LHRH AND ITS ANALOGUES Basic and clinical aspects
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1 LHRH AND ITS ANALOGUES Basic and clinical aspects Proceedings of the International Symposium on LHRH and its Analogues Quebec City, June 28-30, 1984 Editors: Fernand Labrie, Alain Belanger, Andre Dupont Department of Molecular Endocrinology, Centre Hospitalier de l'universite Laval, Quebec, Canada Excerpta Medica, Amsterdam - New York - Oxford
2 Contents OPENING LECTURE LH-RH analogs in contraception and cancer A. V. Schally 3 1. Chemistry of LHRH Agonists and Antagonists Design of cyclic GnRH antagonists J. Rivier, J. Varga, J. Porter, M. Perrin, C. Rivier, W. Vale, S. Struthers and A. Hagler 19 Long acting LHRH agonists and antagonists J.J. Nestor Jr, T.L. Ho, R. Tahilramani, G.I. McRae and B.H. Vickery 24 Design and synthesis of LH-RH agonists and antagonists R. Geiger Delivery Systems for Controlled Release An injectable biodegradable controlled release delivery system for nafarelin acetate L.M. Sanders, G.I. McRae, K.M. Vitale, B.H. Vickery and J.S. Kent 53 A pharmaceutical approach to long-term therapy with peptides W. Petri, R. Seidel and J. Sandow \ 63 Relation between biological activities and blood levels of LH-RH or its analogues by different routes of administration in rats /. Yamazaki Predinical Studies: Pharmacology, Physiology and Toxicology Comparison of LHRH agonist and antagonist: Antifertility and therapeutic developments A. Corbin, F.J. Bex and R.C. Jones 95 Pharmacokinetics and metabolism of LHRH agonists, clinical aspects J. Sandow, G. Jerabek-Sandow, B. Krauss and M. Schmidt-Gollwitzer 123 vn
3 4. Animal Models The dog, a good model for the study of LHRH agonists as blockers of androgen secretion and potential contraceptives A. Belanger, Y. Tremblay, D. Lacoste, M. Giasson, A. Dupont and F. Labrie 141 Interactions between an LHRH analogue and cancer chemotherapeutic agents at the testicular level J.C. Goodpasture, K. Bergstrom, D.P. Waller and B.H. Vickery 156 Manipulation of the pituitary-ovarian axis in the stumptailed macaque by LHRH antibodies, LHRH agonist and antagonist analogues H.M. Fraser 173 The effects of LH-RH inhibitory analogues in the non-human primate. Basic studies in contraception and their direct applications for future clinical uses in both sexes R.H. Asch 188 Studies on the mechanism of infertility associated with endometriosis and the effect of an LHRH agonist (Histrelin; ORF 17070) in an animal model for endometriosis D. W. Hahn, R. Carraher, R. Foldesy and J.L. McGuire 203 LHRH analogs and experimental prostatic cancer models F. Bex and A. Corbin 210 Phospholipid turnover and GnRH action in the pituitary and gonads Z. Naor, J. Molcho, J. Hermon, M. Zilberstein, H. Zakut and N. Dekel Female Contraception Superagonists of LHRH for contraception in women S.J. Nillius, C. Bergquist, J.A. Gudmundsson and L. Wide Male Contraception LHRH agonists and antagonists for male fertility control: Experiments in monkeys and men E. Nieschlag, F.B. Akhtar, T. Schiirmeyer and G. Weinbauer 277 Hormonal effects of GnRH agonist in the human male: An approach to male contraception using combined androgen and GnRH agonist treatment R.S. Swerdloff and S. Bhasin 287 vm
4 7. Prostate Cancer Subcutaneous administration of 'Zoladex' (ICI 118,630 - An LH-RH analogue) in advanced prostatic cancer R.J. Donnelly, R.C. Cotton, S.H. Ellis and D. Richards 305 Clinical response and safety of LHRH agonist treatment in prostatic carcinoma N. Faure, A. Lemay, B. Laroche, G. Robert, R. Plante, M. Thabet, R. Roy, C. Jean, J.-C. Forest and A.T.A. Fazekas 312 Advanced prostatic carcinoma: A therapeutic challenge G. Tolis and M. Koutsilieris 326 GnRH superagonist treatment of prostate cancer: Hormonal effects with and without an androgen biosynthesis inhibitor R.J. Santen, H.F. English and B.A. Warner 336 Three years of experience with the GnRH-analogue buserelin in 100 patients with advanced prostatic cancer U.K. Wenderoth and G.H. Jacobi 349 Response and relapse in patients with prostatic cancer treated with buserelin J.H. Waxman, W.F. Hendry, H.N. Whitfield, DM.A. Wallace andr.t.d. Oliver 359 Complete androgen blockade at start of treatment causes a dramatic improvement of survival in advanced prostate cancer F. Labrie, A. Dupont, A. Be'langer, Y. Lacoursiere and members of the Laval University Prostate Cancer Program Endometriosis Efficacy and safety of LHRH agonist treatment in 10 patients with endometriosis A. Lemay, R. Maheux, N. Faure, C. Jean and A.T.A. Fazekas 383 Reversible hypogonadism induced by a luteinizing hormone releasing hormone (LHRH) agonist (buserelin) as a new therapeutic approach for leiomyomata uteri R. Maheux, C. Guilloteau, A. Lemay, A. Bastide and A.T.A. Fazekas 396 IX
5 9. Breast Cancer and Precocious Puberty Subcutaneous and intranasal D-ser(TBU) 6 EA 10 LHRH (buserelin) in the management of precocious puberty F.J. Holland, L. Fishman, A. Luder, D.C. Costigan, M. Jenner, G. Wielgosz and A.T.A. Fazekas 407 Long-term treatment with the LHRH-agonist buserelin (HOE 766) for metastatic breast cancer in single and combined drug regimens J.G.M. Klijn and F.H. de Jong 425 LHRH analog effect on pubertal development, growth and maturation in precocious puberty F. Comite, O.H. Pescovitz, CM. Foster, F. Cassorla, K. Hench, A. McNemar, M. Skerda, D.L. Loriaux and G.B. Cutler Jr Stimulation of Gonadal Functions Pulsatile administration of Gn-RH in hypothalamic amenorrhea G. Leyendecker and L. Wildt 457 Induction of ovulation with LHRH - Problems, indications and contraindications H.S. Jacobs, J. Adams, S. Franks, C. Kelly, W.P. Mason, D. V. Morris, L. Ross, I. Sutherland, G.R. Chambers and Z.M. van der Spuy 464 The results of long-term GnRH administration in idiopathic hypogonadotropic hypogonadism W.F. Crowley Jr and D. Spratt 479 Does long-term treatment with buserelin improve the fertility chances of cryptorchid testes? F. Hadziselimovic, B. Hoecht, B. Herzog and J. Girard Drug Regulatory Aspects of LHRH Agonists and Antagonists Trends in drug development with special reference to the testing of LHRH analogues J.L. Gueriguian, C.A. Schaffenburg, Y.-Y.H. Chiu and V. Berliner 507 Canadian drug regulations and peptide hormonal Pharmaceuticals O.J. Lucis 517 LHRH agonists and antagonists. Aspects of their safety and efficacy K.-W. von Eickstedt 524 Index of authors 535 Subject index 537
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