Ulipristal Acetate (UPA) in Emergency Contraception: The Mechanism of Action, Toxicity and Perspectives
Main Article Content
Abstract
After recalling that Levonorgestrel Emergency Contraceptive Pills never delay or suppress ovulation, but impair the luteal body functions, and, consequently, the embryo-implantation, we focus on the mechanism of action (MOA) of ellaOne®: micronized UPA (Ulipristal Acetate) 30mg and on UPA- toxicity.
EMA and, after it, the National Drug Regulatory Institutions and the most renowned International Gynecological Societies present ellaOne® as an anti-ovulatory drug which is safe even in repeated assumption, also during the same menstrual cycle. We’ll try to understand whether this dogma is supported by experimental data in literature.
As to the MOA, EMA reports (EMEA-261787-2009) that Ulipristal blocks the synthesis of the proteins necessary to begin and maintain pregnancy, and that Ulipristal and mifepristone were approximately equipotent as to their ability to terminate pregnancy. Besides, EMA further evidences (EMA/73099/2015) that it is unknown whether it is possible to use ellaOne® for abortion.
Data in Literature evidence that ellaOne® can delay ovulation only when is taken in the very first fertile days of the cycle. In the pre-ovulatory, most fertile, days - when most intercourses do occur and over 70% fertilizations ensue - it never prevents ovulation, like placebo. On the contrary, whenever it is taken in the cycle, it consistently impairs the endometrium that becomes an inhospitable ground for the embryo: endometrial gene expression is completely subverted compared with that of the normal luteal phase.
Recently, an UPA-based drug used for uterine fibroids-treatment (Esmya®) was withdrawn from the market because it caused fulminant hepatitis requiring transplantation (EMA/455818/2020). It was prescribed by the hospital for 3-6 months and carefully followed-up. The strict post-marketing surveillance allowed to link UPA-administration and tissue-accumulation to liver-failure. Surprisingly EMA, while revoking Esmya®, warranted for the safety of ellaOne®, though it is taken by millions of women unaware of the risk, repeatedly without prescription, without medical supervision and any possibility of post-marketing surveillance, in UPA-cumulating doses even greater than with Esmya®.
Finally, we criticize the attempt to propose UPA in daily contraceptive pills, at doses even double than in Esmya® and for much longer periods, to fertile women aiming at preserving their fertility and health.
Keywords:
ellaOne, ella, Ulipristal, Emergency Contraception, Mechanism of Action, Ovulation, Endometrium, Embryo-implantation, Toxicity, Esmya
Article Details
How to Cite
MOZZANEGA, Bruno.
Ulipristal Acetate (UPA) in Emergency Contraception: The Mechanism of Action, Toxicity and Perspectives.
Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3387>. Date accessed: 03 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i12.3387.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Dunson DB, Baird DD, Wilcox AJ, et al. Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation. Hum Reprod. 1999;14:1835-1839.
4. Behre HM, Kulhage 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;15:2478-2482.
5. Fine P, Mathé H, Ginde S, et al. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstet Gynecol. 2010;115:257-263.
6. Stirling A, Glasier A. Estimating the efficacy of emergency contraception—how reliable are the data? Contraception. 2002;66:19-22.
7. Dye HM, Stanford JB, Alder SC, et al. Women and postfertilization effects of birth control: consistency of beliefs, intentions and reported use. BMC Womens Health. 2005;5:11.
8. de Irala J, Lopez del Burgo C, Lopez de Fez CM, et al. Women's attitudes towards mechanisms of action of family planning methods: survey in primary health centres in Pamplona, Spain. BMC Womens Health. 2007;7:10.
9. Campbell JW 3rd, Busby SC, Steyer TE. Attitudes and beliefs about emergency contraception among patients at academic family medicine clinics. Ann Fam Med. 2008;6 Suppl 1:S23-27.
10. Lopez-del Burgo C, Lopez-de Fez CM, Osorio A, Guzmán JL, et al. Spanish women's attitudes towards post-fertilization effects of birth control methods. Eur J Obstet Gynecol Reprod Biol. 2010;151(1):56-61.
11. World Health Organization (WHO) Media centre. Emergency contraception: Fact sheet. [Reviewed 2018 February]. http://www.who.int/ [Internet] Available from: http://www.who.int/mediacentre/factsheets/fs244/en/.
12. Advisory Committee for Reproductive Health Drugs. Ulipristal acetate 30 mg tablet.– Briefing Materials. 2010 June 17. http://www.accessdata.fda.gov/ [Internet] Available from: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/reprductivehealthdrugsadvisorycommittee/ucm215510.pdf.
13. Watson Medical Communication. Highlights of Prescribing Information - Ella Tablet. 2010 October. http://www.accessdata.fda.gov/ Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdf.
14. European Medicines Agency (EMA). European Public Assessment Report (EPAR) on ellaOne [updated 16/11/2022. https://www.ema.europa.eu/en/documents/product-information/ellaone-epar-product-information_en.pdf.
15. 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?; 2012 March. http://www.cecinfo.org/ Available from: http://www.cecinfo.org/custom-content/uploads/2014/01/ICEC_MoA_Statement_3-28-12.pdf .
16. Mozzanega B, Cosmi E. How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some considerations. Gynecological Endocrinology. 2011;27:439-442.
17. Peck R, Rella E, Tudela J, Aznar J, Mozzanega B. Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action. The Linacre Quarterly. 2016;83(1):35-51, doi/full/10.1179/2050854915Y.0000000011.
18. Mozzanega B, Nardelli GB. UPA and LNG in Emergency Contraception: the information by EMA and the Scientific Evidences indicate a prevalent anti-implantation effect. Eur J Contracept Reprod Health Care. 2019;24(1):4-10. doi: 10.1080/13625187.2018.1555662. Epub 2019 Jan 18.
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