Divigel gel 0.1%, # 28 1g

• Hormone replacement therapy for symptoms of estrogen deficiency;

• treatment of climacteric syndrome associated with natural or artificial menopause, which developed as a result of surgery.

The drug Divigel is a gel for transdermal use.

The drug Divigel can be used for long-term and cyclic therapy.

The usual starting dose is 1.0 mg estradiol (1.0 g gel, respectively) per day, but the choice of starting dose may be based on the severity of symptoms. Depending on the clinical picture, the dose can be changed after 2-3 cycles individually from 0.5 g to 1.5 g per day, which corresponds to 0.5 to 1.5 mg of estradiol per day.

At the beginning and during the continuation of the treatment of postmenopausal symptoms, the lowest effective dose should be used for the shortest period.

The use of the drug Divigel without the addition of gestagen is possible only in patients with a removed uterus. Patients with an 'intact' (unoperated) uterus are recommended to prescribe progestogen during treatment with Divigel - at least 12-14 days in a row during a month or a 28-day cycle. After the course application of gestagen, menstrual bleeding should occur. In case of extraordinary or prolonged uterine bleeding, it is imperative to establish the cause of their occurrence. In women who have undergone hysterectomy, the addition of a gestagen in the absence of a history of endometriosis is not recommended. In women who have not previously used drugs for hormone replacement therapy (HRT), and in women switching to Divigel from a combined drug for HRT with a continuous regimen,treatment with Divigel can be started on any day convenient for the patient.

In women switching to Divigel from a continuous sequential HRT regimen, treatment should be started after the completion of the previous regimen. If the patient has forgotten to apply the gel, it should be done as soon as possible, but no later than within 12 hours from the moment of applying the drug. If more than 12 hours have passed, then the application of the Divigel preparation should be postponed until the next time.

With irregular use of the drug (missed doses), 'breakthrough' bleeding and 'spotting' spotting may occur.

Method of application 6

The gel is usually applied once a day to clean, dry skin of the lower anterior abdominal wall, lumbar region, shoulders, forearms, or alternately on the right or left buttocks, alternating the places of application daily. The drug Divigel should not be applied to the mammary glands, face, genital area, as well as to irritated skin. The area of ??application should be equal in size to 1-2 palms. After applying the drug, you should wait a few minutes until the gel dries up (2-3 minutes). The area of ??application of the gel must not be rinsed for 1 hour. Avoid accidental eye contact with Divigel. Hands should be washed immediately after applying the gel. Additional information for special patient groups Experience with Divigel in women over 65 years of age is limited. There are no indications for the use of Divigel in children.

estradiol hemihydrate in terms of estradiol

• Hypersensitivity to estradiol and / or any of the excipients of the drug.

• Breast cancer (diagnosed, suspected, or history).

• Diagnosed or suspected estrogen-dependent malignant tumors of the genital organs (including endometrial cancer).

• Vaginal bleeding of unknown etiology.

• Untreated endometrial hyperplasia.

• Identified acquired or hereditary predisposition to venous or arterial thrombosis, including antithrombin III deficiency, protein C deficiency, protein S deficiency).

• Venous thrombosis and thromboembolism at present or in history (including deep vein thrombosis and thrombophlebitis, pulmonary embolism).

• Active or recent arterial thromboembolic diseases (including angina pectoris, myocardial infarction).

• Congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, Rotor syndromes).

• Benign or malignant liver tumors currently or in history.

• Cholestatic jaundice or severe cholestatic pruritus (including an increase in their manifestations during a previous pregnancy or while taking sex medications).

• Acute liver disease or a history of liver disease if liver function tests have not returned to normal.

• Porphyria.

• With caution, the drug Divigel should be used for diseases such as:

• uterine fibroids, endometriosis, the presence of risk factors for thromboembolic disorders, the presence of risk factors for estrogen-dependent tumors (breast cancer in first-line relatives), arterial hypertension, liver disease (including liver adenoma) with normal liver function tests, diabetes mellitus with or without diabetic angiopathy, cholelithiasis, migraine or severe headache, systemic lupus erythematosus, history of endometrial hyperplasia, epilepsy, bronchial asthma, otosclerosis, heart failure, renal failure, ischemic heart disease (IHD), sickle cell anemia, chloasisceria a history of hereditary angioedema. Experience with women over 65 years of age is limited.

Pharmacological properties

Pharmacodynamics

The active substance of the drug Divigel, synthetic 17-estradiol, is chemically and biologically identical to endogenous human estradiol, produced in the body of women by the ovaries, from the first menstruation to menopause. Estrogens form a complex with specific receptors found in the cells of various target organs - in the uterus, vagina, urethra, mammary gland, liver, hypothalamus, pituitary gland. The receptor-ligand complex interacts with estrogen-effector elements of the genome and specific intracellular proteins that induce the synthesis of i-RNA, proteins and the release of cytokines and growth factors. 2 Has a feminizing effect on the body. Stimulates the development of the uterus, fallopian tubes, vagina, stroma and ducts of the mammary glands, pigmentation in the area of ??the nipples and genitals,the formation of secondary sexual characteristics of the female type, the growth and closure of the epiphyses of long tubular bones. Promotes timely endometrial rejection and regular bleeding, in high concentrations causes endometrial hyperplasia, suppresses lactation, inhibits bone resorption, stimulates the synthesis of a number of transport proteins (thyroxin-binding globulin; transcortin; transferrin; globulin that binds sex hormones), fibrinogen. It has a procoagulant effect, increases the synthesis in the liver of vitamin K-dependent coagulation factors (II, VII, IX, X), reduces the concentration of antithrombin III. It increases the concentration of thyroxine, iron, copper, etc. in the blood. It has an anti-atherosclerotic effect, increases the content of HDL, reduces LDL and cholesterol, and increases the concentration of triglycerides.Modulates the sensitivity of receptors to progesterone and sympathetic regulation of smooth muscle tone, stimulates the transition of intravascular fluid into tissues and causes compensatory sodium and water retention. In high doses, it prevents the degradation of endogenous catecholamines, competing for active receptors of catechol-O-methyltransferase. After menopause, only a small amount of estradiol is produced in the body (from estrone found in the liver and in adipose tissue). A decrease in the content of estradiol produced in the ovaries is accompanied in many women by vasomotor and thermoregulatory instability ('hot flushes' of blood to the skin of the face), sleep disorders, as well as progressive atrophy of the mucous membrane of the genitourinary system. Due to estrogen deficiency, osteoporosis develops (mainly of the spine).After oral administration, a larger amount of estradiol is metabolized in the lumen (microflora) and the intestinal wall, as well as in the liver, before entering the bloodstream (which leads to non-physiologically high plasma estrone concentrations, and with prolonged therapy - to the accumulation of estrone and estrone sulfate) ... The consequences of the accumulation of these metabolites in the body for a long time have not yet been elucidated. It is known that oral administration of estrogens causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure (BP).The consequences of the accumulation of these metabolites in the body for a long time have not yet been clarified. It is known that oral administration of estrogens causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure (BP).The consequences of the accumulation of these metabolites in the body for a long time have not yet been elucidated. It is known that oral administration of estrogens causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure (BP).

Pharmacokinetics

The drug Divigel is an alcohol-based gel for external use. When applied to the skin, the alcohol evaporates quickly and estradiol penetrates the skin into the bloodstream. The application of the Divigel preparation on an area of ??200-400 cm2 (the size of one or two palms) does not affect the amount of absorbed estradiol. However, if the drug Divigel is applied over a large area, then the degree of absorption is significantly reduced. To some extent, estradiol is retained in the subcutaneous tissues, from where it is gradually released into the bloodstream. Transdermal application avoids the first stage of hepatic metabolism, due to which fluctuations in the concentration of estradiol in the blood plasma when using Divigel are insignificant. Transdermal administration of 0.5, 1 and 1.5 mg estradiol (0.5, 1 and 1.5 g of the drug Divigel) is accompanied by the achievement of an average maximum concentration of Cmax in blood plasma of 143, 247 and 582 pmol / l, respectively. Average Caverage concentrations over the dose interval are 75, 124, and 210 pmol / L, respectively. Average minimum concentrations Cmin are 92, 101, and 152 pmol / L, respectively. With the use of the drug Divigel, the estradiol / estrone ratio remains at the level of 0.4 to 0.7, while with the use of oral estrogens, it usually decreases to <0.2. The bioavailability of estradiol when using the drug Divigel is 82%. The metabolism and excretion of estradiol with transdermal administration is similar to the metabolism of natural estrogens. Does not cumulate.respectively. Average Caverage concentrations over the dose interval are 75, 124 and 210 pmol / L, respectively. Average minimum concentrations Cmin are 92, 101, and 152 pmol / L, respectively. Against the background of the use of the drug Divigel, the estradiol / estrone ratio remains at the level of 0.4 to 0.7, while with the use of oral estrogens, it usually decreases to <0.2. The bioavailability of estradiol when using the drug Divigel is 82%. The metabolism and excretion of estradiol with transdermal administration is similar to the metabolism of natural estrogens. Does not cumulate.respectively. Average Caverage concentrations over the dose interval are 75, 124, and 210 pmol / L, respectively. Average minimum concentrations Cmin are 92, 101, and 152 pmol / L, respectively. Against the background of the use of the drug Divigel, the estradiol / estrone ratio remains at the level of 0.4 to 0.7, while with the use of oral estrogens, it usually decreases to <0.2. The bioavailability of estradiol when using the drug Divigel is 82%. The metabolism and excretion of estradiol with transdermal administration is similar to the metabolism of natural estrogens. Does not cumulate.With the use of the drug Divigel, the estradiol / estrone ratio remains at the level of 0.4 to 0.7, while with the use of oral estrogens, it usually decreases to <0.2. The bioavailability of estradiol when using the drug Divigel is 82%. The metabolism and excretion of estradiol with transdermal administration is similar to the metabolism of natural estrogens. Does not cumulate.Against the background of the use of the drug Divigel, the estradiol / estrone ratio remains at the level of 0.4 to 0.7, while with the use of oral estrogens, it usually decreases to <0.2. The bioavailability of estradiol when using the drug Divigel is 82%. The metabolism and excretion of estradiol with transdermal administration is similar to that of natural estrogens. Does not cumulate.

Side effect

During the first few months of treatment, there may be 'breakthrough' bleeding, 'spotting' spotting, and tenderness or enlargement of the mammary glands. As a rule, these effects are transient and usually disappear with continued treatment. Adverse drug reactions have been reported, in particular, in three phase III clinical trials. Listed below are adverse drug reactions noted in clinical studies (only those cases that had a possible connection with transdermal use of estradiol at a dose of 50 mcg or 100 mcg per day), as well as adverse drug reactions observed in the post-marketing period. In general, it can be expected that adverse drug reactions may occur in 76% of patients.In clinical studies, local reactions and pain in the mammary glands occurred in more than 10% of patients.

The frequency of side effects of the drug is estimated as follows:

Frequent: 1/100, 1/10 Infrequent: 1/1000, 1/100 Rare: 1/10 000, 1/1000 Frequency unknown (noted in post-marketing period).

Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequent - benign neoplasms of the breast, benign neoplasms of the endometrium; frequency unknown - uterine fibroids. Immune system disorders: infrequent - hypersensitivity reactions; frequency unknown - exacerbation of hereditary angioedema. Nutrition and metabolic disorders: frequent - edema, weight gain, weight loss; infrequently - increased appetite, hypercholesterolemia 1. Mental disorders: frequent - depression, nervousness, drowsiness; infrequent - anxiety, insomnia, apathy, emotional lability, impaired concentration, changes in libido and mood, euphoria1, agitation1. Nervous system disorders: frequent - headache, dizziness; infrequent - migraine,paresthesia, tremor 1. Violations of the organ of vision: infrequent - visual impairment1, dry eye syndrome1; rare - intolerance to contact lenses. Heart disorders: infrequent - palpitations. Vascular disorders: frequent - 'hot flashes'; infrequently - increased blood pressure1, superficial phlebitis1, purpura1; rare - venous thromboembolism (including deep vein thrombosis of the lower extremities and small pelvis and pulmonary embolism); frequency unknown - cerebral ischemic disorders. Disturbances from the respiratory system, chest and mediastinal organs: infrequent - shortness of breath1, rhinitis1. Disturbances from the gastrointestinal tract: frequent - nausea, vomiting, stomach cramps, flatulence; infrequent - constipation, dyspepsia1, diarrhea1, rectal disorders1; frequency unknown - abdominal pain, bloating.Liver and biliary tract disorders: rare - liver dysfunction, cholestasis; frequency unknown - cholestatic jaundice. Skin and subcutaneous tissue disorders: infrequent - acne, alopecia, dry skin, nail pathology1, skin nodules1, hirsutism1; rare - rash; frequency unknown - contact dermatitis, eczema. Musculoskeletal and connective tissue disorders: infrequent - joint pathology, muscle spasms. Renal and urinary tract disorders: infrequent - frequent urination, urinary retention, urinary incontinence1, cystitis1, discoloration of urine1, hematuria. Disturbances from the reproductive system and mammary glands: frequent - acyclic bleeding from the vagina or 'smearing' spotting, vaginal discharge, vulvovaginitis, menstrual irregularities,pain or soreness of the mammary glands; infrequent - enlargement of the mammary glands, tenderness on palpation of the mammary glands, endometrial hyperplasia, uterine disorders1; rare - dysmenorrhea, a condition resembling premenstrual syndrome. General disorders and disorders at the injection site: frequent - skin irritation, itching at the site of application of the drug, pain, excessive sweating; infrequent - fatigue, asthenia1, fever1, flu-like syndrome1, malaise1. Laboratory and instrumental data: infrequent - deviations from the norm of laboratory test results 1.frequent - skin irritation, itching at the site of application of the drug, pain, excessive sweating; infrequent - fatigue, asthenia1, fever1, flu-like syndrome1, malaise1. Laboratory and instrumental data: infrequent - deviations from the norm of laboratory test results 1.frequent - skin irritation, itching at the site of application of the drug, pain, excessive sweating; infrequent - fatigue, asthenia1, fever1, flu-like syndrome1, malaise1. Laboratory and instrumental data: infrequent - deviations from the norm of laboratory test results 1.

1) Were observed in clinical studies in isolated cases. Given the small population size (n = 611), it is impossible to determine from these results whether these events were infrequent or rare. During treatment with estrogens / gestagens, other undesirable reactions were observed: - Benign and malignant estrogen-dependent neoplasms, in particular, endometrial cancer. - Myocardial infarction and stroke. - Disorders of the skin and subcutaneous tissue: chloasma, erythema multiforme, erythema nodosum, thrombocytopenic purpura. - There is an increase in the risk of developing dementia when starting HRT over the age of 65 years. In women using combined estrogen-progestin drugs for more than 5 years, there is a 2-fold increase in the risk of diagnosing breast cancer.Due to the content of propylene glycol, Divigel may cause skin irritation. The risk of developing ovarian cancer The use of HRT in the form of estrogen monotherapy or combination therapy with estrogen-progestogen has been associated with a slightly increased risk of developing ovarian cancer (see section Special instructions). A meta-analysis of 52 epidemiological studies indicates an increased risk of ovarian cancer in women currently using HRT compared with women who have never taken HRT (RR 1.43, 95% CI 1.31-1.56). Among women aged 50 to 54 who have been taking HRT for 5 years, this translates to approximately 1 additional case in 2000 women. Among women aged 50 to 54 who did not take HRT, about 2 women in 2000 were diagnosed with ovarian cancer within 5 years.The risk of developing ovarian cancer The use of HRT in the form of estrogen monotherapy or combination therapy with estrogen-progestogen has been associated with a slightly increased risk of developing ovarian cancer (see section Special instructions). A meta-analysis of 52 epidemiological studies indicates an increased risk of ovarian cancer in women currently using HRT compared with women who have never taken HRT (RR 1.43, 95% CI 1.31-1.56). Among women aged 50 to 54 who have been taking HRT for 5 years, this translates to approximately 1 additional case in 2000 women. Among women aged 50 to 54 who did not take HRT, about 2 women in 2000 were diagnosed with ovarian cancer within 5 years.The risk of developing ovarian cancer The use of HRT in the form of estrogen monotherapy or combination therapy with estrogen-progestogen has been associated with a slightly increased risk of developing ovarian cancer (see section Special instructions). A meta-analysis of 52 epidemiological studies indicates an increased risk of ovarian cancer in women currently using HRT compared with women who have never taken HRT (RR 1.43, 95% CI 1.31-1.56). Among women aged 50 to 54 who have been taking HRT for 5 years, this translates to approximately 1 additional case in 2000 women. Among women aged 50 to 54 who did not take HRT, about 2 women in 2000 were diagnosed with ovarian cancer within 5 years.currently using HRT, compared with women who have never taken HRT (RR 1.43, 95% CI 1.31-1.56). Among women aged 50 to 54 who have been taking HRT for 5 years, this translates to approximately 1 additional case in 2000 women. Among women aged 50 to 54 who did not take HRT, about 2 women in 2000 were diagnosed with ovarian cancer within 5 years.currently using HRT, compared with women who have never taken HRT (RR 1.43, 95% CI 1.31-1.56). Among women aged 50 to 54 who have been taking HRT for 5 years, this translates to approximately 1 additional case in 2000 women. Among women aged 50 to 54 who did not take HRT, about 2 women in 2000 were diagnosed with ovarian cancer within 5 years.

Overdose

Symptoms: pain in the mammary glands, anxiety, irritability, nausea, vomiting, in some cases - metrorrhagia. With transdermal use, overdose is unlikely. Treatment is symptomatic. The gel must be washed off the skin. Symptoms disappear when the dose is reduced or when the drug is discontinued.

Interaction with other medicinal products

The metabolism of estradiol is accelerated when taken simultaneously with barbiturates, tranquilizers (anxiolytics), narcotic analgesics, anesthetics, some antiepileptic drugs (carbamazepine, phenytoin), inducers of liver microsomal enzymes; herbal preparations containing St. John's wort. The concentration of estradiol in the blood also decreases with the simultaneous use of phenylbutazone and some antibiotics and antiviral drugs (ampicillin, rifampicin, rifabutin, nevirapine, efavirenz). Ritonavir and nelfinavir, also known as potent inhibitors, when used together with sex hormones, in contrast, exhibit inducing properties. The effect of estradiol is enhanced by taking folic acid and thyroid hormone preparations.With transdermal administration, it is possible to avoid the effect of 'primary' passage through the liver, thus, the effect of drugs for HRT with transdermal application of estrogens, possibly to a lesser extent than with oral administration, depends on the action of inducers of liver microsomal enzymes. In clinical practice, increased estrogen metabolism can lead to a weakening of the effect and changes in the nature of uterine bleeding. Estradiol: - increases the effectiveness of lipid-lowering drugs; - weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants.depends on the action of inducers of liver microsomal enzymes. In clinical practice, increased estrogen metabolism can lead to a weakening of the effect and changes in the nature of uterine bleeding. Estradiol: - increases the effectiveness of lipid-lowering drugs; - weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants.depends on the action of inducers of liver microsomal enzymes. In clinical practice, increased estrogen metabolism can lead to a weakening of the effect and changes in the nature of uterine bleeding. Estradiol: - increases the effectiveness of lipid-lowering drugs; - weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants.

special instructions

When treating postmenopausal symptoms, HRT should only be started if symptoms that adversely affect quality of life are present. A detailed risk and benefit assessment should be carried out at least once 10 times a year and HRT should be prescribed only if the benefits outweigh the risks. Data on the risks associated with HRT for the treatment of early menopause are limited. However, given the low absolute risk of HRT in young women, the benefit-to-risk ratio in these women is perhaps more favorable than in older women. Before starting or re-prescribing HRT, a complete personal and family history must be collected.A medical examination should be carried out in order to identify possible contraindications and observe the necessary precautions when taking the drug (including examination of the pelvic organs and mammary glands). In the course of treatment, it is recommended to carry out periodic examinations, the frequency and methods included in it are determined for each specific case individually. Research, including mammography, must be carried out in accordance with accepted standards and adapted to the individual clinical needs of each individual case. While the patient is taking drugs for HRT, a careful assessment of all the benefits and risks of therapy should be carried out.including mammography, should be performed in accordance with accepted standards and adapted to the individual clinical needs of each individual case. While the patient is taking drugs for HRT, a careful assessment of all the benefits and risks of therapy should be carried out.including mammography, should be performed in accordance with accepted standards and adapted to the individual clinical needs of each individual case. While the patient is taking drugs for HRT, a careful assessment of all the benefits and risks of therapy should be carried out.

Conditions that require monitoring

If any of the following conditions are present, have been encountered previously and / or worsened during pregnancy or previous hormonal therapy, the patient should be under constant medical supervision. It should be taken into account that these conditions can, in rare cases, recur or worsen during treatment with Divigel, in particular: uterine fibroids or endometriosis; risk factors for the development of thromboembolic diseases; risk factors for estrogen-dependent tumors (the presence of first-line relatives with breast cancer); arterial hypertension; liver disease (eg, liver adenoma); diabetes mellitus with or without diabetic angiopathy; cholelithiasis; migraine and / or severe headache; systemic lupus erythematosus; a history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis,hereditary angioedema.

Reasons for immediate discontinuation of therapy

Therapy should be discontinued if contraindications are found and / or in the following situations: jaundice or deterioration of liver function; marked increase in blood pressure; newly arisen attacks of migraine-like headache; pregnancy.

Endometrial hyperplasia and cancer

The risk of endometrial hyperplasia and cancer is increased when estrogen is taken for a long time. According to available data, the risk of developing endometrial cancer in women using only estrogens increases 2-12 times compared with women who do not use estrogens, depending on the duration of treatment and the dose of estrogen. After stopping treatment, the increased risk may persist for at least 10 years. To reduce the risk, it is necessary to combine estrogen therapy in women with an unremoved uterus with gestagens for at least 12 days during the treatment cycle or to take combined estrogen-gestagenic drugs continuously. During the first months of treatment, breakthrough bleeding and spotting bleeding may occur.If breakthrough bleeding or spotting bleeding occurs after a period of treatment or continues after treatment is discontinued, an examination should be performed to identify the cause, including endometrial biopsy (to exclude endometrial malignancy). The use of drugs for HRT containing only estrogen can lead to precancerous or malignant transformation of residual foci of endometriosis. Thus, in women who have undergone a hysterectomy for endometriosis, the addition of gestagens to estrogen replacement therapy in order to prevent endometrial cancer should be considered if they are known to have residual foci of endometriosis.including endometrial biopsy (to exclude endometrial malignancy). The use of drugs for HRT containing only estrogen can lead to precancerous or malignant transformation of residual foci of endometriosis. Thus, in women who have undergone a hysterectomy for endometriosis, the addition of gestagens to estrogen replacement therapy in order to prevent endometrial cancer should be considered if they are known to have residual foci of endometriosis.including endometrial biopsy (to exclude endometrial malignancy). The use of drugs for HRT containing only estrogen can lead to precancerous or malignant transformation of residual foci of endometriosis. Thus, in women who have undergone a hysterectomy for endometriosis, the addition of gestagens to estrogen replacement therapy in order to prevent endometrial cancer should be considered if they are known to have residual foci of endometriosis.the addition of gestagens to estrogen replacement therapy should be considered to prevent endometrial cancer if it is known that they have residual foci of endometriosis.the addition of gestagens to estrogen replacement therapy should be considered to prevent endometrial cancer if it is known that they have residual foci of endometriosis.

Mammary cancer

The available data generally indicate an increased risk of breast cancer in women receiving combined estrogen-progestin drugs and, possibly, also drugs for HRT containing only estrogen; this risk depends on the duration of HRT use. Use of combined estrogen-progestogen drugs for HRT In a randomized placebo-controlled study (study 'Women's Health Initiative', WHI) and in epidemiological studies, there was congruent data on an increased risk of breast cancer in women receiving combined estrogen-gestagenic drugs for HRT; increased risk was found after about 3 years of treatment. Use of estrogen-only HRT medications 12 The WHI study found no increased risk of breast cancer in womenundergone hysterectomy and using drugs for HRT containing only estrogen. In observational studies, in most cases, a small increase in the risk of being diagnosed with breast cancer is reported, which is significantly lower than in women using a combination of estrogen and gestagen. Additional risk begins to appear after several years of treatment, but returns to baseline within a few (no more than five) years after stopping treatment. HRT, in particular, with combined estrogen-progestin drugs, leads to an increase in mammographic image density, which may interfere with radiological detection of breast cancer.In observational studies, in most cases, a small increase in the risk of being diagnosed with breast cancer is reported, which is significantly lower than in women using a combination of estrogen and gestagen. Additional risk begins to appear after several years of treatment, but returns to baseline within a few (no more than five) years after stopping treatment. HRT, in particular with combined estrogen-gestagenic drugs, leads to an increase in mammographic image density, which may interfere with radiological detection of breast cancer.In observational studies, in most cases, a small increase in the risk of being diagnosed with breast cancer is reported, which is significantly lower than in women using a combination of estrogen and gestagen. Additional risk begins to appear after several years of treatment, but returns to baseline within a few (no more than five) years after stopping treatment. HRT, in particular with combined estrogen-gestagenic drugs, leads to an increase in mammographic image density, which may interfere with radiological detection of breast cancer.but returns to baseline within a few (no more than five) years after stopping treatment. HRT, in particular with combined estrogen-gestagenic drugs, leads to an increase in mammographic image density, which may interfere with radiological detection of breast cancer.but returns to baseline within a few (no more than five) years after stopping treatment. HRT, in particular with combined estrogen-gestagenic drugs, leads to an increase in mammographic image density, which may interfere with radiological detection of breast cancer.

–ак ¤ичников

–ак ¤ичников встречаетс¤ с меньшей частотой, чем рак молочной железы. Ёпидемиологические данные, полученные из большого мета-анализа свидетельствуют о несколько повышенным риске у женщин, принимающих монопрепараты эстрогена или комбинированную эстроген-гестаген «v“; риск становитс¤ ¤вным в течение 5 лет применени¤ и уменьшаетс¤ со временем после прекращени¤ приема. Ќекоторые другие исследовани¤, включа¤ исследование WHI, предполагают, что применение комбинированной «v“ может быть св¤зано с аналогичны