A new ECP being tested in Clinical Trials...

[sandi1743.livejournal.com]

*This is just the abstract, i have the whole article if anyone wants it*
*also cross posted to the WH community*
The Lancet, Early Online Publication, 29 January 2010
doi:10.1016/S0140-6736(10)60101-8
Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis
Prof Anna F Glasier MD a b Corresponding, Sharon T Cameron MD a b, Paul M Fine MD c, Susan JS Logan MD d, William Casale MD e, Jennifer Van Horn MD f, Laszlo Sogor MD g, Diana L Blithe PhD h, Bruno Scherrer PhD i, Henri Mathe MSc j, Amelie Jaspart MSc j, Andre Ulmann MD j, Erin Gainer PhD j

Background
Emergency contraception can prevent unintended pregnancies, but current methods are only effective if used as soon as possible after sexual intercourse and before ovulation. We compared the efficacy and safety of ulipristal acetate with levonorgestrel for emergency contraception.
Methods
Women with regular menstrual cycles who presented to a participating family planning clinic requesting emergency contraception within 5 days of unprotected sexual intercourse were eligible for enrolment in this randomised, multicentre, non-inferiority trial. 2221 women were randomly assigned to receive a single, supervised dose of 30 mg ulipristal acetate (n=1104) or 1·5 mg levonorgestrel (n=1117) orally. Allocation was by block randomisation stratified by centre and time from unprotected sexual intercourse to treatment, with allocation concealment by identical opaque boxes labelled with a unique treatment number. Participants were masked to treatment assignment whereas investigators were not. Follow-up was done 5—7 days after expected onset of next menses. The primary endpoint was pregnancy rate in women who received emergency contraception within 72 h of unprotected sexual intercourse, with a non-inferiority margin of 1% point difference between groups (limit of 1·6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those aged over 35 years, women with unknown follow-up pregnancy status, and those who had re-enrolled in the study. Additionally, we undertook a meta-analysis of our trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel. This trial is registered with ClinicalTrials.gov, number NCT00551616.
Findings
In the efficacy-evaluable population, 1696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n=844; levonorgestrel, n=852). There were 15 pregnancies in the ulipristal acetate group (1·8%, 95% CI 1·0—3·0) and 22 in the levonorgestrel group (2·6%, 1·7—3·9; odds ratio [OR] 0·68, 95% CI 0·35—1·31). In 203 women who received emergency contraception between 72 h and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse event was headache (ulipristal acetate, 213 events [19·3%] in 1104 women; levonorgestrel, 211 events [18·9%] in 1117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis (0—72 h), there were 22 (1·4%) pregnancies in 1617 women in the ulipristal acetate group and 35 (2·2%) in 1625 women in the levonorgestrel group (OR 0·58, 0·33—0·99; p=0·046).
Interpretation
Ulipristal acetate provides women and health-care providers with an effective alternative for emergency contraception that can be used up to 5 days after unprotected sexual intercourse.

Comments

[paraxeni.livejournal.com]

Anna Glasier is an amazing person. She has done a great deal of EC-based research here. This was the new research I referred to during a recent 'EC Wars' type debate in here, I'm glad to see that it's been published now as details were a bit sketchy beforehand.

Do you have a pdf copy of it by any chance? Would love to bang it onto my ereader and go over the nitty-gritty. Actually most formats will work on it. Do you have a link or would you need my email address?

[kort-ni.livejournal.com]

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960101-8/fulltext

[kort-ni.livejournal.com]

after looking at it though, the OP posted the full text. It looks like since it's an early pub, it's kind of a teaser. Not sure...

[sandi1743.livejournal.com]

nope - this is the abstract - i have the pdf down loaded if you want an email copy

[kort-ni.livejournal.com]

yeah (Science direct was being a bit of a pain for me), I have the pdf now. Thanks for the offer though

[sandi1743.livejournal.com]

NP - most people are not at a place where they have access to peer reviewed publications w/o paying which is why i made the offer. :)

[kort-ni.livejournal.com]

Sometimes I think graduate school makes me forget that the whole world is not spending their life locked in a lab

[sandi1743.livejournal.com]

lol - welcome to my world...

[kort-ni.livejournal.com]

ok, sorry I have the pdf now (science direct was being a pain...) I'd be happy to email it to you

[sandi1743.livejournal.com]

i have the PDF - would you like copy? just email me sandi1743(at) gmail.com

[sandi1743.livejournal.com]

well for people like myself that a copper IUD is not an option, it is good to know that if needed there are other things!

[atalanta0jess.livejournal.com]

effective longer, but also effective after a longer time after the sex (if that sentence makes any sense) and much MORE effective!

[nickelshoe.livejournal.com]

I read about this in the news last night and bored my husband with information about emergency contraception for several hours after. From what I understand, ulipristal is also an abortifacent (unlike levonorgestrel/Plan B), which makes me doubt that it will be approved for use in the U.S. Nonetheless, I'm glad the research is being done.

[sandi1743.livejournal.com]

it seems that pretty much only wiki is saying that it is embryotoxic, but does not actually source it - maybe another example of a wiki fail by user edits?
Who knows...we DO know that it can delay ovulation if taken in time as it binds to progesterone receptors...the European Medicines Agency(the EU's version of the FDA) has pretty much approved it at this point for use...

http://www.ema.europa.eu/humandocs/PDFs/EPAR/ellaone/H-1027-en1.pdf

[nickelshoe.livejournal.com]

I wasn't so much swayed by the "embryotoxic" thing. I got the impression that ulipristal worked similarly to mifespristone, which is used to induce abortions. None of this is to say that it is not an emergency contraceptive. The mechanism, the timing, and the dosage would probably all be different for the different uses.

I'm searching for better information now.

[nickelshoe.livejournal.com]

Okay, here's what I've found.

On page six of the study you posted, the researchers state,

"Progesterone-receptor modulators, including ulipristal acetate, given at high or repeated doses have an effect on endometrial histology and histochemistry that could theoretically impair implantation of a fertilised oocyte. Although an endometrial effect, and therefore an additional postovulatory mechanism of action, cannot be excluded, the dose of ulipristal acetate used in this trial was specifically titrated for emergency contraception on the basis of inhibition of ovulation and might be too low
to inhibit implantation."

Here they're saying that although ulipristal acetate is expected to work by preventing ovulation (what levonorgestrel does), it may also inhibit implantation of a fertilized egg. This isn't technically abortion, but it's important to know for those who oppose any method of birth control that occurs after fertilization.

This article http://diss.kib.ki.se/2009/978-91-7409-662-0/thesis.pdf goes into more detail about the mechanism by which ulipristal acetate works. As far as I can tell, it is more effective than levonorgestrel in delaying ovulation at the last minute.

This report http://ec.princeton.edu/questions/ec-review.pdf and this abtract http://humupd.oxfordjournals.org/cgi/content/short/11/3/293 explain a bit how ulipristal acetate is similar to mifepristone.

Finally, I tracked down the Wikipedia edit http://en.wikipedia.org/w/index.php?title=Ulipristal_acetate&diff=prev&oldid=327339845 that added the term "embryotoxic". I found that the source probably was the European Medicines Agency http://www.ema.europa.eu/humandocs/PDFs/EPAR/ellaone/H-1027-en6.pdf, page 16, specifically referring to rabbits and rats. I also asked the user who added the information if he could help.

Let me know if there's a problem with the links.

Long story short, I don't think ulipristal acetate has been tested as an abortifacient on humans, but theoretically it could work that way, to abort an established pregnancy much like mifepristone.

[sandi1743.livejournal.com]

if you look back to the original data on POP's (and ECP that are progesterone based) you'll see that the mice/rats used had changes in their uterine lining after being given the medication that could prevent implantation via electron microscopy. As far as it not being approved in the US, tech HBC is an abortifacient so i am not too worried about it not being approved just b/c of that. In the case of mifepristone - it works by a different methodology than any of these other things we are talking about, so IMHO a totally different line of thinking/discussion.

[nickelshoe.livejournal.com]

Are you sure about this? Here's where I'm getting a lot of my information: http://humupd.oxfordjournals.org/cgi/reprint/11/3/293 As far as I know, HBC is not an abortifacient, it does not harm an existing pregnancy. On page 301-2, the researchers state that "The progestin levonorgestrel may also delay or inhibit ovulation if administered early enough in the follicular phase. However, once fertilization has taken place, levonorgestrel is not efficient in preventing ongoing pregnancy."

I acknowledge that ulipristal acetate is not exactly like mifepristone. But they are alike in important ways. If you use mifepristone as an abortifacient it works differently than if you use it as an ECP. The dosage for an abortion is higher, and as an ECP mifepristone, like levonorgestrel and ulipristal acetate, delays ovulation.

Levonorgestrel is a progestin. Mifepristone is an antiprogesterone. Ulipristal acetate is a selective progesterone receptor modulator. So they all work differently.

This article talks at length about progesterone antagonists and selective progesterone receptor modulators. It talks specifically about mifepristone but not ulipristal acetate. Check out page 302 for information about mifepristone as emergency contraception. Check out page 293 and 300 for comparison/contrast of PAs and SPRMs.

I suppose that even if ulipristal acetate can be used as an abortifacient, the fact that it isn't currently known as such (where mifepristone is) would make a difference on its acceptance by the public.

[sandi1743.livejournal.com]

1. i am NOT trying to start a debate here as it is against VP's rule to debate abortion. The medication in this paper is not an anti-progesterone like mifepristone but is a selective progesterone receptor modulator which is different. They are NOT the same things at all. I guess for some, if this pill iwas approved they will put it up with all other HBC's methods - a no go, and for many others we'll just know that it tech it could be an abortifacient but most likely is working by other well studied mechanisms and move on with our lives.
2. but yes, as HBC changes the lining of the uterus, if ovulation and conception were to occur the lining of the uterus is made less hospitable place for an embryo/
Many sites link POP's and other HBC's as possible abortifacients:
http://en.wikipedia.org/wiki/Abortifacient
http://www.webmd.com/sex/birth-control/progestin-only-hormonal-methods-mini-pills-shots
http://www.goaskalice.columbia.edu/0663.html
http://www.plannedparenthood.org/health-topics/birth-control/birth-control-pill-4228.htm

[nickelshoe.livejournal.com]

I know this is an old post, but just an update, Ella is in the news now as being controversial because of the possibility it could be used off-label as an abortifacent.

http://www.washingtonpost.com/wp-dyn/content/article/2010/06/11/AR2010061103522.html