Femoston® 1 (Femoston® 1)
The drug is prescribed only in the presence of symptoms that adversely affect the quality of life. All patients receiving HRT at least once a year require a benefit/risk assessment. Therapy should be continued until the benefits of taking the drug outweigh the risk of adverse reactions. Experience with the drug in women over 65 years of age is limited.
Information about the risks associated with 3HT in cases of premature menopause is limited. Due to the lower absolute risk in younger women, their benefit/risk ratio may be more favorable than in older women.
Medical examination
Before starting or resuming taking Femoston® 1, it is necessary to collect a complete medical and family history and conduct a general and gynecological examination (including the mammary glands) of the patient in order to identify possible contraindications and conditions requiring precautions. While taking Femoston® 1, it is recommended to conduct periodic examinations, the frequency and nature of which are determined individually, but not less than once every 6 months. It is advisable to perform mammography for additional examination of the mammary glands. Women should be informed about those possible changes in the mammary glands that need to be reported to their doctor.
If there is a family history of thrombosis or thromboembolism in first-degree relatives under the age of 50 years while taking the drug for HRT, careful medical supervision is necessary.
The use of estrogens may affect the results of the following laboratory tests: determination of glucose tolerance, study of thyroid and liver functions.
Reasons for immediate discontinuation of therapy:
Therapy should be discontinued if contraindications are established, as well as in the following cases:
-Jaundice or deterioration of liver function
- Significant increase in blood pressure
-Onset of migraine-type headaches
-Pregnancy
Hyperplasia and endometrial cancer
The risk of developing endometrial hyperplasia and cancer when using HRT drugs containing only estrogen depends on the dose and duration of treatment and increases from 2 to 12 times compared to patients not receiving therapy; the risk may remain elevated for 10 years after stopping therapy.
In women with a preserved uterus, the use of HRT drugs containing only estrogen is not recommended due to the increased risk of developing endometrial cancer. Cyclic use of progestogen (at least 12 days of a 28-day cycle), or use of a continuous combined HRT regimen in women with a preserved uterus, prevents the increased risk of endometrial hyperplasia and cancer associated with estrogen use.
For the purpose of timely diagnosis, it is advisable to conduct ultrasound (US) screening and, if necessary, conduct a histological (cytological) examination.
Bloody vaginal discharge
In the first months of taking the drug, there may be bleeding and/or scanty spotting from the vagina. If such bleeding appears some time after the start of therapy or continues after cessation of treatment, its cause should be determined. An endometrial biopsy may be performed to rule out malignancy.
Venous thromboembolism
HRT is associated with a 1.3-3-fold risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The development of this phenomenon is most likely during the first year of HRT.
If there are thromboembolic complications in first-degree relatives at a young age, as well as with a history of recurrent miscarriage, it is necessary to conduct a hemostasis study (during screening, only some disorders of the blood coagulation system are detected). If the patient is taking anticoagulants, it is necessary to carefully consider the prescription of Femoston® 1 from the point of view of the benefit/risk ratio. Until a thorough assessment of the factors for the possible development of thromboembolism or the initiation of anticoagulant therapy is completed, Femoston 1 is not prescribed.
If a hereditary or acquired predisposition to arterial or venous thrombosis is identified (for example, hyperhomocysteinemia, protein C deficiency, protein S deficiency, antithrombin III deficiency, etc., as well as their combination) and/or the presence of such conditions in the family history (in relatives 1st degree of relationship) taking Femoston® 1 is contraindicated due to the increased risk of thrombosis and thromboembolism, including venous.
In most cases, risk factors for developing VTE include: estrogen use, older age, major surgery, prolonged immobilization, obesity (body mass index > 30 kg/m2), pregnancy or the postpartum period, systemic lupus erythematosus and cancer. There is no consensus on the possible role of varicose veins in the development of VTE.
To prevent VTE after surgery, prophylactic measures should be considered in all postoperative patients.
In case of prolonged immobilization after surgery, you should stop taking Femoston® 1 4-6 weeks before and not resume taking the drug until the woman’s motor activity is completely restored.
If VTE develops after initiation of therapy, the drug should be discontinued and patients should be informed that they should contact their physician immediately if any of the symptoms indicating possible thrombosis or thromboembolism occur (for example, pain or swelling of the lower extremities, sudden chest pain, shortness of breath).
Mammary cancer
In women who have been receiving HRT for a long time containing only estrogen or combined (estrogen + progestogen) drugs, the incidence of breast cancer diagnosis increases, which returns to the original level within 5 years after cessation of therapy.
The increase in risk depends on the duration of HRT use. In women taking combined HRT drugs for more than 5 years, the risk of developing breast cancer can increase up to 2 times.
Combination therapy with estrogen and progestogen
The results of a randomized placebo-controlled trial (Women's Health Initiative (WHI)) and epidemiological studies showed an increased risk of developing breast cancer in women taking combined drugs for HRT (estrogen + progestogen). This increase becomes noticeable after approximately three years of therapy.
While taking HRT medications, there may be an increase in the density of breast tissue during mammography, which can make it difficult to diagnose breast cancer.
Ovarian cancer
Ovarian cancer is much less common than breast cancer. Epidemiological data from a large meta-analysis suggest a small increase in the risk of ovarian cancer for women receiving combined or estrogen-only HRT.
These studies (increased risk) become more apparent when therapy lasts more than five years, and after discontinuation, the risk gradually decreases over time. Findings from a number of other studies, including the WHI, indicate that combined HRT is associated with a similar or slightly lower risk of ovarian cancer.
Risk of ischemic stroke
Combination therapy with estrogen and progestogen or therapy with estrogen alone is associated with a 1.5-fold increase in the relative risk of ischemic stroke. The risk of hemorrhagic stroke does not increase when receiving HRT.
The relative risk does not depend on age, time of menopause, or duration of therapy. However, the baseline risk is highly dependent on age, so the overall risk of stroke in women taking HRT will increase with age.
Coronary heart disease (CHD)
Randomized controlled clinical trials provided no evidence of a protective effect of HRT against myocardial infarction in women with or without CAD who received combined estrogen and progestogen HRT or estrogen alone.
Combination therapy with estrogen and progestogen
The relative risk of coronary heart disease during the use of combined estrogen and progestogen HRT is slightly increased. Because the absolute risk of CAD is highly dependent on age, the number of additional cases of CAD due to combined HRT use in healthy premenopausal women is very small, but increases with age. The risk is slightly higher in women over 60 years of age.
Other states
Estrogens can cause fluid retention, which may adversely affect patients with impaired renal or cardiac function. This group of patients should be under medical supervision. Patients with hypertriglyceridemia while taking HRT medications should also be under medical supervision, because There are reports of very rare cases of significant increases in the concentration of triglycerides in the blood plasma, which contributes to the development of pancreatitis.
Estrogens increase the concentration of thyroxine-binding globulin, which leads to an overall increase in the concentration of circulating thyroid hormones (measured by determination of iodine bound to plasma proteins), the concentration of thyroxine (T4) - chromatographic or radioimmunoassay, or triiodothyronine (T3) - radioimmunoassay. The labeled triiodothyronine uptake test shows an increased concentration of thyroxine-binding globulin. The concentrations of free hormones T3 and T4 usually do not change. Plasma concentrations of other binding proteins (eg, transcortin and sex hormone binding globulin) may also increase, resulting in increased concentrations of circulating corticosteroids and sex hormones.
The concentrations of free or biologically active hormones do not change. It is possible to increase the concentration of other plasma proteins (angiotensinogen/renin system, α-1-antitrypsin, ceruloplasmin).
The use of HRT does not improve cognitive function. There are reports of an increased risk of developing dementia in women who start using HRT (combined or estrogen-containing only) after 65 years.
Femoston® 1 is not a contraceptive.
Pharmacological properties of the drug Femoston
Pharmacodynamics. combined estrogen-progestin drug. Estradiol Estradiol is chemically and biologically identical to the natural human sex hormone estradiol. Among ovarian hormones, it has the highest activity. Estradiol causes cyclic changes in the uterus, cervix and vagina and ensures the maintenance of tone and elasticity of the genitourinary tract. Estradiol also plays an important role in the preservation of bone tissue, ensuring the prevention of osteoporosis and fractures. Oral intake of estrogens has a positive effect on lipid metabolism, has a beneficial effect on the autonomic nervous system and an indirect positive effect on the psycho-emotional sphere. Dydrogesterone Dydrogesterone is an orally effective progestogen whose effects are comparable to those of parenterally administered progesterone. In the context of hormone replacement therapy, dydrogesterone promotes complete secretory transformation of the uterine endometrium, thus preventing the risk of developing estrogen-induced endometrial hyperplasia and/or carcinoma, without excluding androgenic side effects. Due to the fact that estrogens stimulate endometrial growth, estrogen monotherapy increases the risk of developing endometrial hyperplasia and cancer. The use of progestogen in therapy reduces the estrogen-induced risk of developing endometrial hyperplasia in women with a preserved uterus. Clinical trial data Reduction of symptoms of estrogen deficiency and improvement of bleeding profile Reduction in the severity of menopausal symptoms was achieved during the first weeks of treatment. Regular menstrual-like reactions (average duration 5 days) when using Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, were observed in approximately 90% of women. Menstruation usually began on the day of taking the last tablet of the progestogen phase. Breakthrough uterine bleeding and/or spotting was reported in approximately 10% of women. During the first year of therapy, amenorrhea (absence of bleeding or spotting) was observed in 5–15% of women per cycle. Regular menstrual-like reactions when using the drug Femoston, which contains 1 mg of estradiol and 10 mg of dydrogesterone, were observed in 75–80% of women. The day of the onset of menstruation, its duration, as well as the number of women with periodic menstrual-like reactions were the same as with the use of the drug Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, but there were more women with no menstruation (10–25% per 1 cycle). Prevention of osteoporosis Estrogen deficiency during menopause is associated with increased bone turnover and decreased bone mass. The effect of estrogens on bone mineral density is dose-dependent. The protective effect of estrogens only occurs during their use. After stopping hormone replacement therapy (HRT), the rate of bone loss is the same as in women who did not receive this therapy. Data from the WHI (Women's Health Initiative) study and objective analysis of studies suggest that current HRT, primarily in healthy women, either as monotherapy or in combination with a progestogen, reduces the risk of hip, vertebral and other types of fractures that occur due to osteoporosis. HRT may also prevent fractures in women with low bone density and/or known osteoporosis, but data on this are limited. After two years of treatment with Femoston, which contains 2 mg estradiol and 10 mg dydrogesterone, bone mineral density (BMD) in the lumbar spine increased by 6.7% ± 3.9%. During treatment, BMD in the lumbar spine increased or remained unchanged in 94.4% of women. In women who took the drug Femoston, which contains 1 mg of estradiol and 10 mg of dydrogesterone, BMD in the lumbar spine increased by 5.2% + 3.8%. BMD in the lumbar spine increased or remained unchanged during treatment in 93.0% of women. Femoston affects BMD of the femur. After two years of therapy with 1 mg estradiol, BMD of the femoral neck increased by 2.7% ± 4.2%, by 3.5% ± 5.0% in the trochanteric area and by 2.7% ± 6.7% in the Ward triangle . After two years of treatment with estradiol at a dose of 2 mg, these figures were 2.6% ± 5.0%; 4.6% ± 5.0% and 4.1% ± 7.4%, respectively. BMD in three areas of the femur increased or remained unchanged after treatment with estradiol at a dose of 1 and 2 mg in 67–78% and 71–88% of women, respectively. Pharmacokinetics. Estradiol After oral administration, micronized estradiol is rapidly absorbed and extensively metabolized. The main unconjugated and conjugated metabolites are estrone and estrone sulfate. These metabolites have estrogenic activity both directly and after their conversion to estradiol. Estrone sulfate may be subject to enterohepatic metabolism. The main compounds found in urine are the glucuronides of estrone and estradiol. Estrogens pass into breast milk. Dydrogesterone After oral administration, approximately 63% of dydrogesterone is excreted in the urine. The drug is completely eliminated after 72 hours. Dydrogesterone is completely metabolized in the body. The main metabolite of dydrogesterone is 20-α-dihydrodydrogesterone (DHD), which is found primarily in urine as a glucuronic acid conjugate. A common feature of all metabolites is that they retain the 4,6-dien-3-one configuration and the absence of hydroxylation reaction under the action of 17α-hydroxylase. This explains the lack of estrogenic and androgenic effects of dydrogesterone. After oral administration of dydrogesterone, the concentration of DHD in the blood plasma significantly exceeds the level of the parent substance. Dydrogesterone is rapidly absorbed. The time to reach maximum concentration for dydrogesterone and DGD varies between 0.5–2.5 hours. The half-lives for dydrogesterone and DGD are 5–7 and 14–17 hours, respectively. Unlike progesterone, dydrogesterone is not excreted in the urine in the form of pregnanediol. Thus, it remains possible to analyze the formation of endogenous progesterone based on the measurement of pregnanediol excretion.
Use of the drug Femoston
To initiate and maintain treatment of postmenopausal symptoms, the minimum effective dose should be prescribed for the minimum period of time. Femoston is taken daily in the first 14 days of a 28-day cycle, 1 tablet containing 1 or 2 mg of estradiol, and in the remaining 14 days - daily, 1 tablet containing 1 mg of estradiol and 10 mg of dydrogesterone or 2 mg of estradiol and 10 mg of dydrogesterone. After the end of the 28-day cycle, a new cycle should begin. Treatment must be continuous. The tablets should be taken in the order indicated on the package. Treatment of postmenopausal symptoms Usually begins with taking the drug Femoston, containing 1 mg of estradiol and 10 mg of dydrogesterone. Depending on the clinical effect, the dose is then selected individually. If the severity of symptoms associated with estrogen deficiency does not decrease, the dose can be increased by prescribing a drug that contains 2 mg of estradiol and 10 mg of dydrogesterone. Prevention of osteoporosis When hormone replacement therapy is used, it is necessary to take into account individual tolerance to treatment and that the expected effect of the drug on bone tissue is dose-dependent. Femoston Conti 1 tablet 1 time per day daily, without breaks, regardless of meals. Prevention of osteoporosis When hormone replacement therapy is used, it is necessary to take into account individual tolerance to treatment and that the expected effect of the drug on bone tissue is dose-dependent.
Contraindications to the use of Femoston
Hypersensitivity to the components of the drug; diagnosed or suspected breast cancer, endometrial carcinoma and other hormone-dependent tumors diagnosed or suspected; vaginal bleeding of unknown etiology; untreated endometrial hyperplasia; history of acute deep vein thrombosis, pulmonary embolism or idiopathic venous thromboembolism; arterial thromboembolism, including recent ones (for example, angina pectoris, myocardial infarction); acute and chronic liver diseases, as well as their history in the absence of normalization of functional state indicators; porphyria; established or suspected pregnancy.
Interactions of the drug Femoston
The metabolism of estrogens can be enhanced when used simultaneously with substances that activate enzymes (cytochrome P450 systems) that are involved in the metabolism of drugs. These substances include anticonvulsants (eg, phenobarbital, carbamazepine, phenytoin) and antimicrobials (eg, rifampicin, rifabutin, nevirapine, efavirens). Ritonavir and nelvinavir, when used simultaneously with steroid hormones, activate the above enzymes. Herbal preparations, the component of which is St. John's wort (Hypericum perforatum), increase the metabolism of estrogens and progestogens, which can lead to a weakening of their effect and a change in the profile of uterine bleeding. There is no information on the interaction of dydrogesterone with other drugs.
