Estrogele® (Oestrogel®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceEstradiolEstradiol
Similar drugsTo uncover
  • Divigel
    gel externally 
    Orion Corporation     Finland
  • Klimara®
    patch through. 
    Bayer Pharma AG     Germany
  • Estrogele®
    gel through. 
    Bezen Helskea SA     Belgium
  • Estrofem®
    pills inwards 
    Novo Nordisk A / S     Denmark
    • Dosage form: & nbspTransdermal Gel
    Composition:

    Composition for 1 g of gel:

    Active substance:

    Estradiol hemihydrate 0.6 mg

    [in terms of estradiol]

    Excipients:

    Carbomer (carbopol 980) 5.0 mg, trolamine (triethanolamine) 5.0 mg, ethanol 400 mg, purified water q.s. up to 1 g.

    Description:Colorless transparent gel with the smell of ethanol.
    Pharmacotherapeutic group:Estrogen
    ATX: & nbsp

    G.03.C.A.03   Estradiol

    Pharmacodynamics:

    The active substance of the drug is Estrogel® - 17β-Estradiol is chemically and biologically identical to endogenous human estradiol.

    Has an estrogenic effect on the main target organs: ovaries, endometrium, vaginal epithelium, mammary glands, urethra, hypothalamus, pituitary gland, liver - similar to the action of endogenous estrogens in the follicular phase of the menstrual cycle.

    Replenishes the deficiency of estrogen in a woman during menopause and reduces the severity of menopausal disorders, including "hot flashes", increased sweating at night, atrophic changes in the urinary tract (atrophic vulvovaginitis, dyspareunia, urinary incontinence), and psychoemotional disorders.

    Clinical efficacy of the drug Estrozel® when treating the symptoms of menopause is comparable with that when taking estrogens inwards.

    Estradiol helps to reduce the concentration of total cholesterol without changing the ratio of cholesterol / HDL.

    It has a procoagulant effect, increases the synthesis in the liver of vitamin K-dependent clotting factors (II, VII, IX, X), reduces the concentration of antithrombin III.

    Estradiol prevents loss of bone mass associated with natural menopause or ovariectomy.

    Estrogen deficiency in the postmenopausal period is associated with a decrease in bone mineral density (BMD). The effect of estrogens on MPCM is dose-dependent and continues, apparently, as long as hormone replacement therapy (HRT) is under way. After the abolition of HRT, MPCM begins to decrease at the same rate as before the beginning of the procedure.
    Data from the randomized placebo-controlled study "Women's Health Initiative" (WHI) and a meta-analysis of clinical studies showed that HRT alone with estrogens or estrogens combined with gestagens in healthy women during postmenopause reduces the risk of fractures of the hip, spine and other osteoporotic fractures.There is also limited evidence that HRT can prevent bone fractures in women with low BMD and / or established osteoporosis.

    Pharmacokinetics:

    Absorption and distribution

    When the gel is applied locally on a large surface of the skin, the alcohol evaporates and approximately 10% of estradiol is absorbed through the skin into the vascular system, regardless of the patient's age. Daily use of 2.5 g or 5 g of the drug ESTROGEL® on an area of ​​400-750 cm2 leads to a gradual increase in the concentration of estradiol and estrone and ensures their equilibrium concentration in the blood plasma after about 3-5 days in a ratio characteristic for the onset of the middle of the follicular phase of the menstrual cycle. When using the drug Estrozel® in 17 postmenopausal women 1 time per day by applying on the back surface of one hand from the wrist to the shoulder for 14 days the maximum concentration (Cmax) Estradiol and estrone in blood plasma for

    The 12th day of application was 117 pg / ml and 128 pg / ml, respectively. The average concentration of estradiol and estrone in the blood plasma for a 24-hour interval after application of 2.5 g of the drug Estrozel® on the 12th day of administration was 76.8 pg / ml and 95.7 pg / ml, respectively.

    Metabolism and excretion

    Estradiol is metabolized, mainly, in the liver to estriol, estrone and their conjugated metabolites (glucuronides, sulfates). These metabolites are subjected to intestinal hepatic recirculation. After discontinuation of treatment, the concentration of estradiol returns to the baseline level after about 76 hours.

    Indications:
    • Hormone replacement therapy with symptoms of estrogen deficiency; treatment of climacteric syndrome associated with natural or surgical menopause.
    • Prevention of osteoporosis in the postmenopausal period in women with a high risk of fractures with intolerance or the presence of contraindications to other drugs for the prevention of osteoporosis.
    Contraindications:
    • Hypersensitivity to estradiol and / or any of the excipients of the drug.
    • Breast cancer (diagnosed, suspected or in history).
    • Diagnosed, suspected estrogen-dependent malignant tumors of the genital organs (eg, endometrial cancer) or their presence in the anamnesis.
    • Bleeding from the genital tract of an unknown etiology.
    • Untreated hyperplasia of the endometrium.
    • Revealed acquired or hereditary predisposition to venous or arterial thrombosis, including an antithrombin III deficiency, protein C deficiency, protein S deficiency).
    • Venous thrombosis and thromboembolism are currently or in history (including thrombosis and deep vein thrombophlebitis, pulmonary embolism).
    • Active or recently transferred arterial thromboembolic diseases (including angina pectoris, myocardial infarction).
    • Congenital hyperbilirubinemia (syndromes Gilbert, Dubin-Johnson, Rotor).
    • Benign or malignant liver tumors are currently or in the anamnesis.
    • Cholestatic jaundice or severe cholestatic itching (including during the previous pregnancy or on the background of taking sex hormones).
    • Acute liver disease or a history of liver disease if the results of functional liver tests have not returned to normal.
    • Pregnancy, the period of breastfeeding (see section "Application during pregnancy and the period of breastfeeding ").
    • Porphyria.
    Carefully:

    Carefully should use the drug Estrozel® with such diseases and conditions as: uterine myoma; endometriosis; endometrial hyperplasia in the anamnesis; the presence of risk factors for estrogen-dependent tumors (breast cancer in relatives of the first line of kinship); presence of risk factors for thromboembolic disorders; arterial hypertension; liver diseases (including liver adenoma) with normal liver function tests; diseases of the gallbladder (including cholelithiasis); diabetes mellitus with or without diabetic angiopathy; migraine or severe headache; systemic lupus erythematosus; epilepsy; bronchial asthma; otosclerosis, chronic heart failure; kidney failure; ischemic heart disease (IHD); sickle-cell anemia; a history of chloasma; hypertriglyceridemia in history; pancreatitis; hereditary angioedema.

    The experience of treating women over 65 is limited.

    Pregnancy and lactation:Preparation Estroges® contraindicated for use during pregnancy.

    If pregnancy occurs during the use of the drug, treatment should be stopped immediately.

    The results of most epidemiological studies on the random effects of estrogen on the fetus do not indicate a teratogenic or fetotoxic effect.

    Preparation Estroges® is contraindicated for use during breastfeeding.

    Dosing and Administration:

    Preparation Estroges® prescribe externally, continuously or in cycles.

    The dose and duration of therapy are set individually.

    Usually, the initial dose of the drug is 2.5 g of gel once a day, which corresponds to 1.5 mg of estradiol. In most patients, this dose is effective to alleviate the symptoms of menopause. If after one month of therapy the efficacy is not achieved, an increase in the daily dose of the drug to a maximum of 5 g of gel is possible, which corresponds to 3.0 mg of estradiol.

    To start and continue therapy for menopausal symptoms, the minimum effective dose should be used for a minimum period of time.

    Prevention of osteoporosis in postmenopausal women

    The minimum effective dose in most patients is 2.5 g of the drug Estrozel® 1 per day.

    When the drug is used in the form of a "tuba" release, a plastic dose applicator is used to determine the daily dose:

    1 dose of the applicator corresponds to 2.5 g of gel (corresponding to 1.5 mg of estradiol).

    When using the drug in the form of a "vial", when one presses the dosage pump, 1.25 g of gel is released (corresponding to 0.75 mg of estradiol) equal to half the daily dose. The average daily dose of the drug is 2.5 g of gel (2 clicks on the dosage pump).

    Application of the drug in the form of the release of "tuba": you should open the tube and pierce the metal membrane of the tube with a small punch that is in the top of the tube cover. The required dose is extracted from the tube by the applicator's ruler.

    1 dose corresponds to the column of the extracted gel with a diameter corresponding to the diameter of the outlet of the tube, the length of which coincides with the depression in the applicator ruler. The groove has a dash, which allows you to divide the daily dose in half. One tube with gel is designed for 30 doses.

    The use of the drug in the form of a vial": it is necessary to remove the cap from the vial and press strongly on the dosage pump by substituting another hand to collect the gel.The dose that is released by the first pressing may be inaccurate.It is recommended to discard it. The bottle is designed for 64 clicks. After 64 clicks, the amount of gel that is released by one press can be less than necessary. Therefore, it is not recommended to use the bottle after 64 clicks on the dispensing pump.

    Application of Estrozel® without the addition of progestogen is possible only in patients with a deleted uterus.

    Patients with an intact (unremoved) uterus during treatment with the drug Estrogel® it is recommended to prescribe progestin.

    In the period of the menopausal transition treatment should be conducted for at least 3 weeks in a row, then should be followed by a break of 1 week, at the same time, orally prescribe progestin within 12-14 days of the month.

    During the perimenopause treatment can be carried out from 1 to 25 of the month at the same time as oral administration of progestin. During the week-long break, menstrual bleeding may occur, due to a decrease in the content of sex hormones. It is recommended to use only those gestagens, whose administration is allowed simultaneously with estrogens.

    In the postmenopausal period treatment with estrogens in combination with gestagens is carried out in a constant mode.

    Prolonged monotherapy with estrogens is indicated in women after hysterectomy.In women who underwent hysterectomy, the addition of progestogen in the absence of an anamnesis of endometriosis is not recommended.

    Depending on the clinical symptomatology after 2-3 cycles of treatment, dose adjustment is carried out, namely:

    - with the appearance of symptoms of hyperestrogenism, such as a feeling of tension in the mammary glands, a feeling of overflow in the abdomen and pelvis, feelings of anxiety, nervousness, aggressiveness, a dose reduction is necessary;

    - with symptoms of hypoestrogenism, such as persistent "hot flashes", dryness of the vaginal mucosa, headache, sleep disorders, asthenia, a propensity for depression, the dose should be increased.

    In women who did not previously use drugs for HRT, and in women who switched to the drug Estrozel® with a combined drug for HRT with a continuous regimen of reception, treatment with the drug Estrozel® You can start any day that is convenient for the patient. In women, switching to the drug Estrogel® with a continuous sequential HRT regimen, treatment should begin after completion of the previous regimen.

    If the patient has forgotten to apply the gel, you should do this as soon as possible, however no later than within 12 hours from the time of application. If more than 12 hours have passed, the application of the drug Estrozel® it is worth to postpone until next time. With irregular use of the drug (missed doses), there may be "breakthrough" bleeding and "spotting" bleeding.

    Mode of application

    The gel is applied by the patients themselves on a thin, thin layer to the clean, dry skin of the abdomen, lumbar region, shoulders or forearms until it is completely absorbed. The area of ​​application should be at least 2 palms.

    Do not massage the place of application of the gel. It is necessary to avoid getting the gel on the mammary glands and mucous membrane of the vulva and vagina.

    Application is considered correct and effective if the gel is absorbed completely within 2-3 minutes.

    If the sticky consistency persists for more than 5 minutes after application, the gel is covered with a too small skin surface.

    Wash hands immediately after applying the gel.

    Side effects:

    The following table describes the possible side effects of HRT:

    System of organs

    Frequent

    >1/100; <1/10

    Infrequent

    >1/1000; <1/100

    Rare

    >1/10000; <1/1000

    Immune system disorders



    Anaphylactic reactions (in women with allergic reactions in the anamnesis)

    Disorders from the metabolism and nutrition



    Impairment of glucose tolerance

    Disorders of the psyche


    Depression, mood swings

    Changing libido

    Disturbances from the nervous system

    Headache

    Migraine, dizziness

    Exacerbation of epilepsy

    Vascular disorders


    Venous thromboembolism

    Increased blood pressure

    Disorders from the gastrointestinal tract

    Nausea, abdominal pain

    Flatulence, vomiting


    Disturbances from the liver and bile ducts



    Deviations from the norm of indicators of functional liver

    Disturbances from the skin and subcutaneous tissues


    Itchy skin

    Skin discoloration, acne

    Violations of the genitals and mammary gland

    Swelling of the mammary glands, pain in the mammary glands, enlargement of the mammary glands, dysmenorrhea, menorrhagia, metrorrhagia, leukorrhea, endometrial hyperplasia

    Benign breast tumors, increased uterine size, uterine fibroids, vaginitis, vaginal candidiasis

    Galactorrhea

    General disorders

    Change in body weight (decrease or increase), fluid retention with peripheral edema

    Asthenia


    Other adverse reactions identified with estrogen-progestogen therapy are:

    • diseases of the gallbladder;
    • from the skin and subcutaneous tissues: chloasma, erythema multiforme, erythema nodosum, thrombocytopenic purpura;
    • increased risk of developing dementia over the age of 65.

    The risk of breast cancer

    • In women who use combined estrogen-progestational drugs for more than 5 years, there is an increased risk of diagnosing breast cancer by a factor of 2.
    • When carrying out HRT with estrogen alone, the risk of developing breast cancer is significantly lower than with combined estrogen-progestational medications.
    • The risk of developing breast cancer depends on the duration of HRT.

    Risk of endometrial cancer

    In postmenopausal women with an intact uterus

    The incidence of endometrial cancer is about 5 cases for every 1000 women with an intact uterus who are not receiving HRT. In women with an intact uterus, HRT is not recommended for estrogen alone, as this increases the risk of endometrial cancer.

    Depending on the duration of application of only estrogen and its dose, the increased risk of endometrial cancer in epidemiological studies ranged from 5 to 55 additional cases diagnosed in every 1000 women aged 50 to 65 years.Addition of a progestogen for at least 12 days to an estrogen-only therapy can prevent this increased risk. In the WHI study, when carrying out HRT (sequential or continuous) with combined estrogen-progestational drugs for five years, there was no increase in the risk of endometrial cancer (PP 1.0 (0.8-1.2)).

    Ovarian Cancer

    Prolonged use of HRT alone with estrogens and combined estrogen-progestational medications was associated with a small increase in the risk of developing ovarian cancer. In the WHI study, in HRT for five years, 1 additional case of ovarian cancer was detected for 2500 women.

    Risk of venous thromboembolism

    In women receiving HRT, there is an increased risk of developing venous thromboembolism (VTE), in particular deep vein thrombosis or pulmonary embolism, compared with women who did not receive HRT 1.3-3 times. The probability of VTE development is higher in the first year of HRT than in subsequent years.

    Overdose:

    The pain in the mammary glands or the excess production of cervical secretion may indicate a too high dose of the drug.

    No symptoms of acute overdose were reported.

    Symptoms of an overdose Estrogens can be nausea and bleeding "cancellation."

    Treatment: there is no specific antidote; it is necessary to cancel the drug, symptomatic therapy.

    Interaction:

    Application of Estrozel® together with surfactants (eg sodium lauryl sulfate) or other substances that alter the structure or barrier function of the skin, may reduce its effectiveness. Therefore, joint use of the drug with strong detergents and detergents (for example, containing benzalkonium or benzethonium chloride), skin care products with a high alcohol content (astringent, sunscreen) and keratolytic agents (eg, salicylic or lactic acid).

    It should avoid the use of any concomitant medications that have a damaging effect on the skin (for example, cytotoxic).

    Metabolism of estradiol is accelerated by simultaneous use with inductors of microsomal liver enzymes, such as antiepileptic drugs (phenobarbital, phenytoin, carbamazepine); some antibiotics and antiviral drugs (rifampicin, rifabutin, nevirapine, efavirenz); herbal preparations containing St. John's Wort.

    Ritonavir and nelfinavir, also known as strong inhibitors, when combined with sex hormones, on the contrary, exhibit inducing properties.

    With transdermal application, the effect of "primary" passage through the liver can be avoided, so the effect of preparations for HRT with transdermal application of estrogens, possibly to a lesser degree than with oral administration, depends on the effect of inducers of microsomal liver enzymes.

    Metabolism of estradiol is accelerated with simultaneous use with tranquilizers (anxiolytics), narcotic analgesics, means for anesthesia.

    The concentration of estradiol in blood plasma also decreases with simultaneous use with certain antibiotics (penicillins and tetracyclines).

    The effect of estradiol is enhanced by the intake of folic acid and thyroid hormone preparations.

    In clinical practice, increased estrogen metabolism can lead to a weakening of the effect and changesthe nature of uterine bleeding.

    Estradiol:

    • increases the effectiveness of lipid-lowering drugs;
    • weaken the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants.
    Special instructions:

    In the treatment of postmenopausal symptoms, HRT should be started only if there are symptoms adversely affecting the quality of life. It should be at least once a year to conduct a detailed assessment of the risks and benefits and appoint HRT only if the benefit exceeds the risk.

    Data on the risks associated with HRT for the treatment of premature menopause are limited. However, given the low absolute risk of HRT in young women, the ratio of benefits and risks in such women may be more favorable than in older women.

    Before starting or re-appointing HRT, you must collect a complete personal and family history. A medical examination should be conducted to identify possible contraindications and to observe the necessary precautions when taking the drug (including examination of pelvic organs and mammary glands).During the treatment it is recommended to conduct a periodic examination. The frequency and methods included in it are determined for each individual case individually. Studies, including mammography, should be conducted in accordance with accepted norms and adapt to the individual clinical needs of each individual case.

    During the patient's admission of drugs for HRT, a thorough evaluation of all the benefits and risks of therapy should be conducted.

    Conditions that require observation

    If any of the following conditions are present, previously met 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 aggravate during treatment with the drug Estrogel®, in particular:

    • uterine myoma or endometriosis;
    • risk factors for thromboembolic disease;
    • risk factors for estrogen-dependent tumors (presence of relatives of the first line of kinship 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;
    • endometrial hyperplasia in the anamnesis;
    • epilepsy;
    • bronchial asthma;
    • otosclerosis;
    • hereditary angioedema.

    Reasons for immediate cessation of therapy

    Therapy should be discontinued if contraindications and / or in the following situations are detected:

    • jaundice or worsening of liver function;
    • marked increase in blood pressure;
    • newly emerged seizures of migraine-like headache;
    • pregnancy.

    Hyperplasia and endometrial cancer

    In women with an intact uterus, the risk of hyperplasia and endometrial cancer increases with estrogen for a long time. According to available data, the risk of developing endometrial cancer in women using only estrogens increases 2-12 times compared to women who do not use estrogens, depending on the duration of treatment and the dose of estrogens. After cessation of treatment, the increased risk may persist for at least 10 years.

    Addition of progestogen in the last 12 days of the month / 28 days of the cycle or continuous combinedestrogen-progestational therapy in women with an unrefined uterus reduces the increased risk of hyperplasia and endometrial cancer associated with HRT with estrogen alone.

    During the first months of treatment, there may be "breakthrough" bleeding and "spotting" bleeding. If "breakthrough" bleeding or "spotting" spotting occurs after a certain period of treatment or continues after the withdrawal of the treatment, a check should be conducted to determine the cause of their occurrence, including an endometrial biopsy to exclude the malignant neoplasm of the endometrium.

    The use of drugs for HRT containing only estrogen can lead to precancerous or malignant transformation of residual foci of endometriosis. Thus, women who underwent a hysterectomy due to endometriosis should be provided with the addition of progestogen to estrogen replacement therapy in order to prevent endometrial cancer if it is known that they have residual foci of endometriosis.

    Mammary cancer

    The available data indicate an increased risk of breast cancer in women,receiving combined estrogen-progestational medications and, possibly, also hormone-only preparations containing estrogen alone; this risk depends on the duration of HRT use.

    The use of drugs for HRT that contain only estrogen

    The WHI study found no increased risk of developing breast cancer in women who underwent a hysterectomy and used hormone-eluting drugs containing only estrogen.

    In observational studies, in most cases, there is a slight increase in the risk of diagnosing breast cancer, which is significantly lower than that of women using combined estrogen-progestational drugs.

    The use of combined estrogen-progestogen drugs for HRT

    In the WHI study and epidemiological studies received matching data of an increased risk of breast cancer in women receiving combined estrogen-progestogen HRT; increased risk was detected after about 3 years of treatment.

    Additional risk begins to appear after several years of treatment, but returns to baseline within a few (not more than five) years after cessation of treatment.

    HRT, in particular combined estrogen-progestogen, leads to an increase in the density of mammographic images, which can prevent radiographic detection of breast cancer.

    Ovarian Cancer

    Ovarian cancer is much less common than breast cancer. Long-term (no less than 5-10 years) use of drugs for HRT that contain only estrogen is associated with an increased risk of ovarian cancer. Some studies, including the WHI study, have found that prolonged use of combination drugs for HRT may give rise to a similar or even less significant risk.

    Venous thromboembolism

    In women receiving HRT, there is an increased risk of developing VTE, in particular deep vein thrombosis or pulmonary embolism, compared with women who did not receive HRT 1.3-3 times. The probability of VTE development is higher in the first year of HRT than in subsequent years.

    Patients with known thrombophilic disorders may have an increased risk of developing VTE, and HRT may further increase it. Therefore, HRT in such patients is contraindicated.

    The main risk factors for VTE: individual or family history, use of estrogens, advanced age, serious surgery, prolonged immobilization, severe obesity (body mass index more than 30 kg / m2), pregnancy and the postpartum period, systemic lupus erythematosus, malignant neoplasms.

    There is no consensus on the possible role of varicose veins in the development of VTE.

    The risk of VTE increases with prolonged immobilization, extensive injuries or extensive surgical interventions. The intake of drugs for HRT should be discontinued 4 to 6 weeks before the planned surgical operations on the abdominal organs or orthopedic operations on the lower limbs. Treatment can be resumed after a complete recovery of motor ability.

    Women who do not have a history of VTE, but who have first-degree relatives who have survived thrombosis at a young age, can be screened after a detailed discussion of its limitations (screening reveals only a few thrombophilic disorders).

    If the patient is diagnosed with a thrombophilic disorder manifested by thrombosis in family members,as well as in the presence of "severe" defects (such as deficiency of antithrombin, protein S or protein C, or a combination of defects), HRT is contraindicated.

    Women who are already receiving continuous treatment with anticoagulants require a thorough evaluation of the ratio of the benefits and risks of HRT.

    If VTE develops after the start of treatment, the drug should be discontinued.

    Patients should be advised to immediately contact a physician if there are potential symptoms of thromboembolism (soreness and / or swelling of the lower limb, sudden chest pains, shortness of breath).

    Cardiac ischemia

    In the randomized controlled trials, no data were obtained on the prophylactic effect of myocardial infarction in women with or without IHD who received HRT with combined estrogen-progestational medications or estrogens alone.

    The use of drugs for HRT that contain only estrogen

    In randomized controlled trials, there was no evidence of an increased risk of coronary heart disease in patients who underwent hysterectomy and who received estrogen-only preparations for HRT.

    The use of combined estrogen-progestogen drugs for HRT

    When combined estrogen-progestational drugs for HRT are used, there is a slight increase in the relative risk of coronary heart disease. Since the initial absolute risk of CHD depends largely on age, the number of additional cases of IHD caused by the use of estrogens in combination with gestagens in healthy women approaching menopause is extremely small, but increases with age.

    Ischemic stroke

    HRT combined estrogen-progestogen and estrogen alone is associated with an increased risk of ischemic stroke by almost 1.5 times. Relative risk does not change with age and depending on the time that has passed since the onset of menopause. However, since the baseline risk of stroke largely depends on age, the overall risk of stroke in women receiving HRT will increase with age.

    Other states

    • Estrogens cause fluid retention in the body. Patients with cardiac or renal failure should be under constant medical supervision.
    • It is necessary to closely monitor the use of HRT in women with hypertriglyceridemia in the anamnesis,because in this state against the background of estrogen therapy, rare cases of a sharp increase in the concentration of triglycerides in the blood plasma, leading to the development of pancreatitis, are described.
    • Estrogens increase the concentration of thyroxine-binding globulin, leading to an increase in the total concentration of circulating thyroid hormones. Concentrations of free T3 and T4 do not change.

    It may increase the content of other proteins, for example, corticosteroid-binding globulin and globulin, binding sex hormones, which can lead, respectively, to an increase in the total concentration of circulating glucocorticosteroids and sex hormones. Concentrations of free or biological active hormones do not change. It is also possible to increase the content of other proteins of blood plasma (angiotensinogen (renin substrate), alpha-1-antitrypsin, ceruloplasmin).

    Chloasma

    In some cases, chloasma may develop, especially in women who have a history of chloasma during pregnancy. Women with a tendency to develop chloasma, against the background of HRT, should minimize exposure to sun or ultraviolet radiation.

    Effect on cognitive function

    HRT does not affect the improvement of cognitive function. The WHI study showed a trend towards a possible increase in the risk of developing dementia in women who started long-term HRT with combined estrogen-progestational medications or estrogens only over the age of 65 years.

    Application of Estrozel® should be produced:

    • the woman herself,
    • morning or evening, on clean skin.

    Preparation Estroges® does not leave stains.

    Effect on the ability to drive transp. cf. and fur:

    The effect of estrogens on the ability to drive vehicles and mechanisms has not been studied.

    Form release / dosage:

    Transdermal Gel 0.6 mg / g.

    Packaging:

    To 80 g of gel in a plastic bottle with a dispensing pump, equipped with a protective cap. 1 bottle with instruction for use is placed in a pack of cardboard.

    80 g of gel in an aluminum tube, sealed with a screw cap. The tube with the instruction for use and the applicator-dispenser is placed in a pack of cardboard.

    Storage conditions:

    List B.

    At a temperature not higher than 25 ° C, out of the reach of children.

    Shelf life:3 years. Do not use after the expiration date indicated on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N013773 / 01
    Date of registration:29.12.2009 / 28.09.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Bezen Helskea SABezen Helskea SA Belgium
    Manufacturer: & nbsp
    Representation: & nbspBEZEN HELSKEA ENG LLCBEZEN HELSKEA ENG LLCRussia
    Information update date: & nbsp30.10.2017
    Illustrated instructions
      Instructions
      Up