Lindynette 30
If any of the conditions, diseases or risk factors listed below currently exist, the potential risks and expected benefits of using COCs, including the combination of gestodene + ethinyl estradiol, should be carefully weighed in each individual case and discussed with the woman before starting to take the drug. If any of these conditions, diseases or risk factors worsen, intensify or appear for the first time, a woman should consult her doctor to decide whether to stop taking the drug.
Risk of developing venous and arterial thromboembolism (VTE and ATE)
The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of venous and arterial thrombosis and thromboembolism (such as DVT, PE, myocardial infarction, cerebrovascular disorders). These diseases are rare.
The increased risk of developing VTE associated with the use of COCs is due to the presence of estrogen in its composition. COCs containing levonorgestrel, norgestimate or norethisterone as a progestogen component are associated with the lowest risk of VTE. When using other COCs, such as the combination of gestodene + ethinyl estradiol, the risk of developing VTE is twice as high.
The choice of a COC with a higher risk of VTE should only be made after consultation with the woman to ensure that she fully understands the risk of VTE associated with the contraceptive, the effect of the drug on her existing risk factors and that the risk of developing VTE maximum in the first year of taking such drugs. An increased risk is also observed when COC use is resumed (after a break between doses of the drug of 4 weeks or more). The increased risk of developing VTE is present primarily during the first 3 months.
VTE can be life-threatening or lead to death (in 1-2% of cases). VTE, manifested as DVT and/or PE, can occur with all COCs.
It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels.
Symptoms of DVT:
unilateral swelling of the lower limb or along the vein, pain or discomfort only in an upright position or when walking, local increase in temperature, redness or discoloration of the skin in the affected lower limb.
Symptoms of pulmonary embolism:
difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more common and less severe conditions (eg, respiratory tract infection).
ATE can lead to stroke, vascular occlusion, or myocardial infarction.
Symptoms of a stroke
: sudden weakness or loss of sensation in the face, limbs, especially on one side of the body, sudden confusion, severe or prolonged headache for no apparent reason, one- or two-sided loss of vision; problems with speech and understanding; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden loss of consciousness or fainting with or without a seizure.
Other signs of vascular occlusion
: sudden pain, swelling and slight cyanosis of the extremities, “acute” abdomen.
Symptoms of myocardial infarction
: pain, discomfort, pressure, heaviness, a feeling of compression or fullness in the chest or behind the sternum, radiating to the back, jaw, upper limb, epigastric region; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat. ATE can be life-threatening and lead to death.
In women with a combination of several risk factors or high severity of one of the factors, the possibility of their mutual reinforcement should be considered. In such cases, the degree of increase in risk may be higher than with a simple summation of factors. In this case, taking the combination of gestodene + ethinyl estradiol is contraindicated.
The risk of developing thrombosis (venous and/or arterial) and thromboembolism or cerebrovascular disorders increases:
-with age;
- in women who smoke (with an increase in the number of cigarettes or an increase in age, the risk increases, especially over the age of 35);
- if there is a family history (for example, VTE or ATE in close relatives or parents aged less than 50 years). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking COCs;
- for obesity (with a BMI more than 30 kg/m2);
- with dyslipoproteinemia;
- for arterial hypertension;
- for migraine;
- for diseases of the heart valves;
- with atrial fibrillation;
- in case of prolonged immobilization, serious surgery, any operation on the lower extremities, in the pelvic area or extensive trauma.
In these cases, the use of COCs should be stopped (in the case of planned surgery, at least four weeks before it) and not resumed for two weeks after the woman has fully regained mobility.
Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of VTE, especially in the presence of other risk factors.
The possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.
The increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.
An increase in the frequency and severity of migraine (which may precede cerebrovascular events) during the use of COCs is grounds for immediate discontinuation of these drugs.
Biochemical indicators indicating a hereditary or acquired predisposition to the development of venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition/disease may reduce the associated risk of thrombosis.
Tumors
The most significant risk factor for the development of cervical cancer (CC) is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing CC with long-term use of COCs. However, the connection with taking COCs has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior patterns (less use of barrier methods of contraception, greater number of sexual partners).
A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Due to the fact that breast cancer is rare in women under 40 years of age, the increase in the incidence of breast cancer in women who are currently taking COCs or have recently taken it is insignificant in relation to the overall risk of this disease. Its connection with COC use has not been proven. The observed increase in risk may also be a consequence of earlier diagnosis of breast cancer in women using COCs (they are diagnosed with earlier clinical forms of breast cancer than women not taking COCs), the biological effects of COCs, or a combination of both of these factors.
In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, this should be taken into account when making a differential diagnosis.
Other states
Depressed mood and depression are known adverse reactions when using hormonal contraceptives. Depression can be a serious disorder and is a known risk factor for suicidal behavior and suicide. Women should be advised to contact their doctor if mood changes or depressive symptoms occur, including soon after starting treatment.
In women with hypertriglyceridemia (or a family history of this condition), the risk of developing pancreatitis may increase while taking COCs.
Although slight increases in blood pressure have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent clinically significant increase in blood pressure develops during the use of COCs, the COC should be discontinued and treatment of arterial hypertension should be initiated. COC use can be continued if normal blood pressure values are achieved with antihypertensive therapy.
The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: cholestatic jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described with the use of COCs.
In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.
Acute or chronic liver dysfunction may require discontinuation of COCs until liver function tests return to normal. Recurrence of cholestatic jaundice, which developed for the first time during a previous pregnancy or previous use of sex hormones, requires discontinuation of COC use.
Although COCs may have an effect on insulin resistance and glucose tolerance, in patients with diabetes mellitus using low-dose COCs, as a rule, no dose adjustment of hypoglycemic drugs is required. However, women with diabetes mellitus should be carefully monitored while taking COCs.
Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women with a tendency to chloasma should avoid prolonged exposure to the sun and exposure to ultraviolet radiation while taking COCs.
Effect on liver function tests
In clinical studies involving patients receiving hepatitis C viral therapy (a combination of drugs containing ombitasvir, paritaprevir, ritonavir, dasabuvir, with or without ribavirin), increases in ALT activity more than 5 times the upper limit of normal were recorded more often in patients using ethynyl-containing COCs.
If a course of therapy with this combination of drugs is necessary, a patient using the contraceptive drug gestodene + ethinyl estradiol should be switched to alternative methods of contraception (non-hormonal or contraceptives containing only gestagen) before starting the course of treatment. You can resume taking the combination of gestodene + ethinyl estradiol no earlier than 2 weeks after the end of the course of therapy with antiviral drugs.
Laboratory tests
The use of drugs such as gestodene + ethinyl estradiol may affect the results of some laboratory tests, including biochemical indicators of liver, thyroid, kidney and adrenal function, the concentration of transport proteins in plasma (for example, transcortin, lipid / lipoprotein fractions, parameters of carbohydrate metabolism, coagulation and fibrinolysis). These changes usually remain within normal physiological values.
Reduced efficiency
The effectiveness of COCs may be reduced in the following cases: in case of missed pills, gastrointestinal disorders or as a result of drug interactions.
Effect on bleeding pattern
While taking COCs, irregular bleeding may occur (“spotting” and/or “breakthrough” bleeding), especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately 3 cycles of dosing.
If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.
Some women may not develop bleeding during a break in taking pills. “ooContraindications” and “With caution.”
-Local compaction in the mammary gland.
-Concomitant use of other medications.
-If prolonged immobilization is expected (for example, a cast is applied to the lower extremity), hospitalization or surgery is planned (at least four weeks before the proposed operation).
-Unusually heavy bleeding from the vagina.
-Missed a pill in the first week of taking the drug and had sexual intercourse seven days or less before.
- Absence of regular menstrual-like bleeding two times in a row or suspicion of pregnancy (you should not start taking pills from the next package before consulting your doctor).
You should stop taking the tablets and consult your doctor immediately if there are possible signs of thrombosis, myocardial infarction or stroke: unusual cough; unusually severe pain behind the sternum, radiating to the left arm; unexpected shortness of breath, unusual, severe and prolonged headache or migraine attack; partial or complete loss of vision or double vision; slurred speech; sudden changes in hearing, smell, or taste; dizziness or fainting; weakness or loss of sensation in any part of the body; severe abdominal pain; severe pain in the lower limb or sudden swelling of any of the lower limbs.
This medicine contains lactose (in the form of lactose monohydrate) and sucrose. Patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, as well as rare congenital forms of fructose intolerance or sucrase-isomaltase deficiency should not take this drug.
Contraception in premenopausal women
Choosing a method of contraception in women after 45 years of age, i.e. in the so-called “transitional” period, is often a very difficult task due to the characteristics of this age period associated with the inevitable processes of gradual decline of ovarian function, the presence of a number of gynecological and extragenital diseases, the appearance of vegetative-vascular and other early symptoms of menopause.
Despite the fact that fertility declines in this age period, the birth of children in women over 45 years of age is not so rare. According to statistics, in Western European countries up to 30% of women aged 45-54 years have a regular menstrual cycle and are capable of conceiving. Moreover, against the background of a regular rhythm of menstruation, the frequency of ovulatory cycles reaches 70-95%, and with oligomenorrhea - up to 34%. By this age, many women are already deciding on the number of children in the family; Situations such as remarriage, accidents with children and the need for childbirth occur quite rarely. In most cases, the onset of pregnancy makes one think about abortion.
Abortions in premenopausal women are much more often accompanied by various complications; the frequency of the latter is two to three times higher than that in women of reproductive age. Often after an abortion, inflammatory diseases of the genital organs, complications associated with the presence of uterine fibroids, endometriosis, and exacerbation of extragenital pathology occur. It has been proven that abortion performed in the “transition” period often provokes a severe course of menopausal syndrome and is the background for the development of hyperplastic processes in target organs - the uterus and mammary glands.
When choosing a method of contraception in this age period, in addition to the need for reliable prevention of abortion, the question arises of avoiding the impact on metabolic processes that have undergone (or are undergoing) age-related changes against the background of the high sensitivity of the female body to exogenous influences. Prevention and treatment of the initial symptoms of menopausal syndrome and, if possible, slowing down the aging process are among the main objectives of contraception at this age.
Of course, hormonal contraceptives (HCs) are the most promising in this regard, but before the advent of modern hormonal agents, including microdosed drugs and releasing systems, the use of HCs was associated with a number of problems.
Over the 40-year period of its development, hormonal contraception has established itself not only as one of the most effective ways to prevent pregnancy, but also as a new, promising direction of medicine. Oral contraceptives (OCs) are widely used throughout the world. In recent years, an increasing number of new combined oral contraceptives (COCs) have been developed.
At the end of the 80s. OCs with higher gestagen selectivity for progesterone receptors were synthesized - these are desogestrel, norgestemate and gestodene.
Recent studies have shown that modern microdosed drugs of the latest generation have no or minimal metabolic effect on the female body. Because of this, they can be used by non-smoking women after 40 years of age in the absence of risk factors associated with hypercoagulability (WHO, 1996). Such risk factors when using any type of hormonal contraception include, first of all, cardiovascular diseases, liver disease, heavy smoking in combination with taking COCs.
It should be remembered that hormonal contraceptives are contraindicated if there is a history of thromboembolism, cardiovascular pathology, severe diabetes mellitus, or malignant neoplasms of the reproductive system.
In the absence of the listed contraindications, microdosed drugs can be used quite widely. They are not only highly reliable, but also have a protective effect, including symptoms of menopausal syndrome, which are quickly relieved.
The positive effects of estrogen on brain function and emotional state in perimenopausal women are known. In addition, numerous studies have confirmed the positive effects of oral contraceptives on cognitive processes, improving memory and mood. It has been found that the estrogen component of OCs reduces the concentration of monoamine oxidase (MAO), which leads to an increase in serotonin levels, as well as brain excitability and thereby improves mood.
We studied the effectiveness and feasibility of using the microdose combined oral contraceptive (COC) Novinet in premenopausal women.
Novinet is a microdose COC containing 20 mcg ethinyl estradiol and 0.150 mg desogestrel. The drug contains a third generation progestogen, a derivative of levonorgestrel, desogestrel, which has high selectivity for progesterone receptors and high progestogenic activity.
A distinctive feature of the drug is the minimal content of the estrogen component, which significantly reduces the risk of developing estrogen-dependent side effects.
Under the influence of the drug, the release of FSH and LH is mainly prevented, which interferes with the ovulation process. The effect is enhanced by increasing the viscosity of the cervical mucus, which makes it difficult for sperm to penetrate into the uterine cavity.
We observed 35 somatically healthy women aged 44 to 47 years (average age 45.4+0.4 years) who had no contraindications to hormonal contraception.
In addition to the general clinical examination, we measured blood pressure (BP) and body weight, a blood test for hemostasis and lipid spectrum, extended colposcopy, cytological examination of smears from the surface of the cervix and cervical canal, and ultrasound examination of the pelvic organs.
Dynamic monitoring of patients was carried out every three, six and 12 months from the moment they started using contraception. No menstrual cycle irregularities were detected; only in six (17.1%) patients the cycle duration was reduced to 21 days, which is apparently due to hormonal changes in the body.
During treatment, not a single case of pregnancy was registered, i.e., the contraceptive effectiveness of the drug was 100%. Novinet had a regulating effect on the menstrual cycle, which was expressed in establishing a cycle duration of 25-27 days in all patients. The average duration of the menstrual cycle was 27.5 + 0.3 days.
Menstrual-like reactions lasted 3.4+0.3 days, scanty menstrual-like discharge was observed in three (8.6%) women.
Eight women experienced adverse reactions: in the form of intermenstrual bleeding (two cases), engorgement of the mammary glands (six cases).
All adverse reactions disappeared during the first two to three months of using COCs and did not require therapeutic measures.
Four women who experienced physical discomfort (weakness) and emotional discomfort (bad mood) before contraception were prescribed showed a significant improvement in their condition in the second month after starting contraception. It should be noted that four patients with premenstrual syndrome also showed a positive effect after three months of using Novinet.
There were no significant changes in body weight while taking the drug.
The initial blood lipid parameters of the patients before using Novinet were normal. After 12 months, there was a trend towards an increase in HDL, which has anti-atherogenic potential, and a decrease in LDL, which has atherogenic potential.
The studies also indicated the absence of negative dynamics of changes in the blood coagulation system.
Studies of the condition of the cervix using a complex of the most informative research methods did not reveal any pathological changes.
Thus, the results of the study indicate that the modern microdosed COC Novinet is a highly effective contraceptive, well tolerated by premenopausal women, does not have a significant effect on blood pressure, body weight, blood lipids and hemostasis, and also allows achieving a therapeutic effect in patients with premenstrual syndrome and women experiencing emotional discomfort due to age-related (hormonal) changes in the body.
V. N. Prilepskaya, Doctor of Medical Sciences, Professor N. M. Nazarova NTSAGiP RAMS, Moscow
