title: Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind Phase III trial.
abstract: BACKGROUND
  This double-blind trial investigated the efficacy and safety of estradiol valerate/dienogest (E(2)V/DNG) for the treatment of heavy menstrual bleeding without recognizable organic pathology.
  
  
  METHODS
  Otherwise healthy women with idiopathic heavy, prolonged or frequent menstrual bleeding, confirmed during a 90-day run-in phase, were randomized (2:1) according to a permuted-block, computer-generated schedule to E(2)V/DNG or placebo for 196 days at 34 centres in Europe and Australia. The primary efficacy end-point was the proportion of women with a 'complete' response (i.e. a return to 'menstrual normality') during a 90-day efficacy phase. Secondary end-points included changes in measured menstrual blood loss (MBL) and iron metabolism parameters.
  
  
  RESULTS
  The intention-to-treat population comprised 231 women. The E(2)V/DNG response rate was much higher than with placebo (P < 0.0001). The mean reduction in MBL volume in E(2)V/DNG recipients was 69.4% (median 79.2%) versus 5.8% (median 7.4%) in placebo recipients. The between-treatment difference in MBL volume was 373 ml in favour of E(2)V/DNG (95% confidence interval 490, 255 ml; P < 0.0001). Significant improvements in iron metabolism parameters were observed with E(2)V/DNG but not placebo. Overall, 14 women (9.7%) treated with E(2)V/DNG and 5 (6.2%) treated with placebo prematurely discontinued treatment because of adverse events, headache being the most prevalent. Serious adverse events occurred in both the E(2)V/DNG and placebo groups (each n = 2).
  
  
  CONCLUSIONS
  E(2)V/DNG is an effective treatment in women with heavy and/or prolonged menstrual bleeding without organic pathology. Further study of E(2)V/DNG compared with an active comparator is warranted. ClinicalTrials.gov identifier: NCT00307801.
authors.affiliation: Department of Obstetrics and Gynaecology, Central Clinical School, D02 - QEII Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia. i_fraser@med.usyd.edu.au
authors.forename: I S
authors.initials: IS
authors.lastname: Fraser
authors.forename: T
authors.initials: T
authors.lastname: Römer
authors.forename: S
authors.initials: S
authors.lastname: Parke
authors.forename: S
authors.initials: S
authors.lastname: Zeun
authors.forename: U
authors.initials: U
authors.lastname: Mellinger
authors.forename: A
authors.initials: A
authors.lastname: Machlitt
authors.forename: J T
authors.initials: JT
authors.lastname: Jensen
mesh_terms: D000328:Adult; D001315:Australia; D003270:Contraceptive Agents / Q000627:therapeutic use; D003276:Contraceptives, Oral / Q000627:therapeutic use*; D004311:Double-Blind Method; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005060:Europe; D005260:Female; D006801:Humans; D008595:Menorrhagia / Q000188:drug therapy*; D008598:Menstruation / Q000187:drug effects*; D008599:Menstruation Disturbances / Q000188:drug therapy*; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D016896:Treatment Outcome
chemical_list: D003270:Contraceptive Agents; D003276:Contraceptives, Oral; D010919:Placebos; C023635:dienogest; D004958:Estradiol; D009277:Nandrolone