title: Safety after extended repeated use of ulipristal acetate for uterine fibroids.
abstract: OBJECTIVE
  To assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.
  
  
  METHODS
  This long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.
  
  
  RESULTS
  All data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10-18 days after the start of menses following treatment courses 5-8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.
  
  
  CONCLUSIONS
  The results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.
authors.affiliation: Department of Reproductive Medicine & Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.affiliation: Société de Recherche pour l'Infertilité, Brussels, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Donnez
authors.affiliation: Endocrinology Unit, AP-HP Hospital Saint-Antoine, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.affiliation: College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland, UK and Hamad Medical Corporation, Doha, Qatar.
authors.forename: David H
authors.initials: DH
authors.lastname: Barlow
authors.affiliation: Centro de Estudios de Obstetricia y Ginecología Asociado, Lugo, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vázquez
authors.affiliation: Gedeon Richter/PregLem S.A., Geneva, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Arriagada
authors.affiliation: Division of Reproductive Endocrinology, Dept OB/GYN, Herlev-Gentofte Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sven O
authors.initials: SO
authors.lastname: Skouby
authors.affiliation: Palacios Institute of women's Health, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Palacios
authors.affiliation: Prywatna Klinika Polozniczo-Ginekologiczna, Bialystok, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Tomaszewski
authors.affiliation: Gabinet Lekarski Specjalistyczny Sonus, Warsaw, Poland.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Lemieszczuk
authors.affiliation: University of Edinburgh, Department of Pathology Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: William
mesh_terms: D000328:Adult; D001706:Biopsy; D017326:Clinical Trials, Phase III as Topic; D003270:Contraceptive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D003270:Contraceptive Agents; D009649:Norpregnadienes; C555622:ulipristal acetate