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.
Similar content being viewed by others
References
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.
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.
Seinera P, Arisio R, Decko A, Farina C, Crana F. Laparoscopic myomectomy: indications, surgical technique and complications. Human Reprod. 1997;12:1927–1930.
Davies A, Hart R, Magos AL. The excision of uterine fibroids by vaginal myomectomy: a prospective study. Fertil Steril. 1999;71:961–964.
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.
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.
Carpenter TT, Walker WJ. Pregnancy following uterine artery embolisation for symptomatic fibroids: a series of 26 completed pregnancies. BJOG. 2005;112:321–325.
National Institute for Clinical Excellence. Guide to the methods of technology appraisal (ref. N0515). London: National Institute for Clinical Excellence, April 2004.
Wilson EA, Yang F, Rees ED. Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissue. Obstet Gynecol. 1980;55:20–24.
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.
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.
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.
Campo S, Garcea N. Laparoscopic myomectomy in premenopausal women with and without preoperative treatment using gonadotrophinreleasing hormone analogues. Human Reprod. 1999;14:44–48
Vercellini P, Maddalena S, Giorgi OD, Aimi G, Crosignani PG. Abdominal myomectomy for infertility: a comprehensive review. Human Reprod. 1998;13:873–879.
Fauconnier A, Chapron C, Babaki-Fard K, Dubuisson J-B. Recurrence of leiomyomata after myomectomy. Hum Reprod Update. 2000;6:595–602.
Lethaby A, Vollenhoven B. Fibroids (uterine myomatosis, leiomyomas). Clin Evid. 2002;7:1666–1678.
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.
Spitz IM. Clinical utility of progesterone receptor modulators and their effect on the endometrium. Curr Opin Obstet Gynecol. 2009;21:318–324.
Maruo T, Matsuo H, Samoto T, et al. Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids. 2000;65:585–592.
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.
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.
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.
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.
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.
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.
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.
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.
Horne FM, Blithe DL. Progesterone receptor modulators and the endometrium: changes and consequences. Hum Reprod Update. 2007;13:567–580.
Mutter GL, Bergeron C, Deligdisch L, et al. The spectrum of endometrial pathology induced by progesterone receptor modulators. Mod Pathol. 2008;21:591–598.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
To view enhanced content go to www.advancesintherapy.com
Rights and permissions
About this article
Cite this article
Talaulikar, V.S., Manyonda, I.T. Ulipristal Acetate: a Novel Option for the Medical Management of Symptomatic Uterine Fibroids. Adv Therapy 29, 655–663 (2012). https://doi.org/10.1007/s12325-012-0042-8
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-012-0042-8