Ulipristal acetate: Critical review about endometrial and ovulatory effects in emergency contraception

Reproductive Sciences

Volumn 21, Issue 6, 2014, Pages 678-685

  Mozzanega, Bruno ^a   Gizzo, Salvatore ^a   Di Gangi, Stefania ^a   Cosmi, Erich ^a   Nardelli, Giovanni Battista ^a  

^a Azienda Ospedaliero Universitaria   (Italy)

Author keywords

emergency contraception; endometrial effects; ovulation delay; ulipristal acetate; unexpected pregnancy

Indexed keywords

LEVONORGESTREL; LUTEINIZING HORMONE; MIFEPRISTONE; POSTCOITUS CONTRACEPTIVE AGENT; PROGESTERONE RECEPTOR; PROGESTERONE RECEPTOR MODULATOR; ULIPRISTAL; PREGNANE DERIVATIVE;

DELAYED OVULATION; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG EFFECT; DRUG EFFICACY; EMERGENCY CONTRACEPTION; ENDOMETRIUM; FEMALE; FOOD AND DRUG ADMINISTRATION; HUMAN; MEDICAL SOCIETY; MENSTRUAL CYCLE; META ANALYSIS (TOPIC); ORAL CONTRACEPTION; OUTCOMES RESEARCH; OVARY FOLLICLE DEVELOPMENT; OVULATION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRACTICE GUIDELINE; PREGNANCY RATE; PREGNANCY TERMINATION; PRIORITY JOURNAL; REVIEW; SEXUAL INTERCOURSE; SINGLE DRUG DOSE; SYSTEMATIC REVIEW; TABLET FORMULATION; UNPLANNED PREGNANCY; UNPROTECTED SEX; UTERUS BLEEDING; DRUG EFFECTS; PHYSIOLOGY; PREGNANCY; PROCEDURES;

CONTRACEPTION, POSTCOITAL; ENDOMETRIUM; FEMALE; HUMANS; NORPREGNADIENES; OVULATION; PREGNANCY;

EID: 84900457299     PISSN: 19337191     EISSN: 19337205     Source Type: Journal    
DOI: 10.1177/1933719113519178     Document Type: Review

References (79)

1. Gemzell Danielsson K. Mechanism of action of emergency contraception. Contraception. 2010 ; 82 (5). 404-409
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
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
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
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
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
7. Stirling A, Glasier A. Estimating the efficacy of emergency contraception - how reliable are the data?. Contraception. 2002 ; 66 (1). 19-22
8. Trussell J, Ellertson C, von Hertzen H, et al. Estimating the effectiveness of emergency contraceptive pills. Contraception. 2003 ; 67 (4). 259-265
9. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet. 1998 ; 352 (9126). 428-433
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
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
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
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
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
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
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
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
21. Hapangama D, Glasier AF, Baird DT. The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle. Contraception. 2001 ; 64 (3). 123-129
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
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
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
26. Bodensteiner KJ. Emergency contraception and RU-486 (mifepristone): do bioethical discussions improve learning and retention?. Adv Physiol Educ. 2012 ; 36 (1). 34-41
27. Glasier A. Emergency postcoital contraception. N Engl J Med. 1997 ; 337 (15). 1058-1064
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
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
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
31. Miech RP. Immunopharmacology of ulipristal as an emergency contraceptive. Int J Women's Health. 2011 ; 3: 391-393
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
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
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
36. Watson Medical Communication. Highlights of Prescribing Information - Ella Tablet; 2010. http://www.accessdata.fda.gov/drugsatfda-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
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
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
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
42. Gemzell-Danielsson K, Meng CX. Emergency contraception: potential role of ulipristal acetate. Int J Women's Health. 2010 ; 2: 53-61
43. Gainer EE, Ulmann A. Pharmacologic properties of CDB(VA)-2914. Steroids. 2003 ; 68 (10-13). 1005-1011
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
45. 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
47. Moreau C, Trussell J. Results from pooled phase III studies of ulipristal acetate for emergency contraception. Contraception. 2012 ; 86 (6). 673-680
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
50. Sullivan JL, Bulloch MN. Ulipristal acetate: a new emergency contraceptive. Expert Rev Clin Pharmacol. 2011 ; 4 (4). 417-427
51. Shrader SP, Hall LN, Ragucci KR, Rafie S. Updates in hormonal emergency contraception. Pharmacotherapy. 2011 ; 31 (9). 887-895
52. McKeage K, Croxtall JD. Ulipristal acetate: a review of its use in emergency contraception. Drugs. 2011 ; 71 (7). 935-945
53. Fine PM. Ulipristal acetate: a new emergency contraceptive that is safe and more effective than levonorgestrel. Womens Health. 2011 ; 7 (1). 9-17
54. Russo JA, Creinin MD. Ulipristal acetate for emergency contraception. Drugs Today. 2010 ; 46 (9). 655-660
55. Jadav SP, Parmar DV. Ulipristal acetate, a progesterone receptor modulator for emergency contraception. J Pharmacol Pharmacother. 2012 ; 3 (2). 109-111
56. Snow SE, Melillo SN, Jarvis CI. Ulipristal acetate for emergency contraception. Ann Pharmacother. 2011 ; 45 (6). 780-786
57. Keenan JA. Ulipristal acetate: contraceptive or contragestive?. Ann Pharmacother. 2011 ; 45 (6). 813-815
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
59. Gemzell Danielsson K, Berger C, Lalitkumar PGL. Emergency contraception - mechanisms of action. Contraception. 2013 ; 87 (3). 300-308
60. Lalitkumar PGL, Berger C, Gemzell Danielsson K. Emergency contraception. Best Pract Res Clin Endocrinol Metab. 2013 ; 27 (1). 91-101
61. Gemzell Danielsson K, Rabe T, Cheng L. Emergency contraception. Gynecol Endocrinol. 2013 ; 29 (suppl 1). 1-14
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
63. Shoupe D, Mishell DR,, Lacarra M, et al. Correlation of endometrial maturation with four methods of estimating day of ovulation. Obstet Gynecol. 1989 ; 73 (1). 88-92
64. Mozzanega B, Cosmi E, Nardelli GB. Ulipristal acetate in emergency contraception: mechanism of action. Trends Pharmacol Sci. 2013 ; 34 (4). 196-197
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
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
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
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
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
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
71. Shoupe D, Mishell DR,, 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
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
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
74. Croxatto HB. Mifepristone for luteal phase contraception. Contraception. 2003 ; 68 (6). 483-488
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
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
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
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
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