title: Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.
abstract: BACKGROUND
  This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens.
  
  
  METHODS
  In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (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) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres.
  
  
  RESULTS
  Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens.
  
  
  CONCLUSIONS
  EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.
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*; D015519:Bone Density / Q000187:drug effects; 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; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008796:Metrorrhagia; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D008055:Lipids; C534342:drospirenone and ethinyl estradiol combination; D004997:Ethinyl Estradiol