Transcription
Okay, we have finished the physiology part. Let's move on to the part that is pharmacology, specifically of sex hormones, which are estrogen, progesterone, and contraceptives. This might be the part you need in pharmacology. We will start with estrogen, considering it as the primary hormone, the younger sibling, the assistant to estrogen. However, it is the original one, the one that does all the work. I will start with estrogen, taking it one by one, and talk about its sources, chemistry, mechanism of action, pharmacokinetics, adverse effects, uses, and so on. Then we will move to progesterone, and after that, to hormones related to estrogen.
Regarding the sources of estrogen, I have two sources. I have the estrogen that is in a woman's body, and I have estrogens that we have synthesized in companies, in factories. They are called... Where do they come from? You know the primary source is the ovary, so that's number one. However, don't forget that estrogen can come from other sources, even if they are few, but don't neglect them. And don't forget that estrogen can also come from the adrenal gland, in small amounts. It can also come from adipose tissue. And never forget this information. So, I have three sources of estrogen in a woman's body: the ovary primarily, then the adrenal gland, and then adipose tissue, especially in older women, elderly women.
When they produce estrogen, they don't produce estrogens directly like that. I just told you in physiology a moment ago that when estrogen is produced, it is first produced in a form. It must pass through the testosterone stage. So, all these organs, to produce estrogen, must first produce testosterone. Then, with the help of the enzyme called aromatase, which I just told you about, testosterone is converted into... it undergoes something called aromatization, and it is converted into the hormone called estrogen. Not just estrogen, but a hormone specifically called estradiol. Because when you say estrogen, estrogen is a general name, just like we used to say "digital" in the past. Digital is a general word that includes digoxin, digitoxin. But it's the same story. Estrogen is a general name. We have many types of estrogen. The primary type in a woman's body is the type called estradiol, which comes from... it is the major form of estrogen in a woman's blood. Then, estradiol can be converted in the periphery, in the liver, into another type of estrogen called estrone. And it can also be converted into a third type called estriol. So, I now have three types of estrogens. It would have been correct to write here not just one thing: estradiol is the primary, then it is converted into estrone or estriol. And all three are called... I just want to draw your attention here or ask you some questions that an examiner might catch you on.
Number one, if they ask you what is the major source of estrogen? I've answered you: the ovary. What is the major biological form of estrogen? I've answered you: estradiol. What about a postmenopausal woman? Postmenopausal, meaning she has passed, say, the age of fifty, approximately. Postmenopausal means she no longer has menstruation, and the ovary is no longer functioning. So, what are the sources of estrogen in a postmenopausal woman's body? Only the adrenal gland or adipose tissue. And whether it's adrenal or adipose tissue, it must also be converted into... meaning it must first be produced in the form of testosterone, then undergo aromatization, and then these things are formed.
The next question will be: what about a postmenopausal woman, whose major source of estrogen is no longer the ovary, but rather adipose tissue or the adrenal gland, especially adipose tissue? Which of these three hormones will I find most in the body of a postmenopausal woman? The answer is estrone. Remember estrone, which was called... one. Remember it because this story might remind you of postmenopausal. Postmenopausal has the letter 'n' in it, and estrone also has the letter 'n'. It's the only one of them with an 'n'. There is no 'n' in estraol. There is no 'n' in estradiol. So, the 'n' in postmenopausal reminds you of estrone. So, this is the major or the primary estrogen in the body of a postmenopausal woman.
So, we've asked three questions. The fourth question, chemists used to ask us and confuse us. They would say: why is estrogen or estradiol, its symbol in books is always written as E, capital, with a 2 next to it? Estrone is E1, estriol is E3. Why didn't they call this one E1, considering it's the first one formed, and then these come from it? So, it would be logical for this to be 3. The answer is chemistry, actually. They used to tell us: look at the hydroxyl groups, the OH groups. Look at, for example, estradiol. How many groups does it have? One, two. That's why it was called E2. Look at estrone, which is in the body of a postmenopausal woman. It was called E1. How many hydroxyl groups does it have? They found one, so it was called E1. Estriol, count them: one OH group, another OH group, a third one. So, they called estriol E3. So, if you are a biochemist and want to test... how far you've reached, maybe they'll throw you a chemistry question. They won't hold you accountable for it much, but it's good to answer it.
Let's move on to what is called... The first question related to this. I will ask you: why should I make synthetic estrogens when I have natural ones? What will make me go and synthesize them? The answer is very simple. Some natural estrogens, there might be a problem with their absorption. They are absorbed, but not to a great extent. Or their half-life might be a bit short. So, I want to make other forms of estrogen to achieve what is called in pharmacology, to get good absorption, to get a drug that distributes well in the body, to get a drug whose duration in the body lasts for more than 13, 15, or 20 hours, and so on. So, this is the reason why I make many estrogens. There are very many types of synthetic estrogens, but I don't want to bore you. I will tell you only three. The three famous ones, and even if you manage to remember two, it's enough to memorize two very famous ones, and they might appear in multiple-choice questions. The first one is called... very famous, the most famous synthetic estrogen is ethinylestradiol. This is estradiol, but they put an 'ethinyl' group next to it. Very famous and appears all the time. They made another type called mestranol, also something similar. And they also made a third similar and very famous thing called diethylstilbestrol. So, I have three types of... or three famous ones: ethinylestradiol, mestranol, and diethylstilbestrol. I mention these three because in MCQs, I have seen many times, and unfortunately, students make mistakes. Small things that a student shouldn't make a mistake on. They might give you... and list these three, or one of them, or vice versa. For example, they ask: which of the following is a natural hormone found in a woman's body? They list these three, or a fourth or fifth or sixth one, but they list one of them. So, you must memorize the three natural ones, and at least you must memorize these three synthetic ones. And the most famous of all is ethinylestradiol, followed by diethylstilbestrol in fame.
We have other types of estrogens that are not used in medicine. We cannot talk about them. For example, in the plastics industry, there are many estrogens in environmental pollutants. Some foods, like soy and soy oil, contain estrogen, but these are not natural things. They don't concern me as a pharmacologist. We are talking about the drugs that are available.
Let's move on to the pharmacokinetics of estrogen. This is actually explaining pharmacokinetics to reach something I explained to you a long time ago in the chapter of general principles. But I know you forget. Where are we, and where were those principles? We once explained a full video on a lesson called metabolism of drugs, and we explained a long topic called conjugation. And I gave an example of conjugation in the previous video with the topic of estrogen. Let me remind you of what I said in the old videos of general principles.
Estrogen, I don't have a major problem with its absorption. You can give estrogen orally, or estrogen in the form of a cream, or injections, or any form. There is no problem. By the way, any hormone in the world, its structure... you saw the structure of it a moment ago... this ring structure is called a steroid hormone. You can be sure there is no problem with absorption. It can be absorbed subcutaneously, topically, by injection, etc. So, estrogen applies to the same thing. It is one of the hormones for which we have no problem.
When estrogen reaches the intestine, what happens? It goes to the liver, of course. It won't go directly to the liver. It will distribute in the tissues and have a biological effect and do a lot of work. And finally, it is collected, collected, and goes to the liver to be metabolized. The liver does... Actually, estrogen is very annoying with the liver because... it first undergoes oxidation. It is difficult for it. Hydrolysis? No, it's not possible. So, the liver must convert it into a water-soluble substance to get rid of it through the kidneys. So, the liver finds no way out, no trick, but to attach it to a large molecule called glucuronic acid. This molecule called... but estrogen... the liver doesn't break it down or anything. It's the liver that can't do anything with it. It can't oxidize it, nor can it do anything. So, it is forced to do this thing called... called. You will ask me: does this mean estrogen is purely metabolized? No, some oxidation also occurs, but the major pathway relies on the step I told you about. The liver comes and attaches it to glucuronic acid, saying, "Go away, let's get rid of you." Estrogen is excreted in the intestine in this form, which is attached to glucuronic acid.
Then, the following surprise happens. There are bacteria in the intestine called gut flora, meaning billions of types living there. These gut flora come to the estrogen attached to glucuronic acid. They break the bond between glucuronic acid and... or in scientific terms, they do something called deconjugation. So, estrogen is returned to its free form as it was. And estrogen is still estrogen. It hasn't changed. It hasn't been oxidized. It hasn't been broken down. Therefore, estrogen can be reabsorbed because it has returned as it was. So, reabsorption of estrogen occurs again. It goes to distribute in the tissues, then returns to the liver. The liver... we are not done yet. We are working. We just threw it away and did it. What happened is fate. It returned to me again, and it's still doing the same thing. The gut flora, of course, when they do deconjugation, they don't do it 100% of the amount. Some is excreted, but some remains. This story continues. Estrogen, every time it is excreted, returns to the blood, then to the liver, it is metabolized, then to the blood, then it keeps circulating in a long cycle called enterohepatic circulation. This story, which I explained to you, is responsible for estrogen, which I give to a woman as one pill a day, but this pill lasts for up to 20 hours. Although if you ask me, what is the half-life of estrogen? It is actually eliminated after two hours, after three hours. So, what makes it stay in the blood for 20 hours? This story, the enterohepatic circulation. And take it as a rule from me, from now until the end of your life: any drug that undergoes enterohepatic circulation usually has a long duration of action.
I told you before that some doctors make a small mistake, they don't realize it. A woman comes, say, at the age of 25, 30, married, and complains, for example, of... she has... then the treating doctor makes the mistake of not asking her in her history if she is taking contraceptive pills. Young women, contraceptive pills are... the doctor doesn't ask, he writes what she has, hoping to kill this infection in the woman, whether in the chest or in the urinary tract or elsewhere. What will happen, by default, is that these bacteria will also die from the antibiotic. The woman is taking estrogen, one pill a day. In this case, the bacteria that were doing deconjugation and returning estrogen are dead. The result is that estrogen, with the first cycle of... deconjugation, is lost. All the amount is excreted. Nothing returns. Instead of its half-life being 20 hours, its half-life becomes two, three, four hours. The woman relied on taking one contraceptive pill a day, which was enough for her and lasted all day. In this case, the woman will be prone to pregnancy at any time because the pill she is taking has lost its effectiveness. And something happens that we used to call breakthrough pregnancy, or unexpected unwanted pregnancy.
So, I have reminded you of what we explained a long time ago in the general principles videos. Let's move on to the mechanism of action of estrogen. Estrogen, for the second time, I remind you, is a steroid hormone, meaning it has this ring structure. It is a steroid hormone. What I will say applies to estrogen and all steroid hormones.
This is a model of one of your body's cells, and this is the nucleus. We are entering with a telescope, seeing DNA. And you will see on the DNA, molecules of protein. They are always attached to the DNA. Never think that DNA is a strip like a cassette tape. No, it always has proteins attached to it. These proteins control the action of DNA. These proteins, which are sometimes called nuclear receptors or nuclear proteins, control gene expression, whether genes are activated or deactivated. These proteins... even vitamin D, vitamin D also follows this rule. They come to the cell membrane and knock. "Hello, people inside, hello!" No one answers. So, they enter directly. Estrogen doesn't ask permission. It knocks and enters. "Hello, people inside, hello!" No one answers. So, it walks through the cytoplasm without anything stopping it. Then it enters the nucleus. It finds a protein specifically for estrogen, created by God for estrogen. This protein is called the estrogen receptor. Estrogen sits in its place, in the location God made for it. By the way, it binds in two places, one here and one here. As soon as estrogen binds to its place, this protein's conformation, its three-dimensional shape, changes. As soon as estrogen binds to this protein, it activates genes or does many things, depending on the type of cell you are working on. Whether it's hair cells, skin cells, liver cells, whatever. Your entire body can respond to estrogen, or progesterone, or testosterone, or cortisol. All of them follow this rule, although the receptor for estrogen is not the same as the receptor for cortisol, nor is it the same for all of them. Each of them has a specific protein it binds to, called testosterone receptor, and so on.
So, in summary, the major effect of estrogen works on nuclear receptors inside the cell. They call this genomic effects. Meaning its job is genomic. It goes directly to DNA and controls DNA through this protein. Scientists later said, "But we are confused, because when we give estrogen to some people, we see rapid events happening. Some things happen quickly, and this cannot be done through nuclear receptors." Nuclear receptors, to work and so on, need time for their effects to appear. But if I give you something, for example, it controls the vessels quickly, in some places, and quickly. So, this is not... Let's look for something else. It was found that estrogen can also work in some cases on a small receptor on the membrane, or sometimes on a receptor inside the cytoplasm. The effects that estrogen causes on these receptors are called non-genomic effects. But, ladies and gentlemen, in all cases, this is not the major effect. If you ask me, what is the major biological effect of estrogen? I will tell you that 99% of estrogen's work is genomic, on DNA. And a small part of estrogen's work can be done through non-genomic effects, but it's not the main thing. I am telling you this information in case it comes to you as true or false. Does estrogen absolutely work on genomic receptors? The answer is no. It can work on non-genomic receptors, although it is little and not very significant.
Let's move on to the effects and uses of estrogen. I will start with the effects of estrogen, or its pharmacology. We will not explain physiology now, because this is supposed to be the role of physiology. But I have five things here that I must remind you of, because I need them. I need you to remember them. Estrogen causes secondary sexual characteristics. And I know that sometimes when you study physiology, you curse it and curse people, saying, "Oh, we don't..." and you get confused between them. And it gets worse if the examiner confuses you in a question. First, primary characteristics are the traits or characteristics or organs that exist in a woman's body and have no counterpart in a man's body, meaning they don't exist in a man's body. For example, a woman's external genitalia. We men have different genitalia. For example, we men don't have ovaries. We don't have fallopian tubes. Menstrual cycle. All of these are for women. So, this is called secondary sexual characteristics. Don't get confused about them.
Number three, estrogen increases clotting factors. This is very important to me because I will explain it later. It causes blood clots in a woman's body if taken for long periods. It increases which... I don't want you to memorize which factors increase, but thank you if you know that estrogen increases the formation of clotting factors.
Number four, it reduces bone resorption. It reduces bone resorption. Not the word resorption, but bone. A woman's bone, or a woman's bone, has receptors for estrogen. As long as estrogen is present in a woman's body at a good level, her bones remain strong because estrogen prevents bone loss. As soon as estrogen starts to decrease in a woman's body after menopause, around fifty, estrogen starts to decrease, and her bones start to weaken, and she develops the disease we call osteoporosis.
Number five, estrogen has many effects on the central nervous system, mood, and so on. This is why, for example, a girl during her menstrual cycle, her mood changes. You find estrogen levels high at times and low at others. She has hormonal imbalance. Even girls know this story and know that estrogen changes their mood. A woman over fifty who has reached menopause also complains of symptoms like depression, etc., due to estrogen deficiency. It has many effects. Among the things I haven't written down, and which we might stumble upon later, is that estrogen, ladies and gentlemen, regulates... it has a role in regulation. This is why a postmenopausal woman, whose estrogen starts to decrease or become imbalanced, will start to complain of something called hot flashes, meaning episodes of heat. So, the issue of hot flashes and postmenopausal syndrome, I will explain it on the next page or the page after.
The uses of estrogen are only three things. Memorize them and don't memorize anything else, because these are the three main uses. As a hormone in women who have something called postmenopausal syndrome, which I will talk about now. Women who complain of symptoms of estrogen deficiency. You can give her something called hormone replacement therapy. It can be used in hormonal contraception, which is the most common. Then, number three, for something called dysmenorrhea. This is a group of diseases. We will study them, God willing, when you reach gynecology and obstetrics. Your professors will tell you that there is a big issue called... a woman bleeds when she has amenorrhea, meaning her period comes, or her period is interrupted, or delayed, or she has... all of this is called... most professors of gynecology and obstetrics know that this resulted from... an imbalance in estrogen levels in the woman. They give the woman estrogen in a regulated and calculated manner to regulate her... so that these three things I told you don't happen. These are the three main uses. These are the major three indications, and they are also, by the way, the uses of progesterone when we get to it later. Memorize them.
I will postpone estrogen for a while because I will explain estrogen... or rather, we will explain something called contraception, which includes it. So, instead of repeating myself many times, let's postpone it to hormones. Let's conclude the topic of estrogen with postmenopausal syndrome. The woman in front of you is a woman, say, who has reached the age of fifty. Menopause in women, which we call menopause, starts from... on average at fifty years old. She might have it two or three years earlier, or two or three years later. But, generally, around fifty, you expect any woman to start experiencing ovarian failure. The ovary no longer works and no longer produces eggs. The result is that the woman starts at the age of fifty to complain of many symptoms. She always comes to the clinic saying, "Doctor, I'm sitting, and suddenly a terrible feeling of heat comes over my body." A feeling of intense heat. I can't stand the coolness of my room. Suddenly, this heat that comes over the woman's body is called hot flashes. You can write it with 'a' or 'u'. You will find me writing it with both outside, and you will read it in books like that and like that. This is the result of estrogen deficiency starting to cause imbalance in vascular tone. It happens at the level of the autonomic nervous system, and the central nervous system. Everything gets confused, and the woman starts to complain of... hot flashes. She might say, "Doctor, I don't sleep well. My sleep is disturbed. I sleep for two hours and wake up and can't sleep again." She might also have... cardiovascular issues. She might have... and also vaginal dryness, osteoporosis. All these symptoms are called postmenopausal syndrome. All these symptoms, ladies and gentlemen, are corrected when I start to give this woman estrogen from outside. It's called hormone replacement therapy. All these things get adjusted, the woman's mood improves, and everything gets back to normal. But here's a question that is always asked by people preparing for foreign medical exams. Since this is a common topic and happens in 50% of women, foreign exams always focus on it. They ask: The woman came to you with these symptoms, and you diagnosed her with postmenopausal syndrome. The first question: Is she supposed to have estrogen or progesterone? The answer is: The primary hormone in a woman's body that regulates all her functions is estrogen. So, estrogen is needed, not progesterone. They ask: But we know that when we give it to a woman at the age of 50 or over 50, there is a risk to the uterus. Because estrogen... I told you in physiology, in the physiology lesson, just a moment ago, that estrogen causes hyperplasia in the endometrium. It increases the thickness of the endometrium. So, there is a risk to the uterus. So, they say: Look at the woman in front of you. If the woman who came complaining has had her uterus removed for any reason, meaning she had surgery before and had her uterus removed, then there is no fear. In this case, I need only estrogen. Give her estrogen alone because that's what's needed. However, if this woman who came to the clinic still has her uterus, meaning she hasn't had it removed for any reason, then you cannot give estrogen alone. Estrogen alone can cause a problem in the uterus. It must be taken with progesterone. Why progesterone with estrogen? Both together will not cause endometrial hyperplasia. There will be no risk of cancer. But estrogen alone, alone, in a woman with a uterus, you are at risk to the uterus. Many problems can occur. The third question they ask is: What if the woman who came to you complaining of postmenopausal syndrome is only complaining of osteoporosis? Meaning she doesn't have all these symptoms. She only has osteoporosis. So, you are supposed to treat her osteoporosis. Can osteoporosis be treated with estrogen? Can estrogen be given as a treatment? The answer is never. Absolutely never do that. A woman complaining of osteoporosis will be given treatment for osteoporosis, not estrogen. Because, as we just said, if you give her estrogen to treat it, you will cause endometrial hyperplasia and risk of cancer. Estrogen is only given to a postmenopausal woman if she is complaining of the full symptoms of postmenopausal syndrome, the symptoms I told you about: hot flashes, depression, with all these things. But alone, no, never give it.
Let's go to the very simple hormone. Two small words. We won't go beyond the page you see. I will explain in this page the sources of progesterone, its mechanism, like estrogen, its effects, its uses, and adverse effects. Two words, two small words.
Let's start with the sources of progesterone and its types. There is progesterone, which you see here. This is the hormone that comes from the ovary, called progesterone. Its name is progesterone. If you say progesterone, you mean the natural hormone. However, its half-life was found to be very strange. Progesterone, if you give it, even if you give it... it doesn't stay in the blood. It disappears in five minutes. So, scientists had to do what? Make other types of progesterone. They called them... When you synthesize, don't call it progesterone. Don't use that word. It should be called progestin or progestogen. "Gen" means similar. So, if you say progesterone, you mean the natural hormone. But synthetic ones are not called progesterone. They are called progestins or progestogens. We have three types of progestins. Three important types, but there are also 15 or 16. We have something called... very famous, used in injections for contraception. An injection every three months, which is medroxyprogesterone. We have something called... this is also used in some types of contraceptive pills. We have another thing called... These are three famous ones. If you want to forget this one... the one that is difficult to pronounce... memorize at least two examples of synthetic progestins.
Let's move on to the mechanism. It's exactly like estrogen. The same thing we said about estrogen. Progesterone also enters the cytoplasm, enters the nucleus. It finds a specific protein for it, called the progesterone response element. It binds to it and controls the genes of your body's cells. Meaning it also works on nuclear receptors. Most of its effects are genomic. But it can also, like what we said about estrogen, work on things on the cell membrane, but not much.
Its effects. I need to remind you of what I said in physiology a moment ago. In physiology, didn't I say that the role of progesterone is to maintain the endometrium from breakdown? Estrogen developed the endometrium during the first 14 days, making the endometrium ready for implantation. The role of progesterone is to maintain the endometrium so that it remains ready for implantation. As long as progesterone is present, the endometrium maintains its structure, does not break down, and implantation can occur. However, if you cut off progesterone at any moment, the endometrium will break down. If there is a zygote, it will be expelled, and the woman will have a miscarriage. So, this is a determinant.
When we get to the uses of progesterone, you will find that the uses of progesterone are almost the same as the uses of estrogen. They are always mixed together. Estrogen and progesterone together in the three indications we mentioned. Number one: hormone replacement therapy in a woman who is postmenopausal and complained of postmenopausal syndrome, and her uterus is at risk if she takes estrogen alone. So, you will have to mix it with progesterone. That's one. Two: in hormonal contraception, as we will see, it is mixed with estrogen in something called... Three: progesterone can be used with estrogen in diseases or a group of disorders called dysmenorrhea, meaning irregular periods, or periods that come in pieces, or are delayed, or are absent. The doctor regulates the woman's period with estrogen and progesterone together. However, it alone has an indication that only it can do, not estrogen. This relates to delaying menstruation in any woman for any medical reason. For example, a woman comes to your clinic saying, "Doctor, God has blessed me this year, and I will go for Hajj, but I am afraid of getting my period during Hajj and the rituals." So, what's the solution? She wants, "Doctor, please prescribe something to delay my menstruation." I explained to you in physiology that what delays and maintains the endometrium and prevents menstruation is progesterone. As long as you give the woman progesterone, her menstruation will never occur. The doctor's role will be to give her an injection of something with long-acting progesterone. She will take an injection, say, every three months, and she will not get her period as long as progesterone is high in her blood. So, this use cannot be said for estrogen. Never say this for estrogen. The only thing that can delay menstruation is progesterone.
I also wanted to draw your attention that progesterone is the hormone that maintains the uterus and endometrium, whether there is pregnancy or not. As soon as its effect ends, bleeding occurs, or... the withdrawal of progesterone. And actually, it's a bit gentle, not like estrogen. Estrogen can cause problems like... problems with plasticity, problems with the uterus. But progesterone... they say its effects are close to testosterone. Meaning... its biological effects are close to testosterone. There are similarities. So, it can cause acne, meaning pimples. Hair growth in women. It can increase pigmentation, meaning you find some areas of the skin darker, especially in women with dark skin. Progesterone can darken the skin more. These are its only problems. But it doesn't cause cancer, it doesn't cause problems like estrogen.
We have finished the hormones themselves. Let's move on to the practical application, which is hormonal contraception. It would be logical to explain contraceptive pills or start with them, as books start by explaining the types first, dividing them into... hormonal contraception, and then listing the types. One, you raise them. So, from the beginning, you find many types and similar things, and you get confused. I don't like this method. It's better when you study contraception or hormonal contraception to study it this way: first, study the mechanism, the idea behind it. If you understand the simple idea of hormonal contraception, it will be easy for you to invent types yourself. You can invent types while sitting alone. So, you will understand the types easily. But if you start listing types, combined, not combined, and you don't understand what it is, it becomes difficult. So, let's start with the mechanism. First, understand the idea of contraception, then move on to the types. Basically, you must know that the term hormonal contraception means you are giving two hormones from outside: estrogen and progesterone, one of them or both together. Why? The mechanism of this is that estrogen and progesterone will do the three things in front of you. But it will do one main thing, the mechanism in front of you. This diagram, we have almost explained it when we were explaining the part of physiology that we started with, when I explained something called the hypothalamic-pituitary-ovarian axis. I told you that estrogen and progesterone, if their level increases, estrogen, for example, if its level increases, it will go and do negative feedback on the pituitary, saying, "Please, stop releasing FSH." And it goes to the hypothalamus, "Please, stop releasing GnRH." On the other hand, progesterone. I told you when I was explaining physiology, I'm repeating what I said. When progesterone level increases, it goes and does negative feedback on LH, and also does negative feedback on the hypothalamus. When scientists understood this axis, they said, "Okay, we can do it. We can give estrogen from outside. When we give them from outside, their level will increase in the woman's body. They will both go and do... one will do negative feedback on FSH, which is estrogen, and the other will do negative feedback on LH. And both will do... So, as long as you shut down the machine from the top, from the hypothalamus, the ovary will not work, ovulation will not occur, and you have done... it's like working centrally.
Mechanism of hormonal contraception. In short, you will say that hormonal contraception causes negative feedback on the hypothalamus. This is the basis. Number two, it can also do something else, which is called... When I was explaining physiology, I also told you that the endometrium, as it forms during the 28 days of a woman's period or menstrual cycle, starts to form the endometrium. Estrogen starts to build it, then progesterone maintains what has been built. As long as estrogen and progesterone levels are normal, there is no problem. But when you give estrogen and progesterone from outside, you are disrupting the normal process. So, the normal process will not be completed. Therefore, the endometrium becomes unsuitable, unprepared, and not ready to receive any fertilized egg, even if fertilization occurs. So, the endometrium says, "Sorry, I'm not ready to receive anything. I can't."
The third thing is that contraception can change the area called the cervix or cervical canal. Something happens called... it increases the viscosity of the cervical mucus. The cervix, ladies and gentlemen, is a very thin structure that connects the vagina from below to the uterine cavity and then the abdominal cavity inside. If this very thin canal, called the cervical canal, were open all the time, sperm could enter from the vagina into the uterus and cause us problems and infections. That's why God made a normal... a thick layer of mucus that completely seals this canal, sealing the contact between the uterine cavity and the vaginal canal, so that no organism can enter and cause problems. This mucus...
The plaj mucosa that truly the cervix is amazing that it does not allow any organism at all to pass except for one thing, the man's sperm. Sperm is the only organism that is allowed to penetrate this cervix. But anything else is not allowed. When you give the pill, the composition of this mucus changes, it becomes denser, its viscosity increases, so that it no longer allows any organism, not even the sperm itself, to pass. It says, "May God take my enemies and me," no one will pass, neither organism nor even sperm. So this is the mechanism of what? You understood that the main idea is that we want to give from outside the hormone called estrogen and the hormone called progesterone to do these three things. But if you ask me, who is the main one? It is this, which is on the pituitary. What is the effect? After you understood the theory of contraceptive pills and the main idea behind them, it becomes very easy for you to understand the types of contraception. We have two major types of contraception. One type is called combined pills, and one type is called progesterone-only pills. From the name, the pill contains estrogen and progesterone together. Progesterone alone means the pill contains progesterone alone. We will see why they made this and why they made that. This type in the middle, I want you not to worry about it because it is not a third type or anything. It is just a form. Instead of giving tablets, they made it a skin patch. So leave it for now. What you see here is the first tablet that scientists made, and they called it mono-mono-phasic. Monophasic pills. Why this name? Monophasic pills come from the shape you saw. The shape you saw is that all these tablets look alike, 21 tablets, all containing estrogen and progesterone in the same ratio, no difference. The first tablet is like the second, like the third, like the fourth. Six tablets every day, every day until 21, and then you stop. Since the tablet is the same, its composition is one for 21 days, they called this type monophasic. What does it mean? It is the same tablet, it has not changed. But later they said, "No, we can make a better development." What is better, sir? They said they would make something called multiphasic pills. What are multiphasic pills? They said they would make a slight change to be closer to the physiology that God created, so that they do not cause many problems. For example, we know that a woman has estrogen as the dominant hormone in the first week or the first period. So they make her a tablet to take in the first week, estrogen. They said to be in line with what God created. Then in the second week, they start with estrogen and progesterone. Then in the third week, it becomes progesterone only, just as God made it. And in the fourth week, as we agreed, we leave it completely without anything, we give a placebo, an empty tablet, so that the woman has withdrawal bleeding. So, you have given how many types of tablets? You have given one type that contains estrogen alone. You have given one type that contains estrogen and progesterone. You have given one type that is for the third week. Each one is a week. This is one week, this is two, this is three. You have given three types of tablets. So they called this situation not monophasic, it cannot be called monophasic. What should it be called? Triphasic. So you will read it in books, and other books will write multiphasic. It does not make a difference to us in the naming, but you should know where the idea came from. Some women started complaining, "Doctor, I forget the pill every day. I don't know what to do." To the extent that gynecologists turn off their phones and leave the profession because of this. Every now and then someone says, "Doctor, what should I do? Doctor, I forgot the pill yesterday. I don't know." So scientists went back and said, "Okay, we will relieve you completely. Instead of making this oral thing and you forget and get confused, they first started numbering the tablets, putting the day on each tablet." So they put the day so that even if she forgets, she can count the days. She can get an idea of whether she forgot today or not. Even after numbering the tablets like this, women still forget and get confused. So they said, "Okay, we will make these pills in the form of a skin patch." A skin patch is exactly the same as a tablet, but instead of a tablet you swallow, you put on a skin patch. This skin patch stays in your body for a long time. We can make two types of skin patches. The first type of skin patch is for these 21 tablets. Instead of taking them daily, we will put them all in one skin patch. You stick it on, it stays for three weeks, and you remove it. After three weeks, that's it. Because the last week, the fourth week, we agreed it must be hormone-free. What is this type called? It is called a skin patch. They went back and said, "What if we can also make this type in the form of a skin patch?" In this case, the woman will find the box she buys has three types of skin patches. One is colored red. She will stick it on in the first week after menstruation, immediately. She sticks on the patch. For a week, she removes it, sticks on the second patch, which will contain estrogen and progesterone. Then a week, she removes it. And in the third week, she sticks on the patch that contains progesterone alone. Then at the end of the third week, she removes it. So she has used three. Three is still better than taking a pill every day, whether it is this or that. This is a way to improve and prevent people from getting bored with the daily pill and getting confused. They went back and invented the type that I want you to pay attention to, which is progesterone-only pills, or better to say, progestin-only. Progestin alone. The question that will come to your mind is, can progesterone alone do it? My answer is yes, it can. Because we saw in physiology a while ago, we saw that estrogen comes out and has a negative feedback on LH. And who is important for whom? Who is important for whom? Who does it alone? It can alone have negative feedback on the pituitary and can prevent ovulation. It can even prevent the uterus from having any implantation. So it is sufficient alone, but not as effective as combined pills. So, if you ask me, who is more effective in contraception? It is combined pills, and the best type is this. This is the best type. But sometimes we are forced to give a woman progesterone alone in some cases. So, after you asked me, can progestin work alone? Yes, I answered you, it can, but not as effectively as estrogen. What forces me to make progesterone alone, which is less effective than combined pills? What forces me? والله, there are things. First, some women cannot take combined pills that contain estrogen because it causes them a problem. Perhaps this woman had a breast tumor once, and God blessed her and she had it removed, and it did not recur. It would be absurd and foolish for you to give her estrogen because estrogen can cause her problems. Or the second was hidden. If estrogen poses a risk or creates a risk for the patient. Second, a lactating woman, or a woman who is breastfeeding a young child, or breastfeeding an infant. A breastfeeding woman cannot take estrogen either because estrogen passes into the breast milk and will cause complications for this infant who is breastfeeding from her. But progesterone is not. It is safer. So, a lactating woman who comes to your clinic and says, "Doctor, I want a contraceptive method, but my problem is that I am breastfeeding a young child." Then you cannot prescribe anything containing estrogen. You must prescribe something containing progesterone alone, not estrogen. Yes, it is. But it is still capable of. It is still capable of doing what it did before. The tablet you see here is the same as the 21 tablets, and we stop the last week. So, one week, two weeks, three weeks, and we stop for a week. But the only difference is that these tablets contain only progesterone alone. So this is one type called progesterone-only pills. They developed the situation a bit and said, "What if we can give long-acting progesterone?" So they made something called medroxyprogesterone acetate, a type of long-acting progesterone. They made it in the form of an injection, like what you see here. The woman takes this injection, which lasts for three full months. With the injections available in some units that women use, for a period of time. She says, "I want, doctor, I don't want anything oral that bothers me, I don't know what." So we give her this injection, which lasts for three months. They went back and made something more advanced. What did they do? They took progesterone and put it in a form and made something called an implant. An implant is like a capsule that is implanted under the skin. It keeps giving the woman progesterone all day, all day, for how long? For three years. So, instead of months, this will provide her with contraception for three years. Or, if she wants to conceive and become pregnant, she can have the capsule removed, or the doctor can remove it. The capsule will be removed, and her normal cycle will return, and things will go back to how they were. They went back and made something new, or not new, something that is like, even from its name, the emergency pill. They say, for example, "Our role as doctors is to solve problems. Our role as doctors is not to discuss controversial matters. We want, as doctors, to find a solution to a problem." For example, sometimes a woman has sexual intercourse with her husband, and she did not plan for it, and she was not using a contraceptive method, and she came and said, " والله, I am afraid, I don't want to, I am worried about this." So they made her a type of tablet called what? They called it post-coital, morning-after pills. These are all names you will find in books. The woman can take this pill after sexual intercourse, within three days. Three days, meaning the next day, the day after, within three days. This pill is one pill, by the way. One tablet. This one tablet contains a type of progestin, a very strong type of progestin called levonorgestrel. This levonorgestrel is present in a large amount in this tablet, so that when the woman takes this pill, the progestin immediately has a negative feedback on the pituitary, preventing it from releasing. You will ask a question: What if the woman is late, for example, a day or so, and ovulation has already occurred? Still, these pills are capable of preventing implantation. Even if the egg has been released from the ovary and even if it has been fertilized, implantation will not occur at all as long as this prevents it. Of course, scientists say she can take this pill within three days. But after that, four or five days, no. Its effectiveness will be wrong, useless. These are the four types of contraceptive pills that contain progesterone. Please know them because questions are asked about them. The regular pills that contain progesterone. The injections taken every three months that contain medroxyprogesterone. The implant that contains progestin and is used for three years. The pill that contains levonorgestrel, which is called post-coital or morning-after. Now, we have finished the types. Let's move on to the adverse effects. In truth, if you study from any book, you will find that most large foreign books downplay them or not downplay them. They do not like to alarm people because, as you know, the West generally encourages the idea of not having children. They like people to take contraception. So, if every large book starts listing the adverse effects, people will be afraid. So you will open any book, and it will be a long and wide book, perhaps 1500 or 1600 pages, and when you come to the part about adverse effects, the author will say nothing. He will say it is nonsense and simple things, and do not be afraid, as if the matter is very simple. In order to encourage people, to the extent that what I explained to you is dispensed in many countries without a prescription. The woman goes and buys contraception. The pharmacist does not ask her, does not tell her, "Where is your medical prescription?" He does not ask. So, we will say, without exaggeration, we will not exaggerate. We will say what actually happens, the things that are. And this is what we used to ask students the most, by the way, because we want you to know the problems. The problems arising from contraception. The first problem, or the first thing that will happen, is cardiovascular. This is the most important thing for us. Followed by things at the level of the central nervous system, then things at the level of the gastrointestinal tract, then endocrine. All of these, we will still list them, but we will list things under them. And finally, we will talk briefly about the relationship of hormonal contraception with cancer. Let's start with cardiovascular. Two very important things will happen: hypertension. It is logical because contraception is a steroid, and you know that anything steroid in the world causes problems. So the woman will complain that her blood pressure is rising and her body is swelling. That's one thing. The second, and more dangerous, is to have thrombosis. Blood clots. And blood clots occur more in the legs, usually in the lower part. I told you a while ago that estrogen, you know this information, I told you a while ago when I was explaining estrogen, that it increases the formation of clotting factors. But there are two things I hid from you, and I will tell you now. Memorize them. In addition to that, it causes endothelial damage. It comes to the wall of the vein, the inner lining, which is smooth, and damages it. So the lining becomes damaged. Therefore, it becomes easy for a clot to form and stick to it, causing a clot. So it causes something called endotheliosis, meaning it increases the proliferation of the endothelium and thus causes thrombosis. Estrogen, young people, slows down blood flow. It causes a type of stasis. Stasis means the blood pools. Women who take contraceptive pills, they say, "Doctor, these things cause me mood swings over time." This situation improves and disappears. There is no problem with it. It might disappear with time. But the problem is that contraception can cause gallstones. And a woman who has gallstones should never take contraception. Why gallstones? Estrogen and progesterone are both steroid hormones. And if you are good at chemistry, you will know that cholesterol is also a steroid hormone, similar to them. So, the hormones that are given from outside, like estrogen, a part of them is converted into cholesterol, and cholesterol goes into the bile. Its concentration increases, the bile thickens, it crystallizes and forms stones and forms cholesterol gallstones. This is the reason. Effects that are also common and feared. First, blood sugar may rise. Second, weight gain may occur. Why weight gain? As a result of... A woman who has previously complained of a blood clot in her legs, or coronary artery, or something in the brain, never approach her. Let's conclude with the topic of cancer. We have a rule that says that increased estrogen increases the risk of breast and endometrial cancer. Both of these are exposed to types of cancer. Breast cancer and endometrial cancer may occur as a result of estrogen. Your risk, of course, the big books, as I told you, greatly reduce this risk. They say, "Brothers, these are very rare things, and you don't see them, don't be afraid." But the risk remains. At least, my brother, I am warning you, at least so that you do not prescribe contraception for someone who has a history of cancer, meaning she had it, and God blessed her and she was treated. Do not come and add to her with hormones that may activate it. So, be aware of these five things. And these are what are called absolute contraindications. By the way, the first adverse effects of contraceptive pills are considered absolute contraindications. As I told you, do not be lenient with any of these. Do not joke. Do not joke with someone who previously had breast cancer, or joke with someone who has gallstones, or has, I don't know, thrombosis, or has hypertension. Do not joke with any category of these women.