Classification of progestin agents according to Schindler A.E., 1999; Goeretzleher G., 2001 as amended.

Group	Typical	Hybrid
Progesterone derivatives (pregnane group) Retroprogesterone Prod. 17-hydroxyprogesterone Prod. 19-norprogesterone Prod. 17-hydroxy-19-norprogesterone	dydrogesterone hydroxyprogesterone medroxyprogesterone megestrol Chlomadynon cyproterone demegaston	promegestone nomegestrol
19-Nortestosterone derivatives Estrana group Gonan group	norethisterone ethynodione norgestrel levonorgestrel gestodene desogestrel norgestimate tibolone	dienogest
Spironolactone derivatives		drospirenone

Progesterone (Prigesterone, Akrolutin).

Biosynthesis and regulation of progesterone secretion. The main stimulator of progesterone synthesis and secretion is pituitary LH. In the first half of the menstrual cycle, when LH levels are low, almost all of the progesterone produced is converted to androgens and then to estradiol. The signal for the start of active progesterone synthesis is the release of LH during ovulation. High concentrations of LH cause inactivation of aromatase and 17-hydroxysteroid dehydrogenase in the cells of the former follicle and therefore in the corpus luteum (which formed at the site of the follicle after ovulation) the synthesis of steroids stops at the stage of progesterone formation from pregnenolone.

If pregnancy does not occur, then after the corpus luteum fades, the level of progesterone drops and this coincides with the onset of menstruation. In case of pregnancy, the placenta takes over the function of progesterone synthesis.

Progesterone, which is secreted into the blood, activates pituitary receptors and, through a negative feedback mechanism, suppresses the synthesis and secretion of LH.

In the male body, the main source of progesterone is the testes and adrenal glands.

Mechanism of action: Progesterone penetrates the membrane of target cells and activates progesterone receptors (PR), which are located in the cytoplasm. After activation, progesterone receptors are combined into pairs Pgs-PR/PR-Pgs, and the resulting complex enters the cell nucleus, where it binds to the receptor sequence of DNA nucleotides.

There are 2 groups of progestin receptors: PR-A and PR-B.

The main role of PR-A receptors is to inhibit the transcription of genes for the synthesis of receptors for other steroid hormones: glucocorticoids, mineralocorticoids, androgens and estrogens. Activation of this type of receptor leads to a decrease in the content of receptors for these hormones in tissues.

PR-B receptors, after activation and binding to DNA, attach coactivator proteins SRC-1, NcoA-1 and NcoA-2, which, like estrogen receptor coactivators, acetylate histone proteins and cause DNA to unwind with nucleosomes, preparing it for gene transcription.

Physiological and pharmacological effects of progesterone.

A. Effect on the organs of the reproductive system and mammary glands.

Progesterone released during the luteal phase of the menstrual cycle inhibits endometrial proliferation in response to estrogens (the number of estrogen receptors decreases) and causes its secretory transformation. Secretory transformation consists of an increase in the number of glands and mucous cells in the endometrium and the accumulation of glycogen in epithelial cells. As a result, the endometrium is prepared for implantation of a fertilized egg.

Progesterone reduces the sensitivity of the myometrium to oxytocin and prostaglandins, ensuring the rest of the uterus necessary for pregnancy.

Progesterone changes the secretion of cervical mucus in the uterus, making this mucus more viscous and rich in glycogen. This leads to a decrease in the ability of sperm to penetrate through the cervix into its cavity and the likelihood of fertilization of the egg decreases.

Progesterone stimulates the division and differentiation of mammary gland cells, promotes the development of alveoli and lobules of the gland, and the growth of blood vessels. That. progesterone prepares the gland for lactation.

Progesterone activates receptors of the pituitary gland and hypothalamus and, through a negative feedback mechanism, suppresses the rhythmic secretion of GnRH and gonadotropic hormones. As a result, the maturation of a new egg and its ovulation are disrupted until the end of the next menstrual cycle or pregnancy.

B. Effect on the central nervous system.

Progesterone increases body temperature by 0.6-1.0°C. It is believed that this is due to its effect on the thermoregulation center in the hypothalamus.

Progesterone activates the respiratory center and increases its sensitivity to CO 2 levels. As a result, ventilation increases and the partial pressure of CO 2 in arterial and venous blood decreases.

Progesterone has a hypnotic and general sedative effect on the central nervous system. It lowers your mood somewhat and can cause depression.

C. Metabolic effects of progesterone. This group of effects is presented in Table 2.

Table 2. Metabolic effects of progesterone.

Target	Effect caused
Lipid metabolism	Increased lipoprotein lipase activity and fat storage. Strengthening ketogenesis. Increased triglyceride levels in the blood.
Carbohydrate metabolism	Increased basal insulin secretion and glucose deposition in the liver.
mineral	Competes with aldosterone for mineralocorticoid receptors and, by blocking them, reduces the resorption of Na +, increases the excretion of water and Na +, and reduces the excretion of K +.
Steroid	By activating PR-A progestin receptors, it inhibits the synthesis of receptors for estrogens and androgens. A decrease in the number of these receptors provides a weak antiestrogenic and antiandrogenic effect of progesterone.

Pharmacokinetics. Progesterone is well absorbed by any route of administration. However, when administered orally, it is almost completely metabolized during the first passage through the liver, so it has virtually no effect. Therefore, progesterone is used only parenterally (usually intramuscularly).

In the blood, progesterone is 70-90% bound to blood proteins, but despite this, it is eliminated extremely quickly (the half-life is only 5 minutes). Metabolism produces inactive pregnanediol and several 20-hydroxy derivatives of progesterone, which have approximately 1/5 of the original biological activity of progesterone. Progesterone is excreted mainly by the kidneys.

Indications for the use of pure progesterone and progestins:

Dysfunctional uterine bleeding associated with luteal phase deficiency. They manifest themselves as periodically occurring irregular bleeding due to reduced production of progesterone in the second phase of the cycle. Progesterone is used intramuscularly at 5-15 mg/day or intravaginally at 200-300 mg/day starting from the 17th day of the cycle for 10 days.

Habitual miscarriage (miscarriage). Progesterone is used 10-25 mg intramuscularly or 100-200 mg intravaginally 2 times a day until the 12th week of pregnancy.

Premenstrual syndrome (neuro-vegetative-endocrine disorders that occur in a woman in the days preceding menstruation) and dysmenorrhea (irregular menstruation). Progesterone is used 5-10 mg/day intramuscularly for 6-8 days. Administration begins 6 days before the expected menstruation.

Diffuse mastopathy and mastodynia - used only locally in the form of a gel, which is applied to the skin of the mammary gland 2 times a day.

Weight gain.

Acne, seborrhea, hirsutism - this group of effects is associated with the androgenic properties of progesterone itself.

Depression, drowsiness.

Changes in libido, breakthrough bleeding - heavy acyclic bleeding that occurs more often after discontinuation of the drug.

Arterial hypertension and progression of atherosclerosis.

Rarely, nausea and vomiting may occur.

FV: oil solution 1 and 2.5% in ampoules of 1 ml; gel 1% -80.0; vaginal capsules 0.1.

The group is hunted down.

ABOUT
xyprogesterone capronate (Hydroxyprogesteronecaproate, Primolut- Depot, 17- OPC). It is a 17-conjugated progesterone ester. Due to conjugation, the elimination of progesterone occurs extremely slowly and its effect after a single administration lasts from 8 to 14 days. However, the development of the effect also begins quite late, so 17-OPK is not suitable for treatment in conditions that require a rapid manifestation of the gestagenic effect (dysfunctional uterine bleeding, premenstrual syndrome).

In general, the biological properties of oxyprogesterone are identical to progesterone.

Application and dosage regimen: Used mainly for the treatment of miscarriage, 125-250 mg once a week until the 12th week of pregnancy inclusive.

FV: oil solution 12.5 and 25% in ampoules of 1 ml.

C iproteroneacetate(Cyproterone acetas, Androcur). It belongs to 17-hydroxyprogesterone derivatives, but has a number of distinctive features:

Cyproterone has a gestagenic effect in combination with a pronounced antiestrogenic and antiandrogenic effect. It is believed that the antiestrogenic effect of cyproterone is associated with its ability to inhibit the synthesis of estrogen receptors in target tissues (due to activation of PR-A type progestogen receptors). The antiandrogenic effect of cyproterone is explained by the following two mechanisms: on the one hand, cyproterone, by activating PR-A receptors, inhibits the synthesis of androgen receptors in target tissues; on the other hand, cyproterone competes with androgens for binding to receptors and, by occupying them, prevents androgens from activating the receptor.

Cyproterone activates gestagen receptors of the hypothalamus and pituitary gland, suppressing the release of GnRH, FSH and LH through a negative feedback mechanism. As a result, the synthesis of the body’s own sex hormones decreases.

Cyproterone has a more pronounced effect on lipid metabolism than other pregnane derivatives. It lowers cholesterol levels in the anti-atherogenic fractions of HDL and increases LDL cholesterol and triglyceride levels.

To reduce libido in men with socially unacceptable forms of behavior. Since cyproterone has an antiandrogenic effect, it significantly weakens libido in men. Use depot preparations (oil solutions) 300-600 mg every 10-14 days intramuscularly.

For the treatment of prostate cancer. Tumor cells in this cancer carry many androgen receptors and male sex hormones act as growth factors for it, causing rapid growth and dissemination of the tumor. Cyproterone blocks androgen receptors and tumor growth slows down. Prescribed orally at 200-300 mg/day in 1-3 doses or intramuscularly at 300 mg every 7-14 days.

For the treatment of androgenization phenomena in women (excess androgens in a woman’s body is manifested by the appearance of acne, seborrhea, hirsutism, voice mutation, etc.). Take 10-100 mg/day orally from days 1 to 10 of the menstrual cycle.

Cyproterone as a progestin component is included in combined oral contraceptives.

FV: tablets of 10 and 50 mg; solution in oil 10% ampoules of 3 ml.

Derivatives of 19-nortestosterone of the estran series.

N orethisterone(Norethisterone, Norkolut, Primolut-Nor). A derivative of 19-nortestosterone of the estran series, its properties occupy an intermediate position between progestins and androgens, combining the properties of both.

Features of the action:

Has the highest gestagenic effect. In addition, it activates estrogen and androgen receptors. The androgenic effect of norethisterone leads to increased libido in women, reduces asthenia, but at the same time enhances the negative effect of the drug on the metabolism of lipids and carbohydrates.

Even in minimal doses, norethisterone activates progestin receptors of the hypothalamus and pituitary gland and, through a negative connection mechanism, inhibits the production of gonadotropins and gonadotropins in a cyclic mode. As a result, the synthesis of one’s own sex hormones is disrupted and ovulation is suppressed (for which the cyclic secretion of gonadotropins is necessary).

Since the administration of norethisterone suppresses the production of its own estrogens and gestagens, proliferative processes in the endometrium stop and its involution occurs. Norethisterone itself is not capable of causing secretory transformation of the endometrium, since the dose of norethisterone, which suppresses hormone synthesis and ovulation, is 100 times less than the dose required for endometrial transformation.

It has a pronounced effect on lipid metabolism: it reduces HDL cholesterol levels and increases the amount of LDL cholesterol and triglycerides.

Features of pharmacokinetics. Norethisterone, like all other 19-nortestosterone derivatives, has high bioavailability because it undergoes only a minor first-pass effect through the liver. Norethisterone has a short half-life (t ½ = 3-10 hours), is excreted 70% by the kidneys and 30% by the intestines. The bound fraction of norethisterone is 96.3% (of which 35.5% is bound to sex globulin). The biologically active free fraction is only 3.7%.

Indications and dosage regimens:

Premenstrual syndrome: prescribed 5 mg orally from the 16th day of the cycle for 10 days (in severe cases, from the 6th day of the cycle for 20 days).

Treatment of dysfunctional uterine bleeding: 5-10 mg orally for 6-12 days.

Treatment of endometriosis (a condition in which uncontrolled growth of endometrioid tissue occurs in the uterus and other organs): 5-10 mg/day orally from days 5 to 25 of the cycle for 6 months.

To prevent pregnancy, norethisterone is included in hormonal contraceptives.

FV: tablets of 5 and 10 mg.

Derivatives of 19-nortestosterone of the gonan series.

Levonorgestrel(Levonorgestrel, Microlut). In general, its properties resemble norethisterone, differing from the latter only in several respects:

Levonorgestrel is used mainly for contraception and its drugs and dosage regimens will be discussed in more detail below.

D yenogest (Dienogest). It belongs to atypical (hybrid) gonan derivatives, since it combines the properties of both derivatives of the gonan and pregnane series:

Like gonan derivatives, dienogest has a powerful gestagenic effect.

Like derivatives of the pregnane series, it has an antiandrogenic effect, which, however, has a number of fundamental differences:

Dienogest activates receptors of the hypothalamus and pituitary gland and, through a negative connection mechanism, inhibits the release of gonadoliberin and gonadotropins. A decrease in FSH and LH levels reduces the synthesis of androgens in the ovaries and adrenal glands.

Dienogest increases the synthesis of sex globulin, but does not bind to it itself (91% of dienogest is bound to albumin and 9% is free). Free sex globulin binds androgens circulating in the blood, reducing the proportion of their free, biologically active fraction.

Dienogest blocks the enzyme 5-reductase, which ensures the conversion of low-active androgens into highly active ones.

Dienogest activates PR-A progestin receptors and this causes inhibition of the synthesis of androgen receptors in target tissues.

Dienogest binds to free androgen receptors and prevents androgens from activating them.

Dienogest does not have any effect on estrogen receptors, unlike progestins of the pregnane and gonan series.

Dienogest does not affect lipid metabolism and does not change the ratio of atherogenic and antiatherogenic fractions.

Dienogest has a beneficial effect on the central nervous system: improves sleep, memory, and eliminates depression.

Unlike all other gestagens, dienogest is metabolized without the participation of cytochromes P 450. Therefore, the use of other drugs against this background (which change the activity of cytochromes) does not affect the implementation of the effect of dienogest.

Indications for use and dosage regimens:

Treatment of endometriosis: 1 mg orally 2 times a day for 60 days.

As part of products for hormone replacement therapy in postmenopausal women, contraceptives.

Table 3. Comparative characteristics of progestins.

A drug	Influence at receptors						Dose (mg/day)
							transform. endometrium	suppressed ovulation
Progesterone 17-OPK Cyproterone
Norethisterone Levonorgestrel Dienogest	Ë / ▬
Drospirenone

Note: "+ " - stimulating effect, "- "- blocking effect, "0 " – no effect, " " - level up, " » – level decrease

The latest birth control pills: freedom of choice. Hormonal and non-hormonal, used after intercourse. Which ones are better to use?

Thank you

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!

The main priorities of modern medicine are caring for the preservation of women’s reproductive health, protection and ensuring safe motherhood. It is no secret that Russia is one of the first places in terms of the number of abortions. Abortion is a real operation that often leads to infertility, menstrual irregularities, miscarriages, and even maternal mortality. We can draw the following conclusion: measures to prevent abortions can help maintain a woman’s health and give birth to a healthy child.

No wonder they say that children are the flowers of life. But each flower opens only at a time determined by nature. A woman has the right to give birth to a child whenever she wants, at any time in her life, so that the child is desired and happy. This fact is confirmed by law.

For the prevention of unwanted pregnancy and abortion at a certain stage of a woman’s life, plays an important role contraception.

Contraception has been used by women since ancient times. Thus, even in Ancient Africa, intravaginal herbal remedies in the form of a cocoon were used, and in America they used douching with herbal decoctions, lemon juice, and mahogany bark decoction at the end of sexual intercourse.

The number of contraceptives increased over time, but effective methods and reliable drugs appeared only in the 20th century.

New contraceptives appear almost every day. Science does not stand still. They are easy to use, reliable, safe for health, and moreover, they have a therapeutic effect for certain diseases.

Currently, medicine offers various contraception, and a woman can always choose which methods and drugs to use. Our country provides freedom of choice of contraceptives, but a woman cannot always decide for herself what is best for her. In deciding on the choice of a contraceptive, a consultation with the attending physician will help - only a qualified specialist can assess the woman’s health status, determine the indications for prescribing a particular method of contraception, and suggest the best drug for the patient.

Hormonal oral contraceptives

Every year, an increasing number of women use hormonal contraception. In Russia, over the past ten years, the use of hormonal contraceptives has increased more than 5 times. Reliability, ease of use, a minimum of side effects, and a beneficial effect on the organs and systems of the body allow hormonal drugs to find more and more grateful fans. Women today prefer hormonal oral contraceptives as the most effective. Combined birth control pills are the gold standard of contraception, their effectiveness is 99%. The newest hormonal contraceptives have created a sensation, a real revolution among other means of contraception.

The effectiveness of contraceptive drugs is assessed by experts by counting the number of unplanned pregnancies per 100 women during the year. This indicator is called the Pearl index.

Types and composition of birth control pills

The first oral contraceptives appeared in the fifties and sixties of the 20th century. The predecessor of all drugs for practical use is the contraceptive Enovid, which contained 0.15 mg of mestranol and 15 mg of norethinodrel. Then the development of hormonal agents developed and underwent the following changes:

• New birth control pills began to contain small dosages of hormones, while at the same time their effectiveness and reliability were maintained.
• New analogues of female sex hormones have been obtained: ethanyl estradiol and levonorgestrel.
• Third generation progestogens appeared - norgestimate, desogestrel, gestodene.
• The newest contraceptives have been developed - mini-pills that do not contain gestagen.

Taking drugs with low concentrations of hormones helps reduce side effects and complications.

Combined contraceptives contain two components:
1. Synthetic estrogen ethinyl estradiol, which is the estrogenic component of drugs.
2. Progestational component in the form of various progestogens.

All birth control pills, depending on the dosage of hormones, are divided into the following types:

• monophasic;
• two-phase;
• three-phase.

In monophasic hormonal contraceptives, the daily dose of active components is constant, but the composition may vary. It is clear that monophasic drugs consist of tablets with the same dose of hormones. These tablets are the same color and are used during one course. Popular monophasic contraceptives include: Regulon, Marvelon, Silest, Novinet, Mercilon, Rigevidon.

Biphasic drugs involve changing hormone doses twice per course, three-phase drugs - three times. Typically, such tablets for one course have different colors. Two-phase contraceptives include Anteovin, three-phase contraceptives include Tri-mercy, Triquilar, Tri-regol, Triziston.

“Mini-pill” contraceptives are monophasic and are intended for the period of breastfeeding and lactation. These include: Lactinet, Exluton, Charozetta.

The action of combined oral contraceptives (COCs) is based on blocking ovulation. In this way they protect against unplanned pregnancy. Only progestogen has the ability to block the ovulation process, the dose of which is the same in all combined contraceptive pills. The difference between microdose and low-dose drugs is only in the dosage of estrogen. Estrogens affect a woman's menstrual cycle.

Depending on the dosage of the active ingredients, birth control pills are divided into four types:

Microdosed birth control pills
As a rule, these products contain minimal doses of the hormone ethinyl estradiol. Side effects when using them are minimal. In some cases, they have the ability to eliminate hormonal imbalances: acne (especially in adolescence), painful menstruation. These pills are best suited for young girls under 25 years of age who have not given birth and have regular sex life. They can also be used by mature women over 35 years of age, and by women who have never used hormonal contraception. The most popular are: Tri-Mercy, Jess, Mercilon, Lindinet -20, Klaira, Novinet.

Low-dose birth control pills
The drugs contain the same ethinyl estradiol, but in combination with various hormones: desogestrel, gestodene, norgestimate, dienogest or levonorgestrel. These birth control pills are recommended for young women who have given birth. In addition to the contraceptive effect, these products have a pronounced antiandrogenic effect: they help eliminate unwanted hair growth on the face, prevent the appearance of acne and hair loss due to hormonal imbalance. Popular tablets: Regulon, Belara, Marvelon, Yarina, Janine, Midiana, Femoden.

Medium-dose contraceptive pills
Typically contain two hormones: ethinyl estradiol and levonorgestrel. Less commonly, they may contain other combinations of hormones. Medium-dose contraceptive pills are intended for women who have given birth, especially those over 30 years of age. They also have an antiandrogenic effect, which is important for women who have not recovered from pregnancy and childbirth. However, when choosing a drug, one condition must be observed - these products are not suitable for nursing mothers. Popular tablets: Diana 35, Demoulin, Tri-Regol, Chloe.

High dose birth control pills
They contain ethinyl estradiol and levonorgestrel, but only in high doses. Such drugs are primarily used to treat and prevent hormonal diseases. Contraceptives of this type can be taken by women over 35 years of age, if drugs with a low dosage of hormones are ineffective. These include: Triquilar, Tri-regol, Ovidon, Milvane, Non-Ovlon.

Newest birth control pills: how to choose?

A woman wants a fulfilling life, and fear and reluctance of an unplanned pregnancy should not be a reason for refusing sexual relations. There are many ways to protect yourself. The most reliable are birth control pills.

Choosing a contraceptive is difficult and should be taken seriously.

Ideally, a specialist should select contraceptive drugs, but sometimes the woman decides for herself which pills to take. In these cases, it is necessary to carefully collect information about the product. Where to start?
1. Familiarize yourself with the different types of birth control medications.
2. Compare all the pros and cons.
3. Define your goal - decide what you want to get from using oral contraceptives.

What do you need to know to make the right choice? Let's figure it out.

A woman should find information about drugs and their effect on the body. It should be borne in mind that birth control pills differ in parameters, degree of reliability and side effects.

Combined contraceptives usually contain two analogs of female sex hormones, so they come first in terms of reliability. Combined oral medications are used both to protect against pregnancy and to treat diseases and hormonal disorders. Women who choose hormonal birth control pills are still advised to consult with their doctor and undergo a hormonal test.

New contraceptives are the so-called “mini-pills”. They contain only one hormone - therefore the reliability of the drugs is 90%. Their advantage is the possibility of use during lactation, as well as by women who are intolerant to estrogen (part of COCs).

The next type of birth control pill is represented by emergency contraception. These tablets are not intended for long-term use, but are used immediately after sexual intercourse. The hormone content in them is very high, so these products can only be used once a month.

Currently, contraceptive drugs of the second to fifth generations have appeared on the market. These newer drugs contain a small dose of hormones and have mild side effects. It should be understood that there are no good or bad contraceptives. There are products that are suitable or not suitable for a woman. Therefore, to select contraceptives, the individual characteristics of a particular woman’s body must be taken into account.

When making your own selection, you must first determine the phenotype—the woman’s body type.

The following types of female phenotype are distinguished:
1. With a predominance of estrogens - estrogenic type.
2. With a balance of estrogens and gestagens - a balanced type.
3. With a predominance of gestagens and androgens - gestagenic type.

The phenotype is determined by the following characteristics: general appearance, volume and condition of the mammary glands, skin type, the nature of menstruation, duration of the menstrual cycle, the presence of toxicosis during a previous pregnancy, the woman’s body weight and tendency to be overweight.

A balanced phenotype is characterized by average indicators of these traits. In this case, it is recommended to take Marvelon, Triquilar, Microgynon, Triziston, Mercilon, Tri-Mercy, Regulon.

When the estrogenic phenotype predominates, it is characterized by a very feminine appearance, a very long menstrual cycle, very heavy menstrual and vaginal discharge, and moderate fullness. It is advisable to take drugs such as Anteovin, Minulet, Norinil, Rigevidon, Miniziston.

When the gestagenic phenotype predominates, all the signs are less pronounced: unfeminine appearance, small volume of mammary glands, scanty periods, short duration of the menstrual cycle, oily skin. The following remedies are effective: Bisekurin, Chloe, Non-ovlon, Yarina, Ovidon, Jess, Janine, Klaira, Diane, Midiana, Belara.

No matter how carefully the choice is made, it still happens that the drug is not suitable. The ideal selection method has not yet been invented. Often you have to act by trial and error, but sometimes this is inevitable, because every woman’s body is unique.

It has been proven that the criterion for a successful choice of contraceptive is the absence of menstruation for three months - i.e. adaptation period. Then this drug can be taken for a long time.

Non-hormonal birth control pills

Along with hormonal contraceptives, non-hormonal birth control pills appeared at one time. Today there is a rise in the popularity of these funds, which is explained by some of the features of their action.

The fact is that the use of non-hormonal birth control pills is not contraindicated for women immediately after childbirth, nursing mothers, and women who cannot take hormones. And another important detail: non-hormonal drugs for preventing pregnancy not only have the ability to destroy sperm, but also contribute to the formation of a protective film on the vaginal mucosa and thickening of mucus in the cervical canal. Moreover, active substances - spermicides - reduce the speed of sperm movement, and the resulting mucus is a barrier to their penetration into the uterus. This is good protection against unwanted pregnancy. Non-hormonal contraceptive pills, which is important in our time, protect women from sexually transmitted infections, as they have both antiseptic and antimicrobial effects.

It follows that non-hormonal contraceptives can be used by many women at different periods of life. The use of tablets is a barrier chemical method of contraception. They are easy to use, do not disrupt hormonal levels, can be used at any reproductive age of a woman, and are a prevention of sexually transmitted diseases.

Birth control pills Pharmatex

The most popular non-hormonal contraceptive currently is the drug Farmatex. Pharmatex has spermicidal, antiseptic and antimicrobial effects.

In addition to the contraceptive effect, Pharmatex birth control pills prevent the transmission of sexually transmitted infections and reduce the risk of their consequences: infertility, miscarriage, cervical diseases, tumors caused by HIV infection.

A huge advantage of using Pharmatex is that it in no way affects either hormonal levels or the vaginal microflora.

Pharmatex, like other non-hormonal tablets, affects such types of microorganisms as Trichomonas, gonococci, chlamydia, Candida fungi, and herpes virus. Pharmatex acts locally, which does not cause side effects on organs and systems of the whole body.

The use of vaginal tablets is more suitable for women in the postpartum period, during lactation and breastfeeding, after an abortion, and with irregular sex life, when there is no permanent partner.

Mode of application
The manufacturer of the product usually includes instructions for use. Basically, non-hormonal vaginal tablets are inserted into the vagina to a sufficient depth 10 minutes before sexual intercourse. For more convenient administration of tablets and other dosage forms, a special applicator is included in the package of the medicine.

You need to know that before each subsequent sexual intercourse, and in the case of sexual intercourse that occurs later than two hours after the administration of the tablet, a new tablet must be administered. Of course, this is inconvenient to a certain extent, since a woman cannot afford to re-inject the pill after accidental or unexpected sex. She needs to plan the timing of intercourse, which is unnatural.

The effect of the drug is believed to last from 40 minutes to several hours. But you need to remember that the use of vaginal tablets is not combined with water procedures before and after sexual intercourse using intimate hygiene products.

In some women, the drug may cause a burning sensation in the vagina. In this case, you should consult your doctor about continuing or discontinuing Pharmatex. The reliability of Pharmatex is 80-82%.

Contraceptive suppositories and creams

Although the reliability of vaginal contraceptives is less high compared to hormonal contraceptives, they continue to gain popularity ratings. Only improper use of these products can lead to unwanted pregnancy.

In addition to tablets, manufacturers offer the use of other dosage forms: suppositories, creams, ointments. The active substance in the suppositories is either nonoxynol or benzalkonium chloride.

Pharmatex is also available in various forms: vaginal suppositories, tampons, cream, capsules.

Advantages of using contraceptive suppositories
Contraceptive suppositories are easy to use, easily inserted into the vagina, and have minor side effects. Another advantage of using non-hormonal vaginal suppositories is the effect of additional lubrication. They are especially suitable for partners who have problems with natural lubrication and dryness in the genitals.

Vaginal suppositories protect a woman from sexually transmitted infections and are indispensable for casual sexual intercourse, infrequent sexual intercourse, or in the absence of a permanent partner.
Disadvantages of using contraceptive suppositories
Vaginal contraceptive suppositories can affect the microflora of the vagina, since in addition to the active substance they contain acids. Burning and itching, allergic rashes that occur when using suppositories are indications for their discontinuation.

Dosing
Vaginal suppositories. The suppository is inserted into the vagina 10 minutes before sexual intercourse. The drug is effective for 4 hours.

Vaginal tampon. The tampon is taken out of the package and inserted into the vagina using a finger, right up to the cervix. The protection effect occurs immediately and lasts 24 hours. The tampon does not need to be changed during this period, which is very convenient. The tampon does not change even if there are several sexual intercourses that follow each other during the day. The tampon is removed no earlier than 2 hours after the last sexual intercourse, but no later than 24 hours after its first insertion into the vagina.

Vaginal cream. It is inserted into the vagina using a special syringe. The device should be filled to the mark without the formation of air bubbles. Then slowly insert into the vagina before sexual intercourse. The introduction is made lying down. The effect of the product begins immediately and lasts about 10 hours. Before repeated sexual intercourse, it is necessary to re-administer a portion of the cream.

Popular drugs: Pharmatex, Nonoxynol, Patentex Oval, Contraceptin T.

Birth control pills after intercourse

One method that prevents unplanned pregnancy is called emergency contraception. This is the only protection in emergency situations: rape, forced sexual intercourse and mental conditions associated with them. Emergency contraception is also used during unprotected sexual intercourse, as post-coital protection against possible pregnancy.

Sometimes this method is simply called: emergency, fire, emergency contraception, contraception the morning after. But it is still correct to call it emergency, since this method is used in emergency situations.

Emergency contraception aims to prevent pregnancy at the following stages: ovulation, fertilization and consolidation of the fertilized egg in the endometrium (inner layer of the uterine mucosa).

• in emergency situations involving violent acts on the part of a partner, as well as when the integrity of the condom is broken or a woman misses taking a contraceptive pill;
• with rare sexual contacts;
• during unprotected sex, when no contraceptive methods were used.

Contraindications for this method are the same as for taking other birth control pills, namely:

• thrombosis and thromboembolism (even in history);
• liver diseases with a high degree of failure;
• kidney diseases;
• oncological diseases.

For this method, hormonal drugs containing estrogens, combined hormonal contraceptives, as well as drugs containing gestagens and intrauterine devices can be used.

Estrogens for emergency contraception have not been used so often lately, since they contain high doses of hormones, which leads to side effects - nausea and vomiting.

Combined contraceptive pills are used within 72 hours after sexual intercourse, twice, with a break of 12 hours. You can use any drug from this group.

The most well-known drug for emergency contraception in Russia is Postinor. It is recommended to take it twice, one tablet at a time. The first tablet is taken no later than 72 hours after sexual intercourse, the second - 12 hours after the first.

The second emergency contraceptive drug, Escapelle, is taken once within 96 hours after sexual intercourse.

Combined oral contraceptives are taken daily for 21 days. Then a break of 7 days is taken, and the next package of the drug begins. The course begins with an active tablet.

"Mini-pills" are taken without interruption. Immediately after finishing the package, the next one begins.

Break in reception

It is recommended to take birth control pills for a long time, but you should see a gynecologist once a year. If the doctor does not determine any contraindications to taking your usual medications, then you can safely continue taking them.

Menstruation upon admission

When taking COCs, your periods may stop if you take them for a long time. When using other oral contraceptives, periods may become scanty and last a shorter time.

If you have been taking contraceptives regularly, without omissions or breaks, but your periods have stopped, then you need to continue taking them.

But if the intake was irregular, you should suspect the onset of pregnancy, immediately stop using the contraceptive and contact a gynecologist to identify it.

Menstruation after cancellation

Menstruation returns completely within one to two months after stopping birth control pills. According to experts, approximately 80% of women have a planned pregnancy. If your periods have not returned within six months, you should consult a doctor.

Bleeding when taken

After starting to take the pills, a woman may experience spotting. You should not interrupt the course for this reason. The spotting disappears as you continue taking it.

If heavy bleeding occurs, consult a doctor.

Is it possible to get pregnant while taking birth control pills?

Pregnancy can occur only if the contraceptive regimen is violated. If the delay in taking the pill is more than 12 hours, the effectiveness of the contraceptive effect is weakened.

Another situation is when a woman vomits when taking it. Then you need to take the next pill, since the first one is not absorbed. If vomiting occurs repeatedly, it is better to switch to another type of medication. The same steps should be taken for loose stools.

The reliability of contraceptives may decrease when taking other medications - for example, antibiotics, St. John's wort infusions, etc. In this case, the use of an additional method of contraception is recommended.

How long can you take the pills?

Unfortunately, fear of hormonal drugs among Russian women is passed on from generation to generation. Women ask a lot of questions and try to find answers to them.

According to scientists, fifth-generation contraceptives have already appeared in Russia, which have minor side effects. But the number of questions is not decreasing.

Is it possible to take birth control pills continuously for more than a year?

In the absence of side effects of the drugs taken by a woman, as well as medical contraindications for their use, it is allowed to take contraceptives for quite a long time, even several years. Changing pills to others, or taking breaks in taking them, is not useful, but on the contrary, harmful. The body adjusts to one type of pill; switching to other contraceptives forces it to work in a different rhythm. Research by scientists has proven that breaks do not affect the incidence of complications or the development of subsequent pregnancies.

Pregnancy after stopping birth control pills

Calculations confirm that pregnancy can occur immediately after stopping birth control pills, or after a short period of time. Interestingly, after discontinuation, the likelihood of pregnancy increases several times. Doctors use this circumstance in the treatment of infertility.

Is it possible to stop taking birth control pills?

A woman has the right to stop taking contraceptives whenever she wishes.

Which is better: birth control pills or the IUD?

Women often ask: “Isn’t it better to insert an intrauterine device than to take pills?” Again, the same fear of hormones makes us think about canceling combined oral medications. It must be taken into account that the spiral is a foreign body in the uterine cavity, which can cause inflammation. Tablets are more reliable and safe.

The best birth control pills

We have already said that it is impossible to determine the best pills for a particular woman. Every woman should choose the pills that are suitable only for her. Currently, fifth-generation drugs have appeared, and side effects such as obesity and infertility are a thing of the past. Modern contraceptives contain minimal doses of hormones and have virtually no side effects. We will try to give short descriptions of some drugs.

Jess

Jess contraceptive pills are a new, practical solution for preventing unwanted pregnancy for young women. This drug contains small doses of estrogen - 20 mcg, and progestogen drospirenone - 3 mg, which reduces the risk of vascular complications. The tablets are well tolerated and do not have a negative effect on the gastrointestinal tract.

This drug belongs to the fourth generation of contraceptive drugs.

It is recommended to use the drug for a long time. The package contains 28 tablets. Take the tablets daily, preferably at the same time. Start taking Jess on the first day of menstrual bleeding, then drink continuously.

Jess is a novelty in medicine. The popularity of the drug is growing. Jess provides reliable protection, controls the menstrual cycle, is used to treat symptoms of premenstrual syndrome, acne, and has a beneficial effect on hair and nails. At the same time, the weight of women using Jess remains stable. The period of adaptation to the contraceptive is 1-2 months.

No wonder the drug Jess is called the contraceptive of the twenty-first century.

Novinet

The action of the new contraceptive Novinet is based on blocking ovulation and the production of luteinizing hormone. This makes it possible to delay the movement of sperm into the uterus by increasing the viscosity of the mucus in the cervical canal.

The drug has minimal side effects, does not cause pain during menstruation, and does not affect a woman’s weight gain.

When taking Novinet, nausea, rarely vomiting, partial hair loss, and headaches may occur.

Novinet is taken 1 tablet daily for 21 days. The break is 7 days, on the eighth day a new package is started.

Breastfeeding women can start taking the drug three weeks after giving birth. It should be remembered that Novinet dramatically increases the amount of breast milk.

Reviews about Novinet are mostly positive.

Janine

Janine refers to monophasic low-dose contraceptives. The contraceptive effect of the drug is due to a combination of three actions: inhibition of ovulation, increased viscosity of cervical secretions and changes in the endometrium in terms of preventing the introduction of sperm.

The active ingredients are dienogest and ethinyl estradiol.

Janine take 1 tablet per day for three weeks. Then they take a break for a week, after which the course is repeated.

Reviews about Janine prove a truly pronounced contraceptive effect.

Regulon

Regulon is a combined oral contraceptive. Active substances - 0.03 mg ethinyl estradiol and 0.15 mg desogestrel. Regulon acts similarly to the previous drug.

Regulon helps with menstrual disorders and uterine bleeding.

Reviews about Regulon
Women who have taken this drug note the quality of the drug and its reliability. Regulon acts much more gently than other drugs. It was often recommended by doctors for use by teenagers and young girls. With long-term use it does not cause side effects, reliably protects against unwanted pregnancy and does not contribute to weight gain.

Women who have used it for medicinal purposes speak positively about Regulon. The drug helps with uterine bleeding, heavy vaginal discharge, improves the quality and appearance of hair, nails and skin.

Yarina

The drug Yarina is also popular in Russia. This is an effective new generation oral contraceptive. The active substances are drospirenone and ethinyl estradiol.

The drug is well tolerated and has minor side effects. During administration, the woman’s weight remains unchanged, there is no nausea or vomiting, and the therapeutic effect is pronounced - a decrease in premenstrual symptoms, symptoms of seborrhea, acne.

Women taking Yarina noted the high reliability of the drug, as well as improved mood, restoration of libido, and normalization of the menstrual cycle.

The minimum cost of a monthly dose of the drug in Russia ranges from 600 rubles.

Logest

Logest is a modern new generation contraceptive. It contains a minimal amount of hormones. In addition to a persistent contraceptive effect, it has a therapeutic and prophylactic effect on the course of female cancer, which is an advantage of the drug.

The effect of the drug is based on inhibition of ovulation, increasing the viscosity of the secretion, which impedes the movement of sperm and prevents implantation of the egg in the uterus.

Taking the pills starts on the first day of the menstrual cycle. Take 1 tablet daily for 21 days. Then they take a week break, after which the course is repeated.

When the drug is discontinued, the body's ability to conceive is completely restored.

The price of the drug ranges from 330 to 450 rubles per package.

Claira

Quite recently, new birth control pills, Qlaira, appeared in our country. Qlaira is the first fifth generation contraceptive, the latest and highest quality contraceptive.

Qlaira is a natural oral contraceptive. For the first time, the composition of a combined hormonal contraceptive preparation did not include ethinyl estradiol as an active substance. It was successfully replaced by the softer and safer hormone estradiolavalerate, which is a hormone with a natural formula. This hormone has been well studied and is used mainly to treat symptoms of menopause.

To enhance contraceptive functions, scientists added the active substance dienogest to estradiol valeriat, which also solved the problem of intermenstrual bleeding.

The procedure for taking the drug has also been changed. It has a unique dynamic dosing mode. Qlaira is a four-phase hormonal drug. The package contains two placebo tablets, that is, they do not contain the active ingredient, and 26 active tablets with different doses of the active substance. Doses of estrogen when taken are gradually reduced, and doses of gestagen are increased. This dosage regimen increases the effectiveness of the drug several times.

At the present stage of development of contraception, the drug Qlaira is revolutionary, providing a high degree of protection and treatment of female diseases.

Despite a very large selection of birth control pills, the percentage of abortions remains high in our country. Women do not have sufficient information about the drugs, they experience panic fear of using hormonal drugs, not allowing the idea that safe and reliable contraceptives have appeared at the present stage. New generation birth control pills, containing reduced doses of active substances, can help women plan a pregnancy without the risk of complications and abortions.

Before use, you should consult a specialist.

The progestogenic effect is aimed at developing effects in the body similar to the action of the corpus luteum hormone. The mechanism of the progestogenic effect on the body is associated with the suppression of the secretion of pituitary gonadotropins, which in turn prevents the maturation of follicles, causing anovulation in women of childbearing age. Ensures the onset of the secretion phase in the endometrium, reduces the risk of endometrial hyperplasia and/or carcinogenesis. This action may also reduce the severity of vasomotor symptoms in menopausal women. Causes changes in the mucus of the cervical canal (inhibits arborization), increases its viscosity, thus complicating the penetration of sperm, and also increases the number of intermediate cells in the maturity index of the vaginal epithelium. Reduces the excitability and contractility of the uterine muscles, stimulates the development of the end elements of the mammary gland. Suppresses the function of Leydig cells in men, that is, it inhibits testosterone synthesis. Preparations with a progestogenic effect are used for all types of progestin deficiency (infertility, habitual and threatened miscarriage, premenstrual syndrome, algomenorrhea), irregular menstrual cycles, dysfunctional uterine bleeding, for the purpose of hormone replacement therapy (in combination with estrogens), contraception, endometriosis, mastopathy. For the treatment of malignant neoplasms of the endometrium, mammary glands, and kidneys.

Modern hormonal contraception

ABSTRACT. Modern hormonal contraception. Modern hormonal contraceptives have the ability to prevent pregnancy in almost 100% of cases and, when used skillfully, have a beneficial effect on a woman’s health. The mechanisms of action of various hormonal contraceptives are considered. The significance of their estrogenic and progestogen components is discussed in detail. It is noted that hormonal contraceptives can be used not only to prevent pregnancy, but also for the prevention and treatment of many gynecological diseases and functional disorders. The features of the use of various hormonal contraceptives (combined oral monophasic and multiphasic, mini-pills, depot preparations) are discussed.

V.N. Serov
Scientific Center for Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences, Moscow

Modern hormonal contraceptives have the ability to prevent pregnancy in almost 100% of cases and, when used skillfully, have a beneficial effect on a woman’s health.

The first hormonal contraceptive, Enovid, containing 0.15 mg mestranol and 15 mg norethinodrel, began to be used in 1960, therefore, hormonal contraception has been used for more than 40 years. Currently, it is used to prevent unwanted pregnancies for at least 200 million women. Over the years of widespread use, hormonal contraceptives have been constantly improved, their effect on reproduction and the body of women has been studied in detail, the negative and positive aspects of the effects of these drugs have been assessed depending on individual characteristics, social conditions, age, parity, and the presence of certain diseases.

The emergence of combined oral contraceptives (COCs) was preceded by a number of important scientific discoveries. The physiology of the menstrual cycle and the role of the hypothalamic-pituitary system in ovulation were studied. Experimental and clinical studies have demonstrated the possibility of suppressing ovulation with progesterone. This served as a prerequisite for the creation of progesterone-like compounds with a long-lasting effect, unlike progesterone. Based on 19-nortestosterone, progestogens were synthesized (often they are not entirely correctly called gestagens), which are part of COCs. The discovery of G. Pincus et al. was of great importance for the development of COCs. (1950), who found that the inhibitory effect of estrogen and progesterone on ovulation is mutually potentiated, which makes it possible to reduce the dose of each of them when used in combination.

In the following decades, great strides were made in the field of hormonal contraception. The synthesis of new highly active hormonal substances has made it possible to switch to the use of low-dose COCs that maintain high contraceptive reliability. Long-acting drugs have been created. New methods of hormonal contraception have been developed for women in the postpartum period and with low reproductive potential - the use of mini-pills, as well as in late reproductive age - injectable drugs and subcutaneous silastic capsules. Multiphase COCs with minimal hormone content have appeared, seemingly simulating the normal menstrual cycle. Third generation progestogens, similar in action to progesterone, with low androgenic activity, have been obtained.

The last 10-12 years have been marked by events that can significantly affect the nature of contraception. In particular, an intrauterine device (IUD) with a hormonal component (Mirena) has been developed, which opens up new prospects. A new method of administering hormonal contraceptives - vaginal rings that release steroids (Nova-Ring) - also seems promising. A cotraceptive ring inserted into the vagina is capable of releasing 120 mcg of ethinyl estradiol and 15 mcg of etonogestrel (an active metabolite of the third generation progestogen, desogestrel) per day. If we take into account other existing methods of contraception (IUDs, barrier, spermicides, “physiological”), it becomes clear how large the amount of information should be that guides doctors who give advice on preventing unwanted pregnancy. Certain difficulties are also created by the idea that many people have about the harmfulness of contraception, especially hormonal contraception, about which even medical workers often have a negative opinion. This is facilitated by insufficient knowledge, the position of some religious denominations and social bias. The lack of family medicine, insufficient training in family planning issues, and excessive specialization of doctors also create objective conditions for the formation of misconceptions about hormonal contraception.

Before moving on to a consideration of modern hormonal contraceptives, it is important to emphasize that their main pharmacological property is to turn off ovulation while maintaining menstrual-like bleeding.

The menstrual and reproductive functions of women are influenced mainly by stimulating factors. Their natural inhibitors are pregnancy and lactation, during which there are no menstruation and the “system” seems to rest. Unfortunately, in the conditions of modern life, women often find themselves in conditions of ecological-reproductive dissonance (V.N. Serov, A.A. Kozhin, 1986), when the only childbirth is combined with abortion. Against the backdrop of environmental and social difficulties, the consequences of abortion become especially significant. When studying the long-term consequences of repeated abortions, a number of specialists (E.I. Sotnikova, 1996) note that in the first 2 years, complications of inflammatory etiology are detected in about 8% of women. 4-5 years after repeated abortions, in 20-25% of women, menstrual function is disrupted, insufficiency of the 2nd phase of the cycle, anovulation, and relative hyperestrogenia occur. The consequences of this may be internal endometriosis, endometrial hyperplasia, uterine fibroids, and mastopathy. As a result of the stress reaction that accompanies abortion, some women develop neuroendocrine (metabolic) syndrome with obesity, insulin resistance, followed by the development of secondary polycystic disease, infertility, and dysfunctional uterine bleeding.

In terms of the number of abortions, Russia ranks second (after Romania) among European countries. It is easy to calculate that if about 2 million abortions are performed annually in our country (including 1 million repeat ones), then with a delay of 4-5 years in Russia for this reason (also annually) 250-300 thousand will be added. gynecological patients. Reducing the number of abortions and replacing them with modern methods of contraception actually means the prevention of gynecological diseases, incl. and infertility.

In addition to blocking ovulation, hormonal contraceptives to a certain extent act as an inhibitor of menstrual function and prevent diseases such as endometriosis, dysfunctional uterine bleeding, endometrial hyperplasia and precancer, mastopathy, secondary polycystic ovaries, etc.

In our experimental studies, conducted jointly with physiologists (V.N. Serov, A.A. Kozhin, 1986), the pathogenesis of secondary polycystic disease was studied in the process of acute and subacute stress in animals. In all cases, the ovarian cycle was disrupted, ovulation was switched off, and polycystic ovary syndrome developed within 1-1.5 months. If, against a background of stress, rats were fed an estrogen-progestogen contraceptive (Stediril and Infekundin were used), pathological changes in the ovaries did not occur.

The positive therapeutic effect of COCs was observed in women with postpartum neuroendocrine syndrome, which occurred with activation of the hypothalamic-pituitary system (V.N. Serov, 1980). We have obtained interesting data regarding the preventive effect of COCs after abortion. 4.5-5 years after they were carried out, two groups of women were examined. In the first group, rehabilitation after abortion was not carried out, and 5% of women showed signs of internal endometriosis (characteristic changes on ultrasound and clinical manifestations). In the second group, after the abortion, hormonal contraception (Marvelon or Rigevidon) was carried out for 6 months to 2-2.5 years. There were no signs of endometriosis in this group; menstruation was regular and moderate.

The question of the effect of COCs on hemostasis remains controversial. First-generation drugs increased the risk of thrombosis by 2.5-3 times, which was associated with a high dose of their estrogenic component (50 mcg). At the same time, the use of low-dose COCs (the dose of ethinyl estradiol does not exceed 35 mcg) does not increase the risk of thromboembolism compared with women who do not use hormonal contraceptives. Numerous studies have shown that the risk of thrombosis when using COCs increases in women with antiphospholipid syndrome and genetic abnormalities of hemostasis (Leiden mutation, defects in methyltetrafolate reductase, proteins C and S, prothrombin). Currently, it is recommended to consider the presence of thrombosis or myocardial infarction in close relatives at a young age (up to 40 years) as a contraindication to the use of COCs. This significantly reduces the risk of genetically determined thrombosis.

When using COCs, metabolic changes occur in a woman's body due to the influence of both estrogenic and progestogen components. Similar changes are observed during pregnancy. Synthetic estrogens included in COCs can lead to changes in carbohydrate metabolism - a decrease in glucose tolerance and an increase in insulin levels. Progestogens of COCs, which in most cases are derivatives of 19-norsteroids (androgens), increase insulin resistance and its content in the blood plasma. Numerous studies have shown that when taking low-dose COCs, changes in carbohydrate metabolism are insignificant and do not have adverse consequences. Preparations containing third-generation progestogens have a beneficial effect on cholesterol, high- and low-density lipoprotein levels.

The undoubted advantages of COCs include their therapeutic and preventive effects for various gynecological diseases.

While taking COCs, the menstrual cycle stabilizes, the duration and intensity of menstrual-like bleeding normalizes, which leads to the elimination of iron deficiency anemia. The manifestations of primary dysmenorrhea and ovulatory pain are reduced. A beneficial effect of monophasic COCs on the manifestations of premenstrual syndrome was noted. Improving the barrier properties of cervical mucus under the influence of the progestogen component of COCs makes it possible to reduce the incidence of inflammatory diseases of the pelvic organs by 2 times.

The use of COCs for a year reduces the risk of endometrial cancer by 50% (due to the antiproliferative effect of progestogens), ovarian cancer by 30%, benign tumors and functional ovarian cysts by 2-3 times (due to the antigonadotropic effect). Taking COCs for 2 years provides a protective effect for 10-15 years. Long-term use of COCs reduces the incidence of dysfunctional uterine bleeding and associated intrauterine interventions by an average of 50%.

Currently, COCs are used for the treatment and prevention of benign diseases of the mammary glands. Taking monophasic COCs for a year (especially those containing progestogens with low androgenic activity) reduces the risk of developing mastopathy by 50-75%, the protective effect increases as the duration of COC use increases.

The therapeutic effect of COCs is due to a decrease in the frequency of hyperplastic processes in the mammary glands and a regulatory effect on the menstrual cycle. It has been reliably established that there is no increase in the risk of developing breast cancer associated with the use of COCs. The slight increase in the incidence of this form of cancer observed in a number of epidemiological studies may be a consequence of earlier diagnosis during regular examinations of women using COCs. Breast cancer in women who had ever used COCs was clinically less severe, and the results of their treatment were more favorable than in women who had never taken these drugs.

Hormonal contraceptives have an antiandrogenic effect, as they help suppress the production of androgens in the ovaries due to blockade of luteinizing hormone secretion. The antiandrogenic effect is enhanced by the use of COCs containing progestogens with antiandrogenic effects (cyproterone acetate, dienogest, chlormadinone acetate). Treatment of virile symptoms (acne, seborrhea, hirsutism) is also effective with the use of drugs containing progesterones with low androgenic activity (desogestrel, gestodene, norgestimate). Important mechanisms of the antiandrogenic action of COCs are the competitive binding of androgen receptors by progestogens and increased synthesis of sex steroid binding protein under the influence of ethinyl estradiol.

While taking COCs, there is an increase in bone tissue density. This is due to the action of estrogens, which stimulate the formation and inhibit the resorption of bone tissue, thereby preventing the development of osteoporosis.

In women with congenital and hereditary blood diseases (von Willebrand disease, factor VII deficiency, thrombocytopenia, etc.), the use of COCs is considered the optimal method of contraception, since their use reduces hemorrhagic manifestations.

COCs contain active estrogen - ethinyl estradiol, which is presented in various doses. The progestogenic components of most COCs are 19-nortestosterone derivatives. The first generation of progestogens (estrans) include norethinodrel and norethisterone, the second (gonans) - levonorgestrel and norgestrel, the third (gonans) - desogestrel, gestodene and norgestimate. COCs also contain derivatives of 17α-hydroxyprogesterone, for example, cyproterone acetate. Relatively recently, new compounds with gestagenic activity have appeared - dienogest (a derivative of 19-norsteroids) and drospirenone (a derivative of 17α-spironolactone). Individual progestogens differ significantly in gestagenic, androgenic (antiandrogenic), estrogenic (antiestrogenic), antimineralocorticoid and glucocorticoid activity.

Table 1. Characteristics of progestogens
Progestogens	Bioavailability, %	Ovulation inhibitory dose, mg/day	Dose for endometrial transformation, mg
Desogestrel	80	0,06	2
Gestogen	100	0,03	2-3
Norgestimate	60-80	0,2	8
Dienogest	95	1,0	6
Levonorgestrel	100	0,05	4

The latest generation of progestogens - desogestrel, gestaden, norgestimate, dienogest - are characterized by minimal androgenic activity, do not disrupt lipid metabolism, and do not affect body weight.

Doses that ensure transformation of the endometrium and suppression of ovulation (antigonadotropic effect), as well as bioavailability (the amount of the drug entering the systemic circulation after passing through the liver) determine the individual characteristics of various progestogens (Table 1).

In modern COCs, the content of the estrogen component is reduced to 20-35 mcg, and the progestogen component to 50-150 mcg, i.e. 5 and 10-100 times, respectively, compared to the first combined contraceptives. Drugs containing less than 35 mcg of ethinyl estradiol are called low-dose, and less than 30 mcg are called ultra-low-dose (microdose). Depending on the type and dose of estrogen and progestogen, COCs have predominantly estrogenic, progestogenic, androgenic or anabolic effects. They are also divided into monophasic and multiphasic drugs.

Each tablet of monophasic COCs contains stable doses of estrogen and progestogen (Table 2).

Table 2. Composition of monophasic COCs
Drug name	Dose of ethinyl estradiol, mg	Name and dose of progestogen, mg
Cileste (USA)	0,035	Norgestimate 0.25
Femoden (Germany)	0,03	Gestodene 0.075
Marvelon(Netherlands)	0,03	Desogestrel 0.15
Belara (Germany)	0,03	Chlormadinone acetate 2.0
Logest (Germany)	0,02	Gestodene 0.075
Novinet (Hungary)	0,02	Desogestrel 0.15
Regulon (Hungary)	0,03	Desogestrel 0.15
Yarina (Germany)	0,03	Drospirenone 3.0
Diane-35 (Germany)	0,035	Cyproterone acetate 2.0
Jeannine (Germany)	0,03	Dienogest 2.0

Modern oral contraceptives differ from their predecessors, first of all, in the progestogen component. Progestogens with antiandrogenic properties have important advantages over other representatives of this class, as they potentiate the protective effect of estrogens on the cardiovascular system and eliminate the side effects associated with androgenization (seborrhea, acne, hirsutism and alopecia). These include, in particular, a derivative of 17α-hydroxyprogesterone - chlormadinone acetate (CMA), which is a derivative of progesterone secreted naturally. It blocks androgen receptors in target organs and reduces the activity of 5α-reductase, which is responsible for converting testosterone in the sebaceous glands and hair follicles into a more active androgen - 5α-dihydrotestosterone. In addition, CMA reduces the number of androgen receptors and suppresses the secretion of gonadotropin, which leads to a decrease in androgen production in the ovaries and adrenal glands. Unlike 19-nortestosterone derivatives, CMA does not counteract the increase in plasma levels of sex steroid binding proteins caused by ethinyl estradiol, and does not inhibit isoenzymes of the cytochrome P450 system in the liver, and therefore does not affect the metabolism of ethinyl estradiol and is safer with respect to drug interactions . CMA (2 mg) is part of the low-dose monophasic COC Belar, which also contains 30 mcg ethinyl estradiol.

Clinical studies have shown that Belara provides a high level of contraception and allows one to achieve good control of the menstrual cycle. Women taking Belara experience regular menstrual-like bleeding, constant high cycle stability, a favorable reduction in the duration and intensity of menstrual-like bleeding, and a very low incidence of amenorrhea. According to a large observational study conducted in Germany and including 21,820 women observed for 6 menstrual cycles by 3,600 gynecologists, the adjusted Pearl index for Belara, calculated from 125,634 cycles, was 0.076 (unadjusted - 0.344). There was a significant decrease in the frequency of intracyclic bleeding (from 22.9% in cycle 1 to 1.6% in cycle 6), amenorrhea, severe withdrawal bleeding and dysmenorrhea.

In addition, Belara significantly reduces the symptoms of androgenization or even provides complete cure for seboria in 80% of cases, acne in 59-70%, hirsutism in 36% and androgen-dependent alopecia in 86%.

Along with its high effectiveness and beneficial effect on the psychological state of women (according to clinical and epidemiological studies), Belara is well tolerated by patients. Unlike COCs containing progestogens with partial androgenic activity, Belara did not have a clinically significant negative effect on carbohydrate metabolism and hemostasis. This suggests that the risk of thromboembolism when using Belara does not exceed that for other second-generation COCs. Even with long-term use, the drug has virtually no effect on body weight. The drug only slightly increases body weight. No negative effects on libido, mood or appetite have been observed with long-term use. Changes in the blood lipid profile caused by Belara are beneficial from the point of view of reducing the risk of atherogenic diseases such as stroke and myocardial infarction.

Table 3. Composition of multiphase COCs
Drug name	Component content, mg
Tri-Mercy (Netherlands)	0.035 ethinyl estradiol + 0.05 desogestrel 0.03 ethinyl estradiol + 0.1 desogestrel 0.03 ethinyl estradiol + 0.15 desogestrel
Triziston (Germany)	0.03 ethinyl estradiol + 0.05 levonorgestrel
Triquilar (Germany)	0.03 etintlestradiol + 0.05 levonorgestrel 0.04 ethinyl estradiol + 0.075 levonorgestrel 0.03 ethinyl estradiod + 0.125 levonorgestrel
Tri-Regol (Hungary)	0.03 ethinyl estradiol + 0.005 levonorgestrel 0.04 ethinyl estradiol + 0.075 levonorgestrel 0.03 ethinyl estradiol + 0.125 levonorgestrel

Multiphasic COCs (Table 3) contain a reduced dose of progestogens and a slightly increased dose of ethinyl estadiol compared to monophasic ones. The dose of progestogen in them, unlike monophasic COCs, changes, increasing in the 2nd phase of the cycle. The content of hormones in these drugs imitates changes in their levels during the menstrual cycle.

You should pay attention to the antiandrogenic effect of other COCs. The preparations Diane-35 and Zhanine contain progestogens (cyproterone acetate and dienogest) with an antiandrogenic effect, and the Tri-Mercy COC includes desogestrel, a progestogen with a pronounced progesterone-like effect that competes with androgens at the receptor level, and an optimal dose of estrogens that stimulate the production of sex steroid-binding globulin and thereby reducing the content of free androgens.

Yarina's drug contains drospirenone, a progestogen derived from spironolactone; its use is especially advisable in women with premenstrual syndrome and diffuse mastopathy. The moderate antialdosterone effect inherent in drospirenone reduces fluid retention and swelling when taking Yarina.

Summarizing the above, we can formulate indications for the use of COCs, which include reliable reversible contraception, menstrual irregularities, dysfunctional uterine bleeding, dysmenorrhea, premenstrual syndrome, ovulatory pain, some forms of acne, seborrhea and hyperandrogenism. Contraindications for the use of COCs, according to WHO recommendations, include: pregnancy, thromboembolic diseases, deep vein thrombosis of the legs, other vascular diseases, arterial hypertension (BP 160/100 mm Hg and above), coronary heart disease, history of stroke, complicated diabetes mellitus, malignant tumors of the reproductive system and mammary glands, severe liver dysfunction (cirrhosis, acute viral hepatitis), headaches with severe focal neurological symptoms, active smoking (more than 10-12 cigarettes per day) over the age of 35 years.

Oral contraceptives containing only microdoses of progestogens (300-500 mcg) are called “mini-pills”. They are used during lactation (6 weeks after birth), as they do not affect the quality, quantity of milk and duration of lactation; in late reproductive age; if there are contraindications to the administration of estrogens; for obesity. The contraceptive effectiveness of these drugs is significantly lower than that of COCs. The main representatives of the “mini-pill” class are: Microlut (levonorgestrel 0.3 mg), Exluton (linestrenol 0.5 mg), Sirazet (desogestrel 0.75 mg). The latter drug has higher contraceptive activity, comparable to that of COCs. Contraindications for mini-pill drugs are almost the same as for COCs.

Injectable depot preparations are used less frequently and have their own characteristics. Some of them - Depo-Provera (medroxyprogesterone acetate 150 mg), Norethisterate enanthate 200 mg - can be used 6 weeks after birth, within 7 days after an induced abortion, in late reproductive age, if there are contraindications for the use of estrogens. The contraceptive effectiveness of depot preparations approaches that of COCs.

Thus, the data presented in this review indicate that hormonal contraceptives are highly reliable in preventing unwanted pregnancy. They are most suitable for use at a young age. In addition to preventing pregnancy, hormonal contraceptives have a multifaceted therapeutic and preventive effect. With the help of hormonal contraception, abortions and, consequently, their complications such as menstrual irregularities, severe gynecological diseases and infertility can be reliably prevented.

Literature [show]

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Source: PHARMATEKA No. 11 - 2003

Progestogens are hormones that are normally secreted in the female body.

Also, the pharmacological market offers various types of gestagens - drugs that correct hormonal status.

The mechanism of action of biological substances has been known for a long time. The main properties of gestagens are the preservation and maintenance of reproductive function.

Preparations based on these substances are widely used for the treatment of hormone-dependent pathologies.

Many women know that gestagens are contraceptives. However, the hormone produced in the body does not have such an effect.

Only medications taken according to a specific regimen provide a contraceptive effect.

Estrogen and gestagen are the main hormones of the female body produced by the sex glands.

They provide menstrual and reproductive function, support the functioning of organs and systems, preserve youthful skin and are responsible for secondary sexual characteristics, forming attractive curves of the body.

The progestogen hormone has no meaning for a woman without estrogen.

Therefore, for the normal function of organs and systems, a combination of biological substances is necessary.

Progestogens are produced throughout the menstrual cycle, but increased activity is observed in the luteal phase - after ovulation.

Progestin hormones, which in medicine are also called progestins or progestogens, are synthesized in the ovaries by the temporary endocrine gland.

Also sources of biological substance of the second phase are the adrenal glands and the placenta, which forms from the second trimester of pregnancy in the cavity of the reproductive organ.

The main hormone with a gestagenic effect is.

It determines the physiological function of progestins, ensuring the possibility of fertilization, implantation and pregnancy.

The effect of gestagens on the mammary gland

The mechanism of action of gestagens on the mammary gland is still being studied to this day. Numerous studies give the right to assert that the hormone is a hormone of certain elements of glandular tissue.

The set of biological actions ensures the completion of breast development in girls during puberty and the formation of a round shape instead of the teenage conical shape.

Hormones provoke tissue maturation for subsequent lactation.

Thanks to progesterone, the negative effect of estrogen on the mammary glands is reduced. This provides a preventive effect for diseases such as hyperplasia, mastopathy, and glandular cystic formations.

For the endometrium

Gestagens act on the functional layer of the uterus after ovulation. In the first phase of the cycle, proliferative activity of the functional layer is noted.

With the onset of the second phase, the endometrium becomes secretory. In simple words, the hormone produced allows the mucous membrane to “mature” to such a state as to accept the fertilized egg.

Biological substances secreted by the gonads have a preventive effect on the endometrium, preventing the development of hyperplasia, adenomyosis and fibrocystic lesions.

To the genitals

Gestagens have a relaxing effect on the genitals. Hormones are of particular importance for the fallopian tubes and the muscular layer of the reproductive organ.

Thanks to progesterone, vasopressin and oxytocin are broken down. This helps prevent premature contraction of the uterus and separation of the functional layer.

By their action, biological substances provide a decrease in sensitivity during menstruation.

With a lack of gestagens, women experience an irregular cycle with spotting breakthrough bleeding. Deficiency of sex hormones causes painful menstruation and severe PMS.

For pregnancy

Despite the fact that synthetic gestagens are a natural hormone, it is important for pregnancy.

The very origin of the term denoting biological matter comes from the words gesto and gens, which mean to bear, continue, produce.

Produced in the second half of the cycle, the hormone prepares the uterine lining to accept the embryo.

If implantation has taken place, then over the next 10-12 weeks the corpus luteum will support new life, preventing the muscle layer from contracting and rejecting it.

The formed placenta subsequently takes on this task.

When to use progestin drugs

The progestin component of drugs can be of natural or synthetic origin.

Medicines are used to achieve the following results:

• transition of the functional layer of the uterus to the secretory phase;
• increased cervical activity and thickening of mucus;
• suppression of contractile activity of muscle tissue;
• increase in basal temperature;
• stimulation of breast tissue.

All progestin agents are used in the treatment of cycle disorders, endometriosis and for the purpose of contraception.

Also used during menopause and menopause.

They are used as additional medications in the complex treatment of acne, PCOS, endometrial and mammary hyperplasia, and prostate cancer in men.

Treatment

Progestogenic activity depends on the active substance on which the medicine is based.

Name of gestagen	Action
	Progestin	Antiestrogenic	Androgenic	Antiandrogenic
Progesterone (Utrozhestan, Crinon)	Moderate	Moderate	Absent	Absent
Norethisterone (Norkolut, Kliogest)	High	High	High	Absent
(Mirena, Postinor, Tri-regol)	Very high	Very high	Very high	Absent
Desogestrel (Mersilon, Escapelle, Novinet)	Very high	High	Moderate	Absent
Gestodene (Charosetta, Logest)	Very high	High	Moderate	Absent
Norgestimate (Sileste)	Very high	High	Moderate	Absent
Dydrogestarone (Femoston, Duphaston)	Moderate	Moderate	Absent	Absent
Dienogest (Janine)	High	Absent	Absent	Moderate

All substances, with the exception of norethisterone, do not have an estrogenic effect. In accordance with the indications and individual hormonal status, a specific drug is prescribed.

Medicines are available in the form of injections, oral capsules, tablets and intrauterine devices.

Contraceptives

Combined estrogen-gestagen drugs are used for contraception.

Medicines regulate the menstrual cycle, reduce the severity of premenstrual syndrome, and improve the condition of the epidermis.

The active component of contraceptives blocks the release of luteinizing hormone, which triggers ovulation in a woman’s body.

The drugs also reduce the concentration and increase the viscosity of cervical mucus.

The principle of action of contraceptives

provides a double protective effect: the oocyte does not leave the ovary, and sperm cannot overcome the barrier of vaginal secretion.

Among progestin agents, you can choose drugs in a convenient form:

• implant - inserted subcutaneously and valid for 3-6 months;
• intrauterine devices - used for 5 years;
• oral medications – taken continuously.

Side effects

The latest generation of progestogens, like any medicine, can cause adverse reactions:

• migraine, drowsiness, dizziness;
• digestive disorders;
• breakthrough bleeding;
• pain in the mammary glands;
• increased blood pressure;
• blood clot formation;
• decreased sex drive;
• change in body weight up or down;
• skin manifestations;
• fluid retention and swelling.

When considering the likelihood of negative manifestations, each drug should be studied individually.