History and Efficacy of Emergency Contraception: Beyond Coca-Cola. (ARTICLES).

As affirmed at the 1994 International Conference on Population and Development in Cairo, women have the right to control the number and timing of their pregnancies. To realize this right, women throughout the world need access to a broad range of contraceptives, as well as to safe abortion services. While most contraceptives are intended for use before or during intercourse, some methods can be used within a short time after unprotected intercourse. Rumored folk methods such as postcoital douching with Coca-Cola are of dubious efficacy. but fortunately are not a woman's only alternative. Within the last 30 years, a number of approaches, which seem safe and efficacious, have been developed.

These options, predominantly variations on oral contraceptive regimens, are often called "morning-after pills." A more appropriate name for them, however, is "emergency contraception," which would dispel the idea that the user must wait until the morning after unprotected intercourse to start treatment--or that she will be too late if she cannot obtain treatment until the afternoon or night after. The name "emergency contraception" also stresses that the regimens are not intended for ongoing use.

The roots of modern emergency contraception date back to the 1920s, when researchers initially demonstrated that estrogenic ovarian extracts interfere with pregnancy in mammals. (1) Veterinarians were the first to apply this finding, administering estrogens to dogs and to horses that had mated when their owner had not wanted them to. Despite scattered reports of clinical use of postcoital estrogens in humans as early as the 1940s, (2) the first documented cases were not published until the mid-1960s, when physicians in the Netherlands applied the veterinary practice of postcoital estrogen administration to a 13-year-old girl who had been raped at midcycle. (3)

At around the same time, U.S. researchers were investigating the efficacy of high-dose estrogens, and toward the end of the decade, these preparations became the standard. Women typically received either conjugated estrogens, the steroidal estrogen ethinyl estradiol or the nonsteroidal estrogen diethylstilbestrol (DES). Today, in places where high-dose estrogens are still used, they are administered in the so-called 5x5 regimen: 5 mg of ethinyl estradiol per day for five days. (4)

In the early 1970s, the high-dose estrogen regimens gave way to a combined estrogen-progestin standard. Canadian physician Albert Yuzpe and his colleagues began studies in 1972 on this combined regimen, guided by their observation that a single dose of 100 mcg of estrogen coupled with 1.0 mg of the progestin dlnorgestrel induces endometrial changes that are incompatible with implantation. (5) The "Yuzpe method," as it came to be known, replaced high-dose estrogen formulations, chiefly because it offered a lower incidence of side effects, but also because the commonly used DES was linked to vaginal cancer in the daughters of women who had taken it to prevent miscarriages. The regimen now begins within 72 hours after unprotected intercourse and typically consists of 200 mcg of ethinyl estradiol and 1.0mg of levonorgestrel.

Research on regimens that omitted estrogen also began in the early 1970s, predominantly in Latin America. A 1973 report described the results of a large-scale trial investigating five doses of levonorgestrel: 150 mcg, 250 mcg, 300 mcg, 350 mcg and 400 mcg per tablet. The regimen was tested as an ongoing postcoital method, rather than an emergency formulation. Participants in the trial were instructed to take a tablet as soon as possible within three hours after intercourse and could use the method as often as necessary; some continued to use this method for two years. (6) The results showed that the lower doses were not efficacious and caused some menstrual disruption, chiefly a shortening of the cycle. This experiment marked the first major venture into ongoing postcoital contraception and laid the groundwork for the levonorgestrel methods that have become available in many developing countries and in Eastern Europe.

The late 1970s were to offer the chief nonhormonal method available today, the copper-releasing RID. This device causes endometrial changes that inhibit implantation; in addition, the copper ions released appear to be directly embryotoxic. (7)