Is Ulipristal Acetate a Liver Toxic Biomolecule? Toxicity assessment of ulipristal acetate

Abstract

Progesterone is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Its main functions are playing a key role in the development, differentiation, and normal functioning of female reproduction-related target tissues including the uterus (endometrium and myometrium), the ovary, and the mammary gland, as well as regulating the hypothalamic�pituitary�gonadal axis. Soon after the discovery of the progesterone receptor (PR) it was appreciated that the development of a PR antagonist would have a major therapeutic potential. Numerous related compounds have been synthesized exhibiting a spectrum of activity ranging from pure progesterone receptor antagonists (PA), to mixed agonists/antagonists. These latter compounds are also known as selective progesterone receptor modulators (SPRM), progesterone receptor modulators (PRM), mesoprogestins or partial agonist�antagonists. Ulipristal acetate is a SPRM used in Europe for preoperative treatment of moderate-to-severe symptoms of uterine leiomyomas in adult women of reproductive age. This is a retrospective cohort study conducted in two medical units, Saint John Hospital and Egometacs Clinic, between january 2017-december 2018, on women treated with UPA (ulipristal acetate) for symptomatic uterine fibroids, in order to evaluate if there were any liver function changes after the treatment. In the mentioned period, 74 women were treated with UPA for symptomatic uterine myomas in the two units. After checking the records, 6 women were lost on follow up (only the first visit was recorded), 4 didn�t complete the treatment course and 7 had incomplete laboratory evaluation, either at the beginning or at the end of treatment. Finally, our cohort was comprised of 57 women, aged between 20 and 50 years old, treated with UPA for various conditions (myomas, abnormal bleeding, pelvic pain etc.) during a period of 3 month�, and adherence to treatment was 100%. We performed a paired T-test on the before and after values of the AST, ALT, GGT enzymes and total bilirubin levels, for our statistical analysis we used SPPS 20, and the charts were built using Microsoft Excel. There were no significant statistical differences between the before and after values of the variables measured in our study. In our study the paired T-test determined that there were no statistical significant differences between the liver function after Esmya administration. Altough there was no evidence of hepatic impairment in the 3 months course of treatment, precautions as the one recomended by EMA, should be respected. Still, more studies are needed in order to rule out the potential harmful effect of UPA on the liver, taking into account detailed liver function evaluation and extended laboratory tests. Until then, the temporary safety measures issued by the European Medicines Agency, are to be respected. The measures include: no use of UPA for women with known liver conditions, careful monitoring of liver function monthly for the patients under treatment and at four weeks after, and immediate discontinuation and report of any adverse complaints.