Emergency contraception mechanism of action: Difference between revisions

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==Mechanism of action==
==Mechanism of action==
A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the [[endometrium]]<ref>{{cite journal | author=Ling WY, Robichaud A, Zayid I, Wrixon W, MacLeod SC | title=Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception | journal=Fertil Steril | year=1983 |pages=631-6 | volume=40| issue=5 | id=PMID 6628707}}<br />{{cite journal | author=Kubba AA, White JO, Guillebaud J, Elder MG | title=The biochemistry of human endometrium after two regimens of postcoital contraception: a dl-norgestrel/ethinylestradiol combination or danazol | journal=Fertil Steril | year=1986 | pages=512-516 | volume=45 |issue=4 | id=PMID 3956767}}<br />{{cite journal | author=Yuzpe AA, Thurlow HJ, Ramzy I, Leyshon JI | title=Post coital contraception—a pilot study | journal=J Reprod Med |year=1974 | pages=53-8 | volume=13 | issue=2|id=PMID 4844513}}</ref> that would prevent implantation of an early-stage [[embryo]] in the [[uterus]]. This research led many[[pro-life]] advocates, who believe that [[beginning of pregnancy controversy|pregnancy begins at fertilization]], to oppose ECPs as an [[abortifacient]].
A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the [[endometrium]]<ref>{{cite journal | author=Ling WY, Robichaud A, Zayid I, Wrixon W, MacLeod SC | title=Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception | journal=Fertil Steril | year=1983 |pages=631-6 | volume=40| issue=5 | id=PMID 6628707}}<br />{{cite journal | author=Kubba AA, White JO, Guillebaud J, Elder MG | title=The biochemistry of human endometrium after two regimens of postcoital contraception: a dl-norgestrel/ethinylestradiol combination or danazol | journal=Fertil Steril | year=1986 | pages=512-516 | volume=45 |issue=4 | id=PMID 3956767}}<br />{{cite journal | author=Yuzpe AA, Thurlow HJ, Ramzy I, Leyshon JI | title=Post coital contraception—a pilot study | journal=J Reprod Med |year=1974 | pages=53-8 | volume=13 | issue=2|id=PMID 4844513}}</ref> that would prevent implantation of an early-stage [[embryo]] in the [[uterus]]. This research led many [[pro-life]] advocates, who believe that [[beginning of pregnancy controversy|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, introducing doubt into the argument that ECPs prevent implantation. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates.<ref>{{cite journal | author = Ortiz ME, Ortiz RE, Fuentes MA, Parraguez VH, Croxatto HB | title = Post-coital administration of levonorgestrel does not interfere with post-fertilization events in the new-world monkey ''Cebus apella'' | journal = Human Reproduction | volume = 19 | issue = 6 | pages = 1352-1356 | publisher = European Society of Human Reproduction and Embryology | date = June 2004 | url = http://humrep.oxfordjournals.org/cgi/content/abstract/19/6/1352 | accessdate = 2007-04-11}}</ref> Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills,<ref name="cycle day">{{cite journal | author=Durand M, del Carmen Cravioto M, Raymond EG, Duran-Sanchez O, De la Luz Cruz-Hinojosa M, Castell-Rodriguez A, Schiavon R, Larrea F | title=On the mechanisms of action of short-term levonorgestrel administration in emergency contraception | journal=Contraception | year=2001 | pages=227-34 | volume=64 | issue=4 |id=PMID 11747872}}</ref><ref>{{cite journal | author = Croxatto HB, Brache V, Pavez M, Cochon L, Forcelledo ML, Alvarez F, Massai R, Faundes A, Salvatierra AM | title = Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation | journal = Contraception | volume = 70 | issue = 6 | pages = 442-450 | date = December 2004 | id=PMID 15541405 }}</ref> suggesting that might be the only mechanism by which they prevent pregnancy.
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, introducing doubt into the argument that ECPs prevent implantation. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates.<ref>{{cite journal | author = Ortiz ME, Ortiz RE, Fuentes MA, Parraguez VH, Croxatto HB | title = Post-coital administration of levonorgestrel does not interfere with post-fertilization events in the new-world monkey ''Cebus apella'' | journal = Human Reproduction | volume = 19 | issue = 6 | pages = 1352-1356 | publisher = European Society of Human Reproduction and Embryology | date = June 2004 | url = http://humrep.oxfordjournals.org/cgi/content/abstract/19/6/1352 | accessdate = 2007-04-11}}</ref> Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills,<ref name="cycle day">{{cite journal | author=Durand M, del Carmen Cravioto M, Raymond EG, Duran-Sanchez O, De la Luz Cruz-Hinojosa M, Castell-Rodriguez A, Schiavon R, Larrea F | title=On the mechanisms of action of short-term levonorgestrel administration in emergency contraception | journal=Contraception | year=2001 | pages=227-34 | volume=64 | issue=4 |id=PMID 11747872}}</ref><ref>{{cite journal | author = Croxatto HB, Brache V, Pavez M, Cochon L, Forcelledo ML, Alvarez F, Massai R, Faundes A, Salvatierra AM | title = Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation | journal = Contraception | volume = 70 | issue = 6 | pages = 442-450 | date = December 2004 | id=PMID 15541405 }}</ref> suggesting that might be the only mechanism by which they prevent pregnancy.
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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]].<ref name="cycle day" /> These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying embryos 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.
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]].<ref name="cycle day" /> These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying embryos 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.


The Food and Drug Administration recently stopped its practice<ref>{{cite web | title = FDA's Decision Regarding Plan B: Questions and Answers | date = 2004-05-07 |publisher = Center for Drug Evaluation and Research | url = http://www.fda.gov/cder/drug/infopage/planB/planBQandA.htm| | accessdate = 2006-08-25}}</ref> of referring to all three mechanisms in its publications on emergency contraception.<ref>{{cite web | title = FDA's Decision Regarding Plan B: Questions and Answers: August 24, 2006 | date = 2006-08-24 | publisher = Center for Drug Evaluation and Research | url = http://www.fda.gov/cder/drug/infopage/planB/planBQandA20060824.htm| accessdate = 2006-08-25}}</ref> However, the approved box design for Plan B still carries a notification that it may prevent implantation.<ref>{{cite web | last = Galson | first = Stephen | title = Notification to Duramed Research, Inc. of FDA Approval of Plan B | date = 2006-08-24 | format = PDF | publisher = Center for Drug Evaluation and Research | url =http://www.fda.gov/cder/drug/infopage/planB/approval.pdf | accessdate = 2006-08-25}}</ref>
The Food and Drug Administration recently stopped its practice of referring to all three mechanisms in its publications on emergency contraception.


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 embryos that have not yet implanted.<ref>{{cite web | title = Mechanisms of the Contraceptive Action of Hormonal Methods and Intrauterine Devices (IUDs) | work = Family Health International | year = 2006 | url = http://www.fhi.org/en/RH/Pubs/booksReports/methodaction.htm | accessdate = 2006-07-05 }}<br />{{cite web | last = Keller | first = Sarah | title = IUDs Block Fertilization | work = Network | publisher = Family Health International | year = Winter 1996, Vol. 16, No. 2 | url = http://www.fhi.org/en}}</ref>
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 embryos that have not yet implanted.


Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as [[Yuzpe regimen]] or Plan B are different from the anti-hormonal drug[[mifepristone]] (also known as Mifeprex and RU-486), an abortifacient which can induce abortion if taken after implantation. Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation.
Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as [[Yuzpe regimen]] or Plan B are different from the anti-hormonal drug[[mifepristone]] (also known as Mifeprex and RU-486), an abortifacient which can induce abortion if taken after implantation. Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation.
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==References==
==References==
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Latest revision as of 21:33, 29 July 2020

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Mechanism of action

A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the endometrium[1] 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, introducing doubt into the argument that ECPs prevent implantation. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates.[2] Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills,[3][4] 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.[3] These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying embryos 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.

The Food and Drug Administration recently stopped its practice of referring to all three mechanisms in its publications on emergency contraception.

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 embryos that have not yet implanted.

Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as Yuzpe regimen or Plan B are different from the anti-hormonal drugmifepristone (also known as Mifeprex and RU-486), an abortifacient which can induce abortion if taken after implantation. Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation.

References

  1. Ling WY, Robichaud A, Zayid I, Wrixon W, MacLeod SC (1983). "Mode of action of dl-norgestrel and ethinylestradiol combination in postcoital contraception". Fertil Steril. 40 (5): 631–6. PMID 6628707.
    Kubba AA, White JO, Guillebaud J, Elder MG (1986). "The biochemistry of human endometrium after two regimens of postcoital contraception: a dl-norgestrel/ethinylestradiol combination or danazol". Fertil Steril. 45 (4): 512–516. PMID 3956767.
    Yuzpe AA, Thurlow HJ, Ramzy I, Leyshon JI (1974). "Post coital contraception—a pilot study". J Reprod Med. 13 (2): 53–8. PMID 4844513.
  2. Ortiz ME, Ortiz RE, Fuentes MA, Parraguez VH, Croxatto HB (June 2004). "Post-coital administration of levonorgestrel does not interfere with post-fertilization events in the new-world monkey Cebus apella". Human Reproduction. European Society of Human Reproduction and Embryology. 19 (6): 1352–1356. Retrieved 2007-04-11.
  3. 3.0 3.1 Durand M, del Carmen Cravioto M, Raymond EG, Duran-Sanchez O, De la Luz Cruz-Hinojosa M, Castell-Rodriguez A, Schiavon R, Larrea F (2001). "On the mechanisms of action of short-term levonorgestrel administration in emergency contraception". Contraception. 64 (4): 227–34. PMID 11747872.
  4. Croxatto HB, Brache V, Pavez M, Cochon L, Forcelledo ML, Alvarez F, Massai R, Faundes A, Salvatierra AM (December 2004). "Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation". Contraception. 70 (6): 442–450. PMID 15541405.

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