Entry overview: Contraceptive drugs, the full name of oral contraceptives, usually refers to a class of drugs that women take for birth control. There are female oral contraceptives and male oral contraceptives. Its contraceptive principle is mainly by inhibiting ovulation, changing the cervical mucus, making it difficult for sperm to penetrate, or reducing the production of glycogen in the uterine glands, making it difficult for blastocysts to survive, or changing the way the uterus and fallopian tubes move, hindering the Delivery of fertilized eggs.
A drug that prevents sperm and eggs from combining to form fertilized eggs, thereby achieving the purpose of contraception. The side effects of birth control pills may cause endocrine disorders, irregular menstruation, amenorrhea, infertility, or gastrointestinal discomfort, headache, weight gain, nervousness, low mood, skin discoloration and acne. Contraceptive pills should not be used more than three times a year, and other contraceptive measures are recommended.
basic introduction
In real life, there are many cases where women use oral contraceptives for contraception. with more than 20 years of experience, different women have different feelings. Some women are willing to use this method for contraception, while some do not want to use it. .
Birth control pills have been used since 1960, and about 75 million women in the world currently use birth control pills for contraception.
There have been long-term misunderstandings and concerns about combined contraceptives in Asian countries such as China and Japan. The reason may be that the early long-acting contraceptives and emergency contraceptives caused relatively large side effects, and many people could not distinguish different types of contraceptives. Most effective” concept; China and Japan advertise condoms as the safest means to prevent the spread of STDs, but confuse the safety of preventing STDs and preventing unwanted pregnancy.
Development History
contraception history
The history of contraception is very peculiar. In ancient times, women made sperm to pass through some vigorous exercise. Soranus, a 2nd century Greek physician, advised Greek women to jump seven times after intercourse to avoid contraception. Women in Europe use the "more reliable method," with doctors encouraging them to push back and forth four times in the middle of the night.
Barrier contraception has been the most effective form of contraception in the past, preventing sperm from "meeting" with the egg. Pessaries appeared in the second century, and many materials were used to make pessaries, such as pomegranate pulp, a mixture of elephant or crocodile dung with honey or gum. It's hard to imagine how difficult it was to place a so-called peg, a square wooden shield that was carved in a concave shape to resemble a doorbolt; some data suggest that in the Victorian era (ending in the 19th century), this way relatively popular. It wasn't until the 1930s that the device was reprimanded for its torture of women. For condoms, animal tissues were used in ancient times, such as sheep intestines and snake skins. Women sometimes use a natural sponge for contraception, which is dipped in ginger, lemon or tobacco juice before inserting. Oral contraceptives, which have been around since ancient Egypt, women take a mixture of oils, grains, fruits, and other vegetables, and sometimes urine and other animal parts. Soranus recommends drinking the water that blacksmiths use to cool metals. More than 4,000 years ago, Chinese women drank mercury, arsenic, or strychnine for contraception.
The history of the IUD dates back to Arab times, when herders stuffed small pebbles into the wombs of camels to avoid them getting pregnant on long journeys across the desert. At the end of the 19th century, the need for birth control increased, and contraceptive methods changed considerably, starting with the development of the "modern" IUD, which shows the different shapes and sizes of IUDs used during that era.
Now, many different contraceptive methods have been created, ranging from traditional methods such as rhythm, intercourse interruption, to the more modern and credible methods shown here. As we can see, oral contraceptives make up 14% of modern contraceptive methods. Sterilization is the most commonly used form of contraception worldwide. (Data sourced from theUnitedNationsPopulationDivision:WorldContraceptiveUse2001) It should be pointed out that this is a general overview of modern contraceptive methods, and will vary between countries and at different ages (the rate of contraceptive use will decrease with age).
History of contraception
Today, many women around the world consider the pill to be the most effective, reversible, and easy-to-use form of birth control. Of course, scientists continue to find new and better ways.
The reliability of any contraceptive method can be measured by the Pearl Index. It refers to the possible pregnancy rate for 100 women in one year. The lower the pearl index, the stronger the reliability. A PI of 1 means that if 100 women use one form of contraception for a year, 1 will have an unintended pregnancy. This table shows the Pearl Index for different contraceptive methods. With an Implanon Pearl Index < 1, it is currently the most reliable and reversible form of contraception compared to sterilization.
Many believe the history of birth control pills began with this gentleman, Russel Marker. He was an unusual American pharmacist who thought it was not cost-effective to get progesterone from animals, since 1 mg of progesterone would require the ovaries of 2,500 pregnant pigs. It was known then that Australian sheep grazing in one place were less likely to become pregnant, because it was related to a clover, a plant, and that Dutch women who ate tulip stems during World War II were also less likely to become pregnant. based on the above experience, Russel Marker set out to find a steroid hormone that could be extracted from plants.
In the 1930s, he finally discovered that a Mexican plant used by women to relieve dysmenorrhea had high concentrations of steroid sapogenins in its roots. When he extracted progesterone from these steroid hormones in Mexico, it became a milestone for contraceptives. It is still used as a raw material for the production of the progestin hormone desogestrel. There are also many people who do not consider Russel Marker to be the father of the contraceptive pill, but it is certain that his work was pivotal to the development of the contraceptive pill.
Gregory Pincus was a pioneer in the study of oral contraceptives. He is considered by many to be the true "father of the contraceptive pill". In the late 1950s, he did a study in Puerto Rico, and because he knew that his experiments could not risk pregnancy, the contraceptives he used had high doses of estrogen and progestin. In fact he completed his study without a single pregnancy. In 1960, the first oral contraceptive pill, Enovid, was introduced to the United States, and soon, to Europe in 1961. Although his first high-dose steroid pill (containing 150 μg of estrogen) was highly contraceptive, his studies at the time found no adverse effects.
The history of contraceptives can be divided into two main trends, the reduction of estrogen doses on the one hand, and the development of more selective progestin formulations to reduce progestin doses while maintaining their high efficacy, good cycle control, and adverse effects. The reaction rate is low.
1) The dose of estrogen is reduced. In order to reduce side effects, the dose of estrogen in oral contraceptives is gradually reduced from the initial 150 μg per tablet to 20-35 μg, called low-dose contraceptives, and the latest is even only 15 μg. The reasons are as follows: It has been suggested that the dose of estrogen is related to the occurrence of thrombosis, it has been shown that the dose of estrogen is related to the degree of change in the coagulation mechanism, and many side effects are not serious but inconvenient to the user, such as nausea, breast tenderness, vomiting , mainly caused by estrogen.
2) Develop a more selective progestogen. At the same time that the dose of estrogen is reduced, the dose of progesterone is also reduced, which is made possible by the production of high-potency progestogen. Studies have found that progestin doses are associated with the incidence of arterial disease, and even at low doses, these older-generation progestins still have adverse effects on the balance of cholesterol LDL and HDL. The above reasons lead to more research to develop new progestogens to improve the effect of OC on lipid metabolism. It has been confirmed that the stronger the androgenic effect of progesterone, the greater the adverse effect on lipid metabolism.
Therefore, the first 40 years of the development of contraceptives were mainly in terms of improving safety. Reduce the amount of estrogen and progesterone to reduce side effects, and develop new progestogen preparations to reduce the total amount of progesterone. Reasons for reducing estrogen doses: Higher doses of oral contraceptives cause increased risk of thrombotic disease, changes in the blood coagulation system, and other side effects such as nausea, breast tenderness, and vomiting. Reasons for the development of progestogens with strong progestogenic activity and low androgenic activity: Contraceptives with high androgenic activity are prone to arterial disease.
Since the introduction of oral contraceptives in the 1960s, estrogen doses have been gradually reduced, from 150 μg to less than 50 μg, even to 15 μg. It has been proved that it can not achieve the purpose of safe contraception when the estrogen content is less than 30μg in combination with the older generation of progesterone, and it is possible to reduce the dose of estrogen when it is compatible with the highly selective progestogen desogestrel.
Data come from epidemiological studies. Pregnant women, who were not included in the study, had twice the risk of developing thrombotic disease compared with low-dose oral contraceptives.
Studies have shown that the risk of thrombosis with different types of oral contraceptives: · Higher estrogen doses are associated with higher risk; · Contraceptives with different types of progestins and similar estrogen doses have similar risk of thrombosis; · The above data are extremely great support for the past 30 years of research to reduce the dose of estrogen to minimize the occurrence of side effects.
With the development of a new generation of progestogens, the dose of progestogens tends to be lowered, with the goal of discovering more selective progestins. The most selective progesterone was introduced in the 1980s.
The selectivity index is the ratio of the affinity for binding to the progesterone receptor to the binding affinity for androgen, which reflects the favorable and unfavorable properties of the hormone. Clinically high selectivity reflects lower androgenic adverse effects, such as acne, hirsutism, and more favorable effects on certain lipid parameters closely associated with arterial disease. Here, the higher selectivity of third-generation progestins was //confirm/i/ied, and among the third-generation progestins, 3-keto-desogestrel was the most selective progestin.
The current development of contraceptives focuses more on how to best individualize women's needs.
The user of modern oral contraceptives gets more information about the drug (benefits, side effects, additional benefits) and is more attentive to her own needs. These have led to more demand for contraceptives.
The development of contraceptives has shifted to suiting individual women's needs, such as improving bleeding patterns, improving skin conditions, providing reliable contraception to women who are unable or unwilling to use estrogen (eg, lactating women), improving or promoting adherence, And how to meet women's need for non-oral contraceptive methods.
significance
A direct measure of population control is birth control, including contraception and abortion. The history of contraception is almost as old as human history. The emergence of contraceptive pills disintegrated the traditional connection between marriage, sex and fertility, and women were freed from the suffering of fertility and gained higher sexual freedom. But at the same time, the number of non-marriage relationships has increased, which has brought serious challenges to the ethics of society.
Introduction to Pharmacology
1. Female contraceptives
The most basic method of research is the anti-fertility experiment, which is to administer drugs to female animals before and during co-mating with male animals to observe the effect of drugs on fertility. The percentage of pregnancy in female animals and the number of embryos per pregnant mouse were checked as indicators. If a drug could be found that would prevent implantation of a fertilized egg or interrupt early pregnancy, it would not be necessary to take it every day, but only when needed. This is a vision of contraceptive researchers for years. Anti-implantation and anti-early pregnancy tests are often required.
In the anti-implantation experiment, the female mice and the male mice were caged together, and the vaginal orifice of the female mice was checked every morning for the presence of vaginal suppositories. The drug was administered once a day on the 1st to 5th days after the vaginal plugs appeared, and on the 12th day after the vaginal plugs appeared. Animals were sacrificed on the day, and the number of embryos and the percentage of pregnancy were used as indicators. Vaginal plug is a white serous substance formed immediately after mating of some rodents, blocking the cavity from the vagina to the cervix, called a vaginal plug (Vaginal plug). It is a sign to check whether the animal has been mated, and the day of the vaginal plug is counted as the "zero day" of pregnancy. The vaginal suppository is a product formed by the solidification of the secretions of the seminal vesicles and coagulation glands of male rats in the vagina. Mice are generally formed within 4 to 5 minutes after mating. Large vaginal plugs can protrude out of the vaginal opening, and small vaginal or cervix can be seen by opening the vaginal opening. The vaginal plug usually softens gradually one hour after mating, and falls off after 16 to 24 hours. But there are only 4 to 5 hours, and the most can exist for more than 48 hours. The vaginal suppository of mice is relatively firm, and the vaginal suppository of rats is not firm and easy to fall off. Therefore, when examining the vaginal suppository of rats, in addition to examining the vagina, the vaginal suppository should also be found at the bottom of the cage. You can also wash the vagina with normal saline, and check whether there are sperm in the washing fluid under a microscope.
The anti-early pregnancy test is administered after implantation (implantation on the 5th day after the appearance of vaginal plug), usually on the 6th to 9th day after the appearance of vaginal plug. as an indicator. The most commonly used animals in anti-fertility, anti-implantation and anti-early pregnancy experiments are 28-35g mice in prime age, and rats weighing 200-250g can also be used. When discussing how a contraceptive works, it is sometimes necessary to check whether a drug has the effect of inhibiting ovulation. Anti-ovulation experiments are required, and female rabbits weighing 2 to 3.5 kg are often used for experiments.
2. Research on male contraceptives
For a long time, research on male contraceptives has not been reproduced very much, and progress has been slow. Drugs can inhibit the process of sperm production, interfere with the hormone regulation of male reproductive activities, interfere with accessory gonads and change the physical and chemical properties of semen, etc., all of which can achieve the purpose of infertility. It is now believed that the morphological maturation of sperm occurs in the testis, while the physiological maturation occurs in the epididymis. It seems ideal for male infertility caused by drugs acting on the accessory gonads, interfering with sperm maturation or changing the physical and chemical properties of semen. Adult male rats are often used for experiments, such as observing the effect of drugs on the fertility of rats; the effect on sperm count in rats; the effect on sperm motility in rats and the effect on male hormones.
The main function
mechanism of action
The mechanism of action is multi-segment and multi-faceted, and varies with its ingredients, preparations, dosages and usage. For example, the compound preparation of estrogen and progesterone is mainly to inhibit ovulation, the low-dose progesterone is mainly to hinder fertilization, and the high-dose progesterone is mainly to resist implantation. The above classification of application mechanisms is relative.
Steroid hormones that inhibit ovulation
The blood concentration of estrogen and progesterone increases after oral absorption, which inhibits the secretion of hypothalamic gonadotropin through negative feedback; in addition, blood sex hormones also have a direct inhibitory effect on the anterior pituitary, which can reduce the secretion of anterior pituitary gonadotropin , the amount of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the blood are both reduced. Because the secretion of FSH is inhibited, the growth and maturation of follicles are hindered, and there are no mature follicles available for ovulation, which also cancels the peak of estrogen before ovulation. . The ovulation process is inhibited due to the disappearance of the LH peak in mid-menstrual period.
steroid hormones that hinder fertilization
After oral administration of small doses of progesterone, it changes the physical and chemical properties of cervical mucus and hinders fertilization. Progesterone can inhibit the secretion of cervical mucus, reduce the amount of mucus but increase its viscosity and increase the cell content, which is not conducive to sperm penetration, making it difficult for sperm to pass through, and hindering fertilization. Under the predominance of progesterone, sperm capacitation is inhibited and fertilization ability is lost, thus affecting fertilization. Continuous use of low-dose progesterone throughout the menstrual cycle can hinder fertilization. Its advantages are that it does not contain estrogen and has fewer side effects, but the contraceptive effect is worse than the combination of estrogen and progestin, and the incidence of irregular bleeding is higher. . Used less.
The human hypothalamus secretes "gonadotropin-releasing hormone" (GnRH). GnRH promotes the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. In women, FSH promotes the growth and development of follicles in the ovaries. Under the combined action of FSH and LH, mature follicles secrete estrogen and progesterone.
Both progesterone and estrogen levels in a woman's body decrease during menstruation. After menstruation ends, the secretion of these two hormones begins to increase. The first is that estrogen increases faster. Prior to ovulation, higher estrogen levels can stimulate the pituitary to secrete LH, either directly or through the hypothalamus, leading to ovulation (positive feedback).
After ovulation, the progesterone content begins to peak (luteal phase). At this time, due to the high levels of estrogen and progesterone in the blood, progesterone reduces the secretion of GnRH in the hypothalamus, thereby inhibiting ovulation and inhibiting women's own pregnancy. secretion of hormones and estrogens (negative feedback). Therefore, after ovulation, after the peak of progesterone, the level of estrogen and progesterone in a woman's body will begin to decline, and the decline to a certain extent is the period of menstruation. The so-called "safety period" includes the luteal phase. During the luteal phase, women have higher levels of progesterone, so they neither ovulate nor become pregnant.
Commonly referred to as long-term contraceptives, its medical name is short-acting oral contraceptives. Long-term (ie short-acting) contraceptives include Mindingou, Mafulong, and Tejule, which means that they must be taken every day, long-term, and each pill can only be taken for one day. Progesterone is indeed used for contraception. Another name for long-term contraceptives is short-acting oral contraceptives. no way.
Long-term short-acting oral contraceptives (Minding, Mafulong, Tejule) contain progesterone and a small amount of estrogen. Among them, progesterone reduces the secretion of GnRH in the human hypothalamus through negative feedback after oral administration, thereby reducing the secretion of FSH and LH, so that it is difficult for the follicles in the female body to grow and develop and ovulate, thereby inhibiting ovulation, and also inhibiting females The body's own ability to produce progesterone and estrogen. By inhibiting ovulation, its contraceptive effectiveness is almost 100 percent. By reducing the secretion of women's own progesterone and estrogen, the progesterone and estrogen contained in long-term short-acting oral contraceptives replace the women's own secretion of progesterone and estrogen. In the case of taking long-term short-acting oral contraceptives, the female body will only have the luteal phase and the menstrual period, and the ovulation period will be cancelled.
In fact, progesterone alone can achieve the purpose of contraception. The reason why long-term short-acting oral contraceptives contain a small amount of estrogen in addition to progesterone is to prevent women's estrogen levels from dropping too much.
Because the contraceptive mechanism of long-term short-acting oral contraceptives is to inhibit ovulation, and as long as there are no eggs, fertilized eggs will not be formed, so long-term short-acting oral contraceptives can effectively prevent ectopic pregnancy while preventing ectopic pregnancy, and can also prevent ovarian cancer to a certain extent. .
In addition to the common long-term short-acting oral contraceptives, long-term contraceptives also include long-term long-acting contraceptives. Long-term long-acting birth control pills only need to be taken twice a month. But think about it stupidly: if a long-term short-acting oral contraceptive pill is equivalent to drinking two liters of water a day, then a long-term long-acting contraceptive pill is equivalent to drinking only two 3 liters of water a month.
drug effect
Drugs that can make birth control pills ineffective
The easy-to-use oral short-acting contraceptive pill has a high contraceptive rate and has become one of the main contraceptive methods in life. However, some drugs can make oral contraceptives ineffective, and it should be noted that contraceptives cannot be taken with the following drugs:
Rifampicin: Rifampicin can accelerate the metabolism of the main components of oral contraceptives, reduce the concentration of the drug in the blood, and may also cause part of the endometrium to fall off, resulting in continuous spotting or leaching, and at the same time reduce the efficacy of contraceptives. resulting in contraceptive failure.
Antibiotics: Taking antibiotics can inhibit the bacterial flora in the intestinal tract, thereby affecting the absorption of contraceptives in the large intestine and reducing the concentration of contraceptives in the blood.
Antiepileptic drugs: Mainly include phenobarbital, phenytoin, carbamazepine, caprolidone, etc. When women with epilepsy take these drugs, they can promote the increase of drug metabolizing enzymes in liver cells, accelerate the destruction of oral contraceptives, and also increase the binding rate of progesterone, which greatly reduces the free drug concentration. , leading to contraceptive failure.
Enzyme accelerators: such as sedative and sleeping pills such as membranil, and drugs for rheumatoid arthritis such as phenylbutazone. These drugs have enzymatic effects, which can promote the metabolic activity of hepatic microsomal enzymes to catalyze drugs and accelerate the metabolism of oral contraceptives , reduce the contraceptive effect. If you must use sleeping pills, you can use diazepam instead.
Hormones: such as prednisone, dexamethasone, etc., can delay the metabolism of corticosteroids when taking contraceptives at the same time, which greatly increases the side effects.
In addition, during the period of taking oral contraceptives, if you often drink alcohol, it can also increase its metabolism, so that the effect is reduced and pregnancy is caused. Long-term smokers may also make oral contraceptives less effective.
Medications that are incompatible with birth control pills
Oral contraceptives are simple and easy to use. According to reports, there are currently 50 to 60 million women in the world using this method of contraception. However, what is less well known is that women taking birth control pills can still fail to contraception if they take certain special medicines. Stability is one of them. The drug is an inducer of liver microsomal enzymes, which can accelerate the metabolism of oral contraceptives in the body, thereby reducing their contraceptive effect. Long-term use of diazepam in small doses to aid sleep is undoubtedly interfering with the effect of contraceptives. In addition to stability, in recent years, it has been found that there are many drugs that can interfere with the effect of oral contraceptives, such as phenytoin sodium, phenobarbital, primidone, etc., which can affect the contraceptive effect of women taking contraceptives. In addition, longer-term use of penicillin, erythromycin, chloramphenicol, and anti-tuberculosis drugs such as rifampin may also affect contraceptive effects. The reason for this is that, under normal circumstances, oral contraceptives release a hydrolase by means of intestinal bacteria, which are reabsorbed in the enterohepatic circulation. once this enterohepatic circulation is blocked, it may lead to contraceptive failure. The above-mentioned antibacterial drugs have this effect.
Therefore, during the period of oral contraceptives for women of childbearing age, if they are ill and need to take other medicines for a long time, they should explain the situation of taking contraceptives to the doctor for the doctor's reference. It is safer to stop oral contraceptives and switch to other effective contraceptives.
Advantages of conventional short-acting oral contraceptives
Taking conventional short-acting oral contraceptives (Mindingou, Mafulong, Tejule) for contraception is a safe and effective method of contraception, suitable for all normal healthy women except breastfeeding. The advantages of conventional short-acting oral contraceptives (Mindingou, Mafulong, Tejule) are that the success rate is relatively high, and if they are used consistently, the contraceptive rate can reach more than 99%. Second, it is reversible, and you can get pregnant again after stopping the drug. Third, it has some therapeutic effects, in some cases, it can regulate menstruation and treat dysmenorrhea. Fourth, it can effectively avoid ectopic pregnancy.
Health effects of conventional short-acting oral contraceptives
· Regular menstrual cycle
· Decreased menstrual blood volume
· Less or no dysmenorrhea
· Smooth skin
Reduced risk of breast, ovarian and endometrial cancer
Reduce the chance of pelvic inflammation
Fewer uterine cysts
Can help maintain the ability to conceive
· Makes bones stronger
Reduce heavy bleeding during menstrual cycle
Reduce iron deficiency anemia
prevent conception
