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GnRH Analogs and Safety

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GnRH Analogues in Cancer and Human Reproduction

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Abstract

Potential broad clinical uses of GnRH analogs in gynecological applications raise several issues regarding the safety of these peptide hormones in women. These analogs have widespread applicability in a variety of disorders such as leiomyomata uteri, polycystic ovarian disease, prior to laser ablation for dysfunctional uterine bleeding, and infertility [1–10]. Included in these indications is the treatment of endometriosis [2], a ubiquitous disease in reproductive-aged women. GnRH analogs decrease ovarian steroidogenesis through selective hypophysectomy with reduced gonadotropin release; and thus diminish estradiol levels. The GnRH induced hypoestrogenic state raises concerns about effects on bone mass, especially in women with endometriosis, a disease which is associated with decreased bone [11], as well as in the treatment of fibroids in perimenopausal women, who may already have altered bone turnover. This potential side effect of GnRH analog therapy is important, since estrogen appears to be a critical factor in the regulation of bone turnover. Consequently, bone density response during GnRH analog use must be carefully assessed in all women, and particularly in the perimenopausal population.

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References

  1. Andreyko, JL, Marshall, LA, Dumesic, DA, and Jaffe, RB (1987). Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv, 421, 1

    Google Scholar 

  2. Henzl, MR, Corson, SL, Moghissi, K, Buttram, VC, Berquist, C, and Jacobson, J (1988). Administration of nasal nafarelin as compared with oral danazol for endometriosis: a multicenter double-blind comparative clinical trial. N Engl J Med, 318, 485

    Article  PubMed  CAS  Google Scholar 

  3. Barbieri, RL (1988). New therapy for endometriosis. N Engl J Med, 318, 512

    Article  PubMed  CAS  Google Scholar 

  4. Comite, F, Cassorla, F, Barnes, KM, Hench, KD, Dwyer, A, Skerda, MC, Loriaux, DL, Cutler, GB, and Pescovitz, OH (1986). Luteinizing hormone releasing hormone analogue therapy for central precocious puberty: long term effect on somatic growth, bone maturation, and predicted height. JAMA, 255, 2613

    Article  PubMed  CAS  Google Scholar 

  5. Friedman, AJ, Barbieri, RL, Benacerraf, BR, and Schiff, I (1987). Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin-releasing hormone agonist. Fertil Steril, 48, 560

    PubMed  CAS  Google Scholar 

  6. Andreyko, JL, Blumenfeld, Z, Marshall, LA, Monroe, SE, Hricak, H, and Jaffe, RB (1988). Use of an agonistic analog of gonadotropin- releasing hormone (nafarelin) to treat leiomyomas: assessment by magnetic resonance imaging. Am J Obstet Gynecol, 158, 903

    PubMed  CAS  Google Scholar 

  7. Muse, KN, Cetel, NS, Futterman, LA, and Yen, SSC (1984). The premenstrual syndrome: effects of “medical ovariectomy”. N Engl J Med, 311, 1345

    Article  PubMed  CAS  Google Scholar 

  8. Vaitukaitis, JL (1984). Premenstrual syndrome. N Engl J Med, 311, 1371

    Article  PubMed  CAS  Google Scholar 

  9. Meggs, WJ, Pescovitz, OH, Metcalfe, D, Loriaux, DL, Cutler, G, and Kaliner, M (1984). Progesterone sensitivity as a cause of recurrent anaphylaxis. N Engl J Med, 311, 1236

    Article  PubMed  CAS  Google Scholar 

  10. Anderson, KE, Spitz, IM, Sassa, S, Bardin, CW, and Kappas, A (1984). Prevention of cyclical attacks of acute intermittent porphyria with a long-acting agonist of luteinizing hormone-releasing hormone. N Engl J Med, 311, 643

    Article  PubMed  CAS  Google Scholar 

  11. Comite, F, Jensen, P, and Hutchinson, K (1987). Decreased bone mass in endometriosis. The American Fertility Society, Reno, Nevada, (abstract)

    Google Scholar 

  12. Gotfredsen, A, Christiansen, C, and Palshof, T (1984). The effect of tamoxifen on bone mineral content in premenopausal women with breast cancer. Cancer, 53, 853

    Article  PubMed  CAS  Google Scholar 

  13. Comite, F, Jensen, P, Lewis, A, Hutchinson, K, Polan, ML, and DeCherney, AH (1987). GnRH analog therapy in endometriosis: impact on bone mass. Society for Gynecologic Investigation, Atlanta, Georgia, (abstract)

    Google Scholar 

  14. Comite, F, and Jensen, P (1988). Bone density changes associated with GnRH analogs. International Symposium on GnRH Analogues in Cancer and Human Reproduction. Geneva, Switzerland

    Google Scholar 

  15. Gudmundsson, JA, Ljunghall, S, Bergquist, C, Wide, L, and Nillius, SJ (1987). Increased bone turnover during gonadotropin-releasing hormone superagonist-induced ovulation inhibition. J Clin Endocrinol Metab, 65, 1

    Article  Google Scholar 

  16. Tummon, IA, Ali, A, Pepping, MA, Radwanska, E, Binor, Z, and Dmowski, WP (1988). Bone mineral density in women with endometriosis before and during ovarian suppression with gonadotropin-releasing hormone agonists or danazol. Fertil Steril, 49, 5

    Google Scholar 

  17. Barnes, RB, Mercer, LJ, and Montner, S (1988). Characterization of bone loss during treatment with a depot gonadotropin-releasing hormone agonist (GnRHa). The American Fertility Society, Atlanta, Georgia, (abstract)

    Google Scholar 

  18. Dawood, MY, Lewis, V, and Ramos, J (1988). Bone mineral content in women with endometriosis: effect of Buserelin and Danazol. The American Fertility Society, Atlanta, Georgia, (abstract)

    Google Scholar 

  19. Johansen, JS, Riis, BJ, Hassager, C, Moen, M, Jacobson, J, and Christiansen, C (1988). The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab, 67, 701

    Article  PubMed  CAS  Google Scholar 

  20. Ott, SM, Kilcoyne, RF, and Chestnut, CH III (1987). Ability of four different techniques of measuring bone mass to diagnose vertebral fractures in postmenopausal women. J Bone Mineral Res, 2, 201

    Article  CAS  Google Scholar 

  21. Hall, FM, Davis, MA, and Baran, DT (1987). Bone mineral screening for osteoporosis. N Engl J Med, 316, 212

    Article  PubMed  CAS  Google Scholar 

  22. Davis, MR. Screening for postmenopausal osteoporosis. Am J Obstst Gynec 1987, 156

    Google Scholar 

  23. Kelly, TL, Slovik, DM, Schoenfeld, DA, and Neer, RM (1988). Quantitative digital radiography versus dual photon absorptiometry of the lumbar spine. J Clin Endocrinol Metab, 67, 839

    Article  PubMed  CAS  Google Scholar 

  24. Health and Public Policy Committee, American College of Physicians (1984). Radiologic methods to evaluate bone mineral content. Ann Int Med, 100

    Google Scholar 

  25. Cann, CE, Henzl, M, Burry, K, Andreko, J, Hanson, F, Adamson, D, and Trobough, G (1986). Reversible bone loss is induced by GnRH Agonists. The Endocrine Society, Anaheim, California, (abstract)

    Google Scholar 

  26. Kenigsberg, D, Hull, M, Yasumura, S, Cohn, S, and Ellis, K (1987). Total body calcium (TBC) by neutron activation (NA) and osteocalcin (OC) in GnRH agonist (GnRHa) treated women with endometriosis. Society for Gynecologic Investigation, Atlanta, Georgia, (abstract)

    Google Scholar 

  27. Lewis, V, Ramos, M, Yusoff, M, and Dawood, MY (1987). Changes in bone mineral content in endometriosis patients treated with GnRH agonist. Society for Gynecologic Investigation, Atlanda, Georgia, (abstract)

    Google Scholar 

  28. Devogelaer, JP, Huaux, JP, Donnez, J, Thomas, K, and Nagant de Deuschaisnes, C (1987). Differential effects of the GnRH agonist buserelin on the axial and the appendicular skeleton at different scanning sites. Preferential loss of trabecular bone. In: Christiansen, C, Johansen, JS, and Riis, BJ (eds) Osteoporosis. Proceedings of the International Symposium on Osteoporosis. Norhaven Bogtrykkeri, Viborg

    Google Scholar 

  29. Cann, CE, Henzl, M, Burry, K, Andreyko, J, Hanson, F, Adamson, GD, Trobough, G, Henrichs, L and Stewart, G (1987). Reversible bone loss is produced by the GnRH agonist nafarelin. In: Cohn DV, Martin TJ, and Meunier PJ (eds.) “Calcium regulation and bone metabolism. Basic and clinical aspects”, p.123. (Amsterdam: Elsevier)

    Google Scholar 

  30. Matta, WH, Shaw, RW, Hesp, R, and Katz, D (1987). Hypogonadism induced by luteinising hormone releasing hormone agonist analogues: effects on bone density in premenopausal women. Brit Med J, 294, 1523

    Article  CAS  Google Scholar 

  31. Singh, M, Nagrath, AR, and Maini, PS (1970). Changes in the trabecular pattern of the upper end of the femur as an index of osteoporosis. J Bone Joint Surg (AM), 52, 457

    CAS  Google Scholar 

  32. Gallagher, JC, Melton, LJ, Riggs, BL, and Bergstrath, E (1980). Epidemiology of fractures of the proximal femur in Rochester, Minnesota. Clin Orthop, 150, 163

    PubMed  Google Scholar 

  33. Roberts, JG, DiTomasso, E, and Webber, CE. (1982). Photon scattering measurements of calcaneal bone density; results of in vivo cross-sectional studies. Invest Radiol, 17, 20

    Article  PubMed  CAS  Google Scholar 

  34. Jensen, PS, and Orphanoudakis, SC (1985). Clinical results from longitudinal determination of bone mass using quantitative computed tomography. J Comput Assist Tomogr, 9, 627

    Article  Google Scholar 

  35. Orphanoudakis, SC, Jensen, PS, Rauschkolb, EN, Lang, R, and Rasmussen, H (1979). Bone mineral analysis using single energy computed tomography. Invest Radiol, 14, 122

    Article  PubMed  CAS  Google Scholar 

  36. Jensen, PS, Orphanoudakis, SC, Holman, H, Broadus, A, Baron, R, and Rasmussen, H (1982). Quantitative computed tomographic bone mass changes in the distal radius in primary hyperparathyroidism. Invest Radiol, 17, 27

    Article  Google Scholar 

  37. Gotfredsen, A, Nilas, L, Riis, BJ, Thomsen, K, and Christiansen, C (1986). Bone changes occurring spontaneously and caused by oestrogen in early postmenopausal women: a local or generalised phenomenon? Brit Med J, 292, 1098

    Article  CAS  Google Scholar 

  38. Meier, DE, Orwoll, ES, and Jones, JM (1984). Marked disparity between trabecular and cortical loss with age in healthy men. Ann Int Med, 101, 605

    PubMed  CAS  Google Scholar 

  39. Sartoris, DJ, Resnick, D, and Guerra, J (1985). Vertebral venous channels: CT appearance and differential considerations. Radiology, 155, 745

    PubMed  CAS  Google Scholar 

  40. Laval-Jeantet, MH, Roger, B, Laval-Jeantet, AM, Bergot, C and Preteux, F (1984). Anatomical basis of vetebral densitometry. In Fourth International Workshop on Bone and Soft Tissue Densitometry using Computed Tomography. Fontevraud, France, 49

    Google Scholar 

  41. Genant, HK, and Boyd, DB (1980). Quantitative bone mineral analysis using dual energy computed tomography. Invest Radiol, 12, 545

    Article  Google Scholar 

  42. Jensen, PS, Orphanoudakis, SC, Rauschkolb, EN, Baron, R, Lang, R and Rasmussen, H (1980). Assessment of bone mass in the radius by computed tomography. AJR Am J Roentgenol, 134, 285

    PubMed  CAS  Google Scholar 

  43. Pacifici, R, Rupich, R, Vered, I, Fischer, KC, Griffin, M, Susman, N, and Avioli, LV (1988). Dual energy radiography (DER): a preliminary comparative study. Calcif Tissue Int, 43, 189

    Article  PubMed  CAS  Google Scholar 

  44. Brzyski, RJ, and Comite, F (1987). Nafarelin, an intranasal GnRH analog, for infertility associated with endometriosis. The American Fertility Society, Reno, Nevada, (abstract)

    Google Scholar 

  45. Comite, F, DeCherney, A, and Vulté, J (1989). GnRH analog use in reproductive-aged women: impact on bone. Endoc Soc (abstract)

    Google Scholar 

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Author information

Authors and Affiliations

  1. Departments of Medicine and Gynecology, Yale University School of Medicine, New Haven, CT, USA

    Florence Comite

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  1. Florence Comite
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Editors and Affiliations

  1. Syntex Research, Institute of Biological Science, Palo Alto, CA, 94304, USA

    B. H. Vickery

  2. Institute of Endocrinology, Sheba Medical Center and Bar Ilan University, Remat Gan, 52621, Israel

    B. Lunenfeld

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© 1990 Kluwer Academic Publishers

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Comite, F. (1990). GnRH Analogs and Safety. In: Vickery, B.H., Lunenfeld, B. (eds) GnRH Analogues in Cancer and Human Reproduction. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0725-6_18

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  • DOI: https://doi.org/10.1007/978-94-009-0725-6_18

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6811-6

  • Online ISBN: 978-94-009-0725-6

  • eBook Packages: Springer Book Archive

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