Emergency contraception
Encyclopedia
Emergency contraception (EC), or emergency postcoital contraception, refers to birth control
measures that, if taken after sexual intercourse, may prevent pregnancy
.
Forms of EC include:
s of the same hormone
s (estrogen
s, progestin
s, or both) found in regular combined oral contraceptive pills. Taken after unprotected sexual intercourse or contraceptive failure, such higher doses may prevent pregnancy from occurring. Mifepristone
can also be used as EC, though this drug is not considered an "emergency contraceptive pill." It is an anti-hormonal drug, and does not contain estrogen or progestins.
The phrase "morning-after pill" is a misnomer; ECPs are effective when used shortly after intercourse. Depending on the drug, they are licensed for use for up to 107 to 120 hours after unprotected sexual intercourse or contraceptive failure.
in a dose of 1.5 mg, either as two 750 μg doses 12 hours apart, or more recently as a single dose. Progestin-only EC is available as a dedicated emergency contraceptive product under many names worldwide, including: in the U.S., Canada and Honduras as Plan B; in Great Britain, Ireland, Australia, New Zealand, Portugal and Italy as Levonelle; in South Africa as Escapelle; in 44 nations including France, most of Western Europe, India, and several countries in Africa, Asia and Latin America as NorLevo; and in 44 nations including most of Eastern Europe, Mexico and many other Latin American countries, Portugal, Australia and New Zealand, Israel, China, Hong Kong, Taiwan and Singapore as Postinor-2. This pill typically works up to 72 hours after intercourse.
The combined or Yuzpe regimen
uses large doses of both estrogen and progestin, taken as two doses at a 12-hour interval. This method is now believed to be less effective and less well-tolerated than the progestin-only method.
It is possible to obtain the same dosage of hormones, and therefore the same effect, by taking several regular combined oral contraceptive pills
. For example, 4 Ovral pills are the same as 4 Preven pills. The United States Food and Drug Administration (FDA) approved this off-label use of certain brands of regular combined oral contraceptive pills in 1997.
Ulipristal acetate
(known as ella in the US and Ellaone in Europe) was approved as an ECP in Europe in early 2009 and in the US in August 2010. It works for up to 120 hours after intercourse. It prevents pregnancy by delaying or inhibiting ovulation and inhibiting follicle rupture. Watson Pharmaceuticals
announced the availability of ella in the United States on December 1, 2010, in retail pharmacies, clinics and one online pharmacy, KwikMed
.
Emergency contraceptive pills (ECPs) are not to be confused with mifepristone
(RU486, Mifeprex), which is used as an "abortion pill". The term "emergency contraceptive pill" does not refer to mifespristone, which is most commonly used in 200- or 600-mg doses as an abortifacient. However, in China
and Russia
only, mifepristone is available as either emergency contraception or as an abortifacient
, depending on whether it is used before or after implantation. If used as emergency contraception, a low dose of mifepristone is slightly less effective than higher doses, but has fewer side effects. , the smallest dose available in the USA was 200 mg. Mifepristone, however, is not approved for emergency contraceptive use in the United States. A review of studies in humans concluded that the contraceptive effects of the 10-mg dose are due to its effects on ovulation, but understanding of its mechanism of action remains incomplete. Higher doses of mifepristone can disrupt implantation and, unlike levonorgestrel, mifepristone can be effective in terminating established pregnancies.
explains the effectiveness calculation thus:
The progestin-only regimen (using levonorgestrel) is reported by the U.S. FDA to have an 89% effectiveness. , 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."
In 1999, a meta-analysis of eight studies of the combined (Yuzpe) regimen concluded that the best point estimate of effectiveness was 74%. A 2003 analysis of two of the largest combined (Yuzpe) regimen studies, using a different calculation method, found effectiveness estimates of 47% and 53%.
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.
While most studies of emergency contraception have only enrolled women within 72 hours of unprotected intercourse, a 2002 study by the World Health Organization
(WHO) suggested that reasonable effectiveness may continue for up to 120 hours (5 days) after intercourse.
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%. A review found that many trials found a regimen of 25–50 mg of mifepristone to have higher effectiveness. However, when reviewers looked at only high-quality trials, the difference in effectiveness was not statistically significant.
Placebo-controlled trials that could give a precise measure of the pregnancy rate without treatment would be unethical, so the effectiveness percentage is based on estimated pregnancy rates. These are currently estimated using variants of the calendar method.
Women with irregular cycles for any reason (including recent hormone use such as oral contraceptives and breastfeeding
) must be excluded from such calculations. Even for women included in the calculation, the limitations of calendar methods of fertility determination have long been recognized. In their April 2007 emergency review article, Trussell and Raymond note:
Recently, hormonal assay has been suggested as a more accurate method of estimating fertility for EC studies.
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.
The World Health Organization
(WHO) lists no medical condition for which the risks of emergency contraceptive pills outweigh the benefits. The American Academy of Pediatrics
(AAP) and experts on emergency contraception have concluded that progestin-only ECPs may be preferable to combined ECPs containing estrogen in women with a history of blood clots, stroke, or migraine.
The AAP, American College of Obstetricians and Gynecologists (ACOG), U.S. Food and Drug Administration
, WHO, Royal College of Obstetricians and Gynaecologists
, and other experts on emergency contraception state that there are no medical conditions in which progestin-only ECPs are contraindicated. RCOG specifically note current venous thromboembolism
, current or past history of breast cancer
, inflammatory bowel disease
, and acute intermittent porphyria
as conditions where the advantages of using emergency contraceptive pills generally outweigh the theoretical or proven risks.
The herbal preparation of St John's wort
and some enzyme-inducing drugs (e.g. anticonvulsant
s or rifampicin
) may reduce the effectiveness of ECP, and a larger dose may be required.
The AAP, ACOG, FDA, WHO, RCOG, and experts on emergency contraception have concluded that ECPs, like all other contraceptives, reduce the absolute risk of ectopic pregnancy
by preventing pregnancies, and that the best available evidence, obtained from over 7,800 women in randomized controlled trial
s, indicates there is no increase in the relative risk of ectopic pregnancy in women who become pregnant after using progestin-only ECPs.
(50.5% of 979 Yuzpe regimen users and 23.1% of 977 levonorgestrel-only users in the 1998 WHO trial; 14.3% of 2,720 levonorgestrel-only users in the 2002 WHO trial); vomiting
is much less common and unusual with levonorgestrel-only ECPs (18.8% of 979 Yuzpe regimen users and 5.6% of levonorgestrel-only users in the 1998 WHO trial; 1.4% of 2,720 levonorgestrel-only users in the 2002 WHO trial).
Anti-emetic
s are not routinely recommended with levonorgestrel-only ECPs.
If a woman vomits within 2 hours of taking a levonorgestrel-only ECP, she should take a further dose as soon as possible.
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
.
Side effects usually do not occur for more than a few days after treatment, and they generally resolve within 24 hours.
Temporary disruption of the menstrual cycle is also 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. If levonorgestrel is taken after ovulation, it may increase the length of the luteal phase
, thus delaying menstruation by a few days. Mifepristone, if taken before ovulation, may delay ovulation by 3–4 days. (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. If a woman's menstrual period is delayed by two weeks or more, it is advised that she take a pregnancy test
. (Earlier testing may not give accurate results.)
(IUD) which can be used up to 5 days after unprotected intercourse to prevent pregnancy. Insertion of an IUD is more effective than use of Emergency Contraceptive Pills - pregnancy rates when used as emergency contraception are the same as with normal IUD use. IUDs may be left in place following the subsequent menstruation to provide ongoing contraception (3–10 years depending upon type).
ECPs are generally recommended for backup or "emergency" use, rather than as the primary means of contraception. They are intended for use when other means of contraception have failed—for example, if a woman has forgotten to take a birth control pill or when a condom
is torn during sex.
The first widely used methods were five-day treatments with high-dose estrogens, using diethylstilbestrol (DES) in the US and ethinyl estradiol in the Netherlands.
In the early 1970s, the Yuzpe regimen was developed by AA Yuzpe (1974); progestin-only postcoital contraception was investigated (1975); and the copper IUD was first studied for use as emergency contraception (1975). 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.
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. Schering introduced a second prescription-only combined product, Tetragynon (ethinylestradiol and levonorgestrel) in Germany in 1985.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3774816 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.http://www.fda.gov/cder/foi/nda/99/21-045_Plan%20B_medr.pdfhttp://www.amwa-doc.org/index.cfm?objectid=1413E9D2-D567-0B25-593F3D9007E7AA63http://ec.princeton.edu/questions/dedicated.html 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.
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." After the WHO conducted a large trial comparing Yuzpe and levonorgestrel in 1998, 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.
United States & Canada
convened a meeting to discuss emergency contraception. After the meeting, a group of seven international organizations formed The International Consortium for Emergency Contraception (ICEC) to promote EC as a part of mainstream reproductive health care worldwide. Dedicated products for EC were "virtually unknown" in 1995, there was little awareness of EC as an option, and EC was not used as public health measure.
The seven founding member organizations were the Concept Foundation
, the International Planned Parenthood Federation
(IPPF), the Pacific Institute for Women's Health, the World Health Organization
(WHO), the Population Council
, Population Services International
, and the Program for Appropriate Technology in Health (PATH).
The Concept Foundation is the distribution arm of ICEC; its funding for the development of Postinor-2 came from the Rockefeller Foundation and the David and Lucile Packard Foundation
, as well as the other ICEC organizations.
The Consortium helped promote the availability of EC by:
An ICEC member organization, the International Planned Parenthood Federation (IPPF), has launched its own dedicated levonorgestrel EC product, Optinor.
Policy Statement on Emergency Contraception states: "The concern that widespread emergency contraception use would encourage unprotected coitus in teens is not supported in the literature."
The current (December 2005) ACOG Practice Bulletin on Emergency Contraception states: "A prominent concern among both women and health care providers is that making emergency contraception more readily available could encourage irresponsible sexual behavior, which would increase the risks of both unintended pregnancy
and sexually transmitted disease
s. However, numerous studies have shown that this concern is unfounded."
The latest (April 2007) review by emergency contraception experts Trussell and Raymond states: "Reported evidence demonstrates that making ECPs more widely available does not increase risk-taking
and that women who are the most diligent about ongoing contraceptive use are those most likely to seek emergency treatment."
However, the availability of ECPs has not been shown to lower abortion rates. In France, Sweden, and Britain—where Yuzpe-regimen EC had been available by prescription for more than a decade and progestin-only EC has been available without a prescription for 8, 6, and 2 years respectively—the abortion rate was stable or higher during that time period. Another study concluded that distribution of free, advance supplies of EC to large numbers of women in Scotland did not reduce abortion rates. A randomized controlled trial
of 2000 women in China compared women with advance access to EC to women without access, and noted that the pregnancy rate was the same between the two groups. The study observed that "...providing EC in advance increases use, but there is no direct evidence that it reduces unintended pregnancy" and concluded that EC may not lower abortion rates.
In September 2006, emergency contraception expert Anna Glasier wrote a BMJ
editorial entitled "Emergency Contraception. Is it worth all the fuss?" that said in closing: "So is emergency contraception worth the fuss? If you are a woman who has had unprotected sex then of course it is, because emergency contraception will prevent pregnancy in some women some of the time—and if you don’t want to get pregnant anything is better than nothing. If you are the CMAJ
’s editor or FDA commissioner then yes, because scientific freedom is worth the fight. If you are looking for an intervention that will reduce abortion rates, emergency contraception may not be the solution, and perhaps you should concentrate most on encouraging people to use contraception before or during sex, not after it."
Before EC was used in the general population or defined as "emergency contraception," it was used, beginning in the 1960s and 70s, specifically as a treatment for victims of sexual assault. Pregnancy rates among rape victims of child-bearing age are around 5%; in the U.S., about half of rape victims who become pregnant have abortions. Although EC is commonly used as an option for victims of sexual assault, some researchers believe such use is a public health measure that is not sufficiently widespread.
states that progestin-only ECPs like Plan B work by preventing ovulation. It also says "it is possible" that progestin-only ECPs may interfere with the blastocyst implanting in the uterine lining, and that they have no effect on pregnancies if taken after implantation.
A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the endometrium
that would prevent implantation of an early-stage embryo
in the uterus
. This research led many pro-life
advocates, who believe that pregnancy begins at fertilization
, to oppose ECPs as an abortifacient
.
In recent years—especially in light of U.S. ethical controversy over the research's claims—the scientific community has begun to critically reevaluate the early studies. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates. Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills, suggesting that might be the only mechanism by which they prevent pregnancy.
However, these studies have also shown that, in women who ovulate despite taking ECP before ovulation, there are changes in certain hormones such as progesterone and in the length of luteal phase
. These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying zygotes inside the uterus and fallopian tubes prior to implantation, both sides of this debate concede that completely proving or disproving the theory may be impossible.
When used as a regular method of contraception, IUDs have been proven to act primarily through spermicidal and ovicidal mechanisms, but it is considered possible that these same mechanisms are also harmful to zygotes that have not yet implanted.
Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as Yuzpe regimen
or Plan B differ from the anti-hormonal drug mifepristone
(also known as Mifeprex and RU-486). Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation, whereas mifepristone can induce abortion if taken after implantation.
(OTC) access to Plan B. Supporters of over-the-counter access believe that easier access will reduce unintended pregnancy and abortion rates; some abortion opponents believe that EC itself is a form of abortion. The American Medical Association
, the American Academy of Family Physicians
, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics
, and other leading U.S. medical organizations all supported OTC access. An advisory committee to the FDA recommended that Plan B be made available over the counter in 2003. In 2004, the FDA refused the advisory board's recommendation and prohibited over-the-counter sale, citing insufficient evidence that ECPs could be used safely by adolescents without medical supervision. Reproductive rights
supporters accused the FDA of basing the decision on political pressure from the pro-life lobby. The Center for Reproductive Rights filed a lawsuit regarding the approval process, which had not been resolved . In the legal proceedings, two senior FDA officials alleged in deposition
s that the decision to reject the OTC application was made on political, rather than scientific, grounds to "appease the administration's
constituents". Depositions taken from other FDA officials do not indicate White House involvement. In 2006, the FDA approved over-the-counter access to Plan B for women 18 years of age and older. In April 2009, the FDA followed the ruling of a New York Federal District Court and loosened the restrictions to allow Duramed Pharmaceuticals to provide Plan B without a prescription to 17-year-olds. However, as of June 2009, Duramed had not yet put a non-prescription Plan B product for 17-year-olds through FDA approval, a process that could take some time.
A Massachusetts
law that went into effect on 14 December 2005 requires all hospital
s in the state to provide emergency contraception to any "female rape victim of childbearing age" including Catholic Hospitals who oppose the provision of emergency contraception. In a letter criticizing the joint UN
/WHO
Inter-agency Field Manual on Reproductive Health in Refugee Situations, the Catholic Church explains its belief that emergency contraception, along with IUDs and hormonal
contraception
, cannot be considered "solely contraceptive because in the case of effective fertilization a chemical abortion would be carried out during the first days of pregnancy." The Catholic position on family planning is explained further in Ethical and Religious Directives for Catholic Health Care Services. Because of this expressed moral stance against emergency contraception, the Massachusetts Catholic Conference opposed this law, stating interference with religious freedom
. According to The New England Journal of Medicine, "compelling arguments can be made both for and against a pharmacist's right to refuse prescriptions for emergency contraception."
In isolated instances across the United States, pharmacists have refused to dispense emergency contraception even when presented with a legal prescription. In 2010, the Washington State Pharmacy Board decided that pharmacists do have a right to refuse to dispense emergency contraception. In addition, Wal-Mart
, the nation's fifth-largest distributor of pharmaceuticals, refused to stock EC, beginning with Preven in 1999. However, Wal-Mart reversed this position when it was announced that stores would sell Plan B in March 2006.
The Congregation for the Doctrine of the Faith
in the 2008 Instruction Dignitas Personae
(Paragraph 23) stated that: "Alongside methods of preventing pregnancy which are, properly speaking, contraceptive, that is, which prevent conception following from a sexual act, there are other technical means which act after fertilization, when the embryo is already constituted, either before or after implantation in the uterine wall. Such methods are interceptive if they interfere with the embryo before implantation and contragestative if they cause the elimination of the embryo once implanted...Therefore, the use of means of interception and contragestation fall within the sin of abortion and are gravely immoral. Furthermore, when there is certainty that an abortion has resulted, there are serious penalties in canon law."
Birth control
Birth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
measures that, if taken after sexual intercourse, may prevent pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
.
Forms of EC include:
- Emergency contraceptive pills (ECPs)—sometimes simply referred to as emergency contraceptives (ECs) or the "morning-after pill"—are drugs intended to disrupt ovulationOvulationOvulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
or fertilization in order to prevent pregnancy (contraceptives). There is controversy about whether such drugs may in some cases act not as a contraceptive but as a contragestive, a drug that prevents the implantation of a human embryo in the uterus, although one study has concluded that this mechanism is unlikely. - Intrauterine deviceIntrauterine deviceA copper IUD is a type of intrauterine device. Most IUDs have a plastic T- or U-shaped frame which is wrapped in copper wire, with the exception of Gynefix, which is a plastic string with several copper beads, affixed to the fundus of the uterus...
s (IUDs)—usually used as a primary contraceptive method, but sometimes used as emergency contraception.
Emergency contraceptive pills (ECPs)
Emergency contraceptive pills (sometimes referred to as emergency hormonal contraception (EHC) in Great Britain) may contain higher doseEffective dose
Effective dose may refer to:*Effective dose the dose of pharmacologic agent which will have a therapeutic effect in some fraction of the population receiving the drug...
s of the same hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s (estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s, progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
s, or both) found in regular combined oral contraceptive pills. Taken after unprotected sexual intercourse or contraceptive failure, such higher doses may prevent pregnancy from occurring. Mifepristone
Mifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
can also be used as EC, though this drug is not considered an "emergency contraceptive pill." It is an anti-hormonal drug, and does not contain estrogen or progestins.
The phrase "morning-after pill" is a misnomer; ECPs are effective when used shortly after intercourse. Depending on the drug, they are licensed for use for up to 107 to 120 hours after unprotected sexual intercourse or contraceptive failure.
Types of ECPs
The progestin-only method uses the progestin levonorgestrelLevonorgestrel
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
in a dose of 1.5 mg, either as two 750 μg doses 12 hours apart, or more recently as a single dose. Progestin-only EC is available as a dedicated emergency contraceptive product under many names worldwide, including: in the U.S., Canada and Honduras as Plan B; in Great Britain, Ireland, Australia, New Zealand, Portugal and Italy as Levonelle; in South Africa as Escapelle; in 44 nations including France, most of Western Europe, India, and several countries in Africa, Asia and Latin America as NorLevo; and in 44 nations including most of Eastern Europe, Mexico and many other Latin American countries, Portugal, Australia and New Zealand, Israel, China, Hong Kong, Taiwan and Singapore as Postinor-2. This pill typically works up to 72 hours after intercourse.
The combined or Yuzpe regimen
Yuzpe regimen
The Yuzpe Regimen is a method of emergency contraception using a combination of estrogen and progestogen hormones and started within 72 hours of sexual intercourse. It has been superseded by a progestogen-only hormonal regimen.-History:...
uses large doses of both estrogen and progestin, taken as two doses at a 12-hour interval. This method is now believed to be less effective and less well-tolerated than the progestin-only method.
It is possible to obtain the same dosage of hormones, and therefore the same effect, by taking several regular combined oral contraceptive pills
Oral contraceptive formulations
Oral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
. For example, 4 Ovral pills are the same as 4 Preven pills. The United States Food and Drug Administration (FDA) approved this off-label use of certain brands of regular combined oral contraceptive pills in 1997.
Ulipristal acetate
Ulipristal acetate
Ulipristal acetate is a selective progesterone receptor modulator for emergency contraception within 120 hours after an unprotected intercourse or contraceptive failure...
(known as ella in the US and Ellaone in Europe) was approved as an ECP in Europe in early 2009 and in the US in August 2010. It works for up to 120 hours after intercourse. It prevents pregnancy by delaying or inhibiting ovulation and inhibiting follicle rupture. Watson Pharmaceuticals
Watson Pharmaceuticals
Watson Pharmaceuticals, Incorporated is the 5th largest pharmaceutical company in the United States based on number of prescriptions dispensed...
announced the availability of ella in the United States on December 1, 2010, in retail pharmacies, clinics and one online pharmacy, KwikMed
KwikMed
KwikMed is an approved online pharmacy in the United States which has been granted regulatory approval to operate and sell medications online. Based in Salt Lake City, Utah, KwikMed's parent company, Phoenix Capital Management, is located in Scottsdale, Arizona...
.
Emergency contraceptive pills (ECPs) are not to be confused with mifepristone
Mifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
(RU486, Mifeprex), which is used as an "abortion pill". The term "emergency contraceptive pill" does not refer to mifespristone, which is most commonly used in 200- or 600-mg doses as an abortifacient. However, in China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
and Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
only, mifepristone is available as either emergency contraception or as an abortifacient
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
, depending on whether it is used before or after implantation. If used as emergency contraception, a low dose of mifepristone is slightly less effective than higher doses, but has fewer side effects. , the smallest dose available in the USA was 200 mg. Mifepristone, however, is not approved for emergency contraceptive use in the United States. A review of studies in humans concluded that the contraceptive effects of the 10-mg dose are due to its effects on ovulation, but understanding of its mechanism of action remains incomplete. Higher doses of mifepristone can disrupt implantation and, unlike levonorgestrel, mifepristone can be effective in terminating established pregnancies.
Effectiveness of ECPs
The effectiveness of emergency contraception is presented differently from the effectiveness of ongoing methods of birth control: it is expressed as a percentage reduction in pregnancy rate for a single use of EC. Different ECP regimens have different effectiveness levels, and even for a single regimen different studies may find varying rates of effectiveness. Using an example of "75% effective", an article in American Family PhysicianAmerican Family Physician
American Family Physician is a semimonthly, peer-reviewed medical journal of the American Academy of Family Physicians. AFP’s chief objective is to provide high-quality continuing medical education for more than 190,000 family physicians and other primary care clinicians...
explains 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.
The progestin-only regimen (using levonorgestrel) is reported by the U.S. FDA to have an 89% effectiveness. , 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."
In 1999, a meta-analysis of eight studies of the combined (Yuzpe) regimen concluded that the best point estimate of effectiveness was 74%. A 2003 analysis of two of the largest combined (Yuzpe) regimen studies, using a different calculation method, found effectiveness estimates of 47% and 53%.
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.
While most studies of emergency contraception have only enrolled women within 72 hours of unprotected intercourse, a 2002 study by the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) suggested that reasonable effectiveness may continue for up to 120 hours (5 days) after intercourse.
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%. A review found that many trials found a regimen of 25–50 mg of mifepristone to have higher effectiveness. However, when reviewers looked at only high-quality trials, the difference in effectiveness was not statistically significant.
History of calculation methods
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 without treatment.Placebo-controlled trials that could give a precise measure of the pregnancy rate without treatment would be unethical, so the effectiveness percentage is based on estimated pregnancy rates. These are currently estimated using variants of the calendar method.
Women with irregular cycles for any reason (including recent hormone use such as oral contraceptives and breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
) must be excluded from such calculations. Even for women included in the calculation, the limitations of calendar methods of fertility determination have long been recognized. In their April 2007 emergency review article, Trussell and Raymond note:
Calculation of effectiveness, and particularly the denominator of the fraction, involves many assumptions that are difficult to validate. Therefore, reported figures on the efficacy of emergency contraception may be underestimates or, more probably, overestimates. Yet, precise estimates of efficacy may not be highly relevant to many women who have had unprotected intercourse, since ECPs are often the only available treatment.
Recently, hormonal assay has been suggested as a more accurate method of estimating fertility for EC studies.
Safety
Existing pregnancy is not a contraindicationContraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
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
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
for a woman with a known or suspected pregnancy because it is not effective in women who are already pregnant.
The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) lists no medical condition for which the risks of emergency contraceptive pills outweigh the benefits. The American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
(AAP) and experts on emergency contraception have concluded that progestin-only ECPs may be preferable to combined ECPs containing estrogen in women with a history of blood clots, stroke, or migraine.
The AAP, American College of Obstetricians and Gynecologists (ACOG), U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
, WHO, Royal College of Obstetricians and Gynaecologists
Royal College of Obstetricians and Gynaecologists
The Royal College of Obstetricians and Gynaecologists is a professional association based in the UK. Its members, including people with and without medical degrees, work in the field of obstetrics and gynaecology, that is, pregnancy, childbirth, and female sexual and reproductive health...
, and other experts on emergency contraception state that there are no medical conditions in which progestin-only ECPs are contraindicated. RCOG specifically note current venous thromboembolism
Venous thrombosis
A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein. (Thrombosis is a medical term for blood clotting (Haemostasis) occurring in the wrong place, i.e...
, current or past history of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, and acute intermittent porphyria
Acute intermittent porphyria
Acute intermittent porphyria is a rare autosomal dominant metabolic disorder affecting the production of heme, the oxygen-binding prosthetic group of hemoglobin. It is characterized by a deficiency of the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the second most common...
as conditions where the advantages of using emergency contraceptive pills generally outweigh the theoretical or proven risks.
The herbal preparation of St John's wort
St John's wort
St John's wort is the plant species Hypericum perforatum, and is also known as Tipton's Weed, Chase-devil, or Klamath weed....
and some enzyme-inducing drugs (e.g. anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s or rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
) may reduce the effectiveness of ECP, and a larger dose may be required.
The AAP, ACOG, FDA, WHO, RCOG, and experts on emergency contraception have concluded that ECPs, like all other contraceptives, reduce the absolute risk of ectopic pregnancy
Ectopic pregnancy
An ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...
by preventing pregnancies, and that the best available evidence, obtained from over 7,800 women in randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s, indicates there is no increase in the relative risk of ectopic pregnancy in women who become pregnant after using progestin-only ECPs.
Side effects
The most common side effect reported by users of emergency contraceptive pills was nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
(50.5% of 979 Yuzpe regimen users and 23.1% of 977 levonorgestrel-only users in the 1998 WHO trial; 14.3% of 2,720 levonorgestrel-only users in the 2002 WHO trial); vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
is much less common and unusual with levonorgestrel-only ECPs (18.8% of 979 Yuzpe regimen users and 5.6% of levonorgestrel-only users in the 1998 WHO trial; 1.4% of 2,720 levonorgestrel-only users in the 2002 WHO trial).
Anti-emetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
s are not routinely recommended with levonorgestrel-only ECPs.
If a woman vomits within 2 hours of taking a levonorgestrel-only ECP, she should take a further dose as soon as possible.
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
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, and breast tenderness
Mastalgia
Mastodynia, mastalgia or mammalgia are names for a medical symptom that means breast pain .Pain can range from minor discomfort to severely incapacitating pain...
.
Side effects usually do not occur for more than a few days after treatment, and they generally resolve within 24 hours.
Temporary disruption of the menstrual cycle is also 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. If levonorgestrel is taken after ovulation, it may increase the length of the luteal phase
Luteal phase
The luteal phase is the latter phase of the menstrual cycle or the estrous cycle . It begins with the formation of the corpus luteum and ends in either pregnancy or luteolysis...
, thus delaying menstruation by a few days. Mifepristone, if taken before ovulation, may delay ovulation by 3–4 days. (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. If a woman's menstrual period is delayed by two weeks or more, it is advised that she take a pregnancy test
Pregnancy test
A pregnancy test attempts to determine whether or not a woman is pregnant.These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The first of these markers to be discovered, human chorionic gonadotropin , was discovered in 1930 to be produced by...
. (Earlier testing may not give accurate results.)
Intrauterine device (IUD) for emergency contraception
An alternative to emergency contraceptive pills is the copper-T intrauterine deviceIntrauterine device
A copper IUD is a type of intrauterine device. Most IUDs have a plastic T- or U-shaped frame which is wrapped in copper wire, with the exception of Gynefix, which is a plastic string with several copper beads, affixed to the fundus of the uterus...
(IUD) which can be used up to 5 days after unprotected intercourse to prevent pregnancy. Insertion of an IUD is more effective than use of Emergency Contraceptive Pills - pregnancy rates when used as emergency contraception are the same as with normal IUD use. IUDs may be left in place following the subsequent menstruation to provide ongoing contraception (3–10 years depending upon type).
Postcoital high-dose progestin-only oral contraceptive pills as ongoing contraception
One brand of levonorgestrel pills, Postinor, was marketed as an ongoing method of postcoital contraception. However, there are serious drawbacks to such use of postcoital high-dose progestin-only oral contraceptive pills, especially if they are not used according to their package directions, but are instead used according to the package directions of emergency contraceptive pills:- Due to the increasing severity of side effects with frequent use, Postinor is only recommended for women who have intercourse four or fewer times per month.
- If not used according to their package directions, but instead used according to the directions of levonorgestrel emergency contraceptive pills (up to 72 hours after intercourse), they would be estimated to have a "perfect-use" (when not used according to their package directions but used as directed on the package directions for levonorgestrel emergency contraception pills) pregnancy rate of 20% per year when used as the sole means of contraception (as compared to a 40% annual pregnancy rate for the Yuzpe regimen). These failure rates would be higher than those of almost all other birth control methods, including the rhythm method and withdrawalCoitus interruptusCoitus interruptus, also known as the rejected sexual intercourse, withdrawal or pull-out method, is a method of birth-control in which a man, during intercourse withdraws his penis from a woman's vagina prior to ejaculation...
. - Like all hormonal methods, postcoital high-dose progestin-only oral contraceptive pills do not protect against sexually transmitted infections.
ECPs are generally recommended for backup or "emergency" use, rather than as the primary means of contraception. They are intended for use when other means of contraception have failed—for example, if a woman has forgotten to take a birth control pill or when a condom
Condom
A condom is a barrier device most commonly used during sexual intercourse to reduce the probability of pregnancy and spreading sexually transmitted diseases . It is put on a man's erect penis and physically blocks ejaculated semen from entering the body of a sexual partner...
is torn during sex.
History
The use of synthetic estrogens as a post coital contraceptive was discovered by Dr. John McLean Morris in 1966. 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.The first widely used methods were five-day treatments with high-dose estrogens, using diethylstilbestrol (DES) in the US and ethinyl estradiol in the Netherlands.
In the early 1970s, the Yuzpe regimen was developed by AA Yuzpe (1974); progestin-only postcoital contraception was investigated (1975); and the copper IUD was first studied for use as emergency contraception (1975). Danazol
Danazol
Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. It was approved by the U.S. Food and Drug Administration as the...
was tested in the early 1980s in the hopes that it would have fewer side effects than Yuzpe, but was found to be ineffective.
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. Schering introduced a second prescription-only combined product, Tetragynon (ethinylestradiol and levonorgestrel) in Germany in 1985.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3774816 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.http://www.fda.gov/cder/foi/nda/99/21-045_Plan%20B_medr.pdfhttp://www.amwa-doc.org/index.cfm?objectid=1413E9D2-D567-0B25-593F3D9007E7AA63http://ec.princeton.edu/questions/dedicated.html 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.
Over time, interest in progestin-only treatments increased. The Special Program on Human Reproduction (HRP), an international organization whose members include the World Bank
World Bank
The World Bank is an international financial institution that provides loans to developing countries for capital programmes.The World Bank's official goal is the reduction of poverty...
and World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
, "played a pioneering role in emergency contraception" by "confirming the effectiveness of levonorgestrel." After the WHO conducted a large trial comparing Yuzpe and levonorgestrel in 1998, combined estrogen-progestin products were gradually withdrawn from some markets (Preven in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
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.
United States & Canada
- DESDiethylstilbestrolDiethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
- In 1971, a New England Journal of MedicineNew England Journal of MedicineThe New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
editorial calling attention to previously published studies on the use of DES as a postcoital contraceptive at Yale UniversityYale UniversityYale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
, and a large study published in JAMAJournal of the American Medical AssociationThe Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...
on the use of DES as a postcoital contraceptive at the University of MichiganUniversity of MichiganThe University of Michigan is a public research university located in Ann Arbor, Michigan in the United States. It is the state's oldest university and the flagship campus of the University of Michigan...
, led to off-label use of DES as a postcoital contraceptive becoming prevalent at many university health services. - In May 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive to emergency situations such as rapeRapeRape is a type of sexual assault usually involving sexual intercourse, which is initiated by one or more persons against another person without that person's consent. The act may be carried out by physical force, coercion, abuse of authority or with a person who is incapable of valid consent. The...
, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES. (In February 1975, the FDA Commissioner testified that the only error in the May 1973 FDA Drug Bulletin was that the FDA had not approved postcoital contraceptive use of DES.) - In September 1973, the FDA published a proposed rule specifying patient labeling and special packaging requirements for any manufacturer seeking FDA approval to market DES as a postcoital contraceptive, inviting manufacturers to submit abbreviated new drug applicationNew drug applicationThe New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
s (ANDAs) for that indication, and notifying manufacturers that the FDA intended to order the withdrawal of DES 25 mg tablets (which were being used off-label as postcoital contraceptives). - In late 1973, Eli LillyEli Lilly and CompanyEli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
, the largest U.S. manufacturer of DES, discontinued its DES 25 mg tablets and in March 1974 sent a letter to all U.S. physicians and pharmacists telling them it did not recommend use of DES as a postcoital contraceptive. - Only one pharmaceutical company, Tablicaps, Inc., a small manufacturer of generic drugGeneric drugA generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
s, ever submitted (in January 1974) an ANDA for use of DES as an emergency postcoital contraceptive, and the FDA never approved it. - In February 1975, the FDA said it had not yet approved DES as a postcoital contraceptive, but would after March 8, 1975 permit marketing of DES for that indication in emergency situations such as rape or incest if a manufacturer obtained an approved ANDA that provided patient labeling and special packaging as set out in a FDA final rule published in February 1975. To discourage off-label use of DES as a postcoital contraceptive, in February 1975 the FDA ordered DES 25 mg (and higher) tablets removed from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications be changed to state: "THIS DRUG PRODUCT SHOULD NOT BE USED AS A POSTCOITAL CONTRACEPTIVE" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label.
- In March 1978, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists which said: "FDA has not yet given approval for any manufacturer to market DES as a postcoital contraceptive. The Agency, however, will approve this indication for emergency situations such as rape or incest if a manufacturer provides patient labeling and special packaging. To discourage 'morning after' use of DES without patient labeling, FDA has removed from the market the 25 mg tablets of DES, formerly used for this purpose."
- In the 1980s, off-label use of the Yuzpe regimen superseded off-label use of DES for postcoital contraception.
- DES is no longer commercially available in the U.S.; Eli Lilly, the last U.S. manufacturer, ceased production in spring 1997.
- In 1971, a New England Journal of Medicine
- Yuzpe regimen & Preven
- On February 25, 1997, the FDA posted a notice in the Federal RegisterFederal RegisterThe Federal Register , abbreviated FR, or sometimes Fed. Reg.) is the official journal of the federal government of the United States that contains most routine publications and public notices of government agencies...
saying it had concluded that the Yuzpe regimen was safe and effective for off-label use as postcoital EC, was prepared to accept NDAs for COCPs labeled as ECPs, and listed 6 then available COCPs (there are now 22) that could be used as ECPs. - On September 1, 1998, the FDA approved the prescription Yuzpe regimen Preven Emergency Contraception Kit (which contained a urine pregnancy test and 4 COCPs). Preven was discontinued in May 2004.
- On February 25, 1997, the FDA posted a notice in the Federal Register
- Plan BLevonorgestrelLevonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
- On July 28, 1999, the FDA approved the prescription progestin-only Plan B (two 750 µg levonorgestrelLevonorgestrelLevonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
pills) emergency contraceptive. - On August 24, 2006, the FDA approved nonprescription behind-the-counter access to Plan B from pharmacies staffed by a licensed pharmacist for women 18 or older; a prescription-only form of Plan B was made available for younger females aged 17 and younger.
- On November 6, 2006, Barr PharmaceuticalsBarr PharmaceuticalsBarr Pharmaceuticals was a global specialty pharmaceutical company that operated in more than 30 countries worldwide. Barr were engaged in the development, manufacture and marketing of generic and proprietary pharmaceuticals, biopharmaceuticals and active pharmaceutical ingredients.-History:Barr...
announced that its subsidiary, Duramed Pharmaceuticals, had initiated shipment of dual-label Plan B OTC/Rx and it would be available in pharmacies across the U.S. by mid-November 2006. - On March 23, 2009, a US judge ordered the FDA to allow 17 year olds to acquire Plan B without a prescription. This now changes the August 24, 2006 ruling and Plan B is now available "behind the counter" for men and women. There is a prescription method available for girls under 17.
- On July 28, 1999, the FDA approved the prescription progestin-only Plan B (two 750 µg levonorgestrel
International Consortium for Emergency Contraception
In 1995, the Rockefeller FoundationRockefeller Foundation
The Rockefeller Foundation is a prominent philanthropic organization and private foundation based at 420 Fifth Avenue, New York City. The preeminent institution established by the six-generation Rockefeller family, it was founded by John D. Rockefeller , along with his son John D. Rockefeller, Jr...
convened a meeting to discuss emergency contraception. After the meeting, a group of seven international organizations formed The International Consortium for Emergency Contraception (ICEC) to promote EC as a part of mainstream reproductive health care worldwide. Dedicated products for EC were "virtually unknown" in 1995, there was little awareness of EC as an option, and EC was not used as public health measure.
The seven founding member organizations were the Concept Foundation
Concept Foundation
The Concept Foundation is a non-profit foundation which was established by the UNDP/UNFPA/WHO/WB Special program in Reproductive Health , PATH, the World Bank in 1989 in Bangkok, Thailand, "as a mechanism through which WHO’s rights associated with an injectable contraceptive, Cyclofem, could be...
, the International Planned Parenthood Federation
International Planned Parenthood Federation
The International Planned Parenthood Federation is a global non-governmental organization with the broad aims of promoting sexual and reproductive health, and advocating the right of individuals to make their own choices in family planning. It was first formed in 1952 in Bombay, India, and now...
(IPPF), the Pacific Institute for Women's Health, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO), the Population Council
Population Council
The Population Council is an international, nonprofit, non-governmental organization. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. One-third of its research relates to HIV and AIDS; its other major program...
, Population Services International
Population Services International
Population Services International is a global health organization with programs targeting malaria, child survival, HIV and reproductive health...
, and the Program for Appropriate Technology in Health (PATH).
The Concept Foundation is the distribution arm of ICEC; its funding for the development of Postinor-2 came from the Rockefeller Foundation and the David and Lucile Packard Foundation
David and Lucile Packard Foundation
The David and Lucile Packard Foundation is a private foundation that provides grants to not-for-profit organizations. It was created in 1964 by David Packard and his wife Lucile Salter Packard. Following David Packard's death in 1996, the Foundation became the beneficiary of part of his estate...
, as well as the other ICEC organizations.
The Consortium helped promote the availability of EC by:
- Manufacturing an EC product. The ICEC worked with the Hungarian pharmaceutical firm Gedeon Richter to repackage its contraceptive Postinor as an emergency contraceptive, called Postinor-2. Distributing Postinor-2, principally in developing countries, was the primary work of the ICEC.
- Facilitating product registration in two ways. First, the ICEC encouraged interest in EC products through meetings with public-sector agencies and non-governmental organizations (NGOs) who they perceived would benefit from adding EC to the products they distribute. Second, by helping organizations applying for EC registration through the country-specific approval process, including lobbying of local leaders who may be influential in the registration decision.
- Negtiotiating a public-sector price. The ICEC's agreement with Gedeon Richter provided a discount price at which EC could be obtained by public-sector agencies in developing countries.
- Marketing and social marketingSocial marketingSocial marketing is the systematic application of marketing, along with other concepts and techniques, to achieve specific behavioral goals for a social good. Social marketing can be applied to promote merit goods, or to make a society avoid demerit goods and thus to promote society's well being as...
.
An ICEC member organization, the International Planned Parenthood Federation (IPPF), has launched its own dedicated levonorgestrel EC product, Optinor.
Relationship to high risk sex and abortion
The current (October 2005) AAPAmerican Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
Policy Statement on Emergency Contraception states: "The concern that widespread emergency contraception use would encourage unprotected coitus in teens is not supported in the literature."
The current (December 2005) ACOG Practice Bulletin on Emergency Contraception states: "A prominent concern among both women and health care providers is that making emergency contraception more readily available could encourage irresponsible sexual behavior, which would increase the risks of both unintended pregnancy
Unintended pregnancy
Unintended pregnancies are those in which conception was not intended by the female sexual partner. Worldwide, 38% of pregnancies were unintended in 1999 . Unintended pregnancies are the primary cause of induced abortion, resulting in about 42 million induced abortions per year...
and sexually transmitted disease
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
s. However, numerous studies have shown that this concern is unfounded."
The latest (April 2007) review by emergency contraception experts Trussell and Raymond states: "Reported evidence demonstrates that making ECPs more widely available does not increase risk-taking
and that women who are the most diligent about ongoing contraceptive use are those most likely to seek emergency treatment."
However, the availability of ECPs has not been shown to lower abortion rates. In France, Sweden, and Britain—where Yuzpe-regimen EC had been available by prescription for more than a decade and progestin-only EC has been available without a prescription for 8, 6, and 2 years respectively—the abortion rate was stable or higher during that time period. Another study concluded that distribution of free, advance supplies of EC to large numbers of women in Scotland did not reduce abortion rates. A randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
of 2000 women in China compared women with advance access to EC to women without access, and noted that the pregnancy rate was the same between the two groups. The study observed that "...providing EC in advance increases use, but there is no direct evidence that it reduces unintended pregnancy" and concluded that EC may not lower abortion rates.
In September 2006, emergency contraception expert Anna Glasier wrote a BMJ
British Medical Journal
BMJ is a partially open-access peer-reviewed medical journal. Originally called the British Medical Journal, the title was officially shortened to BMJ in 1988. The journal is published by the BMJ Group, a wholly owned subsidiary of the British Medical Association...
editorial entitled "Emergency Contraception. Is it worth all the fuss?" that said in closing: "So is emergency contraception worth the fuss? If you are a woman who has had unprotected sex then of course it is, because emergency contraception will prevent pregnancy in some women some of the time—and if you don’t want to get pregnant anything is better than nothing. If you are the CMAJ
Canadian Medical Association Journal
The Canadian Medical Association Journal is a general medical journal that is published biweekly by the Canadian Medical Association . It covers research and ideas aimed at improving health for people in Canada and globally. CMAJ publishes original clinical research, analyses and reviews, news,...
’s editor or FDA commissioner then yes, because scientific freedom is worth the fight. If you are looking for an intervention that will reduce abortion rates, emergency contraception may not be the solution, and perhaps you should concentrate most on encouraging people to use contraception before or during sex, not after it."
EC and sexual assault
Before EC was used in the general population or defined as "emergency contraception," it was used, beginning in the 1960s and 70s, specifically as a treatment for victims of sexual assault. Pregnancy rates among rape victims of child-bearing age are around 5%; in the U.S., about half of rape victims who become pregnant have abortions. Although EC is commonly used as an option for victims of sexual assault, some researchers believe such use is a public health measure that is not sufficiently widespread.
Mechanism of action
The United States FDAFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
states that progestin-only ECPs like Plan B work by preventing ovulation. It also says "it is possible" that progestin-only ECPs may interfere with the blastocyst implanting in the uterine lining, and that they have no effect on pregnancies if taken after implantation.
A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
that would prevent implantation of an early-stage embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
in the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
. This research led many pro-life
Pro-life
Opposition to the legalization of abortion is centered around the pro-life, or anti-abortion, movement, a social and political movement opposing elective abortion on moral grounds and supporting its legal prohibition or restriction...
advocates, who believe that pregnancy begins at fertilization
Beginning of pregnancy controversy
Controversy over the beginning of pregnancy usually occurs in the context of the abortion debate. Depending on where pregnancy is considered to begin, some methods of birth control or infertility treatment might be considered abortifacient...
, to oppose ECPs as an abortifacient
Abortifacient
An abortifacient is a substance that induces abortion. Abortifacients for animals that have mated undesirably are known as mismating shots....
.
In recent years—especially in light of U.S. ethical controversy over the research's claims—the scientific community has begun to critically reevaluate the early studies. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates. Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills, suggesting that might be the only mechanism by which they prevent pregnancy.
However, these studies have also shown that, in women who ovulate despite taking ECP before ovulation, there are changes in certain hormones such as progesterone and in the length of luteal phase
Luteal phase
The luteal phase is the latter phase of the menstrual cycle or the estrous cycle . It begins with the formation of the corpus luteum and ends in either pregnancy or luteolysis...
. These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying zygotes inside the uterus and fallopian tubes prior to implantation, both sides of this debate concede that completely proving or disproving the theory may be impossible.
When used as a regular method of contraception, IUDs have been proven to act primarily through spermicidal and ovicidal mechanisms, but it is considered possible that these same mechanisms are also harmful to zygotes that have not yet implanted.
Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as Yuzpe regimen
Yuzpe regimen
The Yuzpe Regimen is a method of emergency contraception using a combination of estrogen and progestogen hormones and started within 72 hours of sexual intercourse. It has been superseded by a progestogen-only hormonal regimen.-History:...
or Plan B differ from the anti-hormonal drug mifepristone
Mifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
(also known as Mifeprex and RU-486). Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation, whereas mifepristone can induce abortion if taken after implantation.
United States legal and ethical controversies
A great deal of controversy accompanied the FDA approval of over-the-counterOver-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
(OTC) access to Plan B. Supporters of over-the-counter access believe that easier access will reduce unintended pregnancy and abortion rates; some abortion opponents believe that EC itself is a form of abortion. The American Medical Association
American Medical Association
The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
, the American Academy of Family Physicians
American Academy of Family Physicians
The American Academy of Family Physicians was founded in 1947 to promote the science and art of family medicine. It is one of the largest medical organizations in the United States, with over 100,000 members...
, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
, and other leading U.S. medical organizations all supported OTC access. An advisory committee to the FDA recommended that Plan B be made available over the counter in 2003. In 2004, the FDA refused the advisory board's recommendation and prohibited over-the-counter sale, citing insufficient evidence that ECPs could be used safely by adolescents without medical supervision. Reproductive rights
Reproductive rights
Reproductive rights are legal rights and freedoms relating to reproduction and reproductive health. The World Health Organization defines reproductive rights as follows:...
supporters accused the FDA of basing the decision on political pressure from the pro-life lobby. The Center for Reproductive Rights filed a lawsuit regarding the approval process, which had not been resolved . In the legal proceedings, two senior FDA officials alleged in deposition
Deposition (law)
In the law of the United States, a deposition is the out-of-court oral testimony of a witness that is reduced to writing for later use in court or for discovery purposes. It is commonly used in litigation in the United States and Canada and is almost always conducted outside of court by the...
s that the decision to reject the OTC application was made on political, rather than scientific, grounds to "appease the administration's
George W. Bush administration
The presidency of George W. Bush began on January 20, 2001, when he was inaugurated as the 43rd President of the United States of America. The oldest son of former president George H. W. Bush, George W...
constituents". Depositions taken from other FDA officials do not indicate White House involvement. In 2006, the FDA approved over-the-counter access to Plan B for women 18 years of age and older. In April 2009, the FDA followed the ruling of a New York Federal District Court and loosened the restrictions to allow Duramed Pharmaceuticals to provide Plan B without a prescription to 17-year-olds. However, as of June 2009, Duramed had not yet put a non-prescription Plan B product for 17-year-olds through FDA approval, a process that could take some time.
A Massachusetts
Massachusetts
The Commonwealth of Massachusetts is a state in the New England region of the northeastern United States of America. It is bordered by Rhode Island and Connecticut to the south, New York to the west, and Vermont and New Hampshire to the north; at its east lies the Atlantic Ocean. As of the 2010...
law that went into effect on 14 December 2005 requires all hospital
Hospital
A hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....
s in the state to provide emergency contraception to any "female rape victim of childbearing age" including Catholic Hospitals who oppose the provision of emergency contraception. In a letter criticizing the joint UN
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...
/WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
Inter-agency Field Manual on Reproductive Health in Refugee Situations, the Catholic Church explains its belief that emergency contraception, along with IUDs and hormonal
Progestagen
Progestogens are a group of hormones including progesterone.The progestogens are one of the five major classes of steroid hormones, in addition to the estrogens, androgens, mineralocorticoids, and glucocorticoids. All progestogens are characterized by their basic 21-carbon skeleton, called a...
contraception
Birth control
Birth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
, cannot be considered "solely contraceptive because in the case of effective fertilization a chemical abortion would be carried out during the first days of pregnancy." The Catholic position on family planning is explained further in Ethical and Religious Directives for Catholic Health Care Services. Because of this expressed moral stance against emergency contraception, the Massachusetts Catholic Conference opposed this law, stating interference with religious freedom
Freedom of religion
Freedom of religion is a principle that supports the freedom of an individual or community, in public or private, to manifest religion or belief in teaching, practice, worship, and observance; the concept is generally recognized also to include the freedom to change religion or not to follow any...
. According to The New England Journal of Medicine, "compelling arguments can be made both for and against a pharmacist's right to refuse prescriptions for emergency contraception."
In isolated instances across the United States, pharmacists have refused to dispense emergency contraception even when presented with a legal prescription. In 2010, the Washington State Pharmacy Board decided that pharmacists do have a right to refuse to dispense emergency contraception. In addition, Wal-Mart
Wal-Mart
Wal-Mart Stores, Inc. , branded as Walmart since 2008 and Wal-Mart before then, is an American public multinational corporation that runs chains of large discount department stores and warehouse stores. The company is the world's 18th largest public corporation, according to the Forbes Global 2000...
, the nation's fifth-largest distributor of pharmaceuticals, refused to stock EC, beginning with Preven in 1999. However, Wal-Mart reversed this position when it was announced that stores would sell Plan B in March 2006.
The Congregation for the Doctrine of the Faith
Congregation for the Doctrine of the Faith
The Congregation for the Doctrine of the Faith , previously known as the Supreme Sacred Congregation of the Roman and Universal Inquisition , and after 1904 called the Supreme...
in the 2008 Instruction Dignitas Personae
Dignitas Personae
Dignitas Personae is the title of a 2008 instruction by the Congregation for the Doctrine of the Faith giving doctrinal directives on certain embryonic ethical controversies that had emerged since 1987, after Donum Vitae was released....
(Paragraph 23) stated that: "Alongside methods of preventing pregnancy which are, properly speaking, contraceptive, that is, which prevent conception following from a sexual act, there are other technical means which act after fertilization, when the embryo is already constituted, either before or after implantation in the uterine wall. Such methods are interceptive if they interfere with the embryo before implantation and contragestative if they cause the elimination of the embryo once implanted...Therefore, the use of means of interception and contragestation fall within the sin of abortion and are gravely immoral. Furthermore, when there is certainty that an abortion has resulted, there are serious penalties in canon law."
See also
- Rape crisis center
- Ulipristal acetateUlipristal acetateUlipristal acetate is a selective progesterone receptor modulator for emergency contraception within 120 hours after an unprotected intercourse or contraceptive failure...
- Another emergency contraceptive, marketed as Ella, was approved in the U.S. in 2010, and is effective up to five days after sex
External links
- The Emergency Contraception Website (not-2-late.com) by the Office of Population ResearchOffice of Population ResearchThe Office of Population Research at Princeton University is the oldest population research center in the United States. It was founded in 1936....
at Princeton UniversityPrinceton UniversityPrinceton University is a private research university located in Princeton, New Jersey, United States. The school is one of the eight universities of the Ivy League, and is one of the nine Colonial Colleges founded before the American Revolution....
and the Association of Reproductive Health ProfessionalsAssociation of Reproductive Health ProfessionalsThe Association of Reproductive Health Professionals is a non-profit organization founded in 1963 by Alan Frank Guttmacher. It is a membership association with members who are nurse practitioners, nurse midwives, pharmacists, physician assistants, physicians, researchers, educators, and other...
- International Consortium for Emergency Contraception
- Emergency contraception by the Adolescent Medicine Committee, Canadian Pediatric Society (CPS), Paediatrics and Child Health ACSA-CAAH