Monday, June 16, 2008

Does a Thin Uterine Lining Support the "Pill as Baby Killer" Theory? [Serge]

I believe the most frequently cited evidence for a "baby-killing" mechanism for oral contraceptives (OCs) is the thinning of the uterine lining that occurs when a woman is on OCs. First, I do not dispute this fact: when women are on OCs their uterine lining becomes considerably thinner than when they are not. This is the reason that many women report lighter periods when they are on OCs. I will also concede that this evidence appears compelling at first glance: if a thick, receptive uterine lining is necessary for implantation, and we can show that OCs thin the lining, it almost has to effect implantation. This is the predominant reasoning used by those who support the abortifacient theory.

However, this only covers the issue very shallowly. In order to understand what it really occurring, we have to go deep. This can be complicated and confusing, but I will do my best to simplify it where I can. In order to understand how OCs effect a woman's uterus, we must first examine the regular menstrual cycle in detail.

Normal Physiology

To the right you see a graphical representation of a woman's menstrual cycle. You can see that the cycle can roughly be divided into the follicular phase and the luteal phase. During the follicular phase, the hormones secreted by the pituitary gland, namely LH and FSH stiffly peak at day 13-15 - which results in ovulation. At the time of ovulation, the uterine lining (seen at the bottom) is quite thin and in fact is unreceptive to implantation . This is a surprise to some, but the truth is that if an embryo attempted to implant at the time a woman ovulates, it would most likely not be successful. Thankfully, implantation naturally occurs days later.

The next phase after ovulation is the luteal phase, in which the uterine lining is prepared to accept an embryo. This phase is controlled by the corpus luteum (thus the name), which arises from the follicle from which the ovum is generated. During the luteal phase, the corpus luteum secretes progesterone (and some estrogen) in order to increase the thickness of the uterine lining in preparation for implantation. If implantation occurs, the CL continues to secrete estrogen and progesterone that support the embryo for 2 more months until the embryonic placenta takes over. The pituitary is able to sense these elevated hormones during pregnancy and will not allow the woman to ovulate during this time (in other words, it will not allow the LH and FSH peak to occur). However, if implantation does not occur, then the thickened uterine lining is lost during menstruation.

I hope you're still with me. The point here is during normal cycles, the luteal phase, which is characterized by the hormones secreted by the corpus luteum is in control of preparing the uterine lining for implantation. The progesterone secreted by the CL during the luteal phase is about 20 times its baseline level, and is far greater than hormone concentrations that are found in formulations of OCs.

What happens on the pill?

What about women on the pill? The primary mechanism of action if OCs is to "trick" the pituitary into believing the woman is pregnant. It does so by elevating the amount of estrogen and progesterone to mimic their levels during pregnancy. As in pregnancy, the LH and FSH peak that would normally occur does not, and the woman does not ovulate, at least in theory.

If ovulation does not occur, then there is no corpus luteum formation, so the uterine lining does not thicken as it normally would. Essentially, women on the pill who do not ovulate have no luteal phase of their cycle. Since their uterine lining does not thicken, you would expect, and it is observed, that their uterine linings are thinner than women who are not on the pill. Their linings would be similar to the thickness at time of ovulation for a woman not on the pill, and as I stated before, this lining is most likely unable to accept an embryo.

What if Ovulation Occurs?

So it seems clear that thickening of the uterine lining in preparation for acceptance of the embryo occurs during the luteal phase of the cycle. A woman on OCs that does not ovulate will not have a luteal phase, thus her uterine lining will be thin. It is also reasonable to believe that this thin uterine lining would not accept an embryo - which is not really a problem because ovulation did not occur. However, what if ovulation does occur? What would happen then?

If so-called "breakthrough" ovulation occurs, then the follicle that released the ovum would turn into a corpus luteum, and the woman would once again have a luteal phase to her cycle. Since the luteal phase is responsible for preparing the uterine lining for implantation, and the hormones secreted by the CL are of far greater magnitude then those found in OCs, it seems reasonable to me that the uterine lining would be thickened and prepared to a similar extent than would a woman who was not on OCs. All of the studies that showed a thinned uterine lining did so an a non-ovulatory cycle. It gives us very little information on what would occur if a woman actually ovulates, which of course is a necessary condition for pregnancy.

I have heard some question this thinking, being skeptical that somehow it would be miraculous that a woman's uterine lining could rebound so quickly from a thin state to one that could accept an embryo. However, what is often forgotten is that this happens every single month for women who are not on OCs! Every month the luteal phase, by using hormones secreted by the CL, turns a thin, "hostile" uterine lining into one that is thick and can support pregnancy. If OCs do create a "hostile environment" for an embryo, then you would have to have some evidence that OCs either negatively influence the CL hormones themselves are that they somehow decrease the effectiveness of the hormonal receptors found in the uterine lining. I have not seem even a possible mechanism for any of these events to occur in the literature, so I remain skeptical regarding this theory.

Whew, thats enough for now. I welcome and covet challenges and corrections regarding this information. However, seeing that this topic is a medical issues, and separate from the ethical issues surrounding contraception, I ask for medical citations and documentation regarding claims that are made.

Update: Tired Typos corrected

32 comments:

  1. This is good news, and it eliminates a front in the battle.

    I wish prolifers would divert their attention away from the Pill, which recent reserach indicates does not have the tertiary abortifacient effect after all, and instead pay attention to the routine and deliberate desstruction of intentionally-created human embryos in IVF centers.

    The Pill, even when we believed the worst of it, would have been an inadvertent unknown killing of an occasional embryo. IVF clinics make it their business to either destroy embroys or turn them over for lethal experiments. Even if the Pill was the killer it was once believed to be, it would be nowhere near as problematic about the casual attitude toward killing and destroying life that is an ordinary part of IVF facilities. Focus our efforts on DELIBERATE DESTRUCTION of human lives that we have confirmed, and leave the Pill alone.

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  2. True, let us focus our efforts on that, but let us not forget that the Pill does create a hostile environment for a fertilised egg (aka a baby). I *could* put my toddler down to sleep in an unventilated room in the summertime with the space heaters running full blast and deny her water. That wouldn't be murder, it would just be creating an unfavorable environment. If she can crawl out of there, deactivate the heaters and open the windows while finding water, great. If not, not my problem.

    No no, let's attack the big stuff (granny is right) and also educate especially young marrieds about the danger of the Pill. We can do both; it doesn't take much to do the latter.

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  3. Rhology,

    I assume you read this post. What evidence do you have that would support the idea that the pill creates a hostile environment?

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  4. Serge,
    Stellar stuff, as usual. Thanks for keeping us honest on this stuff.

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  5. Fascinating. Thanks for your objective, concise summary, Serge.

    Makes me long for a pro-life website that has unbiased, clear, concise factual scientific information on human procreation that's accessible to the average person, yet trustworthy, with complete references.

    Oh, wait, is bias creeping in? Do we call it "reproductivity" or "procreation"? One casts humans as products, while the other term introduces the idea of a "Creator".

    But aren't products created? Oh well...

    We're having a hard enough battle with terms never mind the facts!

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  6. Serge,

    I apologize in advance for the length of my comments, but I’ve had lingering doubts and questions about this issue for some time, and I am hoping you can help me resolve them.

    I have researched this issue (though I doubt to the extent you have), and listened to both sides of the debate. It has become clear to me that both the hostile endometrium theory, as well as the “ovulation will normalize the endometrium” theory are…well…theories. Neither has been proven, and ethical barriers will prevent us from doing so anytime in the near future. The fact of the matter is that we don’t really know what happens in the event of breakthrough evolution.

    I doubt:
    (1) whether ovulation normalizes the endometrium in Pill users, even if the CL is functioning, and functioning normally;
    (2) whether pro-lifers can, in good conscience, say with confidence that it is morally acceptable to use the Pill, when we cannot be equally confident that ovulation will override the function of the Pill, always resulting in a normalized endometrium; i.e. it cannot function as an abortifacient.

    Regarding (1), I agree with you that there is no good reason to doubt that if ovulation occurs, the luteal phase will begin, and the progesterone released from the CL will work on building up the endometrium. Indeed, it must do so because women on the Pill get pregnant [Of course, that does not necessarily mean it always does so. The Pill, or at least types of it, could conceivably interfere with the CL so that progesterone production is severely diminished, disallowing for sufficient thickening of the endometrium, and preventing implantation.]

    What I question is whether this is sufficient to ALWAYS build up the endometrium to normal, or at least implantation-friendly levels. Clearly it does at least some of the time because women on the Pill are known to have babies, but this fact alone does not give me confidence that ovulation will always normalize the endometrium so it is hospitable for the embryo (in other words, just because Pill users can get pregnant while on the Pill does not necessarily mean the implantation rate for Pill users is the same as non-Pill users). The reason I am skeptical is because of what does not happen in the follicular phase in a woman on the Pill. Let me explain.

    It is my understanding that the thickening of the endometrium is accomplished by two hormones (progesterone and estrogen), not just one (the progesterone released by the CL). Of the two, estrogen is responsible for MOST of the work, and that work starts well BEFORE ovulation. Estrogen released from the ovaries in the follicular phase begins thickening the endometrium around day 5 of a woman’s cycle. By the time of ovulation 8-9 days later, the endometrium has already reached 2/3 its final thickness. Estrogen levels plummet, and progesterone kicks in to finish the job by inducing swelling and secretion, making the endometrium stronger and spongier for optimal preparedness to receive an embryo.

    The Pill suppresses estrogen production by injecting enough estrogen into a woman’s body to prevent the hypothalamus from releasing GnRH, which prevents the pituitary gland from releasing FSH, which prevents the ovaries from producing estrogen, which prevents the endometrium from thickening in the follicular stage. It only reaches a thickness of about 1mm. For non-Pill users, the combined efforts of estrogen and progesterone create an endometrium that is 8-13mm thick. If 2/3 of that thickness is the work of estrogen, that means there was already an endometrium base of 5-8mm by the time progesterone takes over after ovulation. Contrast this to Pill users, who only give progesterone a 1mm base to build on.

    Here’s my concern: What reason do we have to think that in the event of breakthrough ovulation, the progesterone released by the CL can normalize this 1mm thick endometrium to 8-13mm, when progesterone normally contributes only 3-5mm of the endometrium’s thickness? According to what I have read, an endometrium needs to be at least 6mm thick for implantation to be successful (at least likely). Combining the 1mm of endometrium produced by estrogen with the 3-5mm of endometrium produced by progesterone, we should expect the endometrium of a woman on the Pill to reach a thickness of 4-6mm. In some cases that may be enough, but in other cases it may not.

    My point is that even if it’s true that breakthrough ovulation will result in progesterone production, there is no reason to think it can, by itself, normalize the endometrium. It would seem that high levels of estrogen are needed as well, but by that time the estrogen ship has already sailed. The workers were on strike in the follicular stage, and can’t make up for lost production in the luteal.

    The bottom line is that we don’t know what happens in the event of breakthrough ovulation. Maybe the Pill disables the CL, making implantation impossible. Mabye the CL works normally, but can’t make up for lost work due to estrogen’s strike. Then again, maybe it can. Maybe estrogen levels experience an abnormal increase to make up for the lack. Maybe. Maybe. Maybe. Which brings me to my second doubt.

    What do we do with all of these maybes? I am uncomfortable with the conclusion that it is ok to use the Pill when, we don’t know the answers to these vital questions. In the abortion debate it is common to hear people justify abortion on the basis that no one knows when life begins. One of our responses to this objection is that, if true, this would be one of the best reasons to forego abortions. We should err on the side of life when we are uncertain as to what it is that we are killing. We do not demolish a building until we are certain there are no people left in it. Why is it any different for the Pill? It is entirely possible that the Pill results in a hostile endometrium, diminishing the chances for a viable embryo to continue its life trajectory. Seeing that we are not and cannot be sure, isn’t it better to err on the side of life and forego using it?

    Consider this analogy. Let’s say your child has a non-terminal, but disabling disease. The doctor is not able to properly diagnose him because the symptoms fit the description of two different diseases, and it is beyond the medical profession’s current knowledge to be able to tell precisely which is which. Treatments have been developed to cure both diseases. Treatment A cures disease X, and treatment B cures disease Y. Here’s the rub: treatment A kills those with disease Y, and treatment B kills those with disease X. What do you do? Do you try one of the cures, risking your son’s life, or do you forego the process altogether? I think most people would forego the treatment because they have little to gain, but everything to lose. It would not be wise to proceed with the treatment before one could be reasonably certain that treatment would cure, rather than kill their child. Should we not exercise that same kind of caution with the Pill? Should we be risking the lives of our unborn children, reasoning that it’s ok to “take the treatment” because we cannot be certain if it will kill or cure? It seems to me that until we have evidence that the Pill cannot function as an abortifacient, it is best to pro-lifers to forego our use of the Pill.

    I’m open for correction on my facts or reasoning. Thanks!

    Jason

    p.s. What are your thoughts on the argument for an abortifacient function of the Pill based on the fact that ectopic pregnancy vs. uterine pregnancy ratios are smaller for women on the Pill than those who are not? I thought I recalled you addressing this before, debunking the research, but I can’t recall.

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  7. Thanks for your thoughtful comment Jason. I applaud you for looking into this issue. You have asked many excellent questions, and I wish to get to many of them, but I'll start here:

    The Pill suppresses estrogen production by injecting enough estrogen into a woman’s body to prevent the hypothalamus from releasing GnRH, which prevents the pituitary gland from releasing FSH, which prevents the ovaries from producing estrogen, which prevents the endometrium from thickening in the follicular stage. It only reaches a thickness of about 1mm.

    Your theory is that OCs prevents the pituitary from producing FSH, thus the ovary will not produce estrogen in the follicular phase, thus the endometrium will not grow at all in the follicular phase.

    Do you have evidence that FSH is effected to that level, and that the ovaries fail to produce any estrogen during the follicular phase. I wish to research this further, but right off the top of my head there are at three reasons why I would question your theory.

    1. There is follicular activity from women who are on OCs verified through ultrasound. The medical standard for ovulation is a dominant follicle >15 mm that ruptures. Women on Ocs frequently show growth of follicles up to 10mm, but they fail to rupture. This would indicate that there is presence of FSH but the LH surge, which controls the follicular rupture and conversion to the CL.

    2. Women who are on conventional pill schedules do go through menstruation (albeit lighter than those not on OCs). This seems to indicate that their uterine lining did become thinker despite the lack of a luteal phase to their cycle.

    3. I don't remember seeing that FSH has such a strong impact on the ovaries' ability to secrete estrogen. I would appreciate some more evidence here - although I certainly could be wrong.

    I'll address some of your ethical issues in another post, since you have offered so many good questions.

    Thanks again Jason

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  8. Thanks for the detailed discussion and the arguments you present are compelling. I appreciate Jason's reply too. I would recommend to readers Randy Alcorn's book "Does the Birth Control Pill Cause Abortions?". Mr. Alcorn presents an even handed and well referenced argument there as well but comes to a different conclusion than Serge.

    I do find it a bit disturbing that some would quickly say that "pro-lifers should divert their attention away from the Pill" when the Pill could very well be the biggest killer of human beings the world has ever seen. If the Pill does indeed act as an abortifacient then even if a small fraction of break-throughs occurr, due to the huge number of women that use the Pill the number of people killed by this drug would be huge.

    I would have to concur with Jason that if there is doubt, then we should error on the side of caution. And clearly there is a sufficient amount of evidence indicating there is a risk and there is clearly a sufficient number of unknown variables that would cast doubt as to how safe the Pill is.

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  9. I would like to address one thing Jason said. Being familiar with Jason from the past I am certain he did not mean it like he wrote it.

    He wrote:

    "In the abortion debate it is common to hear people justify abortion on the basis that no one knows when life begins. One of our responses to this objection is that, if true, this would be one of the best reasons to forego abortions."

    I do not know any serious person who considers the objection that we do not know when life begins valid. Any person that raises that objection is immediately schooled in exhaustive detail as to how we are quite certain when human life begins.

    The obvious point of contention is when that life aquires value or if it is inherently valuable from the outset. Then I see the sense of the "err to the side of caution" argument.

    Here it impacts this discussion in one way. To claim that the "Pill Kills" is an agressive stance that is not supported by evidence. It may or may not kill anything. "Abortion Kills" is absolutley true. The question is not does something die, but what dies. That seems a significant difference to me.

    I am not saying that we should endorse the use of OC's or that we should not err to the side of caution. I am merely pointing out that in one scenario there may or may not ever be a life present that dies as a result of OC's. In the other case, there is ceratinly a life present and it is brutally destroyed. These are not equally balanced.

    Given that, I think Granny's point is well taken. We have a hill to die on with surgical abortion. No need to escalate the battle to other hills that have not yet been proven to be as important. We need to scout it out and know what we are doing. We do not need to equate it with surgical abortion just yet. The evidence denies us such certainty.

    God bless,
    Jay

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  10. Serge,

    Thanks for your quick response to my tome.

    You asked if I “have evidence that FSH is effected to that level, and that the ovaries fail to produce any estrogen during the follicular phase.” My evidence would be the result: a 1.1mm thick endometrium. I got this figure from Walter Larimore’s paper, “The Growing Debate About the Abortifacient Effect of the Birth Control Pill and the Principle of the Double Effect.” He cited MRI studies for this figure, referencing Stanford JB, Daly KD. Menstrual and mucus cycle characteristics in women discontinuing oral contraceptives (abstract). Paediatr Perinat Epidemiol 1995;9(4): A9.. Is that info wrong? It is important to my case, so if it is wrong, much of my doubt in this area can be resolved.

    For your specific points:

    (1) If a mature follicle is 15mm, and some women on the Pill have follicles that reach 10mm, we might infer that FSH levels can reach a max of 2/3 their norm, and that the ovaries in turn produce 2/3 their normal amount of estrogen. If so, then the 5-8mm of endometrium estrogen normally builds would be about 2-3mm in Pill users, rather than 1mm as cited by Larimore. But how much estrogen is released by the follicle itself, separate from the ovaries? At http://www.healthsquare.com/fgwh/wh1ch17.htm I read that the mature follicle produces a lot of estrogen. Could it be that since no follicle fully matures, estrogen production never reaches its normal potential, keeping the endometrium to 1mm thick?

    (2) I acknowledged this in my comments. But their flow is light, because the endometrium did not experience much thickening (but it did get to 1mm or so, again, assuming that figure is accurate).

    (3) One of my sources was http://sprojects.mmi.mcgill.ca/menstrualcycle/endocrinology.html. There may have been others as well, but that’s the only reference I had in my notes. If the presence of FSH in the ovaries is not what stimulates them to produce estrogen, then what stimulates estrogen production?

    Jason

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  11. Jay,

    I would agree with everything you said, but I stand by my comments at the same time. While I agree with you that the pro-abortion objection is based in ignorance, one of the pro-life responses to the objection shows that even if we assume this were true, it does not argue for abortion, but against it, based on the principle that we should err on the side of life.

    My point was that this same principle should inform our decision to use the Pill. Beyond that, there is no 1:1 analogy between the two issues. As you pointed out, in the case of abortion we know something is being killed but are uncertain as to whether that thing has value. In the case of the Pill, we are both uncertain if anything is being killed, and if something is, whether that thing has value. All this shows is that we are less certain about the morality of taking the Pill than we are about the morality of abortion. It doesn’t mean we should not equally err on the side of life, due to our ignorance of the answers to these decisive questions.

    Jason

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  12. Jason,

    I was quite confident in what you meant. I wanted to be certain that what I knew was clear to anyone less familiar with all of this than you. It was a clarification comment.

    I think it is important to point out that Serge has said that he thinks that using OC's is probably not a good idea. His original object, and my continued objection, is to those who say "the Pill Kills," and then campaign against OC's as if this question was settled. That is overstating the case.

    We need to educate people as to why we ought to consider the effects of oral contraceptives. On a personal note, my wife and I stopped using OC's after reading a little about it. We cannot claim that we know that OC's kill babies and be operating in a spirit of honesty. Worse than fear mongering, it is distracting dishonest fear mongering. That never seems the right tactic for those objecting on moral principles.

    Your objections and thoughtful considerations are a far cry from that.

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  13. Jason,

    I certainly agree with Jay's comments. Your thoughtful investigation into this issue is refreshing.

    Your citation of Stanford can be found here (http://www.aafcp.org/files/sci_res_forum95.pdf), and no mention of endometrial thickness is in that abstract. I am not having an easy time finding a paper that investigates the endometrial thickness in the late follicular phase for women taking OCs. It would be a very good study to perform (and shouldn't be very difficult.) Since the thickness varies throughout the cycle, the time that the US examination is performed is essential.

    In looking at the effect at FSH and estrogen levels in the follicular phase - it seems clear that women on OCs have less FSH and estrogen, but certainly not zero. I will concede that it is reasonable to believe that this has some effect on the endometrial thickness in the follicular phase, but not to the extent that you state.

    Lastly, most investigators point to the endometrial changes in the luteal phase as being by far the most essential aspect of preparing the endometrium for accepting an embryo. Its not merely a matter of endometrial thickness, but a host of changes that appear necessary (at least most of the time) for the uterine lining to accept an embryo.

    In short, I have stated and still do that I cannot prove that OCs do not impair the ability to the uterine lining to accept an embryo. I am not convinced, but reasonable persons (such as yourself) disagree with me.

    The problem that I have are those who believe this issue is a settled one. Overstating our case does nothing to help us. I applaud you for not doing so.

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  14. Jay,

    Serge can correct me, but it is my understanding that he thinks it best to avoid the Pill, but not because of its supposed potential abortifacient effects. In the comments section of his prior post he wrote, "I actually think it may be advisable to eschew the pill regardless of whether or not it causes a hostile endometrium. However, since I believe that the likelihood of the pill causing an embryo to fail to implant is extremely small and may be zero, I would not use the potential impact on the endometrium as a sole basis to avoid the pill." I, in contrast, think a possible abortifacient effect of the Pill alone is sufficient to advise people to eschew the Pill (although there are other health-related reasons to do so as well).

    But I also agree with you and Serge that we should not overstate our case. We cannot claim the Pill does have an abortifacient effect, but only that it might.

    Jason

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  15. Serge,

    I looked at Larimore's paper again. The most immediate reference is to one of his own papers, found at http://archfami.ama-assn.org/cgi/content/full/9/2/126?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Postfertilization+effects+of+oral+contraceptives+and+their+relationship+to+informed+consent&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT#REF-FSA8035-50.

    When I went there, this was his reference for the claim that the endometrium is only 1.1mm thick for women on the Pill: McCarthy S, Tauber C, Gore J. Female pelvic anatomy: MR assessment of variations during the menstrual cycle and with use of oral contraceptives. Radiology. 1986;160:119-123. He provides a link to this study: http://radiology.rsnajnls.org/cgi/content/abstract/160/1/119?ijkey=ef9f223a35051ddb173cd72c06fddc68547629cd&keytype2=tf_ipsecsha

    Check it out and tell me what you think. Thanks!

    Jason

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  16. Jason,

    My mentioning Serge's caution was to counter the sense that Serge is pro-pill or anti-pill and to highlight that he is pro caution and anti overstatement.

    If I connected Serge in some way to a sentiment that he does not endorse by accident then I apologize.

    I want to say that I personally love this thread and it is this type of exchange that restores my faith in the value of comment threads.

    God bless,
    Jay

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  18. Jay,

    I would agree that Serge comes off as anti-overstatement (rightly so), but a little less pro-caution. I think I have my foot on the brakes a little more than him, but for good reason. He is pretty confident that the Pill poses no abortifacient risk to an embryo, and that if it does, it is as negligible as other standard medical risks, and thus does not warrant total abstention. The more one is confident of this, the less reason there is for them to caution people against using the Pill. Indeed, if he is able to show me that my concerns about the development of the endometrium in the follicular phase are medically invalid, I'm sure my pro-caution advocacy will be turned down a few notches as well.

    I agree with you about the quality of the dialogue here. Not only is it civil, but it has remained on point, and is helping people to better understand the issues, and sort out the truth. I would like to say publicly how invaluable I find Serge's knowledge in this area to be, and how happy I am to have him interact with me on this topic. It's not an easy thing to sort out, and I appreciate the time he has taken to do so.

    Jason

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  19. Jason,

    I have much to say but time is short today. Here is the abstract of the study you cited:

    "Magnetic resonance (MR) imaging was performed on 21 women in different phases of the menstrual cycle, nine who used oral contraceptives and 12 who did not. Sagittal images in a dual spin-echo sequence were obtained to assess conspicuity and dimensions of the corpus uteri, cervix, vagina, and their component tissues. The endometrium, junctional zone, myometrium, cervical canal, fibrous stroma, and vaginal canal were seen in all cases and the vesicovaginal septum, rectovaginal septum, and levator ani in 90%, 86%, and 100%, respectively. The uterus was retrodisplaced in 19% of the women. In the nonpill group, endometrial width was significantly larger (P less than .025) in the secretory phase (mean, 5 mm) than in the follicular phase (3.1 mm). In the pill-using group, endometrial width was 1.1 mm in both phases, significantly smaller than in the nonpill group (P less than .025, follicular; P less than .0005, secretory). Junctional zone width was significantly smaller in the pill-using group (P less than .005). Qualitatively, the myometrium was relatively brighter on second echo images in the pill-using group, compatible with known edema that occurs with use of oral contraceptives. MR can reliably demonstrate gynecologic structure and anatomic changes that occur during the menstrual cycle and with use of oral contraceptives."

    There are two questions I have here. First, as you know the uterine lining changes at different points in the follicular phase (although not as much as the luteal phase). Where in the cycle was the 1.1mm figure taken, and how was that determined?

    Secondly, how is it even possible that the uterine lining did not change at all in these 10 women throughout the cycle? Assuming that they menstruated, why was there not some variation in uterine thickness?

    I may try to pick up the original paper when I get a chance.

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  20. That was easier than I thought. I was able to view the full article here (http://radiology.rsnajnls.org/cgi/reprint/160/1/119)

    The number did not change because they are mean values. They did not distinguish between the different days of the cycle, but only characterized the 21 women in the study as in either the follicular or the secretory (luteal) phase.

    Even more interesting, the author states that the pill may change the lining in the follicular phase, but follows it with this sentence:

    "However, since there were fewer parous women in the pill-using group than in the non-pill group, this explanation is somewhat speculative".

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  21. This has been a really good. To close a loop in my mind, is it possible for someone to comment on differences between what is mentioned here and 'Emergency Contraception'.

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  22. Serge,

    Yes, the 1.1mm figure is an average thickness, but the authors do state: “Endometnial thickness was not significantly different between the follicular and secretory phases in the pill-using group; whereas in the nonpill group, the endometnium was significantly larger (P < .025) in the secretory than in the follicular phase.” It seems, then, that the data on which I based my concern is correct.

    Regarding the portion of the paper you quoted, the full quote is as follows: “Prolonged use of the pill can cause a decrease in corpus size, perhaps accounting for the smaller size of the uteri in the pill-using group in the follicular phase. Indeed, the combination pill may obliterate the uterine growth that occurs with increasing estrogen titers in the follicular phase. However, since there were fewer parous women in the pill-using group than in the nonpill group, this explanation is somewhat speculative.”

    Questions:
    1. In the first sentence, do they mean the uterus itself is smaller, or the thickness of the endometrium? It seems to me that they are saying the pill shrinks the uterus, but the second sentence seems to be speaking of endometrial thickness.
    2. How could a past pregnancy affect how the pill works? It seems to me that the pill would suppress estrogen production (and thus endometrial growth in the follicular phase) in every woman, regardless of her childbearing history.

    I think we should also be clear on what they are speculating about. They are speculating that the reason the endometrium is only 1mm thick in pill users is because the pill suppresses estrogen production. They are not speculating that the pill is responsible for keeping the endometrium at 1mm thickness. As they write, “Endometrial thickness was significantly smaller in the pill-using group, correlating with the well-established fact that oral contraceptives cause atrophy of the endometrium.” Indeed, earlier in the paper they are clear that “as the estrogen level rises due to follicular growth, the endometrium thickens.” If that is why the endometrium thickens in non-pill users, I don’t think it is very speculative to think that the endometrium is thin in pill users because the pill interferes with estrogen production.

    What are your thoughts?

    Jason

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  23. Serge, can you give quickly the source citation for your great chart here of all the occurrences in the cycle? I'm writing something up on this for my own use and want to print out the entry, including the chart, and give the source for the chart.

    It's interesting for me to see as I look up some other sources that it appears fairly common for popular-level writing on this subject to imply quite explicitly that the _thickness_ of the endometrium is determined _before_ ovulation. For example, I have a book called _How to Get Pregnant_ that says pretty much exactly that. The author states that the corpus luteum causes the endometrium to become "spongy" and receptive but says that the thickness is built up (he implies, entirely) prior to ovulation by the estrogen in the woman's system during the follicular phase. This obviously is incorrect.

    An interesting point in response to some of the considerations Jason is raising is this: If the corpus luteum makes a significant increase in the thickness endometrium in a case of break-through ovulation (which we can assume it would do), and if it also makes the endometrium more receptive in other ways (which we can assume it would do), how plausible is it that implantation would be prevented entirely by a somewhat different "start point" for that thickening process? Even if the final thickness were not as great as for a woman not taking OC's, do we have reason to think that a significantly thickened and otherwise receptive endometrium would in fact be "hostile" to implantation?

    Another point: If breakthrough ovulation occurs, presumably it occurs because of some hormonal events before ovulation. Perhaps only a couple of days before, but nonetheless, breakthrough ovulation doesn't occur by magic or for no hormonal reason. Is there not reason to think that the very hormonal causes that permitted breakthrough ovulation--the body's "overriding" the pill to that extent--would also result in a higher release of estrogen in the days prior to ovulation and hence in a thicker endometrium even at the time of ovulation than one finds in the typical, non-ovulatory, woman using the pill?

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  24. Jason, I think the reason they are mentioning past history of pregnancy is because they are measuring overall uterus size, which would be affected by past pregnancy. One of their speculations is that the women on the pill had smaller uteri because the uterus apparently gets bigger with increased estrogen during the cycle, but pill users would have less estrogen in their systems. But I think they are saying that they couldn't get a good comparison sample that allowed them to "control" for the effect of past pregnancy on overall uterus size. In other words, it might be that the women on the pill had, on average, smaller uteri simply because most of them had never been pregnant before.

    There is, of course, no question that women taking the pill have less estrogen in their systems than women not taking the pill. The major question for purposes of this discussion, however, is whether that is true only, or only to any significant extent, for women on the pill *who do not ovulate* and whether breakthrough ovulation would give us an entirely different sample group with an entirely different endometrial profile.

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  25. I’m not Serge, but I did want to interact with some of what you said.

    Regarding your 2nd paragraph in your 1st post, it is true that most of the thickness of the endometrium has been built up by the time of ovulation. It continues to be built in the luteal phase, as estrogen continues to be present. Progesterone also increases to the thickness. From what I have read it induces swelling, and increases secretion by stimulating glands in the endometrium, making it spongy and strong. I like to think of the process as water being applied to a very dry sponge. A dry sponge is porous, but stiff and of no use for cleaning. But once water is applied, it thickens up, and becomes receptive to gook. In a similar fashion, estrogen builds the sponge, but progesterone hydrates it (and just like the sponge, the endometrium expands when “hydrated” by the secretory fluids).

    Regarding your 3rd paragraph in your 1st post, your suggestion is plausible. To stick with my analogy, even a very thin sponge, when hydrated, can clean up gook. It just doesn’t do it as well as a thicker sponge. Maybe the same is true of the endometrium. Then again, maybe not. Maybe it is like seed in soil. Seed grows best in deep soil. While some seed manage to grow in well-watered, shallow soil, some cannot take root. Likewise, it could be that the endometrium is too “shallow” for the embryo to “take root,” even though it is “well watered.” I don’t know. I’m just bringing up possibilities.

    Regarding your final paragraph, it’s my understanding that breakthrough ovulation does not occur because the natural body processes were able to “override” the pill, but because the pill was not used properly, and in the absence of its hormonal regiment, the normal cycle processes resumed. And if it is just the normal process resuming, I see no reason to think the body will produce “catch-up” estrogen to try to normalize the endometrium by the time of ovulation.

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  26. Lydia,

    That explanation makes sense, which makes me question all the more whether they are talking about the thickness of the endometrium. It is one thing to say that the baloons in group X are larger than those in group Y, but a wholly other matter to say the baloons in group X are thicker than the baloons in group Y. Are they talking about size or thickness?

    Clearly they are talking about size in the first sentence, but are they doing so in the second when they speak of endometrial "growth?" If not, then this quote does not pertain to the issue I raised after all, and there is nothing in the paper that would deem the notion that the pill causes a thin endometrium.

    I am inclined to think they are referring to endometrial thickness, because earlier in the paper they used "growth" to refer to thickness. And yet, by starting off with "indeed," the second sentence seems to be an expansion on the point of the first sentence, which is about the size of the uterus, not the thickness of its wall. That makes me think this entire paragraph is about how the pill affects the size of the uterus, not the endometrium. I am hoping Serge can shed some more light on this.

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  27. "{I}t’s my understanding that breakthrough ovulation does not occur because the natural body processes were able to “override” the pill, but because the pill was not used properly, and in the absence of its hormonal regiment, the normal cycle processes resumed. And if it is just the normal process resuming, I see no reason to think the body will produce “catch-up” estrogen to try to normalize the endometrium by the time of ovulation."

    Several points are relevant here. First of all, if breakthrough ovulation occurs _only_ when the pill is used improperly, this hardly should be a major conscience problem, or perhaps any conscience problem at all, *in and of itself*, to a conscientious Christian woman using the pill. For she is not a careless person and is intending to use the pill properly. Moreover, other methods can be used as back-up if she misses a single pill. It's hardly fair to say "the pill kills" if one means "the pill kills (or might kill) when you don't use it the way you are supposed to." In the paper I linked in Serge's other thread, which I _highly recommend_, by the AAPLOG guys, they expressly use only the known pregnancy rate of the pill with compliant users for their calculations. This seems only fair.

    Second of all, you speak about the "normal processes" resuming. But I think it's very important to understand that, as a part of a normal process, ovulation does not occur for no reason. The hormonal cascade necessary to cause ovulation is rather precise. If there isn't estrogen, and a lot of it, there isn't the LH surge. And if there isn't a good bit of estrogen, the cervical mucus is not receptive, and conception cannot take place. If there isn't FSH, then no follicle gets to the point of being ready to burst out when the LH surge comes. But FSH causes the body to produce more estrogen, etc.

    Now, that _is_ the normal process. I get the impression that you know that, but in that case, it seems that there is something to my point that even if one were to miss a pill or, with perfect compliance, the ovaries were to ovulate despite the pill, there would *have to be* significant quantities of estrogen and FSH in the system prior to ovulation, or else ovulation simply wouldn't happen. It's not literally impossible, I suppose, that a brief and sky-high spike of estrogen--say, for just one or two days prior to ovulation--should produce all the effects necessary for ovulation, but even that would (I would think) produce some pre-ovulatory endometrial thickening, more so than in a cycle where ovulation was not going to occur and the ovaries were responding fully to the pill. Moreover, it seems to be an open question whether only one or two days' worth of estrogen and FSH _all by itself_ would be enough to bring about ovulation. It isn't usually enough, as far as I can tell. The normal cycle involves about 7 days post-menstruation of stimulation of the ovaries by FSH and of increasing amounts of estrogen before ovulation occurs at all. These things are _causal_ for ovulation, and they are also _causal_ for endometrial thickening. It wouldn't be a matter of the body's "trying to catch up" but rather of the fact that hormonal events pre-ovulation that produce endometrial thickening--specifically, the presence of lots of estrogen--also produce ovulation.

    I think an easy mistake to fall into here is to treat all of these physical events as causally independent so that one then uses a faulty "all else being equal" assumption. "Suppose ovulation occurs, all else being equal." Well, for one thing, if that _were_ possible, the cervical mucus would be totally unreceptive, and you wouldn't have to worry about fertilization! But then, it's as though one is trying to _create_ a worry. "Suppose ovulation occurred, and there were _just enough_ estrogen in the system prior to ovulation to prepare receptive cervical mucus, but there had been _just too little_ estrogen in the system prior to ovulation to thicken the endometrium, and even though all the luteal phase thickening and preparation occurred, that pre-ovulatory difference were just enough to prevent implantation."

    This seems to me, given the causal interconnectedness of the events involved, like an artificial worry from an empirical perspective.

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  28. Are there any peer reviewed articles on this subject yet, or any 2009 or 2010 information? I'm really looking into this issue... So far, this is one of the most helpful resources I have found. Does anyone know of any more recent info?

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  29. I've provided some links on this subject in a June entry in my blog, which you can find a link to in my name. I've also commented on this subject in a couple of December entries and a few others.

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  31. I just recently found this post. Do you have any updates that would either strengthen or weaken your case?

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  32. Jason's comments are more in line with what I learned at UIUC as an Animal Science major while taking Animal Reproduction, Lactation, and Growth. While we were talking farm animals, the same principles apply. From my recollection, artificial hormones work primarily on the biofeedback loop, preventing the appropriate levels of natural hormone production (estrogen and progesterone). Without sufficient estrogen, the uterine lining does not develop sufficiently, even if progesterone is not blocked. I'd recommend you delve into animal science research if you are looking for greater detail. They can (and do) experiment with animals in ways not possible with humans, that is, they can apply the hormones, then slaughter the animals and measure the organs. (The experiment we did with mice, with estrogen, progesterone, and both, was such an experiment.)

    The original human contraceptives were more effective at preventing pregnancy, as the levels of estrogen were higher and less break-through ovulations occurred, but that came at a steep price in women dying in greater numbers from blood clots and strokes. Even if you cling to the possibility that hormonal contraceptives don't abort a newly conceived child, why would you want to subject yourself (if you're a woman) or the woman you love to powerful hormones that are known to cause breast cancer (WHO 2005, NIH 2007), heart disease, strokes, and death, among other harms? Especially when modern Natural Family Planning is available for spacing or avoiding pregnancy if a serious reason exists? NFP is 100% safe for mothers and babies, over 99% effective when used correctly, and builds relationships through communication. The Couple to Couple League has more information.

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