Bleeding profile of a flexible extended regimen of ethinylestradiol/drospirenone in US women: an open-label, three-arm, active-controlled, multicenter study

Contraception. 2012 Aug;86(2):110-8. doi: 10.1016/j.contraception.2011.12.009. Epub 2012 Jan 26.


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.

Study design: 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.

Conclusion: 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.

Trial registration: NCT00567164.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Androstenes / administration & dosage
  • Androstenes / adverse effects*
  • Contraception Behavior
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / adverse effects*
  • Drug Monitoring
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / adverse effects*
  • Female
  • Humans
  • Medication Adherence
  • Menstrual Cycle / drug effects*
  • Middle Aged
  • Patient Dropouts
  • Patient Satisfaction
  • Pregnancy
  • Pregnancy Rate
  • Self Administration
  • Severity of Illness Index
  • United States
  • Uterine Hemorrhage / chemically induced
  • Uterine Hemorrhage / physiopathology
  • Uterine Hemorrhage / prevention & control*
  • Young Adult


  • Androstenes
  • Contraceptives, Oral, Combined
  • drospirenone and ethinyl estradiol combination
  • Ethinyl Estradiol

Associated data