Objective To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas. Design Retrospective histologic and immunohistochemical (IHC) study of myomas. Setting Academic research unit. Patient(s) Among 59 women with symptomatic myomas who underwent myomectomy, 42 were treated preoperatively with UPA, while 17 were not. Intervention(s) Histology and IHC were analyzed on tissue microarrays obtained from surgical specimens. Main Outcome Measure(s) Proliferation, apoptosis, extracellular matrix (ECM) remodeling, and matrix metalloproteinase 2 (MMP-2) expression. Result(s) Proliferation was low in all conditions, with no statistical difference between groups. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay showed an increase in cell death in UPA-treated myomas compared with untreated myomas, but only after short-term treatment; this was not associated with elevated levels of cleaved caspase-3. After long-term treatment, cell density was higher and the ECM volume fraction lower in UPA-treated myomas than in untreated myomas. MMP-2 expression was found to be increased after treatment, showing the highest level after long-term treatment, compared with untreated myomas. Conclusion(s) Regarding sustained clinical volume reduction of myomas, this study strongly points to multifactorial mechanisms of action of UPA, involving: 1) a persistently low cell proliferation rate; 2) a limited period of cell death; and 3) ECM remodeling concomitant with stimulation of MMP-2 expression.
Courtoy, G. E., Donnez, J., Marbaix, E., & Dolmans, M. M. (2015). In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment. Fertility and Sterility, 104(2), 426-434.e1. https://doi.org/10.1016/j.fertnstert.2015.04.025