Ulipristal Acetate (UPA) in Emergency Contraception: The Mechanism of Action, Toxicity and Perspectives

Main Article Content

Bruno Mozzanega, MD


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Recently, an UPA-based drug used for uterine fibroids-treatment (Esmya®) was withdrawn from the market because it caused fulminant hepatitis requiring transplantation (EMA/455818/2020).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: 29 jan. 2023. doi: https://doi.org/10.18103/mra.v10i12.3387.
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