FDA approves Plan B emergency contraception

GrandForksHerald.com ^ | 8/25/06 | Marie McCullough/The Philadelphia Inquirer

[hocndoc]

http://www.freerepublic.com/focus/f-news/1689548/posts

No redefinition, just good, ethical, yet definitive but nearly, research.

[hocndoc]

There's no evidence that there are changes and lots of evidence that there are *no* changes to the uterine wall with Plan B.

Please consider this research
http://www.freerepublic.com/focus/f-news/1689548/posts

I can email more information by regular email attachment if you want.

[hocndoc]

Make that "not yet definitive."

It's late, sorry for the goof. (and good night)

[Brian Allen]

<< ... since 1029 ... >>

Should have been: "1920s" - seems a plea is in order of "guilty of typing while asleep!"

(And whilst apparently extremely dyslexic!)

[MHGinTN]

Did you happen to see the astonishing assertion earlier: "... science seems to indicate that a zygote is not a human life form as it lacks most human traits, and possesses other traits that human beings lack. Where you are in error is in staking your claim that it is "obvious" that life begins at conception." It is astonishing to me when I come across such blatant denial of the very claims of Science ... usually indicates a deepseated need to have reality to be something it is not, so deep denial of the facts and truth drive the mind to a fringe assertion such as that.

[hocndoc]

I believe that I've explained to the poster that in nature, life begins at fertilization and in the fallopian tubes. I've also referred him to the recent glossary of the International Society for Stem Cell Research proposed draft of Guidelines for human stem cell research, which defines embryo as

Embryo: The term “embryo” has been defined and used differently in different biological contexts. Classical embryology has used the term embryo to connote different stages of post-implantation stages of development (e.g. the primitive streak and onwards to fetal stages). Dorland’s Illustrated Medical Dictionary (27th edition,1988 edition, W. B. Saunders Company) provides the definition: “in animals, those derivatives of the fertilized ovum that eventually become the offspring, during their period of most rapid development, i.e., after the long axis appears until all major structures are represented. In man, the developing organism is an embryo from about 2 weeks after fertilization to the end of seventh or eighth week.” An entry in Random House Webster’s College Dictionary reads: “in humans, the stage approximately from attachment of the fertilized egg to the uterine wall until about the eighth week of pregnancy.” However, the nomenclature has now been used generically by modern embryologists to also include the stage of first cleavage of the fertilized ovum onwards to nine weeks of gestation in the human and to term in the mouse. Two, four, and eight cell stages, the compacting morula, and the blastocyst are all more precise terms for pre-implantation embryos. Prior to implantation, the embryo represents a simple cellular structure with minimal cellular specialization, but soon after implantation a defined axis of development called the primitive streak begins to form. After this time twinning of the embryo can no longer occur as there is irreversible commitment to the development of more complex and specialized tissues and organs.

(emphasis is mine)

Those links, again:

International Society for Stem Cell Research: http://www.isscr.org/

The guidelines in pdf: http://www.isscr.org/StaticContent/StaticPages/ISSCRTaskForceGuidelinesDRAFT6-30-06.pdf

[Raquel]

http://www.polycarp.org/postfertilization_polycarp_1.htm


Here's some evidence that says there are changes to the uterine wall, and other factors as well, that at times can cause an "early abortion".

[Raquel]

Sales will definitely rise (some are estimating by 300%), that's why there's the big push for it, but insurance companies won't be paying for it anymore, because usually once a drug is sold over the counter it is not covered, so people will be paying out of pocket. I'm not sure how it works with Medicaid.

[hocndoc]

First, all of the data used to write the articles at Polycarp was obtained *before* the Durand and Croxatto studies. As the authors say, when they did the article review, there had been no controlled studies. There are several, now. I have wondered why Drs. Larimore, Kahlenborn, and Stanford haven't addressed these new findings.

However, if you'll look at what Walt and the others suggest for a more convincing study, you'll see that Durand and Croxatto did exactly that: they used ovulating women, confirmed that the women had normal cycles and the timing of those cycles by various means, performed the studies in order to focus on the fertile days. They did serial serum and urine tests, serial ultrasounds, and Durand's lab even did biopsies 9 days after the LH surge.

The conclusion from both labs was that the major effect is the delay or failure of ovulation, and that a secondary effect was to prevent the sperm from fertilizing the oocyte by thickening the mucus in the cervix and by making the sperm unable to penetrate the zona pellucida. There were no findings on the ultrasounds, serum and urinary hormones or the biopsied uterine specimens that were consistent with an inhibition of implantation. Animal studies in rats and Cebus monkeys have shown that there is no effect on implantation in those animals after fertilization.

All of which is understandable, when we remember that we give women progesterone in early pregnancy to prevent miscarriage.

(No one has done a study after fertilization in humans, because that would be unethical. However, if there's no change that would prevent implantation when there is no embryo present, there's no reason to think that the presence of an embryo would cause them.)

[MHGinTN]

There is only ONE active ingredient in the Plan B contraceptive. If I can get it to load here at FR, I'll post the prescribing information.

PRESCRIBING INFORMATION

Plan B (Levonorgestrel) tablets, 0.75 mg

Plan B is intended to prevent pregnancy after known or suspected contraceptive failure or unprotected intercourse. Emergency contraceptive pills (like all oral contraceptives) do not protect against infection with HIV (the virus that causes AIDS) and other sexually transmitted diseases.

DESCRIPTION

Emergency contraceptive tablet. Each Plan B tablet contains 0.75 mg of a single active steroid ingredient, levonorgestrel [18,19-Dinorpregn-4-en-20-yn-3-one-13-ethyl-17-hydroxy-, (17á)-(-)-], a totally synthetic progestogen. The inactive ingredients present are colloidal silicon dioxide, potato starch, gelatin, magnesium stearate, talc, corn starch, and lactose monohydrate. Levonorgestrel has a molecular weight of 312.45 ...

CLINICAL PHARMACOLOGY

Emergency contraceptives are not effective if the woman is already pregnant. Plan B is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). ...

CONTRAINDICATIONS

Progestin-only contraceptive pills (POPs) are used as a routine method of birth control over longer periods of time, and are contraindicated in some conditions. It is not known whether these same conditions apply to the Plan B regimen consisting of the emergency use of two progestin pills. POPs however, are not recommended for use in the following conditions:

Known or suspected pregnancy

Hypersensitivity to any component of the product

Undiagnosed abnormal genital bleeding

WARNINGS

Plan B is not recommended for routine use as a contraceptive.

Plan B is not effective in terminating an existing pregnancy.

Effects on Menses

Menstrual bleeding patterns are often irregular among women using progestin-only oral contraceptives and in clinical studies of levonorgestrel for postcoital and emergency contraceptive use. Some women may experience spotting a few days after taking Plan B. At the time of expected menses, approximately 75% of women using Plan B had vaginal bleeding similar to their normal menses, 12-13% bled more than usual, and 12% bled less than usual. The majority of women (87%) had their next menstrual period at the expected time or within ± 7 days, while 13% had a delay of more than 7 days beyond the anticipated onset of menses. If there is a delay in the onset of menses beyond 1 week, the possibility of pregnancy should be considered.

Ectopic Pregnancy

Ectopic pregnancies account for approximately 2% of reported pregnancies (19.7 per 1000 reported pregnancies). Up to 10% of pregnancies reported in clinical studies of routine use of progestin-only contraceptives are ectopic. A history of ectopic pregnancy need not be considered a contraindication to use of this emergency contraceptive method. Health providers, however, should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking Plan B.

PRECAUTIONS

Pregnancy

Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins (POPs). The few studies of infant growth and development that have been conducted with POPs have not demonstrated significant adverse effects.

DOSAGE AND ADMINISTRATION

One tablet of Plan B should be taken orally within 72 hours after unprotected intercourse. The second tablet should be taken 12 hours after the first dose. Efficacy is better if Plan B is taken as directed as soon as possible after unprotected intercourse. Plan B can be used at any time during the menstrual cycle.

The user should be instructed that if she vomits within one hour of taking either dose of medication she should contact her healthcare professional to discuss whether to repeat that dose.

HOW SUPPLIED

Plan B (Levonorgestrel) tablets, 0.75 mg are available for a single course of treatment in PVC/aluminum foil blister packages of two tablets each. The tablet is white, round, and marked: INOR.

[hocndoc]

By "components," I think Raquel meant functions.

[MHGinTN]

Uh, not according to her earlier posts.

[hocndoc]

You may be right. I was trying to understand her posts, and that's the explanation I came up with.

[cgk]

Pro-Life/Pro-Baby ping!

A matter of time:

Please FReepmail me if you would like to be added to, or removed from, the Pro-Life/Pro-Baby ping list...

_{* - I am moving so will be away from FR and computers in general from September 1st to September 10th. Please bear with me as I attempt to resume my 'duties'! :) Thanks!}

[Raquel]

Yes, I clearly see the "components" with respect to Plan B as being inaccurate. I changed it to "functions", thanks!

[Raquel]

http://www.polycarp.org/postfertilization_polycarp_1.htm


EFFECTS ON IMPLANTATION

"OCs are known to adversely affect the implantation process,6 which has implications for the Yuzpe regimen and Plan B because they are composed of the same (or similar) hormones contained in today's OCs. OCs affect integrins, a group of adhesion molecules that have been implicated as playing an important role in the area of fertilization and implantation. Somkuti et al.30 noted: “These alterations in epithelial and stromal integrin expression suggest that impaired uterine receptivity is one mechanism whereby OCs exert their contraceptive action.” In addition, prostaglandins are critical for implantation, but OC use lowers uterine prostaglandin concentrations.31 ,32 Finally, it is well known that OC use decreases the thickness of the endometrium as verified by magnetic resonance imaging scans,33 ,34 and a thinner endometrium makes implantation more difficult.35–39 Because hormonal EC consists of hormones contained within OCs, it is possible that the use of hormonal EC has some of the same effects on the endometrium as does the use of OCs. A number of studies support this hypothesis, noting changes in endometrial histology,1 ,40 or uterine hormone receptor levels41 that persist for days after women used the Yuzpe regimen. All of these findings imply that use of the Yuzpe regimen unfavorably alters the endometrium.

In addition to the theoretical evidence that EC use adversely affects implantation, Hertzen and Van Look12 found that both use of the Yuzpe regimen and Plan B reduced the expected number of pregnancies when they were used in the ovulatory phase (17–13 d prior to the next menstrual cycle) and postovulatory phase (13 d prior to the expected menstrual cycle), as well as in the preovulatory phase (as discussed earlier). In the groups that used the Yuzpe regimen in the ovulatory phase, 17 pregnancies occurred (54 were expected if EC was not used), whereas 7 occurred in the postovulatory phase (11 were expected). In the group that used Plan B, 7 pregnancies occurred (53 were expected) in the ovulatory phase, whereas 2 occurred in the postovulatory phase (10 were expected). These data are highly consistent with the hypothesis that hormonal EC has a postfertilization effect on the endometrium. In the case of the use of hormonal EC in the ovulatory phase, it is still possible that other mechanisms might come into play (i.e., a change in the viscosity of cervical mucus and/or an alteration in the tubal transport of either the sperm, ovum, or embryo). However, we could find no data to support these theories."

I guess for me, the argument of effect is more powerful than the named "components". If one keeps the traditional definition of pregnancy, you'll see that the result is the same, breakdown of the uterus wall, and prevention of implantation or an "early abortion". Although I have read your earlier post and I understand that it is a more recent study, I also understand (to the best of my ability, I am not a doctor nor an expert) that the studies you link have different approaches, and different circumstances, but I don't see that they negate the earlier position.

[MHGinTN]

I guess for me, the argument of effect is more powerful than the named "components". You have 100% agreement from this old man. You may want to review the comparison found in the study which hocndoc posted, because this Plan B approach is contrasted to the Yuzpe approach where bolus dosing of the combination oral contraceptives is recommended for a 'morning after' effect.

It is my understanding (and twenty years of dealing with this subject may stand me in good stead here) that in the Yuzpe approach, both artifical estrogen and prostaglandin are in the bolus dose and the endometrial lining is effected by such a combination dose (by inhibiting the arterial build up in the uterine tissues). With Plan B, only one of the two compounds is bolus dosed and that artifical hormone (the prostaglandin) mimics the hormone released naturally when the ovary follicle sends feedback messaging to the pituitary signaling that an ovum has been released, setting up the build up of arterial blood supply in the uterine tissue in order to support a conceptus should fertilization happen. In other words, the Plan B bolus dose mimics signaling that is natural to the female body, while the Yuzpe plan does not work in the same way.

Freeper Polycarp is a practicing physician and he could clear this up for you since it is not sound to transfer his excellently explained argument against the Yuzpe regimen to the Plan B regimen ... you may also note that one of the named side effects of this morning after approach is an increase in ectopic pregnancies since motility in the fallopian tubes is effected with the combination bolus dosing.

[Raquel]

The references made in my article to the let's say abortifacient component that directly mutilates the cervix wall are connected to the birth control pill and other contraceptive pills. That's why I stand by the article. While my main argument is that Plan B is dangerous and may have abortifacient tendencies, a second theme is the destructive nature of contraceptive pills themselves. Strong doses of the drug that inhibits ovulation caused serious complication in studies done in the 1960's in Puerto Rico. Has that method changed? Are there new components in Plan B that make the drug effective without the need for the directly abortifacient component that is contained in other contraceptive pills?
How will the drug be produced and what about competing contraceptive pills on the market? Plan B won't be the only. I do mention the possibility of ectopic pregnancy in my article.
I know we're on the same side, as I've read your posts before. Thank you from this humble, Catholic and concerned lady.

[MHGinTN]

Permit me to respond to your questions: Has that method changed? Are there new components in Plan B that make the drug effective without the need for the directly abortifacient component that is contained in other contraceptive pills?

The studies done in Puerto Rico were due to the advent of Enovid, Searle's first big 'breakthrough' in female contraception. Since Envoid, dramatic changes in amounts of the estradiol and the prostaglandin have been made. The prostaglandin of Plan B is a close mimic to a naturally occurring prostaglandin in the female follicular stimulating hormone feedback system that works naturally to build up arterial supply in the uterine tissue where the conceptus desires to implant. That is the only active ingrediant to the Plan B pill regimen; there is no additional compound added to change the uterine lining. It works to trick the female body into believing an ovary has released an ovum already and thus delay release of an actual ovum. My only question revolves around what possible Ph changes may be brought about in the fallopian tubes and the uterine lining by a bolus dose of this artificial prostaglandin.

[Raquel]

I question the understanding that Plan B only acts to create a scenario where an egg has already been released, whereby no egg will be released again because that's what I was told about the birth control pill. If it's possible for Plan B to operate successfully without the need for the 2nd component contained in other contraceptive pills, then why hasn't the contraception lobby worked to correct the birth control pill to work without the abortificient tendency? With this revelation, the country can return to the traditional definition of pregnancy, and tell the truth that the birth control pill. I believed them then, and they were lying.Why should I trust them now?