Matrix Metalloproteinase Activity Correlates with Uterine Myoma Volume Reduction after Ulipristal Acetate Treatment

Abstract

Context Ulipristal acetate (UPA), a selective progesterone receptor modulator, clinically reduces uterine myoma size in 80% of cases. However, the molecular mechanism of action is still poorly understood, as is the reason why 20% of myomas do not respond to treatment. Objective To elucidate whether matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are associated with myoma volume shrinkage after UPA therapy. Design Prospective study. Setting Academic research unit of a university hospital. Patients Uterine biopsies were obtained from 59 patients with symptomatic myomas undergoing myomectomy, 45 of whom were treated preoperatively with either one or greater than or equal to two, 3-month courses of UPA and 14 not given any hormone therapy to serve as controls. Myoma volume was individually monitored during UPA therapy to determine any substantial clinical response (defined as a reduction in volume of >25%). Three groups were established based on the response to treatment: responsive (R) after one course (n = 12); R after two to four courses (n = 15); and nonresponsive (NR; n = 18). Interventions UPA treatment given as preoperative management for symptomatic myomas. Main Outcome Measures MMP and TIMP expression assessed by zymography and immunohistochemistry. Results Compared with controls and NR myomas, responders showed significantly higher expression levels for MMP-1 (P < 0.0001) and MMP-2 (P = 0.009) and significantly lower expression levels for TIMP-1 (P = 0.040). Conclusions The correlation found between MMP expression and volume fold change supports the notion that MMPs play a key role in UPA-induced myoma shrinkage.