Composition, form of production and packaging
The tablets covered with a film membrane of two kinds.
The tablets covered with a film cover of yellow-orange color, round, biconcave (21 pieces in a blister).
1 tab.
ethinylestradiol 35 Ојg
cyproterone acetate 2 mg
Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch (type A), silicon dioxide colloidal anhydrous, aluminum oxide colloid, magnesium stearate.
Composition of the coating: dye Opaprai Yellow II OY-L-32901 (Opadry II Yellow OY-L-32901) (lactose monohydrate, hypromellose 2910, titanium dioxide, macrogol 4000, iron oxide yellow, iron oxide black, iron oxide red, purified water) .
Tablets (placebo) are white, round, biconvex (7 pcs in blister).
Excipients: lactose monohydrate, povidone, sodium carboxymethyl starch (type A), silicon dioxide colloidal anhydrous, aluminum oxide colloid, magnesium stearate.
28 pcs. - blisters (1) - packs of cardboard.
28 pcs. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Combined low-dose monophasic oral contraceptive with anti-androgenic activity. The mechanism of action is due to the anti-androgenic preparation of the steroid structure, cyproterone acetate and oral estrogen, ethinyl estradiol, which enter into its composition.
Cyproterone acetate
Has the ability to competitively bind to receptors of natural androgens (including testosterone, dihydroepiandrosterone, androstenedione), formed in small amounts in the body of women, mainly in the adrenal glands, ovaries and skin. By blocking the androgen receptors in target organs, it reduces the phenomenon of androgenization in women (due to disruption of the processes mediated by hormone-receptor complexes at the level of the main intracellular mechanisms). Thus, it becomes possible to treat diseases caused by increased formation of androgens or specific sensitivity to these hormones.
Against the background of taking the drug, the increased activity of the sebaceous glands is reduced, which plays an important role in the appearance of acne and seborrhea. After 3-4 months of therapy, the existing rash usually disappears. Excessive fatness of hair and skin disappears even earlier. Also decreases hair loss, often accompanying seborrhea.
Chloe В® therapy in women of reproductive age reduces clinical manifestations of mild forms of hirsutism; However, the effect of treatment should be expected only after several months of use.
Along with anti-androgenic properties, cyproterone acetate has gestagenic activity that mimics the properties of the hormone of the yellow body. Oppressing pituitary gland secretion of gonadotropic hormones and inhibits ovulation, which causes a contraceptive effect.
Ethinylestradiol
Strengthens the central and peripheral effects of cyproterone acetate on ovulation, retains a high viscosity of the cervical mucus, making it difficult to penetrate the spermatozoon into the uterine cavity and contributing to a reliable contraceptive effect.
Against the background of taking the drug, the cycle becomes more regular, less painful menstruation, less intensity of bleeding, less risk of iron deficiency anemia.
PHARMACOKINETICS
Cyproterone acetate
Suction
After taking the drug inside the cyproterone, the acetate is completely absorbed from the digestive tract. C max in blood plasma is achieved through 1.6 h and is 15 ng / ml. Bioavailability is 88%.
Distribution
Ciproterone acetate almost completely binds to blood plasma albumin, in the free state is approximately 3.5-4%. Since protein binding is not specific, changes in the level of globulin binding to sex steroids (HESC) do not affect the pharmacokinetics of cyproterone acetate.
Metabolism
Biotransformed by hydroxylation and conjugation, the main metabolite is the 15b-hydroxyl derivative.
Excretion
The pharmacokinetics of cyproterone acetate are two-phase: T 1/2 is 0.8 h and 2.3 d, respectively, for the first and second phases. The total plasma clearance is 3.6 ml / min / kg. It is excreted primarily in the form of metabolites by the kidneys and through the intestine in a ratio of 1: 2, a small part - unchanged through the intestine.Breast milk releases up to 0.2% of the dose of cyproterone acetate. T 1/2 for the metabolites of cyproterone acetate is 1.8 days.
Ethinylestradiol
Suction
After taking the drug, ethinyl estradiol is quickly and completely absorbed from the digestive tract. Cmax is about 80 pg / ml and is achieved after 1.7 hours. Bioavailability of about 45% has a significant individual variability.
Distribution
The binding with proteins (albumin) of blood plasma is high: only 2% are in the plasma in a free form.
Ethinyl estradiol increases the hepatic synthesis of HSA and corticosteroid-binding globulin (CSG) with continuous use. Against the backdrop of ChloeВ® treatment, serum GSPC concentration rises from about 100 nmol / l to 300 nmol / l, and the serum CSF concentration increases from about 50 Ојg / ml to 95 Ојg / ml.
Metabolism
In the process of absorption and "first passage" through the liver, ethinyl estradiol undergoes intensive metabolism.
Excretion
The pharmacokinetics of ethinyl estradiol are biphasic: T 1/2 1-2 hours and approximately 20 hours, respectively. Plasma clearance is about 5 ml / min / kg. Ethinyl estradiol is excreted from the body in the form of metabolites: about 40% - by the kidneys, 60% - through the intestine. With breast milk, up to 0.02% of the dose of ethinyl estradiol is released.
INDICATIONS
- contraception in women with androgenization phenomena.
Androgen-dependent diseases in women:
- acne, especially their expressed forms, accompanied by seborrhea, inflammatory phenomena with the formation of nodes (papular-pustular acne, nodular-cystic acne);
- Androgenic alopecia;
- light forms of hirsutism.
DOSING MODE
The drug should be taken orally 1 tablet / day. The tablet is taken without chewing, and washed down with a small amount of liquid. It is recommended to take the drug at the same time, preferably after breakfast or dinner.
In the absence of taking any hormonal contraceptives in the previous month
Reception Chloe В® begins on the 1st day of the cycle (ie on the first day of menstrual bleeding), using a tablet of the corresponding day of the week from the calendar package. It is allowed to start taking the menstrual cycle on day 2-5, but in this case it is recommended to additionally use the barrier method of contraception during the first 7 days of taking the pills from the first package.
Daily administration of the drug is carried out using tablets from the calendar pack in sequence along the direction of the foil-applied arrow until all the tablets are taken. After the end of the intake of all 21 tablets of yellow-orange color from the calendar package, it is necessary to take the remaining white tablets in the next 7 days. During the last 7 days of the treatment cycle (28 days), menstrual bleeding (due to cancellation of treatment) should occur. Menstruation-like bleeding usually begins 2-3 days after the 21st day of the drug treatment cycle. The next package should be started the day after the completely completed taking of the tablets from the previous package, regardless of whether bleeding continues or not.
When switching from combined contraceptive drugs (oral contraceptives (COC), vaginal ring or contraceptive patch)
The administration of Chloe В® should be started the day after the last active tablet of the previous preparation, but in no case later than the next day after the usual 7-day break in admission (for preparations containing 21 tablets). Then follow the scheme described above.
If the patient took the previous contraceptive daily for 28 days, the Chloe В® drug should be taken after the last inactive tablet was taken. Reception of Chloe В® should be started on the day of removal of the vaginal ring or contraceptive patch, but no later than the day when a new ring is to be inserted or a new adhesive is pasted.
When switching from contraceptives containing only gestagens ("mini-pili", injection forms, implants, gestagen releasing intrauterine contraceptive)
When switching from a mini-saw, you can start taking ChloeВ® without interruption.
When using injectable forms of contraceptives, taking Chloe В® should be taken from the day the next injection is to be taken.
When moving from an implant ChloeВ® should be applied already on the day of its removal.
In all cases, it is necessary to use an additional barrier method of contraception during the first 7 days of taking the drug.
After abortion in the first trimester of pregnancy, a woman can start using ChloeВ® immediately. In this case, there is no need for additional methods of contraception.
After giving birth in the absence of breastfeeding or abortion in the second trimester of pregnancy , the drug should be taken on the 21-28th day. If the reception is started later, it is necessary to use an additional barrier method of contraception during the first 7 days of application of the drug.
If a woman has had sex during the period between childbirth or abortion, before starting taking Chloe В® , you must first exclude pregnancy or you must wait for the first menstruation.
Acceptance of missed tablets
The missed tablet should be taken as soon as possible, the next tablet - at the usual time. At a delay of <12 h, the reliability of contraception does not decrease. If the delay in taking the tablet is > 12 hours , the reliability of contraception can be reduced. The more pills are missed and the closer the pass to a 7-day break in taking pills, the greater the probability of pregnancy. In this case, you can follow the following two basic rules:
- taking the drug should never be interrupted for more than 7 days;
-to achieve adequate suppression of hypothalamic-pituitary-ovarian regulation requires 7 days of continuous intake of the drug.
Accordingly, the following recommendations may be given if the delay in taking the tablets is more than 12 hours (the interval from the time of the last tablet is more than 36 hours).
The first week of taking the drug
The woman should take the last missed tablet as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The next tablet should be taken at the usual time. Additionally, a barrier method of contraception should be used for the next 7 days. If sexual intercourse took place within a week before passing the pill, it is necessary to consider the likelihood of pregnancy.
The second week of taking the drug
The woman should take the last missed tablet as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The next tablet should be taken at the usual time.
Provided that the woman took the pill correctly for 7 days preceding the first missed pill, there is no need to use additional contraceptive measures. Otherwise, as well as when two or more tablets are missed, barrier methods of contraception (for example, a condom) should be used additionally within 7 days.
The third week of taking the drug
The risk of pregnancy is increased due to the upcoming pause in taking the tablets, however, if all the pills were taken correctly within 7 days preceding the first missed tablet, there is no need to use additional contraceptive methods.
1. The woman should take the last missed tablet as soon as possible, as soon as she remembers (even if it means taking two tablets at the same time). The following tablets are taken at the usual time, until the tablets from the current package run out. The next package should be started immediately. Bleeding "cancellation" is unlikely until the tablets from the second package run out, but there may be spotting and "breakthrough" bleeding during taking the tablets.
2. A woman can also interrupt the taking of tablets from the current package. She then needs to take a break for 7 days, including the day the tablet is missed, and then start taking the tablets out of the new package. If the woman missed taking the pill, and then during a break in the reception she does not have a bleeding "withdrawal", it is necessary to exclude pregnancy.
Recommendations for gastrointestinal disorders
If a woman has vomiting within 3 to 4 hours after taking the drug, the absorption of the active substances may be incomplete. In this case, you need to focus on recommendations when you skip the tablet.
Change in menstrual bleeding day
In order to delay the onset of menstrual bleeding, a woman should continue taking the pills from the new package of the drug immediately after taking all the pills from the previous package, without interruption in admission. Tablets from this new package can be taken for as long as the woman wishes (until the packaging is finished). Against the background of taking the drug from the second package, a woman may have spotting or "breakthrough" uterine bleeding. Renewal of Chloe В®from the new pack follows the usual 7-day break.
In order to transfer the day of the onset of menstrual bleeding to another day of the week, the woman should shorten the nearest break in taking the pills for as many days as she wants. The shorter the interval, the higher the risk that it will not have the bleeding "cancellation" and thereafter will be spotting spotting and "breakthrough" bleeding during the second package (as well as in the case when it would like to delay the onset of menstrual bleeding) .
In the treatment of hyperandrogenic conditions
Duration of admission is determined by the severity of the disease. After the disappearance of the symptoms, it is recommended to take the drug for at least 3-4 more months. In the case of relapse after a few weeks or months after completion of the course, you can re-use the drug Chloe В® . If the drug is resumed (after a 4-week break or more), an increased risk of VTE should be considered.
Children and teens
The drug Chloe В® is shown only after the onset of menarche.
Patients in postmenopausal women
Chloe В® is not indicated after menopause.
Dysfunction of the liver
The drug ChloeВ® is contraindicated in women with severe liver disease until the liver function test results are normal.
Renal impairment
The drug Chloe В® has not been specifically studied in patients with impaired renal function. The available data do not imply dose correction in such cases.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (? 1/10); often (? 1/100 to <1/10); infrequently (? 1/1000 to <1/100); rarely (? 1/10 000 to <1/1000);very rarely (<1/10 000); the frequency is unknown (the frequency can not be estimated from the available data).
From the side of the nervous system: often - headache; infrequently - migraine; frequency unknown - worsening of epilepsy.
From the side of the organ of vision: rarely - intolerance of contact lenses.
From the side of the digestive system: often - nausea, abdominal pain; infrequently - vomiting, diarrhea.
From the skin and subcutaneous tissues: infrequently - rash, hives; frequency is unknown - erythema nodosum, erythema multiforme.
From the side of metabolism and nutrition: often - an increase in body weight; infrequently - fluid retention; rarely - weight loss.
From the immune system: rarely - hypersensitivity reactions.
From the genitals and breast: often - pain / tenderness in the mammary glands, engorgement of the mammary glands; infrequently - enlargement of mammary glands;rarely - discharge from the vagina, discharge from the mammary glands *; frequency unknown - acyclic bleeding / bleeding (metrorrhagia).
Mental disorders: often - reduced mood, mood swings; infrequently - decreased libido; rarely - increased libido; frequency unknown - worsening of the course of endogenous depression.
From the cardiovascular system: rarely - thromboembolism.
* Postmarketing studies reported painful menstrual bleeding and the absence of menstrual bleeding, the frequency of which was not assessed.
Serious adverse events reported in women using COCs (which include Chloe В® )
From the cardiovascular system: venous thromboembolic disorders, arterial thromboembolic disorders, stroke, increased blood pressure.
From the side of metabolism: hypertriglyceridemia, impaired glucose tolerance or influence on peripheral insulin resistance.
On the part of the digestive system: liver tumors (benign and malignant), impaired liver function, pancreatitis, cholecystitis.
From the skin and subcutaneous tissues: chloasma.
Allergic reactions: in women with hereditary angioedema, exogenous estrogens can cause or exacerbate symptoms of angioedema.
From the nervous system and sensory organs: visual impairment, dizziness.
The appearance or worsening of states, whose connection with the use KOC (to which the drug ChloГ« В® ) is not undisputed: jaundice and / or itching associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; Sydenham's chorea; herpes during a previous pregnancy; hearing loss associated with otosclerosis; Crohn's disease; ulcerative colitis; cervical cancer.
Frequency of diagnosing breast cancer in women using COC (to which the drug ChloГ« В®), Increased only slightly. Breast cancer is rare in women under 40 years, exceeding the frequency slightly relative to the total risk of breast cancer. Causation of breast cancer with the use of COCs not installed.
CONTRAINDICATIONS
- simultaneous use with other hormonal contraceptives;
- thrombosis and thromboembolism, including a history (deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders, e.g., stroke);
- state prior thrombosis (including transient ischemic attack, angina pectoris);
- multiple or severe venous or arterial thrombosis risk factors (including complicated valvular defects, atrial fibrillation, cerebrovascular disease or coronary arteries, uncontrolled hypertension, severe dislipoproteinemia, subacute bacterial endocarditis, prolonged immobilization, surgery on the lower extremities, neurosurgical operations, extensive trauma, smoking, older than 35 years, obesity with a BMI over 30 kg / m 2 );
- detection of hereditary or acquired predisposition for venous or arterial thrombosis,
e.g. resistance to activated protein C (APC), antithrombin III deficiency, protein C deficiency, protein deficit S, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant);
- Diabetes mellitus with diabetic angiopathy;
- severe liver disease at present or in history or severe liver function abnormalities not earlier than 6 months after normalization of liver function tests;
- liver tumors (benign or malignant);
- hormone-dependent malignancies or suspicion on them, including breast tumors or genital organs (including history);
bleeding from the vagina of an unclear etiology;
- pancreatitis with severe hypertriglyceridemia (including history);
- the presence in history of migraine, which was accompanied by focal neurological symptoms;
- pregnancy or suspected it;
- the period of breastfeeding;
- congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson and Rotor);
- age over 40 years;
- hyperprolactinemia;
- lactose intolerance, lactase deficiency, malabsorption syndrome glucose / galactose;
- Hypersensitivity to the components of the drug.
If any of these conditions develop for the first time while taking Chloe В® , the drug should be discontinued immediately.
The drug Chloe В® is not intended for use in men.
With caution should be used ChloГ« В® epilepsy, depression, ulcerative colitis, diseases of the liver and gall bladder, uterine myoma, mastopathy, chorea, tetany, porphyria, multiple sclerosis, varicose veins, tuberculosis, renal diseases, in adolescence (without regular ovulatory cycles), dislipoproteinemia, sickle cell anemia, idiopathic jaundice or pruritus during a previous pregnancy, otosclerosis with deterioration of hearing during a previous pregnancy.
PREGNANCY AND LACTATION
Do not use this drug during pregnancy, suspected pregnancy and during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions should be used when the drug kidney disease.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Do not use this drug in the diseases or disorders expressed in the liver, liver tumors (including history), congenital hyperbilirubinemia (Gilbert syndrome, Dubin-Johnson syndrome, Rotor), idiopathic pruritus or jaundice during late pregnancy.
Precautions should be used drug for liver and gall bladder.
APPLICATION IN ELDERLY PATIENTS
Contraindicated at the age of over 40 years.
SPECIAL INSTRUCTIONS
Before the start of application ChloГ« В® necessary to general medical examination (including breast and cytology of cervical mucus) exclude pregnancy, disorders of the blood coagulation system. With long-term use of the drug prevention control examinations should be carried out every 6 months.
In the presence of risk factors should carefully evaluate the potential risks and expected benefits of the therapy and to discuss it with the woman before the start of the drug.
By increasing the severity, amplification or at the first sign of any of the conditions or risk factors listed below may require removal of the drug.
Use of the drug Chloe В® increases the riskVenous thromboembolism (VTE), compared to the risk in women not taking the drug. Additional risk of VTE is highest during the first year of the drug ChloГ« В® or resumption of reception after a break duration of 4 weeks or more. VTE in 1-2% of cases may be fatal. Approximate incidence of VTE with oral contraceptives with low estrogen dose (less than 50 mcg ethinyl estradiol) amounts to 4 10 000 women per year compared to 0.5-1 per 10 000 women not taking COCs. The frequency at VTE COC is less than the frequency of VTE associated with pregnancy (6 10 000 pregnant women per year).
Epidemiological studies have shown that the incidence of VTE from 1.5 to 2 times higher in women taking the drug Chloe В®Compared with COC containing levonorgestrel, and similar for HEC containing desogestrel / gestodene / Drospirenone. In patients with polycystic ovary syndrome are at increased risk of developing cardiovascular disease. Epidemiological studies have also shown an association of hormonal contraceptives with an increased risk of arterial thromboembolic events (myocardial infarction, transient ischemic attack).
Very rarely reported thrombosis and other vessels, namely, the veins and arteries of the liver, mesenteric, renal, cerebral or retinal, in patients taking hormonal contraceptives.
The patient should be warned that in the development of venous or arterial thrombosis symptoms should seek immediate medical attention. These symptoms include unilateral lower limb pain and / or swelling; sudden severe chest pain radiating to the left arm or without irradiation; sudden shortness of breath; sudden onset of coughing; any unusual, severe, prolonged headache; gain frequency and severity of migraine; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; dizziness; collapse with / or without partial seizure; weakness or significant loss of sensitivity, suddenly appear on one side or in one part of the body; motor disturbances; symptom "acute abdomen".
VTE risk increases:
- with increasing age;
- when smoking (. Under intense smoking and increasing age the risk further increases, especially in women over 35 years, women older than 35 years should be strongly advised to stop smoking if they want to take the drug Chloe В® );
- with a family history (ie, those with a history of venous thromboembolism cases at a relatively young age, parents or close relatives). In the case of suspected hereditary predisposition, before deciding about any hormonal contraception, women should consult a specialist;
- with prolonged immobilization, surgical procedures on the lower extremities, neurosurgical operations or major trauma. In these situations it is necessary to stop the application (in the case of elective surgery is not less than 4 weeks) and did not renew it until 2 weeks after full restoration of motor activity. If the use of the drug Chloe В® has not been discontinued in advance should consider antithrombotic therapy;
- obesity (BMI over 30 kg / m 2 ).
The risk of arterial thromboembolic complications or cerebrovascular accident increases:
- with increasing age;
- when smoking (. Under intense smoking and increasing age the risk further increases, especially in women over 35 years, women older than 35 years should be strongly advised to stop smoking if they want to take the drug Chloe В® );
- when dislipoproteinemia;
- arterial hypertension;
- migraine;
- in diseases of the heart valves;
- atrial fibrillation;
- with a family history (ie, with a history of arterial thrombosis cases in the relatively young age of the parents or close relatives). In the case of suspected hereditary predisposition, before deciding about any hormonal contraception, women should consult with a specialist.
Peripheral circulatory disorders as may occur in diabetes mellitus, systemic lupus erythematosus, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (i.e. Crohn's disease or ulcerative colitis) and sickle cell anemia.
It is necessary to take into account the increased risk of thromboembolism during the postpartum period.
Increasing the frequency or severity of migraine attacks during use ChloГ« preparation В®(which can be a precursor of cerebral circulation) is grounds for immediate withdrawal of the drug.
With respect to the potential role of varicose veins and superficial thrombophlebitis in venous thromboembolism no consensus development.
Biochemical factors that may indicate inherited or acquired predisposition to venous or arterial thrombosis include resistance to activated protein C (APC), hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein deficit S, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant) .
In assessing the risk / benefit, the physician should take into account that the appropriate treatment of the underlying disease may reduce the risk of thrombosis. Women taking ChloeВ® , should explain the need for timely communication physician about the case of possible symptoms of thrombosis. In the case of suspected thrombosis or its appearance, treatment with ChloГ« В® should be discontinued. Given coagulants teratogenicity (coumarin), to start the application of adequate contraceptive methods.
Other conditions
Women with hypertriglyceridemia during COC use (in the presence of this condition have a family history) may increase the risk of pancreatitis.
The relationship between COC and hypertension has not been established. In the event of persistent hypertension ChloГ« В®to cancel and assign the appropriate antihypertensive therapy. Oral contraceptives can be continued in the normalization of blood pressure.
In the event of liver dysfunction may require temporary removal of the drug ChloГ« В® before normalization laboratory parameters. Recurrent cholestatic jaundice that develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of COCs.
Although COCs have an impact on insulin resistance and glucose tolerance, there is usually no need to correct the dose of hypoglycemic drugs in patients with diabetes mellitus. However, this category of patients should be under close medical supervision.
Women with a tendency to chloasma during COC should avoid prolonged exposure to sunlight and ultraviolet radiation.
If the symptoms have developed recently or significantly increased in women with hirsutism, the differential diagnosis should take into account other factors, such as androgen tumor, congenital adrenal hyperplasia.
In patients receiving the drug ChloГ« В® occasionally may experience irregular bleeding (spotting or breakthrough bleeding), especially during the first few months of therapy. Therefore, assessment of any irregular bleeding should be performed only after a period of adaptation of approximately 3 cycles.
If irregular bleeding or develop after repeated previous regular cycles, it must be considered and implemented hormonal causes adequate diagnostic measures for exclusion of cancer (including diagnostic curettage) or pregnancy. In some cases, withdrawal bleeding may not occur during tablet-free interval. When irregular pill or in the absence of two consecutive bleedings menstrualnopodobnoe should exclude pregnancy to continue taking the drug.
To change the results of skin allergy tests, reducing the concentration of LH and FSH. Due to the fact that the contraceptive effect is fully manifested day 7 from the start of the drug during the first week recommended additional hormonal contraceptive methods.
Prescribe medication after delivery without Breastfeeding is recommended only after completion of the first normal menstrual cycle.
Treatment should be discontinued 3 months before a planned pregnancy.
Diarrhea and vomiting contraceptive effect is reduced (not stopping the drug must be used additional methods of hormonal contraception).
Tumors
There are reports of some increase in the risk of cervical cancer in long-term use of COCs. Communication with the COC has not been proved. Controversy remains as to the extent to which these findings are associated with cervical pathology, or with the sexual behavior (a rare use of barrier methods of contraception). The most significant factor in cervical cancer risk is persistent HPV infection. A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of breast cancer diagnosed in women taking COCs now (relative risk 1.24). The increased risk disappears gradually within 10 years after discontinuation of these drugs. Due to the fact that breast cancer is rare in women under 40 years,increase in the number of diagnoses of breast cancer in women taking COCs cancer currently taking or recently is insignificant in relation to the total risk of the disease. His connection with the COC has not been proved. The observed increase in risk may be due to an earlier diagnosis of breast cancer in women using COCs cancer. Women who had ever used COCs identified earlier stages of breast cancer than women who never let them apply.revealed earlier stages of breast cancer than women who never let them apply.revealed earlier stages of breast cancer than women who never let them apply.
In rare cases on the background of COCs observed development of liver tumors, which in some cases lead to life-threatening intraabdominal bleeding. This should be considered in the differential diagnosis in the case of severe pain in the abdomen, liver enlargement or signs of intra-abdominal bleeding.
Laboratory tests
Execu
