Lisa M. Johnson
Melanie A. Gold
Emergency contraception (EC) has a tremendous potential to reduce the numbers of unplanned pregnancies and to decrease the need for abortion in women of all ages. It has been estimated that, with proper use, EC could prevent 1.7 million unplanned pregnancies and 800,000 abortions each year (Glasier and Baird 1998). EC use among women of all ages has increased from 17,000/year in 1995 to 634,000/year in 2002 and it remains an important pregnancy prevention measure because unprotected or poorly protected intercourse occurs at a higher rate from unanticipated intercourse (e.g., impulse, date, or rape), lack of perceived need for protection, and/or incorrect or inconsistent contraceptive use.
Emergency Contraception Methods
Three types of EC are available in the United States. The first two are hormonal methods that should be started within 120 hours (5 days) of exposure. The Yuzpe regimen, which has been available for >25 years, entails two doses of at least 100 µg ethinyl estradiol and 0.5 mg levonorgestrel (or 1.0 mg norgestrel) taken 12 hours apart. The progestin-only method entails either two single doses of 0.75 mg levonorgestrel (or 1.5 mg norgestrel) taken 12 hours apart or a single dose of 1.5 mg of levonorgestrel. The third method is insertion of a copper intrauterine device (IUD) within 5 days of unprotected intercourse.
The Yuzpe regimen, introduced in 1974, was the most commonly used EC method. Table 46.1 lists combination oral contraceptives that can be used to make up the Yuzpe regimen and their appropriate doses. In 1998, the U.S. Food and Drug Administration (FDA) approved the first dedicated EC product (Preven emergency contraceptive kit) using the Yuzpe regimen. Preven was taken off the market in 2004 when rights to the product were acquired by the company that makes the only current dedicated EC product (Plan B).
In 1999, the FDA approved a dedicated progestin-only product (Plan B), which contains two tablets each containing 0.75 mg of levonorgestrel. The FDA-approved instructions for Plan B are to take a single tablet as soon as possible after unprotected intercourse (up to 72 hours after coitus) and to take the second single tablet 12 hours later. More recently, von Hertzen et al. (2002) found that levonorgestrel could be given as a single dose of two tablets taken up to 120 hours after unprotected intercourse without causing any increase in side effects or decrease in efficacy. A progestin-only EC product should be used whenever possible because it is the current product of choice.
The progestin-only method of EC has several advantages over the Yuzpe method (Ho and Kwan, 1993; Task Force on Postovulatory Methods of Fertility Regulation, 1998). The efficacy of the progestin-only method is superior to that of the Yuzpe method (Table 46.2). Virtually every nonpregnant woman is eligible to use it, and side effects (especially gastrointestinal complaints such as
nausea and vomiting) occur significantly less often with the progestin-only method as compared to the Yuzpe regimen (Table 46.3).
The third type of EC, the T-380A copper IUD (or Para-Gard), can be inserted up to 5 days after unprotected coitus and provides the best pregnancy protection. Although the copper IUD is more effective than the hormonal options for EC, it is rarely used for EC in female adolescents or among women who may be at risk for having a sexually transmitted infection (see Chapter 44 on IUD in adolescents). The copper IUD is also very expensive for single use for EC. Therefore, its use in the United States for this indication has been quite limited.
Several large studies conducted outside the United States found that when mifepristone is used for EC it is more effective than the Yuzpe regimen and equally effective as the progestin-only regimen (Ashok et al., 2002). There are very few side effects with low dose mifepristone used for EC; one study found the incidence of nausea was 1% (Ashok et al., 2004). When mifepristone is used for EC there is more of a delay in the timing of the next menstrual period than with other hormonal EC regimens. However, mifepristone is only available in the United States for use in medical abortions and off label use for EC is rare. Furthermore, studies have shown that 1/60th of the dose of mifepristone used for abortion (600 mg) is needed for EC (10 mg). No such 10 mg preparation is available in the United States, although mifepristone is used for EC in other parts of the world (Task Force on Postovulatory Methods of Fertility Regulation, 1999).
The expected pregnancy rate per single act of unprotected intercourse is estimated to be 8%. Efficacy for EC can be expressed in two ways—the observed pregnancy rate or the percentage reduction in the expected number of pregnancies (Table 46.2). For example, the single-use failure rate for the Yuzpe regimen is a little more than 3.2%, which represents a 75% reduction in expected pregnancies. Levonorgestrel alone is more effective, with a failure rate of only 1.1% (when compared with the Yuzpe regimen), which is an 89% reduction in the expected number of pregnancies (Lancet, 1998). The copper IUD is the most effective EC method currently available; its failure rate is 0.1%, which is a 99% reduction in the expected number of pregnancies. The estimates of overall efficacy for the Yuzpe regimen were calculated from a wide range of results observed in different
clinical trials. One trial found a 56% reduction in expected pregnancy rates with the Yuzpe regimen, while another found 89% (Trussell et al., 1999). In part, this variation may have reflected the inclusion of women who were already pregnant at the time they were treated. A recent, large-scale World Health Organization (WHO) trial demonstrated that the effectiveness of hormonal EC depends on how soon it is initiated after intercourse (Piaggio et al., 1999; Task Force on Postovulatory Methods of Fertility Regulation, 1998) (Table46.4), although earlier studies did not show such a temporal relationship (Trussell et al., 1996). In the WHO study, when hormonal EC was started within the first 12 hours, the pregnancy rate was 0.5% (a 94% reduction), but if the first dose was delayed until 60 to 72 hours after the exposure, the pregnancy rate was 4% (a 50% reduction). The 72-hour limit is expandable to 120 hours, but there is controversy over whether later use is associated with diminished protection. Some studies show no impact in efficacy based on timing whereas others do show a decline in efficacy with later use. In a 2003 study, 675 women using the Yuzpe regimen within 72 hours of unprotected intercourse were compared with 111 women using the Yuzpe regimen between 72 hours to 120 hours after unprotected intercourse; no statistically significant difference was found in failure rate between the two groups (Ellerston et al., 2003). However, the observation that earlier use of EC may be more efficacious has influenced prescribing patterns and led to the approval for behind-the-counter availability for people age 18 and over with government identification.
Mechanisms of Action
Hormonal methods of EC (Yuzpe or progestin-only) are approved by the FDA as contraceptives. This classification is supported by the observations (a) that most conceptions occur when intercourse precedes ovulation and (b) that EC with oral contraceptives is more effective when administered early after coitus. The primary action of the hormonal methods of EC appears to be delaying or inhibiting ovulation, but new analysis suggests that other mechanisms may be important (Trussell and Raymond, 1999). Studies have found that levonorgestrel and the Yuzpe regimen suppress or delay the luteinizing hormone (LH) peak and inhibit follicle rupture (Croxatto et al., 2003; Marions et al., 2004). EC may also alter tubal motility, production of progesterone by the corpus luteum, and the composition of the endometrium to block implantation (Glasier, 1997).
Although it may not always be clear whether oral EC is working by delaying ovulation or impeding implantation, EC does not work as an abortifacient. EC taken after a pregnancy has been established to have no effect; it will not cause a miscarriage, and it will not increase the risk of fetal malformations (Raman-Wilms et al., 1995; Blumenthal and McIntosh, 1996). EC is contraindicated in pregnancy because it is ineffective once implantation of a fertilized egg has occurred.
The mechanisms of action for the copper IUD as a postcoital method have not been well elucidated. It is unclear how important the copper ions are to the copper IUD's contraceptive effect when used as an EC (Rivera et al., 1999). Because sperm can live in the cervical canal for up to 5 days before fertilization, the spermicidal action of the copper IUD could be important. The presence of a foreign body (the IUD) may alter the endometrium and prevent implantation.
EC is indicated any time a woman of reproductive age wishes to lower her risk of becoming pregnant following unprotected intercourse (e.g., following sexual assault or unplanned intercourse.) EC is also indicated after inadequately protected sexual intercourse from failure or misuse of a contraceptive method (Table 46.5).
The FDA labeling for combination oral contraceptives used for EC includes the same contraindications as when combination oral contraceptives are taken on a daily basis (see Chapter 43). However, approximately four decades of use has shown that such stringent restrictions for a single use of the Yuzpe regimen are not necessary. Current pregnancy, allergy, and acute current migraine with neurological deficits are the only absolute contraindications to prescribing the Yuzpe regimen. A history of previous thrombosis should not be a contraindication to a single course of the Yuzpe regimen (Webb and Tabemer, 1993), although, if available, progestin-only pills would be preferable for medicolegal reasons in addition to being more effective and having fewer side effects compared with the Yuzpe regimen. The risk of a clot for a patient with prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE) remains higher in pregnancy than for a single course of the Yuzpe regimen.
The three contraindications for progestin-only oral contraceptives including Plan B are:
However, in an adolescent who is having abnormal genital bleeding, as long as pregnancy is ruled out, EC can
be given. The progestin-only method is preferred for breast-feeding women because the estrogen in the Yuzpe regimen has the potential to decrease breast milk production.
Copper Intrauterine Device Method
The copper IUD for long-term has several contraindications (see Chapter 44 on IUDs). Because short-term use cannot be ensured, these same contraindications have been applied to the use of the copper IUD for EC.
Side effects of the Yuzpe regimen and progestin-only EC are largely hormone related and can last for 2 to 3 days. The most common side effects are gastrointestinal. With the Yuzpe method, 30% to 66% of women report nausea, and 12% to 22% have vomiting. Gastrointestinal complaints can be reduced by routinely giving a long-acting antiemetic over-the-counter (OTC) agent such as meclizine 50 mg 1 hour before the first EC dose. Raymond et al. (2000) found that meclizine can halve the risk of nausea and vomiting, but most women experience drowsiness. The progestin-only method has a lower incidence of gastrointestinal side effects; only 23% of women report nausea, 6% vomiting, and 5% report diarrhea, therefore antiemetics are not routinely offered when prescribing progestin-only EC.
Other hormone-related side effects include breast tenderness, headache, abdominal bloating, fatigue, and dizziness. Among women who took the Yuzpe regimen, 10% had vaginal spotting at some point before the next menses which usually lasted 1 to 2 days. There was no difference in spotting rates between women who became pregnant following EC use and those who did not. Women who took EC in the first half of the menstrual cycle (before day 12) were more likely to have their next period earlier than expected (by >3 days) (Webb et al., 2004). Depending on when in the cycle EC is used, the timing and flow of
the next menses may be altered. However, 98% of women should have menstrual bleeding within 3 weeks of EC use; if an EC user has not started menses 3 weeks after EC use, she should get a pregnancy test. Some adolescent health care providers recommend a pregnancy test 14 days after EC use, regardless of menses.
Management of Side Effects
Patients can learn the names and addresses of local providers of EC by accessing the EC hotline, either by telephone at 1-888-NOT-2-LATE (Trussell et al., 1998) or on the Internet at http://www.NOT-2-LATE.com/. Physicians and clinics can contact these same hotlines to join the network of EC providers.
Some European countries and recently Canada have allowed levonorgestrel EC to be sold as an OTC medication. After a 3 year delay, the FDA approved OTC sales of Plan B in August 2006 to individuals ages 18 years and older. However, Plan B remains prescribtion-only status for female adolescents ages 17 years and under. There is ongoing lobbying of the FDA to extend OTC access of Plan B to adolescents under the age of 18.
For Teenagers and Parents
EC Web site from Office of Population Research with list of providers, information, news, EC availability by country, and references: http://ec.princeton.edu/or http://www.NOT-2-LATE.com
EC information from the Planned Parenthood Federation of America: http://www.plannedparenthood.org/ec/
Duke University Student Health Center information site on EC: http://healthydevil.studentaffairs.duke.edu/health_info/emergency%20contraception.html
Duke University Student Health Center information site on Sexual Health: http:healthydevil.studentaffairs.duke.edu/health_info/
Women's Capital Corporation Web site for Plan B: http://www.go2planb.com/
Boston Children's Hospital website with EC information: www.youngwomenshealth.org/emergencycontraception.html
For Health Professionals
American Academy of Pediatrics Policy Statement on EC, Fact Sheet for Parents and Adolescents, and Speaking Points for Pediatricians: http://www.aap.org (Policy Statement and Fact Sheet)
http://www.aap.org/moc (Speaking Points for Pediatricians at AAP member center)
Information about EC and directory of providers on the internet: http://www.NOT-2-LATE.com
Toll-free telephone information about EC and provider referrals 1-888-NOT-2-LATE (English and Spanish instructions)
Information about enrolling as a provider in the U.S. directory http://ec.princeton.edu/questions/ecsignup.html
EC and other information about contraception: http://www.managingcontraception.com
EC information from the Planned Parenthood Federation of America http://www.plannedparenthood.org/ec/
Article from Hospital Practice on EC: http://www.hosppract.com/issues/1998/08/stewart.htm
Sites to download PowerPoint presentation on EC from Association of Reproductive Health Professionals:
http://www.arhp.org/files/clinical.ppt and http://www.arhp.org/file/strategy.ppt
References and Additional Readings
Aiken AM, Gold MA, Parker AM. Changes in young women's awareness, attitudes, and perceived barriers to using emergency contraception. J Pediatr Adolesc Gynecol2005;18(1):25.
American College of Obstetricians and Gynecologists. ACOG practice bulletin: clinical management guidelines for obstetricians-gynecologists: emergency contraception. No. 69, December 2005. (Replaces No. 25, March 2001). Obstet Gynecol 2005;106(6):1443.
Ashok PW, Hamoda H, Flett GM, et al. Mifepristone versus the Yuzpe regimen (PC4) for emergency contraception. Int J Gynaecol Obstet 2004;87(2):188.
Ashok PW, Stalder C, Wagaarachchi PT, et al. A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception. Br J Obstet Gynaecol 2002;109(5):553.
Blumenthal P, McIntosh N. Emergency contraception. In: Oliveras E, ed. Pocket guide for family planning service providers, 3rd ed. Baltimore: JHPIEGO Corporation, 1996:65.
Brownfield v. Daniel Freeman Marina Hospital. No. B032109. Court of Appeals of California, Second Appellate District, Division Four, 208 Cal. App. 3d 405; 1989 Cal. App. LEXIS 157;256 Cal. Rptr. 240. March 2, 1989.
Cohen SA. Objections, confusion among pharmacists threaten access to emergency contraception. Guttmacher Rep Public Policy 1999;2:1.
Conard LE, Gold MA. Emergency contraception update: providing emergency contraception in the pediatrician's office. Contemp Pediatr 2006;23(2):49.
Croxatto HB, Oritz ME, Müller AL. Mechanisms of action of emergency contraception. Steroids 2003;68:1095.
Delbanco SF, Mauldon J, Smith MD. Little knowledge and limited practice: emergency contraceptive pills, the public, and the obstetrician-gynecologist. Obstet Gynecol1997;89:1006.
Delbanco SF, Parker ML, McIntosh M, et al. Missed opportunities: teenagers and emergency contraception. Arch Pediatr Adolesc Med 1998;152:727.
Ellertson C, Ambardekar S, Hedley A, et al. Emergency contraception: randomized comparison of advance provision and information only. Obstet Gynecol 2001;98(4):570.
Ellertson C, Webb A, Blanchard K, et al. Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized controlled trial. Obstet Gynecol 2003;101(6):1160.
Glasier A. Emergency postcoital contraception. N Engl J Med 1997;337:1058.
Glasier A, Baird D. The effects of self-administering emergency contraception. N Engl J Med 1998;339:1.
Gold MA, Schein A, Coupey SM. Emergency contraception: a national survey of adolescent health experts. Fam Plann Perspect 1997;29:15.
Gold MA, Sucato G, Conard LE, et al. Provision of emergency contraception to adolescents: position paper of the Society for Adolescent Medicine. J Adolesc Health 2004a;35:66.
Gold MA, Wolford JE, Smith KA, et al. The effects of advance provision of emergency contraception on adolescent women's sexual and contraceptive behaviors. J Pediatr Adolesc Gynecol 2004b;17:87.
Henry J. Kaiser Family Foundation. National survey of health care providers on emergency contraception, 2000. MenloPark, CA: Kaiser Family Foundation, 2000.
von Hertzen H, Piaggio G, Ding J, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomized trial. Lancet2002; 360:1803–1810.
Ho PC, Kwan MS. A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception. Hum Reprod 1993;8:389.
Jackson RA, Schwarz EB, Freedman L, et al. Advance supply of emergency contraception: effect on use and usual contraception—a randomized trial. Obstet Gynecol2003;102(1):8.
Lo SST, Fan SYS, Ho PC, et al. Effect of advanced provision of emergency contraception on women's contraceptive behaviour: a randomized controlled trial. Hum Reprod 2004; 19(10):2404.
Lovvorn A, Nerquaye-Tetteh J, Glover EK, et al. Provision of emergency contraceptive pills to spermicide users in Ghana. Contraception 2000;61:287.
Marions L, Cekan SZ, Bygdeman M, et al. Effect of emergency contraception with levonorgestrel or mifepristone on ovarian function. Contraception 2004;69:373.
Piaggio G, von Hertzen H, Grimes DA, et al. Task Force on Postovulatory Methods of Fertility Regulation. Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Lancet 1999;353:721.
Raine T, Harper C, Leon K, et al. Emergency contraception: advance provision in a young, high-risk clinic population. Obstet Gynecol 2000;96:1.
Raine TR, Harper CC, Rocca CH, et al. Direct access to emergency contraception through pharmacies and effect on contraception and STDs: a randomized controlled trial. JAMA2005;293:54.
Raman-Wilms L, Tseng AL, Wighardt S, et al. Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. Obstet Gynecol 1995;85:141.
Raymond EG, Creinin MD, Barnhart KT, et al. Meclizine for prevention of nausea associated with use of emergency contraceptive pills: a randomized trial. Obstet Gynecol 2000; 95:271.
Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol 1999;181:1263.
Rowlands S, Devalia H, Lawrenson R, et al. Repeated use of hormonal emergency contraception by younger women in the UK. Br J Fam Plann 2000;26:138.
Sills MR, Chamberlain JM, Teach SJ. The associations among pediatricians' knowledge, attitudes, and practices regarding emergency contraception. Pediatrics 2000;105:954.
Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998;352:428.
Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999; 353:697.
Trussell J, Bull J, Koenig J, et al. Call 1-888-NOT-2-LATE: promoting emergency contraception in the United States. J Am Med Womens Assoc 1998;53:247.
Trussell J, Ellertson C, Rodriguez G. The Yuzpe regimen of emergency contraception: how long after the morning after? Obstet Gynecol 1996;88:150.
Trussell J, Koenig J, Ellertson C, et al. Preventing unintended pregnancy: the cost-effectiveness of three methods of emergency contraception. Am J Public Health 1997;87: 932.
Trussell J, Raymond EG. Statistical evidence about the mechanism of action of the Yuzpe regimen of emergency contraception. Obstet Gynecol 1999;93:872.
Trussell J, Rodriguez G, Ellertson C. Updated estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception 1999;59:147.
Webb A, Shochet T, Bigrigg A, et al. Effect of hormonal emergency contraception on bleeding patterns. Contraception 2004;69:133.
Webb A, Tabemer D. Clotting factors after emergency contraception. Adv Contracept 1993;9:75.
Wilcox AJ, Dunson D, Baird DD. The timing of the “fertile window” in the menstrual cycle: day specific estimates from aprospectivestudy. Br Med J 2000;321:1259.
Yuzpe AA, Lancee WJ. Ethinylestradiol and Dl-norgestrel as a postcoital contraceptive. Fertil Steril 1977;9:932.