Treatment of Precocious Puberty with LHRH Agonists

A Pilot Study of the Efficiency of Periodic Administration of a Delayed-Release Preparation of D-Trp6-LHRH
  • Marc Roger
  • Jean-Louis Chaussain
  • Francoise Raynaud
  • Jean-Edmond Toublanc
  • Pierre Canlorbe
  • Jean-Claude Job
  • Andrew V. Schally
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


A better understanding of the paradoxical inhibitory effects of LHRH agonists has led to the discovery of new therapeutic agents, thanks largely to the experimental studies of Knobil’s group (Belchetz et al., 1978). Certain structural analogues have proven to be powerful suppressors of the pituitary-gonadal axis, as well as devoid of toxic effects.


Precocious Puberty Pubic Hair Klinefelter Syndrome Cyproterone Acetate LHRH Agonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Belchetz, P. E., Plant, T. M., Nakai, Y., Keogh, E. J., and Knobil, E., 1978, Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone, Science 202:631–633.PubMedCrossRefGoogle Scholar
  2. Bex, F. J., and Corbin, A., 1984, LHRH and analogs: Reproductive pharmacology and contraceptive and therapeutic utility, in: Frontiers in Neuroendocrinology, Vol. 8 (L. Martini and W. F. Ganong, eds.), Raven Press, New York, pp. 85–151.Google Scholar
  3. Chaussain, J. L., Roger, M., Vassal, J., Canlorbe, P., and Job, J. C., 1980, La fonction androgénique testiculaire dans les pubertés précoces du garcon. Effets du traitement, in: XVI International Congress of Pediatrics (A. Ballabriga and A. Gallart, eds.), Spanish Pediatrics Association, Barcelona, p. 432.Google Scholar
  4. Comite, F., Cutler, G. B., Rivier, J., Vale, W. W., Loriaux, D. L., and Crowley, W. F., Jr., 1981, Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. A preliminary report, N. Engl. J. Med. 305:1546–1550.PubMedCrossRefGoogle Scholar
  5. Comite, F., Pescovitz, O. H., Rieth, K. G., Dwyer, A. J., Hench, K., McNemar, A., Loriaux, D. L., and Cutler, G. B., Jr., 1984, Luteinizing hormone-releasing hormone analog treatment of boys with hypothalamic harmatoma and true precocious puberty, J. Clin. Endocrinol. Metab. 59:888–892.PubMedCrossRefGoogle Scholar
  6. Coy, D. H., Vilchez-Martinez, J. A., Coy, E. J., and Schally, A. V., 1976, Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6, J. Med. Chem. 19:423–425.PubMedCrossRefGoogle Scholar
  7. Crowley, W. F., Comite, F., Vale, W., Rivier, J., Loriaux, D. L., and Cutler, G. B., 1981, Therapeutic use of pituitary desensitization with a long-acting LHRH agonist: A potential new treatment for idiopathic precocious puberty, J. Clin. Endocrinol. Metabl. 52:370–372.CrossRefGoogle Scholar
  8. Donaldson, M. D. C., Stanhope, R., Lee, T. J., Price, D. A., Brook, C. G. D., and Savage, D. C. L., 1984, Gonadotropin responses to GnRH in precocious puberty treated with GnRH analogue, Clin. Endocrinol. 21:499–503.CrossRefGoogle Scholar
  9. Dufau, M. L., Winters, C. A., Hattori, M., Aquilano, D., Baranao, J. L. S., Nozu, K., Baukal, A., and Catt, K. J., 1984, Hormonal regulation of androgen production by the Leydig cell, J. Steroid Biochem. 20:61–173.CrossRefGoogle Scholar
  10. Evans, R. M., Doelle, G. C., Lindner, J., Bradley, V., and Rabin, D., 1984, A luteinizing hormone-releasing hormone agonist decreases biological activity and modifies Chromatographic behavior of luteinizing hormone in man, J. Clin. Invest. 73:262–266.PubMedCrossRefGoogle Scholar
  11. Fraser, H. M., Sandow, J., and Krauss, B., 1983, Antibody production against an agonist analogue of luteinizing hormone-releasing hormone: Evaluation of immunochemical and physiological consequences, Acta Endocrinol. (Kbh.) 103:151–157.Google Scholar
  12. Greulich, N. N., and Pyle, S. I. (eds.), 1959, Radiographie Atlas of Skeletal Development of the Hand and Wrist, Stanford University Press, Stanford, CA.Google Scholar
  13. Holland, F. J., Fishman, L., Costigan, D. C., Leeder, J. S., and Fasekas, A. T., 1985, D-Ser(TBU)6EA9LHRH in precocious puberty: Pharmacokinetics of SC, IV and intranasal use, Pe-diatr. Res. 19:633.CrossRefGoogle Scholar
  14. Kauli, R., Pertzelan, A., Ben-Zeev, Z., Prager Lewin, R., Kaufman, H., Comaru-Schally, A. M., Schally, A. V., and Laron, Z., 1984, Treatment of precocious puberty with LHRH analogue in combination with cyproterone acetate—Further experience, Clin. Endocrinol. 20:377–387.CrossRefGoogle Scholar
  15. Lahlou, N., Roger, M., Canlorbe, P., Chaussain, J. L., Raynaud, F., Toublanc, J. E., and Schally, A. V., 1985, Plasma levels of D-TRP-6-LH-RH (Decapeptyl) after intramuscular injection of long-acting microcapsules in children treated for precocious puberty (PP), Pediatr. Res. 19:635.CrossRefGoogle Scholar
  16. Laron, Z., Kauli, R., Ben Zeev, Z., Comaru-Schally, A. M., and Schally, A. V., 1981, D-TRP6 analogue of luteinising hormone releasing hormone in combination with cyproterone acetate to treat precocious puberty, Lancet 2:955–956.PubMedCrossRefGoogle Scholar
  17. Lefebvre, F. A., Bélanger, A., Pelletier, G., and Labrie, F., 1984, Recovery of gonadal functions in the adult male rat following cessation of five-month daily treatment with an LHRH agonist, J. Androl. 5:181–192.PubMedGoogle Scholar
  18. Lemay, A., Maheux, R., Faure, N., Jean, C., and Fazekas, A. T. A., 1984, Reversible hypogonadism induced by a luteinizing hormone-releasing hormone (LH-RH) agonist (Buserelin) as a new therapeutic approach for endometriosis, Fertil. Steril. 41:863–871.PubMedGoogle Scholar
  19. Luder, A. S., Holland, F. J., Costigan, D. C., Jenner, M. R., Wielgosz, G., and Fazekas, A. T. A., 1984, Intranasal and subcutaneous treatment of central precocious puberty in both sexes with a long-acting analog of luteinizing hormone-releasing hormone, J. Clin. Endocrinol. Metab. 58:966–972.PubMedCrossRefGoogle Scholar
  20. Mansfield, M. J., Beardsworth, D. E., Loughlin, J. S., Crawford, J. D., Bode, H. H., Rivier, J., Vale, W., Kushner, D. C., Crigler, J. F., and Crowley, W. F., 1983, Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. Effects on somatic growth and skeletal maturation, N. Engl. J. Med. 309:1286–1290.PubMedCrossRefGoogle Scholar
  21. Mason-Garcia, M., Vigh, S., Comaru-Schally, A. M., Redding, T. W., Somogyvari-Vigh, A., Horvath, J., and Schally, A. V., 1985, Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: Measurement of serum levels after administration of long-acting microcapsule formulations, Proc. Natl. Acad. Sci. U.S.A. 82:1547–1551.PubMedCrossRefGoogle Scholar
  22. Rabin, D., Evans, R. M., Alexander, A. N., Doelle, G. C., Rivier, J., Vale, W., and Liddle, G. W., 1984, Heterogeneity of sperm density profiles following 20-week therapy with high-dose LHRH analog plus testosterone, J. Androl. 5:176–180.PubMedGoogle Scholar
  23. Redding, T. W., Schally, A. V., Tice, T. R., and Meyers, W. E., 1984, Long-acting delivery systems for peptides: Inhibition of rat prostate tumors by controlled release of D-Trp6 luteinizing hormone-releasing hormone from injectable microcapsules, Proc. Natl. Acad. Sci. U.S.A. 81:5845–5848.PubMedCrossRefGoogle Scholar
  24. Roger, M., 1983, La maturation des fonctions gonadotropes de la naissance á l’adolescence, Contraception Fertil. Sexual. 11:1139–1151.Google Scholar
  25. Roger, M., Nahoul, K., Toublanc, J. E., Castanier, M., Canlorbe, P., and Job, J. C., 1979, Les androgènes plasmatiques chez le garcon de la naissance à l’adolescence, Ann. Pediatr. 26:239–245.Google Scholar
  26. Roger, M., Chaussain, J. L., Evain, D., Toublanc, J. E., Canlorbe, P., and Scholler, R., 1984, Les formes habituelles et inhabituelles des précocités sexuelles féminines et leur diagnostic biologique, Ann. Pediatr. 31:183–192.Google Scholar
  27. Roger, M., Duchier, J., Lahlou, N., Nahoul, K., and Schally, A. V., 1985, Treatment of prostatic carcinoma with D-TRP-6-LH-RH: Plasma hormone levels after daily subcutaneous injections and periodic administration of delayed release preparations, Prostate 7:271–282.CrossRefGoogle Scholar
  28. Roger, M., Chaussain, J.-L., Berlier, P., Bost, M., Canlorbe, P., Colle, M., Francois, R., Garandeau, P., Lahlou, N., Morel, Y., and Schally, A. V., 1986, Long-term treatment of male and female precocious puberty by periodic administration of a long acting preparation of D-Trp-6-LH-RH microcapsules, J. Clin. Endocrin. Metab. 62:670–677.CrossRefGoogle Scholar
  29. Sandow, J., 1983, Clinical applications of LHRH and its analogues, Clin. Endocrinol. 18:571–592.CrossRefGoogle Scholar
  30. Schally, A. V., Redding, T. W., and Comaru-Schally, A. M., 1984, Potential use of analogs of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms, Cancer Treat. Rep. 68:281–289.PubMedGoogle Scholar
  31. Sempé, P., and Sempé, M. (eds.), 1979, Auxologie: Méthode et Séquences, Théraplix, Paris.Google Scholar
  32. Tanner, J. M. (ed.), 1962, Growth at Adolescence, Blackwell Scientific, Oxford.Google Scholar
  33. Vickery, B. H., McRae, G. I., Briones, W., Worden, A., Scidenberg, R., Schanbacher, B. D., and Falvo, R., 1984, Effects of an LHRH agonist analog upon sexual function in male dogs, J. Androl. 5:28–42.PubMedGoogle Scholar
  34. Zachmann, M., Sobradillo, B., Frank, M., Frisch, H., and Prader, A., 1978, Bayley-Pinneau, Roche-Wainer-Thissen and Tanner height predictions in normal children and in patients with various pathological conditions, J. Pediatr. 93:749–755.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Marc Roger
    • 1
  • Jean-Louis Chaussain
    • 2
  • Francoise Raynaud
    • 2
  • Jean-Edmond Toublanc
    • 2
  • Pierre Canlorbe
    • 2
  • Jean-Claude Job
    • 2
  • Andrew V. Schally
    • 3
  1. 1.Fondation de Recherche en HormonologieFresnesFrance
  2. 2.Hôpital St. Vincent de PaulParisFrance
  3. 3.Veterans Administration Medical Center and Tulane University School of MedicineNew OrleansUSA

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