Advances in Therapy

, Volume 29, Issue 8, pp 655–663

Ulipristal Acetate: a Novel Option for the Medical Management of Symptomatic Uterine Fibroids

Review

Abstract

Fibroids, the most common tumor in women of reproductive age, impact negatively on women’s health and quality of life, and have significant cost implications for their management. The current mainstay treatments are surgical (myomectomy and hysterectomy) and more recently radiological (UAE and focused ultrasound surgery). Hysterectomy is curative but precludes future fertility, whereas the impact of the other treatments on reproduction is uncertain. With women in Western societies deferring childbearing to their 30s and 40s, when fibroids are most symptomatic, there is a pressing need for a uterus-sparing medical therapy that is cheap, effective, and enhances reproductive potential. Serendipity and meticulous translational research has shown that progesterone augments fibroid proliferation, raising the possibility that progesterone receptor modulators could inhibit fibroid growth; this research has culminated in the emergence of ulipristal acetate (UA), a first-in-class, oral selective progesterone receptor modulator (SPRM) that has successfully completed phase III clinical trials. It has been licensed in Western Europe for short-term clinical use prior to surgery, and has shown efficacy with a significant reduction in uterine bleeding, fibroid volume, and improved quality of life, without the side effects associated with other medications such as gonadotropin-releasing hormone (GnRH) agonists. As with all new medicines, there are concerns surrounding UA, not least its effect on the endometrium and the long-term impact on general health and reproduction. Research to date has tended to be industry led, and therefore, there is a need for researcher/clinician-led studies to address the wider issues concerning SPRMs. UA may not turn out to be the “Holy Grail” of medical therapy in the treatment of symptomatic uterine fibroids, but it has rightly given cause for a huge optimism. Further laboratory and clinical research into PRMs and related compounds will no doubt lead to more refined medications.

Keywords

Fibroids Selective progesterone Receptor modulators Ulipristal acetate Women’s health 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wise LA, Palmer JR, Stewart EA, Rosenberg L. Agespecific incidence rates for self-reported uterine leiomyomata in the Black Women’s Health Study. Obstet Gynecol. 2005;105:563–568.PubMedCrossRefGoogle Scholar
  2. 2.
    Walker WJ, Barton-Smith P. Long-term followup of uterine artery embolisation — an effective alternative in the treatment of fibroids. Br J Obstet Gynaecol. 2006;113:464–468.CrossRefGoogle Scholar
  3. 3.
    Seinera P, Arisio R, Decko A, Farina C, Crana F. Laparoscopic myomectomy: indications, surgical technique and complications. Human Reprod. 1997;12:1927–1930.CrossRefGoogle Scholar
  4. 4.
    Davies A, Hart R, Magos AL. The excision of uterine fibroids by vaginal myomectomy: a prospective study. Fertil Steril. 1999;71:961–964.PubMedCrossRefGoogle Scholar
  5. 5.
    Spies JB, Cooper JM, Worthington-Kirsch R, Lipman JC, Mills BB, Benenati JF. Outcome of uterine embolization and hysterectomy for leiomyomas: results of a multi-centre study. Am J Obstet Gynecol. 2004;191:22–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Hindley J, Gedroyc WMW, Regan L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004;183:1713–1719.PubMedGoogle Scholar
  7. 7.
    Carpenter TT, Walker WJ. Pregnancy following uterine artery embolisation for symptomatic fibroids: a series of 26 completed pregnancies. BJOG. 2005;112:321–325.PubMedCrossRefGoogle Scholar
  8. 8.
    National Institute for Clinical Excellence. Guide to the methods of technology appraisal (ref. N0515). London: National Institute for Clinical Excellence, April 2004.Google Scholar
  9. 9.
    Wilson EA, Yang F, Rees ED. Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissue. Obstet Gynecol. 1980;55:20–24.PubMedGoogle Scholar
  10. 10.
    Tamaya T, Fujimoto J, Okada H. Comparison of cellular levels of steroid receptors in uterine leiomyomas and myometrium. Acta Gynaecol Scand. 1985;64:307–309.CrossRefGoogle Scholar
  11. 11.
    Talaulikar VS, Belli A, Manyonda I. GnRH agonists: do they have a place in the modern management of fibroid disease? J Obstet Gynecol India. In Press.Google Scholar
  12. 12.
    Dubuisson JB, Fauconnier A, Fourchotte V, Babaki-Fard K, Coste J, Chapron C. Laparoscopic myomectomy: predicting the risk of conversion to an open procedure. Human Reprod. 2001;16:1726–1731.CrossRefGoogle Scholar
  13. 13.
    Campo S, Garcea N. Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophinreleasing hormone analogues. Human Reprod. 1999;14:44–48CrossRefGoogle Scholar
  14. 14.
    Vercellini P, Maddalena S, Giorgi OD, Aimi G, Crosignani PG. Abdominal myomectomy for infertility: a comprehensive review. Human Reprod. 1998;13:873–879.CrossRefGoogle Scholar
  15. 15.
    Fauconnier A, Chapron C, Babaki-Fard K, Dubuisson J-B. Recurrence of leiomyomata after myomectomy. Hum Reprod Update. 2000;6:595–602.PubMedCrossRefGoogle Scholar
  16. 16.
    Lethaby A, Vollenhoven B. Fibroids (uterine myomatosis, leiomyomas). Clin Evid. 2002;7:1666–1678.PubMedGoogle Scholar
  17. 17.
    Lähteenmäki P, Haukkamaa M, Puolakka J, et al. Open randomised study of use of levonorgestrel releasing intrauterine system as an alternative to hysterectomy. BMJ. 1998;316:1122–1126.PubMedCrossRefGoogle Scholar
  18. 18.
    Spitz IM. Clinical utility of progesterone receptor modulators and their effect on the endometrium. Curr Opin Obstet Gynecol. 2009;21:318–324.PubMedCrossRefGoogle Scholar
  19. 19.
    Maruo T, Matsuo H, Samoto T, et al. Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids. 2000;65:585–592.PubMedCrossRefGoogle Scholar
  20. 20.
    Maruo T. Translational research in women’s health: From bedside to bench and from bench to bedside. Int J Gynecol Obstet. 2010;109:83–84.CrossRefGoogle Scholar
  21. 21.
    Ohara N, Morikawa A, Chen W, et al. Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells. Reprod Sci. 2007;14(Suppl.): 20–27.PubMedCrossRefGoogle Scholar
  22. 22.
    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;14:181–191.PubMedCrossRefGoogle Scholar
  23. 23.
    Yoshida S, Ohara N, Xu Q, et al. Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth. Semin Reprod Med. 2010;28:260–273.PubMedCrossRefGoogle Scholar
  24. 24.
    Levens ED, Potlog-Nahari C, Armstrong AY, et al. CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial. Obstetr Gynecol. 2008;111:1129–1136.CrossRefGoogle Scholar
  25. 25.
    Nieman LK, Blocker W, Nansel T, et al. Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril. 2011;95:767–772. 1–2.PubMedCrossRefGoogle Scholar
  26. 26.
    Donnez J, Tatarchuk TF, Bouchard P, et al.; PEARL I Study Group. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366:409–420.PubMedCrossRefGoogle Scholar
  27. 27.
    Donnez J, Tomaszewski J, Vázquez F, et al; PEARL II Study Group. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012;366:421–432.PubMedCrossRefGoogle Scholar
  28. 28.
    Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update. 2007;13:567–580.PubMedCrossRefGoogle Scholar
  29. 29.
    Mutter GL, Bergeron C, Deligdisch L, et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol. 2008;21:591–598.PubMedCrossRefGoogle Scholar
  30. 30.
    Chabbert-Buffet N, Pintiaux-Kairis A, Bouchard P. Effects of the progesterone receptor modulator VA2914 in a continuous low dose on the hypothalamicpituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2007;92:3582–3589.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2012

Authors and Affiliations

  1. 1.Department of Obstetrics & GynaecologySt. George’s Hospital and University of LondonLondonUK

Personalised recommendations