Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder

Contraception. 2012 Jan;85(1):19-27. doi: 10.1016/j.contraception.2011.05.008. Epub 2011 Jul 13.


Background: The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD).

Study design: In this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE (n=186) or placebo (n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP).

Results: Mean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (-30.52±1.73 [SE] vs. -22.47±1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (-26.77±1.83 vs. -20.89±1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (≥50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥1 improvement) at last on-therapy cycle (p=.025).

Conclusions: Continuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD.

Trial registration: NCT00128934.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Contraceptive Agents, Female / administration & dosage*
  • Contraceptive Agents, Female / adverse effects
  • Double-Blind Method
  • Estrogens / administration & dosage*
  • Estrogens / adverse effects
  • Ethinyl Estradiol / administration & dosage*
  • Ethinyl Estradiol / adverse effects
  • Female
  • Humans
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / adverse effects
  • Middle Aged
  • Premenstrual Syndrome / drug therapy*
  • Treatment Outcome
  • Young Adult


  • Contraceptive Agents, Female
  • Estrogens
  • Ethinyl Estradiol
  • Levonorgestrel

Associated data