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Ulipristal Acetate: Critical Review About Endometrial and Ovulatory Effects in Emergency Contraception

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Abstract

The effectiveness of emergency contraception (EC) is usually estimated by comparing the number of observed pregnancies to that of expected pregnancies after unprotected intercourse. Second-generation selective progesterone receptors modulators have been developed and evaluated for EC use. Among these compounds, ulipristal acetate (UPA) has been proven to share the same antiprogestin activity as mifepristone, and as with mifepristone, UPA has been demonstrated to be effective up to 120 hours after unprotected intercourse. The UPA is more effective than levonorgestrel (LNG) in preventing the appearance of clinically evident pregnancies. The LNG delays ovulation only when taken at the beginning of the fertile period; taken later, it is ineffective on ovulation, while it has been proven to impair the subsequent luteal function. The effectiveness of LNG decreases as time elapses and is limited to 72 hours after unprotected intercourse. The UPA maintains consistent effectiveness for 5 days after unprotected intercourse, and this effectiveness is independent on which of these 5 days it is taken. The ability of UPA to delay ovulation decreases progressively as ovulation approaches and is null at the time of the luteinizing hormone (LH) peak: 1 to 2 days before ovulation, UPA behaves as a placebo. The persistent effectiveness of the drug cannot be due to antiovulatory action, as it decreases sharply as LH approaches its peak level. The effectiveness is most likely due to the dramatic endometrial effects of the drug that are produced regardless of when it is taken. These effects are consistently present, as the threshold for altering endometrial morphology is lower than the threshold for altering folliculogenesis.

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References

  1. Gemzell Danielsson K. Mechanism of action of emergency contraception. Contraception. 2010;82(5):404–409.

    Article  CAS  PubMed  Google Scholar 

  2. Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med. 1995;333(23):1517–1521.

    Article  CAS  PubMed  Google Scholar 

  3. Wilcox AJ, Baird DD, Dunson DB, McConnaughey DR, Kesner JS, Weinberg CR. On the frequency of intercourse around ovulation: evidence for biological influences. Hum Reprod. 2004;19(7): 1539–1543.

    Article  CAS  PubMed  Google Scholar 

  4. Dunson DB, Baird DD, Wilcox AJ, Weinberg CR. Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation. Hum Reprod. 1999;14(7): 1835–1839.

    Article  CAS  PubMed  Google Scholar 

  5. Trussel J, Rodriguez G, Ellertson C. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception. 1998;57(6):363–369.

    Article  Google Scholar 

  6. Fine P, Mathé H, Ginde S, Cullins V, Morfesis J, Gainer E. Ulipristal acetate taken 48–120 hours after intercourse for emergency contraception. Obstet Gynecol. 2010;115(2 pt 1):257–263.

    Article  PubMed  Google Scholar 

  7. Stirling A, Glasier A. Estimating the efficacy of emergency contraception—how reliable are the data? Contraception. 2002; 66(1):19–22.

    Article  PubMed  Google Scholar 

  8. Trussell J, Ellertson C, von Hertzen H, et al. Estimating the effectiveness of emergency contraceptive pills. Contraception. 2003; 67(4):259–265.

    Article  PubMed  Google Scholar 

  9. Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet. 1998;352(9126):428–433.

    Article  Google Scholar 

  10. Cheng L, Gülmezoglu AM, Piaggio G, Ezcurra E, Van Look PF. Interventions for emergency contraception. Cochrane Database Syst Rev. 2008;(2):CD001324.

  11. Mozzanega B, Cosmi E. How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some considerations. Gynecol Endocrinol. 2011;27(6):439–442.

    Article  PubMed  Google Scholar 

  12. Croxatto HB, Brache V, Pavez M, et al. Pituitary–ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation. Contraception. 2004;70(6):442–450.

    Article  CAS  PubMed  Google Scholar 

  13. Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and metaanalysis. Lancet. 2010; 375(9714):555–562.

    Article  CAS  PubMed  Google Scholar 

  14. Brache V, Cochon L, Jesam C, et al. Immediate preovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod. 2010;25(9):2256–2263.

    Article  CAS  PubMed  Google Scholar 

  15. Noé G, Croxatto HB, Salvatierra AM, Reyes V, Villarroel C, Muñoz C, et al. Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation. Contraception. 2010;81(5):414–420.

    Article  PubMed  CAS  Google Scholar 

  16. International Federation of Gynecology & Obstetrics (FIGO) and International Consortium for Emergency Contraception (ICEC). How do Levonorgestrel-only emergency contraceptive pills (LNG ECPs) work to prevent pregnancy? http://www.cecinfo.org/custom-content/uploads/2012/12/ICEC_FIGO_MoA_Statement_March_2012.pdf. Accessed March 1, 2013.

  17. The European Society of Contraception and Reproductive Health. “How do Levonorgestrelonly emergency contraceptive pills (LNG ECPs) work to prevent pregnancy?”. http://www.escrh.eu/about-esc/news/how-do-levonorgestrel. Accessed March 1, 2013.

  18. Massai MR, Forcelledo ML, Brache V, et al. Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study. Hum Reprod. 2007;22(2):434–439.

    Article  CAS  PubMed  Google Scholar 

  19. Marions L, Hultenby K, Lindell I, Sun X, Ståbi B, Gemzell Danielsson K. Emergency contraception with mifepristone and levonorgestrel: mechanism of action. Obstet Gynecol. 2002;100(1):65–71.

    CAS  PubMed  Google Scholar 

  20. Durand M, del Carmen Cravioto M, Raymond EG, et al. On the mechanisms of action of short-term levonorgestrel administration in emergency contraception. Contraception. 2001;64(4): 227–234.

    Article  CAS  PubMed  Google Scholar 

  21. Hapangama D, Glasier AF, Baird DT. The effects of periovulatory administration of levonorgestrel on the menstrual cycle. Contraception. 2001;64(3):123–129.

    Article  Google Scholar 

  22. Okewole IA, Arowojolu AO, Odusoga OL, et al. Effect of single administration of levonorgestrel on the menstrual cycle. Contraception. 2007;75(5):372–377.

    Article  CAS  PubMed  Google Scholar 

  23. Durand M, Seppala M, Cravioto Mdel C, et al. Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle. Contraception. 2005;71(6):451–457.

    Article  CAS  PubMed  Google Scholar 

  24. Cheng L, Che Y, Gülmezoglu AM. Intervention for emergency contraception. Cochrane Database Syst Rev. 2012;8:CD001324.

  25. Taneepanichskul S. Emergency contraception with mifepristone 10 mg in Thai women. J Med Assoc Thai. 2009;92(8):999–1002.

    PubMed  Google Scholar 

  26. Bodensteiner KJ. Emergency contraception and RU-486 (mifepristone): do bioethical discussions improve learning and retention? Adv Physiol Educ. 2012;36(1):34–41.

    Article  PubMed  Google Scholar 

  27. Glasier A. Emergency postcoital contraception. N Engl J Med. 1997;337(15):1058–1064.

    Article  CAS  PubMed  Google Scholar 

  28. Glasier A, Thong KJ, Dewar M, Mackie M, Baird DT. Mifepristone (RU486) compared with high dose estrogen and progestin for emergency postcoital contraception. N Engl J Med. 1992;327(15): 1041–1044.

    Article  CAS  PubMed  Google Scholar 

  29. Richardson AR, Maltz FN. Ulipristal acetate: review of the efficacy and safety of a newly approved agent for emergency contraception. Clin Ther. 2012;34(1):24–36.

    Article  CAS  PubMed  Google Scholar 

  30. Zhu HX, Zhang WW, Zhuang YL, Huang LL. Mifepristone as an anti-implantation contraceptive drug: roles in regulation of uterine natural killer cells during implantation phase. Am J Reprod Immunol. 2009;61(1):68–74.

    Article  PubMed  Google Scholar 

  31. Miech RP. Immunopharmacology of ulipristal as an emergency contraceptive. Int J Women’s Health. 2011;3:391–393.

    Article  Google Scholar 

  32. Advisory Committee for Reproductive Health Drugs. Ulipristal acetate 30 mg tablet. Briefing materials. http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/reprductivehealthdrugsadvisorycommittee/ucm215510.pdf. Accessed June 17, 2010.

  33. Stratton P, Hartog B, Hajizadeh N, et al. A single midfollicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women. Hum Reprod. 2000;15(5):1092–1099.

    Article  CAS  PubMed  Google Scholar 

  34. Stratton P, Levens ED, Hartog B, et al. Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914. Fertil Steril. 2010;93(6):2035–2041.

    Article  CAS  PubMed  Google Scholar 

  35. Passaro MD, Piquion J, Mullen N, et al. Luteal phase doseresponse relationships of the antiprogestin CDB-2914 in normally cycling women. Hum Reprod. 2003;18(9):1820–1827.

    Article  CAS  PubMed  Google Scholar 

  36. Watson Medical Communication. Highlights of Prescribing Information—Ella Tablet; 2010. http://www.accessdata.fda.gov/drug-satfda_docs/label/2010/022474s000lbl.pdf. Accessed March 1, 2013.

  37. European Medicines Agency. EllaOne: EPAR—Product Information. Annex 1—Survey of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/001027/WC500023670.pdf. Accessed March 1, 2013.

  38. Wagner BL, Pollio G, Giangrande P, et al. The novel progesterone receptor antagonist RTI 3021-3012 and RTI 3021-3022 exhibit complex glucocorticoid receptor activities: implications for the development of dissociated antiprogestins. Endocrinology. 1999;140(3):1449–1458.

    Article  CAS  PubMed  Google Scholar 

  39. Blithe DL, Nieman LK, Blye RP, Stratton P, Passaro M. Development of the selective progesterone receptor modulator CDB-2914 for clinical indications. Steroids. 2003;68(10–13):1013–1017.

    Article  CAS  PubMed  Google Scholar 

  40. Attardi BJ, Burgenson J, Hild SA, Reel JR. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol. 2004;88(3):277–288.

    Article  CAS  PubMed  Google Scholar 

  41. Attardi BJ, Burgenson J, Hild SA, Reel JR, Blye RP. 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;188(1–2):111–123.

    Article  CAS  PubMed  Google Scholar 

  42. Gemzell-Danielsson K, Meng CX. Emergency contraception: potential role of ulipristal acetate. Int J Women’s Health. 2010; 2:53–61.

    Article  CAS  Google Scholar 

  43. Gainer EE, Ulmann A. Pharmacologic properties of CDB(VA)-2914. Steroids. 2003;68(10–13):1005–1011.

    Article  CAS  PubMed  Google Scholar 

  44. Rao PN, Wang Z, Cessac JW, Rosenberg RS, Jenkins DJ, Diamandis EP. New 11beta-arylsubstituted steroids exhibit both progestational and antiprogestational activity. Steroids. 1998;63(10):523–530.

    Article  CAS  PubMed  Google Scholar 

  45. US Food and Drug Administration. Ulipristal Acetate: New Drug Review Application 22–474. Center for Drug Evaluation and Research; 2009.

  46. Creinin MD, Schlaff W, Archer DF, et al. Progestin receptor modulator for emergency contraception: a randomized control trial. Obstet Gynecol. 2006;108(5):1089–1097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Moreau C, Trussell J. Results from pooled phase III studies of ulipristal acetate for emergency contraception. Contraception. 2012; 86(6):673–680.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. International Federation of Gynecology & Obstetrics (FIGO) and International Consortium for Emergency Contraception (ICEC). Emergency Contraceptive Pills—Medical and Service Delivery Guidelines; 2012. http://www.sexualityandu.ca/uploads/files/Medical_and_Service_Delivery_Guidelines_Eng_2012.pdf. Accessed March 1, 2013.

  49. Wilton JM. Ulipristal acetate—the newest emergency contraceptive. Nurs Womens Health. 2012;16(4):331–335.

    Article  PubMed  Google Scholar 

  50. Sullivan JL, Bulloch MN. Ulipristal acetate: a new emergency contraceptive. Expert Rev Clin Pharmacol. 2011;4(4): 417–427.

    Article  PubMed  Google Scholar 

  51. Shrader SP, Hall LN, Ragucci KR, Rafie S. Updates in hormonal emergency contraception. Pharmacotherapy. 2011;31(9): 887–895.

    Article  PubMed  Google Scholar 

  52. McKeage K, Croxtall JD. Ulipristal acetate: a review of its use in emergency contraception. Drugs. 2011;71(7):935–945.

    Article  CAS  PubMed  Google Scholar 

  53. Fine PM. Ulipristal acetate: a new emergency contraceptive that is safe and more effective than levonorgestrel. Womens Health. 2011;7(1):9–17.

    CAS  Google Scholar 

  54. Russo JA, Creinin MD. Ulipristal acetate for emergency contraception. Drugs Today. 2010;46(9):655–660.

    Article  CAS  Google Scholar 

  55. Jadav SP, Parmar DV. Ulipristal acetate, a progesterone receptor modulator for emergency contraception. J Pharmacol Pharmacother. 2012;3(2):109–111.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Snow SE, Melillo SN, Jarvis CI. Ulipristal acetate for emergency contraception. Ann Pharmacother. 2011;45(6):780–786.

    Article  CAS  PubMed  Google Scholar 

  57. Keenan JA. Ulipristal acetate: contraceptive or contragestive? Ann Pharmacother. 2011;45(6):813–815.

    Article  CAS  PubMed  Google Scholar 

  58. Gizzo S, Fanelli T, Di Gangi S, et al. Nowadays which emergency contraception? Comparison between past and present: latest news in terms of clinical efficacy, side effects and contraindications. Gynecol Endocrinol. 2012;28(10):758–763.

    Article  CAS  PubMed  Google Scholar 

  59. Gemzell Danielsson K, Berger C, Lalitkumar PGL. Emergency contraception—mechanisms of action. Contraception. 2013; 87(3):300–308.

    Article  CAS  PubMed  Google Scholar 

  60. Lalitkumar PGL, Berger C, Gemzell Danielsson K. Emergency contraception. Best Pract Res Clin Endocrinol Metab. 2013; 27(1):91–101.

    Article  CAS  PubMed  Google Scholar 

  61. Gemzell Danielsson K, Rabe T, Cheng L. Emergency contraception. Gynecol Endocrinol. 2013;29(suppl 1):1–14.

    Article  CAS  PubMed  Google Scholar 

  62. Behre HM, Kuhlage J, Gassner C, et al. Prediction of ovulation by urinary hormone measurements with the home use ClearPlan Fertility Monitor: comparison with transvaginal ultrasound scans and serum hormone measurements. Hum Reprod. 2000; 15(12):2478–2482.

    Article  CAS  PubMed  Google Scholar 

  63. Shoupe D, Mishell DR Jr, Lacarra M, et al. Correlation of endometrial maturation with four methods of estimating day of ovulation. Obstet Gynecol. 1989;73(1):88–92.

    CAS  PubMed  Google Scholar 

  64. Mozzanega B, Cosmi E, Nardelli GB. Ulipristal acetate in emergency contraception: mechanism of action. Trends Pharmacol Sci. 2013;34(4):196–197.

    Article  CAS  Google Scholar 

  65. Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G. The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod. 1996;11(3): 627–632.

    Article  CAS  PubMed  Google Scholar 

  66. Danielsson KG, Swahn ML, Westlund P, Johannisson E, Seppälä M, Bygdeman M. Effect of low daily doses of mifepristone on ovarian function and endometrial development. Hum Reprod. 1997;12(1):124–131.

    Article  CAS  PubMed  Google Scholar 

  67. Foulk RA, Zdravkovic T, Genbacev O, Prakobphol A. Expression of L-selectin ligand MECA-79 as a predictive marker of human uterine receptivity. J Assist Reprod Genet. 2007;24(7): 316–321.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Genbacev OD, Prakobphol A, Foulk RA, Krtolica AR, Ilic D, Singer MS, et al. Trophoblast L-selectin-mediated adhesion at the maternal–fetal interface. Science. 2003;299(5605): 405–408.

    Article  CAS  PubMed  Google Scholar 

  69. Gemzell Danielsson K, Marions L. Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception. Hum Reprod Update. 2004;10(4):341–348.

    Article  CAS  PubMed  Google Scholar 

  70. Liu JH, Garzo G, Morris S, Stuenkel C, Ulmann A, Yen SS. Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU486. J Clin Endocrinol Metab. 1987;65(6):1135–1140.

    Article  CAS  PubMed  Google Scholar 

  71. Shoupe D, Mishell DR Jr, Page MA, Madkour H, Spitz IM, Lobo RA. Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase. Am J Obstet Gynecol. 1987;157(6):1421–1426.

    Article  CAS  PubMed  Google Scholar 

  72. Hapangama DK, Brown A, Glasier AF, Baird DT. Feasibility of administering mifepristone as a once a month contraceptive pill. Hum Reprod. 2001;16(6):1145–1150.

    Article  CAS  PubMed  Google Scholar 

  73. Agarwal M, Das V, Agarwal A, Pandey A, Srivastava D. Evaluation of mifepristone as a once a month contraceptive pill. Am J Obstet Gynecol. 2009;200(5):e27–e29.

    Article  CAS  PubMed  Google Scholar 

  74. Croxatto HB. Mifepristone for luteal phase contraception. Contraception. 2003;68(6):483–488.

    Article  CAS  PubMed  Google Scholar 

  75. Puri CP, Katkam RR, Sachdeva G, Patil V, Manjramkar DD, Kholkute SD. Endometrial contraception: modulation of molecular determinants of uterine receptivity. Steroids. 2000;65(10–11): 783–794.

    Article  CAS  PubMed  Google Scholar 

  76. Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366(5):409–420.

    Article  CAS  PubMed  Google Scholar 

  77. Koskas M, Chabbert Buffet N, Douvier S, Huchon C, Paganelli E, Derrien J. Role of medical treatment for symptomatic leiomyoma management in premenopausal women. J Gynecol Obstet Biol Reprod. 2011;40(8):858–874.

    Article  CAS  Google Scholar 

  78. Esteve JL, Acosta R, Pérez Y, Campos R, Hernández AV, Texidó CS. Treatment of uterine myoma with 5 or 10 mg mifepristone daily during 6 months, post-treatment evolution over 12 months: double-blind randomised clinical trial. Eur J Obstet Gynecol Reprod Biol. 2012;161(2):202–208.

    Article  CAS  PubMed  Google Scholar 

  79. Carbonell Esteve JL, Riverón AM, Cano M, et al. Mifepristone 2.5 mg versus 5 mg daily in the treatment of leiomyoma before surgery. Int J Womens Health. 2012;4:75–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Woman and Child Health, University of Padua, Padova, Italy

    Bruno Mozzanega MD, Salvatore Gizzo MD, Stefania Di Gangi MD, Erich Cosmi MD & Giovanni Battista Nardelli MD

  2. Dipartimento di Salute della Donna e del Bambino, U.O.C. di Ginecologia e Ostetricia, Via Giustiniani 3, Padova, 35128, Italy

    Salvatore Gizzo MD

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  1. Bruno Mozzanega MD
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  2. Salvatore Gizzo MD
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  5. Giovanni Battista Nardelli MD
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Correspondence to Salvatore Gizzo MD.

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Mozzanega, B., Gizzo, S., Di Gangi, S. et al. Ulipristal Acetate: Critical Review About Endometrial and Ovulatory Effects in Emergency Contraception. Reprod. Sci. 21, 678–685 (2014). https://doi.org/10.1177/1933719113519178

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