Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized controlled trial

Obstet Gynecol. 2003 Jun;101(6):1160-7. doi: 10.1016/s0029-7844(03)00353-3.


Objective: Emergency contraceptives can prevent unintended pregnancy after unprotected intercourse. The best-studied regimen ("Yuzpe") consists of ordinary combined oral contraceptives containing levonorgestrel and ethinyl estradiol. Women traditionally take one dose within 72 hours after unprotected intercourse, and a second dose 12 hours later. Historically, half experience nausea and a fifth vomit. The purpose of this study was to determine whether 1). women could use combined oral contraceptives other than those containing levonorgestrel and 2). eliminating the second dose improves comfort and convenience.

Methods: Women presenting within 72 hours after unprotected intercourse were randomized to receive 1). standard two-dose Yuzpe, 2). a variant of Yuzpe substituting norethindrone for levonorgestrel, or 3). only the first dose of Yuzpe, followed 12 hours later by a placebo.

Results: Perfect-use failure rates were low in all groups and did not differ in a statistically significant way (standard Yuzpe 2.0% [n = 589], norethindrone-ethinyl estradiol 2.7% [n = 547], single dose of Yuzpe 2.9% [n = 546]). Typical-use failure rates were slightly higher but similarly did not differ significantly. Side effects were similar across groups, except that women taking the single dose reported half the vomiting. Taking the pills with food did not seem to reduce nausea or vomiting, and the pills were not more effective when started sooner after unprotected intercourse.

Conclusion: Oral contraceptives containing norethindrone-ethinyl estradiol work approximately as well for emergency contraception as levonorgestrel-ethinyl estradiol formulations and should be offered when first-line therapies are not available.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Postcoital / administration & dosage*
  • Contraceptives, Postcoital / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Ethinyl Estradiol / administration & dosage
  • Female
  • Half-Life
  • Humans
  • Middle Aged
  • Nausea / chemically induced
  • Norethindrone / administration & dosage*
  • Norgestrel / administration & dosage*
  • Pregnancy
  • Treatment Failure
  • Vomiting / chemically induced


  • Contraceptives, Oral, Combined
  • Contraceptives, Postcoital
  • Norgestrel
  • Ethinyl Estradiol
  • Norethindrone