title: Bleeding profile of a flexible extended regimen of ethinylestradiol/drospirenone in US women: an open-label, three-arm, active-controlled, multicenter study.
abstract: BACKGROUND
  Unscheduled bleeding may affect satisfaction and compliance with extended oral contraceptive (OC) regimens. The bleeding patterns of two variants of a flexible dosing regimen designed to manage intracyclic bleeding problems during extended cycles were compared with that of a conventional OC regimen.
  
  
  METHODS
  This was a 1-year, open-label, active-controlled, Phase 3 study conducted in the USA. Healthy women (18-45 years) received an ethinylestradiol (EE) 20 mcg/drospirenone 3 mg OC in two flexible extended regimens or in a conventional 24/4 (i.e., 28-day) regimen. The primary regimen [management of intracyclic bleeding (flexible(MIB)) regimen] was an extended dosing regimen that required subjects to initiate 4-day tablet-free intervals after 3 days of breakthrough bleeding/spotting. An alternative extended regimen [active period control (flexible(APC)) regimen] allowed subjects to initiate a 4-day tablet-free interval irrespective of the occurrence of bleeding. Bleeding profiles were compared between treatments. Efficacy and safety outcomes were also assessed.
  
  
  RESULTS
  The full analysis set comprised 1864 women (flexible(MIB), N=1406; flexible(APC), N=232; conventional 24/4, N=226). Over 1 year, subjects in the flexible(MIB) group experienced significantly fewer (mean±SD, 40±30) bleeding/spotting days than those in the conventional 24/4 group (52±35). The corresponding value in the flexible(APC) group was 47±33 days. The pregnancy rate in the flexible(MIB) group was 1.65 per 100 woman-years (95% confidence interval, 0.96-2.65). All three regimens were well tolerated.
  
  
  CONCLUSIONS
  A flexible(MIB) dosing regimen of EE 20 mcg/drospirenone 3 mg is associated with good contraceptive efficacy and fewer bleeding/spotting days than the conventional 24/4 regimen.
authors.affiliation: Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239-2941, USA. jensenje@ohsu.edu
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Jensen
authors.forename: Sona Grossova
authors.initials: SG
authors.lastname: Garie
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*; D003268:Contraception Behavior; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects*; D016903:Drug Monitoring; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D055118:Medication Adherence; D008597:Menstrual Cycle / Q000187:drug effects*; D008875:Middle Aged; D010352:Patient Dropouts; D017060:Patient Satisfaction; D011247:Pregnancy; D018873:Pregnancy Rate; D012646:Self Administration; D012720:Severity of Illness Index; D014481:United States; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; C534342:drospirenone and ethinyl estradiol combination; D004997:Ethinyl Estradiol