Emergency contraception (EC) is a birth control measure, used after sexual intercourse to prevent pregnancy.
There are different forms of EC. Emergency contraceptive pills (ECPs), sometimes simply referred to as emergency contraceptives (ECs), or the morning-after pill, are medications intended to disrupt or delay ovulation or fertilization, which are necessary for pregnancy.[3][4][5]
Intrauterine devices (IUDs) – usually used as a primary contraceptive method – are sometimes used as the most effective form of emergency contraception.[4][6] However, the use of IUDs for emergency contraception is relatively rare.[1]
Emergency contraception is a birth control measure taken to reduce the risk of pregnancy following unprotected sexual intercourse or when other regular contraceptive measures have not worked properly or have not been used correctly.[7] It is intended to be used occasionally and is not the same as medical abortion.[7][8] Emergency contraception is offered to women who do not wish to conceive but have had unprotected sex on any day of the menstrual cycle, from day 21 after giving birth, or from day five after abortion or miscarriage.[7] Emergency contraception measures include tablets taken by mouth or the insertion of a copper intrauterine device.[7][8]
Emergency contraception is not related to medical abortion, which is a drug regimen administered to terminate pregnancies in any trimester.[9][10][11]
Emergency contraceptive pills (ECPs) are sometimes referred to as emergency hormonal contraception (EHC). They are taken after unprotected sexual intercourse or the breakage of a condom.[12]
A variety of emergency contraceptive pills are available, including combined estrogen and progestin pills; progestin-only (levonorgestrel, LNG) pills; and antiprogestin (ulipristal acetate or mifepristone) pills.[13] Progestin-only and anti-progestin pills are available as specifically packaged pills for use as emergency contraceptive pills.[13][14] Emergency contraceptive pills originally contained higher doses of the same hormones (estrogens, progestins, or both) found in regular combined oral contraceptive pills. Combined estrogen and progestin pills are no longer recommended as dedicated emergency contraceptive pills (because this regimen is less effective and caused more nausea), but certain regular combined oral contraceptive pills (taken 2–5 at a time in what was called "the Yuzpe regimen") have also been shown to be effective as emergency contraceptive pills.[13]
Progestin-only emergency contraceptive pills contain levonorgestrel, either as a single tablet (or historically, as a split dose of two tablets taken 12 hours apart), effective up to 72 hours after intercourse.[13] Progestin-only ECPs are sold under many different brand names.[15][16][17] Progestin-only ECPs are available over-the-counter (OTC) in many countries (e.g. Australia, Bangladesh, Bulgaria, Canada, Cyprus, Czech Republic, Denmark, Estonia, India, Malta, Netherlands, Norway, Portugal, Romania, Slovakia, South Africa, Sweden, United States), from a pharmacist without a prescription, and available with a prescription in some other countries.[15][16][17]
The antiprogestin ulipristal acetate is available as a micronized emergency contraceptive tablet, effective up to 120 hours after intercourse.[13][14] Ulipristal acetate ECPs developed by HRA Pharma are available over the counter in Europe[18] and by prescription in over 50 countries under the brand names ellaOne, ella (marketed by Watson Pharmaceuticals in the United States), Duprisal 30, Ulipristal 30, and UPRIS.[15][16][17][19]
The antiprogestin mifepristone (also known as RU-486) is available in five countries as a low-dose or mid-dose emergency contraceptive tablet, effective up to 120 hours after intercourse.[13][14] Low-dose mifepristone ECPs are available by prescription in Armenia, Russia, Ukraine, and Vietnam and from a pharmacist without a prescription in China.[15][16] Mid-dose mifepristone ECPs are available by prescription in China and Vietnam.[15][16]
Combined estrogen (ethinylestradiol) and progestin (levonorgestrel or norgestrel) pills used to be available as dedicated emergency contraceptive pills under several brand names: Schering PC4, Tetragynon, Neoprimavlar, and Preven (in the United States) but were withdrawn after more effective dedicated progestin-only (levonorgestrel) emergency contraceptive pills with fewer side effects became available.[13] If other more effective dedicated emergency contraceptive pills (levonorgestrel, ulipristal acetate, or mifepristone) are not available, specific combinations of regular combined oral contraceptive pills can be taken in split doses 12 hours apart (the Yuzpe regimen), effective up to 72 hours after intercourse.[13]
The U.S. Food and Drug Administration (FDA) approved this off-label use of certain brands of regular combined oral contraceptive pills in 1997.[12] As of 2014, there are 26 brands of regular combined oral contraceptive pills containing levonorgestrel or norgestrel available in the United States that can be used in the emergency contraceptive Yuzpe regimen,[13] when none of the more effective and better-tolerated options are available.
Ulipristal acetate, and mid-dose mifepristone are both more effective than levonorgestrel, which is more effective than the Yuzpe method.[20]
The effectiveness of emergency contraception is expressed as a percentage reduction in pregnancy rate for a single use of EC. Using an example of "75% effective", the effectiveness calculation thus:
... these numbers do not translate into a pregnancy rate of 25 percent. Rather, they mean that if 1,000 women have unprotected intercourse in the middle two weeks of their menstrual cycles, approximately 80 will become pregnant. Use of emergency contraceptive pills would reduce this number by 75 percent, to 20 women.[21]
The progestin-only regimen (using levonorgestrel) has an 89% effectiveness. As of 2006[update], the labeling on the U.S. brand Plan B explained this effectiveness rate by stating, "Seven out of every eight women who would have gotten pregnant will not become pregnant."[22]
In 1999, a meta-analysis of eight studies of the combined (Yuzpe) regimen concluded that the best point estimate of effectiveness was 74%.[23] A 2003 analysis of two of the largest combined (Yuzpe) regimen studies, using a different calculation method, found effectiveness estimates of 47% and 53%.[24]
For both the progestin-only and Yuzpe regimens, the effectiveness of emergency contraception is highest when taken within 12 hours of intercourse and declines over time.[25][26][27]The World Health Organization (WHO) suggested that reasonable effectiveness may continue for up to 120 hours (5 days) after intercourse.[28]
For 10 mg of mifepristone taken up to 120 hours (5 days) after intercourse, the combined estimate from three trials was an effectiveness of 83%.[29] A review found that a moderate dose of mifepristone is better than LNG or Yuzpe, with delayed return of menstruation being the main adverse effect of most regimes.[20]
HRA Pharma changed its packaging information for Norlevo (levonorgestrel 1.5 mg, which is identical to many other EHCs) in November 2013 warning that according to studies the drug loses effectiveness in women who weigh more than 75 kg (165 lb) and is completely ineffective for women who weigh over 80 kg (176 lb).[30][31] After a review by European Medicines Agency, the statement was deleted from the leaflet. The agency communicated that levonorgestrel is safe and effective method of emergency contraception, regardless of body weight.[32]
The most common side effect reported by users of emergency contraceptive pills was nausea 14 to 23% of levonorgestrel-only users and 50.5% of Yuzpe regimen users; vomiting is much less common and unusual with levonorgestrel-only ECPs (5.6% of levonorgestrel-only users vs 18.8% of 979 Yuzpe regimen users in 1998 WHO trial; 1.4% of 2,720 levonorgestrel-only users in the 2002 WHO trial).[25][28][33] Anti-emetics are not routinely recommended with levonorgestrel-only ECPs.[33][34] If a woman vomits within 2 hours of taking a levonorgestrel-only ECP, she should take a further dose as soon as possible.[33][35]
Other common side effects (each reported by less than 20% of levonorgestrel-only users in both the 1998 and 2002 WHO trials) were abdominal pain, fatigue, headache, dizziness, and breast tenderness.[25][28][33][36] Side effects generally resolve within 24 hours,[13] although temporary disruption of the menstrual cycle is commonly experienced. If taken before ovulation, the high doses of progestogen in levonorgestrel treatments may induce progestogen withdrawal bleeding a few days after the pills are taken.
One study found that about half of women who used levonorgestrel ECPs experienced bleeding within 7 days of taking the pills.[37] If levonorgestrel is taken after ovulation, it may increase the length of the luteal phase, thus delaying menstruation by a few days.[38] Mifepristone, if taken before ovulation, may delay ovulation by 3–4 days[39] (delayed ovulation may result in a delayed menstruation). These disruptions only occur in the cycle in which ECPs were taken; subsequent cycle length is not significantly affected.[37] If a woman's menstrual period is delayed by two weeks or more, it is advised that she take a pregnancy test.[40] (Earlier testing may not give accurate results.)
Existing pregnancy is not a contraindication in terms of safety, as there is no known harm to the woman, the course of her pregnancy, or the fetus if progestin-only or combined emergency contraception pills are accidentally used, but EC is not indicated for a woman with a known or suspected pregnancy because it is not effective in women who are already pregnant.[13][41][42][40][43][44][45][46][47]
The World Health Organization (WHO) lists no medical condition for which the risks of emergency contraceptive pills outweigh the benefits.[44] The American Academy of Pediatrics (AAP) and experts on emergency contraception have concluded that progestin-only ECPs are preferable to combined ECPs containing estrogen for all women, and particularly those with a history of blood clots, stroke, or migraine.[13][41][42]
There are no medical conditions in which progestin-only ECPs are contraindicated.[13][41][42][40][43][44][45] Current venous thromboembolism, current or history of breast cancer, inflammatory bowel disease, and acute intermittent porphyria are conditions where the advantages of using emergency contraceptive pills generally outweigh the theoretical or proven risks.[45]
ECPs, like all other contraceptives, reduce the absolute risk of ectopic pregnancy by preventing pregnancies and there is no increase in the relative risk of ectopic pregnancy in women who become pregnant after using progestin-only ECPs.[13][48][49]
The herbal preparation of St John's wort and some enzyme-inducing drugs (e.g. anticonvulsants or rifampicin) may reduce the effectiveness of ECP, and a larger dose may be required,[33][50] especially in women who weigh more than 165 lbs.[6]
An effective emergency contraception measure is the copper-T intrauterine device (IUD) which is generally recommended up to 5 days after unprotected intercourse or up to 5 days after probable ovulation.[2][7] Some studies have found it to be effective up to 10 days after unprotected intercourse to prevent pregnancy.[2] A 2021 study found that the hormonal IUD was as effective at emergency contraception as the copper IUD, though it is not offered by clinicians at the moment due to the lack of research done into the subject.[51][52]
Insertion of an IUD is more effective than the use of emergency contraceptive pills – pregnancy rates when used as emergency contraception are the same as with normal IUD use. Unlike emergency contraceptive pills, which work by delaying ovulation, the copper-T IUD works by interfering with sperm motility. Therefore, the copper IUD is equally effective as emergency contraception at all weight ranges.[53] IUDs may be left in place following the subsequent menstruation to provide ongoing contraception for as long as desired (12+ years).[54][55][53]
One brand of levonorgestrel pills was marketed as an ongoing method of postcoital contraception.[56] However, with typical use, failure rates are expected to be higher than with the use of other birth control methods.[6]
Like all hormonal methods, postcoital high-dose progestin-only oral contraceptive pills do not protect against sexually transmitted infections.[57]
ECPs are generally recommended for backup or "emergency" use – for example, if a woman has forgotten to take a birth control pill or when a condom is torn during sex.[58] However, for women facing reproductive coercion, who are not able to use regular birth control, repeated use of EC pills may be the most viable option available.[6]
Making ECPs more widely available does not increase sexual risk-taking.[6] While they are effective for individuals who use them in a timely fashion, the availability of EC pills does not appear to decrease abortion rates at the population level.[1]
In 2012 the American Academy of Pediatrics (AAP) stated: "Despite multiple studies showing no increased risk behaviour and evidence that hormonal emergency contraception will not disrupt an established pregnancy, public and medical discourse reflects that personal values of physicians and pharmacists continue to affect emergency-contraception access, particularly for adolescents."[59]
Beginning in the 1960s, women who had been sexually assaulted were offered diethylstilbestrol (DES).[60][61] Currently, the standard of care is to offer ulipristal or prompt placement of a copper IUD which is the most effective form of EC. However, adherence to these best practices varies by the emergency department.[62] Before these EC options were available (in 1996), pregnancy rates among females of child-bearing age who had been raped were around 5%.[63] Although EC is recommended following sexual assault, room for improvement in clinical practice remains.[64]
The primary mechanism of action of progestogen-only emergency contraceptive pills is to prevent fertilization by inhibition of ovulation.[4][33][48][65][66][67] The best available evidence is that they do not have any post-fertilization effects such as the prevention of implantation.[4][33][48][65][66][67] The U.S. FDA-approved labels and European EMA-approved labels (except for HRA Pharma's NorLevo) levonorgestrel emergency contraceptive pills (based on labels for regular oral contraceptive pills) say they may cause endometrial changes that discourage implantation.[68][69][70] Daily use of regular oral contraceptive pills can alter the endometrium (although this has not been proven to interfere with implantation), but the isolated use of a levonorgestrel emergency contraceptive pill does not have time to alter the endometrium.[68]
In March 2011, the International Federation of Gynecology and Obstetrics (FIGO) issued a statement that: "review of the evidence suggests that LNG [levonorgestreol] ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling."[68][71] In June 2012, a New York Times editorial called on the FDA to remove from the label the unsupported suggestion that levonorgestrel emergency contraceptive pills inhibit implantation.[72] In November 2013, the European Medicines Agency (EMA) approved a change to the label for HRA Pharma's NorLevo saying it cannot prevent implantation of a fertilized egg.[73]
Progestogen-only emergency contraceptive does not appear to affect the function of the fallopian tubes or increase the rate of ectopic pregnancies.[47]
The primary mechanism of action of progesterone receptor modulator emergency contraceptive pills like low-dose and mid-dose mifepristone and ulipristal acetate is to prevent fertilization by inhibition or delay of ovulation.[4][33][65][66][67] One clinical study found that post-ovulatory administration of ulipristal acetate altered the endometrium, but whether the changes would inhibit implantation is unknown.[4][74] The European EMA-approved labels for ulipristal acetate emergency contraceptive pills do not mention an effect on implantation, but the U.S. FDA-approved label says: "alterations to the endometrium that may affect implantation may also contribute to efficacy."[68][75][76]
The primary mechanism of action of copper-releasing intrauterine devices (IUDs) as emergency contraceptives is to prevent fertilization because of copper toxicity to sperm and ova.[4][33] The very high effectiveness of copper-releasing IUDs as emergency contraceptives implies that they must also prevent some pregnancies by post-fertilization effects such as prevention of implantation.[4][33][65]
In 1966, gynecologist John McLean Morris and biologist Gertrude Van Wagenen at the Yale School of Medicine, reported the successful use of oral high-dose estrogen pills as post-coital contraceptives in women and rhesus macaque monkeys, respectively.[77][78] A few different drugs were studied, with a focus on high-dose estrogens, and it was originally hoped that postcoital contraception would prove viable as an ongoing contraceptive method.[79]
The first widely used methods were five-day treatments with high-dose estrogens, using diethylstilbestrol (DES) in the US and ethinylestradiol in the Netherlands by Haspels.[80][81]
In the early 1970s, the Yuzpe regimen was developed by A. Albert Yuzpe in 1974;[82] progestin-only postcoital contraception was investigated (1975);[83] and the copper IUD was first studied for use as emergency contraception (1975).[84] Danazol was tested in the early 1980s in the hopes that it would have fewer side effects than Yuzpe, but was found to be ineffective.[85]
The Yuzpe regimen became the standard course of treatment for postcoital contraception in many countries in the 1980s. The first prescription-only combined estrogen-progestin dedicated product, Schering PC4 (ethinylestradiol and norgestrel), was approved in the UK in January 1984 and first marketed in October 1984.[86] Schering introduced a second prescription-only combined product, Tetragynon (ethinylestradiol and levonorgestrel) in Germany in 1985.[87] By 1997, Schering AG dedicated prescription-only combined products had been approved in only 9 countries: the UK (Schering PC4), New Zealand (Schering PC4), South Africa (E-Gen-C), Germany (Tetragynon), Switzerland (Tetragynon), Denmark (Tetragynon), Norway (Tetragynon), Sweden (Tetragynon) and Finland (Neoprimavlar); and had been withdrawn from marketing in New Zealand in 1997 to prevent it being sold over-the-counter.[88][89] Regular combined oral contraceptive pills (which were less expensive and more widely available) were more commonly used for the Yuzpe regimen even in countries where dedicated products were available.[90]
Over time, interest in progestin-only treatments increased. The Special Program on Human Reproduction (HRP), an international organization whose members include the World Bank and World Health Organization, "played a pioneering role in emergency contraception" by "confirming the effectiveness of levonorgestrel."[91] After the WHO conducted a large trial comparing Yuzpe and levonorgestrel in 1998,[25][92] combined estrogen-progestin products were gradually withdrawn from some markets (Preven in the United States discontinued May 2004, Schering PC4 in the UK discontinued October 2001, and Tetragynon in France) in favor of progestin-only EC, although prescription-only dedicated Yuzpe regimen products are still available in some countries.
In 2002, China became the first country in which mifepristone was registered for use as EC.
In 2020, Japan announced it would consider easing regulations on the sale of emergency contraceptive pills without a prescription.[93] Non-profit groups submitted a petition to the health ministry calling for prescription-free access to the pill. They had collected more than 100,000 signatures.[94]
Early studies of emergency contraceptives did not attempt to calculate a failure rate; they simply reported the number of women who became pregnant after using an emergency contraceptive. Since 1980, clinical trials of emergency contraception have first calculated probable pregnancies in the study group if no treatment were given. The effectiveness is calculated by dividing observed pregnancies by the estimated number of pregnancies with