Divigel side effects. Composition and action
In this article you can read the instructions for use of the drug Divigel. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Divigel in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Divigel 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 breastfeeding.
Divigel- estrogen preparation for external use. The active ingredient is synthetic 17beta-estradiol, 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 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.
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 (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 HDL content, reduces LDL and cholesterol (triglyceride levels increase). 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 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 produced in the body (from estrone found in the liver and adipose tissue). A decrease in the content of estradiol produced in the ovaries is accompanied in many women by vasomotor and thermoregulatory instability (flushes to the facial skin), sleep disorders, as well as progressive atrophy of the genitourinary system.
Osteoporosis (mainly of the spine) develops due to estrogen deficiency. After oral administration, larger amounts of estradiol are metabolized in the lumen (microflora) and wall of the intestine, as well as in the liver, before entering the bloodstream (leading to non-physiologically high concentrations of estrone in plasma, and with long-term therapy, to the accumulation of estrone and estrone sulfate) . The consequences of the accumulation of these metabolites in the body over a long period of 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.
Compound
Estradiol (in the form of hemihydrate) + excipients.
Pharmacokinetics
When the gel is applied, the alcohol quickly evaporates and estradiol penetrates the skin, with most of it entering the systemic circulation immediately, and a certain amount of estradiol is retained in the subcutaneous tissue and is 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 that develops as a result of surgical intervention.
Release forms
Gel for external use (transdermal) 0.1% (sometimes mistakenly called ointment).
Instructions for use and method of use
Divigel is prescribed for long-term and cyclic therapy. The initial dose is usually 1 g of gel (corresponding to 1 mg 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 mcg to 1.5 mg of estradiol per day).
For patients with an intact (unoperated) uterus, during treatment with Divigel it is 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 gestagen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, the cause of its occurrence must be determined.
In postmenopausal patients, the cycle duration can be increased to 3 months.
The gel is applied once a day to clean skin of the lower part of the anterior abdominal wall, lumbar region, shoulders, forearms, or alternately to the right or left buttocks, alternating the application sites daily. 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 (2-3 minutes).
The area where the gel is applied should not be rinsed for 1 hour. Accidental contact of Divigel with the eyes should be avoided. You should wash your hands immediately after applying the gel.
If you miss the next application of the gel, you should do so as soon as possible, but no later than within 12 hours from the moment of applying the drug according to the regimen. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. If the drug is not used regularly (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Side effect
- headache;
- migraine;
- dizziness;
- depression;
- increased blood pressure;
- thrombophlebitis;
- nausea, vomiting;
- stomach colic;
- flatulence;
- pain in the epigastric region;
- rash;
- skin irritation;
- skin hyperemia;
- contact dermatitis;
- scanty bleeding;
- increase in the size of uterine leiomyomas;
- endometrial hyperplasia (when prescribed without combination with progesterone);
- endometrial carcinoma (in women with an intact uterus after menopause);
- ovarian sclerosis with long-term use;
- change in libido;
- engorgement (tension and/or enlargement) of the mammary glands;
- weight gain;
- visual impairment (change in corneal curvature);
- chloasma;
- vaginal candidiasis.
Contraindications
- 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 (cervical and uterine cancer, uterine fibroids, vulvar cancer, ovarian cancer) in women under 60 years of age;
- benign breast tumors in women under 60 years of age;
- 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 a 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);
- cerebrovascular accidents (ischemic stroke, hemorrhagic stroke);
- diabetes mellitus, retinopathy, angiopathy;
- sickle cell anemia;
- disorders of fat metabolism;
- cholestatic jaundice or severe cholestatic itching (including increased 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, or to irritated areas of the skin.
Use during pregnancy and breastfeeding
Divigel is contraindicated for use during pregnancy and lactation.
Use in elderly patients
Experience with women over 65 years of age is limited.
special instructions
A complete personal and family history should be obtained before starting or restarting hormone replacement therapy (HRT). A medical examination should be conducted to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
During the treatment process, 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 characteristics in each individual case.
During HRT, all benefits and risks of therapy should be carefully assessed.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were previously observed and/or aggravated during pregnancy or previous hormonal therapy: leiomyoma (uterine fibroids), endometriosis; history of thromboembolic diseases or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; liver dysfunction (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; 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 of liver function; pronounced increase in blood pressure; new attacks of migraine-like headaches; 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.
If breakthrough bleeding and/or scanty spotting occurs after several months of taking Divigel, studies should be conducted to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
For women with a uterus removed due to endometriosis (especially in cases of residual endometriosis), the addition of progesterone to estrogen-dependent therapy is recommended, due to premalignant or malignant transformation of endometriosis foci with estrogen stimulation.
Long-term use of HRT increases the risk of developing breast cancer. An increase in this risk was found mainly in women of thin or normal build. In women of full build (high susceptibility to breast cancer), HRT does not further increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with increasing duration of HRT use and returns to baseline within approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT carries a similar or higher risk compared to estrogen therapy.
In women receiving HRT, the risk of developing venous thromboembolic diseases (thrombosis of the deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The likelihood is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications: individual or family history, severe obesity (body mass index more than 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriages should undergo additional studies to exclude a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for the development of thrombophlebitis and the initiation of anticoagulant therapy. The risk increases with prolonged immobilization, major 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 complete restoration of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), discontinuation of HRT may be required.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to increased levels of estradiol and its metabolites in the blood.
Estrogens increase sensitivity to insulin and increase its excretion. For patients with diabetes mellitus, constant monitoring of blood glucose levels is indicated in the first months of HRT.
Taking estrogen increases the risk of surgically confirmed cholelithiasis.
In rare cases of a sharp increase in the level of triglycerides in the blood while taking Divigel, pancreatitis may develop.
Estrogens increase levels of thyroid binding globulin, increasing the level of total circulating thyroid hormones.
Avoid contact of the gel with the mammary glands and mucous membranes of the vulva and vagina.
Impact on the ability to drive vehicles and operate machinery
Therapy with Divigel does not affect the ability to engage in potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Drug interactions
Estradiol increases the effectiveness of lipid-lowering drugs; weakens the effect 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 the herb St. John's wort (St. John's herb).
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 intestinal microflora.
The effect of estradiol increases when taking folic acid and thyroid medications.
Analogues of the drug Divigel
Structural analogues of the active substance:
- Dermestril;
- Klimara;
- Estrimax;
- Estrogel;
- Estrofem.
Analogs by pharmacological group (estrogens and gestagens):
- Gynepristone;
- Gynoflor E;
- Dailla;
- Depo Provera;
- Jess;
- Jess Plus;
- Diana is 35;
- Divina;
- Dimia;
- Duphaston;
- Eura;
- Janine;
- Individual;
- Claira;
- 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;
- Ethinyl estradiol;
- Yarina;
- Yarina Plus.
If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.
Estrogen preparation for external use.
Drug: DIVIGEL
Active substance of the drug:
estradiol
ATX coding: G03CA03
KFG: Antimenopausal estrogen drug
Registration number: P No. 015526/01
Registration date: 02.25.04
Owner reg. credential: 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 974P), trolamine, propylene glycol, ethanol 96%, purified water - up to 1 g.
Multilayer bags (28) - cardboard packs.
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 is synthetic 17-estradiol, 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 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.
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 (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 (II, VII, IX, X) in the liver, and reduces the concentration of antithrombin III.
Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases HDL content, reduces LDL and cholesterol (triglyceride levels increase). 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 retention of sodium and water. In large doses, it prevents the degradation of endogenous catecholamines by competing for active COMT receptors.
After menopause, only a small amount of estradiol is produced in the body (from estrone found in the liver and adipose tissue). A decrease in the content of estradiol produced in the ovaries is accompanied in many women by vasomotor and thermoregulatory instability (flushes to the facial skin), sleep disorders, as well as progressive atrophy of the genitourinary system.
Osteoporosis (mainly of the spine) develops due to estrogen deficiency. After oral administration, larger amounts of estradiol are metabolized in the lumen (microflora) and intestinal wall, as well as in the liver, before entering the bloodstream (leading to non-physiologically high concentrations of estrone in plasma, and with long-term therapy, to the accumulation of estrone and estrone sulfate) . The consequences of the accumulation of these metabolites in the body over a long period of 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.
Pharmacokinetics of the drug.
Suction and distribution
When the gel is applied, the alcohol quickly evaporates and estradiol penetrates the skin, with most of it entering the systemic circulation immediately, and a certain amount of estradiol is retained in the subcutaneous tissue and is 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 over 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 is almost completely bound 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 with 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 0.4-0.7.
Removal
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 climacteric syndrome associated with natural or artificial menopause that develops as a result of surgical intervention.
Dosage and method of administration of the drug.
Divigel is prescribed for long-term and cyclic therapy. The initial dose is usually 1 g of gel (corresponding to 1 mg 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 mcg to 1.5 mg of estradiol per day).
For patients with an intact (unoperated) uterus, during treatment with Divigel it is recommended to prescribe a gestagen (for example, medroxyprogesterone acetate, norethisterone, norethisterone acetate or dihydrogestron) for 10-12 days in each cycle. After a course of gestagen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, the cause of its occurrence must be determined.
In postmenopausal patients, the cycle duration can be increased to 3 months.
The gel is applied 1 time/day to clean skin of the lower part of the anterior abdominal wall, lumbar region, shoulders, forearms, or alternately to the right or left buttocks, alternating the application sites daily. 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 (2-3 minutes).
The area where the gel is applied should not be rinsed for 1 hour. Accidental contact of Divigel with the eyes should be avoided. You should wash your hands immediately after applying the gel.
If you miss the next application of the gel, you should do so as soon as possible, but no later than within 12 hours from the moment of applying the drug according to the regimen. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. If the drug is not used regularly (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Side effects of Divigel:
From the central nervous system and peripheral nervous system: headache, migraine, dizziness, depression, chorea.
From the cardiovascular system: increased blood pressure, thrombophlebitis.
From the digestive system: nausea, vomiting, stomach colic, flatulence, pain in the epigastric region, cholestatic jaundice, cholelithiasis.
Allergic reactions: at the site of application - rash, skin irritation, skin hyperemia, contact dermatitis.
From the reproductive system: metrorrhagia, scanty bleeding, increased 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 long-term use, changes in libido.
From the endocrine system: engorgement (tension and/or enlargement) of the mammary glands, weight gain, decreased tolerance to carbohydrates.
Metabolism: sodium, calcium and water retention (edema) with prolonged use; attacks of porphyria.
Other: visual impairment (changes in corneal curvature), 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 (cervical and uterine cancer, uterine fibroids, vulvar cancer, ovarian cancer) in women under 60 years of age;
Benign neoplasms of the mammary gland in women under 60 years of age;
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 a 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);
Cerebrovascular accidents (ischemic stroke, hemorrhagic stroke);
Diabetes mellitus, retinopathy, angiopathy;
Sickle cell anemia;
Fat metabolism disorders;
Cholestatic jaundice or severe cholestatic itching (including increased 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, edema syndrome, endometriosis, fibrocystic mastopathy, porphyria. Experience with women over 65 years of age is limited.
Divigel should not be applied to the mammary glands, face, genital area, or to irritated areas of the skin.
Use during pregnancy and lactation.
Divigel is contraindicated for use during pregnancy and lactation.
Special instructions for use of Divigel.
A complete personal and family history should be obtained before starting or restarting hormone replacement therapy. A medical examination should be conducted to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
During the treatment process, 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 characteristics in each individual case.
During HRT, all benefits and risks of therapy should be carefully assessed.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were previously observed and/or aggravated during pregnancy or previous hormonal therapy: leiomyoma (uterine fibroids), endometriosis; history of thromboembolic diseases or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; liver dysfunction (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; 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 of liver function; pronounced increase in blood pressure; new attacks of migraine-like headaches; 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.
If breakthrough bleeding and/or scanty spotting occurs after several months of taking Divigel, studies should be conducted to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
For women with a uterus removed due to endometriosis (especially in cases of residual endometriosis), the addition of progesterone to estrogen-dependent therapy is recommended, due to premalignant or malignant transformation of endometriosis foci with estrogen stimulation.
Long-term use of HRT increases the risk of developing breast cancer. According to epidemiological studies among women aged 50 to 70 years, breast cancer is diagnosed in 45 cases out of 1000. It has been established that among women taking or recently taking HRT, the total number of additional cases of breast cancer during 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 susceptibility to breast cancer), HRT does not further increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with increasing duration of HRT use and returns to baseline within approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT carries a similar or higher risk compared to estrogen therapy.
In women receiving HRT, the risk of developing venous thromboembolic diseases (thrombosis of the deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The likelihood is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications: individual or family history, severe obesity (body mass index more than 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriages should undergo additional studies to exclude a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for the development of thrombophlebitis and the initiation of anticoagulant therapy. The risk increases with prolonged immobilization, major 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 complete restoration of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), discontinuation of HRT may be required.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to increased levels of estradiol and its metabolites in the blood.
Estrogens increase sensitivity to insulin and increase its excretion. For patients with diabetes mellitus, constant monitoring of blood glucose levels is indicated in the first months of HRT.
Taking estrogen increases the risk of surgically confirmed cholelithiasis.
In rare cases of a sharp increase in triglyceride levels in the blood while taking estrogen, pancreatitis may develop.
Estrogens increase levels of thyroid binding globulin, increasing the level of total circulating thyroid hormones.
Avoid contact of the gel with the mammary glands and mucous membranes of the vulva and vagina.
Impact on the ability to drive vehicles and operate machinery
Therapy with Divigel 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 pelvic area, bloating, anxiety, irritability, nausea, vomiting, and in some cases, metrorrhagia.
Treatment: symptomatic therapy.
Symptoms disappear when the dose is reduced or when the drug is discontinued.
Interaction of Divigel with other drugs.
Estradiol increases the effectiveness of lipid-lowering drugs; weakens the effect 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 the herb St. John's wort (St. John's herb).
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 intestinal microflora.
The effect of estradiol increases when taking folic acid and thyroid medications.
Terms of sale in pharmacies.
The drug is available with a prescription.
Terms of storage conditions for the drug Divigel.
The drug should be stored at a temperature not exceeding 25°C. Shelf life: 3 years.
Keep out of the reach of children.
Estrogen preparation for external use. The active ingredient is synthetic 17β-estradiol, 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 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.
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 (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 (II, VII, IX, X) in the liver, and reduces the concentration of antithrombin III.
Increases blood concentrations of thyroxine, iron, copper. It has an anti-atherosclerotic effect, increases HDL content, reduces LDL and cholesterol (triglyceride levels increase). 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 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 produced in the body (from estrone found in the liver and adipose tissue). A decrease in the content of estradiol produced in the ovaries is accompanied in many women by vasomotor and thermoregulatory instability (flushes to the facial skin), sleep disorders, as well as progressive atrophy of the genitourinary system.
Osteoporosis (mainly of the spine) develops due to estrogen deficiency. After oral administration, larger amounts of estradiol are metabolized in the lumen (microflora) and wall of the intestine, as well as in the liver, before entering the bloodstream (leading to non-physiologically high concentrations of estrone in plasma, and with long-term therapy, to the accumulation of estrone and estrone sulfate) . The consequences of the accumulation of these metabolites in the body over a long period of 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.
Pharmacokinetics
Suction and distribution
When the gel is applied, the alcohol quickly evaporates and estradiol penetrates the skin, with most of it entering the systemic circulation immediately, and a certain amount of estradiol is retained in the subcutaneous tissue and is 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 over 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 17β-estradiol is similar to that of natural estrogens. In the blood it is almost completely bound 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 with 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 0.4-0.7.
Removal
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 bags (28) - cardboard packs.
0.5 g - multilayer bags (91) - cardboard packs.
Dosage
Divigel is prescribed for long-term and cyclic therapy. The initial dose is usually 1 g of gel (corresponding to 1 mg 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 mcg to 1.5 mg of estradiol per day).
For patients with an intact (unoperated) uterus, during treatment with Divigel it is 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 gestagen, menstrual-like bleeding should occur. In case of extraordinary or prolonged uterine bleeding, the cause of its occurrence must be determined.
In postmenopausal patients, the cycle duration can be increased to 3 months.
The gel is applied 1 time/day to clean skin of the lower part of the anterior abdominal wall, lumbar region, shoulders, forearms, or alternately to the right or left buttocks, alternating the application sites daily. 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 (2-3 minutes).
The area where the gel is applied should not be rinsed for 1 hour. Accidental contact of Divigel with the eyes should be avoided. You should wash your hands immediately after applying the gel.
If you miss the next application of the gel, you should do so as soon as possible, but no later than within 12 hours from the moment of applying the drug according to the regimen. If more than 12 hours have passed, then the use of Divigel should be postponed until the next time. If the drug is not used regularly (missed doses), menstrual-like uterine breakthrough bleeding may occur.
Overdose
Symptoms: pain in the mammary glands or pelvic area, bloating, anxiety, irritability, nausea, vomiting, and in some cases, metrorrhagia.
Treatment: symptomatic therapy.
Symptoms disappear when the dose is reduced or when the drug is discontinued.
Interaction
Estradiol increases the effectiveness of lipid-lowering drugs; weakens the effect 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 the herb St. John's wort (St. John's herb).
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 intestinal microflora.
The effect of estradiol increases when taking folic acid and thyroid medications.
Side effects
From the central nervous system and peripheral nervous system: headache, migraine, dizziness, depression, chorea.
From the cardiovascular system: increased blood pressure, thrombophlebitis.
From the digestive system: nausea, vomiting, stomach colic, flatulence, pain in the epigastric region, cholestatic jaundice, cholelithiasis.
Allergic reactions: at the site of application - rash, skin irritation, skin hyperemia, contact dermatitis.
From the reproductive system: metrorrhagia, scanty bleeding, increased 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 long-term use, changes in libido.
From the endocrine system: engorgement (tension and/or enlargement) of the mammary glands, weight gain, decreased tolerance to carbohydrates.
Metabolism: sodium, calcium and water retention (edema) with prolonged use; attacks of porphyria.
Other: visual impairment (changes in corneal curvature), chloasma, melasma, vaginal candidiasis.
Indications
- hormone replacement therapy for symptoms of estrogen deficiency;
- treatment of climacteric syndrome associated with natural or artificial menopause that develops as a result of surgical intervention.
Contraindications
- 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 (cervical and uterine cancer, uterine fibroids, vulvar cancer, ovarian cancer) in women under 60 years of age;
- benign breast tumors in women under 60 years of age;
- 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 a 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);
- cerebrovascular accidents (ischemic stroke, hemorrhagic stroke);
- diabetes mellitus, retinopathy, angiopathy;
- sickle cell anemia;
- disorders of fat metabolism;
- cholestatic jaundice or severe cholestatic itching (including increased 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, edema syndrome, endometriosis, fibrocystic mastopathy, porphyria. Experience with women over 65 years of age is limited.
Divigel should not be applied to the mammary glands, face, genital area, or to irritated areas of the skin.
Features of application
Use during pregnancy and breastfeeding
Divigel is contraindicated for use during pregnancy and lactation.Use for liver dysfunction
Prescribe with caution in case of liver failure.Use for renal impairment
Prescribe with caution in case of renal failure.Use in elderly patients
Experience with women over 65 years of age is limited.special instructions
A complete personal and family history should be obtained before starting or restarting hormone replacement therapy. A medical examination should be conducted to identify possible contraindications and observe the necessary precautions when using the drug (including the pelvic organs and mammary glands).
During the treatment process, 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 characteristics in each individual case.
During HRT, all benefits and risks of therapy should be carefully assessed.
The patient should be under constant medical supervision in case of any of the following diseases or conditions that were previously observed and/or aggravated during pregnancy or previous hormonal therapy: leiomyoma (uterine fibroids), endometriosis; history of thromboembolic diseases or risk factors for their occurrence; risk factors for estrogen-dependent tumors (1st degree of heredity of breast cancer); arterial hypertension; liver dysfunction (adenoma); diabetes mellitus with or without vascular lesions; cholelithiasis; migraine and/or (severe) headache; systemic lupus erythematosus; 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 of liver function; pronounced increase in blood pressure; new attacks of migraine-like headaches; 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.
If breakthrough bleeding and/or scanty spotting occurs after several months of taking Divigel, studies should be conducted to identify the causes of their occurrence. Investigations may include endometrial biopsy (to rule out endometrial malignancy).
For women with a uterus removed due to endometriosis (especially in cases of residual endometriosis), the addition of progesterone to estrogen-dependent therapy is recommended, due to premalignant or malignant transformation of endometriosis foci with estrogen stimulation.
Long-term use of HRT increases the risk of developing breast cancer. According to epidemiological studies among women aged 50 to 70 years, breast cancer is diagnosed in 45 cases out of 1000. It has been established that among women taking or recently taking HRT, the total number of additional cases of breast cancer during 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 susceptibility to breast cancer), HRT does not further increase the risk of developing breast cancer.
An additional risk of developing breast cancer appears with increasing duration of HRT use and returns to baseline within approximately 5 years after stopping treatment.
Combined estrogen-progestogen HRT carries a similar or higher risk compared to estrogen therapy.
In women receiving HRT, the risk of developing venous thromboembolic diseases (thrombosis of the deep veins of the lower extremities and pulmonary veins) is increased by 2-3 times compared with women who did not receive HRT. The likelihood is higher in the first year of HRT than in subsequent years.
The main risk factors for thromboembolic complications: individual or family history, severe obesity (body mass index more than 30 kg/m2), systemic lupus erythematosus.
Patients with a history of thromboembolism or recent spontaneous miscarriages should undergo additional studies to exclude a predisposition to thrombophlebitis. The use of HRT in this case should be started after a full assessment of the risk factors for the development of thrombophlebitis and the initiation of anticoagulant therapy. The risk increases with prolonged immobilization, major 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 complete restoration of motor ability. With the development of thromboembolic symptoms (sudden chest pain, dyspnea), discontinuation of HRT may be required.
Estrogens cause fluid retention in the body. Patients with impaired renal function should be under constant medical supervision due to increased levels of estradiol and its metabolites in the blood.
Estrogens increase sensitivity to insulin and increase its excretion. For patients with diabetes mellitus, constant monitoring of blood glucose levels is indicated in the first months of HRT.
Taking estrogen increases the risk of surgically confirmed cholelithiasis.
In rare cases of a sharp increase in triglyceride levels in the blood while taking estrogen, pancreatitis may develop.
Estrogens increase levels of thyroid binding globulin, increasing the level of total circulating thyroid hormones.
Avoid contact of the gel with the mammary glands and mucous membranes of the vulva and vagina.
Impact on the ability to drive vehicles and operate machinery
Therapy with Divigel 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 become pregnant. We are talking about important hormonally sensitive tissue of the uterus. It is the endometrium that becomes the site of implantation of the baby; here the embryo grows and develops.
The endometrium is normally maintained by the hormone estrogen, the main function of which is to prepare the inner 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 is detected by ultrasound. Fortunately, hypoplasia is not a death sentence: the thickness of the endometrium can be increased with the help of drugs that compensate for the hormonal 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 blood cholesterol levels, and the normal functioning of the cardiovascular system.
Why is Divigel prescribed?
When planning pregnancy, doctors prescribe Divigel only if thin endometrium is diagnosed. After all, if a woman is diagnosed with hypoplasia, the fertilized egg cannot attach to the uterus. With an endometrial thickness of less than 5 mm, the chance of becoming pregnant is only 1%.
The endometrium “gets fat” under the influence of 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 disrupted and this becomes a prerequisite for hypoplasia. The endometrium simply has nowhere to come from.
To stimulate endometrial growth, doctors prescribe the use of an artificial analogue of the hormone estrogen. Divigel increases the amount of estrogen, which in turn leads to thickening of the endometrium. Divigel also stimulates the development of the vagina, uterus, fallopian tubes, mammary ducts, promotes active growth and closure of the epiphyses of long tubular bones. The drug increases the concentration of iron, copper, thyroxine, high-density lipoproteins in the blood, and reduces the amount of cholesterol.
This drug can only be taken if doctors diagnose you with hypoplasia. Do not self-medicate or take Divigel without consulting and recommending a doctor.
How does Divigel work when planning 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 clean skin of the lower part of the anterior abdominal wall, on the shoulders, forearms, lower back or buttocks. The gel is quickly absorbed within 1-2 minutes. But you can wet this area of skin with water no sooner than after an hour or two. After the procedure, be sure to wash your hands thoroughly.
Do not experiment with doses of the gel: depending on the symptoms, only the doctor prescribes them. Do not apply the gel to the face, mammary glands, genital mucosa and irritated areas of the skin. If for some reason you do not apply the gel within 12 hours, then the procedure should be carried out the next day. If 12 hours have not yet passed, rub the gel into the skin as soon as possible. Frequent missed sessions of Divigel can cause uterine bleeding.
"Divigel" begins to act very quickly. Part of the drug enters the bloodstream through the skin, while 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, and preparations with St. John's wort extract. But phenylbutazone and some types of antibiotics reduce the intensity of the effects of the gel.
Divigel: contraindications of the drug
In addition to the quick effect, Divigel has many contraindications. You should not take risks and experiment, or 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 (stroke);
- hypersensitivity to the components of the drug;
- pregnancy;
- lactation period.
Use the gel with extreme caution for bronchial asthma, epilepsy, migraine, arterial hypertension, edema syndrome, as well as for heart, liver and kidney failure. You can use Divigel only after this drug has been prescribed to you by a doctor. Self-medication or improper treatment can lead to complications.
Side effects of Divigel
When treated correctly, the drug rarely causes side effects. But one should take into account the fact that Divigel is a hormonal drug, and therefore certain changes in the body cannot be avoided.
In some cases, when taking Divigel, patients may complain of headaches, unscheduled vaginal bleeding, and nausea. A woman’s mammary glands swell, body weight increases, blood pressure rises, a rash, irritation and skin dermatitis appear at the site of rubbing the gel. Treatment with the drug can cause thrombophlebitis and depression.
Sometimes vomiting, flatulence, and stomach cramps appear. Worse, when the patient develops cholestatic jaundice, gallstones form. If you already have a tumor, Divigel will only enhance its growth. With prolonged use, calcium, sodium and water retention is possible. In this regard, swelling appears. Visual impairment, chloasma, and melasma are also possible.
An overdose of the drug causes bloating, nausea, vomiting, irritability and anxiety. Women also experience acute pain in the mammary glands and pelvic area.
If, when planning a pregnancy, your doctor prescribed you Divigel, carefully follow the instructions for using the drug. This gel is truly capable of miracles, but if used incorrectly and improperly, it can play a cruel joke on you. Therefore, take all the recommendations of the gynecologist seriously, do not self-medicate and have patience, strength and endurance. And then you will definitely give birth to a healthy baby!
Especially for Nadezhda Zaitseva
Divigel is an antimenopausal estrogen drug used for symptoms of estrogen deficiency. The active component of the drug, synthetic estradiol, can stimulate the development of the fallopian tubes and uterus. During menopause, due to insufficient amounts of estrogen, sleep disorders, spinal osteoporosis and atrophy of the genitourinary system are noted. External use of the drug does not cause an increase in blood pressure, as occurs in the case of taking oral medications.
