The traditional Yuzpe method of emergency contraception (two doses of 0.1-mg ethinyl estradiol and 0.5-mg levonorgestrel, taken 12 hours apart) is being replaced by more effective treatments with fewer side effects. The two principal newer regimens are based on levonorgestrel (two doses of 0.75 mg administered 12 hours apart) or up to 600 mg of mifepristone in a single dose. A single dose of 10-mg mifepristone has been shown to be as effective as larger doses but with fewer side effects, leading to speculation that levonor-gestrel could also be effective in a single dose. Von Hertzen and colleagues conducted a large international clinical trial to compare a single dose of 10-mg mifepristone, a single dose of 1.5-mg levonorgestrel, and two doses of 0.75-mg levonorgestrel for emergency contraception.

Women requesting emergency contraception within 120 hours of unprotected intercourse at 15 family planning clinics in 10 countries were eligible for the study if they had regular menstrual cycles and agreed to refrain from unprotected sex for the remainder of their current menstrual cycle. After results from a human chorionic gonadotropin pregnancy test were determined to be negative, the women were randomly assigned to one of the three treatment groups. All women took two treatments and the same number of pills with placebos to ensure that the same regimen was followed by all participants. The women kept daily diaries of side effects and were reassessed one week after the date of the next anticipated menses. If menstruation had not occurred, a pregnancy test was performed. If pregnancy was suspected, the gestation was estimated by ultrasonography.

More than 1,300 women completed the study in each of the treatment groups. In each group, about 20 women were lost to follow-up or had unprotected sex during the study. The three groups were comparable; the mean age of the women was 27 years; more than one half had previously been pregnant; about one half had not used any contraception; and 44 percent reported failure of a condom. Overall, 65 pregnancies were diagnosed following treatment. The pregnancy rates were not statistically different between the three treatment groups (see accompanying table).

The treatments prevented 77 to 82 percent of anticipated pregnancies. Women treated more than 72 hours after intercourse had higher pregnancy rates (2.4 percent) than those treated earlier (1.5 percent), but the difference was not statistically significant. The most common side effects were bleeding (19 to 31 percent), nausea (14 to 15 percent), fatigue (13 to 15 percent), lower abdominal pain (14 to 15 percent), and headache (10 percent). Bleeding was more common in women taking levonorgestrel, and delay of menstruation was more common in those taking mifepristone, but otherwise the treatment groups were comparable in side effects.

The authors conclude that all three regimens effectively prevent a high proportion of pregnancies if they are taken within five days of unprotected intercourse. The use of single-dose regimens with low side effect profiles is expected to increase acceptability and success rates of emergency contraception.

editor's note: The topic of emergency contraception is fraught with medical, ethical, and personal difficulties. Some physicians and patients believe the process depends on preventing implantation and is thus unacceptable because it is equivalent to abortion. Others point to the need for strategies to manage human or technical failure of contraception. This study demonstrates that pregnancy can be prevented safely using a single treatment of at least two commonly available agents with an acceptable side effect profile. How shall we use this knowledge? The obvious outcome could be fewer induced abortions if women felt confident to request the treatment soon after lapses of judgment or contraceptive technique. The nightmare would be the repeated use of this technique to substitute for responsible contraception. Is it old-fashioned to believe that each child should be conceived as a deliberate choice by loving parents who are in an enduring relationship?—a.d.w.