ARTICLES

History and Efficacy of Emergency Contraception: Beyond Coca-Cola By Charlotte Ellertson

s affirmed at the 1994 International the Netherlands applied the veterinary take a tablet as soon as possible within three Conference on Population and practice of postcoital estrogen adminis- hours after intercourse and could use the Development in Cairo, women tration to a 13-year-old girl who had been method as often as necessary; some con- A 3 6 have the right to control the number and raped at midcycle. tinued to use this method for two years. timing of their pregnancies. To realize this At around the same time, U.S. re- The results showed that the lower doses right, women throughout the world need searchers were investigating the efficacy were not efficacious and caused some men- access to a broad range of contraceptives, of high-dose estrogens, and toward the strual disruption, chiefly a shortening of the as well as to safe abortion services. While end of the decade, these preparations be- cycle. This experiment marked the first most contraceptives are intended for use came the standard. Women typically re- major venture into ongoing postcoital con- before or during intercourse, some meth- ceived either conjugated estrogens, the traception and laid the groundwork for the ods can be used within a short time after steroidal estrogen ethinyl estradiol or the levonorgestrel methods that have become unprotected intercourse. Rumored folk nonsteroidal estrogen diethylstilbestrol available in many developing countries methods such as postcoital douching with (DES). Today, in places where high-dose and in Eastern Europe. Coca-Cola are of dubious efficacy, but for- estrogens are still used, they are adminis- The late 1970s were to offer the chief tunately are not a woman’s only alterna- tered in the so-called 5x5 regimen: 5 mg nonhormonal method available today, the tive. Within the last 30 years, a number of of ethinyl estradiol per day for five days.4 copper-releasing IUD. This device caus- approaches, which seem safe and effica- In the early 1970s, the high-dose estro- es endometrial changes that inhibit im- cious, have been developed. gen regimens gave way to a combined es- plantation; in addition, the copper ions re- These options, predominantly varia- trogen-progestin standard. Canadian leased appear to be directly embryotoxic.7 tions on oral contraceptive regimens, are physician Albert Yuzpe and his colleagues More recently, two other methods have often called “morning-after pills.” A more began studies in 1972 on this combined been investigated: danazol and mifepris- appropriate name for them, however, is regimen, guided by their observation that tone. Danazol, a synthetic progestin and “emergency contraception,” which would a single dose of 100 mcg of estrogen cou- antigonadotropin, was first used as an dispel the idea that the user must wait pled with 1.0 mg of the progestin dl- emergency contraceptive in the early until the morning after unprotected in- norgestrel induces endometrial changes 1980s.8 Mifepristone, more commonly tercourse to start treatment—or that she that are incompatible with implantation.5 known as RU-486, is a potent antiproges- will be too late if she cannot obtain treat- The “Yuzpe method,” as it came to be terone registered in four countries as an ment until the afternoon or night after. The known, replaced high-dose estrogen for- abortifacient. Relatively little research is name “emergency contraception” also mulations, chiefly because it offered a available on these newer methods, al- stresses that the regimens are not intend- lower incidence of side effects, but also be- though mifepristone in particular appears ed for ongoing use. cause the commonly used DES was linked extremely promising as an emergency The roots of modern emergency con- to vaginal cancer in the daughters of contraceptive. traception date back to the 1920s, when re- women who had taken it to prevent mis- searchers initially demonstrated that es- carriages. The regimen now begins with- Yuzpe Method trogenic ovarian extracts interfere with in 72 hours after unprotected intercourse The Yuzpe method is the best-studied pregnancy in mammals.1 Veterinarians and typically consists of 200 mcg of ethinyl method of oral postcoital contraception.9 were the first to apply this finding, ad- estradiol and 1.0 mg of levonorgestrel. (In addition, trials of vaginal administra- ministering estrogens to dogs and to hors- Research on regimens that omitted es- tion of the Yuzpe method are under way es that had mated when their owner had trogen also began in the early 1970s, pre- in Mexico.10) Although the exact treatment not wanted them to. Despite scattered re- dominantly in Latin America. A 1973 re- varies widely in developing countries,11 ports of clinical use of postcoital estrogens port described the results of a large-scale the regimen typically used in North in humans as early as the 1940s,2 the first trial investigating five doses of levo- America and Europe consists of 200 mcg documented cases were not published norgestrel: 150 mcg, 250 mcg, 300 mcg, 350 of ethinyl estradiol and 1.0 mg of levo- until the mid-1960s, when physicians in mcg and 400 mcg per tablet. The regimen norgestrel. Half the dose is taken within was tested as an ongoing postcoital meth- 72 hours after unprotected intercourse, Charlotte Ellertson is program associate at The Popula- od, rather than an emergency formulation. and the other half is taken 12 hours later. tion Council, New York. Participants in the trial were instructed to One reason for the popularity of the

44 Family Planning Perspectives Yuzpe method is that the hormones it uses ly at times when the probability of preg- renders it less effective remains to be in- are the active ingredients found in sever- nancy is highest, such as following mid- vestigated. Some clinicians also routine- al brands of ordinary combined oral con- cycle intercourse. Therefore, better stud- ly give an antiemetic or antinausea med- traceptives. The brand marketed as Ovral ies of the method limit their scrutiny to ication such as dimenhydrinate or in the United States and Canada, for ex- women with regular cycles. For such cyclizine hydrochloride.18 ample, contains 50 mcg of ethinyl estra- women, an expected number of preg- diol and 0.25 mg of levonorgestrel per nancies can be estimated using published Levonorgestrel tablet; therefore, four Ovral tablets (the fertility tables if investigators record the The levonorgestrel emergency contracep- dosage Yuzpe and his colleagues used cycle day of unprotected intercourse (or tive regimen consists of two doses of 0.75 after their original pilot study) constitute details about a woman’s cycle, such as its mg of levonorgestrel taken 12 hours apart, the complete regimen.* usual length and the first day of the last starting within 48 hours after unprotected Several other brands of combined oral menstrual period). From the 10 available intercourse. Although progestins were contraceptives contain the same hormones studies that approached this optimal de- among the first drugs used in postcoital needed for the Yuzpe method, but in sign,14 it is possible to calculate a propor- contraception, few studies of the emergency lower doses.12 Women using these brands tionate reduction in pregnancy associat- levonorgestrel regimen have controlled for therefore have to take a greater number of ed with the use of the Yuzpe method. By cycle day of unprotected intercourse. pills; for example, women in the United comparing observed and expected preg- The best and most recent of the levo- States can use the brands Nordette, Levlen nancies, investigators have demonstrat- norgestrel emergency contraceptive trials, and Lo/Ovral for the Yuzpe method if ed that the Yuzpe method reduces the conducted in Hong Kong,19 indicates a they simply double the number of tablets chances of pregnancy by about 75%.15 failure rate of 2% and a proportionate re- of these lower dose oral contraceptives. (In Because the regimen consists of the same duction in pregnancy of 60%. The inves- other words, they would take four pills for active ingredients as certain combined oral tigators randomly assigned women re- each half of the regimen.) A number of contraceptives, and because it has never porting for treatment within 48 hours after triphasic oral contraceptive formulations been specifically regulated by the U.S. Food unprotected intercourse to receive either also contain the hormones needed for the and Drug Administration, the contraindi- the Yuzpe or the levonorgestrel regimen. Yuzpe method. For example, eight of the cations for its use sometimes have simply During the trial, 410 women used the lat- yellow tablets (corresponding to cycle been adopted wholesale from those stated ter. Investigators did not detect a statisti- days 12–21) of Triphasil or Tri-Levlen con- for combined pills: current or past throm- cally significant difference between the stitute the complete regimen. boembolic disorders, cerebrovascular dis- methods. This trial is being replicated in In the United States, no contraceptives ease or coronary artery disease, known or a multinational study sponsored by the are specifically marketed and packaged suspected carcinoma of the breast or en- World Health Organization.20 for emergency use. As a result, many clin- dometrium, jaundice, and hepatic adeno- As noted previously, the levonorgestrel icians simply cut up packages of oral con- mas or carcinomas. Women older than 35 regimen has been studied as an ongoing traceptives that contain the appropriate who smoke heavily have also been con- or primary method of postcoital contra- hormones. In several European countries, sidered ineligible for the regimen. Gener- ception. The Hungarian company Gedeon tablets equivalent to Ovral are available al medical consensus, however, is that the Richter once marketed a strip of 10 pills in four-pill strips labeled explicitly for regimen has no contraindications.16 containing 0.75 mg each for this use. Now emergency use. The brands are PC4 in Despite the lack of evidence, some cli- the company markets a four-pill strip, to Britain, Neo-Primovlar in Finland and nicians fear that the Yuzpe regimen may emphasize that the pills are intended for Tetragynon in Switzerland. heighten the risk of fetal malformation if sporadic or emergency contraception. Efficacy studies of the Yuzpe method administered to a woman in early preg- The brand (Postinor) is advertised for have yielded greatly varying results, in nancy. (A meta-analysis of the 12 available women who have intercourse fewer than part because the definition of efficacy is prospective studies failed to detect any four times per month. Like the Latin Amer- slightly different for a postcoital method statistically significant association be- ican progestin-only formulations that paved than for a conventional method. In one ap- tween oral contraceptive use in early preg- its way, Postinor is meant to be taken with- proach, researchers observe women using nancy and fetal malformation.17) To be in eight hours after unprotected intercourse emergency contraception in a given cycle, most conservative, a clinician should talk when used as a primary postcoital meth- note the number of pregnancies that occur with a woman before she begins the reg- od. Unlike commercial formulations of the and divide that number by the number of imen to rule out the possibility of a pre- Yuzpe method, Postinor is available in women who took the drug. When stud- existing pregnancy (i.e., one that resulted many developing countries and is even sold ied in this fashion, the failure rate of the from an act of unprotected intercourse oc- over the counter in some places. Yuzpe method ranges from about 0.2% to curring more than 72 hours earlier). In addition, nine Chinese brands of 2%.13 This rate is useful insofar as it tells Side effects of the Yuzpe method are the “visiting pills” have been developed; eight clinicians that of all women they treat with same as those commonly experienced of them involve a progestin, and some this therapy, 2% or fewer will likely expe- with short-term use of combined oral con- have consisted of levonorgestrel. A ran- rience pregnancy. However, these results traceptives: nausea (including vomiting domized, double-blind, multicenter trial do not account for the fact that some of the in about 20% of cases), headaches, breast was unable to demonstrate a difference women would not have become pregnant tenderness, abdominal pain and dizziness. between one of these Chinese levo- even if they had not used the method Nausea, by far the most common of these, norgestrel formulations and Postinor.21 under study. typically is reported by 50% of users. Tak- Yet women do not generally use the ing the tablets with food or with milk may *In other countries, the same dose and active ingredients are available in brands such as Anfertil, Anulette, An- Yuzpe method cycle after cycle. Instead, lessen nausea, although whether such a ulit, Daphyron, Eugynon, Ovran, Planovar, Primovlar the method is used sporadically, typical- practice inhibits absorption of the drug or and Stediril.

Volume 28, Number 2, March/April 1996 45 History and Efficacy of Emergency Contraception

Certain brands of progestin-only oral Danazol number of pregnancies that would be ex- contraceptives can also be adapted for The synthetic progestin and androgen pected in a group of fecund women is a emergency use. The Ovrette brand, for ex- danazol (marketed in the United States as function primarily of the cycle day on ample, contains 0.075 mg of dl-norgestrel, Danocrine) can be used as an emergency which unprotected intercourse occurred, the equivalent of 0.0375 mg of levo- contraceptive. The danazol regimen con- yet many emergency contraception trials norgestrel, per tablet. Therefore, a total of sists of two doses of 400 mg each, taken 12 fail to control for this factor. 40 tablets makes up the complete regimen. hours apart. Regimens, involving three To reduce the likelihood of error and in- Although such a regimen is impractical for doses of 400 mg each, taken at 12-hour in- crease the reliability of estimates, re- most women, this option may be impor- tervals, and two doses of 600 mg each, searchers should limit study populations tant for women with estrogen con- taken 12 hours apart, have also been in- to women with regular cycles and should traindications.22 vestigated.28 Danazol’s advantages are define midcycle (when ovulation occurs) that its side effects are less prevalent and as 14 days before the expected onset of the Mifepristone less severe than those associated with the next menses for women with 28-day cy- Mifepristone, a potent antiprogesterone, Yuzpe method, and that it can be taken by cles. Using published estimates of the has been tested since the early 1980s for women with contraindications to com- probability of conception on each day of its abortifacient qualities.23 More recent- bined pills or estrogen. However, rela- the cycle,35 researchers can calculate the ly, in two studies evaluating mifepristone tively little information is available about expected number of pregnancies among as an emergency contraceptive,24 the reg- the regimen. Of the two most thorough tri- women in their trials. Results of such cal- imen consisted of 600 mg of the drug als of the regimen, one concluded that the culations, however, should be regarded as taken in a single dose within 72 hours after method is effective,29 while the other con- lower bounds, because the published es- unprotected intercourse. No pregnancies cluded that danazol does not work.30 timates are based in part on women who were observed among mifepristone users have undergone artificial insemination in either trial, despite a combined enroll- Copper IUD using frozen sperm and in part on couples ment of nearly 600 women. The side effect A meta-analysis of 20 studies of the post- who may have been selected for below-av- profile of mifepristone was also general- coital insertion of a copper IUD31 reveals erage fecundity.36 ly superior to that of the Yuzpe regimen, that the failure rate of this approach is prob- Another problem with many trials of although menstrual disturbances ap- ably no higher than 0.1%. The IUD offers the emergency contraception is that they may peared more commonly than with the additional advantage of providing up to 10 include some women who had become Yuzpe method. years of contraceptive protection. The ser- pregnant because of an act of unprotect- Lower doses of mifepristone may also vice delivery challenges raised by the meth- ed intercourse occurring more than 72 be effective, and the time limit in which od, however, may be severe, particularly in hours before the start of the emergency the therapy may be used could extend be- some developing countries. In addition, the contraception regimen. Where feasible, in- yond 72 hours. The 600 mg dose is the method is contraindicated for women at vestigators should establish that no such same dose currently used as part of the risk of sexually transmitted diseases,32 who women are participating in the trial. Sen- medical abortion regimen provided in frequently are the same women who need sitive human chorionic gonadotropin as- France.25 The World Health Organization emergency contraception. says may play a role here, particularly for is investigating the efficacy of mifepristone trials of methods that can be initiated later in much smaller doses (50 mg and 10 Research Guidelines than the traditional 72 hours after unpro- mg).26 If proven safe and effective, a small- Of the hundreds of articles published on tected intercourse. With five-day cutoffs, er dose (e.g., 10 mg or 1 mg) could be more emergency contraception, only a few dozen for example, ultrasensitive pregnancy palatable politically in countries where reflect good research designs and appro- tests could be used to rule out preexisting abortion is restricted, insofar as it might priate methodologies for answering the pregnancies. allay fears that women will hoard pills to basic questions about efficacy, safety and Investigators should also limit analysis use for medical induced abortion. user issues. Consequently, more data, par- of failure to women who did not have fur- ticularly from developing countries, are ther acts of unprotected intercourse during Other Methods needed; additional clinical research is being the treatment cycle. A number of trials have High-Dose Estrogens planned and implemented. Research in made participants’ willingness to abstain Postcoital treatment with high-dose es- Scotland, for instance, will assess the effects or to use condoms for the rest of the cycle trogens (the standard regimen wherever on pregnancy rates of giving women pack- a condition of inclusion. (Of course, trials emergency contraception was offered dur- ets of emergency contraceptive pills to have of the IUD need not impose this rule, since ing the 1960s and early 1970s) is at least on hand when needed.33 Similar research this method is a highly effective ongoing as effective as the Yuzpe method, but pro- is planned in the United States and else- contraceptive.) duces more side effects. These regimens where.34 Also needed are qualitative stud- Because it is unclear whether a rela- must be initiated within 72 hours after un- ies to document women’s experiences, sur- tionship exists between the exact time protected intercourse and are adminis- veys to assess women’s and providers’ elapsed since unprotected intercourse and tered in two daily doses for five days. Each knowledge, and experiments to discover the efficacy of the regimen, investigators dose (2.5 mg of ethinyl estradiol, 10 mg of the optimal ways to educate women, as should record and analyze the number of esterified or conjugated estrogens, or 5 mg well as additional basic research. hours between unprotected intercourse of estrone) is equivalent to 25 mg of DES. and initiation of therapy. One example of a high-dose estrogen still Efficacy Studies Some research suggests also that the prescribed as an emergency contraceptive To evaluate efficacy, a researcher must time limit for the Yuzpe regimen may be is Lynoral, marketed and used in family compare an observed number of preg- extended to five days.37 Additional data planning programs in the Netherlands.27 nancies with an expected number. The on this point would be most valuable.

46 Family Planning Perspectives If proposals to try novel service deliv- pensed at every family planning or med- ception at once, if efficacy and safety con- ery systems, such as vending machines or ical visit for women to keep in case of siderations are the sole criteria. emergency contraception kits dispensed emergency? Should women be issued an Emergency contraceptives are simple to prophylactically, bear fruit, the effects of identification card (equivalent to a stand- use, relatively inexpensive and, in many these new ways to administer the medi- ing prescription) entitling them to the pur- cases, already accessible to the women who cine would be worthy of study. chase of a regimen of emergency contra- need them. The chief remaining obstacle Investigators may also wish to limit ceptives once they have been screened and to their use may well be ignorance. Re- analysis in their studies to women of counseled about the use of the therapy? productive health advocates and providers proven fertility. Although such a practice Would women prefer a specially packaged need to educate each other and to educate may slow the trials unacceptably (because product to a plain cycle or part of a cycle women about these important options. many women seeking emergency contra- of oral contraceptives? How much do ception are young and have never been women know about the methods, and References pregnant), it might afford more precise es- how might they best learn more? The an- 1. A. A. Haspels and R. Andriesse, “The Effect of Large timates of a regimen’s efficacy. Of course, swers to these questions, and many oth- Doses of Estrogens Post Coitum in 2000 Women,” Euro- pean Journal of Obstetrics & Gynecology and Reproductive women who are not of proven fertility ers, will help determine which distribu- Biology, 3:113–117, 1973; and P.F.A. Van Look and H. von may also require emergency contracep- tion systems and use patterns would best Hertzen, “Emergency Contraception,” British Medical Bul- tion. Researchers should not deny such help women avoid unwanted pregnancy. letin, 49:158–170, 1993. women access to the therapy, but should 2. J. Hodgson, Department of Obstetrics and Gynecol- analyze them separately from women re- Further Research ogy, Ramsey Medical Center, University of Minnesota, porting prior pregnancies. While the guidelines noted above apply St. Paul, personal communication, 1994. Similarly, although efficacy tests should to the study of all emergency contracep- 3. A. A. Haspels, “Emergency Contraception: A Review,” exclude women who have had more than tion regimens, some needs are specific to Contraception, 50:101–108, 1994. one act of unprotected intercourse during individual methods. Most important, it 4. Ibid. a menstrual cycle, such women should re- would be extremely convenient for health 5. A. A. Yuzpe and W.J. Lancee, “Ethinylestradiol and ceive treatment when they request it. Stud- care providers and consumers alike if the dl-Norgestrel as a Postcoital Contraceptive,” Fertility and ies that required women to state that they Yuzpe method could be broadened to in- Sterility, 28:932–936, 1977; A.A. Yuzpe et al., “Post Coital had not had any other acts of unprotect- clude all of the progestins used in com- Contraception—A Pilot Study,” Journal of Reproductive Medicine, 13:53–58, 1974; and P.F.A. Van Look and H. von ed intercourse in the cycle prior to the 72 bined oral contraceptives. No published Hertzen, 1993, op. cit. (see reference 1). hours before initiating treatment found trials have evaluated the combined oral that women frequently misreported their contraceptives that use the progestins de- 6. E. Kesserü, A. Larranaga and J. Parada, “Postcoital Contraception with D-Norgestrel,” Contraception, 38 experience in order to obtain treatment. sogestrel, norethindrone or ethynodiol di- 7:367–379, 1973. Later protocols by these same investiga- acetate, for example. While there is no rea- 7. P. F. A. Van Look and H. von Hertzen, 1993, op. cit. (see tors allowed any women requesting the son to believe that these pills would not reference 1). treatment to obtain it, but limited analy- work as emergency contraceptives, their 8. S. Rowlands et al., “Side Effects of Danazol Compared sis to women who had had only one act use for this purpose has yet to be tested with an Ethinyloestradiol/Norgestrel Combination When of unprotected intercourse in the cycle and and established. If it were indeed the case Used for Postcoital Contraception,” Contraception, whose one act had occurred less than 72 that women could use any brand of com- 27:39–49, 1983. hours prior to the start of treatment. bined oral contraceptive in an emergency 9. A. A. Yuzpe and W.J. Lancee, 1977, op. cit. (see refer- Because the conditions of the ideal trial dose, barriers to access would be sub- ence 5); A. A. Yuzpe, R.P. Smith and A. W. Rademaker, may be burdensome to women, investi- stantially lessened for many women. “A Multicenter Clinical Investigation Employing Ethinyl gators must take special care to reassure The mechanisms of action for the vari- Estradiol Combined with dl-Norgestrel as a Postcoital Contraceptive Agent,” Fertility and Sterility, 37:508–513, them that they can receive treatment even ous emergency contraception regimens 1982; A. Glasier et al., “Mifepristone (RU 486) Compared if, for example, they are not willing to ab- are poorly understood. Still, preliminary with High-Dose Estrogen and Progestogen for Emer- stain from intercourse for the balance of research in the United States indicates that gency Postcoital Contraception,” New England Journal of the cycle. It may be best, in fact, for in- the exact mechanism of action, and par- Medicine, 327:1041–1044, 1992; S. N. Bagshaw, D. Edwards vestigators to treat any woman needing ticularly the timing of the action in the and A. K. Tucker, “Ethinyl Oestradiol and d-Norgestrel Is an Effective Emergency Postcoital Contraceptive: A the therapy, and then to analyze data only process of conception, may be important Report of Its Use in 1200 Patients in a Family Planning from those meeting the criteria. If partic- information for women making ethical de- Clinic,” Australian and New Zealand Journal of Obstetrics ipants are given too many instructions or terminations about whether they would and Gynaecology, 28:137–140, 1988; M.R. Van Santen and asked to modify their lifestyles too dras- use various regimens.39 Additional basic A. A. Haspels, “Interception II: Postcoital Low-Dose Es- tically for the sake of a trial, they may research could clarify these mechanisms. trogens and Norgestrel Combination in 633 Women,” Contraception, 31:275–293, 1985; R.K. L. Percival-Smith choose not to disclose additional acts of and B. Abercrombie, “Postcoital Contraception with dl- intercourse or other protocol violations. Conclusion Norgestrel/Ethinyl Estradiol Combination: Six Years Ex- More than 30 years of experience with perience in a Student Medical Clinic,” Contraception, User-Related Studies emergency contraceptives has established 36:287–293, 1987; G. Zuliani, U.F. Colombo and R. Molla, “Hormonal Postcoital Contraception with an Research on how women can best use that the methods can substantially reduce Ethinylestradiol-Norgestrel Combination and Two Dana- emergency contraceptives to suit their the chances of pregnancy, that their side zol Regimens,” European Journal of Obstetrics & Gynecol- needs is crucial, especially in the case of effects are acceptable to women and that ogy and Reproductive Biology, 37:253–260, 1990; P.C. Ho the hormonal methods, which depend far service provision requirements are not and M. S. W. Kwan, “A Prospective Randomized Com- less on providers. Should emergency con- generally onerous to clinicians. While parison of Levonorgestrel with the Yuzpe Regimen in Post-Coital Contraception,” Human Reproduction, traceptive pills be available over the there is a need for additional research, the 8:389–392, 1993; A. M. C. Webb, J. Russell and M. Elstein, counter and from vending machines? available literature sustains a compelling “Comparison of Yuzpe Regimen, Danazol, and Mifepri- Should they be routinely prescribed or dis- case for expanding emergency contra- stone (RU486) in Oral Postcoital Contraception,” British

Volume 28, Number 2, March/April 1996 47 History and Efficacy of Emergency Contraception

Medical Journal, 305:927–931, 1992; and B. Tully, “Post cency Contraception,” IPPF Medical Bulletin, Vol. 26, traception in Seven European Countries, Reproductive Coital Contraception—A Study,” British Journal of Fam- No. 6, 1994, pp. 1–2. Health Technologies Project, Washington, D.C., 1994. ily Planning, 8:119–124, 1983. 17. M. B. Bracken, “Oral Contraception and Congenital 28. G. Zuliani, U.F. Colombo and R. Molla, 1990, op. cit. 10. A. Glasier et al., “Emergency Contraception in the Malformations in Offspring: A Review and Meta-analy- (see reference 9); and A. M. C. Webb, J. Russell and M. El- United Kingdom and the Netherlands,” Family Planning sis of the Prospective Studies,” Obstetrics & Gynecology, stein, 1992, op. cit. (see reference 9). Perspectives, 28:49–51, 1996. 76:552–557, 1990. 29. G. Zuliani, U.F. Colombo and R. Molla, 1990, op. cit. 11. Family Health International, unpublished survey re- 18. R. Hatcher et al., Contraceptive Technology, 16th rev. (see reference 9). sults, reported in “Final Report to Population Action In- ed., Irvington, New York, 1994. 30. A. M. C. Webb, J. Russell and M. Elstein, 1992, op. cit. ternational,” Durham, N.C., 1994. 19. P. C. Ho and M. S. W. Kwan, 1993, op. cit. (see refer- (see reference 9). 12. J. Trussell et al., “Emergency Contraceptive Pills: A ence 9). 31. J. Trussell and C. Ellertson, “The Efficacy of Emer- Simple Proposal to Reduce Unintended Pregnancies,” 20. H. von Hertzen and P.F.A. Van Look, “Research on gency Contraception,” Fertility Control Reviews, Vol. 4, Family Planning Perspectives, 24:269–273, 1992. New Methods of Emergency Contraception,” Family No. 2, 1995, pp. 8–11. 13. P. F. A. Van Look and H. von Hertzen, 1993, op. cit. Planning Perspectives, 28:52–57 & 88, 1996. 32. (see reference 1). R. Hatcher et al., 1994, op. cit. (see reference 18). 21. C. He et al., “A Multicenter Clinical Study on Two 33. 14. A. A. Yuzpe and W.J. Lancee, 1977, op. cit. (see ref- Types of Levonorgestrel Tablets Administered for Post- S. L. Camp, 1994, op. cit. (see reference 27). erence 5); A. A. Yuzpe, R.P. Smith and A. W. Rademak- coital Contraception,” International Journal of Gynecology 34. M. Rosenberg, Health Decisions, Inc., Chapel Hill, er, 1982, op. cit. (see reference 9); A. Glasier et al., 1992, and Obstetrics, 36:43–48, 1991. N.C., personal communication, 1994. op. cit. (see reference 9); S. N. Bagshaw, D. Edwards and 22. R. Hatcher et al., 1994, op. cit. (see reference 18). A. K. Tucker, 1988, op. cit. (see reference 9); M. R. Van San- 35. G. W. Dixon et al., “Ethinyl Estradiol and Conjugat- ten and A. A. Haspels, 1985, op. cit. (see reference 9); 23. W. L. Herrmann et al., “Effet d’un stéroïde an- ed Estrogens as Postcoital Contraceptives,” Journal of the R. K. L. Percival-Smith and B. Abercrombie, 1987, op. cit. tiprogesterone chez la femme: Interruption du cycle men- American Medical Association, 244:1336–1339, 1980. (see reference 9); G. Zuliani, U.F. Colombo and R. Molla, struel et de la grossesse au début,” Comptes Rendus de 36. J. Trussell, C. Ellertson and F. Stewart, 1996, op. cit. 1990, op. cit. (see reference 9); P.C. Ho and M. S. W. Kwan, l’Académie des Sciences, 294:933–938, 1982. (see reference 15). 1993, op. cit. (see reference 9); A. M. C. Webb, J. Russell 24. A. Glasier et al., 1992, op. cit. (see reference 9); and and M. Elstein, 1992, op. cit. (see reference 9); and B. Tully, 37. F. Grou and I. Rodrigues, “The Morning-After Pill— A. M. C. Webb, J. Russell and M. Elstein, 1992, op. cit. (see 1983, op. cit. (see reference 9). How Long After?” American Journal of Obstetrics and Gy- reference 9). necology, 171:1529–1534, 1994. 15. J. Trussell and F. Stewart, “The Effectiveness of Post- 25. R. Peyron et al., “Early Termination of Pregnancy coital Hormonal Contraception,” Family Planning Per- 38. R. K. L. Percival-Smith and B. Abercrombie, 1987, op. with Mifepristone (RU 486) and the Orally Active Pros- spectives, 24:262–264, 1992; and J. Trussell, C. Ellertson cit. (see reference 9); and J. Trussell, C. Ellertson and F. taglandin Misoprostol,” New England Journal of Medicine, and F. Stewart, “The Effectiveness of the Yuzpe Regimen Stewart, 1996, op. cit. (see reference 15). 328:1509–1513, 1993. of Emergency Contraception,” Family Planning Perspec- 39. C. Harper and C. Ellertson, “The Emergency Con- tives, 28:58–64 & 87, 1996. 26. H. von Hertzen and P.F.A. Van Look, 1996, op. cit. traceptive Pill: A Survey of Knowledge and Attitudes (see reference 20). 16. International Medical Advisory Panel, Internation- Among Students at Princeton University,” American Jour- al Planned Parenthood Federation,“Statement on Emer- 27. S. L. Camp, A Study-Tour Report on Emergency Con- nal of Obstetrics and Gynecology, 173:1438–1445, 1995.

48 Family Planning Perspectives