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

Capsule:
In vivo mechanisms of uterine myoma reduction with ulipristal acetate treatment suggest a multifactorial action.

Authors:
Guillaume E. Courtoy, M.Sc., Jacques Donnez, M.D., Ph.D., Etienne Marbaix, M.D., Ph.D., Marie-Madeleine Dolmans, M.D., Ph.D.

Volume 104, Issue 2, Pages 426-434

Abstract:

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.

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