological Research Group (1967) Carcinoma of the prostate: treatment comparisons. J Urol 98:516–520

    Google Scholar 

  35. 35.

    Wenderoth UK, Happ J, Krause U, Adenauer H, Jacobi GH (1982) Endocrine studies with a gonadotropin-releasing hormone analogue to achieve withdrawal of testosterone in prostate carcinoma patients. Eur Urol 8:343–347

    Google Scholar 

  36. 36.

    Wilson JD (1972) Recent studies on the mechanism of action of testosterone. N Engl J Med 287:1284–1291

    Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wenderoth, U.K., Jacobi, G.H. Gonadotropin-releasing hormone analogues for palliation of carcinoma of the prostate. World J Urol 1, 40–48 (1983). https://doi.org/10.1007/BF00326861

Download citation


  • Testosterone
  • Luteinizing Hormone
  • Ureteral Obstruction
  • Buserelin
  • Bilateral Orchiectomy