Treatment of Uterine Leiomyomata by LH-RH Agonists

  • Z. Blumenfeld
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 124)


The rapid development and availability of luteinizing hormone releasing hormone (LH-RH) agonists have led to their widespread utilization in a variety of gynecologic conditions (McLachlan et al. 1986). One of the most common conditions in the practice of the gynecologist is uterine leiomyomata (Heinrichs 1991). Uterine leiomyomata are the most common solid tumor of the female genital tract and may bring about menometrorrhagia, pelvic pain and discomfort, anemia, infertility and habitual abortion (Blumenfeld et al. 1990; Esterday et al. 1983; Filicori et al 1983; Heinrichs 1991). Estrogens are known to play a major role in the development and enlargement of these tumors. High levels of estrogen receptors have been found in this type of tumor, and exogenous administration of estrogens may result in rapid increase in their size (Blumenfeld et al. 1990; Filicori et al. 1983; Heinrichs 1991; Tamaya et al. 1985; Wilson et al. 1980). The estrogen dependence is in agreement with the clinical observations that fibroids are most commonly diagnosed in women aged between 30 and 50 years, that fibroids tend to shrink after the menopause, and that fibroids can rapidly increase in size during pregnancy (Healy 1990). On the other hand, case-control analysis of 535 women who had had leiomyomata showed that the risk of leiomyomata was inversely correlated with the number of term pregnancies (Healy 1990; Ross et al. 1986). This suggested that low, unopposed estradiol (E2) levels, resulting from the several pregnancies and also the subsequent puerperia, reduced the growth of nascent leiomyomata (Healy 1990). The risk of developing leiomyomata was directly correlated with increasing duration of oral contraceptive use, lower body weight, and cigarette smoking (Healy 1990; Ross et al. 1986). Serum E2 concentrations in patients with uterine leiomyomata were similar to those in control women (Healy 1990; Soules and McCarthy 1982; Spellacy et al. 1972).


Uterine Fibroid Medroxyprogesterone Acetate GnRH Analogue LHRH Agonist Leuprolide Acetate 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andreyko JL, Blumenfeld Z, Marshall LA, Monroe SE, Hricak H, Jaffe RB (1988) Use of an agonistic analog of gonadotropin-releasing hormone (Nafarelin) to treat leiomy-omata: assessment by magnetic resonance imaging. Am J Obstet Gynecol 158:903–910PubMedGoogle Scholar
  2. Benagiano G, Morini A, Abbondante A, Aleandri V, Piccinno F, Sala D (1990) Sequential buserelin — medroxyprogesterone acetate treatment of uterine leiomyomata. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 53–62CrossRefGoogle Scholar
  3. Blumenfeld Z, Dirnfeld M, Beck D, Abramovici H, Brandes JM (1990) Comparison of treatment of uterine leiomyomata with 3 different GnRH agonistic analogs. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 45–52CrossRefGoogle Scholar
  4. Blumenfeld Z, Thaler I, Weiner Z, Beck D, Brandes JM (1991) Treatment of uterine leiomyomata with GnRH analogue (Nafarelin): a clinical protocol of interrupted (on and off) treatment. In: Lunenfeld B (ed) GnRH Analogues. Parthenon, Park Ridge, pp 43–51Google Scholar
  5. Cedars MI, Lu JKH, Meldrum DR et al. (1990) Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate. Obstet Gynecol 75:641PubMedGoogle Scholar
  6. Coddington CC, Collins RL, Shawker TH, Anderson R, Loriaux DL, Winkel CA (1986) Long-acting gonadotropin hormone-releasing hormone analog used to treat uteri. Fertil Steril 45:624–629PubMedGoogle Scholar
  7. Cohen J, Elia D (1990) Relevance of an LHRH agonist to the treatment of uterine fibromy-omas. In: Vickey BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 33–44CrossRefGoogle Scholar
  8. Donnez J, Schrurs B, Gillerot S, Sandow J, Clerckx F (1989) Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterogra-phy. Fertil Steril 51:947PubMedGoogle Scholar
  9. Erny R, Milliet E, Boubli L (1990) Treatment of uterine fibroids with intra-nasal buserelin. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 21–26CrossRefGoogle Scholar
  10. Esterday CL, Grimes DA, Riggs JA (1983) Hysterectomy in the United States. Obstet Gynecol 62:203–220Google Scholar
  11. Evans RM, Doelle GC, Lindner J, Bradley V, Rabin D (1984) An LHRH agonist decreases biologic activity and modified Chromatographic behavior of LH in man. J Clin Invest 73:262–270PubMedCrossRefGoogle Scholar
  12. Filcori M, Hall DA, Laughlin JS, Rivier J, Vale W, Crowley WF (1983) A conservative approach to the management of uterine leiomyomata: pituitary desensitization by a luteinizing hormone releasing hormone analogue. Am J Obstet Gynecol 147:726–729Google Scholar
  13. Friedman AJ (1989 a) Vaginal hemorrhage associated with degenerating submucous leiomy-oma during leuprolide acetate treatment. Fertil Steril 52:152PubMedGoogle Scholar
  14. Friedman AJ (1989 b) Treatment of leiomyomata uteri with short-term leuprolide followed by leuprolide plus estrogen-progestin hormone replacement therapy for 2 years: a pilot study. Fertil Steril 51:526PubMedGoogle Scholar
  15. Friedman AJ (1990) Advances in the treatment of leiomyomata uteri with leuprolide. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 27–32CrossRefGoogle Scholar
  16. Friedman AJ, Barbieri RL, Benaceraff BR, Schiff I (1987) Treatment of leiomyomata with intranasal or subcutaneous leuprolide, a gonadotropin releasing-hormone agonist. Fertil Steril 48:560–564PubMedGoogle Scholar
  17. Friedman AJ, Barbieri RL, Doubilet PM, Fine C, Schiff I (1988) A randomized, double-blind trial of a gonadotroph releasing-hormone agonist (leuprolide) with or without medroxy-progesterone acetate in the treatment of leiomyomata uteri. Fertil Steril 49:404–409PubMedGoogle Scholar
  18. Friedman AJ, Harrison-Atlas D, Barbieri RL, Benacerraf B, Gleason R, Schiff I (1989 a) A randomized, placebo-controlled, double-blind study evaluating the efficacy of leuprolide acetate depot in the treatment of uterine leiomyomata. Fertil Steril 51:251PubMedGoogle Scholar
  19. Friedman AJ, Rein MS, Harrison-Atlas D, Garfield JM, Doubilet PM (1989 b) A randomized, placebo-controlled, double-blind study evaluating leuprolide acetate depot treatment before myomectomy. Fertil Steril 52:728–733PubMedGoogle Scholar
  20. Friedman AJ, Rein MS, Pandian MR, Barbieri RL (1990) Fasting serum growth hormone and insulin-like growth factor-I and-II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo. Fertil Steril 53:250PubMedGoogle Scholar
  21. Gardner RL, Shaw RW (1989) Cornual fibroids: a conservative approach to restoring tubal potency using a gonadotropin-releasing hormone agonist (goserelin) with successful pregnancy. Fertil Steril 52:332PubMedGoogle Scholar
  22. George M, L’Homme C, Lefort J, Gras C, Comarn-Schally AM, Schally AV (1989) Long-term use of an LH-RH agonist in the management of uterine leiomyomas: a study of 17 cases. Int J Fertil 34:19PubMedGoogle Scholar
  23. Golan A, Bukovsky I, Schneider D et al. (1989) D-Trp6-luteinizing hormone-releasing hormone microcapsules in the treatment of uterine leiomyomas. Fertil Steril 52:406PubMedGoogle Scholar
  24. Healy DL (1990) The use of LH-RH analogues in the treatment of uterine fibroids. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: III. Benign and malignant tumours. Kluwer, Dordrecht, pp 1–20CrossRefGoogle Scholar
  25. Healy DL, Fräser HM, Lawson SL (1984) Shrinkage of a uterine fibroid after subcutaneous infusion of a LH-RH agonist. BMJ 289:1267PubMedCrossRefGoogle Scholar
  26. Healy DL, Lawson SR, Abbott M, Baird DT, Fraser HM (1986) Toward removing uterine fibroids without surgery: subcutaneous infusion of a luteinizing-hormone releasing hormone agonist commencing in the luteal phase. J Clin Endocrinol Metab 63:619–624PubMedCrossRefGoogle Scholar
  27. Heinrichs WL (1991) Gonadotropin releasing-hormone agonists (GnRH-a) in gynecological practice: endometriosis and leiomyomata uteri. In: Mishell DR, Kirshbaum TH, Morrow CP (eds) Yearbook of obstetrics and gynecology. Mosby, St. Louis, p 333Google Scholar
  28. Kessel B, Liu J, Mortola J, Berger S, Yen SS (1988) Treatment of uterine fibroids with agonist analogs of gonadotropin-releasing hormone. Fertil Steril 49:538PubMedGoogle Scholar
  29. Koutsilieris M, Michand J, Mikolis A (1990) Preferential mitogenic activity for myoblast-like cells can be extracted from uterine leiomyomata tissues. Am J Obstet Gynecol 163:1665PubMedGoogle Scholar
  30. Letterie GS, Coddington CC, Winkel CA, Shawker TH, Loriaux DL, Collins RL (1989) Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata: long-term follow-up. Fertil Steril 51:951PubMedGoogle Scholar
  31. Loong EPL, Wong FWS (1990) Uterine leiomyosarcoma diagnosed during treatment with agonist hormone-releasing hormone for presumed uterine fibroid. Fertil Steril 54:530PubMedGoogle Scholar
  32. Lumsden MA, West CP, Baird DT (1987) Goserelin therapy before surgery for uterine fibroids. Lancet 1:36PubMedCrossRefGoogle Scholar
  33. Lumsden MA, West CP, Bramley T, Rumgay L, Baird DT (1988) The binding of epidermal growth factor to the human uterus and leiomyomata in women rendered hypoestrogenic by continuous administration of an LH-RH agonist. Br J Obstet Gynaecol 95:1299PubMedCrossRefGoogle Scholar
  34. Maheux R, Guilloteau C, Lemay A, Bastide A, Fazekas AIA (1985) Luteinizing hormone-releasing hormone agonist and uterine leiomyoma: a pilot study. Am J Obstet Gynecol 152:1034–1038PubMedGoogle Scholar
  35. Maheux R, Lemay A, Merat P (1987) Use of intranasal luteinizing hormone-releasing hormone agonist in uterine leiomyomas. Fertil Steril 47:229–233PubMedGoogle Scholar
  36. Maheux R, Lemay A, Turcot-Lemay L (1988) Dose-related inhibition of acute luteinizing hormone response during luteinizing hormone-releasing hormone agonist treatment of uterine leiomyomata. Am J Obstet Gynecol 158:361PubMedGoogle Scholar
  37. Matta WH, Shaw RW, Hesp R, Katz D (1987) Hypogonadism induced by luteinizing hormone-releasing hormone agonist analogues: effect on bone density in premenopausal women. BMJ 294:1523–1528PubMedCrossRefGoogle Scholar
  38. Matta WHM, Stabile I, Shaw RW, Campbell S (1988) Doppler assessment of uterine blood flow changes in patients with fibroids receiving the gonadotropin-releasing hormone agonist buserelin. Fertil Steril 49:1083–1085PubMedGoogle Scholar
  39. Matta WHM, Shaw RW, Nye M (1989) Long-term follow-up of patients with uterine fibroids after treatment with the LH-RH agonist buserelin. Br J Obstet Gynaecol 96:200–206PubMedCrossRefGoogle Scholar
  40. Mazess R (1990) Bone densiometry of the axial skeleton. Orthop Clin North Am 21:51PubMedGoogle Scholar
  41. McLachlan RI, Healy DL, Burger HG (1986) Clinical aspects of LH-RH analogues in gynecology: a review. Br J Obstet Gynaecol 93:431–446PubMedGoogle Scholar
  42. Moghissi K (1990) Gonadotropin releasing hormones: clinical applications in gynecology. J Reprod Med 35:1097PubMedGoogle Scholar
  43. Nakamura Y, Yoshimura Y, Yamada H, Ubukata Y, Ando M, Suzuki M (1991) Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. Fertil Steril 55:900–905PubMedGoogle Scholar
  44. Perl V, Leal O, Marquez J, Zacharias S, Serially AV, Gomezu-Lira C, Comaru-Schally AM (1987) Treatment of leiomyomata uteri with [D-TRP6]-luteinizing hormone-releasing hormone. Fertil Steril 48:383–389PubMedGoogle Scholar
  45. Ross RK, Pike NC, Vessey NP, Bull D, Yates D, Casagrande JT (1986) Risk factors for uterine fibroids: reduced risk associated with oral contraceptives. BMJ 293:359–364PubMedCrossRefGoogle Scholar
  46. Schlaff WD, Zerhouni EA, Huth JAM, Chen J, Damewood MD, Rock JA (1989) A placebo-controlled trial of a depot gonadotropin-releasing hormone analogue (leuprolide) in the treatment of uterine leiomyomata. Obstet Gynecol 74:856–862PubMedGoogle Scholar
  47. Shaw RW (1989) Mechanism of LH-RH analogue action in uterine fibroids. Horm Res 32:150PubMedCrossRefGoogle Scholar
  48. Soules MR, McCarty KS (1982) Leiomyomas: steroid receptor content. Am J Obstet Gynecol 143:6–13PubMedGoogle Scholar
  49. Spellacy WN, Lemaire WJ, Buhl WC, Birk SA, Bradley BA (1972) Plasma growth hormone and estradiol levels in women with uterine myomas. Obstet Gynecol 40:829–837PubMedGoogle Scholar
  50. Tamaya T, Fujimoto J, Okada H (1985) Comparison of cellular levels of steroid receptors in uterine leiomyoma and myometrium. Acta Obstet Gynecol Scand 64:307–314PubMedCrossRefGoogle Scholar
  51. Van Leusden HAIM (1986) Rapid reduction of uterine myomas after short term treatment with microencapsulated D-Trp6-LH-RH. Lancet 1:213Google Scholar
  52. Van Leusden HAIM (1988) Triptorelin to prevent hysterectomy in patients with leiomyomas. Lancet 2:508PubMedCrossRefGoogle Scholar
  53. Van der Spuy ZM, Fieggan AG, Wood MJA, Pienaar CA (1989) The short-term use of luteinizing hormone-releasing hormone analogues in uterine fibroids. Horm Res [Suppl l]:137–140Google Scholar
  54. Vollenhoven BJ, Shekleton P, McDonald J, Healy DL (1990) Clinical predictors for buserelin acetate treatment of uterine fibroids: a prospective study of 40 women. Fertil Steril 54:1032–1038PubMedGoogle Scholar
  55. West CP, Williamson J, Lumsden MA, Baird DT, Lawson S (1987) Shrinkage of uterine fibroids during therapy with goserelin (Zoladex): a luteinizing hormone-releasing hormone agonist administered as a monthly subcutaneous depot. Fertil Steril 48:45–51PubMedGoogle Scholar
  56. West CP, Lumsden MA, Baird DT (1989) LH-RH analogues and fibroids-potential for longer-term use. Horm Res 32:146PubMedCrossRefGoogle Scholar
  57. Wilson EA, Yang F, Rees ED (1980) Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissues. Obstet Gynecol 55:20–27PubMedGoogle Scholar
  58. Williams IA, Shaw RW (1990) Effect of nafarelin on uterine fibroids measured by ultrasound and magnetic resonance imaging. Eur J Obstet Gynecol Reprod Biol 34:111PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • Z. Blumenfeld
    • 1
  1. 1.Reproductive Endocrinology & Infertility Section, Department of Obstetrics & GynecologyRambam Medical Center, Faculty of Medicine — Technion, Israel Institute of TechnologyHaifaIsrael

Personalised recommendations