Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen

Contraception. 2009 Sep;80(3):245-53. doi: 10.1016/j.contraception.2009.03.006. Epub 2009 May 2.


Background: A continuous regimen of oral levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg was evaluated for inhibition of ovulation, time to return to ovulation after stopping treatment and safety.

Study design: This open-label study was conducted in healthy women aged 18-35 years. Ovulation was documented before treatment, and then participants received oral tablets containing LNG 90 mcg/EE 20 mcg to be taken continuously for three 28-day intervals. Ovarian activity was assessed three times per week during the treatment period with transvaginal ultrasound scans and measurements of serum 17beta-estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone concentrations. Safety assessments included physical examinations, laboratory evaluations and adverse event records.

Results: Thirty-seven of the 58 subjects who received treatment met predefined criteria for efficacy analysis. No on-treatment ovulations occurred in the efficacy or intent-to-treat population. There was evidence of ovulation within 37 days of stopping treatment for 46 (98%) of 47 subjects evaluated posttreatment. The final subject with a history of polycystic ovarian syndrome ovulated by Day 66. The safety profile observed during this 84-day continuous regimen was similar to that seen with other low-dose oral contraceptives administered in a cyclic regimen.

Conclusions: The continuous LNG/EE regimen completely inhibited ovulation, with little evidence of follicular development and with rapid return of ovulatory capacity after stopping treatment.

Trial registration: ClinicalTrials.gov NCT00254189.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Contraceptives, Oral, Hormonal / administration & dosage*
  • Contraceptives, Oral, Hormonal / adverse effects
  • Drug Administration Schedule
  • Estradiol / blood
  • Ethinyl Estradiol / administration & dosage*
  • Ethinyl Estradiol / adverse effects
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / adverse effects
  • Luteinizing Hormone / blood
  • Ovarian Follicle / diagnostic imaging
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / physiology*
  • Ovulation Inhibition / drug effects*
  • Progesterone / blood
  • Ultrasonography
  • Young Adult


  • Contraceptives, Oral, Hormonal
  • Ethinyl Estradiol
  • Progesterone
  • Estradiol
  • Levonorgestrel
  • Luteinizing Hormone
  • Follicle Stimulating Hormone

Associated data

  • ClinicalTrials.gov/NCT00254189