Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

ABSTRACT

RESEARCH QUESTION What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? DESIGN: A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. RESULTS: Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. CONCLUSION: The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.