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Levonorgestrel Has Fewer Side Effects, But No Statistically Significant Difference in Efficacy When Compared with the Yuzpe Regimen for Emergency Contraception


  • Sexually active adolescent girl comes to the office after having sexual intercourse in which the barrier method failed. In adolescents who have had unprotected sex within the last 48 hours where barrier methods fail, what is the most effective form of oral emergency contraception?

Clinical Bottom Lines

  1. Levonorgestrel only (Plan B) has fewer side effects (nausea/vomiting/fatigue), but no statistically significant difference in efficacy when compared to the Yuzpe Regimen (Preven).1
  2. For pregnancy prevention, Yuzpe method NNT=26, Levonorgestrel only NNT=28.
  3. For side effect reduction in the Levonorgestrel only: nausea NNT=3, vomiting NNT=5 and fatigue NNT=8, in comparison to the Yuzpe regimen.

Summary of Key Evidence

  1. A prospective randomized study comparing the use of the Yuzpe regimen and Levonorgestrel only as forms of emergency contraception.1
    § Yuzpe regimen is 200 mcg of ethinyl estradiol and 2mg of DL-norgestrel given in 2 divided doses 12 hours apart. This study used 0.5mg of levonorgestrel which is equivalent to the DL-norgestrel used in the traditional Yuzpe regimen.
    § Levonorgestrel only is 0.5mg in 2 divided doses taken 12 hours apart.
  2. Study consisted of 880 patients who were between the ages of 16 and 45.
    § Were healthy, had a single act of unprotected sex within 48hr of presentation to the clinic, had menstrual cycles that lasted between 21-35 days in the previous 3 months, and did not have sexual intercourse at any other time during the current cycle.
    § Exclusion Criteria: any medical disorder or taking prescription medication, those who were post-partum/post-abortal who had not resumed regular periods, breastfeeding, or patients using other forms of contraception during the at-risk cycle.
    § Patients placed in groups based on age 16-25, 26-35, >35, were randomized into Yuzpe or Levonorgestrel, received a diary card to record side effects and menstrual cycle and were seen at 3 and 6 weeks for follow-up.
  3. Outcome measures were pregnancy and side effects.
  4. Results: There is no statistical significance in pregnancy reduction between the Yuzpe method and Levonorgestrel only in oral emergency contraception, 2.6% versus 2.4% respectively. Nausea was decreased 30.4%, vomiting was decreased 19.7% and fatigue was decreased 12.9%. NNT=3,5,8 for respective side effects. (P<0.001)
  5. Validity: Prospective randomized clinical trial. Similar patient groups with adequate tracking and appropriate follow-up and exclusion.
  6. Limitations:
    § In the beginning of the materials and methods section, it states patients from 18-45 were included in the study and when dividing patients into age groups, the youngest group starts at age 16.
    § Study not blinded or placebo controlled.
    § Form of pregnancy test was not revealed in the article.
    § No numbers given as to how many individuals were in each age group.
    § Pregnancy prediction method does not take age into account.

Additional Comments

  • A prior review of this topic found that the levonorgestrel only pills were more effective.
  • Each year almost 1 million teenagers become pregnant, and between 74-82% of these pregnancies are unintentional.4
  • Emergency contraception is indicated for the prevention of pregnancy in women after a known/possible contraceptive failure, unprotected sex, or sexual assault.5
  • The most common indication for emergency contraception is thought to be condom failure.2
  • Pregnancy rates are lowest with emergency contraception if taken within 24hr.5
  • Emergency contraception is thought to act primarily by inhibiting or disrupting ovulation. In addition they may interfere with tubal transport of the ova and/or sperm, inhibiting fertilization or by inhibiting implantation through alteration of the endometrium.5
  • The only contraindication to emergency contraception is known pregnancy, and, with the Yuzpe method, those with close family history of thromboembolic disease.3
  • 13% of adolescents reported withdrawal and 15% reported nothing as their form of contraception at last intercourse.4
  • In one study, 44% of adolescents reported use of contraceptives, but only 17% reported use at last intercourse.4
  • At the time of emergency contraception visit, it is imperative that the initiation of long-term contraception is discussed and/or recommended.3
  • Levonorgestrel only (Plan B) is less expensive ($30.99) than the Yuzpe regimen (Preven), $114.00.


  1. Ho PC, Kwan MS. A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception. Human Reproduction. 1993; 8:389-392.
  2. Brill S, Rosenfeld WD. Contraception. Medical Clinics of North America. 2000; 84:907-925.
  3. Cromwell PF, Daley AM. Oral contraceptive pills: Considerations for the adolescent patient. Journal of Pediatric Health Care. 2000; 14:228-234.
  4. Everett SA, et al. Use of birth control pills, condoms, and withdrawal among U.S. high school students. Journal of Adolescent Health. 2000; 27:112-118.
  5. Mendez MN. Emergency contraception: a review of current oral options. Western Journal of Medicine 2002; 176:188-191.

CAT Author: Maia S. McCuiston, MD

CAT Appraisers: Katherine L. Layton, MD

Date appraised: August 26, 2002

Last updated January 27, 2003
Department of Pediatrics and Communicable Diseases
© 1998-2002 University of Michigan Health System