Hormone replacement therapy is designed to treat only those climacteric symptoms that make the patient's daily life difficult. Evaluation of the benefit / risk of treatment with Revmelide® should be carried out throughout the course of treatment, periodic medical examinations should be conducted, the frequency of which is set individually, but at least once every 6 months, and which include measurement of blood pressure, examination of the mammary glands , abdominal and pelvic organs, gynecological examination (incl. analysis of cervical cervical smear and ultrasound to exclude endometrial hyperplasia). Surveys, including mammography, are carried out in accordance with the established order of preventive examination and clinical data of a particular patient.
The drug is administered only to women who have had their last menstruation at least 1 year ago.
The drug is not a contraceptive and does not protect against sexually transmitted diseases.
The drug is not intended for use by children.
Clinical experience in the use of the drug over the age of 65 is not enough.
Conditions requiring immediate cessation of treatment:
- jaundice or liver dysfunction;
- significant increase in blood pressure;
- the appearance of a migraine headache;
- Pregnancy.
Endometrial hyperplasia: the risk of developing hyperplasia and endometrial cancer is higher with prolonged use of estrogens as monotherapy. Periodic, for at least 12 days during the cycle, the additional prescription of progestogen to women who do not undergo hysterectomy significantly reduces the risk of the disease. In the first months of treatment, bleeding from the vagina or spotting can occur. If such bleeding occurs at later stages of treatment, or continues after cessation of it, a re-examination, possibly with endometrial biopsy, should be performed to exclude malignant neoplasm.
Mammary cancer: a randomized, placebo-controlled study of the WHI (Women's Health Initiative) and epidemiological studies, including MWS (Million Women Study), showed that there is an increased risk of developing breast cancer in women taking estrogens, estrogen-progestogen combinations or tibolone in the process of HRT for several years (see the "Side effect" section). In all cases of HRT, the risk becomes evident in the first years of treatment, which increases with the duration of treatment, but after the cessation of treatment for a few, often 5 years, returns to baseline.
During MWS, the relative risk of breast cancer associated with the administration of conjugated equine estrogens (CEE) or estradiol (E2) was higher when the progestogen was added either sequentially or permanently, regardless of the type of progestogen. The degree of risk was the same, regardless of the route of administration of the drug.
In the WHI study, the continuous administration of a combination of conjugated equine estrogen and medroxyprogesterone acetate (CEE + MRA) was associated with breast cancer cases, the number of which was slightly higher, and metastases to local lymph nodes occurred more frequently than in placebo.
In HRT, especially in the combination of estrogen with progestogen, there is an increase in the density of mammograms, which makes it difficult to detect breast cancer.
Venous thromboembolism: HRT is associated with a higher relative risk of venous thromboembolism (VTE), namely deep vein thrombosis or pulmonary thromboembolism. A two to threefold increase in the risk for patients who received HRT treatment in comparison with those who did not receive this course of treatment was found. It was found that for 1000 women aged 50-59 years who did not undergo HRT treatment, there are 3 cases of VTE occurring during a 5-year period, and at the age of 60-69 years - 8 cases per 1000 women. The estimated number of additional cases of VTE among healthy women aged 50-59 years who received HRT for 5 years is 2-6 (the most accurate estimate = 4) per 1000 women, and at the age of 60-69 years - 5-15 of cases (the most accurate estimate = 9) per 1000 women. The development of VTE is most likely in the first year of HRT, than in the following period.
Recognized risk factors for VTE include the presence of a disease in a personal or family history, severe obesity (body mass index greater than 30 kg / m), and systemic lupus erythematosus.
There is no consensus on the possible role of varicose veins in the development of VTE.
An increased risk of VTE occurs when there is a history of VTE or thrombophilia. HRT may increase the risk. If there is a history of thromboembolism or repeated cases of spontaneous abortion, a patient should be examined to exclude a predisposition to thrombophilia. The appointment of HRT to such women is contraindicated until a thorough evaluation of thrombophilic factors or anticoagulant treatment is initiated. It is necessary to carefully weigh the benefit / risk ratio of HRT in women who take anticoagulants.
The risk of VTE may temporarily increase with prolonged immobilization, extensive trauma or radical surgery. In the postoperative period careful attention should be given to preventive measures to prevent cases of VTE. When planning a surgical intervention involving prolonged immobilization of the patient, in particular with abdominal intervention or orthopedic surgery of the lower extremities,for 4-6 weeks before the operation should, if possible, temporarily suspend HRT.
Treatment should not be resumed until the woman has acquired full mobility. If VTE develops after the start of treatment, the drug should be discontinued. Patients should be warned about the need to immediately seek medical help in case of signs of VTE (painful edema of the lower limb, sudden chest pain, shortness of breath).
Cardiac ischemia. Randomized, controlled trials have not identified any benefits for the cardiovascular system of the continuous use of CEE + MPA. Two large clinical trials, the WHI and HERS (Heart and Estrogen / Progestin Replacement Study), showed the possibility of an increased risk of cardiovascular disease in the first year of combined treatment and the lack of benefits. Data from randomized, controlled trials using other HRT drugs to study effects that affect cardiovascular morbidity and mortality are limited. Thus, it remains to be seen whether these data are applicable to other HRT preparations.
Violation of cerebral circulation. Results of a large randomized clinical trial of WHI showed an increased risk of developing cerebral circulation disorders in healthy women who underwent continuous treatment with a combination of CEE + MRA. It has been established that in women who have not undergone HRT, the number of cases of cerebral circulation that may occur during 5 years is approximately 3 per 1,000 women aged 50-59 years and 11 cases per 1000 women aged 60-69 years . In those women who took conjugated estrogens with MPA for 5 years, the number of additional cases of cerebral circulation disorder ranges from 0 to 3 (the most accurate estimate is 1) per 1000 women aged 50-59 years and 1-9 cases per 1000 women aged 60-69 years (the most accurate estimate = 4).
Data on whether this increased risk for other HRT drugs are unknown.
Ovarian cancer. Long-term use (within 5-10 years) of only estrogen preparations for HRT in women with a distant uterus is associated in some epidemiological studies with an increased risk of developing ovarian cancer. It remains unclear,whether prolonged intake of combined HRT drugs increases the risk of ovarian cancer compared to the risk associated with the use of drugs containing only estrogen.
There is no conclusive evidence of improvement cognitive function. There is a study in the WHI that demonstrates the existence of a risk of developing dementia in women who, after age 65, have started taking a combination drug continuously containing CEE and MPA. It is not known whether this applies to women at a younger age in the postmenopausal state or to other HRT preparations.
Other states:
- Patients with diseases of the heart and kidneys require careful monitoring, because Estrogens can cause fluid retention in the body. In the terminal stage of renal failure, strict medical control should be provided due to a possible increase in the plasma concentrations of the active substances of the Rheumelide® preparation. Treatment of women with estrogen with anterior hypertriglyceridemia requires increased caution because of the danger of a significant increase in the concentration of triglycerides in the blood, followed by the development, in rare cases, of pancreatitis.
- Estrogens increase the concentration of thyroxine-binding globulin, which leads to an increase in the total concentration of circulating thyroid hormones, determined by the content of protein-bound iodine, the concentration of thyroxine (determined by column chromatography or radioimmunoassay) or triiodothyronine (determined by radioimmunological method). Concentrations of free thyroxin and triiodothyronine remain unchanged. Concentrations of other binding proteins of blood serum, including corticosteroid-binding globulin, globulin binding sex hormones, can increase, which leads to an increase in the concentration of circulating corticosteroids and sex hormones, respectively. Concentrations of free or biologically active hormones remain unchanged.
The drug is contraindicated for lactose intolerance.