Statistics: Proceed with Caution [Scott]

Jill Stanek's excellent blogsite has a discussion over an article in the journal Contraception. The article covers contraception policy in Spain and the abstract for the study concludes as follows:

STUDY DESIGN: Since 1997, representative samples of Spanish women of childbearing potential (15-49 years) have been surveyed by the Daphne Team every 2 years to gather data of contraceptive methods used.

RESULTS: During the study period, 1997 to 2007, the overall use of contraceptive methods increased from 49.1% to 79.9%. The most commonly used method was the condom (an increase from 21% to 38.8%), followed by the pill (an increase from 14.2% to 20.3%). Female sterilization and IUDs decreased slightly and were used by less than 5% of women in 2007. The elective abortion rate increased from 5.52 to 11.49 per 1000 women.

CONCLUSIONS: The factors responsible for the increased rate of elective abortion need further investigation.

The ensuing discussion about the study (in the comments section of Jill's blog) contains some fiesty exchanges about contraception in general, with some pro-lifers insisting this study proves increased contraceptive use results in more abortions. At least one post claims the pill itself is abortifacient.

What follows is what I said on Jill's blog:

Admittedly, I’m no statistican. However, I have two concerns: First, statistics are slippery things and it’s tempting to quote them when they seem to support our view and downplay them when they don’t. With any study involving the extensive use of stats, it’s best to withhold a declaration of victory until 1) the internal numbers are fully analyzed for strengths and weaknesses, and 2) the methodology of the study is subject to further peer-review. To cite one example, in 1994 (some) pro-lifers went crazy citing a statistic from the Daling study which allegedly indicated that women undergoing first trimester abortions were 800% more likely to develop breast cancer by age 35. Not long after, the alleged statistic was shown to be a fluke, a random statistical error that sometimes creeps up in large samples. Applied to the study in question, I’m not suggesting that pushing contraceptives on unmarried couples has no impact on abortion rates. I’m only appealing for caution while we await further commentary.

Second, regarding some comments above on BC pills functioning as abortifacients, my own organization takes a cautious view while we await further evidence. That is, while we don’t think there is sufficient evidence to say for certain that the pill functions as an abortifacient in the event of breakthrough ovulation, we do think there’s sufficient evidence to indicate it may function that way. Thus, given human life is at stake, we should err on the side of caution while we await further evidence, meaning we do not endorse its use. But we are careful not to overstate our case and claim certitude when the evidence is still open to debate. (We have dealt with that debate on our blog, so I won’t go into it here.)

In short, it’s important that pro-lifers function with intellectual integrity, meaning we go only so far as the evidence allows. Perhaps the Spain study is in the main accurate; if so, it’s useful for confronting the lies of PP. But while we await further review, I think we should hedge our conclusions just a bit.

Kevin DeYoung has helpful posts on being cautious with statistics here and here.

You may also want to read this.

Ella: the Anti-Plan B [Serge]

Elizabeth and Scott have awakened me from my slumber (thanks guys). There is a lot of confusion regarding the new "emergency contraceptive" Ella (ulipristal), and hopefully I'll be able to provide some clarification in the next few posts.

Let me contrast Plan B and Ella. Plan B is basically synthetic progesterone, and is merely a larger dose of a form of oral contraceptive that has been used for years. Ella is a progesterone antagonist, which means that it works by blocking the effect of progesterone. The only other progesterone antagonist on the market at this time is mifepristone, otherwise known as RU-486, the abortion pill.

Its seems a bit strange that the proposed mechanism for both of these drugs is to suppress ovulation, and the evidence is clear that both of them do that. The concern is with any other effects the medications may have on a developing embryo and its ability to attach to the uterine lining.

Since human beings are intrinsically valuable from the moment they become human beings, any medication that serves to end the life of a human being after fertilization is morally wrong. This is true whether or not the medication has a direct effect on an implanted embryo or if it adversely effects that uterine lining to make implantation more difficult. I would oppose any medication that has been shown to have either effect.

In the case of Plan B - there is no direct evidence that it decreases the receptivity of the uterine lining to an embryo that is attempting to implant. There is some indirect evidence that has concerned many in our movement, but there is also evidence from both animal studies and human studies that indicate no post-fertilization effects from Plan B. In the absence of clear evidence, I urge caution, but cannot state that using Plan B is wrong because of its post-fertilization effects. Lots of my older posts on this topic can be found here.

This may seem like a win for the pro-EC crowd, but in truth it is an epic fail. If EC only works before fertilization, than its effectiveness will be far less than the stated 90%. In fact, the evidence now supports this. There have been over 14 studies that have tried to show that taking EC will decrease pregnancies within a certain group. The number of the studies that showed a decrease in pregnancies for those taking Plan B have been a whopping zero.

What about Ella? I will show in following posts that just about everything that I stated about Plan B is completely different than Ella. Ella has been shown conclusively to have an adverse effect on the uterine lining. Investigators admit that if taken in higher doses, Ella will cause an abortion just like her sister RU-486. This is not an emergency contraceptive drug - it is a low dose abortifacient.

"Depressed" about Emergency Contraception [Serge]

Wow. I just finished listening to a web seminar about the efficacy of emergency contraception by Dr. James Trussell, who is one of the most well reknown researchers in the field of contraception. I haven't been putting a while lot of time in studying EC lately, but essentially what Dr. Trussell had to say supports all of my previous postings on the subject, which can be found here. Here are some of the high (low) lights according to the Powerpoint slides that he presented.

1. Trussell previously hoped (published in 1992) that EC would reduce unintended pregnancies and abortion by half.

2. 15 years later 11 studies have consistently showed no decrease of pregnancy rates from use of ECs.

3. Trussell also stated that a future decrease in pregnancy rates from EC use is highly unlikely - an astounding admission.

4. He then quoted TH Huxley when he stated "The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact."

5. Due to difficulties in estimating the expected pregnancy rates, the published efficacy in the package insert of EC is almost certainly too high.

6. The only thing he could say about the actual efficacy of Plan B was that it was "more effective than nothing".

7. According to the latest research, the efficacy of Plan B can be fully explained via a pre-fertilization mechanism. Research continues to lead away from a post-fertilization mechanism.

This is amazing stuff. Since there was extensive news coverage of the effort to get Plan B to OTC status, why the silence in the wake of information that Plan B will not effect pregnancy or abortion rates? Imagine the outcry if a heart medication was thought to reduce heart attacks by 95% - and was made over-the-counter in order to increase its availability to reduce heart disease. A year later evidence comes out that no study had ever found that it had any effect on heart attack rates, and that the only thing that could be said about it is that it is "probably better than nothing". There would be a great outcry, congressional hearings, and accusations that the evil pharmaceutical companies were gouging unsuspecting patients. However, so far there has not been a peep among those concerned about "women's health" that they could be promoting an expensive medication that may not be effective.

Lastly, at the end of the seminar there was a pause before participants asked questions. Dr. Trussell commented that everyone must be too depressed.

Has the Author of the Guttmacher Study Read What They Cite? [Serge]

Science is intended to be an objective, empirical investigation of our world in an effort to discern truth. The scientific literature is intended to aid in that process by the open and truthful dissemination of data and conclusions to be considered by others. It is for this reason that I struggle almost every time I read articles or press reports from "family planning" sources. Here is a prime example.

Here is a press release from the Guttmacher Institute about some study regarding EC in some Carribean countries. I wished to read it with an open mind until I found something that was concerning. It turns out that I did not make it past the first part of the first sentence:

Despite widespread belief that emergency contraception is necessary to reduce levels of unintended pregnancy, almost half of more than 400 health care providers surveyed in Jamaica and Barbados have at some point refused to provide the method to women seeking it.

Eeks. Is it really necessary? Lets first try to forget that logically speaking, pregnancies really do not happen by accident. Pregnancy occurs as a natural consequence of certain sexual activity. Why do we need to imagine that folks are just walking down the street when, oops, a pregnancy just happens? Human beings, by virtue of being able to control our own behavior, have all of the tools necessary to prevent unintended pregnancy.

Even so, is there really a consensus the EC is necessary? This would be a great surprise to one of the biggest proponents of EC, James Trussell. Trussell published an article just last year that had this conclusion:

In all but one study, increased access to emergency contraceptive pills was associated with greater use. However, no study found an effect on pregnancy or abortion rates. CONCLUSION: Increased access to emergency contraceptive pills enhances use but has not been shown to reduce unintended pregnancy rates.

Here's where is gets really interesting. You may think that the author of the Guttmacher study was not aware of Trussell's article. This could not possible be the case, because they actually cited Trussell's article in the study, albeit in order to support a different point. Amazing.

Allow me to review. The Guttmacher Institute claims in a press release that there is a consensus that EC is necessary to reduce unintended pregnancies. However, the study itself cites an article which shows that EC had yet to have an influence on decreasing pregnancy rates regardless of how easy it is to access or how often it is taken.

And this is taken as science. And it happened in the first sentence of the article.

Unbelievable.

Bad Reporting from Our Side [Serge]

It frustrates me greatly when pro-abortion choicers misrepresent scientific data in order to support their ideology. It frustrates me even more when those on our side do the same thing. Here is a report from Catholic News Agency that claims this about Plan B emergency contraception:

The most recent scientific study on Levonorgestrel, the essential component of the “morning-after pill” or “emergency contraceptive,” confirms that the drug does indeed have a third effect on users, which consists in preventing the implantation of a fertilized ovum in the womb of the mother.

Here is another post from prolifeblogs that mirrors this thought:

A study published in the journal Fertility and Sterility found that levonorgestrel, the drug contained in Plan B emergency contraception, does inhibit implantation after all, at least some of the time. (Preventing implantation interrupts an existing pregnancy and is an abortive mechanism.)

Interesting stuff, until you realize that both claims are completely untrue. Here is the abstract of the study in question. The investigators used computer models to determine the effectiveness of LNG as contraception if it acted via a pre-fertilization mechanism and compared it to the effectiveness if it also had a post-fertilization mechanism. The results were this:

With disruption of ovulation alone, the potential effectiveness of levonorgestrel EC ranged from 49% (no delay) to 8% (72-hour delay). With complete inhibition of fertilization before the day of ovulation, the potential effectiveness of levonorgestrel EC ranged from 90% (no delay) to 16% (72-hour delay).

This is not surprising at all, although it may very well be helpful if real experimental data ever come out that confirms the actual effectiveness of LNG. In fact, this post of mine essentially predicts these numbers. In the meantime, the authors do note that the projected effectiveness of LNG if it acts via a pre-fertilization mechanism is lower than the effectiveness rates reported in the literature. However, it is precisely those rates that have been previously reported that are under question not only by me, but by a number of pro-EC researchers. This study does nothing to shed light on the true effectiveness of LNG EC, and thus cannot confirm its actual mechanism at all. The authors understand this when they conclude:

The gap between effectiveness of levonorgestrel EC estimated from clinical studies and what can be attributed to disruption of ovulation may be explained by overestimation of actual effectiveness and supplementary mechanisms of action, including postfertilization effects.

Reporting that this paper confirms a post-fertilization mechanism for Plan B is completely irresponsible. Reporting the results of scientific papers using your ideology to cloud what they actually say is simply wrong.

Back Up Your Contraception with Self Control Day [Serge]

You may have missed it, but yesterday was "Back up your birth control" day. This is a day in which all of these organizations band together to convince women that their contraceptives may not be as effective as they thought so they should "back them up" with emergency contraception. As you can see, there is not a word about the newest medical literature that shows that EC has not decreased the overall pregnancy rate in 23 studies to date and that there is a growing body of evidence that indicates it may not be nearly as effective as first thought. You would think that women's advocate groups would be all over that information, but it is as if another ideology is driving their agenda.

So for those who are concerned that they need to supplement their regular contraception with a "back-up" plan, I suggest using an age old method: self control. You can start with a single day, but eventually you may find it to be a far more healthy alternative to regular contraception.

More Evidence that Plan B is Not Effective After Ovulation [Serge]

This is only a pilot study, and I will be very interested to see the results when more patients are studied. However, the preliminary results seem to support the theory that Plan B is not effective after ovulation. Of course, if this is true, it means that Plan B does not effect implantation of an embryo.

Background

Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation.

Method

Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a ±24-h period with an accuracy of around 80%. Women were followed up 4–6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined.

Results

Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days −1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days −5 to −2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data.

Conclusion

These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.

Crunchin' Some EC Numbers [Serge]

JivinJ asks in the comments:

I'm trying to crunch the numbers to figure out what the effectiveness of EC would have been estimated at if the WHO used the pregnancy risk number from the Canadian study.

Correct me if I'm wrong but my estimations from trying to decipher how they figured out the effectiveness (is it percentage of pregnancies divided by pregnancy risk?) show that if the WHO study used the pregnancy risk number (4.12) from the Canadian study instead of the 7.7 garnered from the traditional method of estimating pregnancy risk and then took the percentage of women who became pregnant from the WHO study then the effectiveness of EC would be somewhere around 75% and not the 85% cited for the WHO.

I actually believe its worse than that. James Trussell, who I believe was an author in the WHO study, uses a meta analysis of all of the studies about plan B when discussing its efficacy. The 1.1% crude pregnancy rate found in that study has not been reproduced. Trussel states:

Therefore, the chance that pregnancy would occur in the absence of emergency contraception is estimated indirectly using published data on the probability of pregnancy on each day of the menstrual cycle.14,15 This estimate is compared to the actual number of pregnancies observed after treatment in observational treatment trials. Effectiveness is calculated as 1-O/E, where O and E are the observed and expected number of pregnancies, respectively...

Eight studies of the levonorgestrel regimen that included a total of more than 9,500 women reported estimates of effectiveness (a reduction in a woman’s chance of pregnancy) between 59% and 94%.7,8,9,17,18,19,20,21 A meta-analysis of eight studies of the combined regimen including more than 3,800 women concluded that the regimen prevents about 74% of expected pregnancies; the proportion ranged from 56% to 89% in the different studies.

Using the 7.7% rate for the traditional method of estimating pregnancies, Trussel's numbers are about a 2% rate of pregnancy when a woman is using Plan B EC (from the 74% number). This translates to an effectiveness of 51%.

One more thing. As the authors of the Canadian study state, even the revised method of estimating pregnancy may not be very accurate. This study of using ultrasound techniques to determine ovulation time was far more accurate than the calender method.

Bottom line: if the Canadian study is accurate, and the data from the meta-analysis of Plan B is used, then its maximum effectiveness is 51%. I believe further data will show that it is actually less than that.

Plan B: More Evidence That Its Effectiveness is "Markedly Lower" Than Previously Thought [Serge]

This study from the Journal of OB-GYN: Canada was the first population based study that used a more accurate method of measuring the risk of pregnancy. The full study is available here. The results are as I would expect: the effectiveness of Plan B is "markedly lower" than previously reported. I'll let the study speak for itself:

When the data for all women are combined, the mean risk of pregnancy is estimated to be 4.12% (95% CI 3.77–4.49). This risk of pregnancy is substantially lower than that estimated in studies comparing the effectiveness of the levonorgestrel and Yuzpe regimens.3,4

This is the first report of risk of pregnancy among a population-based cohort of women requesting EC from pharmacists under conditions of routine use. Overall, in the two groups combined, the estimated risk of pregnancy was 4.12%, which is markedly lower than that reported when effectiveness of EC has been estimated in clinical trials.2–5

If the estimates of risk of pregnancy from the present study and related studies are reasonably accurate, the effectiveness of EC among women in the general population may be markedly lower than is currently believed by professionals and advocates for wider EC use. In light of these observations, consideration should be given to revising the information on effectiveness that physicians, pharmacists and other health care professionals provide to women seeking EC.

Plan B: The Evidence So Far [Serge]

Its been a while since I posted on Plan B, so I'll summarize my thoughts so far:

1) an analysis of the most recent literature supports the theory that Plan B works predominately, if not exclusively, prior to the fertilization event. In other words its effectiveness is primarily associated with its ability to impair ovulation, and not effect implantation.

2) If Plan B does not work after fertilization, the reported effectiveness of the medication must be less than the 85% or 91% that has been reported in the literature and on the package insert.

These two posts address the effectiveness issue of Plan B. If I am right here, we would expect the data that uses a more accurate measure for predicted pregnancy rates to show decreased effectiveness for EC. I have detailed four studies which showed that real world usage of Plan B does not effect pregnancy rates. However, one could argue that factors outside of medication effectiveness were responsible for the number of pregnancies in the Plan B groups. When I wrote the original posts, there was no studies out which showed a decrease in the effectiveness of Plan B using a more accurate way of estimating pregnancy risk. As I will detail in the next post, that is no longer the case.

Another Study Shows No Decrease in Pregnancy Rates for Women With Better Access to EC [Serge]

I've been a bit busy with other projects, and Scott's been busy blowin up the blog (just kidding Scott), but I've recently been able to continue to research Plan B emergency contraceptive. This study right here is the fourth one that has been unable to show a decrease in pregnancy rates with a group with increased access to emergency contraception. This is pretty amazing, and yet I don't believe anyone has reported on it. Here is an excerpt from the abstract:

OBJECTIVE: To assess how a strategy to maximize access to emergency contraceptive pills would affect rates of pregnancy and sexually transmitted infections. METHODS: Sexually active women, 14-24 years old, were randomly assigned to two methods of access to emergency contraceptive pills: increased access (two packages of pills dispensed in advance with unlimited resupply at no charge) or standard access (pills dispensed when needed at usual charges). Participants were followed for 1 year to assess incidence of pregnancy, gonorrhea, chlamydia, and trichomonas. RESULTS: The numbers of women enrolled in the increased and standard access groups were 746 and 744, respectively. More than 93% of participants completed a full year of follow-up. The incidence of pregnancy was similar in both groups (increased access group: 9.9/100 woman years, 95% confidence interval [CI] 7.7-12.6; standard access group: 10.5/100 woman years, 95% CI 8.2-13.2). Aggregate rates of gonorrhea, chlamydia, and trichomonas were also similar in the two groups (increased access group: 6.9/100 woman years, 95% CI 5.1-9.1; standard access group: 7.6/100 woman years, 95% CI 5.7-9.9). The increased access group used emergency contraceptive pills substantially more often and sooner after coitus than the standard access group. No other differences were noted between groups in self-reported measures of sexual behavior and contraceptive use. CONCLUSION: This intensive strategy to enhance access to emergency contraceptive pills substantially increased use of the method and had no adverse impact on risk of sexually transmitted infections. However, it did not show benefit in decreasing pregnancy rates.

In other words, having greater access to EC allowed women to use it more often than standard access, yet there was no statistically significant decrease in pregnancy rates within the two groups.

Plan B EC: Others Question its Effectiveness [Serge]

Here is a very recent letter to the editor in the Journal Pediatrics that poses some of the same questions that I have regarding the efficacy of emergency contraception (Pediatrics 117:4 April 2006, p1448).

To the Editor.-

The American Academy of Pediatrics Committee on Adolescence policy statement on emergency contraception1 reports the effectiveness of the Yuzpe regimen (ethinyl estradiol and levonorgestrel) in terms of a pregnancy reduction of 70% to 80% and of levonorgestrel-only emergency contraception of 85%. These estimates are outdated. Using current methods for estimating effectiveness, the effectiveness rates seem to be in the range of 50% to 66% and 72% to 80%, respectively.2-5 Because there are no randomized trials with a placebo arm, considerable uncertainty remains about the effectiveness of emergency contraception.3,5

The policy statement also proposes that "[e]mergency contraception has tremendous potential to reduce unintended pregnancy rates in teens and adults." This statement remains, as yet, a hypothesis that is unsupported by empirical evidence. Several studies have failed to document a decrease in rates of unintended pregnancy or abortion in populations that are provided with advance access to emergency contraception.6-8 This suggests that the studies that have demonstrated no changes in sexual behavior with advance access (other than increased use of emergency contraception) have used inadequate surrogate end points or have failed to detect small changes in sexual behavior that were nevertheless sufficient to negate any decrease in unintended pregnancy.

Joseph B. Stanford, MD, MSPH

Department of Family and Preventive Medicine

University of Utah

Salt Lake City, UT 84108

Rafael T. Mikolajczyk, MD

Department of Public Health Medicine

School of Public Health

University of Bielefeld

D-33501 Bielefeld, Germany

Plan B: Is the FDA Using Outdated, Inaccurate Information? [Serge]

An e-mailer recently asked about the fact that the FDA does list prevention of implantation as a potential mechanism of action of Plan B. You can see that in the FDA Q&A here as well as the package insert here. Does the FDA know something that we don't?

The FDA relies on information provided by the manufacturer for the mechanism of action of any medication (they do not do their own research). I responded to the information provided by the manufacturer in this post here. In short, the manufacturer has a responsibility to list any possible mechanisms of action for any medications. Since there is an open question in the literature regarding the mechanism of Plan B, and since post-fertilization events are listed as one possible mechanism, it is not surprising (nor particularly helpful) that interruption of implantation is included as a possible mechanism of action.

In other words, the fact that the manufacturer mentions this as a possible mechanism is evidence that the question is an open one that we have no definitive answers to. Therefore, the presence of this information by the FDA does not trump the most recent literature on the topic. In fact, the opposite is true.

I can illustrate this in another way that does not directly address the mechanism of action of Plan B. The manufacturer makes this claim in its literature, and its repeated on the packaging of Plan B that the FDA agreed to:

A double-blind, controlled clinical trial in 1,955 evaluable women compared the efficacy and safety of Plan B (one 0.75 mg tablet of levonorgestrel taken within 72 hours of intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets of 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two tablets taken 12 hours later). Plan B was at least as effective as the Yuzpe regimen in preventing pregnancy. After a single act of intercourse, the expected pregnancy rate of 8% (with no contraception) was reduced to approximately 1% with Plan B. Thus, Plan B reduced the expected number of pregnancies by 89%.

The exact citation isn't listed, but clearly they were citing this study from 1998 (both studies had 1955 women enrolled), Lancet 1998 Aug 8;352(9126):428-33. This is the same study that I posted about here. They used a crude method of determining ovulation: they added 14 days to the last period. The primary author for this paper was H Von Hertzen.

In other words, the FDA is allowing data 8 years old that used a very inaccurate way of determining ovulation, which is essential in determining effectiveness in stopping pregnancy. In fact, the author of that study has more recently contributed to an article which acknowledges the inaccuracy of their data in estimating the expected rate of pregnancy(Contraception 2003 Apr;67(4):259-65.)

This article, in which Von Hertzen is an author, states in the abstract:

The expected pregnancy rate among typical users was 6.2% in the Population Council trial and 7.4% in the WHO trial based on conception probabilities by cycle day relative to the day of ovulation. Based on conception probabilities by cycle day relative to the first day of bleeding, the expected pregnancy rates dropped to 5.4% and 5.2%, respectively. The two trials yield conflicting evidence regarding whether effectiveness declines with treatment delay. CONCLUSIONS: Our results suggest that the absolute levels of effectiveness for the Yuzpe regimen of emergency contraception and the cost-effectiveness of this regimen have probably been overstated when based on conception probabilities by cycle day relative to day of ovulation.

Although the authors only mention the Yuzpe regimen the same pregnancy estimation was also used to determine the efficacy of Plan B. If the effectiveness of the Yuzpe regimen had been overstated, then the same can be inferred with Plan B. It should also be noted that even with the "more accurate" method of determining ovulation, there is a significant chance for error in determining the actual date of ovulation.

I hope I haven't lost anyone. Here's the bottom line: the FDA is allowing the manufacturer of Plan B to claim that it can be almost 90% effective based on a study from 1998. This study has been shown to be inaccurate due to its crude way of estimating ovulation. This fact was pointed out by none other than the author of the original study. Yet there it is on the packaging being readied for OTC sale.

Still confident in the FDA information now? There is significant reason why we should not be. In any event, it should be clear that the information given by the FTC does not refute more recent scientific studies.

Plan B EC: What is its Real Effectiveness? [Serge]

Sixth in a series.

I wish to challenge the most compelling line of evidence that Plan B works at least some if the time via a post-fertilization mechanism. In this post, I believe those who are very pro-emergency contraception will be quite disappointed.

The most common evidence used to support a post-fertilization effect of Plan B is its proposed effectiveness. Quoting from this post:

1. The reported effectiveness of EC cannot be fully explained by a suppression of ovulation. In other words, if EC worked through non-fertilization events, we would not expect it to be as effective as it appears to be. Therefore there must be some post-fertilization event that is responsible for at least part of its effectiveness.

The effectiveness of Plan B is reported to be somewhere between 90 and 75% in stopping an unintended pregnancy. If this is true, it seems impossible that it could work via a purely anti-ovulatory action. As Steve states here, the most important question to ask would be when did a woman ovulate. If Plan B is taken after a woman ovulates, and it contributes to the 75% effectiveness, then it must work at least part of the time via a post-fertilization event.

If, on the other hand, Plan B works through predominantly anti-ovulatory actions, its effectiveness would be expected to be less than 75%. What does the data support? If one looks at some of the more recent studies, it is reasonable to conclude that the effectiveness of EC is significantly less than 75%.

First, it is a known fact that studying the effectiveness of EC is quite challenging. The main reason is that in order to have a comparison group, an accurate determination of the date of ovulation is essential. An ideal study would use a placebo control group - but that would entail giving a woman who is seeking to prevent a pregnancy a placebo, which is considered unethical. For that reason, estimates of ovulation are used. It has been shown that these estimations are often very inaccurate, as shown by this article: (Contraception 2003 Apr;67(4):259-65)

Calculations of the efficacy of EC depend on knowing the timing of intercourse in relation to the estimated day of ovulation. The results of this study suggest that these calculations are likely to be inaccurate for a significant minority of women.

Is there evidence that EC may not be effective as advertised? Absolutely. I will cite two very recent studies. In this article about EC in JAMA (JAMA 2005;293:54-62), the authors specifically choose a number of women that would have direct access to EC vs pharmacy access in order to show a difference in pregnancy rate between the two groups (they choose about 890 women in each group). They say so in the article, and this was not a small study. As it was, the group who had to go to the pharmacy to get EC used it 197 times, while the group who had direct access used it 309 times. The result on pregnancy: absolutely nothing! The pregnancy rate for the first group was identical despite the fact that they used EC one third more often. This caused the authors of the study to state:

While we set out to demonstrate a large reduction in pregnancy rates, even a10% or 20% reduction in unintended pregnancy rates would be a significant and desirable public health achievement.

What ever happened to 75%? They set out to demonstrate a large reduction in pregnancies, and got zero despite the fact that so many more women took EC. Now they would be happy to see a 10-20% reduction. This is solid evidence that in the "real world", EC doesn't work nearly as often as stated.

Here's one more (Contraception 69 (2004) 361-366). These researchers showed that having EC at home did not reduce pregnancy or abortion rates in that population. Lest anyone think that my reasoning is novel here, the authors seem to agree with me:

Finally, it is possible that EC may be less effective than we belief. Estimates of efficacy are unsubstantiated by randomized trials. Efficacy is based on rather unreliable data and a great many assumptions [28] and have been questioned both in the past [29] and more recently [30].

In conclusion, I believe there is an increasing amount of evidence that the proposed efficacy of EC is not nearly what was originally thought. There is no doubt in my mind that those who support increased access of EC as a public policy issue are not in any hurry to publicize this data. On the other hand, the decreased efficacy of EC is also key evidence that Plan B works predominately prior to ovulation.

Plan B EC: No Morphological Changes Found in Endometrium [Serge]

Fifth in a series.

In this post, I spoke of three evidences that have been presented to support a post-fertilization mechanism of action from Plan B EC. I promised to challenge each one, and this was #2:

2. Since EC has the same types of hormones found in regular oral contraceptives, and there is evidence that regular OCs can have a post-fertilization event, then it stands to reason that EC would also have a post-fertilization mechanism of action.

I believe this point is the easiest one to refute, and my research in this area has turned up some surprises.

First, this point implies that there is a known post-fertilization effect from regular OCs. There is no consensus on that issue, and there is no direct evidence that OCs cause a "hostile endometrium." However, even if you believe that regular OCs do cause abortions, that does not indicate that Plan B EC does work via a post-fertilization event. This was a surprising aspect of this research: if Plan B acts after fertilization, the evidence states argues that it must do so by a mechanism that is different than regular OCs. I will show why.

Most who believe that regular OCs can act as an abortifacient use what I call the "hostile endometrium" theory". The theory is that continued use of OCs create a thinner, less vascular endometrium that would be less likely to accept an embryo attempting to implant. Randy Alcorn, who has written extensively on this topic, explains it this way:

When the Pill thins the endometrium, it seems self-evident a zygote attempting to implant has a smaller likelihood of survival. A woman taking the Pill puts any conceived child at greater risk of being aborted than if the Pill were not being taken...

First, after a woman stops taking the Pill, it usually takes several cycles for her menstrual flow to increase to the volume of women who are not on the Pill. This suggests to most objective researchers that the endometrium is slow to recover from its Pill-induced thinning

Now if the effect of regular OCs take months to for a woman's body to "undo", then how does Plan B EC create a hostile environment in a matter of hours? It seems that if EC works via a post-fertilization event, it must use some different mechanism than regular OCs, which appears to be based on a chronic thinning of the endometrium.

However, I did not have to depend on the argument of the last paragraph. There is actually experimental evidence that shows that Plan B taken after ovulation does not have any significant change in the morphology of the endometrium. Take a look at the abstract here and the full article here that presents this evidence. (Contraception. 2001 Oct;64(4):227-34.) They performed endometrial biopsies on women who took Plan B EC and control groups and found no difference in the morphology between the two. The paper states:

No significant changes were observed between treated and control specimens in any of the studied parameters. No significant differences among groups were observed. Of particular importance was the finding that the predecidual changes as evaluated by the presence of prominent spiral arteries, which are considered crucial for implantation [24], were not altered by LNG.

Remember, the proposed mechanism of regular OCs is to create a significantly thinner endometrium. This does not occur when a woman takes Plan B.

Although the medications are the same, if Plan B acts to cause abortions, it seems to have to do so via a different mechanism than does regular OCs. Instead of being evidence for a post-fertilization mechanism of action, this actually gives support to the theory that Plan B does not act after ovulation.