Divigel side effects. Composition and action
In this article, you can read the instructions for using the drug Divigel. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Divigel in their practice are presented. We kindly ask you to actively add your reviews about the drug: the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Divigel analogues in the presence of existing structural analogues. Use for the treatment of menopause, endometrial growth during IVF, planning and replacement therapy in women, including during pregnancy and lactation.
Divigel- an estrogen preparation for external use. The active ingredient, synthetic 17beta-estradiol, is chemically and biologically identical to endogenous human estradiol (formed in the body of women from the first menstruation until menopause) produced by the ovaries. In the cells of organs to which the action of hormones is directed, estrogens form a complex with specific receptors (found in various organs - in the uterus, vagina, urethra, mammary gland, liver, hypothalamus, pituitary gland); the receptor-ligand complex interacts with the estrogen effector elements of the genome and specific intracellular proteins that induce the synthesis of mRNA, proteins and the release of cytokines and growth factors.
It 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 nipples and genitals, the formation of female secondary sexual characteristics, growth and closure of the epiphyses of long tubular bones. Promotes timely rejection of the endometrium and regular bleeding, in high concentrations causes endometrial hyperplasia, inhibits lactation, inhibits bone resorption, stimulates the synthesis of a number of transport proteins (thyroxine-binding globulin, transcortin, transferrin, sex hormone-binding protein), fibrinogen. It has a procoagulant effect, induces the synthesis of vitamin K-dependent blood coagulation factors in the liver (2, 7, 9, 10), reduces the concentration of antithrombin 3.
Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases the content of HDL, reduces LDL and cholesterol (the level of triglycerides increases). It modulates the sensitivity of progesterone receptors and sympathetic regulation of smooth muscle tone, stimulates the transition of intravascular fluid into tissues and causes a compensatory retention of sodium and water. In high doses, it prevents the degradation of endogenous catecholamines by competing for active COMT receptors.
After menopause, only a small amount of estradiol is formed in the body (from estrone located 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 (flushes of blood to the skin of the face), sleep disorders, and progressive atrophy of the genitourinary system.
Due to estrogen deficiency, osteoporosis develops (mainly of the spine). After oral administration, a greater amount of estradiol is metabolized in the lumen (by microflora) and the intestinal wall, as well as in the liver, before entering the bloodstream (leading to non-physiologically high plasma concentrations of estrone, and with long-term 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 estrogen causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure.
Compound
Estradiol (in the form of hemihydrate) + excipients.
Pharmacokinetics
When applying the gel, alcohol evaporates quickly, and estradiol penetrates the skin, while most of it enters the systemic circulation immediately, and some estradiol is retained in the subcutaneous tissue and released into the systemic circulation gradually. The bioavailability of Divigel is 82%. Transdermal application avoids the first stage of hepatic metabolism, due to which fluctuations in the concentration of estrogen in the blood plasma when using Divigel are insignificant. It is excreted mainly by the kidneys in the form of sulfates and glucuronides; small amounts of estradiol, estrone and estriol are also found in the urine.
Indications
- hormone replacement therapy for symptoms of estrogen deficiency;
- treatment of climacteric syndrome associated with natural or artificial menopause, which has developed as a result of surgical intervention.
Release forms
Gel for external use (transdermal) 0.1% (sometimes erroneously called an ointment).
Instructions for use and method of use
Divigel is prescribed for long-term and cyclic therapy. The initial dose, as a rule, is 1 g of gel (corresponding to 1 mg of estradiol) per day, but is determined by the severity of symptoms. Depending on the clinical picture, the dose can be changed after 2-3 cycles individually from 500 mg to 1.5 g of gel per day (which corresponds to 500 μg to 1.5 mg of estradiol per day).
Patients with an intact (non-operated) uterus during treatment with Divigel are recommended to prescribe a gestagen (for example, medroxyprogesterone acetate, norethisterone, norethisterone acetate or dihydrogesterone) for 10-12 days in each cycle. After a course of progestogen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, it is imperative to establish the cause of their occurrence.
In patients in the postmenopausal period, the duration of the cycle can be increased up to 3 months.
The gel is applied once a day to the clean skin of the lower part of the anterior abdominal wall, lumbar region, shoulders, forearms, or alternately on the right or left buttocks, alternating daily application sites. The application area should be equal in size to 1-2 palms. After applying the drug, wait a few minutes until the gel dries (2-3 minutes).
The site of application of the gel should not be rinsed for 1 hour. Accidental contact with Divigel in the eyes should be avoided. Wash your hands immediately after applying the gel.
In case of skipping the next application of the gel, this should be done as soon as possible, but no later than within 12 hours from the moment the drug was applied according to the scheme. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. With irregular use of the drug (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Side effect
- headache;
- migraine;
- dizziness;
- depression;
- increase in blood pressure;
- thrombophlebitis;
- nausea, vomiting;
- stomach colic;
- flatulence;
- pain in the epigastric region;
- rash;
- skin irritation;
- skin hyperemia;
- contact dermatitis;
- scanty spotting;
- an increase in the size of uterine leiomyoma;
- endometrial hyperplasia (when administered without combination with progesterone);
- endometrial carcinoma (in women with an intact uterus after menopause);
- ovarian sclerosis with prolonged use;
- change in libido;
- engorgement (tension and / or increase) of the mammary glands;
- weight gain;
- visual impairment (change in the curvature of the cornea);
- chloasma;
- vaginal candidiasis.
Contraindications
- breast cancer (diagnosed, suspected or in history);
- diagnosed or suspected estrogen-dependent malignant tumors of the ovaries, uterus, endometrium;
- benign and malignant neoplasms of the genital organs (cancer of the cervix and body of the uterus, uterine fibroids, vulvar cancer, ovarian cancer) in women under the age of 60;
- benign neoplasms of the breast in women under the age of 60;
- vaginal bleeding of unknown etiology and a tendency to uterine bleeding;
- endometrial hyperplasia;
- pituitary tumors;
- diffuse connective tissue diseases;
- inflammatory diseases of the female genital organs (salpingoophoritis, endometritis);
- hyperestrogenic stage of menopause;
- spontaneous thromboembolic diseases of the veins (including history);
- deep vein thrombosis, pulmonary embolism (including history);
- thrombophlebitis and acute thrombophlebitis (including history);
- congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, Rotor syndromes);
- liver tumors (hemangioma, liver cancer);
- disorders of cerebral circulation (ischemic stroke, hemorrhagic stroke);
- diabetes mellitus, retinopathy, angiopathy;
- sickle cell anemia;
- disorders of fat metabolism;
- cholestatic jaundice or severe cholestatic itching (including an increase in their manifestations during a previous pregnancy or while taking steroid drugs);
- otosclerosis (including its exacerbation during pregnancy);
- hypersensitivity to estradiol and / or other components of the drug.
Divigel should not be applied to the mammary glands, face, genital area, as well as to irritated skin.
Use during pregnancy and lactation
Divigel is contraindicated for use during pregnancy and lactation.
Use in elderly patients
Experience in women over 65 years of age is limited.
special instructions
Before starting or re-prescribing hormone replacement therapy (HRT), a complete personal and family history should be taken. A medical examination should be carried out to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
In the process of treatment, it is recommended to conduct periodic examinations, the frequency and set of methods included in it are determined for each specific case individually. Studies, including mammography, should be carried out in accordance with accepted standards and taking into account individual clinical features in each individual case.
During HRT, all the benefits and risks of therapy should be carefully evaluated.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were observed earlier and / or worsened during pregnancy or previous hormonal therapy: leiomyoma (uterine fibromyoma), endometriosis; thromboembolic diseases in history or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; abnormal liver function (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; a history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis. It should be borne in mind that during treatment with Divigel, in rare cases, a relapse or exacerbation of the listed diseases is possible.
Therapy should be stopped immediately if contraindications are found and / or in the following situations: jaundice or deterioration in liver function; pronounced increase in blood pressure; new attacks of migraine-like headache; pregnancy.
When taking estrogens for a long time, the risk of developing endometrial hyperplasia and carcinoma increases. To reduce the risk, it is necessary to combine estrogen therapy in women with an unoperated uterus with progesterone for at least 12 days during the treatment cycle.
In the event of breakthrough bleeding and / or scanty spotting after several months of taking Divigel, studies should be carried out to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
Women with a uterus removed due to endometriosis (especially in cases of residual endometriosis) are recommended to add progesterone to estrogen-dependent therapy, due to premalignant or malignant transformation of endometriosis foci during estrogen stimulation.
With prolonged use of HRT, the risk of developing breast cancer increases. An increase in this risk was found mainly in women of thin or normal build. In women of full build (high predisposition to breast cancer), HRT does not additionally increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with an increase in the duration of HRT and returns to baseline approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT causes a similar or higher risk compared to estrogen therapy.
In women who received HRT, the risk of developing thromboembolic vein diseases (thrombosis of deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The probability is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications are: individual or family history, severe obesity (body mass index over 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriage should be further investigated to rule out a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for thrombophlebitis and the start of anticoagulant therapy. The risk increases with prolonged immobilization, extensive trauma, or major surgery. HRT should be discontinued 4-6 weeks before planned abdominal surgery or orthopedic surgery on the lower extremities. Treatment can be resumed after full recovery of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), HRT may need to be discontinued.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to an increase in the level of estradiol and its metabolites in the blood.
Estrogens increase insulin sensitivity and increase its excretion. Patients with diabetes mellitus in the first months of HRT shows constant monitoring of blood glucose levels.
Estrogen use increases the risk of surgically confirmed gallstone disease.
In rare cases, a sharp increase in the level of triglycerides in the blood while taking Divigel may develop pancreatitis.
Estrogens increase thyroid-binding globulin levels, increasing total circulating thyroid hormone levels.
Avoid getting the gel on the mammary glands and mucous membranes of the vulva and vagina.
Influence on the ability to drive vehicles and control mechanisms
Divigel therapy does not affect the ability to engage in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
drug interaction
Estradiol increases the effectiveness of lipid-lowering agents; weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants; reduces glucose tolerance (dose adjustment of hypoglycemic drugs).
The metabolism of Divigel is accelerated when taken simultaneously with barbiturates, tranquilizers (anxiolytics), opioid analgesics, anesthetics, some antiepileptic drugs (carbamazepine, phenytoin), inducers of microsomal liver enzymes; herbal preparations containing St. John's wort (St. John's wort).
The concentration of estradiol in the blood also decreases with the simultaneous use of phenylbutazone and certain antibiotics (ampicillin, rifampicin, rifabutin) and antiviral drugs (nevirapine, efavirenz), which is associated with changes in the intestinal microflora.
The action of estradiol increases against the background of taking folic acid and thyroid preparations.
Divigel's analogues
Structural analogues for the active substance:
- Dermestril;
- Klimara;
- Estrimax;
- estrogel;
- Estrofem.
Analogues by pharmacological group (estrogens and gestagens):
- Ginepriston;
- Gynoflor E;
- Dailla;
- Depo Provera;
- Jess;
- Jess Plus;
- Diana 35;
- Divina;
- Dimia;
- Duphaston;
- Evra;
- Jeanine;
- indivina;
- Qlaira;
- Klimadinon;
- Klimonorm;
- Clomiphene;
- Clostilbegit;
- Lactinet;
- Levonorgestrel;
- Lindinet;
- Logest;
- Marvelon;
- mifepristone;
- NuvaRing;
- Novinet;
- Norkolut;
- Norplant;
- Ovestin;
- Provera;
- Progesterone;
- Proginova;
- Progestogel;
- Regulon;
- Rigevidon;
- Silhouette;
- Tamoxifen;
- Three Mercy;
- Three regol;
- Utrozhestan;
- Femoston;
- Charosetta;
- Escapelle;
- Estriol;
- ethinylestradiol;
- Yarina;
- Yarina Plus.
In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.
Estrogen preparation for external use.
Preparation: DIVIGEL
The active substance of the drug:
estradiol
ATX encoding: G03CA03
CFG: Anticlimacteric estrogenic drug
Registration number: P No. 015526/01
Date of registration: 25.02.04
The owner of the reg. Award: ORION CORPORATION (Finland)
Divigel release form, drug packaging and composition.
1 pack (0.5 g)
500 mcg
Excipients: carbomers (Carbopol 974R), trolamine, propylene glycol, ethanol 96%, purified water - up to 0.5 g.
Gel for external use 0.1% homogeneous, opalescent.
1 pack (1 g)
estradiol (as hemihydrate)
1 mg
Excipients: carbomers (Carbopol 974R), trolamine, propylene glycol, ethanol 96%, purified water - up to 1 g.
Multilayer bags (28) - packs of cardboard.
The description of the drug is based on the officially approved instructions for use.
Pharmacological action Divigel
Estrogen preparation for external use. The active ingredient, synthetic 17-estradiol, is chemically and biologically identical to endogenous human estradiol (formed in the body of women from the first menstruation until menopause) produced by the ovaries. In the cells of the organs to which the action of hormones is directed, estrogens form a complex with specific receptors (found in various organs - in the uterus, vagina, urethra, mammary gland, liver, hypothalamus, pituitary gland); the receptor-ligand complex interacts with the estrogen effector elements of the genome and specific intracellular proteins that induce the synthesis of mRNA, proteins and the release of cytokines and growth factors.
It 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 nipples and genitals, the formation of female secondary sexual characteristics, growth and closure of the epiphyses of long tubular bones. Promotes timely rejection of the endometrium and regular bleeding, in high concentrations causes endometrial hyperplasia, inhibits lactation, inhibits bone resorption, stimulates the synthesis of a number of transport proteins (thyroxine-binding globulin, transcortin, transferrin, sex hormone-binding protein), fibrinogen. It has a procoagulant effect, induces the synthesis in the liver of vitamin K-dependent coagulation factors (II, VII, IX, X), reduces the concentration of antithrombin III.
Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases the content of HDL, reduces LDL and cholesterol (the level of triglycerides increases). It modulates the sensitivity of progesterone receptors and sympathetic regulation of smooth muscle tone, stimulates the transition of intravascular fluid into tissues and causes a compensatory retention of sodium and water. In high doses, it prevents the degradation of endogenous catecholamines by competing for active COMT receptors.
After menopause, only a small amount of estradiol is formed in the body (from estrone located 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 (flushes of blood to the skin of the face), sleep disorders, and progressive atrophy of the genitourinary system.
Due to estrogen deficiency, osteoporosis develops (mainly of the spine). After oral administration, a greater amount of estradiol is metabolized in the lumen (by microflora) and the intestinal wall, as well as in the liver, before entering the bloodstream (leading to non-physiologically high plasma concentrations of estrone, and with long-term 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 estrogen causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure.
Pharmacokinetics of the drug.
Suction and distribution
When applying the gel, alcohol evaporates quickly, and estradiol penetrates the skin, while most of it enters the systemic circulation immediately, and some estradiol is retained in the subcutaneous tissue and released into the systemic circulation gradually. Application of Divigel to an area of 200-400 cm2 (the size of one or two palms) does not affect the amount of absorbed estradiol. However, if Divigel is applied to a large area, the degree of absorption is significantly reduced.
The bioavailability of Divigel is 82%.
With transdermal use of Divigel at a dose of 1 mg of estradiol (1 g of Divigel), Cmax in blood plasma is approximately 157 pmol / l, the average concentration is 112 pmol / l, the minimum concentration is 82 pmol / l.
Does not accumulate.
Metabolism and excretion
Transdermal application avoids the first stage of hepatic metabolism, due to which fluctuations in the concentration of estrogen in the blood plasma when using Divigel are insignificant.
The metabolism of 17-estradiol is similar to that of natural estrogens. In the blood, it almost completely binds to the carrier protein. It undergoes a "first pass" effect through the liver, where it is metabolized to less active products - estrone and estriol. It is excreted in the bile into the lumen of the small intestine and reabsorbed. Finally loses activity as a result of oxidation in the liver.
During treatment with Divigel, the estradiol / estrone ratio remains at the level of 0.4-0.7.
breeding
It is excreted mainly by the kidneys in the form of sulfates and glucuronides; small amounts of estradiol, estrone and estriol are also found in the urine.
Indications for use:
Hormone replacement therapy for symptoms of estrogen deficiency;
Treatment of menopausal syndrome associated with natural or artificial menopause, which has developed as a result of surgical intervention.
Dosage and method of application of the drug.
Divigel is prescribed for long-term and cyclic therapy. The initial dose, as a rule, is 1 g of gel (corresponding to 1 mg of estradiol) per day, but is determined by the severity of symptoms. Depending on the clinical picture, the dose can be changed after 2-3 cycles individually from 500 mg to 1.5 g of gel per day (which corresponds to 500 μg to 1.5 mg of estradiol per day).
Patients with an intact (non-operated) uterus during treatment with Divigel are recommended to prescribe a gestagen (for example, medroxyprogesterone acetate, norethisterone, norethisterone acetate or dihydrogestrone) for 10-12 days in each cycle. After a course of progestogen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, it is imperative to establish the cause of their occurrence.
In patients in the postmenopausal period, the duration of the cycle can be increased up to 3 months.
The gel is applied 1 time / day on clean skin of the lower part of the anterior wall of the abdomen, lumbar region, shoulders, forearms, or alternately on the right or left buttocks, alternating daily application sites. The application area 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 site of application of the gel should not be rinsed for 1 hour. Accidental contact with Divigel in the eyes should be avoided. Wash your hands immediately after applying the gel.
In case of skipping the next application of the gel, this should be done as soon as possible, but no later than within 12 hours from the moment the drug was applied according to the scheme. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. With irregular use of the drug (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Side effects of Divigel:
From the side of the central nervous system and peripheral nervous system: headache, migraine, dizziness, depression, chorea.
From the side of the cardiovascular system: increased blood pressure, thrombophlebitis.
From the digestive system: nausea, vomiting, stomach cramps, flatulence, pain in the epigastric region, cholestatic jaundice, cholelithiasis.
Allergic reactions: at the site of application - rash, skin irritation, skin hyperemia, contact dermatitis.
On the part of the reproductive system: metrorrhagia, scanty spotting, an increase in the size of uterine leiomyoma, endometrial hyperplasia (when prescribed without combination with progesterone), endometrial carcinoma (in women with an intact uterus after menopause), ovarian sclerosis with prolonged use, changes in libido.
From the endocrine system: engorgement (tension and / or enlargement) of the mammary glands, weight gain, decreased carbohydrate tolerance.
From the side of metabolism: retention of sodium, calcium and water (edema) with prolonged use; bouts of porphyria.
Others: visual impairment (change in the curvature of the cornea), chloasma, melasma, vaginal candidiasis.
Contraindications to the drug:
Breast cancer (diagnosed, suspected or history);
Diagnosed or suspected estrogen-dependent malignant tumors of the ovaries, uterus, endometrium;
Benign and malignant neoplasms of the genital organs (cancer of the cervix and body of the uterus, uterine fibroids, vulvar cancer, ovarian cancer) in women under the age of 60;
Benign neoplasms of the breast in women under the age of 60;
Vaginal bleeding of unknown etiology and a tendency to uterine bleeding;
Hyperplasia of the endometrium;
Tumors of the pituitary gland;
Diffuse connective tissue diseases;
Inflammatory diseases of the female genital organs (salpingoophoritis, endometritis);
Hyperestrogenic stage of menopause;
Spontaneous thromboembolic diseases of the veins (including history);
Deep vein thrombosis, pulmonary embolism (including history);
Thrombophlebitis and acute thrombophlebitis (including history);
Congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, Rotor syndromes);
Tumors of the liver (hemangioma, liver cancer);
cerebrovascular accident (ischemic stroke, hemorrhagic stroke);
Diabetes mellitus, retinopathy, angiopathy;
sickle cell anemia;
Violations of fat metabolism;
Cholestatic jaundice or severe cholestatic itching (including an increase in their manifestations during a previous pregnancy or while taking steroid drugs);
Otosclerosis (including its exacerbation during pregnancy);
Hypersensitivity to estradiol and / or other components of the drug.
With caution: bronchial asthma, migraine, epilepsy, arterial hypertension, heart failure, ischemic heart disease, liver and / or kidney failure, edematous syndrome, endometriosis, fibrocystic mastopathy, porphyria. Experience in women over 65 years of age is limited.
Divigel should not be applied to the mammary glands, face, genital area, as well as to irritated skin.
Use during pregnancy and lactation.
Divigel is contraindicated for use during pregnancy and lactation.
Special instructions for the use of Divigel.
A complete personal and family history should be taken before initiating or reinitiating hormone replacement therapy. A medical examination should be carried out to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
In the process of treatment, it is recommended to conduct periodic examinations, the frequency and set of methods included in it are determined for each specific case individually. Studies, including mammography, should be carried out in accordance with accepted standards and taking into account individual clinical features in each individual case.
During HRT, all the benefits and risks of therapy should be carefully evaluated.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were observed earlier and / or worsened during pregnancy or previous hormonal therapy: leiomyoma (uterine fibromyoma), endometriosis; thromboembolic diseases in history or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; abnormal liver function (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; a history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis. It should be borne in mind that during treatment with Divigel, in rare cases, a relapse or exacerbation of the listed diseases is possible.
Therapy should be stopped immediately if contraindications are found and / or in the following situations: jaundice or deterioration in liver function; pronounced increase in blood pressure; new attacks of migraine-like headache; pregnancy.
When taking estrogens for a long time, the risk of developing endometrial hyperplasia and carcinoma increases. To reduce the risk, it is necessary to combine estrogen therapy in women with an unoperated uterus with progesterone for at least 12 days during the treatment cycle.
In the event of breakthrough bleeding and / or scanty spotting after several months of taking Divigel, studies should be carried out to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
Women with a uterus removed due to endometriosis (especially in cases of residual endometriosis) are recommended to add progesterone to estrogen-dependent therapy, due to premalignant or malignant transformation of endometriosis foci during estrogen stimulation.
With prolonged use of HRT, the risk of developing breast cancer increases. According to epidemiological studies among women aged 50 to 70 years, 45 cases out of 1000 are diagnosed with breast cancer. It has been established that among women taking or recently taking HRT, the total number of additional cases of breast cancer in the corresponding period is 1-3 (on average - 2) additional cases per 1000 people receiving HRT for 5 years; 3-9 (average - 6) cases per 1000 people receiving HRT for 10 years and 5-20 (average - 12) cases per 1000 women receiving HRT for 15 years. An increase in this risk was found mainly in women of thin or normal build. In women of full build (high predisposition to breast cancer), HRT does not additionally increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with an increase in the duration of HRT and returns to baseline approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT causes a similar or higher risk compared to estrogen therapy.
In women who received HRT, the risk of developing thromboembolic vein diseases (thrombosis of deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The probability is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications are: individual or family history, severe obesity (body mass index over 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriage should be further investigated to rule out a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for thrombophlebitis and the start of anticoagulant therapy. The risk increases with prolonged immobilization, extensive trauma, or major surgery. HRT should be discontinued 4-6 weeks before planned abdominal surgery or orthopedic surgery on the lower extremities. Treatment can be resumed after full recovery of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), HRT may need to be discontinued.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to an increase in the level of estradiol and its metabolites in the blood.
Estrogens increase insulin sensitivity and increase its excretion. Patients with diabetes mellitus in the first months of HRT shows constant monitoring of blood glucose levels.
Estrogen use increases the risk of surgically confirmed gallstone disease.
In rare cases, a sharp increase in the level of triglycerides in the blood while taking estrogen may develop pancreatitis.
Estrogens increase thyroid-binding globulin levels, increasing total circulating thyroid hormone levels.
Avoid getting the gel on the mammary glands and mucous membranes of the vulva and vagina.
Influence on the ability to drive vehicles and control mechanisms
Divigel therapy does not affect the ability to engage in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Drug overdose:
Symptoms: pain in the mammary glands or in the pelvic region, bloating, anxiety, irritability, nausea, vomiting, and in some cases metrorrhagia.
Treatment: symptomatic therapy.
Symptoms disappear when the dose is reduced or the drug is discontinued.
Interaction Divigel with other drugs.
Estradiol increases the effectiveness of lipid-lowering agents; weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants; reduces glucose tolerance (dose adjustment of hypoglycemic drugs).
The metabolism of estradiol is accelerated when taken simultaneously with barbiturates, tranquilizers (anxiolytics), opioid analgesics, anesthetics, some antiepileptic drugs (carbamazepine, phenytoin), inducers of microsomal liver enzymes; herbal preparations containing St. John's wort (St. John's wort).
The concentration of estradiol in the blood also decreases with the simultaneous use of phenylbutazone and certain antibiotics (ampicillin, rifampicin, rifabutin) and antiviral drugs (nevirapine, efavirenz), which is associated with changes in the intestinal microflora.
The action of estradiol increases against the background of taking folic acid and thyroid preparations.
Conditions of sale in pharmacies.
The drug is dispensed by prescription.
Terms of the storage conditions of the drug Divigel.
The drug should be stored at a temperature not exceeding 25°C. Shelf life - 3 years.
Keep out of reach of children.
Estrogen preparation for external use. The active ingredient, synthetic 17β-estradiol, is chemically and biologically identical to endogenous human estradiol (formed in the body of women from the first menstruation until menopause) produced by the ovaries. In the cells of organs to which the action of hormones is directed, estrogens form a complex with specific receptors (found in various organs - in the uterus, vagina, urethra, mammary gland, liver, hypothalamus, pituitary gland); the receptor-ligand complex interacts with the estrogen effector elements of the genome and specific intracellular proteins that induce the synthesis of mRNA, proteins and the release of cytokines and growth factors.
It 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 nipples and genitals, the formation of female secondary sexual characteristics, growth and closure of the epiphyses of long tubular bones. Promotes timely rejection of the endometrium and regular bleeding, in high concentrations causes endometrial hyperplasia, inhibits lactation, inhibits bone resorption, stimulates the synthesis of a number of transport proteins (thyroxine-binding globulin, transcortin, transferrin, sex hormone-binding protein), fibrinogen. It has a procoagulant effect, induces the synthesis in the liver of vitamin K-dependent coagulation factors (II, VII, IX, X), reduces the concentration of antithrombin III.
Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases the content of HDL, reduces LDL and cholesterol (the level of triglycerides increases). It modulates the sensitivity of progesterone receptors and sympathetic regulation of smooth muscle tone, stimulates the transition of intravascular fluid into tissues and causes a compensatory retention of sodium and water. In high doses, it prevents the degradation of endogenous catecholamines by competing for active COMT receptors.
After menopause, only a small amount of estradiol is formed in the body (from estrone located 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 (flushes of blood to the skin of the face), sleep disorders, and progressive atrophy of the genitourinary system.
Due to estrogen deficiency, osteoporosis develops (mainly of the spine). After oral administration, a greater amount of estradiol is metabolized in the lumen (by microflora) and the intestinal wall, as well as in the liver, before entering the bloodstream (leading to non-physiologically high plasma concentrations of estrone, and with long-term 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 estrogen causes an increase in protein synthesis (including renin), which leads to an increase in blood pressure.
Pharmacokinetics
Suction and distribution
When applying the gel, alcohol evaporates quickly, and estradiol penetrates the skin, while most of it enters the systemic circulation immediately, and some estradiol is retained in the subcutaneous tissue and released into the systemic circulation gradually. Application of Divigel to an area of 200-400 cm 2 (the size of one or two palms) does not affect the amount of absorbed estradiol. However, if Divigel is applied to a large area, the degree of absorption is significantly reduced.
The bioavailability of Divigel is 82%.
With transdermal use of Divigel at a dose of 1 mg of estradiol (1 g of Divigel), C max in blood plasma is approximately 157 pmol / l, the average concentration is 112 pmol / l, the minimum concentration is 82 pmol / l.
Does not accumulate.
Metabolism and excretion
Transdermal application avoids the first stage of hepatic metabolism, due to which fluctuations in the concentration of estrogen in the blood plasma when using Divigel are insignificant.
The metabolism of 17β-estradiol is similar to that of natural estrogens. In the blood, it almost completely binds to the carrier protein. It undergoes a "first pass" effect through the liver, where it is metabolized to less active products - estrone and estriol. It is excreted in the bile into the lumen of the small intestine and reabsorbed. Finally loses activity as a result of oxidation in the liver.
During treatment with Divigel, the estradiol / estrone ratio remains at the level of 0.4-0.7.
breeding
It is excreted mainly by the kidneys in the form of sulfates and glucuronides; small amounts of estradiol, estrone and estriol are also found in the urine.
Release form
Gel for external use 0.1% homogeneous, opalescent.
Excipients: carbomers (Carbopol 974R), trolamine, propylene glycol, ethanol 96%, purified water - up to 0.5 g.
0.5 g - multilayer sachets (28) - packs of cardboard.
0.5 g - multilayer sachets (91) - packs of cardboard.
Dosage
Divigel is prescribed for long-term and cyclic therapy. The initial dose, as a rule, is 1 g of gel (corresponding to 1 mg of estradiol) per day, but is determined by the severity of symptoms. Depending on the clinical picture, the dose can be changed after 2-3 cycles individually from 500 mg to 1.5 g of gel per day (which corresponds to 500 μg to 1.5 mg of estradiol per day).
Patients with an intact (non-operated) uterus during treatment with Divigel are recommended to prescribe a gestagen (for example, medroxyprogesterone acetate, norethisterone, norethisterone acetate or dihydrogesterone) for 10-12 days in each cycle. After a course of progestogen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, it is imperative to establish the cause of their occurrence.
In patients in the postmenopausal period, the duration of the cycle can be increased up to 3 months.
The gel is applied 1 time / day on clean skin of the lower part of the anterior wall of the abdomen, lumbar region, shoulders, forearms, or alternately on the right or left buttocks, alternating daily application sites. The application area 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 site of application of the gel should not be rinsed for 1 hour. Accidental contact with Divigel in the eyes should be avoided. Wash your hands immediately after applying the gel.
In case of skipping the next application of the gel, this should be done as soon as possible, but no later than within 12 hours from the moment the drug was applied according to the scheme. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. With irregular use of the drug (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Overdose
Symptoms: pain in the mammary glands or in the pelvic region, bloating, anxiety, irritability, nausea, vomiting, in some cases - metrorrhagia.
Treatment: symptomatic therapy.
Symptoms disappear when the dose is reduced or the drug is discontinued.
Interaction
Estradiol increases the effectiveness of lipid-lowering agents; weakens the effect of drugs of male sex hormones; hypoglycemic, diuretic, antihypertensive drugs and anticoagulants; reduces glucose tolerance (dose adjustment of hypoglycemic drugs).
The metabolism of estradiol is accelerated when taken simultaneously with barbiturates, tranquilizers (anxiolytics), opioid analgesics, anesthetics, some antiepileptic drugs (carbamazepine, phenytoin), inducers of microsomal liver enzymes; herbal preparations containing St. John's wort (St. John's wort).
The concentration of estradiol in the blood also decreases with the simultaneous use of phenylbutazone and certain antibiotics (ampicillin, rifampicin, rifabutin) and antiviral drugs (nevirapine, efavirenz), which is associated with changes in the intestinal microflora.
The action of estradiol increases against the background of taking folic acid and thyroid preparations.
Side effects
From the side of the central nervous system and peripheral nervous system: headache, migraine, dizziness, depression, chorea.
From the side of the cardiovascular system: increased blood pressure, thrombophlebitis.
From the digestive system: nausea, vomiting, stomach cramps, flatulence, pain in the epigastric region, cholestatic jaundice, cholelithiasis.
Allergic reactions: at the site of application - rash, skin irritation, skin hyperemia, contact dermatitis.
On the part of the reproductive system: metrorrhagia, scanty spotting, an increase in the size of uterine leiomyoma, endometrial hyperplasia (when prescribed without combination with progesterone), endometrial carcinoma (in women with an intact uterus after menopause), ovarian sclerosis with prolonged use, changes in libido.
From the endocrine system: engorgement (tension and / or enlargement) of the mammary glands, weight gain, decreased carbohydrate tolerance.
From the side of metabolism: retention of sodium, calcium and water (edema) with prolonged use; bouts of porphyria.
Others: visual impairment (change in the curvature of the cornea), chloasma, melasma, vaginal candidiasis.
Indications
- hormone replacement therapy for symptoms of estrogen deficiency;
- treatment of climacteric syndrome associated with natural or artificial menopause, which has developed as a result of surgical intervention.
Contraindications
- breast cancer (diagnosed, suspected or in history);
- diagnosed or suspected estrogen-dependent malignant tumors of the ovaries, uterus, endometrium;
- benign and malignant neoplasms of the genital organs (cancer of the cervix and body of the uterus, uterine fibroids, vulvar cancer, ovarian cancer) in women under the age of 60;
- benign neoplasms of the breast in women under the age of 60;
- vaginal bleeding of unknown etiology and a tendency to uterine bleeding;
- endometrial hyperplasia;
- pituitary tumors;
- diffuse connective tissue diseases;
- inflammatory diseases of the female genital organs (salpingoophoritis, endometritis);
- hyperestrogenic stage of menopause;
- spontaneous thromboembolic diseases of the veins (including history);
- deep vein thrombosis, pulmonary embolism (including history);
- thrombophlebitis and acute thrombophlebitis (including history);
- congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, Rotor syndromes);
- liver tumors (hemangioma, liver cancer);
- disorders of cerebral circulation (ischemic stroke, hemorrhagic stroke);
- diabetes mellitus, retinopathy, angiopathy;
- sickle cell anemia;
- disorders of fat metabolism;
- cholestatic jaundice or severe cholestatic itching (including an increase in their manifestations during a previous pregnancy or while taking steroid drugs);
- otosclerosis (including its exacerbation during pregnancy);
- hypersensitivity to estradiol and / or other components of the drug.
With caution: bronchial asthma, migraine, epilepsy, arterial hypertension, heart failure, ischemic heart disease, liver and / or kidney failure, edematous syndrome, endometriosis, fibrocystic mastopathy, porphyria. Experience in women over 65 years of age is limited.
Divigel should not be applied to the mammary glands, face, genital area, as well as to irritated skin.
Application features
Use during pregnancy and lactation
Divigel is contraindicated for use during pregnancy and lactation.Application for violations of liver function
Be wary appoint in liver failure.Application for violations of kidney function
Be wary appoint in renal failure.Use in elderly patients
Experience in women over 65 years of age is limited.special instructions
A complete personal and family history should be taken before initiating or reinitiating hormone replacement therapy. A medical examination should be carried out to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
In the process of treatment, it is recommended to conduct periodic examinations, the frequency and set of methods included in it are determined for each specific case individually. Studies, including mammography, should be carried out in accordance with accepted standards and taking into account individual clinical features in each individual case.
During HRT, all the benefits and risks of therapy should be carefully evaluated.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were observed earlier and / or worsened during pregnancy or previous hormonal therapy: leiomyoma (uterine fibromyoma), endometriosis; thromboembolic diseases in history or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; abnormal liver function (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; a history of endometrial hyperplasia; epilepsy; bronchial asthma; otosclerosis. It should be borne in mind that during treatment with Divigel, in rare cases, a relapse or exacerbation of the listed diseases is possible.
Therapy should be stopped immediately if contraindications are found and / or in the following situations: jaundice or deterioration in liver function; pronounced increase in blood pressure; new attacks of migraine-like headache; pregnancy.
When taking estrogens for a long time, the risk of developing endometrial hyperplasia and carcinoma increases. To reduce the risk, it is necessary to combine estrogen therapy in women with an unoperated uterus with progesterone for at least 12 days during the treatment cycle.
In the event of breakthrough bleeding and / or scanty spotting after several months of taking Divigel, studies should be carried out to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
Women with a uterus removed due to endometriosis (especially in cases of residual endometriosis) are recommended to add progesterone to estrogen-dependent therapy, due to premalignant or malignant transformation of endometriosis foci during estrogen stimulation.
With prolonged use of HRT, the risk of developing breast cancer increases. According to epidemiological studies among women aged 50 to 70 years, 45 cases out of 1000 are diagnosed with breast cancer. It has been established that among women taking or recently taking HRT, the total number of additional cases of breast cancer in the corresponding period is 1-3 (on average - 2) additional cases per 1000 people receiving HRT for 5 years; 3-9 (average - 6) cases per 1000 people receiving HRT for 10 years and 5-20 (average - 12) cases per 1000 women receiving HRT for 15 years. An increase in this risk was found mainly in women of thin or normal build. In women of full build (high predisposition to breast cancer), HRT does not additionally increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with an increase in the duration of HRT and returns to baseline approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT causes a similar or higher risk compared to estrogen therapy.
In women who received HRT, the risk of developing thromboembolic vein diseases (thrombosis of deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The probability is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications are: individual or family history, severe obesity (body mass index over 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriage should be further investigated to rule out a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for thrombophlebitis and the start of anticoagulant therapy. The risk increases with prolonged immobilization, extensive trauma, or major surgery. HRT should be discontinued 4-6 weeks before planned abdominal surgery or orthopedic surgery on the lower extremities. Treatment can be resumed after full recovery of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), HRT may need to be discontinued.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to an increase in the level of estradiol and its metabolites in the blood.
Estrogens increase insulin sensitivity and increase its excretion. Patients with diabetes mellitus in the first months of HRT shows constant monitoring of blood glucose levels.
Estrogen use increases the risk of surgically confirmed gallstone disease.
In rare cases, a sharp increase in the level of triglycerides in the blood while taking estrogen may develop pancreatitis.
Estrogens increase thyroid-binding globulin levels, increasing total circulating thyroid hormone levels.
Avoid getting the gel on the mammary glands and mucous membranes of the vulva and vagina.
Influence on the ability to drive vehicles and control mechanisms
Divigel therapy does not affect the ability to engage in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Expecting a baby brings a lot of joy to the expectant mother. But there are times when a woman’s body does not allow her to fully experience this happiness and get pregnant. We are talking about - an important hormone-sensitive tissue of the uterus. It is the endometrium that becomes the site of the introduction of the crumbs, here the embryo grows and develops.
The endometrium is normally maintained by the hormone estrogen, the main function of which is to prepare the lining of the uterus to receive a fertilized egg. If the endometrium is too thin, then the egg cannot "attach" to the uterus - and pregnancy does not occur. Doctors call this phenomenon hypoplasia and are detected by ultrasound. Fortunately, hypoplasia is not a verdict: the thickness of the endometrium can be increased with the help of drugs that compensate for the hormone deficiency of estrogen.
One of these drugs is Divigel. Its main active ingredient is synthetic estradiol, identical in biological and chemical properties to the natural female hormone. Estradiol is responsible for the development and functioning of the female genital organs and mammary glands, the regularity of the menstrual cycle, the synthesis of certain proteins, lowering cholesterol levels in the blood, and the normal functioning of the organs of the cardiovascular system.
Why appoint Divigel?
When planning a pregnancy, doctors prescribe Divigel only if a thin endometrium is diagnosed. After all, if a woman has hypoplasia, a fertilized egg cannot attach to the uterus. With an endometrial thickness of less than 5 mm, the chance of getting pregnant is only 1%.
The endometrium "gets fat" under the influence of the female hormones estrogen. They are produced by follicles at the end of the early follicular phase of the menstrual cycle. If the level of estrogen in the body increases, then the endometrium also grows. But in some cases, the maturation of the dominant follicle is disturbed and this becomes a prerequisite for hypoplasia. The endometrium simply has nowhere to come from.
To stimulate the growth of the endometrium, doctors prescribe the use of an artificial analogue of the hormone estrogen. "Divigel" increases the amount of estrogen, which in turn leads to a thickening of the endometrium. Also "Divigel" stimulates the development of the vagina, uterus, fallopian tubes, ducts of the mammary glands, promotes active growth and closure of the epiphyses of long bones. The drug increases the level of concentration in the blood of iron, copper, thyroxine, high density lipoproteins, reduces the amount of cholesterol.
This drug should only be taken if doctors diagnose you have hypoplasia. Do not self-medicate and do not take Divigel without the advice and recommendations of a doctor.
How does Divigel work when planning a pregnancy?
"Divigel" is available in the form of a gel and is prescribed once a day at the same time. The drug is applied in a small amount to the clean skin of the lower part of the anterior abdominal wall, on the shoulders, forearms, lower back or buttocks. The gel is rapidly absorbed within 1-2 minutes. But this area of \u200b\u200bthe skin can be wetted with water not earlier than in an hour or two. Be sure to wash your hands thoroughly after the procedure.
Do not experiment with gel doses: depending on the symptoms, only a doctor prescribes them. Do not apply the gel on the face, mammary glands, genital mucosa and irritated skin. If for some reason you have not applied the gel within 12 hours, then the procedure should be carried out the next day. If 12 hours has not yet passed, rub the gel into the skin as soon as possible. Frequent missed "sessions" of "Divigel" can cause uterine bleeding.
"Divigel" starts to act very quickly. Part of the drug enters the bloodstream through the skin, part is gradually released from the subcutaneous tissue. The effect of the gel may be enhanced if you are taking medications containing thyroid hormones and. Divigel is also well absorbed in combination with analgesics, barbiturates, anesthetics, preparations with St. John's wort extract. But phenylbutazone and some types of antibiotics reduce the intensity of the effect of the gel.
Divigel: drug contraindications
In addition to the quick effect, "Divigel" has many contraindications. You should not take risks and experiment, self-medicate, because this can lead to a negative outcome. Do not take this drug if you have:
- mammary cancer;
- pituitary tumor;
- benign and malignant tumors of the genital organs;
- inflammatory diseases of the female reproductive system (endometritis, salpingitis, oophoritis);
- uterine bleeding;
- tendency to thrombosis;
- endometrial hyperplasia;
- lipid metabolism disorders;
- acute and chronic liver diseases;
- severe circulatory disorders in the brain (strokes);
- hypersensitivity to the components of the drug;
- pregnancy;
- lactation period.
Use the gel with extreme caution in bronchial asthma, epilepsy, migraine, arterial hypertension, edematous syndrome, as well as in heart, liver and kidney failure. You can use "Divigel" only after this drug has been prescribed to you by a doctor. Self-medication or inappropriate treatment can lead to complications.
Side effects of Divigel
With proper treatment, the drug rarely leads to side effects. But one should take into account the fact that Divigel is a hormonal agent, and therefore certain changes in the body cannot be avoided.
In some cases, when taking Divigel, patients may complain of headaches, unplanned vaginal bleeding, and nausea. In a woman, the mammary glands swell, body weight increases, blood pressure rises, a rash appears, irritation and dermatitis of the skin at the site of rubbing the gel. Treatment with the drug can cause thrombophlebitis, depression.
Sometimes there is vomiting, flatulence, stomach cramps. Worse, when the patient develops cholestatic jaundice, gallstones form. If you already have a tumor, Divigel will only increase its growth. With prolonged use, calcium, sodium and water retention is possible. As a result, edema appears. Visual disturbances, chloasma, melasma are also possible.
In case of an overdose of the drug, bloating, nausea, vomiting, irritability and anxiety occur. Also, women experience acute pain in the mammary glands and in the pelvic area.
If, when planning a pregnancy, the doctor prescribed Divigel to you, carefully follow the instructions for using the drug. This gel is really capable of a miracle, but if used incorrectly and improperly, it can play a cruel joke on you. Therefore, take seriously all the recommendations of a gynecologist, do not self-medicate and gain patience, strength and endurance. And then you will definitely give birth to a healthy baby!
Especially for Nadezhda Zaitseva
Divigel is an anti-climacteric estrogenic drug used for symptoms of estrogen deficiency. The active ingredient of the drug, synthetic estradiol, is able to stimulate the development of the fallopian tubes and uterus. During menopause, due to an insufficient amount of estrogen, sleep disorders, osteoporosis of the spine, and atrophy of the organs of the genitourinary system are noted. External use of the drug does not cause an increase in blood pressure, as is the case with oral medications.
