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

Courtoy, Guillaume [UCL] Donnez, Jacques Marbaix, Etienne [UCL] Dolmans, Marie-Madeleine [UCL]

(eng) 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.