, Volume 72, Issue 8, pp 1075–1085

Ulipristal Acetate

In Uterine Fibroids
Adis Drug Profile


Ulipristal acetate, a selective progesterone-receptor modulator, inhibits the proliferation and induces apoptosis of leiomyoma cells in vitro. It also modulates the expression of vascular endothelial growth factors and hormone receptors and modulates extracellular matrix breakdown in leiomyoma cells but not in myometrial cells.

In two randomized, double-blind, multinational phase III trials of 13 weeks’ duration in women aged 18–50 years with uterine fibroids, a once-daily regimen of oral ulipristal acetate 5mg/day controlled excessive uterine bleeding (primary endpoint) in ≥90% of patients. Ulipristal acetate 5mg/day was more effective than placebo and was shown to be noninfe-rior to intramuscular leuprolide acetate 3.75mg once monthly in controlling uterine bleeding.

Uterine bleeding was rapidly controlled by ulipristal acetate. Approximately half of recipients of ulipristal acetate 5mg/day became amenorrhoeic within the first 10 days of treatment. Furthermore, uterine bleeding was controlled significantly more rapidly for recipients of ulipristal acetate than recipients of leuprolide acetate.

A significantly greater median reduction from baseline in total fibroid volume was observed for recipients of ulipristal acetate 5mg once daily than recipients of placebo following 13 weeks’ treatment (coprimary endpoint). For patients who did not undergo surgery, the volume reduction was maintained for at least 6 months after discontinuing treatment.

Ulipristal acetate was generally well tolerated in women with uterine fibroids. The incidence of hot flush occurred with a significantly lower frequency for recipients of ulipristal acetate than for recipients of leuprolide acetate.


  1. 1.
    Chegini N. Proinflammatory and profibrotic mediators: principal effectors of leiomyoma development as a fibrotic disorder. Semin Reprod Med 2010; 28 (3): 180–203PubMedCrossRefGoogle Scholar
  2. 2.
    Rein MS, Friedman AJ, Barbieri RL, et al. Cytogenetic abnormalities in uterine leiomyomata. Obstet Gynecol 1991 Jun; 77 (6): 923–6PubMedGoogle Scholar
  3. 3.
    Mashal RD, Fejzo ML, Friedman AJ, et al. Analysis of androgen receptor DNA reveals the independent clonal origins of uterine leiomyomata and the secondary nature of cytogenetic aberrations in the development of leiomyomata. Genes Chromosomes Cancer 1994 Sep; 11 (1): 1–6PubMedCrossRefGoogle Scholar
  4. 4.
    Schwartz PE, Kelly MG. Malignant transformation of myomas: myth or reality?. Obstet Gynecol Clin North Am 2006 Mar; 33 (1): 183–98, xiiPubMedCrossRefGoogle Scholar
  5. 5.
    Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994 Mar; 83 (3): 414–8PubMedGoogle Scholar
  6. 6.
    Ligon A, Morton C. Leiomyomata: heritability and cytogenetic studies. Hum Reprod Update 2001; 7 (1): 8–14PubMedCrossRefGoogle Scholar
  7. 7.
    Baird D, Duson D, Hill M, et al. High cumulative incidence of uterine leiomyoma in Black and White women: ultrasound evidence. Am J Ostet Gynecol 2003; 188 (1): 100–7CrossRefGoogle Scholar
  8. 8.
    Buttram Jr VC, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril 1981 Oct; 36 (4): 433–45PubMedGoogle Scholar
  9. 9.
    Evans P, Brunsell S. Uterine fibroid tumors: diagnosis and treatment. Am FamPhysician 2007 May 15; 75 (10): 1503–8Google Scholar
  10. 10.
    Donnez J, Jadoul P. What are the implications of myomas on fertility? A need for a debate?. Hum Reprod 2002 Jun; 17 (6): 1424–30PubMedCrossRefGoogle Scholar
  11. 11.
    Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Myomas and reproductive function. Fertil Steril 2008; 90 (5 Suppl.): S125–30Google Scholar
  12. 12.
    Parker WH. Uterine myomas: management. Fertil Steril 2007 Aug; 88 (2): 255–71PubMedCrossRefGoogle Scholar
  13. 13.
    Flynn M, Jamison M, Datta S, et al. Health care resource use for uterine fibroid tumors in the United States. Am J Obstet Gynecol 2006 Oct; 195 (4): 955–64PubMedCrossRefGoogle Scholar
  14. 14.
    McCarthy-Keith DM, Armstrong AY. Innovations in uterine fibroid therapy. Therapy 2011; 8 (2): 189–200CrossRefGoogle Scholar
  15. 15.
    Ravina J, Bouret J, Cirary-Vigneron N, et al. Application of particulate arterial embolization in the treatment of uterine fibromyomata. Bull Fr Nat Acad Med 1997; 18 (2): 1–10Google Scholar
  16. 16.
    Duhan N. Current and emerging treatments for uterine myoma: an update. Int J Womens Health 2011; 3 (1): 231–42PubMedCrossRefGoogle Scholar
  17. 17.
    De Leo V, Morgante G, La Marca A, et al. A benefit-risk assessment of medical treatment for uterine leiomyomas. Drug Saf 2002; 25 (11): 759–79PubMedCrossRefGoogle Scholar
  18. 18.
    Stewart EA. Uterine fibroids and evidence-based medicine: not an oxymoron. N Engl J Med 2012 Feb 2; 366 (5): 471–3PubMedCrossRefGoogle Scholar
  19. 19.
    Flake G, Andersen J, Dixon D. Eitiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect 2003; 111 (8): 1037–54PubMedCrossRefGoogle Scholar
  20. 20.
    Cohen O, Schindel B, Homburg R. Uterine leiomyomata: a feature of acromegaly. Hum Reprod 1998 Jul; 13 (7): 1945–6PubMedCrossRefGoogle Scholar
  21. 21.
    Grattarola R, Li CH. Effect of growth hormone and its combination with estradiol-17b on the uterus of hypophysectomized-ovariectomized rats. Endocrinology 1959; 65 (5): 802–10PubMedCrossRefGoogle Scholar
  22. 22.
    Rein MS, Barbieri RL, Friedman AJ. Progesterone: a critical role in the pathogenesis of uterine myomas. Am J Obstet Gynecol 1995 Jan; 172 (1 Pt 1): 14–8Google Scholar
  23. 23.
    Maruo T. Progesterone and progesterone receptor modulator in uterine leiomyoma growth. Gynecol Endocrinol 2007; 23 (4): 186–7PubMedCrossRefGoogle Scholar
  24. 24.
    Hoekstra AV, Sefton EC, Berry E, et al. Progestins activate the AKT pathway in leiomyoma cells and promote survival. J Clin Endocrinol Metab 2009 May; 94 (5): 1768–74PubMedCrossRefGoogle Scholar
  25. 25.
    Ishikawa H, Ishi K, Serna VA, et al. Progesterone is essential for maintenance and growth of uterine leiomyoma. En-docrinology 2010 Jun; 151 (6): 2433–42CrossRefGoogle Scholar
  26. 26.
    Yin P, Lin Z, Cheng YH, et al. Progesterone receptor regulates Bcl-2 gene expression through direct binding to its promoter region in uterine leiomyoma cells. J Clin Endocrinol Metab 2007 Nov; 92 (11): 4459–66PubMedCrossRefGoogle Scholar
  27. 27.
    Yin P, Lin Z, Reierstad S, et al. Transcription factor KLF11 integrates progesterone receptor signaling and proliferation in uterine leiomyoma cells. Cancer Res 2010 Feb 15; 70 (4): 1722–30PubMedCrossRefGoogle Scholar
  28. 28.
    Chwalisz K, Perez MC, DeManno D, et al. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 2005; 26 (3): 423–38PubMedCrossRefGoogle Scholar
  29. 29.
    Pintiaux A, Chabbert-Buffet N, Foidart JM. Gynaecological uses of a new class of steroids: the selective progesterone receptor modulators. Gynecol Endocrinol 2009 Feb; 25 (2): 67–73PubMedCrossRefGoogle Scholar
  30. 30.
    Spitz IM. Clinical utility of progesterone receptor modulators and their effect on the endometrium. Curr Opin Obstet Gynecol 2009; 21 (4): 318–24PubMedCrossRefGoogle Scholar
  31. 31.
    Maruo T, Ohara N, Matsuo H, et al. Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM CDB-2914 on uterine leiomyomas. Contraception 2007; 75 (6 Suppl.): S99–103Google Scholar
  32. 32.
    Bouchard P, Chabbert-Buffet N, Fauser BCJM. Selective progesterone receptor modulators in reproductive medicine: pharmacology, clinical efficacy and safety. Fertil Steril 2011; 96 (5): 1175–89PubMedCrossRefGoogle Scholar
  33. 33.
    Chabbert-Buffet N, Meduri G, Bouchard P, et al. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update 2005; 11 (3): 293–307PubMedCrossRefGoogle Scholar
  34. 34.
    McKeage K, Croxtall JD. Ulipristal acetate: a review of its use in emergency contraception. Drugs 2011 May 7; 71 (7): 935–45PubMedCrossRefGoogle Scholar
  35. 35.
    Electronic Medicines Compendium. Esmya 5mg tablets (ulipristal acetate) [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/26068/SPC/Esmya+5+mg+Tablets+(ulipristal+acetate)/ [Accessed 2012 Mar 7]
  36. 36.
    Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 2012 Feb 2; 366 (5): 409–20PubMedCrossRefGoogle Scholar
  37. 37.
    Donnez J, Tomaszewski J, Vazquez F, et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med 2012 Feb 2; 366 (5): 421–32PubMedCrossRefGoogle Scholar
  38. 38.
    Chabbert-Buffet N, Pintiaux-Kairis A, Bouchard P. Effects of the progesterone receptor modulator VA2914 in a continuous low dose on the hypothalamic-pituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2007 Sep; 92 (9): 3582–9PubMedCrossRefGoogle Scholar
  39. 39.
    Ravet S, Munaut C, Blacher S, et al. Persistence of an intact endometrial matrix and vessels structure in women exposed to VA-2914, a selective progesterone receptor modulator. J Clin Endocrinol Metab 2008 Nov; 93 (11): 4525–31PubMedCrossRefGoogle Scholar
  40. 40.
    Attardi BJ, Burgenson J, Hild SA, et al. 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 2002 Feb 25; 188 (1–2): 111–23Google Scholar
  41. 41.
    Xu Q, Takekida S, Ohara N, et al. Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5’-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells. J Clin Endocrinol Metab 2005; 90 (2): 953–61PubMedCrossRefGoogle Scholar
  42. 42.
    Xu Q, Ohara N, Chen W, et al. 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 2006; 21 (9): 2408–16PubMedCrossRefGoogle Scholar
  43. 43.
    Xu Q, Ohara N, Liu J, et al. Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells. Mol Hum Reprod 2008; 14 (3): 181–91PubMedCrossRefGoogle Scholar
  44. 44.
    Brache V, Cochon L, Jesam C, et al. Immediate preovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 2010 Sep; 25 (9): 2256–63PubMedCrossRefGoogle Scholar
  45. 45.
    Palanisamy GS, Cheon YP, Kim J, et al. A novel pathway involving progesterone receptor, endothelin-2, and endothelin receptor B controls ovulation in mice. Mol Endocrinol 2006 Nov; 20 (11): 2784–95PubMedCrossRefGoogle Scholar
  46. 46.
    Narvekar N, Critchley HO, Cheng L, et al. Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor. Hum Reprod 2006 Sep; 21 (9): 2312–8PubMedCrossRefGoogle Scholar
  47. 47.
    McFarland F, Blithe HaD. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update 2007; 13 (6): 567–80CrossRefGoogle Scholar
  48. 48.
    Mutter GL, Bergeron C, Deligdisch L, et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol 2008 May; 21 (5): 591–8PubMedCrossRefGoogle Scholar
  49. 49.
    European Medicines Agency. Assessment report for Esmya [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002041/WC500124088.pdf [Accessed 2012 Mar 30]

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

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