Matrix metalloproteinase activity correlates with uterine myoma volume reduction after ulipristal acetate treatment.

Matrix metalloproteinase activity correlates with uterine myoma volume reduction after ulipristal acetate treatment.

J Clin Endocrinol Metab. 2018 Feb 01;:

Authors: Courtoy GE, Henriet P, Marbaix E, de Codt M, Luyckx M, Donnez J, Dolmans MM

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 MMPs (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 1 or ≥2 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 significant clinical response (defined as a reduction in volume of more than 25%). Three groups were established based on the response to treatment: responsive after 1 course (n=12); responsive after 2 to 4 courses (n=15); and nonresponsive (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 to controls and nonresponsive 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.

PMID: 29408988 [PubMed - as supplied by publisher]

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