title: In vivo mechanisms of uterine myoma volume reduction with ulipristal acetate treatment.
abstract: OBJECTIVE
  To study the in vivo mechanisms of action of ulipristal acetate (UPA) on uterine myomas.
  
  
  METHODS
  Retrospective histologic and immunohistochemical (IHC) study of myomas.
  
  
  METHODS
  Academic research unit.
  
  
  METHODS
  Among 59 women with symptomatic myomas who underwent myomectomy, 42 were treated preoperatively with UPA, while 17 were not.
  
  
  METHODS
  Histology and IHC were analyzed on tissue microarrays obtained from surgical specimens.
  
  
  METHODS
  Proliferation, apoptosis, extracellular matrix (ECM) remodeling, and matrix metalloproteinase 2 (MMP-2) expression.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pôle de Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Courtoy
authors.affiliation: Société de Recherche pour l'Infertilité, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Donnez
authors.affiliation: Cell Biology Unit, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium; Pathology Department, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.affiliation: Pôle de Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Gynecology Department, Cliniques Universitaires St-Luc, Brussels, Belgium. Electronic address: mari-madeleine.dolmans@uclouvain.be.
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Dolmans
mesh_terms: D000328:Adult; D003270:Contraceptive Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D009214:Myoma / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D009649:Norpregnadienes / Q000008:administration & dosage*; D011300:Preoperative Care / Q000379:methods; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery
chemical_list: D003270:Contraceptive Agents; D009649:Norpregnadienes; C555622:ulipristal acetate
keywords: Uterine myoma; cell death; extracellular matrix; matrix metalloproteinase 2; proliferation; ulipristal acetate