The most commonly used emergency contraceptive is the Yuzpe regimen, which combines 100 mg of ethinyl estradiol with either 0.5 mg of levonorgestrel or 1.0 mg of norgestrel, in two doses over 12 hours. This regimen prevents approximately 75 percent of pregnancies if initiated within 72 hours of unprotected intercourse; however, it frequently causes nausea and vomiting. Levonorgestrel alone has also been marketed as an emergency contraceptive, with similar success in preventing pregnancy. However, vomiting occurred less frequently in women taking levonorgestrel alone. The Task Force on Postovulatory Methods of Fertility Regulation conducted a double-blind, randomized trial to evaluate the effectiveness of levonorgestrel compared with the Yuzpe regimen in preventing pregnancy.

Healthy women who reported regular menstrual cycles and had had only one act of unprotected intercourse within 72 hours of starting the regimen were eligible for the study. Women were excluded if they were breast-feeding, currently using hormonal contraception, had contraindications to the use of hormones for contraception or were uncertain about the date of their last menstrual cycle. Women included in the study provided medical and gynecologic histories and underwent physical examination and pregnancy testing at enrollment. Each participant was given two sets of two tablets. One group received levonorgestrel and the other the Yuzpe regimen. The regimens were identical in appearance and method of administration. The first dose was taken on enrollment at the clinic, and the second dose was taken 12 hours later at home. Each woman was also given one additional dose to be taken if she vomited within four hours of taking a dose. Participants kept diaries of side effects for one week following the second dose and recorded bleeding patterns and dates of any subsequent intercourse. All of the women were asked to return for follow-up assessment and pregnancy testing one week after the expected date of their next menstrual period.

Of the 1,955 women enrolled in the study, 976 received levonorgestrel alone and 979 received the Yuzpe regimen. Women in the levonorgestrel group had 11 (1.1 percent) documented pregnancies compared with 31 pregnancies (3.2 percent) in the Yuzpe group. Patient reports about their intercourse patterns indicated that 75 pregnancies would be expected in the levonorgestrel group and 72 pregnancies would be expected in the Yuzpe group if no emergency contraception were used. Levonorgestrel prevented pregnancy in 85 percent of women; the Yuzpe regimen prevented pregnancy in 57 percent of women. Nausea, vomiting, dizziness and fatigue were less frequent in the levonorgestrel group. Approximately 50 percent of women taking the Yuzpe regimen reported nausea and 18 percent reported vomiting compared with 23 percent reporting nausea and 5 percent reporting vomiting in the levonorgestrel group. The time to return of menstrual periods was similar in both of the groups.

The authors conclude that levonorgestrel was more effective and better tolerated than the Yuzpe regimen for emergency contraception. In addition, the authors believe that treatment is most effective when initiated as soon as possible after unprotected intercourse.