Document Title: lifeissues | The Pill: How it works and fails. THE PILL: HOW IT WORKS AND FAILS. John Wilks, B. Pharm Reproduced with permission QUESTIONS AND ANSWERS Q. I have been prescribed the pill by my doctor. I have read there are different types - could you explain these to me. The commonly used name of 'the pill' is made up of two 'styles' of formulations; the progesterone-only pill (POP) and the combined oral contraceptive pill (COCP). The COCP contains an oestrogen, most frequently ethinyl oestradiol, and a progesterone, either levonorgestrel or norethisterone. Fixed formulations of the combined pill contain the same levels of oestrogen and progesterone for 21 days, followed by an optional 7 sugar tablets. Newer versions have hormonal levels which vary two or three times during the month (hence the bi- and tri-phasic names some of these products carry). Within the last few years, the combined pill has been released containing gestodene or desogestrel as the progesterone component. These products are known as third-generation progesterones. They are made as either a fixed dose formulation eg. Minulet, or as a triphasic formulation eg. Tri-Minulet. They are not very popular because they double the risks of a woman developing a blood clot.1 2 3 Q. How does the pill really work? A. There are four ways the pill acts to stop sperm reaching an egg (ovum). * First, the hormones in the pill try to stop an ovum being released from your ovary each month. This is known as the suppression of ovulation. Research has shown that neither the progesterone-only pill4 nor the combined progesterone-oestrogen formulations always stop ovulation.5 6 7 * Second, all formulations of the pill cause changes to the cervical mucus that your body produces. The cervical mucus may become thicker and more difficult for sperm to fertilize an ovum.8 * Third, all formulations of the pill cause changes to the lining of the womb (properly known as the endometrium). Under the influence of the chemicals in the pill, the lining of the womb doesn't grow to the proper thickness. You will notice that your periods are lighter when you are on the pill. This is because the lining of the womb has not developed properly. But this change also means that the womb is not in the right stage of development to allow a fertilized egg to attach properly (this attachment process is known as implantation).9 10 11 12 This action of the pill will be discussed again in this booklet. * Fourth, the pill causes changes to the movement of the Fallopian tubes. This effect may reduce the possibility of the ovum being fertilized.13 14 15 It is very important for you to understand that none of these ways the pill works is completely reliable.16 Ovulation is not always stopped,17 18 19 20 cervical mucus does not always stop the movement of sperm21 22 the damage to the lining of the womb sometimes allows for implantation to occur,23 24 and Fallopian tube activity does not always stop sperm and ovum from joining to create a new human person.25 Q. I think you may be right because my girl friend had a baby even though she took the pill each day. The doctor said that it will stop me from becoming pregnant and I hope this is correct, but I am a little concerned. A. Your concern is quite reasonable. Your friend's pregnancy is the most obvious and simplest proof that the four inter-connected pill actions do not always operate 'successfully' in every woman. In theory, almost no women should have a baby whilst on the pill. The theoretical success of the combined pill is 99.66%. This means that only 0.34% or 34 women in 10,000 should have a diagnosed pregnancy. But the reality is that the combined pill only prevents a diagnosed pregnancy in 90-96% of women. In other words, 4-10 women in every 100 using the pill for one year do have a diagnosed pregnancy.26 Australian medical and science journalist Melissa Sweet has published 'get-real' figures in the same range.27 Q. OK, if the pill is not quite as successful as promised, why does it fail? A. One part of the answer to this question is some women forget to take a tablet each day. Missing a single tablet may be all that is needed for ovulation to occur. Even the drug companies agree that missing a single dose is significant. Ovulation may occur, which could lead to a diagnosed pregnancy. That is why the leaflet inside the pill packet recommends using something like a condom or diaphragm, even if you are only 12 hours late in taking your daily pill tablet. The pill manufacturers also suggest that a condom or diaphragm should be used for seven days because of the risk of ovulation and pregnancy.28 Another reason some women have a diagnosed pregnancy whilst on the pill can be due to stomach illness such as vomiting or diarrhoea. These illnesses may prevent the full dose of the pill being absorbed into the woman's body.29 The effect of less-than-complete drug absorption is the same as missing a dose - ovulation could occur. Again, the pill manufacturer recommends condom or diaphragm use for a full 7 days to prevent sperm and ovum joining. A third reason for a diagnosed pregnancy whilst taking the pill could be because of a drug interaction with antibiotics (such as amoxycillin, co-trimoxazole, tetracycline, erythromycin and amphotericin), or large doses of vitamin C, or anti-epileptic medication, barbiturates and rifampicin (used for T.B.).30 31 32 The effect of the drug interaction is to reduce the quantity of hormones absorbed. Therefore ovulation might occur. Q. But none of these things happened to my girl friend. She always took her tablet at breakfast time, has not had any stomach upset and hadn't taken any other medicines. How come she is now pregnant? A. One possible answer is that your girl friend had what is known as 'break-through ovulation'. As the name suggests, a woman ovulates even though she always takes her daily dose of the pill, is not sick, and is not taking any other medications. Proof that break-through ovulation (sometimes also called 'escape-ovulation') does occur even under perfect health conditions was first shown by Dr. Nine Van der Vange, State University of Utrecht, The Netherlands, Dept. of Obstetrics & Gynaecology, in 1984.33 Dr Van der Vange's research used high resolution ultra-sound which visually showed that women ovulate on the popularly prescribed low dose pill.34 A blood test confirmed that ovulation had occurred.35 The pill can have a break-through ovulation rate that can be as high as 17 ovulations per 100 women who used the pill for one year. Other researchers have shown that the low dose pill has an even higher rate of break-through ovulation of almost 27 ovulations per 100 women per year.36 Q. I have heard some people say the pill has an abortifacient capacity.What does this word mean, and is it really true anyway? A. Before answering this question it is very important that we all have a correct understanding of the key biological terms relating to pregnancy. The following definitions have been accepted by major medical texts for decades. 'Conception' refers to the moment at which the sperm penetrates and fertilizes the ovum to form a viable zygote.37 It does not refer to the process of implantation of the newly created human embryo, which is a separate event, occurring about 7-8 day's after conception.38 A woman is pregnant because conception has occurred, not because implantation has occurred. This distinction is important. At the precise and unique moment of conception, a woman is 'pregnant' with "a new individual".39 This is an accurate and informed medical description. It is the same terminology used by Prof. John Dwyer, pre-eminent Australian AIDS expert and researcher, who has described the moment that the sperm enters the ovum as the creation of a "new and unique individual".40 Well known medical writer, Professor Derek Llewellyn-Jones, author of every woman, has also written that when the male genetic material from the sperm joins with the female genetic material in the ovum, "a new individual is formed".41 To stop conception occurring, that is, to stop sperm and ovum joining, is contraception. Condoms, diaphragms, spermicides, vasectomy and tubal ligation are accurately described as methods of contraception. Obviously any drug or device used after conception has occurred cannot be termed a contraceptive.42 The correct term to describe any interference with the pregnancy after conception has occurred is 'abortifacient'.4344 This is the precise biological description for any drug or device that acts to end a pregnancy once it has begun at conception. You might be interested to know that many major medical dictionaries have definitions of 'conception', 'pregnancy' and 'contraception' that are the same as those listed above.45 46 47 48 49 50 51 524546474849505152 It is medically dishonest to break from these definitions. And yet, this is precisely what some scientists have recently started to do. They seek to define pregnancy as beginning with implantation, not fertilization.535455 But as I mentioned earlier, implantation occurs 7-8 days after the new human person has come into existence. The pregnancy, and the new human person, are already many days old by the time implantation has occurred. Therefore, what these scientists are trying to do is get people to think that abortifacient drugs such as the pill are really just contraceptive drugs. Do you see the clever shift in definitions these scientists are trying to make? Redefine when a pregnancy and new human life begins, and you redefine the key characteristic of the drug - how it works! Obviously many people object to abortifacient drugs because they can cause a loss of human life. Not so many people object to methods of contraception (condoms, diaphrams etc), because these methods prevent new human life being created. Hence, if scientists succeed in convincing people that human life begins after implantation, eventually most people will have no objection to the pill. They will have been tricked into believing that human life had not begun when the pill exerted its anti-implantation effect. Q. So how do you prove that the pill acts as an abortifacient? A. The answer to this question can be found by comparing the rate of break-through ovulation and the detected pregnancy rate. The ovulation rate has been reported to be about 27 ovulations in 100 women using the pill for one year. But the detected pregnancy rate is much lower at around 4 pregnancies per 100 women using the pill for one year. As you can see, there is a big difference between the number of women who ovulate (27) and the number of detected pregnancies (4). What has happened within the woman's body to reduce the high ovulation rate to such a low number of detected pregnancies? I suggest that one answer to this important question is that pregnancies have begun, because ovulation and fertilization have occurred, but some of these pregnancies are terminated because implantation cannot take place. The pill has damaged the lining of the womb, stopping implanation. Q. You talk about the pill causing damage to the lining of the womb, but what does this really mean? A. The process of implantation of the human embryo into the lining of the womb is a very complex and delicate process. Proper attachment and successful implantation is under the guidance and control of a vast array of 'implantation factors'.565758 These chemical factors, with names such as interleukins, PAF and LIF, actually cause what is referred to in medical journals as "cross-talk" between the embryo and the cells which line the womb.59 That is, the cells of the new human embryo and the cells of the lining of the womb chemically speak to each other. The purpose of this chemical communication is so the womb will be fully prepared and ready to bind with the human embryo when it attempts to implant. The pill's role in all of this is that it alters the levels of these implantation factors. Too much oestrogen and progesterone, via the pill, causes harmful changes to the levels of these implantation factors. Recent research has shown that implantation fails if the levels of oestrogen and progesterone are too high.6061 It is because the levels of these two hormones are wrong that the week-old embryo cannot attach to the womb. Cell talk fails, the proper development of the womb doesn't occur, and the embryo dies from a lack of nutrition normally supplied to it from the lining of the womb. In fact, wrong levels of artificial progesterone have been shown to cause a very thin lining of the womb, making implantation impossible. 62 636263 You can understand this concept more fully by considering the example of a space shuttle, low on fuel and oxygen, which urgently needs to dock with the space station. The mother ship and the shuttle communicate with each other so that the shuttle knows which docking bay to go to. Importantly, the mother ship knows which bay to make ready. If this electronic communication fails - disrupted "cell-talk" -, the shuttle may go to the wrong docking bay, fail to attach to the mother ship, drift away, and the crew dies from a lack of food and oxygen. Or it might go to the right bay but not find all the docking apparatus in place. Again, the attachment between the two fails due to faulty communication and the crew dies. As well, there are a special group of molecules found both on the lining of the womb and on the 7-8 day old human embryo known as integrins. Integrins are referred to as 'adhesion molecules'. Researchers have shown that these adhesion molecules greatly assist the process of implantation. Going back to our example of the docking process between a space shuttle and the mother ship, integrins could be thought of as grappling hooks that 'hold' the human embryo onto the womb whilst the process of implantation is completed. The artificial hormones in the pill have been shown to damage the ability of integrins - the implantation 'hooks'- to function properly. Because of this damage to the proper functioning of integrins, the limited amount of time the human embryonic person has for attaching, known as the 'window of implantation', is closed. As a result, the human embryonic person dies.64656667 As you can see, the pill acts as the great communication wrecker. Q. OK, but I think that all this talk about 'human life' beginning when the sperm and the ovum join is just a bit weird. Isn't it just a bundle of cells? A. This is a very important issue. Consider the following: Given that it was human sperm and human ovum that joined together, you would agree that the result would have to be a human something. But what is that 'something.' Is it a human person even though it starts out looking just like a lump of cells? To answer this question, think about what is added to this clump of cells that attaches to the lining of the womb and grows over 40 weeks to be a born baby. This clump of cells receives only three things from its mother: somewhere to live, food and oxygen. If you say that the clump of cells isn't human at its beginning, then you need to show that there is something magical about where you live, what you eat, or what you drink that can convert you from being non-human to human. I think you would agree that there is nothing. Hence the only logical conclusion can be that it is always human because of where it came from - two human parents. It is very easy to be tricked by the appearance of the human embryo ('it just looks like a lump of cells') or its 'address' -floating in or newly attached to the lining of the womb. But these superficial features are irrelevant. We must look to what it is, not what it looks like. Human in origin means it is human in nature. It is a human person just like you or I; the only difference is that it just hasn't fully grown up yet. Q. What about the morning-after pill? Doesn't it work by stopping pregnancy? A. The morning-after pill is a very high dose of the two female hormones called oestrogen and progesterone. A woman takes a dose of progesterone in the 'morning-after pill' which is 10-20 times the amount of progesterone she would get via her daily birth control tablet. The dose of oestrogen from the morning-after pill is also very high: about 5 times the amount she gets from her daily birth control tablet. As you can see, these doses are much greater than the daily birth control pill dose. Now if the birth control pill can act as a chemical abortifacient in low doses, it would seem reasonable that the morning-after pill would also act as an abortifacient. REFERENCES: 1. Graham A, Grieve F, Davie, Glasier A. Lancet. 1995;346:1430 (Letter). [Back] 2. Choo V. EU agency asks for more data on oral contraceptives. Lancet. 1995;346:1219.(Letter). [Back] 3. Thomas SHL. Mortality from venous thromboembolism and myocardial infarction in young adults in England and Wales. The Lancet.1996;348:#9024. [Back] 4. Australian Prescription Products Guide (APPG) 25th Ed 1996 p.1531. [Back] 5. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Pergammon Press.1990; 8th Ed p.1405. [Back] 6. Micromedex (Clinical Computerised Information System) Vol 86 Triquilar ED monograph. 1995. [Back] 7. Van der Vange, N. Ovarian activity during low dose oral contraceptives. In: Chamberlain G, ed. Contemporary Obstetrics and Gynaecology. Butterworths, London. 1988 p.323. [Back] 8. Rahwan R, Prof. Pharmacology & Toxicology. Ohio State University. Chemical Contraceptives, Interceptives and Abortifacients. 1998 p.9. [Back] 9. MicroMedex, Depo-Provera Monograph, 1995. Vol 85. [Back] 10. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 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Localization, quantification, and activation of platelet-activating factor receptor in human endometrium during the menstrual cycle: PAF stimulates NO, VEGF, and FAK. The FASEB Journal. 1998;12:831-843. [Back] 58. Sawai K et al. Human decidual cell biosynthesis of leukemia inhibitor factor: regulation by decidual cytokines and steroid hormones.Biol Reprod. 1997;56:,5,1274-80. [Back] 59. Simon C, Gimeno MJ et al. Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human endometrial epithelial cells in vitro. J Clin Endocrinol Metab. 1997;82:8,2607-16. [Back] 60. Simon C et al. Increasing uterine receptivity by decreasing estradiol levels during preimplantation period in high responders with the use of a follicle-stimulating hormone step-down regimen.Fert Ster. 1998;70,2: 234-238. [Back] 61. Gidley-Baird AA, O'Neill C et al. Failure of implantation in human in vitro fertilization and embryo transfer patients: the effects of altered progesterone/estrogen ratios in humans and mice. Fert Steril. 1986;45:1,69-74. [Back] 62. Faundes A et al. Endometrial thickness and oestradiol concentration in women with bleeding complaints during use of Norplant implants. Hum Reprod. 1998;13:1,188-91. [Back] 63. Issacs JD Jr et al. Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone. Fert Steril. 1996;65:2,262-6. [Back] 64. Simon C, Gimeno MJ et al. Embryonic regulation of integrins beta 3, alpha 4, and alpha 1 in human endometrial epithelial cells in vitro. J Clin Endocrinol Metab. 1997;82:8,2607-16. [Back] 65. Lessey BA, Ilesanmi AO et al. Luminal and glandular endometrial epithelium express integrins differentially throughout the menstrual cycle: implications for implantation, contraception, and infertility. Am J Reprod Immunol. 1996;35:3,195-204. [Back] 66. Yoshimura Y. Integrins:expression, modulation, and signaling in fertilization, embryogenis and implantation. Keio J Med. 1997;46:1,16-24. [Back] 67. Widra EA et al. Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line.Mol Hum Reprod. 1997;3:7,563-8. [Back] Copyright © 2000. (Lifeissues.net) Kochi, Japan. All Rights Reserved.