In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment

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. (C) 2015 by American Society for Reproductive Medicine.