title: Contraceptive efficacy and tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study.
abstract: BACKGROUND
  The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen.
  
  
  METHODS
  This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only).
  
  
  RESULTS
  Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles.
  
  
  CONCLUSIONS
  EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.
authors.affiliation: Dinox BV, Groningen, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Klipping
authors.forename: Ingrid
authors.initials: I
authors.lastname: Duijkers
authors.forename: Michel P
authors.initials: MP
authors.lastname: Fortier
authors.forename: Joachim
authors.initials: J
authors.lastname: Marr
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trummer
authors.forename: Jörg
authors.initials: J
authors.lastname: Elliesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008796:Metrorrhagia; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; C534342:drospirenone and ethinyl estradiol combination; D004997:Ethinyl Estradiol