Question

• In the sexually active adolescent population, how effective are the different regimens for emergency contraception?

Clinical Bottom Lines

1. Administration of emergency contraception substantially reduces the risk of pregnancy when taken within 72 hours of unprotected intercourse.
2. The regimen of levonorgestrel (a progestin-only regimen) 0.75 mg taken twice, twelve hours apart was more effective in preventing pregnancy than the Yuzpe regimen (a combined regimen using 100 mcg ethinyl estradiol and 0.5 mg levonorgestrel) taken twice, twelve hours apart.
3. In order to prevent one pregnancy, fifteen people would need to be treated with levonorgestrel (NNT=15).  Twenty-four people would need to be treated with the Yuzpe regimen in order to prevent one pregnancy (NNT=24).
4. The earlier the emergency contraception is taken after unprotected intercourse (either regimen), the better the protection against pregnancy.
5. The levonorgestrel was better tolerated with statistically significant reductions in incidence of nausea, vomiting, dizziness, and fatigue.

Summary of Key Evidence

1. 1998  healthy women with regular menses and one episode of unprotected intercourse were enrolled at 21 international sites.¹  They were randomized to receive either the Yuzpe regimen (ethinyl estradiol and levonorgestrel) or levonorgestrel alone, taking the first dose within 72 hours of unprotected intercourse.
2. Primary end-points were pregnancy rates and effectiveness rates (comparison of actual pregnancy rates with expected pregnancy rates, pooling the expected fertility for each woman based on the timing of intercourse in relation to ovulation).  Secondary endpoints included analysis of side effects from subject-kept diaries, and the effect of the timing of the first dose in relation to the time of intercourse on pregnancy rates.
3. 97.8% of participants finished the trial.  Analysis of those lost to follow-up indicates their outcomes would have been extremely unlikely to have affected the outcome of the trial.
4. The two groups were similar in regards to age, fertility, menstrual cycle length, interval from intercourse to treatment, and interval from intercourse to ovulation.
5. The pregnancy rate in the group taking levonorgestrel was 1.1% (95% confidence interval 0.6-2.0%) and in the Yuzpe group 3.2% (2.2-4.5%).
6. The reduction in expected pregnancies was 85% in the levonorgestrel group (74-93%) and 57% in the Yuzpe group (39-71%).
7. For women taking the Yuzpe regimen, the pregnancy rate was 2.0% when taken within 24 hrs of intercourse, 4.1% when taken within 25-48 hrs, and 4.7% when taken within 49-72 hrs.  The corresponding pregnancy rates for the Levonorgestrel group were 0.4%, 1.2%, and 2.7%.
8. The percentage of women experiencing nausea in the Yuzpe group was 50.5% and in the levonorgestrel group was 23.1%.  The percentage of women who vomited was 18.8% in the Yuzpe group and 5.6% in the levonorgestrel group.

Additional Comments

• The study was valid, with appropriate concealed randomization and double blindedness with identical pill appearance in both groups.  The subjects were analyzed based on intention to treat with those who had violated study protocol or who were pregnant before the emergency contraception was taken being analyzed in their appropriate groups.  The loss to follow-up rate was low (2.2%) and likely insignificant to trial outcome.  The subjects were similar at the start of the trial and treated equally throughout.
• The Yuzpe regimen is readily available in the United States (equivalent to two Ovral pills taken at presentation and again twelve hours later).  Levonorgestrel alone is not available in the United States, but norgestrel alone is (marketed as Ordette).  In order to take the appropriate dose of norgestrel to meet the trial doses of levonorgestrel (its metabolite), one would have to take twenty tablets of Ordette at presentation and again twelve hours later.  In Europe and Asia, these regimens are both available in single pill formulations.
• In the United States, assuming a single pack of OCPs cost $30, the cost to prevent one pregnancy using the Yuzpe regimen would be $720.  The cost to prevent one pregnancy using the levonorgestrel regimen would be $900 (higher because two packs would need to be used).  If emergency-contraceptive formulations existed in the U.S., it would presumably be far less expensive.
• Safety and teratogenicity were not reviewed, though one might extrapolate from data on standard doses of hormonal contraception that the risks are low (and probably lower for those taking a progestin-only regimen).
• While method of action was not addressed in this article, most pregnancies are thought to be prevented with either regimen by disrupting ovulation.  Thus emergency contraception is truly a method of contraception, rather than an abortifacient.

Citation

1. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.  Task Force on Postovulatory Methods of Fertility Regulation The Lancet 352 (9126): 428-33, 1998.
2. Wilcox AJ, Weinberg CR, Baird DD.  Timing of sexual intercourse in relation to ovulation: effects on the probability of conception, survival of the pregnancy, and sex of the baby.  New England Journal of Medicine 333: 1517-21,  1995.
3. Glasier A.  Drug Therapy: Emergency Postcoital Contraception.  New England Journal of Medicine 337(15): 1058-1064, 1997.
4. Trussell J, Ellertson C, and Stewart F.  The Effectiveness of the Yuzpe Regimen of Emergency Contraception.  Family Planning Perspectives. 28(2):  58-64, 87, 1996

CAT Author: Sandra Bliss, MD

CAT Appraisers: John Frohna, MD

Date appraised: November 11, 1998