The Medical Treatment of Uterine Fibroids

  • David L. Olive
Part of the Medical Radiology book series (MEDRAD)


Uterine fibroids are the most common benign tumor in women, and cause many symptoms. The treatment for these tumors has traditionally been surgical. However, a variety of medical therapies are now available for use. These drugs are primarily utilized as preoperative adjunctive therapy to ease the difficulty of surgery. However, some may have potential as long-term medical treatments, allowing the patient to delay or even avoid surgery. Current medications include GnRH analogs, selective estrogen receptor modulators, aromatase inhibitors, progesterone receptor modulators, and a variety of other less thoroughly evaluated medications. In addition, a number of drugs are in development that are designed to attack novel, specific targets in the leiomyoma growth, and maintenance process.


Progesterone Receptor GnRH Agonist Uterine Fibroid GnRH Antagonist Abnormal Uterine Bleeding 
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.


  1. Attardi BJ, Hild SA, Reel JR et al (2000) CDB-4124: a potent antiprogestin with antiovulatory and postcoital antifertility activity [abstract 1293]. Proceedings of the 82nd Annual Meeting of the Endocrine Society; Toronto, CanadaGoogle Scholar
  2. Attardi BJ, Burgenson J, Hild SA et al (2002) CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914. Mol Cell Endocrinol 188:111–123PubMedCrossRefGoogle Scholar
  3. Baird DD, Dunson DB, Hill MC et al (2003) High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 188:100–107PubMedCrossRefGoogle Scholar
  4. Bakas P, Liapis A, Vlahopoulos S, Giner M, Logotheti S, Creatsas G, Meligova AK, Alexis MN, Zoumpourlis V (2008) Estrogen receptor alpha and beta in uterine fibroids: a basis for altered estrogen responsiveness. Fertil Steril 90:1878PubMedCrossRefGoogle Scholar
  5. Barbieri RL, Ryan KJ (1981) Danazol: endocrine pharmacology and therapeutic applications. Am J Obstet Gynecol 141:453–463PubMedGoogle Scholar
  6. Benagiano G, Kivinen ST, Fadini R, Cronje H, Klintorp S, van der Spuy ZM (1996) Zoladex (goserelin acetate) and the anemic patient: results of a multicenter fibroid study. Fertil Steril 66:223PubMedGoogle Scholar
  7. Bouchard P, Chabbert-Buffet N, Fauser BC (2011) Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril 96:1175–1189PubMedCrossRefGoogle Scholar
  8. Brandon DD, Erickson TE, Keenan EJ, Strawn EY, Novy MJ, Burry KA, Warner C, Clinton CM (1995) Estrogen receptor gene expression in human uterine leiomyomata. J Clin Endocrinol Metab 80:1876PubMedGoogle Scholar
  9. Bulun SE, Simpson ER, Word RA (1994) Expression of the CYP 19 gene and its product aromatase cytochrome P450 in human uterine leiomyoma tissues and cells in culture. J Clin Endocrinol Metab 78:736PubMedGoogle Scholar
  10. Carr BR, Marshburn PB, Weatherall PT et al (1993) An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial. J Clin Endocrinol Metab 76:1217PubMedGoogle Scholar
  11. Chen W, Ohara N, Wang J et al (2006) A novel selective progesterone receptor modulator Asoprisnil (J 867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells. J Clin Endocrinol Metab 91:1296–1304PubMedCrossRefGoogle Scholar
  12. Chwalisz K, Garg R, Brenner R, et al (2006) Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs) Repro Biol Endocrinol 4 (suppl 1): S8Google Scholar
  13. Chwalisz K, Larsen L, Mattia-Goldberg C et al (2007) A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata. Fertil Steril 87:1399–1412PubMedCrossRefGoogle Scholar
  14. Chwalisz K, Surrey E, Stanczyk FZ (2012) The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis. Reprod Sci 19:563–571PubMedCrossRefGoogle Scholar
  15. Coutinho EM, Boulanger GA, Goncalves MT et al (1986) Regression of uterine leiomyomas after treatment with gestrinone, an antiestrogen, antiprogesterone. Am J Obstet Gynecol 155:761–767PubMedCrossRefGoogle Scholar
  16. Coutinho EM, Goncalves MT (1989) Long-term treatment of leiomyomas with gestrinone. Fertil Steril 51:939–946PubMedGoogle Scholar
  17. De Leo V, la Marca A, Morgante G (1999) Short term treatment of uterine fibromyomas with danazol. Gynecol Obstet Invest 47:258–262PubMedCrossRefGoogle Scholar
  18. Donnez J, Tatarchuk TF, Bouchard P et al (2012a) Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 366:409–420PubMedCrossRefGoogle Scholar
  19. Donnez J, Tomaszewski J, Vazquez F et al (2012b) Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 366:421–432PubMedCrossRefGoogle Scholar
  20. Eisenger SH, Bonfiglio T, Fiscella K et al (2005) Twelve-month safety and efficacy of low dose mifepristone for uterine myomas. J Minim Invasive Gynecol 12:227–233CrossRefGoogle Scholar
  21. Eisinger SH, Fiscella J, Bonfiglio T (2009) Open-label study of ultra low-dose mifepristone for the treatment of uterine leiomyomata. Eur J Obstet Gynecol Reprod Biol 146:215–218PubMedCrossRefGoogle Scholar
  22. Eisenger SH, Meldrum S, Fiscella K et al (2003) Low-dose mifepristone for uterine leiomyomata. Obstet Gynecol 101:243–250CrossRefGoogle Scholar
  23. Esteve JLC, Acosta R, Perez Y et al (2012) Treatment of uterine myoma with 5 or 10 mg mifepristone daily during 6 months, post-treatment evolution over 12 months: double-blind randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 161:202–208PubMedCrossRefGoogle Scholar
  24. Ettinger B, Black DM, Mitlak BH et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 282:637–645PubMedCrossRefGoogle Scholar
  25. Felberbaum RE, Germer U, Ludwig M et al (1998) Treatment of uterine fibroids with a slow-release formulation of the gonadotropin-releasing hormone antagonist Cetrorelix. Hum Reprod 13:1660PubMedCrossRefGoogle Scholar
  26. Felberbaum RE, Kupker W, Krapp M et al (2001) Preoperative reduction of uterine fibroids in only 16 days by administration of a gonadotropin releasing hormone antagonist (Cetrotide). Reprod Biomed online 3:14PubMedCrossRefGoogle Scholar
  27. Flierman PA, Oberye JJ, van der Hulst VP, de Blok S (2005) Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix. BJOG 112:638PubMedCrossRefGoogle Scholar
  28. Friedman AJ (1989) Vaginal hemorrhage associated with degenerating submucous leiomyomata during leuprolide acetate treatment. Fertil Steril 52:152PubMedGoogle Scholar
  29. Friedman AJ, Barbieri RL, Doubilet PM et al (1988) A randomized, double-blind trial of gonadotropin-releasing hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertil Steril 49:404PubMedGoogle Scholar
  30. Friedman AJ, Thomas PP (1995) Does low-dose combination oral contraceptive use affect uterine size or menstrual flow in premenopausal women with leiomyomas? Obstet Gynecol 85:631–635PubMedCrossRefGoogle Scholar
  31. Fritz MA, Speroff L (2011) Clinical gynecologic endocrinology and infertility. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  32. Gonzalez-Barcena D, Alvarez RB, Ochoa EP et al (1997) Treatment of uterine leiomyomas with leutinizing hormone-releasing hormone antagonist Cetrorelix. Hum Reprod 12:2028PubMedCrossRefGoogle Scholar
  33. Grudzien MM, Low PS, Manning PC et al (2010) The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells. Feril Steril 93:1290–1298CrossRefGoogle Scholar
  34. Harrison-Woolrych M, Robinson R (1995) Fibroid growth in response to high-dose progestogen. Fertil Steril 64:191–192PubMedGoogle Scholar
  35. Hasson MH, Fouad H, Bahashwan S et al (2011) Toward non-surgical therapy for uterine fibroids: catechol-O-methyl transferase inhibitor shrinks uterine fibroid lesions in the Eker rat model. Hum Reprod 11:3008–3018CrossRefGoogle Scholar
  36. Hild SA, Reel JR, Blye RP et al (2000) CDB-4124: anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits. Hum Reprod 15:822–829PubMedCrossRefGoogle Scholar
  37. Hornstein MD, Surrey ES, Weisberg GW, Casino LA (1998) Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol 91:16–24PubMedCrossRefGoogle Scholar
  38. Ishihara H, Kitawaki J, Kado N et al (2003) Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertil Steril 79(suppl 1):735–42PubMedCrossRefGoogle Scholar
  39. Ishikawa H, Reierstad S, Demura M et al (2009) High aromatase expression in uterine leiomyoma tissues of African-American women. J Clin Endocrinol Metab 94:1752–1756PubMedCentralPubMedCrossRefGoogle Scholar
  40. Kawaguchi K, Fujii S, Konishi I, Nanbu Y, Nonogaki H, Mori T (1989) Mitotic activity in uterine leiomyomas during the menstrual cycle. Am J Obstet Gynecol 160:637PubMedCrossRefGoogle Scholar
  41. Kim D, Ramachandran S, Seung-hee B et al (2008) Induction of growth inhibition and apoptosis in human uterine leiomyoma cells by isoliquiritigenin. Reprod Sci 15:552–558PubMedCrossRefGoogle Scholar
  42. La Marca A, Musacchio MC, Morgante G et al (2003) Hemodynamic effect of danazol therapy in women with uterine leiomyomata. Fertil Steril 79:1240–1242PubMedCrossRefGoogle Scholar
  43. Loy CJ, Evelyn S, Lim FK et al (2005) Growth dynamics of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated receptor-gamma ligand, pioglitazone. Mol Hum Reprod 11:561–566PubMedCrossRefGoogle Scholar
  44. Malik M, Mendoza M, Payson M et al (2009) Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression. Fertil Steril 91:2177–2184PubMedCrossRefGoogle Scholar
  45. Meagan M, Grudzien MS, Low P et al (2010) The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells. Fertil Steril 93:1290–1298CrossRefGoogle Scholar
  46. Melli MS, Farzadi L, Madarek EO (2007) Comparison of the effect of gonadotropin-releasing hormone analog (Diphereline) and cabergoline (Dostinex) treatment on uterine myoma regression. Saudi Med J 28:445–450PubMedGoogle Scholar
  47. Minaguchi H, Wong JM, Snabes MC (2000) Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature. J Reprod Med 45:481PubMedGoogle Scholar
  48. Miyake A, Takashe T, Isobe A et al (2009) Repressive effect of the phytoestrogen genestein on estradiol-induced uterine leiomyoma cell proliferation. Gynecol Endocrinol 25:403–409PubMedCrossRefGoogle Scholar
  49. Neven P, De Muylder X, Van Belle Y (1989) Tamoxifen and the uterus and endometrium. Lancet 1:375PubMedCrossRefGoogle Scholar
  50. Newton C, Slota D, Yuzpe AA, Tummon IS (1996) Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study. Fertil Steril 65:1253–1255PubMedGoogle Scholar
  51. Olive DL (2000) Review of the evidence for treatment of leiomyomata. Environ Health Perspect 108(suppl 5):841–843PubMedCrossRefGoogle Scholar
  52. Olive DL (2008) Gonadotropin-releasing hormone agonists for endometriosis. N Engl J Med 359:40–46CrossRefGoogle Scholar
  53. Otubu JA, Buttram VC, Besch NF, Besch PK (1982) Unconjugated steroids in leiomyomas and tuor-bearing myometrium. Am J Obstet Gynecol 143:130PubMedGoogle Scholar
  54. Palomba S, Sammartino A, Di Carlo C et al (2001) Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril 76:38–43PubMedCrossRefGoogle Scholar
  55. Palomba S, Orio F Jr, Morelli M et al (2002a) Raloxifene administration in pre-menopausal women with uterine leiomyomas: a pilot study. J Clin Endocrinol Metab 87:3603–3608PubMedCrossRefGoogle Scholar
  56. Palomba S, Russo T, Orio F Jr et al (2002b) Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial. Hum Reprod 17:3213–3219PubMedCrossRefGoogle Scholar
  57. Palomba S, Orio F Jr, Russo T et al (2004) Long term effectiveness and safety of GnRH agonist plus raloxifene administration in women with uterine leiomyomas. Hum Reprod 19:1308–1314PubMedCrossRefGoogle Scholar
  58. Panidis D, Vavilis D, Rousso D et al (1994) Danazol influences gonadotropin secretion acting at the hypothalamic level. Int J Obstet Gynecol 45:241–246CrossRefGoogle Scholar
  59. Parsanezhad ME, Azmoon M, Alborzi S et al (2010) A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status. Fertil Steril 93:192–198PubMedCrossRefGoogle Scholar
  60. Pourmatroud E, Hormozi L, Hemadi M et al (2012) Intravenous ascorbic acid (vitamin C) administration in myomectomy: a prospective, randomized, clinical trial. Arch Gynecol Obstet 285:111–115PubMedCrossRefGoogle Scholar
  61. Rein MS, Friedman AJ, Stuart JM, MacLaughlin DT (1990) Fibroid and myometrial steroid receptors in women treated with the gonadotropin-releasing hormone agonist leuprolide acetate. Fertil Steril 53:1018PubMedGoogle Scholar
  62. Salama S, Nasr A, Dubey R et al (2006) Estrogen metabolite 2-methoxyestradiol induces apoptosis and inhibits cell proliferation and collagen production in rat and human leiomyoma cells: a potential medicinal treatment for uterine fibroids. J Soc Gynecol Investig 13:542–550PubMedCrossRefGoogle Scholar
  63. Sayyah-Melli M, Tehrani-Gadim S, Dastranj-Tabrizi A et al (2009) Comparison of the effect of gonadotropin-releasing hormone agonist and dopamine receptor agonist on uterine myoma growth. Histologic, sonographic, and intra-operative changes. Saudi Med J 30:1024–1033PubMedGoogle Scholar
  64. Scialli AR, Levi AJ (2000) Intermittent leuprolide acetate for the nonsurgical management of women with leiomyomata uteri. Fertil Steril 74:540–546PubMedCrossRefGoogle Scholar
  65. Sherwin BB, Tulandi T (1996) “Add-back” estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri. J Clin Endocrinol Metab 81:2545–2549PubMedGoogle Scholar
  66. Shushan A, Ben-Bassat H, Mishani E et al (2007) Inhibition of leiomyoma cell proliferation in vitro by genestein and the protein tyrosine kinase inhibitor TKS050. Fertil Steril 87:127–135PubMedCrossRefGoogle Scholar
  67. Shushan A, Rojansky N, Laufer N et al (2004) The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth. Hum Reprod 19:1957–1967PubMedCrossRefGoogle Scholar
  68. Steinauer J, Pritts EA, Jackson R et al (2004) Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstet Gynecol 103:1331–1336PubMedCrossRefGoogle Scholar
  69. Tiltman AJ (1985) The effect of progestins on the mitotic activity of uterine fibromyomas. Int J Gynecol 4:89CrossRefGoogle Scholar
  70. Tsuiji K, Takeda T, Li B et al (2011) Inhibitory effect of curcumin on uterine leiomyoma cell proliferation. Gynecol Endocrinol 27:512–517PubMedCrossRefGoogle Scholar
  71. Walker CL (2002) Role of hormonal and reproductive factors in the etiology and treatment of uterine leiomyoma. Recent Prog Horm Res 57:277–294PubMedCrossRefGoogle Scholar
  72. Wang J, Ohara N, Wang Z et al (2006) A novel selective progesterone receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-1, TGF beta 3 and their receptors in cultured uterine leiomyoma cells. Hum Reprod 21:1869–77PubMedCrossRefGoogle Scholar
  73. Wilkens J, Chwalisz K, Han C et al (2008) Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J Clin Endocrinol Metab 93:4664–4671PubMedCrossRefGoogle Scholar
  74. Xu Q, Ohara N, Chen W et al (2006) Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells. Hum Reprod 21:2408–2416PubMedCrossRefGoogle Scholar
  75. Yin P, Lin Z, Cheng YH, Marsh EE, Utsunomiya H, Ishikawa H, Xue Q, Reierstad S, Innes J, Thung S, Kim JJ, Xu E, Bulun SE (2007) Progesterone receptor regulates Bcl-2 gene expression through direct binding to its promotor region in uterine leiomyoma cells. J Clin Endocrinol Metab 92:4459PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Wisconsin Fertility Institute, MiddletonWIUSA

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