Estradiol

When ATH:
G03CA03

Characteristic.

Estradiol - hormonal estrogenic agent (17b-эстрадиол), identical эndogennomu эstradiolu, produced by the ovaries (formed in the body women, beginning the first menstrual period and ending with menopause). Synthetic estradiol - a white crystalline powder. Practically insoluble in water; easily soluble in alcohol; soluble in acetone, dioxane and other organic solvents; it is soluble in vegetable oils. Molecular weight 272,37.

In medical practice used in the form of estradiol hemihydrate and esters (benzoate, dipropionate).

Эstradiola benzoate - stable vozduhe; soluble in alcohol, acetone, dioksane, slightly soluble in ether, vegetable oils; molecular weight 376,49.

Estradiol dipropionate - a white crystalline powder, practically insoluble in water, it is soluble in alcohol and vegetable oils. Molecular weight 384,51.

Estradiol is used in various dosage forms: gely transdermalynыy, solution for the / m of oil, spray nazalynыy, tablets, coated, transdermalynaya terapevticheskaya system (TDTS).

Pharmacological action.
Estrogenic.

Application.

Estrogen deficiency in menopause and surgical menopause, incl. ovariectomized, radiation castration; primary and secondary amenorrhea, gipomenoreя, spanomenorrhea, dysmenorrhoea, secondary estrogen deficiency, alopecia in giperandrogenemii; hirsutism in polycystic ovary syndrome, vaginitis (in girls and in old age), gipogenitalizm, infertility, uterine inertia, prolonged pregnancy, to suppress lactation, virilnoe hypertrichosis in women; prevention of postmenopausal osteoporosis in women, Breast cancer in men and women with metastases (palliativnaya therapy), prostate carcinoma (palliativnaya therapy), urogenital disorders (dyspareunia, Atrophic vulvovaginitis, uretrit, tryhonyt); as a means of, stimulating hematopoiesis in men with acute radiation injury.

Contraindications.

Hypersensitivity, estrogen dependent neoplastic processes or are suspected, liver tumors (incl. history), drepanocytemia, herpes, otosclerosis (incl. aggravation during pregnancy), retinopathy or angiopathy, cholestatic jaundice or persistent itching (incl. strengthening their symptoms during a previous pregnancy or while taking steroids), gallbladder disease in history (especially cholelithiasis), unusual or undiagnosed genital or uterine bleeding (use of estrogen can inhibit the diagnosis), thrombophlebitis or thromboembolic condition in the active phase (except for treatment of breast or prostate); tromboflebit, thrombosis or thromboembolic condition, associated with taking estrogen (history); inflammatory diseases of the female genital organs (salpingo-oophoritis, endometritis); hypercalcemia, associated with bone metastases of breast cancer.

Only for the treatment of breast and prostate (additionally): diseases of the coronary or cerebral vessels, active thrombophlebitis or thromboembolic disease (High doses of estrogen, is used to treat, increase the risk of myocardial infarction, pulmonary vessels, tromboflebita).

Restrictions apply.

Bronchial asthma, diabetes, migraine, epilepsy, arterial hypertension, heart failure, CHD; renal failure; acute or chronic liver disease (incl. history) If you change the parameters of the functional liver samples, Hyperlipoproteinemia, edematous syndrome, endometriosis, shotty breast, porphyria, pituitary tumor, diffuse connective tissue disease, Dubin-Johnson or Rotor.

Pregnancy and breast-feeding.

Contraindicated in pregnancy, incl. alleged (Estrogens may have embryotoxic effects). The research shows the relationship of congenital malformations with the use of certain estrogen during pregnancy.

Category actions result in FDA - X. (Animal tests or clinical trials revealed a violation of the fetus and / or there is evidence of the risk of adverse effects on the human fetus, obtained in research or practice; risk, associated with the use of drugs in pregnancy, greater than the potential benefits.)

At the time of treatment must stop breastfeeding (estrogen passes into breast milk).

Side effects.

From the nervous system and sensory organs: dizziness, headache, migraine, depression, xoreja, blurred vision (change in the curvature of the cornea), discomfort while wearing contact lenses.

Cardio-vascular system and blood (hematopoiesis, hemostasis): increased blood pressure, thromboembolism.

From the digestive tract: nausea, vomiting (mainly central origin with high doses), epigastric pain, flatulence, diarrhea, anorexia, cholestatic jaundice, cholelithiasis, hepatitis, pancreatitis, kišečnaâ and how želčnaâ.

With the genitourinary system: women - bleeding "breakthrough", uterine bleeding of unknown etiology, the changing nature of uterine bleeding and spotting, metrorragija (Symptoms of overdose of estradiol), premenstrual syndrome, amenorrhea, dysmenorrhoea, increasing the size of the fibroids or uterine leiomyoma, changes in the cervical secretion, the changing nature of vaginal discharge, vaginal candidiasis, endometrial hyperplasia (the appointment without progestogen), cancer endometrio (postmenopausal women with an intact uterus), symptoms of cystitis (no bacterial contamination); long-term use - ovarian sclerosis; soreness, sensitivity and increase the size of the breast, increased libido; men - tenderness and sensitivity of the breast, gynecomastia, decreased libido.

For the skin: chloasma or melanodermiя, contact dermatitis, Hemorrhagic rash, uzlovataya эritema, erythema multiforme, alopecia, girsutizm, itchiness and redness of the skin (at the application site of the patch-TDTS).

Other: weight change, reduced tolerance to carbohydrates, worsening of porphyria, cramping calf muscles; long-term use - the metabolism of sodium, calcium and water to form peripheral edema.

Cooperation.

Estradiol reduces the activity of diuretics, antykoahulyantov, antihypertensive and hypoglycemic agents. It reduces glucose tolerance (may require correction dosing regimen hypoglycemic drugs). Estradiol increases the effectiveness of lipid-lowering drugs.

Inductors of microsomal liver enzymes, such as some anticonvulsants and antimicrobials (incl. hydantoins, barbiturates, prymydon, Carbamazepine, rifampicin), can accelerate the metabolism of estradiol, increase the clearance of sex hormones and reduce the clinical efficacy.

Folic acid and thyroid medications increase the effect of oestradiol. Substantial consumption of alcohol during treatment may lead to increased levels of circulating estradiol.

Overdose.

Symptoms: nausea, vomiting, in some cases - metrorrhagia.

Treatment: maintaining vital functions (against the background of drug withdrawal), simptomaticheskaya therapy.

Dosing and Administration.

Dose and duration of therapy is determined individually. Inside. Primary and secondary estrogen deficiency - 2 mg 1 once a day, every day without interruption. Treatment of women with hysterectomy or postmenopausal women can be started any day; when stored menstrual cycle, take the first pill on the 5th day of the menstrual cycle. Duration of treatment - 6 Months, and then carried out a survey to decide on whether to continue replacement estrogen therapy.

Locally. The gel is applied 1 once daily on the skin in the lower part of the abdominal wall, or turn to the right or the left buttock. The initial dose - 1 g gel (1 mg estradiol). The average dose - 0.5-1.5 g of gel per day. The area of ​​application is equal in magnitude 1-2 palms. Patch fasten 1 every week. Treatment is carried out continuously or 3-week course with a break in 1 Sun. In the presence of the uterus simultaneously administered progesterone each month within 10-12 days.

Intranasal, 1 once a day. The daily dose depends on the individual and, usually, It varies between 150 to 600 g, Initial - 300 mg / day, during therapy should pick up the minimum effective dose; depending on the therapeutic effect of the treatment dose reduced, or increase.

/ M, 0,1% dissolved in an oil of 1 ml 1 every 3-5 days.

Precautions.

Before the start of the application necessary to carry out a full general medical and gynecological examination, including a study of the abdomen and pelvis, Breast, measurement of blood pressure, Endometrial cytologic analysis. It is necessary to exclude pregnancy. When long-term therapy such testing should be performed every 6-12 months.

For 4-6 weeks before planned surgery and during prolonged immobilization is recommended to discontinue treatment in order to prevent thrombotic events.

The drug should be discontinued immediately in the following cases: deep vein thrombosis, thromboembolic disease, a significant increase in blood pressure, jaundice, the appearance of migraine headaches, sudden blurred vision.

While hormone replacement therapy in patients, hypertensive, should regularly monitor blood pressure.

In the initial period of treatment of patients with diabetes requires careful monitoring because of the possible reduction in glucose tolerance.

Changes in the level of estrogen in the blood can affect the performance of analyzes certain endocrine and liver function.

Estrogens can cause fluid retention, therefore, patients with impaired cardiac or renal function requires close monitoring.

Please inform your doctor about the same time taking barbiturates, fenilʙutazona, gidantoinov, rifampicin, the appearance of irregular bleeding or unusually heavy bleeding during the period between the use of the drug, discomfort in the epigastric region.

In case of irregular uterine bleeding during treatment should be carried out cytological analysis of the endometrium.

In the treatment should take into account, that long-term use only estrogen in menopause may lead to endometrial hyperplasia and increases the risk of endometrial cancer. To reduce the risk of endometrial cancer requires additional intake of progestogen (normally within 10-12 days per month), which leads to a transition endometrium in the secretory phase of its rejection and the subsequent menstrualnopodobnoe bleeding after cessation of progestogen. When irregular menses (in women with an intact uterus) during treatment with estradiol is necessary to conduct a diagnostic curettage to exclude malignancy of the uterus.

In postmenopausal women,, long are on hormone replacement therapy, increased risk of breast cancer. If the duration of treatment more 5 s need to carefully weigh the positive effects of the treatment of the adverse effects.

Patients, are on long-term treatment, need regular breast examination, incl. should teach them regular self. It should be particularly careful in appointing women to estrogen, or have had in the past knotty or fibrocystic breast changes of mammary glands. In such cases, careful monitoring and regular mammography.

Women, taking menopause estrogenic drugs, there is an increased risk of gallstone disease (Estrogens increase bile lithogenicity).

The drug is not a contraceptive and does not restore the ability to fertilize.

Do not place the patch on the breast or waist. If the patch is applied correctly, you can take a bath or shower, However, it should be taken into account, in hot water the patch may come off.

Avoid getting gel on the breast and the mucous membranes of the vulva and vagina.

Cooperation