Combined oral contraceptives (COCs)

Combined tablets (combined oral contraceptives - COCs) are the most common form of hormonal contraception.

According to the content of the estrogen component in the form of ethinylestradiol (EE), these preparations are divided into highly dosed, having in their composition more than 40 meg of EE, and low-dose components - 35 meg and less than EE. In monophasic preparations, the content of the estrogen and gestagen component in the tablet is unchanged throughout the entire menstrual cycle. In two-phase tablets in the second phase of the cycle, the content of the gestagenic component increases. In three-phase COC, an increase in the dose of the progestogen occurs stepwise in three stages, and the dose of EE increases in the middle of the cycle and remains unchanged at the beginning and at the end of the admission. Variable content of sex steroids in two- and three-phase preparations throughout the cycle allowed to reduce the total exchange rate of hormones.

Combined oral contraceptives are highly effective reversible means of preventing pregnancy. The Perl index (IP) of modern COCs is 0.05-1.0 and depends mainly on compliance with the rules for taking the drug.

Each tablet of combined oral contraceptive (COC) contains estrogen and progestogen. As an estrogen component of COC, synthetic estrogen - ethinyl estradiol (EE) is used, as progestagen - various synthetic progestogens (a synonym - progestins).

The gestagen contraceptives contain only one sex steroid - gestagen, which provides a contraceptive effect.

[1], [2], [3], [4], [5],

Advantages of combined oral contraceptives

Contraceptive

• High efficiency at daily reception IP = 0.05-1.0
• Fast effect
• Lack of communication with sexual intercourse
• Few side effects
• The method is convenient in application
• The patient can stop taking it herself

Non-contraceptive

• Reduce menstrual like bleeding
• Reduce menstrual pain
• May reduce the severity of anemia
• Can facilitate the establishment of a regular cycle
• Prevention of ovarian and endometrial cancer
• Reduce the risk of developing benign breast tumors and ovarian cysts
• Protect from ectopic pregnancy
• Provide some protection against pelvic inflammatory disease
• Provide prevention of osteoporosis

Currently, COCs are very popular all over the world due to the advantages listed below.

• High contraceptive reliability.
• Good tolerability.
• Accessibility and ease of use.
• Lack of communication with sexual intercourse.
• Adequate control of the menstrual cycle.
• Reversibility (complete restoration of fertility within 1-12 months after discontinuation of admission).
• Safety for most somatically healthy women.
• Therapeutic effects:
  • regulation of the menstrual cycle;
  • elimination or reduction of dysmenorrhea;
  • reduction of menstrual blood loss and, as a result, treatment and prevention of iron deficiency anemia;
  • elimination of ovulatory pain;
  • decrease in the incidence of inflammatory diseases of the pelvic organs;
  • therapeutic action in premenstrual syndrome;
  • therapeutic effect in hyperandrogenic conditions.
• Preventive effects:
  • reduced risk of developing endometrial and ovarian cancer, colorectal cancer;
  • reducing the risk of developing benign breast tumors;
  • reducing the risk of iron deficiency anemia;
  • reducing the risk of ectopic pregnancy.
• Removing the "fear of unwanted pregnancy."
• Possibility of "postponement" of another menstruation, for example, during exams, competitions, rest.
• Emergency contraception.

[6], [7], [8]

Types and composition of modern combined oral contraceptives

The daily dose of the estrogen component of COC is divided into high-dose, low-dose and microdosed:

• high-dose - 50 mcg EE / day;
• low-dose - no more than 30-35 μg EE / day;
• microdosed, containing micro-doses of EE, 15-20 mcg / day.

Depending on the scheme of the combination of estrogen and progestogen COC are divided into:

• monophasic - 21 tablets with an unchanged dose of estrogen and progestogen for 1 cycle of admission;
• biphasic - two kinds of tablets with a different ratio of estrogen to progestogen;
• three-phase - three kinds of tablets with a different ratio of estrogen and progestogen. The main idea of three-phase - the reduction of the total (cyclic) dose of progestogen due to a three-step increase in its dose during the cycle. In the first group of tablets, the dose of the progestogen is very low - approximately from that in the monophasic COC; in the middle of the cycle the dose increases slightly and only in the last group of tablets corresponds to the dose in the monophasic preparation. Reliability of suppression of ovulation is achieved by increasing the dose of estrogen at the beginning or middle of the intake cycle. The number of tablets of different phases varies in different preparations;
• multiphase - 21 tablets with a variable ratio of estrogen to progestogen in tablets of the same cycle (one package).

Currently, low- and micro-dosed drugs should be used for contraception. High-dose COCs can be used for routine contraception only for a short time (if necessary, increase the dose of estrogen). In addition, they are used for medicinal purposes and for emergency contraception.

The mechanism of contraceptive effect of combined oral contraceptives

• Suppression of ovulation.
• Thickening of the cervical mucus.
• Changes in the endometrium that prevent implantation. The mechanism of action of COC as a whole is the same for all drugs, it does not depend on the composition of the drug, the dose of components and the phase. The contraceptive effect of COCs is mainly due to the progestogen component. EE in the COC supports the proliferation of the endometrium and thus provides control of the cycle (no intermediate bleeding when taking COCs). In addition, EE is necessary for the replacement of endogenous estradiol, since there is no growth of the follicle with COCs, and therefore oestradiol is not secreted.

Classification and pharmacological effects

Chemical synthetic progestogens are steroids and are classified by origin. The table lists only progestogens that are part of the registered hormonal contraceptives in Russia.

Classification of progestogens

Testosterone derivatives	Progesterone derivatives	Derivatives of spironolactone
Containing the ethynyl group at C-17: Norethisterone Norgestrel Levonorgestrel Gestoden Desogestrel Norgestimate Ethinyl group free: Dienogest	Cyproterone acetate Chlormadinone acetate Medroxyprogesterone acetate	Drospirenone

Like natural progesterone, synthetic progestogens cause a secretory transformation of estrogen-stimulated (proliferative) endometrium. This effect is due to the interaction of synthetic progestogens with progesterone receptors of the endometrium. In addition to affecting the endometrium, synthetic progestogens also act on other target organs of progesterone. The differences between synthetic progestogens and natural progesterone are as follows.

• Higher affinity for progesterone receptors and, as a consequence, a more pronounced progestogenic effect. Due to the high affinity for the progesterone receptors of the hypothalamic-pituitary region, synthetic progestogens in low doses cause a negative feedback effect and block the release of gonadotropins and ovulation. This is the basis of their use for oral contraception.
• Interaction with receptors to some other steroid hormones: androgens, gluco- and mineralocorticoids - and the presence of appropriate hormonal effects. These effects are relatively weak and are therefore called residual (partial or partial). Synthetic progestogens differ in the spectrum (set) of these effects; some progestogens block receptors and have a corresponding anti-hormonal effect. For oral contraception, antiandrogenic and antimineralocorticoid effects of progestogens are favorable, androgenic effect is undesirable.

[9], [10]

Clinical significance of individual pharmacological effects of progestogens

The pronounced residual androgenic effect is undesirable, since it can cause:

• androgen dependent symptoms - acne, seborrhea;
• a change in the lipoprotein spectrum towards the predominance of low density fractions: low-density lipoproteins (LDL) and very low-density lipoproteins, since the synthesis of apolipoproteins and the destruction of LDL are inhibited in the liver (the effect opposite to the effect of estrogens);
• deterioration of tolerance to carbohydrates;
• weight gain due to anabolic effects.

By the expression of androgenic properties, progestogens can be divided into the following groups.

• Highly androgenic progestogens (norethisterone, linestrenol, ethynodiol diacetate).
• Progestogens with moderate androgenic activity (norgestrel, levonorgestrel in high doses - 150-250 mcg / day).
• Progestogens with minimal androgenicity (levonorgestrel at a dose of no more than 125 mcg / day, gestoden, desogestrel, norgestimate, medroxyprogesterone). The androgenic properties of these progestogens are found only in pharmacological tests, in most cases they have no clinical significance. WHO recommends the use of predominantly oral contraceptives with low-androgenic progestogens.

The antiandrogenic effect of cyproterone, dienogest and drospirenone, as well as chloromadinone is of clinical importance. Clinically, the anti-androgenic effect is manifested in a decrease in androgen-dependent symptoms - acne, seborrhea, hirsutism. Therefore, COCs with antiandrogenic progestogens are used not only for contraception, but also for the treatment of androgenization in women, for example, in the syndrome of polycystic ovaries (PCOS), idiopathic androgenization and some other conditions.

Severity of antiandrogenic effect (according to pharmacological tests):

• cyproterone - 100%;
• dienogest - 40%;
• drospirenone - 30%;
• Chlormadinone - 15%.

Thus, all the progestogens that make up the COC can be arranged in a series in accordance with the severity of both the residual androgenic and antiandrogenic effects.

Admission COC should start from the 1st day of the menstrual cycle, after taking 21 tablets, a break takes 7 days or (with 28 tablets in the package) 7 tablets taken.

[11], [12], [13], [14], [15], [16]

The rules of the missed pill

The following rules regarding missed tablets have now been adopted. In cases where less than 12 hours have passed, it is necessary to take the pill at a time when the woman remembered about the admission, and then the next pill - at the usual time. This does not require additional precautions. If more than 12 hours have elapsed since the pass, it is necessary to do the same, but within 7 days apply additional measures of protection from pregnancy. In those cases where two or more tablets are missed in a row, two tablets per day should be taken until reception is included in the regular schedule, using additional methods of contraception within 7 days. If after the missed tablets bloody discharge begins, take the tablets better stop and start a new package after 7 days (counting from the beginning of missing the tablets). If you miss even one of the last seven hormone-containing tablets, the next package should start without a seven-day break.

Rules for changing drugs

The transition from more highly-dosed drugs to low-dose drugs is performed with the onset of low-dose COCs without a seven-day break the day after the end of the 21st day of taking high-dose contraceptives. The replacement of low-dosage drugs with highly-licensed drugs takes place after a seven-day break.

Symptoms of possible complications when using COCs

• Severe chest pain or shortness of breath
• Severe headaches or blurred vision
• Severe pain in lower limbs
• Complete absence of any bleeding or discharge during a week without tablets (pack of 21 tablets) or while taking 7 inactive tablets (from a 28-day package)

If any of the above symptoms occur, an urgent medical consultation is required!

Recovery of fertility

After stopping the COC, the normal functioning of the hypothalamic-pituitary-ovary system is quickly restored. More than 85-90% of women are able to become pregnant within 1 year, which corresponds to the biological level of fertility. Admission of COCs prior to the beginning of the conception cycle does not adversely affect the fetus, course and outcome of pregnancy. Accidental reception of COC in early stages of pregnancy is not dangerous and is not the basis for abortion, but at the first suspicion of pregnancy a woman should immediately stop taking COC.

Short-term reception of COC (within 3 months) causes an increase in the sensitivity of the receptors of the hypothalamus-pituitary-ovary system, so when the COC is abolished, ejection of tropic hormones and stimulation of ovulation occur. This mechanism is called "rebound-effect" and is used for some forms of anovulation.

In rare cases, after withdrawal of COC, amenorrhea is observed. It can be a consequence of atrophic changes in the endometrium, developing when taking COC. Menstruation occurs when the functional layer of the endometrium is restored independently or under the influence of therapy with zestrogens. Approximately 2% of women, especially in the early and late fertility periods, after stopping the COC, amenorrhea lasting more than 6 months (the so-called post-pill amenorrhoea - hyperdrug syndrome) is observed. The nature and causes of amenorrhea, as well as the response to therapy in women using COCs, do not increase the risk, but can mask the development of amenorrhea by regular menstrual bleeding.

Rules for the individual selection of combined oral contraceptives

COCs are selected strictly for a woman, taking into account the features of the somatic and gynecological status, the data of individual and family history. The selection of the COC takes place according to the following scheme.

• Targeted interrogation, assessment of the somatic and gynecological status and definition of the category of acceptability of the method of combined oral contraception for this woman in accordance with WHO eligibility criteria.
• The choice of a specific drug, taking into account its properties and, if necessary, therapeutic effects; advising a woman on the method of combined oral contraception.
• Observing a woman for 3-4 months, assessing the tolerability and acceptability of the drug; if necessary, a decision to change or cancel the COC.
• Clinical follow-up of a woman during the entire period of use of COCs.

A woman's survey is aimed at identifying possible risk factors. It necessarily includes the following series of aspects.

• Character of the menstrual cycle and gynecological anamnesis.
  • When there was a last menstruation, whether it was normal (it is necessary to exclude pregnancy now).
  • Is the menstrual cycle regular. Otherwise, a special examination is necessary to identify the causes of the irregular cycle (hormonal disorders, infection).
  • The course of previous pregnancies.
  • Abortions.
• Previous use of hormonal contraceptives (oral or other):
  • whether there were side effects; if so, which;
  • for what reasons the patient stopped using hormonal contraceptives.
• Individual history: age, blood pressure, body mass index, smoking, medication, liver disease, vascular disease and thrombosis, presence of diabetes, oncological diseases.
• Family history (illness in relatives who developed before the age of 40): arterial hypertension, venous thrombosis or hereditary thrombophilia, breast cancer.

In accordance with the conclusion of the WHO, the following survey methods are not relevant for assessing the safety of the use of COCs.

• Examination of mammary glands.
• Gynecological examination.
• Examination for the presence of atypical cells.
• Standard biochemical tests.
• Tests for inflammatory diseases of the pelvic organs, AIDS. The drug of the first choice should be a monophasic COC with an estrogen content of no more than 35 μg / day and a low androgenic gestagen. Such COCs include Logest, Femoden, Zhanin, Yarina, Mersilon, Marvelon, Novinet, Regulon, Belara, Miniziston, Lindineth, Silest ".

Three-phase COCs can be considered as reserve drugs when there are signs of estrogen deficiency against a background of monophasic contraception (poor control of the cycle, dryness of the vaginal mucosa, decreased libido). In addition, three-phase drugs are indicated for primary use in women with signs of estrogen deficiency.

When choosing a drug should also take into account the state of health of the patient.

In the first months after the onset of COC intake, the body adapts to hormonal reorganization. During this period, intermenstrual smearing or, more rarely, breakthrough bleeding may occur (in 30-80% of women), as well as other side effects associated with hormonal imbalance (in 10-40% of women). If unwanted events do not occur within 3-4 months, it is possible that the contraceptive should be changed (after excluding other causes - organic diseases of the reproductive system, skipping tablets, drug interactions). It should be emphasized that at present the selection of COC is large enough to select them for the majority of women who are shown this method of contraception. If the woman is not satisfied with the drug of the first choice, the drug of the second choice is selected taking into account the specific problems and side effects that the patient has.

Choosing a COC

Clinical situation	Preparations
Acne and / or hirsutism, hyperandrogenia	Preparations with antiandrogenic progestogens: "Diane-35" (for severe acne, hirsutism), "Zhanin", "Yarina" (for acne of mild and moderate degree), "Belara"
Violation of the menstrual cycle (dysmenorrhea, dysfunctional uterine bleeding, oligomenorrhoea)	COC with a pronounced progestogen effect ("Microgonon", "Femoden", "Marvelon", "Janine"), when combined with hyperandrogenism - "Diane-35". When DMC is combined with recurrent endometrial hyperplastic processes, the duration of treatment should be at least 6 months
Endometriosis	Monophasic COCs with dienogest ("Jeanine"), or levonorgestrel, or gestodene or gestagenic oral contraceptives are indicated for prolonged use. The use of COC can help restore the generative function
Diabetes without complications	Preparations with a minimum content of estrogen - 20 mcg / day (intrauterine hormonal system "Mirena")
Primary or repeated administration of oral contraceptives to a patient who smokes	Smoking patients under 35 years of age - COCs with a minimum estrogen content, smokers over 35 years of age, are contraindicated
Previous methods of oral contraceptives were accompanied by weight gain, fluid retention in the body, mastodynia	"Yarina"
In previous oral contraceptive methods, poor control of the menstrual cycle was observed (in cases where other causes other than oral contraceptives are excluded)	Monophase or three-phase COCs

[21], [22],

Basic principles of monitoring patients using COCs

• Annual gynecological examination, including colposcopy and cytological examination.
• Once or twice a year, the examination of the mammary glands (in women who have a history of benign breast tumors and / or breast cancer in the family), once a year, mammography (in patients in perimenopause).
• Regular measurement of blood pressure. With an increase in diastolic blood pressure to 90 mm Hg. Art. And the reception of the COC is stopped.
• Special examinations for indications (with the development of side effects, the appearance of complaints).
• With violations of menstrual function - the exclusion of pregnancy and transvaginal ultrasound scanning of the uterus and its appendages. If intermenstrual bleeding persists for more than three cycles or appears with further administration of COC, the following recommendations should be adhered to.
  • Eliminate the error in taking COC (skipping tablets, non-compliance with the reception scheme).
  • Exclude pregnancy, including ectopic pregnancy.
  • Exclude organic diseases of the uterus and appendages (myoma, endometriosis, hyperplastic processes in the endometrium, cervical polyps, cervical cancer or uterine body).
  • Exclude infection and inflammation.
  • If you exclude these reasons - change the drug in accordance with the recommendations.
  • In the absence of bleeding cancellation should be deleted:
    • COC reception without 7-day breaks;
    • pregnancy.
  • If these reasons are excluded, the most likely cause of the absence of bleeding cancellation is endometrial atrophy, caused by the influence of progestogen, which can be detected with ultrasound of the endometrium. This condition is called "mute menstruation", "pseudoamenorrhea". It is not associated with hormonal disorders and does not require the withdrawal of COCs.

[23], [24], [25],

Rules for the reception of COCs

Women with a regular menstrual cycle

• Primary reception of the drug to begin within the first 5 days after the onset of menstruation - in this case, the contraceptive effect is provided already in the first cycle, additional measures of protection from pregnancy are not necessary. Reception of monophasic COCs starts with a tablet with the label of the corresponding day of the week, multiphase COCs - from a tablet labeled "start of reception." If the first tablet is taken later than 5 days after the onset of menstruation, in the first cycle of COC intake an additional method of contraception for 7 days is needed.
• Take 1 tablet (pills) daily at about the same time of day for 21 days. In case of missing the tablet, follow the "Rules of forgotten and missed tablets" (see below).
• After taking all (21) tablets from the package, make a 7-day break, during which there is a bleeding withdrawal ("menstruation"). After the break, the taking of tablets from the next package begins. For a reliable contraception, the interval between receiving cycles should not exceed 7 days!

All modern COCs are issued in "calendar" packages, designed for one cycle of reception (21 tablets - 1 per day). There are also packages with 28 tablets; in this case, the last 7 tablets do not contain hormones ("pacifiers"). In this case, the break between the packages does not: it is replaced by taking placebo, since in this case the patients are less likely to forget to start receiving the next package on time.

Women with amenorrhea

• To start reception at any time under condition of reliably excluded pregnancy. In the first 7 days, use an additional method of contraception.

Breastfeeding women

• Earlier than 6 weeks after childbirth COC is not appointed!
• The period from 6 weeks to 6 months after birth, if a woman is breastfeeding, use the COC only in case of emergency (the method of choice is mini-saws).
• More than 6 months after childbirth:
  • with amenorrhea the same as in the section "Women with amenorrhea";
  • with the restored menstrual cycle.

[26], [27], [28], [29]

"Rules of forgotten and missed tablets"

• If you missed 1 tablet.
  • Delay in the intake of less than 12 hours - take the missed tablet and continue taking the drug until the end of the cycle according to the previous scheme.
  • Delay in the reception for more than 12 hours - the same actions as in the previous paragraph, plus:
    • when a pill is missed at week 1, use a condom for the next 7 days;
    • when a tablet is skipped during the second week, there is no need for additional means of protection;
    • when you miss a pill at the 3rd week, after completing one package, the next start without interruption; There is no need for additional means of protection.
• If you missed 2 tablets or more.
  • Take 2 tablets a day until the reception goes into the regular schedule, plus use additional methods of contraception within 7 days. If after the missed tablets bloody discharge begins, it is better to stop the taking of tablets from the current package and start a new package after 7 days (counting from the beginning of the missing tablets).

Rules for assigning COCs

• Primary appointment - from the 1st day of the menstrual cycle. If the reception is started later (but no later than the 5th day of the cycle), then in the first 7 days it is necessary to use additional methods of contraception.
• The appointment after the abortion - immediately after the abortion. Abortion in I, II trimesters, and also septic abortion belong to the category 1 states (there are no restrictions to using the method) for the designation of COCs.
• Appointment after childbirth - in the absence of lactation begin taking COC no earlier than the 21st day after giving birth (category 1). If there is lactation, the COC should not be prescribed, minipills should be used no earlier than 6 weeks after the delivery (category 1).
• Transition from high-dose COCs (50 μg EE) to low-dose (30 μg EE or less) - without a 7-day break (so that the hypothalamic-pituitary system is not activated due to dose reduction).
• Transition from one low-dose COC to another - after an ordinary 7-day break.
• The transition from mini-drank to COC - on the 1 st day of the next bleeding.
• The transition from an injection to a COC is the day of the next injection.

Recommendations for patients taking COCs

• It is advisable to reduce the number of cigarettes smoked or to stop smoking altogether.
• Observe the regimen of the drug: do not skip the pills, strictly adhere to the 7-day break.
• The drug should be taken at the same time (in the evening before going to bed) with a small amount of water.
• Have the "Rules of forgotten and missed tablets" at hand.
• In the first months of taking the drug, intermenstrual bloody discharge of varying intensity is possible, usually disappearing after the third cycle. With ongoing intermenstrual bleeding at a later date, you should consult your doctor to determine their cause.
• In the absence of a menstrual-like reaction, you should continue taking the pill according to the usual schedule and urgently seek medical attention to exclude pregnancy; When confirming pregnancy, immediately stop taking COC.
• After discontinuation of the drug, pregnancy may occur already in the first cycle.
• Simultaneous use of antibiotics, as well as anticonvulsants, leads to a decrease in the contraceptive effect of COCs.
• When vomiting occurs (within 3 hours after taking the drug), one more pill should be taken additionally.
• Diarrhea that lasts for several days requires the use of an additional contraceptive method before another menstrual reaction.
• With sudden localized severe headache, migraine attack, chest pain, acute visual impairment, shortness of breath, jaundice, increased blood pressure above 160/100 mm Hg. Art. Immediately stop taking the drug and consult a doctor.

Disadvantages of combined oral contraceptives

• The method depends on users (requires motivation and discipline)
• There may be nausea, dizziness, tenderness of the mammary glands, headaches, as well as smearing or mild bleeding from the genital tract and middle of the cycle
• The effectiveness of the method may decrease with simultaneous use of certain medications
• Possible, though very rare, thrombolytic complications
• The need to replenish the contraceptive reserve
• Do not protect against STDs, including hepatitis and HIV infection

[17], [18]

Contraindications to the use of combined oral contraceptives

Absolute contraindications

• Deep vein thrombosis, pulmonary embolism (including history), high risk of thrombosis and thromboembolism (with extensive surgery associated with prolonged immobilization, with congenital thrombophilia with pathological levels of coagulation factors).
• Ischemic heart disease, stroke (the presence of a cerebral vascular crisis in the history).
• Arterial hypertension with systolic blood pressure of 160 mm Hg. Art. And above and / or diastolic arterial pressure of 100 mm Hg. Art. And above and / or with the presence of angiopathy.
• Complicated diseases of the valvular heart apparatus (low blood circulation hypertension, atrial fibrillation, septic endocarditis in the anamnesis).
• The aggregate of several factors of development of arterial cardiovascular diseases (age over 35, smoking, diabetes, hypertension).
• Diseases of the liver (acute viral hepatitis, chronic active hepatitis, cirrhosis, hepatocerebral dystrophy, liver tumor).
• Migraine with focal neurological symptoms.
• Diabetes mellitus with angiopathy and / or duration of the disease for more than 20 years.
• Breast cancer, confirmed or suspected.
• Smoking more than 15 cigarettes a day over the age of 35 years.
• Lactation.
• Pregnancy. Relative contraindications
• Arterial hypertension with systolic blood pressure below 160 mm Hg. Art. And / or diastolic blood pressure below 100 mm Hg. Art. (a single increase in blood pressure is not a basis for diagnosing arterial hypertension - a primary diagnosis can be established with an increase in blood pressure to 159/99 mm Hg with three visits to the doctor).
• Confirmed hyperlipidemia.
• Headache of a vascular nature or migraine, which appeared against the background of COCs, as well as migraine without focal neurological symptoms in women older than 35 years.
• Gallstone disease with clinical manifestations in the anamnesis or at present.
• Cholestasis associated with pregnancy or COC administration.
• Systemic lupus erythematosus, systemic scleroderma.
• Breast cancer in the anamnesis.
• Epilepsy and other conditions requiring the use of anticonvulsants and barbiturates - phenytoin, carbamazepine, phenobarbital and their analogues (anticonvulsants reduce the effectiveness of COC, inducing microsomal liver enzymes).
• Taking rifampicin or griseofulvin (for example, with tuberculosis) due to their effect on microsomal liver enzymes.
• Lactation from 6 weeks to 6 months after birth, postpartum period without lactation until 3 weeks.
• Smoking is less than 15 cigarettes a day over the age of 35 years. Conditions requiring special control when taking COCs
• Increased blood pressure during pregnancy.
• Family history of deep vein thrombosis, thromboembolism, death from myocardial infarction under the age of 50 years (I degree of kinship), hyperlipidemia (evaluation of hereditary factors of thrombophilia and lipid profile is necessary).
• Upcoming surgical intervention without prolonged immobilization.
• Thrombophlebitis of superficial veins.
• Uncomplicated diseases of the valvular heart apparatus.
• Migraine without focal neurological symptoms in women younger than 35 years, headache that began with the use of COCs.
• Diabetes mellitus without angiopathy with a duration of disease of less than 20 years.
• Gallstone disease without clinical manifestations; condition after cholecystectomy.
• Sickle-cell anemia.
• Bleeding from the genital tract of an unknown etiology.
• Severe dysplasia and cervical cancer.
• Conditions that make it difficult to take pills (mental illness associated with memory loss, etc.).
• Age over 40 years.
• Lactation more than 6 months after childbirth.
• Smoking in the age of 35 years.
• Obesity with a body mass index of more than 30 kg / m ².

[19], [20]

Side effects of combined oral contraceptives

Side effects are most often negligible, appear in the first months of taking COC (10-40% of women), then their frequency decreases to 5-10%.

Side effects of COCs are divided into clinical and hormone-dependent mechanisms. The clinical side effects of COCs, in turn, are divided into general and causing disturbances of the menstrual cycle.

Are common:

• headache;
• dizziness;
• nervousness, irritability;
• depression;
• discomfort in the gastrointestinal tract;
• nausea, vomiting;
• flatulence;
• dyskinesia of bile ducts, exacerbation of cholelithiasis;
• tension in the mammary glands (mastodynia);
• arterial hypertension;
• change in libido;
• thrombophlebitis;
• leukorrhea;
• Chloasma;
• leg cramps;
• weight gain;
• deterioration of the tolerance of contact lenses;
• dryness of the mucous membranes of the vagina;
• increase in the total coagulation potential of blood;
• increasing the transition of fluid from the vessels to the intercellular space with compensatory retention in the body of sodium and water;
• change in glucose tolerance;
• hypernatremia, increased osmotic pressure of blood plasma. Violations of the menstrual cycle:
• intermenstrual spotting spotting;
• breakthrough bleeding;
• amenorrhoea during or after taking COC.

If the side effects persist longer than 3-4 months after the onset of admission and / or worsen, you should change or cancel the contraceptive.

Serious complications when taking COCs are extremely rare. These include thrombosis and thromboembolism (deep vein thrombosis, pulmonary embolism). For women's health, the risk of these complications when taking COC with a dose of EE of 20-35 μg / day is very small - lower than in pregnancy. Nevertheless, at least one risk factor for thrombosis (smoking, diabetes, high obesity, hypertension, etc.) is a relative contraindication to the administration of COCs. The combination of two or more listed risk factors (for example, the combination of obesity with smoking over the age of 35) generally excludes the use of COCs.

Thrombosis and thromboembolism in both COC and pregnancy can be manifestations of latent genetic forms of thrombophilia (resistance to activated protein C, hyperhomocysteinemia, deficiency of antithrombin III, protein C, protein S, antiphospholipid syndrome). In connection with this, it should be emphasized that the routine determination of prothrombin in the blood does not give an idea of the hemostatic system and can not be a criterion for the appointment or abolition of COCs. If suspicion of latent forms of thrombophilia should be a special study of hemostasis.