Estrofem®
Treatment of estrogen-dependent postmenopausal symptoms with HRT should only be initiated in cases of their adverse impact on the woman’s quality of life. To assess the balance of benefits and risks from treatment with the drug, it is necessary to regularly, taking into account the individual characteristics of the patient, but at least once a year, conduct a medical examination using clinical and laboratory data. HRT should only be continued as long as the benefits outweigh the risks.
Medical examination/control
Before starting/resuming HRT, you should collect an anamnesis and study the patient’s medical history, conduct the necessary examination (including the pelvic organs and mammary glands), become familiar with contraindications and special precautions for using the drug. Women should be advised to report any changes in the mammary glands to a doctor or nurse for the purpose of timely further examination, incl. mammography.
Reasons for immediate discontinuation of treatment
Treatment should be discontinued if contraindications are identified and the following conditions occur:
- jaundice or liver dysfunction;
- significant increase in blood pressure;
- a new attack of migraine-type headache;
- pregnancy.
Endometrial hyperplasia
The risk of developing endometrial hyperplasia and carcinoma in women with an intact uterus increases with long-term estrogen monotherapy (see section “Side Effects”).
According to epidemiological studies, approximately 5 out of 1000 women aged 50-65 years who did not receive HRT may be diagnosed with endometrial cancer. While estrogen monotherapy, depending on its dose and duration of treatment, increases this risk by 2-12 times.
Adding a progestogen for at least 12 days each cycle significantly reduces this risk. You should also not use estradiol in a dose of more than 2 mg per day, even in combination with a progestogen.
During the first months of treatment, bleeding/spotting from the vagina is possible. However, if bleeding/spotting is observed after starting treatment or continues after discontinuation of the drug, you should immediately consult a doctor to rule out malignant changes in the endometrium.
Monotherapy with estrogen without progestogen can lead to precancer or malignancy of endometriosis.
Mammary cancer
Epidemiological studies and one randomized, placebo-controlled study within the framework of the Women's Right to Health (WHI) program have confirmed an increase in the risk of developing breast cancer depending on the duration of HRT with estrogens, estrogen-progestogen drugs or tibolone (see section "Side effects" ), however, it returns to its original state within several (maximum up to 5) years after cessation of treatment. According to the results of 51 epidemiological studies, incl. According to the epidemiological Million Women Study (MWS), the relative risk (RR) of developing breast cancer during estrogen-only HRT was 1.3-1.35.
The relative risk of breast cancer increases with the addition of a progestogen to estradiol, regardless of its type and mode of administration. According to the MWS results, compared with women who have never received HRT, the use of various types of combined (estrogen + progestogen) replacement therapy increases the risk of breast cancer (RR = 2), while with estrogen monotherapy RR = 1.3 . According to the WHI, for women receiving combined (estrogen + progestogen) HRT for 5.6 years, the relative risk of developing breast cancer compared with placebo was 1.24.
Absolute risk indicators calculated from MWS and WHI data are presented below. Thus, according to MWS, when assessing data on the incidence of breast cancer in women in developed countries, it was found that:
- approximately 32 out of 1000 women who have not undergone HRT will develop breast cancer, diagnosed between the ages of 50 and 64 years;
- per 1000 women undergoing or recently undergoing HRT, the number of additional cases of breast cancer will be:
- with estrogen replacement monotherapy: over 5 years - from 0 to 3 cases (average 1.5); within 10 years - from 3 to 7 cases (average 5);
- with combined (estrogen + progestogen) HRT: over 5 years - from 5 to 7 cases (on average 6); within 10 years - from 18 to 20 cases (average 19).
A WHI study found that 8 additional cases of breast cancer diagnosed among 1000 women aged 50-79 years after 5.6 years of follow-up could be attributed to combination therapy (conjugated equine estrogens (CEE) + medroxyprogesterone acetate (MPA)). Based on the results obtained, it was established that:
- When taking a placebo for 5 years, approximately 16 out of 1000 women may develop breast cancer;
- with combined (CLE + MPA) HRT over 5 years, the number of additional cases of breast cancer can range from 0 to 9 (on average 4) - per 1000 women;
- the number of additional cases of breast cancer per 1000 women starting or continuing combined (estrogen + progestogen) HRT is the same and does not depend on age at the time of initiation of use (age between 45 and 65 years).
There are no data on the existence of differences in the risk of developing breast cancer depending on the route of administration of the drug.
HRT, especially combined treatment (estrogen + progestogen), increases the density of nodes during mammography, which may have a negative effect on the timely diagnosis of breast cancer.
Venous thromboembolism
HRT is associated with a higher relative risk of developing venous thromboembolism (VTE) - deep vein thrombosis or pulmonary embolism. Studies have shown a 2-3 fold increase in the risk of VTE during HRT. It has been established that over a 5-year period in patients who have not undergone such treatment, the number of cases of VTE is approximately 3 per 1000 women aged 50-59 years and 8 per 1000 - at the age of 60-69 years. As a rough estimate, in healthy women who have completed a 5-year course of HRT, the number of additional cases of VTE over 5 years is 2-6 (average 4) per 1000 women aged 50-59 years and 5-15 (average 9 ) per 1000 women aged 60-69 years. The likelihood of VTE occurring is greater in the first year of HRT than in subsequent years. As a rule, risk factors for venous thromboembolism include a history of VTE (including in close relatives) and corresponding changes in the coagulogram, significant obesity (body mass index >30 kg/m2), and systemic lupus erythematosus. There is no consensus on the possible role of varicose veins in the development of VTE. HRT may increase this risk. It is necessary to analyze all cases of thromboembolism and/or spontaneous abortions in a personal or family history to exclude a predisposition to thrombophilia. Until an appropriate examination has been carried out, HRT is contraindicated.
Prescribing HRT to women taking anticoagulants is possible only taking into account the benefit/risk ratio of HRT use. The risk of VTE may temporarily increase with prolonged immobilization, including due to injury, surgery, or in the postoperative period. When planning operations, it is necessary to consider the advisability of stopping HRT 4-6 weeks before the intervention in each specific case. Treatment should not be resumed until the coagulogram is normalized and mobility is restored. If VTE develops after starting treatment, HRT should be discontinued. The patient should stop HRT and immediately inform her doctor if symptoms such as pain and/or swelling of the lower extremity, sudden chest pain, or shortness of breath appear.
Cardiac ischemia
The effectiveness of HRT for coronary heart disease has not been proven. Two large randomized controlled clinical trials showed a significant increase in the risk of cardiovascular disease in the first year of use of combined HRT (CLE + MPA). The results of clinical studies of other drugs for HRT are limited and contradictory.
Cerebrovascular accident
A large randomized clinical trial within the WHI found an increased risk of cerebrovascular accidents in healthy women when undergoing combined HRT (CLE + MPA). Thus, in the absence of HRT, the number of cases of cerebrovascular accident per 1000 women over 5 years was about 3 - at the age of 50-59 years and about 11 - at the age of 60-69 years. Per 1000 women who used conjugated estrogens and MPA for 5 years, the number of additional cases of cerebrovascular accident ranged from 0 to 3 (average 1) - at the age of 50-59 years and 1-9 (average 4) - at the age of 60 -69 years old. It is unknown whether this increased risk applies to other HRT products.
Ovarian cancer
The increased risk of ovarian cancer in women with a history of hysterectomy has been associated in some epidemiological studies with long-term (5-10 years) estrogen monotherapy with HRT. It remains unclear whether the risk of developing ovarian cancer increases with long-term use of combined (containing estrogen and progestogen) drugs for HRT, compared with that with estrogen monotherapy.
Other states
Estrogens can cause fluid retention in the body, which can worsen the condition of patients with impaired heart or kidney function. When taking Estrofem® in end-stage renal failure, the level of circulating active components increases.
Also, women with a history of hypertriglyceridemia are subject to careful examination and monitoring during HRT, since treatment with estrogen may significantly increase the content of triglycerides in plasma, leading to 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, thyroxine (by column chromatography or radioimmunoassay), triiodothyronine (by radioimmunoassay). The concentrations of free thyroxine and triiodothyronine remain unchanged.
Concentrations of other serum binding proteins may increase, incl. corticoid-binding globulin and sex hormone-binding globulins, which leads to increased concentrations of circulating corticosteroids and sex hormones. The concentrations of free or biologically active hormones do not change.
The concentration of other plasma proteins angiotensinogen/renin, alpha 1-antitrypsin, and ceruloplasmin may also increase.
There is insufficient evidence of improvement in cognitive function. Moreover, the WHI study showed an increased risk of possible dementia during combined (CLE + MPA) HRT in women over 65 years of age. It is unknown whether this applies to other HRT products and/or when HRT is given to younger postmenopausal women.
Estrofem® contains lactose. Patients with rare hereditary diseases - galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use this medication.
Estrofem
Orally, without chewing, with a small amount of liquid, 2 mg/day, for 21 days, followed by a break for 7 days, after which treatment is continued. The duration of treatment is up to 6 months, after which an examination is carried out to decide whether it is advisable to continue estrogen replacement therapy. In women with a uterus removed or in menopausal women, treatment with the drug can be started on any day. If the menstrual cycle is preserved, the first tablet should be taken on the 5th day of the cycle (1st day of the cycle = 1st day of menstruation).
IM, in the form of a 0.1% solution in oil: for primary amenorrhea with underdevelopment of the genital organs and secondary sexual characteristics - 1-2 mg daily or every other day for 1-2 months or more, until palpable enlargement of the uterus; after this - progesterone intramuscularly, 5 mg daily for 6-8 days. If necessary, repeat courses of hormone therapy are carried out. For secondary amenorrhea - 1 mg daily for 15-16 days, followed by progesterone or pregnin for 6-8 days. If there is no persistent clinical effect, the course of treatment is repeated. For hypo- and oligomenorrhea, dysmenorrhea, infertility due to ovarian hypofunction and underdevelopment of the uterus - 0.5-1 mg for 15-16 days after the end of menstruation and then, if indicated, progesterone or pregnin for 6-8 days. The course of treatment can be repeated several times at the same time, after the end of menstruation. For pathological phenomena associated with the onset of menopause and surgical removal of the ovaries - 0.5-1 mg daily or every 1-2 days, in courses of 10-15 injections. If symptoms return, the course of treatment is repeated. Doses should be selected strictly individually depending on the phase of menopause and the severity of the disease. In case of weakness of labor and post-term pregnancy - intramuscularly, 4-5 mg 2-3 hours before the introduction of birth-stimulating drugs. As a hemostimulating drug, when the number of leukocytes decreases below 2 thousand/μl of blood (usually from 10-20 days after irradiation for severe lesions and from 15-18 days for milder lesions) - 1 mg every 1-2 days. The course of treatment is 10 injections (if necessary - up to 15 injections).
TTS is attached to a clean, dry and intact area of body skin (lumbar region, abdomen) 2 times a week. Treatment begins with TTC 50 mcg, followed by individual dose selection (the appearance of a feeling of tension in the mammary gland or intermediate bleeding is a sign of an increased dosage that needs to be reduced). If after 2-3 weeks the signs and symptoms of estrogen deficiency do not stop, the dose should be increased. TTC is applied cyclically: after 3 weeks of treatment (6 applications) - an interval of 7 days, during which metrorrhagia is possible. Continuous, non-cyclic therapy is indicated for women following a hysterectomy or in cases where symptoms of estrogen deficiency become severe again during the 7-day interval. Subsequent therapy with gestagens should be carried out according to the following scheme: with continuous use of TTC, it is recommended to additionally prescribe a gestagen (10 mg medroxyprogesterone acetate, 5 mg norethisterone, 5 mg norethisterone acetate or 20 mg dydrogesterone in the first 10-12 days of each month). When using TTC cyclically, it is recommended to additionally take gestagen in the last 10-12 days of therapy so that the fourth week of each cycle remains free from therapy with any hormone. In both cases, after the end of 10-12 days of gestagen therapy, bleeding occurs.
The gel is used once a day, in the morning or evening, 1.5 mg (2.5 g of gel or 1-2 doses) - applied in a thin layer to clean skin of the abdomen, lumbar region, shoulders and forearms. The application area should be equal in size to 1-2 palms. The gel should be absorbed in less than 2-3 minutes. If it remains on the surface of the skin for more than 5 minutes, then the drug was applied to too small a surface of the skin. The gel is prescribed continuously or in cycles. Doses and duration of therapy are determined individually.
