Insurance Discussion

[LT_Oneal_PAC]

Mechanism of action of emergency contraception 

• Kristina Gemzell-Danielsson

Contraception, 2010-11-01, Volume 82, Issue 5, Pages 404-409,

Endometrial receptivity and embryo implantation

A considerable number of factors have been suggested as markers of endometrial receptivity. Treatment with LNG (1.5 mg) on Day LH-2 did not affect endometrial morphology or any studied markers of receptivity during the mid-luteal phase at the expected time of endometrial receptivity and implantation [46] .

The dose-dependent endometrial effects of mifepristone administered postovulatory has been investigated in several studies. Once-a-month treatment with a single dose of 200 mg mifepristone on day LH +2 has been shown to be an effective contraceptive method 47484950 . Early luteal phase treatment causes pronounced changes in endometrial development and function 5152535455 . The normal menstrual rhythm remained undisturbed and serum levels of estradiol and progesterone were essentially unchanged [56] . Treatment with 5 mg mifepristone once a week or 0.5 mg daily was administered for three cycles; ovulation was not inhibited but endometrial development was retarded or desynchronized [5758] An increase in PR levels was observed as well as impaired secretory activity. Both regimens were shown to significantly impair fertility although not sufficient for contraceptive use [5960] . When a single dose of 10 mg mifepristone was administered on day LH +2, the observed effect on the endometrium showed individual variation but only minor effects on the endometrium [29] . Consistent with this finding, repeat administration of 10 mg mifepristone once a week was not effective to prevent pregnancy [61] .

To allow studies on human embryo implantation, a three-dimensional endometrial construct comprising endometrial stromal cells in collagen matrix with a surface of epithelial cells was developed [6263] ( Fig. 2 ). Our in vitro study shows that the molecular profile of this three-dimensional endometrial construct is similar to the receptive endometrium in vivo . Exposure to a high concentration of mifepristone caused significant changes in the in vitro luminal epithelium and resulted in inhibition of blastocyst attachment. In contrast, LNG had no effect on blastocyst viability or hatching and did not prevent blastocyst attachment and early implantation ( Fig. 3 ).

29. Marions L., Hultenby K., Lindell I., Sun X., Stabi B.: Gemzell Danielsson K Emergency contraception with mifepristone and levonorgestrel: mechanism of action. Obstet Gynecol 2002; 100: pp. 65-71.

46. Durand M., del Carmen Cravioto M., Raymond E.G., et. al.: The mechanism of action of short-term levonorgestrel administration in emergency contraception. Contraception 2001; 64: pp. 227-234.

56. Swahn M.L., Bygdeman M., Xing S., Cekan S., Masironi B., Johannisson E.: The effect of RU 486 administered during the early luteal phase on bleeding pattern, hormonal parameters and endometrium. Hum Reprod 1990; 5: pp. 402-408.

61. Godfrey E.M., Mawson J.T., Stanwood N.L., Fielding S.L., Schaff E.A.: Low-dose mifepristone for contraception: a weekly versus planned postcoital randomized pilot study. Contraception 2004; 70: pp. 41-46.

[Boatswain2PA]

Perused through what you posted.  Most of that is about the UPA, not the LNG.  At the beginning it does though, where it says UPA has the most effect on ovulation, whereas LNG only delays ovulation by 5 days in 14% of patients.

Seems to me that your post shows LNG, which is HIGHLY effective in preventing birth, must do its work mostly downstream of ovulation.

Am I reading that wrong?

[LT_Oneal_PAC]

13 hours ago, Boatswain2PA said:

We should be able to respectfully talk about anything.  Medical ethics is important to our field, and abortion is obviously fraught with ethical challenges.

 

Because someone inevitably gets out of line, then when mods step in, they talk about how they are being censored and treated so differently from everyone else. We have people on both sides saying we are too liberal or too conservative. 

The fact this thread is still up is monument to the fact that we keep trying to let these things play out.

[LT_Oneal_PAC]

3 hours ago, Boatswain2PA said:

Perused through what you posted.  Most of that is about the UPA, not the LNG.  At the beginning it does though, where it says UPA has the most effect on ovulation, whereas LNG only delays ovulation by 5 days in 14% of patients.

Seems to me that your post shows LNG, which is HIGHLY effective in preventing birth, must do its work mostly downstream of ovulation.

Am I reading that wrong?

You are missing the post immediately preceding the one I’m quoting, that details LNG. There is also more talk about LNG in the highlighted portions of that original post as well.
 

yes, you are reading wrong, as LNG is not as efficacious as UPA and has even less effect after ovulation than UPA.

[ANESMCR]

12 hours ago, Boatswain2PA said:

This was sent to me from a source who wants to remain anonymous.  I have not been able to read the link yet.

"Drop this on them:  https://pubmed.ncbi.nlm.nih.gov/25698840/

I don't post on the forum anymore.  Too much bullshit and favoritism, with selective censors."

Did you actually read this? 

[Boatswain2PA]

8 hours ago, LT_Oneal_PAC said:

You are missing the post immediately preceding the one I’m quoting, that details LNG. There is also more talk about LNG in the highlighted portions of that original post as well.

I am not tracking what you mean here.
 

8 hours ago, LT_Oneal_PAC said:

es, you are reading wrong, as LNG is not as efficacious as UPA and has even less effect after ovulation than UPA.

I carefully read what you posted.  Majority of it was about UPA, or even misopristol.  

What I get from it all is UPA is much better at preventing follicle rupture (59% for 5 days) than LNG (no better than placebo).

And in-vitro studies show no change in endometrial receptors or decrease in human (or monkey) implantation with LNG (at what appears to be extremely low doses).

So...how does LNG work then?  We know it DOES work to prevent births, but if it only delays ovulation 14% of time, and doesn't prevent implantation, how does it work?   And why did well respected textbooks from 10 years ago say that it DID prevent implantation?  And why does so much literature today report that it prevents ovulation, despite the study summary you posted saying it only does 14% of the time?  

3 hours ago, ANESMCR said:

Did you actually read this? 

I clearly said I had not.  And you even quoted me saying "I have not been able to read the link yet."



 

[ANESMCR]

14 minutes ago, Boatswain2PA said:

I clearly said I had not.  And you even quoted me saying "I have not been able to read the link yet."

Then read it....

[LT_Oneal_PAC]

5 hours ago, Boatswain2PA said:

I am not tracking what you mean here.
 

I carefully read what you posted.  Majority of it was about UPA, or even misopristol.  

What I get from it all is UPA is much better at preventing follicle rupture (59% for 5 days) than LNG (no better than placebo).

And in-vitro studies show no change in endometrial receptors or decrease in human (or monkey) implantation with LNG (at what appears to be extremely low doses).

So...how does LNG work then?  We know it DOES work to prevent births, but if it only delays ovulation 14% of time, and doesn't prevent implantation, how does it work?   And why did well respected textbooks from 10 years ago say that it DID prevent implantation?  And why does so much literature today report that it prevents ovulation, despite the study summary you posted saying it only does 14% of the time?  

I clearly said I had not.  And you even quoted me saying "I have not been able to read the link yet."



 

You need to read the long post specifically on LNG on this page (at least on my screen its the first post on this page, you're set up may be different), where it specifically shows it does not have an effect on implantation. Then you need to where it is explained in other posts that LNG is only effective if taken early. 

You read it wrong, because that is a study on specifically late LH phase, when we know it is ineffective. It was only used to compare to UPA. LNG is very effective if given early. It does not have an overall 14% efficacy.

Directly from that same post "UPA delays ovulation in both the pre-ovulatory period and after the LH surge has started [1,3]. This extended period of activity may explain UPA's greater efficacy in preventing pregnancy compared with oral LNG. However, neither LNG nor UPA prevents ovulation if taken on the day of the LH peak or later, nor do they prevent implantation"

Further, from my original post in this thread:

" LNG prevents ovulation if taken in the pre-ovulatory period by blocking the luteinizing hormone (LH) surge, thus inhibiting follicular development and egg release. UPA delays ovulation in both the pre-ovulatory period and after the LH surge has started [1,3]. This extended period of activity may explain UPA's greater efficacy in preventing pregnancy compared with oral LNG. However, neither LNG nor UPA prevents ovulation if taken on the day of the LH peak or later, nor do they prevent implantation"

 

Effect of emergency contraception with levonorgestrel or mifepristone on ovarian function.

AU

Marions L, Cekan SZ, Bygdeman M, Gemzell-Danielsson K 

SO

Contraception. 2004;69(5):373. 

 

The mechanism of action of levonorgestrel (LNG) and mifepristone (MIF) in emergency contraception (EC), is still not fully known. The purpose of this study was to evaluate the effect of preovulatory treatment with LNG and MIF on luteal function in more detail. Two days prior to ovulation (day -2; assessed by ultrasound), we administered LNG (0.75 mg twice, 12 h apart) or MIF (10 mg, single dose) to seven women in different cycles. Follicle development was followed by ultrasound. Urinary estrone glucuronide (E1), pregnanediol glucuronide (P4) and luteinizing hormone (LH) were analyzed by enzyme immunoassays daily starting with day -2 for the rest of the menstrual cycle, along with urinary creatinine (C). The treatment caused either a delay or an inhibition of the LH peak in all subjects. A significant delay in P4 levels and an initial suppression of E1 levels were also noted. The development of the leading follicle was either arrested or continued without signs of rupture. This study indicates that, when used for EC, LNG or MIF administered prior to ovulation acts through an impaired ovulatory process and luteal function.

 

 

Why did the text change? That was postulated and not verified. Science evolves as we investigate further, is fluid, and is not static. It does not pretend to know everything and isn't afraid to admit it can be wrong, but it must always follow the data.

[Aunt Val]

I just want to say thanks to the moderators for allowing this discussion to stay up, even though it has strayed from its original topic of "Insurance Discussion."  And thanks to the contributors for keeping things relatively civil.  This is an important subject for those of us interested in medical ethics, but it's hard to find solid scientific studies and evidence.  Glad we can share information here.  I'm following with interest. 

[MediMike]

On 10/2/2020 at 4:41 PM, Boatswain2PA said:

 

Sorry Boats, not trying to quote you but I can't seem to make the box go away.

Any thoughts on the ability of public figures to check themselves into hospital as a precaution? Viz a vis Chris Christie? I have worked inpatient ICU my whole career with no knowledge on justifying admissions to an insurance company. How hard is it to get admitted with knowledge that insurance will pay for it, and how hard is it to say you'll just cover the bill out of pocket if you will admit me?

Or is the ability to do that just an elite thing?

[Boatswain2PA]

On 10/3/2020 at 4:22 PM, LT_Oneal_PAC said:

You need to read the long post specifically on LNG on this page (at least on my screen its the first post on this page, you're set up may be different), where it specifically shows it does not have an effect on implantation. Then you need to where it is explained in other posts that LNG is only effective if taken early. 

Maybe you can repost that (with a source if you don't mind), because I'm not seeing where LNG is shown "not to have an effect on implantation."  I saw where one of your cut-n-pastes said under one studied dosage it didn't appear to have any change in endometrial thickness.   

Efficacy studies have shown it's most effective if taken early (after coitus).

 

On 10/3/2020 at 4:22 PM, LT_Oneal_PAC said:

LNG is very effective if given early. It does not have an overall 14% efficacy.

The ultrasound guided study you posted said it only had an 14% efficacy in delaying follicular rupture by 5 days, much less than UPA.  

 

On 10/3/2020 at 4:22 PM, LT_Oneal_PAC said:

Further, from my original post in this thread:

" LNG prevents ovulation if taken in the pre-ovulatory period by blocking the luteinizing hormone (LH) surge, thus inhibiting follicular development and egg release. UPA delays ovulation in both the pre-ovulatory period and after the LH surge has started [1,3].

I don't disagree it can prevent ovulation if early in the cycle.

The question I have though, is WHY did textbooks of 10 years ago clearly say that it blocks implantation?  And what data changed that belief?  

I'm not seeing it. 

[CAAdmission]

22 hours ago, MediMike said:

Any thoughts on the ability of public figures to check themselves into hospital as a precaution?

I'm thinking it is nice to be rich and famous. I hope to try it one day, but my prospects don't look too good. 

[LT_Oneal_PAC]

23 hours ago, MediMike said:

Sorry Boats, not trying to quote you but I can't seem to make the box go away.

Any thoughts on the ability of public figures to check themselves into hospital as a precaution? Viz a vis Chris Christie? I have worked inpatient ICU my whole career with no knowledge on justifying admissions to an insurance company. How hard is it to get admitted with knowledge that insurance will pay for it, and how hard is it to say you'll just cover the bill out of pocket if you will admit me?

Or is the ability to do that just an elite thing?

It’s not common, but there are times we admit someone with no indication because they want to, or really need to for social issues. They are essentially in the worlds most expensive hotel. We never do it and think insurance will pay for it. Obviously we never do it for famous people, or even super rich. 
 

there was a lot of “old money” at my previous job. The hospital was all too happy to admit you and take your money. My new job will do it, but more for social problems like a frail spouse can’t be left at home, but the other spouse is being airlifted for a stemi.

[LT_Oneal_PAC]

1 hour ago, Boatswain2PA said:

Maybe you can repost that (with a source if you don't mind), because I'm not seeing where LNG is shown "not to have an effect on implantation."  I saw where one of your cut-n-pastes said under one studied dosage it didn't appear to have any change in endometrial thickness.   

Efficacy studies have shown it's most effective if taken early (after coitus).

 

The ultrasound guided study you posted said it only had an 14% efficacy in delaying follicular rupture by 5 days, much less than UPA.  

 

I don't disagree it can prevent ovulation if early in the cycle.

The question I have though, is WHY did textbooks of 10 years ago clearly say that it blocks implantation?  And what data changed that belief?  

I'm not seeing it. 

No thanks. The answers are all there. I’ve explained it twice now. I’ve given you all the data. If you can’t get it, then you just can’t.

 

i never posted any of this to convince you, but for others who could actually be shown the truth in data.

[Boatswain2PA]

11 hours ago, LT_Oneal_PAC said:

The answers are all there

Well, this is NEVER true in science.

I've read what you've posted several times.  Some info saying that during certain days of cycle certain doses of LNG delay rupture by 5 days 14% of time, and a summary saying that when doses on day 2 of cycle no change in endometrial morphology or receptivity of studied receptors.

I dont think you have posted anything else about LNG.

That opens to the question I have asked: How DOES it work?  And why did textbooks from 10 years ago say it prevented implantation?

I am open to LNG not preventing implantation.  I hope we CAN show that its efficacy in prevents births comes from another method.