More fun with EC

[ultracet]

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Found this article regarding Plan B....

thought you all might be interested...

http://www.uspharmacist.com/index.asp?show=article&page=8_1567.htm

 

[Caverject]

Great article!

 

[ultracet]

This topic is so funny at my school...

I am amazed at how many "educated" pharmacy students take an ignorant position when it comes to Plan B...

I know that we are very early in the "comment period" but has anything been said about this really so far?

 

[Caverject]

Nothing has been posted as of yet, but comments can be made at the following link

http://www.accessdata.fda.gov/scrip...C_DOCUMENT_ID=750&SUBTYP=NEXT&CID=&AGENCY=FDA

 

[28657]

Great article!

What is it that makes this article so great? There is nothing revolutionary or new this article added. Just my 2 cents! 😛

 

[bananaface]

I keep hearing over and over in class that Plan B (when used sparingly, I suppose...) ought not to have thickening of the cervical mucus listed as an MOA, as this is an effect only seen after a patient has been on a progesterone for a more extensive time period than a single day.

I also don't like the part where it is implied that another MOA is involved because a 70-80% rate of ovulation suppression for Plan B leads to 90% efficacy. Does anyone ever stop to think that not every act of sexual intercourse leads to pregnancy, barring human intervention? Or, that many of these women have pre-existing thickened cervical mucus due to oral contraceptive use? Anyway, I just have issues with using those stats as the basis for inferring the existence of another MOA.

*climbs off soapbox*

 

[Caverject]

I keep hearing over and over in class that Plan B (when used sparingly, I suppose...) ought not to have thickening of the cervical mucus listed as an MOA, as this is an effect only seen after a patient has been on a progesterone for a more extensive time period than a single day.

You keep saying it over and over again, however you are the only one and not only that, you never give any evidence other than your teacher told you so.

What is it that makes this article so great? There is nothing revolutionary or new this article added. Just my 2 cents!

Thats why it's called a review article! It's good for people that talk out of their derrieres and have no idea what they are talking about! 🙂

 

[bananaface]

You keep saying it over and over again, however you are the only one and not only that, you never give any evidence other than your teacher told you so.

http://www.ncbi.nlm.nih.gov/entrez/...&dopt=Abstract&list_uids=14668003&query_hl=18

I would look at the articles this one reviewed, but it's time for me to go to work.

 

[ultracet]

I keep hearing over and over in class that Plan B (when used sparingly, I suppose...) ought not to have thickening of the cervical mucus listed as an MOA, as this is an effect only seen after a patient has been on a progesterone for a more extensive time period than a single day.

hmm... i wasn't able to access the article you recommended so i can't really look to see what articles you were talking about.

i did a brief (read very brief) search and found that the effects of progesterone on cervical mucus were seen as early as the first 24 hours.

Do you mind posting some of the citations to the others that you are referring to?


I do agree with your point about pregnancy not occuring every time you have sex.

 

[bananaface]

hmm... i wasn't able to access the article you recommended so i can't really look to see what articles you were talking about.

i did a brief (read very brief) search and found that the effects of progesterone on cervical mucus were seen as early as the first 24 hours.

Do you mind posting some of the citations to the others that you are referring to?


I do agree with your point about pregnancy not occuring every time you have sex.

Odd. I thought everyone could get to it as it's just on pubmed. You have to watch out when you do your search. Articles on the depot preps are more common but less relevant than those involving single day dosing. I'm gonna dig up some more stuff. Here is the abstract for the article I linked to, for those who can't access it.

Steroids. 2003 Nov;68(10-13):1095-8.
Mechanisms of action of emergency contraception.

Croxatto HB, Ortiz ME, Muller AL.

Instituto Chileno de Medicina Reproductiva, Jose Ramon Gutierrez 295, Dpto. 3, Santiago, Chile. [email protected]

The use of levonorgestrel (LNG) alone or combined with ethinylestradiol (Yuzpe regimen), for hormonal emergency contraception (HEC) has been approved in several countries whereas in others it is still under debate or has been rejected under the claim that these formulations abort the developmental potential of the embryo. The issue is whether they act by preventing fertilization or by impeding the successful development of the zygote through and beyond implantation. Until now, published work has left this issue largely unresolved, and this paucity of knowledge sustains heated controversies in many settings. A single study indicates that LNG impairs sperm migration in the genital tract of women in ways that could interfere with fertilization. Several studies in women examined the effects of HEC on the outcome of the leading follicle, but lack of precision in the timing of treatment relative to follicular growth, maturation, or rupture confers great variability and inconsistency of results within and between studies. Nonetheless, results indicate that ovulatory dysfunction may account for the prevention of pregnancy in a large proportion of cases. Studies searching for possible alterations of the endometrium at the time implantation would normally take place, found minimal changes of doubtful significance. Recent studies in animals cast serious doubts that LNG prevents pregnancy by interfering with post-fertilization events. Failure to prevent expected pregnancies is close to 25% in women, and this is likely to be accounted for entirely by treatment given too late to prevent fertilization. The exact mode of action of HEC remains undetermined.

 

[bananaface]

more

Contraception. 2003 May;67(5):415-9. Postcoital treatment with levonorgestrel does not disrupt postfertilization events in the rat. Muller AL, Llados CM, Croxatto HB.

Pontificia Universidad Catolica de Chile, Facultad de Ciencias Biologicas, Unidad de Reproduccion y Desarrollo, Av. Alameda Bernardo O'Higgins 340, Santiago, Chile.

Levonorgestrel (LNG), a progestin widely used for regular hormonal contraception, is also used for emergency contraception (EC) to prevent pregnancy after unprotected intercourse. However, its mode of action in EC is only partially understood. One unresolved question is whether or not EC prevents pregnancy by interfering with postfertilization events. Here, we report the effects of acute treatment with LNG upon ovulation, fertilization and implantation in the rat. LNG inhibited ovulation totally or partially, depending on the timing of treatment and/or total dose administered, whereas it had no effect on fertilization or implantation when it was administered shortly before or after mating, or before implantation. It is concluded that acute postcoital administration of LNG at doses several-fold higher than those used for EC in women, which are able to inhibit ovulation, had no postfertilization effect that impairs fertility in the rat.

PMID: 12742567 [PubMed - indexed for MEDLINE]

 

[bananaface]

more

Hum Reprod. 2004 Jun;19(6):1352-6. Epub 2004 Apr 22. Related Articles, Links

Comment in:

* Hum Reprod. 2005 May;20(5):1428; author reply 1428-9.

Click here to read
Post-coital administration of levonorgestrel does not interfere with post-fertilization events in the new-world monkey Cebus apella.

Ortiz ME, Ortiz RE, Fuentes MA, Parraguez VH, Croxatto HB.

Unit of Reproductive Biology and Development, Faculty of Biological Sciences, Catholic University of Chile, Chile. [email protected]

BACKGROUND: Experimental evidence to disprove the belief that emergency contraception with levonorgestrel (LNG) prevents pregnancy by interfering with post-fertilization events is lacking. Here we determined the effect of post-coital and pre-ovulatory administration of LNG on fertility and ovulation, respectively, in the Cebus monkey. METHODS: To determine the effect on fertility, LNG 0.75 mg or vehicle were administered orally or s.c. once or twice within the first 24 h after mating occurring very close to the time of ovulation. Females that became pregnant were aborted with mifepristone and re-entered the study after a resting cycle until each of 12 females had contributed, in a randomized order, two LNG and two vehicle-treated cycles. To determine the effect on ovulation, LNG 0.75 mg or vehicle were injected twice coinciding with follicles smaller or larger than 5 mm in diameter. Six females contributed five treated cycles each. RESULTS: The pregnancy rate was identical in vehicle- and LNG-treated cycles. LNG inhibited or delayed ovulation only when treatment coincided with a follicle <5 mm diameter. CONCLUSION: In Cebus monkeys, LNG can inhibit or delay ovulation but, once fertilization has taken place, it cannot prevent the establishment of pregnancy. These findings do not support the hypothesis that emergency contraception with LNG prevents pregnancy by interfering with post-fertilization events.

PMID: 15105392 [PubMed - indexed for MEDLINE]

 

[ultracet]

Odd. I thought everyone could get to it as it's just on pubmed. You have to watch out when you do your search. Articles on the depot preps are more common but less relevant than those involving single day dosing. I'm gonna dig up some more stuff. Here is the abstract for the article I linked to, for those who can't access it.

yeah i got the abstract... i was talking about the actual article. And yeah i did notice that about the depot preps. however i did see some other with the PO too.

i thought you were talking about the references in that article (as in the other articles it used).

 

[bananaface]

more

1: Am J Obstet Gynecol. 1999 Nov;181(5 Pt 1):1263-9. Related Articles, Links
Click here to read
The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.

Rivera R, Yacobson I, Grimes D.

Family Health International, Research Triangle Park, NC 27709, USA.

Modern hormonal contraceptives and intrauterine contraceptive devices have multiple biologic effects. Some of them may be the primary mechanism of contraceptive action, whereas others are secondary. For combined oral contraceptives and progestin-only methods, the main mechanisms are ovulation inhibition and changes in the cervical mucus that inhibit sperm penetration. The hormonal methods, particularly the low-dose progestin-only products and emergency contraceptive pills, have effects on the endometrium that, theoretically, could affect implantation. However, no scientific evidence indicates that prevention of implantation actually results from the use of these methods. Once pregnancy begins, none of these methods has an abortifacient action. The precise mechanism of intrauterine contraceptive devices is unclear. Current evidence indicates they exert their primary effect before fertilization, reducing the opportunity of sperm to fertilize an ovum.

PIP: The mechanism of action of contraceptive method is essential for the development of new methods. It also influences cultural and individual acceptability of a contraceptive method. Modern hormonal contraceptives and intrauterine contraceptive devices have multiple biologic effects. Some of them may be the primary mechanism of contraceptive action, whereas others are secondary. For the combined oral contraceptives and progestin-only methods, the main mechanism of action are the inhibition of follicular development, ovulation, and as consequence, corpus luteum formation. Further, it is also involved in the alteration of the cervical mucus that inhibit sperm penetration. For hormonal methods, particularly the low-dose progestin-only products and emergency contraceptive pills have effects on the endometrium that, theoretically, could affect implantation. However, no scientific evidence will indicate that prevention of implantation actually results from the use of these methods. Once implantation has taken place, none of these methods are effective and pregnancy proceeds normally. The precise mechanism of IUDs remains unclear because of difficulties in carrying out relevant investigations in humans and the limitations of extrapolating findings from animal studies. However, several studies evidenced that IUDs exert their primary effect before fertilization, by impeding the ascent of sperm to the fallopian tubes or by reducing the ability of sperm to fertilize an ovum.

Publication Types:

* Review
* Review, Tutorial


PMID: 10561657 [PubMed - indexed for MEDLINE]

 

[bananaface]

about sperm movement

Contraception. 2002 Dec;66(6):453-7. Related Articles, Links
Click here to read
The effects of levonorgestrel on various sperm functions.

Yeung WS, Chiu PC, Wang CH, Yao YQ, Ho PC.

Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong, China. [email protected]

Two doses of 750-microg levonorgestrel at 12 h apart is one of the regimens for emergency contraception. The mechanism of action of this regimen is not fully known. We investigated whether levonorgestrel influences sperm functions and thereby, exerts contraceptive activity. The motility, acrosome reaction, zona binding capacity, and oocyte fusion capacity of human spermatozoa treated with 1, 10, and 100 ng/mL levonorgestrel for 3 h were evaluated. Levonorgestrel decreased the curvilinear velocity of the treated spermatozoa in a dose-dependent manner. A significant decrease in straight-line velocity, average path velocity and linearity were also found with 100 ng/mL levonorgestrel treatment. This concentration of levonorgestrel, but not others, also marginally decreased (p = 0.045) the zona binding capacity of the treated spermatozoa. The steroid had no effect on acrosome reaction but had a dose-dependent inhibition on spermatozoa-oocyte fusion. These data show that levonorgestrel affects sperm function only at high concentration and the contribution of these effects to emergency contraception is unlikely to be significant. Copyright 2002 Elsevier Science Inc.

PMID: 12499039 [PubMed - indexed for MEDLINE]

 

[bananaface]

more

Contraception. 2001 Oct;64(4):227-34. Related Articles, Links
Click here to read
On the mechanisms of action of short-term levonorgestrel administration in emergency contraception.

Durand M, del Carmen Cravioto M, Raymond EG, Duran-Sanchez O, De la Luz Cruz-Hinojosa M, Castell-Rodriguez A, Schiavon R, Larrea F.

Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

The effects of short-term administration of levonorgestrel (LNG) at different stages of the ovarian cycle on the pituitary-ovarian axis, corpus luteum function, and endometrium were investigated. Forty-five surgically sterilized women were studied during two menstrual cycles. In the second cycle, each women received two doses of 0.75 mg LNG taken 12 h apart on day 10 of the cycle (Group A), at the time of serum luteinizing hormone (LH) surge (Group B), 48 h after positive detection of urinary LH (Group C), or late follicular phase (Group D). In both cycles, transvaginal ultrasound and serum LH were performed from the detection of urinary LH until ovulation. Serum estradiol (E2) and progesterone (P(4)) were measured during the complete luteal phase. In addition, an endometrial biopsy was taken at day LH + 9. Eighty percent of participants in Group A were anovulatory, the remaining (three participants) presented significant shortness of the luteal phase with notably lower luteal P4 serum concentrations. In Groups B and C, no significant differences on either cycle length or luteal P4 and E2 serum concentrations were observed between the untreated and treated cycles. Participants in Group D had normal cycle length but significantly lower luteal P4 serum concentrations. Endometrial histology was normal in all ovulatory-treated cycles. It is suggested that interference of LNG with the mechanisms initiating the LH preovulatory surge depends on the stage of follicle development. Thus, anovulation results from disrupting the normal development and/or the hormonal activity of the growing follicle only when LNG is given preovulatory. In addition, peri- and post-ovulatory administration of LNG did not impair corpus luteum function or endometrial morphology.

Publication Types:

* Clinical Trial
* Randomized Controlled Trial


PMID: 11747872 [PubMed - indexed for MEDLINE]

 

[bananaface]

more

Hum Reprod Update. 2004 Jul-Aug;10(4):341-8. Epub 2004 Jun 10. Related Articles, Links
Click here to read
Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception.

Gemzell-Danielsson K, Marions L.

Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Hospital/Institute, S-171 76 Stockholm, Sweden. [email protected]

An emergency contraceptive method is used after coitus but before pregnancy occurs. The use of emergency contraception is largely under-utilized worldwide. One of the main barriers to widespread use is concern about the mechanism of action. Recently, treatment with either 10 mg mifepristone or 1.5 mg of levonorgestrel has emerged as the most effective hormonal method for emergency contraception with very low side-effects. However, the knowledge of the mechanism of action of mifepristone and levonorgestrel in humans, when used for contraceptive purposes and especially for emergency contraception, remains incomplete. The objective of this review is to summarize available data on the effects of mifepristone and levonorgestrel on female reproductive functions relevant to the emergency use of the compounds. When summarized, available data from studies in humans indicate that the contraceptive effects of both levonorgestrel and mifepristone, when used in single low doses for emergency contraception, involve either blockade or delay of ovulation, due to either prevention or delay of the LH surge, rather than to inhibition of implantation.

Publication Types:

* Review
* Review, Tutorial


PMID: 15192056 [PubMed - indexed for MEDLINE]

 

[ultracet]

thanks bananaface

very interesting

 

[bananaface]

yeah i got the abstract... i was talking about the actual article. And yeah i did notice that about the depot preps. however i did see some other with the PO too.

i thought you were talking about the references in that article (as in the other articles it used).

Somethign is goofed up with my off-campus login for that particular resource. It won't let me at the full article. If you want me to get it when I am on campus, I can. I don't have classes till next Wed, though.

 

[bananaface]

thanks bananaface

very interesting

no problem. At least it gives you some places to look.

 

[Caverject]

This is the reason why I discount the articles posted above. First of all, all but one article is from authors of different countries. To that point, the evidence of what you are trying to prove is very sketchy at best. You are basing it off of one's opinion. The only article posted above that is from American authors, the one particular author, David Grimes, is very liberal in his views. In his views and opinions, I believe he sometimes lets his political agenda get in the way of his work. What it boils down to is no one knows if it does it or not.

 

[bananaface]

I did a lit search for observation of cervical mucus following administration of Plan B and these are the articles that came up. To assert that research done outside the US is invalid is just wrong. I also have issues with your dismissal of the articles, based on politcal motivations. Are you going to accuse anyone you disagree with of not being trustworthy as a researcher? If so, you aren't being objective. The bottom line is that if people suspect that there are changes to the cervical mucus, they ought to research the topic and come up with grounds for disputing the current body of evidence. I am not saying that the current evidence is indisputable, just that with science we base our decisions upon the best evidence we have at the moment, and that evidence would seem to be that changes to the cervical mucus are not a factor with EC. Are we not taking a scientific approach here?

 

[bananaface]

I did a lit search for observation of cervical mucus following administration of Plan B and these are the articles that came up. To assert that research done outside the US is invalid is just wrong. I also have issues with your dismissal of the articles, based on politcal motivations. Are you going to accuse anyone you disagree with of not being trustworthy as a researcher? If so, you aren't being objective. The bottom line is that if people suspect that there are changes to the cervical mucus, they ought to research the topic and come up with grounds for disputing the current body of evidence. I am not saying that the current evidence is indisputable, just that with science we base our decisions upon the best evidence we have at the moment, and that evidence would seem to be that changes to the cervical mucus are not a factor with EC. Are we not taking a scientific approach here?

 

[Caverject]

I did a lit search for observation of cervical mucus following administration of Plan B and these are the articles that came up. To assert that research done outside the US is invalid is just wrong. I also have issues with your dismissal of the articles, based on politcal motivations. Are you going to accuse anyone you disagree with of not being trustworthy as a researcher? If so, you aren't being objective. The bottom line is that if people suspect that there are changes to the cervical mucus, they ought to research the topic and come up with grounds for disputing the current body of evidence. I am not saying that the current evidence is indisputable, just that with science we base our decisions upon the best evidence we have at the moment, and that evidence would seem to be that changes to the cervical mucus are not a factor with EC. Are we not taking a scientific approach here?

I never said it was invalid. I would have liked to seen a good study done here or a more modernized country than Chile or China. If i was to assert that, thats like saying the 4S study is wrong, which it's not. Also, I never said Grimes was not trustworthy. If you happen to read the New England Journal on a regular basis, he writes a lot of opinion papers that are just that, his opinion. He is quite liberal in my opinion. That doesn't make him an invalid researcher or evan a bad one. However, I would like to see another study that agrees with what he says, especially on this subject, and usually there is. However, in this case in the article you presented, the only thing that agrees with him are a few obscure studies conducted elsewhere. I take his opinion into consideration, but it's just that, an opinion.

As far as scientific approach here goes, since when is it not okay to question a result that has not been replicated too many times? I thought that was the whole point of science. Just because my argument doesn't fall into agreement with yours doesn't mean I am not taking a scientific attitude. As far as it not being indisputable, you are correct. It is not. However, we do know the numbers of efficacy and we do have the research to show how effective levonorgestrel is for the prevention of ovulation. So why are the two numbers so drastically different? Is it theoretically possible that something else is happening?

 

[bananaface]

We're back to you believeing what you want to believe. Personally, I don't care if it turns out to have cervical mucus changes as an MOA. I'll go with the current literature - stuff that involves observations, not just theory and commentary. I don't see how that is the weaker of the two positions.

Of course it's possible that something else is going on. I don't feel like delving into the nature of scientific "truth" at the moment, but I guarantee you I can give you an earful. 😛 BTW, I can't say scientific "truth" without either putting it in quotes, or making the hand gesture.