Oral contraceptives: a list of drugs. Hormonal contraception and concomitant pharmacotherapy. How to use COC

The synthetic estrogen ethinylestradiol (EE) is used as the estrogen component of COCs, and various synthetic progestogens are used as the progestogenic component.

Currently, COCs are very popular all over the world, providing:

High contraceptive reliability;

Good tolerance;

Availability and ease of use;

Lack of connection with sexual intercourse;

Adequate control menstrual cycle;

Reversibility ( full recovery fertility within 1-12 months. after discontinuation);

Safety for the majority somatically healthy women;

Healing effects:

regulation of the menstrual cycle,

Elimination or reduction of symptoms of dysmenorrhea,

Reducing menstrual blood loss and, as a result, treatment and prevention of iron deficiency anemia,

Elimination of ovulatory pains,

Frequency reduction inflammatory diseases pelvic organs (PID),

Treatment for premenstrual syndrome

Therapeutic effect in hyperandrogenic conditions;

Preventive effects:

Reducing the risk of developing endometrial and ovarian cancer, as well as colorectal cancer,

Reducing the risk of benign neoplasms breast,

Reducing the risk of developing iron deficiency anemia,

Reduced risk of ectopic pregnancy;

Removal of "fear of unwanted pregnancy";

The possibility of "delaying" the next menstruation, for example, during exams, competitions, rest and for medical reasons.

Types and composition of modern COCs, mechanism of action

All existing combined oral contraceptives, for the convenience of determining their properties, are classified by the type of progestogen component, by the dose of each ethinyl estradiol tablet B and by composition. The presence of various classification features was the result of a long, almost half-century history of the creation of KOC.

According to the amount of the estrogen component in the composition of COC tablets, they are divided into:

High-dose - 50 mcg EE / day. (Ovidon);

Low-dose - no more than 30-35 mcg EE / day. (Dia-not-35, Jeanine, Femoden, Yarina, Silest, Marvelon, Regu-lon, Triquilar, Tri-Regol, Tri-Merci, etc.);

Microdosed - 15-20 mcg EE / day. (Logest, Mirelle, Novinet, Mercilon, Lindinet, etc.).

Currently synthesized COCs, depending on the combination scheme of estrogen and progestogen, are divided into two main types:

Monophasic: with a constant daily dose of estrogen and progestogen throughout the intake;

Multiphasic: three-phase, with a variable dose of estrogen and progestogen, simulating fluctuations in the content of natural ovarian hormones during a normal menstrual cycle (3 types of tablets with different estrogen / progestogen ratios).

Qualitative and quantitative composition hormonal contraceptives continues to improve and expand. Currently, according to WHO recommendations, the dose of the estrogen component in COCs used for planned contraception should not exceed 35 micrograms of ethinyl estradiol (low-dose contraceptives). It should be emphasized that for the purpose of planned contraception, low- and micro-dose drugs should be used (see Table 2.3). High-dose COCs are mainly used for emergency contraception and sometimes for medicinal purposes.

The introduction of three-phase combined estrogen-gestagenic drugs into clinical practice was the next stage in the development of contraception. The variable content of steroids in these preparations made it possible to reduce the total course dose of the progestogen component by almost 40% compared with the dose obtained with the use of similar monophasic preparations. The stepwise regimen of the use of three-phase drugs ensures good tolerability of the drugs. In this regard, multi-phase oral contraceptives can be prescribed not only to women reproductive age, but

Table 2.3

Compound

And girls and teenagers whose hormonal parameters of the menstrual cycle are not yet stable enough.

Taking into account the progestogenic component, COCs are divided into generations, counting from the time of their first synthesis. In the early 60s from C-19-nortestosterone plant origin, which has a good contraceptive property, first-generation progestogens (no-retinodrel, etinodiol diacetate and norethindrone acetate) were synthesized. These substances of a progestogenic nature had certain androgenic properties.

Studies have shown that first-generation progestogens in the human body are transformed into norethisterone. This made it possible by 1970 to establish its synthesis, and then the synthesis of new C-19-norsteroids (norgestrel and levonorgestrel) - the second generation. Moreover, the progesterone activity of levonorgestrel, contained in most modern COCs of the second generation, turned out to be 10 times higher compared to norethinodrel and etinodiol acetate, and androgenic - the same number of times lower.

The appearance in the 80s of the 20th century of derivatives that are chemically close to levonorgestrel, but have only a minimal residual affinity for androgen receptors, marked the beginning of the production of the last, third generation of COCs (desogestrel, gestodene, norgestimate, dienogest, drospirenone). These substances have more pronounced progesterone-like properties, which made it possible to significantly reduce the dose of progestogen required to suppress ovulation.

The progesterone effect of C-19-norsteroids in target organs depends on the degree of their affinity for progesterone and androgen receptors. Gestodene and desogestrel have the highest affinity for progesterone receptors. In addition, the active metabolite of desogestrel (3-ketodesogestrel) has a lower affinity for androgen receptors, which ensures its pronounced selectivity, i.e. selectivity of interaction with progesterone receptors. Norgestimate quickly enough in the body turns into levonorgestrel, and its derivatives acquire the properties of a second-generation progestogen in the process of metabolism.

The advantages of COCs containing third generation progestogens are to minimize their effect on carbohydrate metabolism and insulin resistance, on the cholesterol-lipoprotein blood profile, and on the hemostasis system.

Combined oral contraceptives are the most popular method of contraception. So, in Germany, these drugs

Used by more than 30% of women aged 15 to 45, and in the Netherlands - more than 40% of women in this age group, and Belgium and France - 50%. In Russia, the number of users of this method is 8%, according to the State Statistics Committee of Russia (2004).

Apart from high efficiency and low frequency of side effects, oral contraceptives are easy to use (unlike many methods of contraception), do not create inconvenience in the intimate area.

These drugs are widespread throughout the world. Today all over the world oral contraceptives accept more than 150 million women. The composition of these drugs has changed, which has led to an increase in their acceptability and safety.

The mechanism of action of COCs (Fig. 2.1) is the same for all drugs, it does not depend on the composition of the drug, the dose of its components and phase.

The contraceptive action of OK is carried out at various levels of the hypothalamus-pituitary-ovaries-uterus-fallopian tubes system. This mechanism includes suppression of the gonadotropic function of the pituitary gland by inhibiting the production of releasing hormones synthesized by the hypothalamus, which leads to inhibition of ovulation and temporary sterility. The direct inhibitory effect of oral contraceptives on ovarian function has also been proven. When COCs are used, the ovaries decrease in size, contain many atretic follicles, and the secretion of estrogen by the ovaries is almost halved. The endometrium also undergoes changes: it undergoes rapid regression in the proliferative phase of the cycle and premature secretory transformation, sometimes atrophic changes which have an anti-implantation effect. Also, under the influence of hormonal contraceptives, the peristalsis of the fallopian tubes and the passage of the egg through them slow down.

COCs contribute to a change in the biochemical composition cervical mucus, and the absence of cyclic changes in it, characteristic of a normal menstrual cycle, makes it viscous, which significantly impairs sperm penetration.

Thus, COCs, when used correctly, have almost one hundred percent contraceptive efficacy. As already mentioned, at present the most objective indicator of contraceptive effectiveness is the Pearl index, which reflects the pregnancy rate in 100 women during 1 year of drug use.

Rice. 2.1. Mechanism of action of COC.

Ratov. When using COC, the Pearl index ranges from 0.05 to 0.4. The great advantage of tablet preparations is their good tolerability and reversibility of action; in addition to high reliability, they meet increased safety requirements.

In order to improve the safety of prescribing means and methods of contraception, WHO in 1996 published for the first time criteria for the acceptability of the use of contraceptive methods. According to these criteria, all users of contraception can be divided into 4 categories according to their condition. Moreover, it is proposed to understand the state as the biological characteristics of the user, including age and reproductive history, as well as various pathological processes and diseases. Since then, the criteria have been repeatedly revised and supplemented with new recommendations, and the last revision took place in 2004 (see Appendix 2).

Category III should include users for whom the method is generally not recommended, as the risks of using it usually outweigh the benefits. The exception is when a more suitable method or remedy is not available or acceptable. Prescribing a contraceptive method to a woman in category III requires careful consideration. body clinical assessment and availability of clinical on-| observation.

It is important to note that the entry into force of these recommendations, on the one hand, made it possible to more flexibly and clearly choose the consumer and the method of protection against unwanted conception, on the other hand, it made it possible to significantly reduce the list absolute contraindications to hormonal contraception.

Absolute contraindications to the use of combined oral contraceptives (WHO, 2004, category IV) are:

The presence of multiple risk factors for cardiovascular disease;

Arterial hypertension (BP system > 160 mm Hg and BP diast. > 100 mm Hg);

Thrombophlebitis, thromboembolic diseases, disorders cerebral circulation, cerebrovascular strokes, myocardial infarction (history);

Surgical operations with prolonged immobilization;

Thrombogenic mutations (factor V Leiden, protein S deficiency, etc.);

Diseases of the heart valves with complications;

Migraine with neurological symptoms;

Diabetes mellitus with vascular complications, or in combination with other vascular diseases, or with a duration of more than 20 years;

Acute liver disease (hepatitis), liver cirrhosis in the stage of decompensation;

benign or malignant tumors liver;

Uterine bleeding of unknown etiology;

current breast cancer;

Breastfeeding up to 6 weeks. after childbirth;

Pregnancy;

Smoking (15 cigarettes per day or more) over the age of 35.

Researchers pay special attention to the effect of estrogen-gestagenic drugs on the cardiovascular system. Summarizing the results of epidemiological studies, we can conclude that for non-smoking women under 40 years of age, taking OCs is not a risk factor and is not statistically significantly associated with an increase in the incidence of cardiovascular diseases, if there are no additional factors(hereditary predisposition, concomitant cardiovascular diseases, obesity, smoking) (see section "Systemic effects of COCs").

Comparative characteristics of progestogens that are part of modern COCs

Progestogens are steroid hormones. The mechanism of their action is associated with an effect on steroid receptors. The first structure with which progestogens interact in the process of implementing biological activity at the cellular level is the plasma membrane of target cells. It contains specific receptors that perform very important features. Firstly, this is the stage of recognition, identification of the corresponding hormone; secondly, when binding to a hormone, a change occurs functional state cells by changing the permeability of membranes for various ions, changes in active

Tee enzymes, the formation of second messengers inside the cell. This mediates the non-genomic effects of progestogens, which develop rapidly, within minutes or hours. Penetrating into the cell, progestogens bind to cytosolic receptors, which are nuclear proteins. As a result, the transcription of specific genes changes, which causes physiological and morphological changes in target organs. These are the genomic, slow effects of progestogens. They develop over several hours and even days.

There are 5 types of steroid receptors: for glucocorticoids, mineralocorticoids, estrogens, gestagens and androgens. Progesterone and progestogens specifically bind to progestogen receptors, but can to some extent bind to other types of steroid receptors, which determines the features of their action. So, progesterone and drospirenone, in addition to gestagenic receptors, bind to mineralocorticoid receptors, which causes their antimineralocorticoid action, medroxyprogesterone acetate - to glucocorticoid receptors, so it has a small glucocorticoid activity, a number of gestagens (cyproterone acetate, chlormadinone, dienogest, drospirenone) bind with androgen receptors.

It should be emphasized that the contraceptive effect of hormonal drugs is mainly due to the action of progestogens. Estrogens only potentiate the inhibitory effect of progestogens on ovulation at the level of the hypothalamic-pituitary system and the ovarian level. In addition, progestogens slow down the peristalsis of the fallopian tubes, which makes it difficult for the egg to pass into the uterine cavity; have an anti-implantation effect due to early secretory transformation of the endometrium and, finally, increase the viscosity of cervical mucus, which makes it difficult for spermatozoa to move into the uterine cavity. Each of the listed mechanisms separately is capable of providing a contraceptive effect, while their combination in hormonal preparations provides a high reliability of the method.

currently synthesized. a large number of a variety of progestogens, which opens up great opportunities for individual choice of a hormonal drug. This is especially important in view of the fact that today we actually have one synthetic estrogen - ethinylest-radiol, which is part of the COC; its main function is the control of the menstrual cycle, i.e. prevention of intermenstrual spotting due to action

progesterone on the endometrium. Progestogens are divided into two groups: derivatives of progesterone and 19-nortestosterone (Fig. 2.2). The chemical structure of the latter is close to natural progesterone. Progesterone derivatives, when taken orally, do not have a contraceptive effect. These include: dydrogesterone, chlormadinone acetate, megestrol acetate, medroxyprogesterone acetate, cyproterone acetate.

Further intensive research and development in the field of hormonal contraception during recent years would seem to have made further improvements in hormonal contraceptives impossible. However, focusing primarily on the additional effects of gestagens, scientists in 1980 developed the progestogen dienogest, which does not contain an ethynyl group at position 17a, which combines the advantages of progesterone derivatives and 19-norsteroids.

AT last years synthesized a new progestogen - a derivative of spirolactone - drospirenone.

Rice. 2.2. Classification of progestogens.

Derivatives of 19-nortestosterone are used in clinical practice most often. They are divided into 2 groups: norethisterone derivatives and levo-norgestrel derivatives.

The norethisterone group includes norethisterone, nor-ethinodrel, ethinodiol diacetate, linestrenol. All of them are metabolized in the body to norethisterone and only then become biologically active, since only norethisterone binds to progesterone receptors. Metabolism in the liver reduces them biological activity by 40%, therefore, high doses are required to obtain a contraceptive effect.

Dydrogesterone

Dydrogesterone is a retroprogesterone, a stereoisomer of progesterone with an additional double bond between carbon atoms in positions 6 and 7. The retroprogesterone molecule differs from the progesterone molecule by the transition of the methyl group of carbon 10 from position p to position a and hydrogen C19 from position a to position p. Dydrogesterone is a highly selective progestogen that almost completely binds to the progesterone receptor.Although this binding ability is less pronounced than that of progesterone, its bioavailability is better and the dose to achieve endometrial proliferation is 10-20 times less than other progestogens.As a result of this selectivity effects due to binding to other receptors are minimal.

Progesterone derivatives (17a-hydroxyprogesterone)

Position 17 is the main factor determining the activity of progestogens. The addition of a hydroxyl group to progesterone at position 17 leads to a loss of progestogenic activity. Although 17cx-hydroxyprogesterone is hormonally inactive, the formation of esters with acetate causes weak progestogenic activity, and with caproate - high activity; 17-hydroxyprogesterone caproate (17-OPC) is used in the clinic in the form of intramuscular injections for the treatment of endometrial hyperplastic processes.

Chlormadinone acetate

After oral administration of chlormadinone acetate is rapidly absorbed and almost does not undergo the first stage of metabolism in the liver. Therefore, its bioavailability is approximately 100%. Chlormadinone acetate accumulates in adipose tissue and is slowly excreted from the body: in 7 days, only 34% of the dose of the drug. The most important metabolite is 3-hydroxychlormadinone acetate, which accounts for 70% of the antiandrogenic activity of chlormadinone acetate.

Cyproterone acetate

The bioavailability of cyproterone acetate is about 100%. It does not bind to sex hormone-binding globulins (SHBG) and corticosteroid-binding globulins (GSKs), but is 93% bound to serum albumin. The drug accumulates in adipose tissue and is slowly excreted. Daily administration of high doses of cyproterone acetate leads to the accumulation and creation of a depot of the drug. Main metabolic functions cyproterone acetate - hydroxylation and deacetylation.

Rice. 2.3. Chemical structure of cyproterone acetate.

Cyproterone acetate, contained in Diane-35, has a pronounced antiandrogenic activity (Fig. 2.3). After taking Diane-35 cyproterone acetate is completely absorbed from the gastrointestinal tract. After ingestion of 1 tablet of Diane-35, Stakh is reached after 1.6 hours and is 15 ng / ml. Cyproterone acetate is almost completely bound to plasma albumin, approximately 3.5-4.0% is in the free state. Since protein binding is nonspecific, changes in SHBG levels do not affect the pharmacokinetics of cyproterone acetate. The pharmacokinetics of the drug is two-phase with a half-life (T1 / 2) of 0.8 hours and 2.3 days. respectively for the first and second phases. The total plasma clearance is 3.6 ml/min/kg. Cyproterone acetate is biotransformed by hydroxylation and conjugation. It is excreted mainly in the form of metabolites with urine and bile in a ratio of 1: 2, a small part - unchanged with bile. T in combination with ethinylestradiol.

The successful use of progestogens, as well as any other hormonal contraceptives, depends on careful consideration of contraindications for use, knowledge of the basics of clinical pharmacology, prediction and accounting possible complications and adverse reactions, an individual approach depending on the age, state of health and tolerability of the drug.

The biological action of various progestogens is shown in figure 2.9.

Rice. 2.9. Progesterone tree (Gynaecology Forum Vol. 9, No. 2, 2004).

More than 55 years have passed since the appearance of the first hormonal contraceptive, Enovida. Today, drugs have become more low-dose, safer and more diverse in form.

Combined oral contraceptives (COCs)

Most drugs use the estrogen ethinyl estradiol at a dosage of 20 micrograms. As a gestagen is used:

• norethindrone;
• levonorgestrel;
• norgestrel;
• norethindrone acetate;
• norgestimate;
• desogestrel;
• drospirenone is the most modern progestin.

A new trend in the production of COCs is the release of drugs that increase the level of folates in the blood. These COCs contain drospirenone, ethinyl estradiol, and calcium levomefolate (a metabolite folic acid) and are shown to women planning a pregnancy in the near future.

Monophasic COCs have a constant dose of estrogen and progestin. Biphasic COCs contain two, three-phase - three, and four-phase - four combinations of estrogen and progestogen. Multiphasic drugs do not have advantages over monophasic combined oral contraceptives in terms of efficacy and side effects.

About three dozen COCs are available on the pharmaceutical market, the vast majority of which are monophasic. They are available in the form of 21+7:21 hormonally active tablet and 7 placebo tablets. This facilitates consistent daily monitoring of regular COC use.

Combined oral contraceptives (COCs) list: types and names

Mechanism of action

The basic principle of COCs is to inhibit ovulation. Drugs reduce the synthesis of FSH and LH. The combination of estrogen and progestin gives a synergistic effect and increases their antigonadotropic and antiovulatory properties. In addition, COC contraceptives change the consistency of cervical mucus, cause endometrial hypoplasia and reduce the contractility of the fallopian tubes.

Efficiency largely depends on compliance. The frequency of pregnancy during the year ranges from 0.1% with correct use to 5% with violations in the regimen.

Advantages

Combined hormonal contraceptives are widely used to treat menstrual disorders, reduce or eliminate ovulatory syndrome. Taking COCs reduces blood loss, so it is advisable to prescribe them for menorrhagia. COCs can be used to adjust the menstrual cycle - if necessary, delay the onset of the next menstruation.

COCs reduce the risk of developing benign formations breast, inflammatory diseases of the pelvic organs, functional cysts. Taking COCs with existing functional cysts contributes to their significant reduction or complete resorption. The use of COCs helps to reduce the risk of malignant ovarian diseases by 40%, endometrial adenocarcinoma by 50%. The protective effect lasts up to 15 years after drug withdrawal.

Flaws

Side effects: Nausea, breast tenderness, breakthrough bleeding, amenorrhea, headache.

Estrogen, which is part of the COC, is able to activate the blood coagulation mechanism, which can lead to the development of thromboembolism. The risk group for the development of such complications while taking COCs includes women with high levels of LDL and low levels of HDL blood, a severe form of diabetes, accompanied by damage to the arteries, uncontrolled arterial hypertension, obesity. In addition, women who smoke are more likely to develop clotting disorders.

Contraindications for the use of combined oral contraceptives

• thrombosis, thromboembolism;
• angina pectoris, transient ischemic attacks;
• migraine;
• diabetes mellitus with vascular complications;
• pancreatitis with severe triglyceridemia;
• liver disease;
• hormone-dependent malignant diseases;
• vaginal bleeding of unknown etiology;
• lactation.

COCs and breast cancer

Most complete analysis cases of breast cancer development while taking COCs was presented in 1996 by the Joint Study Group hormonal factors breast cancer (Collaborative Group on Hormonal Factors in Breast Cancer). The study evaluated epidemiological data from more than 20 countries around the world. The results of the study showed that women who are currently taking COCs, as well as those who have taken them over the past 1-4 years, have slightly increased risk development of breast cancer. The study emphasized that the patients participating in the experiment were much more likely to undergo breast examinations than women who did not take COCs.

Today it is assumed that the use of COCs can act as a cofactor, which only interacts with the main cause of breast cancer and possibly potentiates it.

Transdermal Therapeutic System (TTS)

The transdermal therapeutic system patch is applied for 7 days. The used patch is removed and immediately replaced with a new one on the same day of the week, on the 8th and 15th days of the menstrual cycle.

TTS appeared on the market in 2001 ("Evra"). Each patch contains a week's supply of norelgestromin and ethinylestradiol. TTS is glued to dry, clean skin of the buttocks, abdomen, outer surface the upper part of the shoulder or torso with minimal body hair. It is important to monitor the density of TTS attachment every day and not apply nearby. cosmetics. The daily release of sex steroids (203 mcg norelgestromin + 33.9 mcg ethinyl estradiol) is comparable to a dose of low-dose COCs. On the 22nd day of the menstrual cycle, the TTC is removed and a new patch is applied after 7 days (on the 29th day).

The mechanism of action, efficacy, disadvantages and advantages are the same as those of COCs.

vaginal ring

Hormonal vaginal ring ("NovaRing") contains etonogestrel and ethinylestradiol (daily release 15 mcg + 120 mcg, respectively). The ring is set for three weeks, after which it is removed and kept for a week break. On the 29th day of the cycle, a new ring is introduced.

The dosage of ethinyl estradiol in the vaginal ring is lower than that of COCs, due to the fact that absorption occurs directly through the vaginal mucosa, bypassing the gastrointestinal tract. Due to the complete suppression of ovulation and the regular release, independent of the patient, the effectiveness is higher than that of COCs (0.3-6 %). Another advantage of the ring is the low chance of dyspeptic side effects. Some patients develop vaginal irritation, discharge. In addition, the ring may accidentally slip out.

The effect of hormonal contraceptives on libido is not well understood, research data are contradictory and depend on the average age in the sample and gynecological diseases, drugs used, quality assessment methods sexual life. In general, 10-20 percent of women may experience a decrease in libido while taking drugs. In most patients, the use of GCs does not affect libido.

Acne and hirsutism usually have low levels of sex hormone-binding globulin (SHBG). COCs increase the concentration of this globulin, having a beneficial effect on the condition of the skin.

Subtleties of application

The estrogen in the composition of COCs promotes the elimination of LDL and an increase in HDL and triglycerides. Progestins counteract the estrogen-induced change in lipid levels in the body.

1. For acne, preparations containing cyproterone acetate, drospirenone, or desogestrel as a progestin are prescribed. COCs containing cyproterone acetate and ethinylestradiol are more effective for acne than the combination of ethinylestradiol and levonorgestrel.
2. With hirsutism, drugs containing progestogens with antiandrogenic properties are recommended: cyproterone acetate or drospirenone.
3. Combinations of estradiol valerate and dienogest are more effective in reducing menstrual blood loss than ethinyl estradiol and levonorgestrel. In addition, an intrauterine system is indicated for the treatment of menorrhagia.
4. Preparations containing drospirenone 3 mg and ethinylestradiol 20 mcg are recognized as the most effective combination for correction PMS symptoms, including psychogenic nature .
5. Taking oral contraceptives increases systolic arterial pressure(BP) at 8 mm Hg. Art., and diastolic - 6 mm Hg. Art. . There is evidence of an increased risk of cardiovascular events in women taking COCs. Due to the increased likelihood of developing myocardial infarction and stroke in patients with arterial hypertension, when prescribing COCs, the benefit / risk ratio must be carefully weighed.
6. In non-smoking women under 35 years of age with compensated hypertension, COCs may be prescribed with careful monitoring of blood pressure during the first months of admission.
7. In the case of an increase in blood pressure against the background of taking COCs or women with severe hypertension shown intrauterine system or DMPA.
8. The selection of a contraceptive for patients with dyslipidemia should be carried out taking into account the effect of drugs on lipid levels (see Table 5).
9. Since the absolute risk of cardiovascular events in women with controlled dyslipidemia is low, in most cases, COCs containing estrogen at a dosage of 35 mcg or less can be used. For patients with LDL levels above 4.14 mmol / l, alternative means contraception.
10. The use of COCs in women with diabetes associated with vascular complications is not recommended. A suitable option for hormonal contraception in diabetes mellitus is the intrauterine levonorgestrel-releasing system, while dose adjustment of hypoglycemic drugs is usually not required.
11. Results of epidemiological studies studying the risk of developing myocardial infarction when prescribing oral contraceptives smoking women, are contradictory. because of limited quantity Convincing data COCs are recommended to be used with caution in all women who smoke over 35 years of age.
12. Obesity with a body mass index of 30 kg/m2 and above reduces the effectiveness of COCs and transdermal GCs. In addition, the use of COCs in obesity is a risk factor for venous thromboembolism. Therefore, the method of choice for such patients are mini-pills (gestagen-containing tablet contraceptives) and intrauterine contraceptives(levonorgesterel-releasing system).
13. The use of COCs with estrogen dosages of less than 50 mcg in non-smoking, healthy women over the age of 35 may have a beneficial effect on density bone tissue and vasomotor symptoms in perimenopause. This benefit must be viewed through the lens of the risk of venous thromboembolism and cardiovascular factors. Therefore, COCs are prescribed individually for women of the late reproductive period.

List of sources

1. Van Vliet H. A. A. M. et al. Biphasic versus triphasic oral contraceptives for contraception //The Cochrane Library. - 2006.
2. Omnia M Samra-Latif. contraception. Available from http://emedicine.medscape.com
3. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347(9017):1713–1727.
4. Carlborg L. Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne. Results of a multicenter study. Acta Obstetricia et Gynecologica Scandinavica 1986;65:29–32.
5. Batukan C et al. Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism. Gynecol Endocrinol 2007;23:38–44.
6. Fruzzetti F, Tremollieres F, Bitzer J. An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest. Gynecol Endocrinol 2012;28:400–8.
7. Lopez LM, Kaptein AA, Helmerhorst FM. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev 2012.
8. Armstrong C, Coughlin L. ACOG releases guidelines on hormonal contraceptives in women with coexisting medical conditions. - 2007.
9. Carr BR, Ory H. Estrogen and progestin components of oral contraceptives: relationship to vascular disease. Contraception 1997; 55:267–272.
10. Burrows LJ, Basha M, Goldstein AT. The effects of hormonal contraceptives on female sexuality: a review. The journal of sexual medicine 2012; 9:2213–23.

Oral contraceptives- contraceptive pills taken by mouth to prevent pregnancy. They contain synthetic analogues of two hormones produced in the body, and are called COCs (COCs) - combined oral contraceptives. Estrogen and progestin (gestagen) regulate the woman's menstrual cycle, so taking them in the required dosages according to a certain schedule - effective method pregnancy prevention. Studies show that less than 1% of women taking oral contraceptives become pregnant during the first year of their use. That is, the efficiency of the PDA is more than 99%.

Birth control pills come in a wide range of estrogen and progestin combinations. The drugs used today contain lower doses of estrogen than those available in the past, greatly reducing the chance of serious side effects.

The essence of contraceptive pills and the mechanism of action of CPC

For conception to occur, the egg must mature in the ovary and move to the fallopian tube. When the spermatozoa reach the fallopian tubes, the egg is fertilized. The fertilized egg then travels to the uterus, where the embryo develops. Oral contraceptives do not allow the egg to mature completely: the progestins contained in the tablets block the release of statins (releasing factors), the secretion of gonadoliberin is inhibited, which slows down. An immature egg cannot be fertilized. In addition, birth control pills thicken mucus in cervical canal preventing the passage of spermatozoa. Oral contraceptives also change the structure of the endometrium, which prevents a fertilized egg from attaching to the wall of the uterus and developing. The estrogen component of CPC stabilizes the menstrual cycle.

Classification of combined oral contraceptives

According to the dosing regimen, oral contraceptives are divided into:

• monophasic,
• two-phase,
• three-phase.

The composition of monophasic (non-ovlon, rigevidon, ovidon) includes estrogen and progestogen in certain quantities. Reception scheme: daily for 21 days.

Two- and three-phase (anteovin, triziston, tri-regol, triquilar) are taken according to the same scheme, but they are released in sets / containers, which include tablets with different concentrations of estrogen and progestogen, corresponding physiological cycle. This package helps a woman to "track" the daily intake of contraceptive pills. Tablets have different colors, indicating the amount of hormones contained.

Some drugs are released with additional dummy tablets (without the active ingredient). They are designed to develop a "conditioned reflex" - the habit of taking a contraceptive daily, and not just in certain days menstrual cycle. Since the amount of hormones in two- and three-phase preparations is less, they have a weaker effect on metabolic processes without reducing the contraceptive effect.

According to the estrogen component, COCs are divided into: ethinylestradiol-containing and NOCs (natural oral contraceptives) based on estradiol valerate . Ethinylestradiol (EE)-containing COCs are divided into:

1. High-dose 50 mcg EE (anteovine, non-ovlon) is not currently used due to the high risk of side effects.
2. Low-dose - 30-35 mcg EE (Yarina, Marvelon, Janine, Diane-35) with high contraceptive reliability.
3. Microdosed - 15-20 mcg of EE (Jess, Mercilon, Logest).

A drug based on estradiol valerate (EV) - qlaira. EV is chemically identical natural hormone the female body, so it acts softer than EE, hence the name - NOC.

According to the gestagenic component, there is no clear division. First, testosterone derivatives with residual androgenic activity were used as progestins. Next came preparations containing levonorgestrel, desogestrel, gestodene. Then they created progestins with antiandrogenic action: dienogest, drospirenone, cyproterone acetate.

PDA Advantages

In addition to being 99% effective, drugs containing progestin and estrogen have the following advantages:

• reduction of symptoms of dysmenorrhea, menorrhagia;
• reliability, reversibility of action;
• reducing the frequency of unpleasant pulling premenstrual pain;
• "Insurance" against the occurrence of benign neoplasms of the mammary glands;
• risk reduction inflammatory processes in the pelvis (as opposed to the use of intrauterine devices);
• reduction in the risk of endometrial cancer (by 50%), ovarian cancer (by 80%).

How to use COC

Important: the regimen depends on the type of oral contraceptives. For a 21 day schedule: take one tablet daily for 21 days, then skip 7 days and repeat cycle. For a 28-day schedule: take one tablet for 28 days, then repeat the cycle. Careful study of the instructions attached to the drug will help to avoid mistakes.

Skipping a dose for more than 24 hours increases not only the risk of conception, but also the chance of side effects. It is desirable to take PDA at the same time “on the machine”, then a habit will appear: we do not forget to brush our teeth. If a dose is missed, follow the instructions or consult the prescribing physician for advice. It is better to take birth control pills with food or at bedtime. This will help prevent the nausea that sometimes occurs during the first few weeks.

Side effects of hormonal contraception

serious side effects more often manifested in women who smoke over 35 years of age, in patients with specific health problems (arterial hypertension, diabetes, history of breast or uterine cancer). All risks and benefits of this type of contraception should be discussed with a gynecologist, taking into account the state of health.

Side effects are rare in healthy women, but still better to know about them. Oral contraceptives can cause:

• liver tumors, including malignant;
• increased blood pressure;
• stroke;
• nausea/vomiting;
• spastic pains in the abdomen;
• chest pain;
• swelling of the legs (ankles);
• fatigue;
• acne
• menstrual changes, including bleeding in the middle of the cycle;
• headache;
• vaginal infections;
• itching/irritation of the vulva;
• heaviness in the chest;
• change in libido;
• venous thromboembolism;
• depression
• skin reactions;
• fluid retention, weight gain;
• increase in blood sugar levels.

Birth control pills cause photosensitivity - sensitivity to sunlight therefore, prolonged exposure to the sun and solarium should be avoided. Sometimes appear dark spots, disappearing a few months after the abolition of the PDA. Oral contraceptives can cause bleeding gums, corneal irritation when wearing contact lenses.

More details about the side effects of oral contraceptives are described in the video review:

Mini-pill - gestagenic contraception

Mini-drank - the so-called oral contraceptives containing only the hormone progesterone (without estrogen). Mini-pills (exluton, microlut, ovrett) are prescribed for women who cannot use COCs: over 35 years old, suffering from hypertension, with a tendency to thrombosis, overweight.

Mini-pills can be used:

• with heart disease;
• liver diseases;
• breast cancer;
• vaginal bleeding of unknown etiology;
• ovarian cyst.

Tablets are safe to take while breastfeeding: a small amount of progestogen can pass into breast milk, but this is not harmful to the baby.

Mini-pills are generally well tolerated and side effects are rare. The first few months may be:

• acne
• soreness, swelling of the breast;
• increase / decrease in sexual desire;
• mood change;
• headache/migraine;
• nausea, vomiting;
• small ovarian cysts (disappear without treatment);
• stomach upset;
• weight gain.

Oral contraceptives: pros and cons

COCs have been used for 55 years. The "horror stories" associated with the side effects of the "pioneers" of hormonal contraception are gradually forgotten: "mustache will grow", "get fat" and others. Birth control pills not only help women control reproductive function, they are prescribed for hormonal disorders, hirsutism, acne, dysmenorrhea, PMS. But we must not forget that it is still hormonal preparations having a number of contraindications, therefore, a doctor should prescribe them.

More useful information about the advantages and disadvantages of oral contraceptives you will get by watching the video clip.

The most reliable method of protection against unplanned pregnancy is hormonal contraception, which is used in the form of intrauterine devices, injections, patches, vaginal rings, subcutaneous implants. The most popular and convenient form of taking hormones are birth control pills. The history of the use of oral contraceptives began in the 1950s and 1960s. XX century (drug Enovid, USA). Since then, they have been constantly improved, dosages have been reduced, new synthetic analogues have been studied, and the risks of side effects have decreased.

• suppression of ovulation by blocking the production of luteinizing and follicle-stimulating hormones in the pituitary gland;
• an increase in the viscosity of cervical mucus, which greatly complicates the movement of spermatozoa into the uterine cavity;
• a change in the structure and activity of the endometrium in such a way that it becomes incapable of implanting an egg if fertilization does occur.

Oral contraceptives, due to their high efficiency and reliability, are currently positioned as the gold standard among all contraceptive methods. They contain synthetic analogues of sex hormones (estrogens and progestins) that affect the menstrual cycle and the ability to conceive.

Types of drugs

All used oral contraceptives are divided into two main groups:

1. Combined oral contraceptives (COCs) containing two hormones estrogen (ethinylestradiol, estradiol valerate) and progestin (norethisterone, norgestrel, gestodene, desogestrel, dienogest).
2. Progestin-only mini-pills (microlut, exluton, charosetta, micronor, lactinet).

COCs can be:

• single-phase (microgynon, marvelon, rigevidon, lindinet) with the same unchanged doses of estrogen and progestin;
• two-phase (divina, anteovin, klimen, sequilar) with constant dose estrogen and progestin variable;
• three-phase (trikvilar, tri-regol, trisiston), where the dosage of estrogen and progestin changes three times, taking into account the phase of the menstrual cycle (follicular, ovulatory, luteal).

In polyphasic contraceptives, coatings of different colors are used to designate tablets with a different content of hormones. For example, in the biphasic COC Divina, there are 11 tablets in the package. white color and 10 blue.

COCs, depending on the amount of estrogen, are distinguished by high-dose (more than 35 mcg - Silest, Anteovin, Diane-35, non-ovlon, trisiston, ovidon, triquilar), low-dose (30 mcg - Microgynon, Marvelon, Regulon, Femodene, Belara, Yarina, Lindinet , chloe) and microdosed (20 mcg - logest, mersilon, mirelle, minisiston, zoeli, lindinet-20, jess, novinet).

Features of choice

When choosing oral contraceptives, you should understand that there is no better or worse drug, so you should not rely on the reviews of girlfriends or someone else's advice. Each organism is individual and has its own characteristics. There are tools that are suitable and not suitable in a particular situation.

If a woman decides to take contraceptives, then first of all she should contact a gynecologist and undergo an examination, since many factors are taken into account when choosing. Only a doctor will be able to choose the best drug by examining the results of the tests, the age and phenotype of the patient, the state of the reproductive system, plans for the birth of a child in the future.

However, there are some general recommendations optionally:

1. Microdosed birth control pills are recommended for girls just starting out sexual life women who use COCs for the first time, patients under 25 and over 35 years of age.
2. Low-dose monophasic oral contraceptives have an antiandrogenic effect. Helps reduce hair growth in unwanted areas upper lip, lower abdomen, cheeks, chin), oily skin of the face and head, seborrhea, acne. Designed for young and middle-aged women who have given birth and for those who are not suitable for microdosed drugs, as can be judged by the appearance of intermenstrual bleeding.
3. High-dose oral contraceptives are mainly used to correct hormonal disorders, therapy of endometriosis and other pathologies of the female genital organs.
4. Mini-pills are prescribed for women over 35 years of age who smoke, women during lactation, and also if there are contraindications for taking COCs.

Minipills are slightly less protective than COCs, but are less likely to cause adverse health effects.

Choice of contraceptives by phenotype

When choosing oral contraceptives, the constitutional features and phenotype of a woman are taken into account. There are three of them.

estrogen type. It includes women of short or medium height, with soft and thick hair, dry skin, well-developed mammary glands, high timbre of voice. Their periods are long, profuse and painful, accompanied by PMS. They are recommended oral contraceptives with an enhanced progestogen component: with gestodene (Logest, Lindinet-20, Femodene) or levonorgestrel (minisiston, microgynon, rigevidon, triquilar, trisiston).

balanced type. Representatives of the weaker sex with this phenotype are feminine, of medium height, have normal skin, medium-sized breasts. Menstruation lasts about 5 days, proceeds with moderate discharge, and is rarely accompanied by PMS. From oral contraceptives, they are prescribed micro- or low-dose drugs (Marvelon, Novinet, Logest, Trimersi, Silest, Femoden, Lindinet-30, Triquilar).

gestagenic type. It includes women with a boyish physique, tall, excessive activity of the sebaceous glands, low timbre of voice, small breasts. Monthly scanty, painless, before them often there are lethargy, depressive states, pain in the lower abdomen, in the back and muscles. With this phenotype, oral contraceptives with an enhanced estrogen component (jazz, belara, chloe, midian, claira, yarina, zoeli) are suitable, and in the presence of pronounced signs of hyperandrogenism, high-dose COCs (ovidon, bisekurin, non-ovlon, diane-35).

Popular drugs

Oral contraceptives commonly used in gynecology include charozetta, triquilar, marvelon, jess, yarina, marvelon.

Marvelon

The drug is produced by the pharmaceutical company Organon (Netherlands). Refers to low-dose COCs, is single-phase, contains 0.15 mg of desogestrel and 0.03 mg of ethinyl estradiol. The package contains 21 white tablets.

Marvelon is used for contraception, to compensate for hormone deficiency and to correct menstrual irregularities. It should be taken every day for three weeks, and then after a week break, start new packaging. During the termination of the contraceptive, menstruation should begin.

Triquilar

Triquilar is produced by the world famous company Bayer (Germany) and is a three-phase COC. Packaged:

• 5 white tablets containing 0.075 mg of levonorgestrel and 0.04 mg of ethinyl estradiol;
• 6 light brown tablets containing 0.05 mg levonorgestrel and 0.03 mg ethinyl estradiol;
• 10 yellow tablets containing levonorgestrel 0.125 mg and ethinyl estradiol 0.03 mg.

Jess

Jess is a fourth-generation microdosed monophasic oral contraceptive. Produced by Bayer, 28 tablets per pack, 24 of which are light pink in color and contain 3 mg of drospirenone and 0.02 mg of ethinyl estradiol, and 4 are white and are placebo, that is, they do not contain active ingredients.

Used for contraception for young girls and women, for the treatment of acne, severe forms of PMS, regulation of the menstrual cycle. Jess does not affect a woman's weight, does not cause swelling, improves the condition of hair and nails. The drug should be taken continuously, after the end of the package the next day, start a new one.

Yarina

Yarina, like the oral contraceptive Jess, belongs to monophasic COCs, contains drospirenone and ethinylestradiol and is manufactured by Bayer. There are two types of the drug: Yarina and Yarina Plus. Yarina Plus additionally includes calcium levomefolate, a source of folic acid, used when signs of vitamin B9 deficiency are detected.

Yarina contains 21 tablets and is taken in courses with a break of 7 days, and Yarina Plus contains 28 tablets, of which 7 (light orange) do not contain hormones, therefore they are used on a regular basis. Prescribe these hormonal oral tablets to prevent unwanted pregnancy and establish a regular menstrual cycle.

Charosetta

Charosetta is produced by Organon (Netherlands) and belongs to progestogen oral contraceptives. active ingredient is desogestrel at a dosage of 0.075 mg.

The drug is intended for contraception in women after childbirth during breastfeeding, after abortion, with estrogen intolerance and the impossibility of taking COCs for other reasons. The package contains 28 tablets.

Silest

Silest is produced in Switzerland, refers to high-dose monophasic COCs. Ethinylestradiol (0.035 mg) and norgestimate (0.25 mg) are used as active ingredients. May cause side effects due to increased dosage estrogen.

It is prescribed for contraception and for therapeutic purposes in some gynecological diseases. Not recommended for use by girls under the age of 18.

Advantages and disadvantages

When comparing oral contraceptives with alternative ways contraception can be found both advantages and disadvantages.

To the virtues birth control pills relate:

• maximum level of reliability (more than 99%);
• comfortable dosage form;
• availability and a wide range of drugs;
• correction of hormonal disorders, menstrual cycle and treatment of gynecological diseases;
• elimination unpleasant symptoms PMS;
• improving the condition of hair, nails, getting rid of acne, increased fat content of skin and hair;
• the possibility of use at any age;
• no discomfort during intercourse (as when using barrier contraception, contraceptive vaginal suppositories, ointments, creams);
• the possibility of a quick and painless restoration of the ability to conceive and childbearing, and against the background of discontinuation of drugs, the chances of becoming pregnant increase.

However, oral contraceptives also have disadvantages that must also be taken into account. So, you must strictly follow the instructions, drink the drug every day at the same time. If the tablets are taken incorrectly or skipped, a significant decrease in the degree of protection occurs.

This form of contraceptive has side effects (headaches, gastrointestinal disorders, decreased libido, swelling, pain in the mammary glands, nausea, depression), so you should carefully select the drug, taking into account many factors. Available big list contraindications, especially for COCs ( cardiovascular pathologies, liver and kidney diseases, diabetes mellitus, etc.).

It should be noted that the contraceptive effect occurs slowly (from 7 days), while there is no protection against sexually transmitted infections.

Video: Obstetrician-gynecologist about the types and use of oral contraceptives

Oral contraceptives what is this means of protection from unwanted pregnancy? On the basis of what you need to choose one or the other hormonal pills? How does taking oral contraceptives affect the body and for what diseases is it prohibited? Let's consider these questions.

Benefits of hormonal contraception

1. Reliability. Almost 100% efficiency if you follow the rules of the instructions. And they are very simple:

• take the drug at a certain time (you can in the morning or in the evening, as it is more convenient) for 21 days, do not skip the dose;
• do not drink medicines that can reduce the effectiveness of the contraceptive (a list is attached to the instructions);
• in case of vomiting, diarrhea that occurred within the first three hours after taking the pill, take another one, because the first one is most likely not digested.

2. Convenience. Took 1 pill a day and don't worry about getting pregnant. Menstruation comes regularly and, if necessary, they can be "transferred" if you continue to take combined oral contraceptives in a seven-day break.

3. Safety. Modern drugs contain a minimum concentration of hormones and can be taken without harm to health for several years, before planning a pregnancy or menopause. Oral contraceptives are well tolerated and have only minor side effects.

4. Health benefits. When taking pills, menstruation becomes moderate or even scarce. And reducing blood loss is the prevention of anemia. No anemia - the woman feels well, she has good hair and nails.

Prescribing the drug

If you have never taken hormonal contraceptives Be sure to consult your doctor about this. He will tell you how to choose oral contraceptives in the same place, at the reception, more often even without prior testing. The choice of drug does not depend on hormonal background women. That is, there is absolutely no need to take tests for progesterone, estrogen, etc. All drugs have a similar composition. Only the content of ethinyl estradiol and the type of synthetic progesterone differ.

There are low-dose monophasic oral contraceptives that are prescribed for endometriosis, acne, oily hair and other cosmetic issues. Usually, a conversation with the patient is enough for the doctor to prescribe the drug. Its financial capabilities are also taken into account. The list of oral contraceptives, available on the table of every gynecologist, helps to choose, if necessary, a generic drug, at a cost much more affordable than the original, but not worse in quality.

In the first three cycles of taking the drug, a woman may periodically appear intermenstrual daub. This is the so-called habituation of the body. But if the spotting persists for more than three months, it makes sense to replace the drug with a higher dosage of ethinyl estradiol, and sometimes with the now less popular three-phase one.

Oral contraceptives are contraindicated in patients with a history of thrombosis, diabetes mellitus, severe forms of migraine, a hormone-dependent form of breast cancer in history or at present, endometrial cancer, serious illnesses kidneys, liver, cardiovascular system.