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The Pill
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<p class="Heading1A"><span style="color: black;">The Pill: What are we talking about?</span></p>
<p class="MsoNormal">by Luciene Borowik, MD<a name="GoBack"></a></p>
<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">“The pill” was back in the media in the last week. “The pill.” Yes, the same old pill that’s been with us since the early 1960s. If you are in your fifties, chances are that your mother used the pill, maybe after you were born, or before she was ready to have children. I am not going to talk about what put the pill back into media shouting matches. I just want to talk about the pill itself.</span></p>
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<p class="Heading2A"><span style="color: black;">How the pill was born </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The principle behind contraception using hormones had been studied, and was somewhat understood, by scientists since the 1920s. In the 1950s, Margaret Sanger, an American social reformer, and another American, Katharine McCormick, a biologist and a philanthropist, tried to convince reluctant scientists and physicians to create chemical preparations that could work as contraceptives. The first paper on a compound that would stop ovulation was published in 1956 by the American endocrinologist Gregory Pincus, and another American, the gynecologist and researcher John Rock. The FDA approved the oral contraceptive in 1960. Great Britain approved the pill in 1962. (Thanks, Encyclopedia Britannica, for this paragraph.)</span></p>
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<p class="Heading2A"><span style="color: black;">What is the pill?</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The name of the compound that stops ovulation is ethinyl estradiol.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Estrogen works in several different ways in a woman’s body. In contraception, its most important role is to stop the pituitary gland from telling the ovaries to make a new egg available for fertilization. Ethinyl estradiol cheats the pituitary gland into “thinking” there is already estrogen in the system.</span></p>
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<p class="Heading2A"><span style="color: black;">What does the pituitary gland do?</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Let’s use an orchestra as a metaphor. The pituitary gland is the conductor. The other glands are the musicians. Glands like the thyroid, ovaries, and adrenals depend upon the conductor to tell them when to begin playing, and how forcefully to play. The conductor also sets the rhythm and the tempo, so that the music is nuanced and coordinated. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The pituitary gland “listens” to hormones the glands have been making. It tells the glands to make more, make less, or to stop making them. This is called negative feedback. Too much hormone and the pituitary gland will signal the glands to stop. Too little, and the pituitary gland tells them to make more. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Contraceptive pills are all about the ovaries. The ovaries make two types of hormones: estrogen and progesterone. The conductor, that small pituitary gland</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">located in the brain, behind the nose</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif'; color: #d90b00;">-</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';"> tells the ovaries to make one or the other, depending on the time of a woman’s cycle. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The pituitary wants the ovaries to make estradiol, so that the immature oocyte becomes </span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif'; color: #d90b00;">a </span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">mature one, and is ready for fertilization. Oocytes are those eggs kept in the ovary since the woman was </span><span class="Strikethrough">still</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';"> a fetus, in an arrested state of meiosis, waiting to grow into a human being. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">At some point the pituitary gland says, “There will be a follicle,” and releases FSH (follicle stimulating hormone) into the bloodstream. The follicle is a little island of cells that will take care of the oocyte, make it grow, and nurture it. The follicle also grows bigger and bigger until it’s big enough to break, setting the egg free. The process is very complicated, and includes a second pituitary hormone, LH, that can only do something about the egg when the follicle is ready to respond to it. The LH peaks in the middle of the cycle, when the follicle starts making progesterone.</span></p>
<p class="Heading2A"><span style="color: black;">What does the pill do?</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Most pills have some chemical compound of estradiol and progesterone in them. They are called “Combination Oral Contraceptive.” Some hormonal contraceptives have only progesterone. (I’ll talk about the progesterone-only contraceptives later.) The combination contraceptives tell the pituitary gland, “There you go. We’ve got enough estrogen.” The pituitary gland calms down, “thinking” the ovaries are the ones making the estrogen, and therefore, are already working on the follicle.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The pituitary concludes that the ovaries no longer need FSH.</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">No FSH gets out. The ovaries, on the other hand, cannot fully mature the egg, and put it to work. Without FSH and LH, the egg remains in its arrested state. No ovulation this time.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">The pill is very effective. Statistics say that its theoretical failure rate is 0.1 percent. It is a two-tiered defense: the estrogen in the pill stops the ovaries from ovulating; the progesterone in the pill makes the cervical mucus too thick for sperm to barge in, say howdy, and meet the egg. The progesterone also changes the way the fallopian tube moves, slowing it down, and making it difficult for an egg to travel from the ovary to the uterus. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">In the uterus itself, the pill makes the endometrium less suitable for a fertilized egg to implant and start growing. Endometrium? Oh, sorry, it is the inner layer of the uterus. It responds to the hormones, growing thicker in order to welcome the fertilized egg. If there is no egg, the endometrium starts shrinking and finally separates from the other layer, causing the menstrual bleeding.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Other uses? You betcha. Other uses for the pill are seldom mentioned in public debates. The pill does much more than contraception. It is used to treat medical conditions such as <em>polycystic ovary syndrome</em>, painful menstruation, including those very painful periods women with endometriosis have to deal with. The pill also treats heavy periods, making women bleed less or not at all. </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">If the pill is given to control bleeding, the doctor must first investigate the cause of the bleed, so it is the doctor’s decision to start the pill, or another treatment. The pills that make women have no periods, the so-called “continuous pills,” also help women who suffer from menstrual migraines. Some special preparations of the pill are used to control mood-instability in women suffering from <em>premenstrual dysphoric disorder</em>. Recent studies have been showing that the pill may protect against endometrial, ovarian, and colon cancer.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Very good, right? Yes, but the pill also has a downside. Possible adverse effects include bloating, nausea, breast tenderness, abnormal bleeding, and weight gain. It may also cause high blood pressure, or makes the high blood pressure dangerously high in women with poorly controlled hypertension. Women who smoke, or have a family history of thrombophilia should stay away from the pill, since the pill may cause them to have blood clots.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Women who have had breast cancer or a blood clot should never try to use the pill in any of its forms. The World Health Organization recommends that women over the age of 35 with migraines, or any women with migraine with aura, should not use oral contraceptives. Diabetes is not a contraindication for the pill, but it makes</span><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">more difficult to control the blood sugar. Some antibiotics and medications to control seizures make the pill less effective as a contraceptive. Epilepsy is yet another problem. The World Health Organization suggests that women with epilepsy should not use hormonal contraception—with the exception of the injection, the so-called “Depo,” or depo-medroxyprogesterone acetate.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Depo is an example of progesterone-only contraceptive. The advantage of the Depo injection is that it offers women the option taking the contraceptive only every three months, instead of every day. Besides, with Depo, there will be no menstrual bleeding. Yay! </span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">About that: I remember a cocksure male gynecologist in the 1980s telling me, “Having periods is very important for women. It is a psychological need to them. No woman in the world will want to take the injection.” To which I replied, “Ha-ha-ha-ha.” What else could I do? Give him some Anti-cluelessness injection? They’re not even in the pre-clinical trial stage today.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Other examples of the progestin-only contraceptives are the mini-pills, the implants, and the intrauterine-contraception. Risks? Yes. Again, women with thrombophilia should stay away from hormone contraception. It is also not recommended for women who have had breast cancer, or any hormone-related cancer. Women who smoke cigarettes are also in more risk for developing blood clots when they use the pill. Also—and most women know this—progestin-only contraceptives cause osteoporosis.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">Well, that’s probably enough about the pill for now. I did not mention emergency contraception. I may go there, if you guys want.</span></p>
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<p class="PlainText1"><span style="font-size: 12.0pt; mso-bidi-font-size: 10.0pt; font-family: 'Times New Roman','serif';">A final reminder. I would like to repeat that the pill is not only used as a contraceptive. Many women, as mentioned above, need the pill to keep their medical conditions under control.</span></p>
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<p class="MsoNormal" style="text-align: center;" align="center">References</p>
<p class="MsoNormal">"Contraception." Encyclopædia Britannica. <span style="text-decoration: underline;">Encyclopædia Britannica 2007 Deluxe Edition</span>. Chicago: Encyclopædia Britannica, 2012.</p>
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<p class="MsoNormal" style="background: white;">UpToDate. Overview of the use of estrogen-progestin contraceptives</p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Authors</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Kathryn A Martin, MD</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Robert L Barbieri, MD</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Section Editors</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Peter J Snyder, MD</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">William F Crowley, Jr, MD</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Deputy Editor</span></a></p>
<p class="MsoNormal" style="background-image: initial; background-attachment: initial; background-origin: initial; background-clip: initial; background-color: white; background-position: initial initial; background-repeat: initial initial;"><a href="http://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/contributors"><span style="color: black;">Kathryn A Martin, MD</span></a></p>
<p class="MsoNormal">Literature review current through: Jan 2012. | This topic last updated: Oct 20, 2011.</p>
<p class="MsoNormal"> </p>
<p class="MsoNormal">Where to learn more:</p>
<p class="MsoNormal">Mayo Clinic</p>
<p class="MsoNormal"><a href="http://www.mayoclinic.com/health/birth-control-pill/WO00098/NSECTIONGROUP=2"><span class="Hyperlink1">http://www.mayoclinic.com/health/birth-control-pill/WO00098/NSECTIONGROUP=2</span></a></p>;
<p class="MsoNormal"> </p>
<p class="MsoNormal">UpToDate</p>
<p class="MsoNormal"><a href="http://www.uptodate.com/contents/search?search=the+pill&sp=3&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset="><span class="Hyperlink1">http://www.uptodate.com/contents/search?search=the+pill&sp=3&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=</span></a></p>;
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