In our country, many patients, and even some specialists, are wary of HRT as charlatanism, although in the West the value of such therapy is highly valued. What is it really and is it worth trusting such a method - let's figure it out.

Hormone therapy - pros and cons

In the early 2000s, when the use of hormone replacement therapy was no longer questioned, scientists began to receive information about the increasing side effects associated with such treatment. As a result, many specialists have stopped actively prescribing drugs for postmenopausal women after 50 years of age. However, recent studies by scientists at Yale University have shown a high percentage of premature death among patients who refuse to take. The results of the survey are published in the American Journal of Public Health.

Did you know? Studies by Danish endocrinologists have shown that the timely administration of hormones in the first two years of menopause reduces the risk of developing tumors. The results are published in the British Medical Journal.

Mechanisms of hormonal regulation

Hormone replacement therapy is a course of treatment to restore a deficiency in the sex hormones of the steroid group. Such treatment is prescribed at the first symptoms of menopause, to alleviate the patient's condition, and can last up to 10 years, for example, in the prevention of osteoporosis. With the onset of female menopause, estrogen production by the ovaries worsens, and this leads to the appearance of various autonomic, psychological and genitourinary disorders. The only way out is to replenish the hormone deficiency with the help of appropriate HRT preparations, which are taken either orally or topically. What is it? By nature, these compounds are similar to natural female steroids. The woman's body recognizes them and starts the mechanism for the production of sex hormones. The activity of synthetic estrogens is three orders of magnitude lower than that characteristic of the hormones produced by the female ovaries, but their continuous use leads to the required concentration in.

Important! Hormonal balance is especially important for women after removal or extirpation. Women who have undergone such operations may die during menopause if they refuse hormonal treatment. Female steroid hormones reduce the risk of osteoporosis and heart disease in these patients.

Rationale for the need to use HRT

Before prescribing HRT, the endocrinologist directs patients to mandatory medical examinations:

• study of anamnesis in the sections of gynecology and psychosomatics;
• using an intravaginal sensor;
• examination of the mammary glands;
• study of hormone secretion, and if it is impossible to perform this procedure, the use of functional diagnostics: analysis of a vaginal smear, daily measurements, analysis of cervical mucus;
• allergic tests for drugs;
• study of lifestyle and alternative therapies.

According to the results of observations, therapy is prescribed, which is used either for prevention purposes or as a long-term treatment. In the first case, we are talking about the prevention of such diseases in women in menopause as:

• angina;
• ischemia;
• myocardial infarction;
• atherosclerosis;
• dementia;
• cognitive;
• urogenital and other chronic disorders.

In the second case, we are talking about a high probability of developing osteoporosis at the menopause stage, when a woman after 45 cannot do without hormone replacement therapy, since osteoporosis is the main risk factor for fractures in the elderly. In addition, it has been found that the risk of developing cancer of the uterine mucosa is significantly reduced if HRT is supplemented with progesterone. This combination of steroids is prescribed to all patients in menopause, except for those whose uterus has been removed.

Important! The decision on treatment is made by the patient, and only the patient, based on the recommendations of the doctor.

The main types of HRT

Hormone replacement therapy has several types, and preparations for women after 40 years of age, respectively, contain different groups of hormones:

• estrogen-based monotypic treatment;
• combination of estrogens with progestins;
• combining female steroids with male ones;
• monotypic progestin-based treatment
• androgen-based monotypic treatment;
• tissue-selective stimulation of hormonal activity.

Forms of drug release are very different: tablets, suppositories, ointments, patches, parenteral implants.

Impact on appearance

Hormonal imbalance accelerates and intensifies age-related changes in women, which affects their appearance and negatively affects their psychological state: the loss of external attractiveness reduces self-esteem. These are the following processes:

• Overweight. With age, muscle tissue decreases, while fatty tissue, on the contrary, increases. More than 60% of women of “Balzac age”, who previously had no problems with being overweight, are subject to such changes. After all, with the help of the accumulation of subcutaneous fat, the female body "compensates" for the decrease in the functionality of the ovaries and thyroid gland. The result is a metabolic disorder.
• Violation of the general hormonal background during menopause, which leads to the redistribution of adipose tissue.
• deterioration in health and During menopause, the synthesis of proteins responsible for the elasticity and strength of tissues deteriorates. As a result, the skin becomes thinner, becomes dry and irritable, loses elasticity, wrinkles and sags. And the reason for this is a decrease in the level of sex hormones. Similar processes occur with hair: they become thinner and begin to fall out more intensively. At the same time, hair growth begins on the chin and above the upper lip.
• Deterioration of the dental picture during menopause: demineralization of bone tissues, disorders in the connective tissues of the gums and tooth loss.

Did you know? In the Far East and Southeast Asia, where the menu is dominated by plant foods containing phytoestrogens, menopausal disorders are 4 times less common than in Europe and America. Asian women are less likely to suffer from dementia because they consume up to 200 mg of plant estrogens daily with food.

HRT, prescribed in the premenopausal period or at the very beginning of menopause, prevents the development of negative changes in appearance associated with aging.

Hormone therapy drugs for menopause

New generation drugs intended for different types of HRT with menopause are divided into several groups. Synthetic estrogenic products used at the beginning of postmenopause and at its last stage are recommended after removal of the uterus, with mental disorders and impaired performance of the organs of the urinary-genital system. These include such pharmaceutical products as Sygethinum, Estrofem, Dermestril, Proginova and Divigel. Products based on a combination of synthetic estrogen and synthetic progesterone are used to eliminate the unpleasant physiological manifestations of menopause (increased sweating, nervousness, palpitations, etc.) and prevent the development of atherosclerosis, endometrial inflammation and osteoporosis.

This group includes: Divina, Klimonorm, Trisequens, Cyclo-Proginova and Climen. Combined steroids that relieve the painful symptoms of menopause and prevent the development of osteoporosis: Divitren and Kliogest. Vaginal tablets and suppositories based on synthetic estradiol are intended for the treatment of genitourinary disorders and the revival of the vaginal microflora. Vagifem and Ovestin. Highly effective, harmless and non-addictive, prescribed to relieve chronic menopausal stress and neurotic disorders, as well as vegetative somatic manifestations (vertigo, dizziness, hypertension, respiratory distress, etc.): Atarax and Grandaxin.

Drug regimens

The regimen for taking steroids with HRT depends on the clinical picture and the stage of postmenopause. There are only two schemes:

• Short-term therapy - for the prevention of menopausal syndrome. It is prescribed for a short time, from 3 to 6 months, with possible repetitions.
• Long-term therapy - to prevent late consequences, such as osteoporosis, senile dementia, heart disease. Appointed for 5-10 years.

Taking synthetic hormones in tablets can be prescribed in three different modes:

• cyclic or continuous monotherapy with one or another type of endogenous steroid;
• cyclic or continuous, 2-phase and 3-phase treatment with combinations of estrogens and progestins;
• a combination of female sex steroids with male ones.

Hormone replacement therapy (HRT) is used to balance the levels of estrogen and progesterone in a woman's body during menopause.

HRT is also called hormone therapy or menopausal hormone therapy. This type of treatment eliminates, and other symptoms characteristic of menopause. HRT may also reduce the risk of developing osteoporosis.

Hormone replacement is also used in male hormone therapy and in the treatment of individuals who have undergone sex reassignment surgery.

As part of this article, we will focus on studying information about hormone replacement therapy used to relieve symptoms in women during.

The content of the article:

Fast Facts About Hormone Replacement Therapy

1. Hormone replacement therapy is an effective way to get rid of symptoms and menopause.
2. This type of treatment can reduce the intensity of hot flashes and reduce the risk of osteoporosis.
3. Studies have found a link between HRT and cancer, but this link has not been fully explored at this time.
4. HRT can rejuvenate the skin, but it cannot reverse or slow down the aging process.
5. If a woman is considering using hormone replacement therapy, she should first discuss it with a doctor who is intimately familiar with her medical history.

Benefits of hormone replacement therapy

Menopause can be uncomfortable for a woman and increase health risks, but hormone replacement therapy usually relieves menopausal symptoms and reduces its harmful effects.

Progesterone and estrogen are two important hormones for the female reproductive system.

Estrogen stimulates the release of eggs, and progesterone prepares the uterus for the implantation of one of them.

As the body ages, the number of released eggs naturally decreases.

Along with the decrease in egg production, the volume of estrogen excretion also decreases.

Most women begin to observe these changes in themselves in the second half of the forties. During this period, menopause begins to manifest itself with hot flashes, or other problems.

perimenopause

For some time, women are still observed, although changes are already taking place. This period is called perimenopause, and its duration can be from three to ten years. On average, perimenopause lasts four years.

Menopause

When perimenopause ends, menopause begins. The average age at which this phenomenon is observed in women is 51 years.

Postmenopause

After 12 months from the time of the last menstruation, a woman enters a period. Symptoms usually last another two to five years, but it can last ten years or more.

Women also have an increased risk of osteoporosis after menopause.

Besides the natural aging process, menopause is also brought about with the removal of both ovaries and cancer treatment.

Smoking also speeds up the onset of menopause.

Consequences of menopause

Changes in hormonal levels can cause severe discomfort and increase health risks.

The effects of menopause include:

• dryness of the vagina;
• decreased bone density or osteoporosis;
• problems with urination;
• hair loss;
• sleep disorders;
• hot flashes and night sweats;
• psychological depression;
• reduced fertility;
• difficulty concentrating and memory;
• breast reduction and accumulation of fat deposits in the abdominal region.

Hormone replacement therapy can reduce or eliminate these symptoms.

Hormone replacement therapy and cancer

Hormone replacement therapy is used to relieve the symptoms of menopause, protect against osteoporosis and diseases of the cardiovascular system.

However, the benefits of this type of treatment were called into question after two studies, the results of which were published in 2002 and 2003. It turned out that HRT is associated with endometrial, breast and ovarian cancer.

This has led many people to stop using this type of treatment, and it is now less widely practiced.

Further studies of this issue called into question the above studies. Critics point out that their results were not unambiguous, and because different combinations of hormones can have different effects, the results did not fully show how dangerous or how safe HRT can be.

In the case of breast cancer, the combination of progesterone and estrogen causes one case per thousand women per year.

More recent research has shown that the benefits of hormone replacement therapy may outweigh the risks, but so far there is no certainty in this regard.

Other studies suggest that hormone replacement therapy is able to:

• improve muscle function;
• reduce the risk of heart failure and heart attacks;
• reduce mortality in young postmenopausal women;
• show efficacy in preventing skin aging in some women and when used with caution.

Currently, it is believed that HRT is not as dangerous for women as previously discussed. The considered type of therapy in many developed countries is officially approved for the treatment of menopausal symptoms, the prevention or treatment of osteoporosis.

However, every woman who is considering using hormone replacement therapy should make such a decision carefully and only after talking with a doctor who understands the individual risks.

More data is needed to understand the association between HRT and cancer, and research is ongoing.

It is important to understand that human aging is a natural process. If hormone replacement therapy is able to protect a woman from some age-related changes, then it cannot prevent aging.

Who should not use HRT?

HRT should not be used in the treatment of women who have a history of:

• uncontrolled hypertension or high blood pressure;
• heavy;
• thrombosis;
• stroke
• heart disease;
• endometrial, ovarian, or breast cancer.

It is now believed that the risk of developing breast cancer increases if hormone replacement therapy is used for more than five years. The risk of stroke and blood clotting problems is not considered high for women aged 50 to 59.

This type of treatment should not be used by women who are pregnant or may become pregnant.

One of the most common misconceptions about hormone replacement therapy is that it causes weight gain. Women often gain weight around menopause, but studies have shown that HRT is not necessarily the cause.

Other possible causes of weight gain are reduced physical activity, redistribution of body fat due to changes in hormonal levels, and increased appetite as a result of falling estrogen levels.

A healthy diet and regular exercise will help keep you in shape.

Types of HRT used in menopause

Hormone replacement therapy is done with pills, patches, creams, or vaginal rings.

HRT involves the use of various combinations of hormones and the intake of various forms of the corresponding drugs.

• Estrogen HRT. It is used for women who do not need progesterone after they have had a hysterectomy where their uterus or uterus and ovaries have been removed.

• Cyclic HRT. It can be used by women who are menstruating and have perimenopausal symptoms. Usually such cycles are carried out monthly with the intake of portions of estrogen and progesterone, which are prescribed at the end of the menstrual cycle for 14 days. Or it could be daily doses of estrogen and progesterone for 14 days every 13 weeks.

• Long-term HRT. Used during postmenopause. The patient has been taking doses of estrogen and progesterone for a long time.

• Local estrogenic HRT. Includes the use of pills, creams and rings. It can help in solving urogenital problems, reduce vaginal dryness and irritation.

How does a patient go through the process of hormone replacement therapy?

The doctor prescribes the smallest possible doses to treat the symptoms. Their quantitative content can be found by trial and error.

Ways to take HRT include:

• creams and gels;
• vaginal rings;
• tablets;
• skin applications (plasters).

When treatment is no longer required, the patient gradually stops taking doses.

Alternatives to Hormone Replacement Therapy

Alternative methods for reducing menopausal symptoms include using a ventilator

Women going through perimenopause can use alternative methods to reduce their symptoms.

They include:

• reducing the amount of caffeine, alcohol and spicy foods consumed;
• to give up smoking;
• regular exercise;
• wearing loose clothing;
• sleep in a well-ventilated, cool room;
• using a fan, applying cooling gels and cooling pads.

Some SSRI antidepressants (SSRIs) selective serotonin reuptake inhibitors) help relieve hot flashes. Antihypertensive drugs, clonidine, can also help in this regard.

Ginseng, black cohosh, red clover, soybeans, and intoxicating pepper are believed to be effective for menopausal symptoms. At the same time, reputable health organizations do not recommend regular treatment with herbs or supplements, since no research has established their benefit.

Hormone replacement therapy is an effective treatment for excessive sweating and hot flashes, but before practicing HRT, you should discuss its safety with your doctor.

It is constantly expanding, as is the scope of indications for their use. Today, modern medicine has a fairly wide selection of good drugs for HRT, experience in the use of drugs for HRT, indicating a marked predominance of benefits over the risk of HRT, good diagnostic capabilities, which makes it possible to monitor both positive and negative effects of treatment.

Although there is all evidence of a positive effect of taking HRT on health, in general, the risks and benefits of this therapy, according to many authors, can be considered comparable. In many cases, the benefits of long-term HRT will outweigh the risks; in others, the potential risks will outweigh the benefits. Therefore, the use of HRT should meet the needs and demands of a particular patient, be individual and permanent. When selecting a dose, it is necessary to take into account both the age and weight of the patients, and the characteristics of the anamnesis, as well as the relative risk and contraindications for use, which will ensure the best treatment result.

A comprehensive and differentiated approach to the appointment of HRT, as well as knowledge about the features and properties of the components that make up most drugs, will help to avoid possible undesirable consequences and side effects and lead to the successful achievement of the intended goals.

It must be remembered that the use of HRT is not a prolongation of life, but an improvement in its quality, which may decrease under the influence of the adverse effects of estrogen deficiency. And the timely solution of the problems of menopause is a real way to good health and well-being, maintaining efficiency and improving the quality of life of an ever-increasing number of women entering this "autumn" period.

Various classes of estrogens are used to provide hormone replacement therapy that relieves menopausal problems and the difficulties of the transition period in most women.

• The first group includes native estrogens - estradiol, estrone and estriol.
• The second group includes conjugated estrogens, mainly sulfates - estrone, equilin and 17-beta-dihydroequilin, which are obtained from the urine of pregnant mares.

As you know, the most active estrogen is ethinyl estradiol used in preparations for oral contraception. Its doses, which are necessary for the relief of menopausal symptoms, are 5-10 mcg / day, orally. However, due to the narrow range of therapeutic doses, the high likelihood of side effects and not such a favorable effect on metabolic processes as natural estrogens, it is not advisable to use this hormone for the purposes of HRT.

Currently, the following types of estrogens are most widely used in HRT:

1. PRODUCTS FOR ORAL ADMINISTRATION
   • Esters of estradiol [show] .

     Estradiol esters are

     • Estradiol valerate
     • Estradiol benzoate.
     • Estriol succinate.
     • Estradiol hemihydrate.

     Estradiol valerate is an ester of the crystalline form of 17-beta-estradiol, which, when administered orally, is well absorbed in the gastrointestinal tract (GIT). For oral administration, the crystalline form of 17-beta-estradiol cannot be used, since in this case it is practically not absorbed from the gastrointestinal tract. Estradiol valerate is rapidly metabolized to 17-beta-estradiol, so it can be considered a precursor to natural estrogen. Estradiol is not a metabolite or end product of estrogen metabolism, but is the main circulating estrogen in premenopausal women. Therefore, estradiol valerate seems to be an ideal estrogen for oral hormone replacement therapy, given that its goal is to restore hormonal balance to levels that existed before ovarian failure.

     Regardless of the form of estrogen used, its dosage should be sufficient both for the relief of the most pronounced menopausal disorders and the prevention of chronic pathology. In particular, effective prevention of osteoporosis involves taking 2 mg of estradiol valerate per day.

     Estradiol valerate has a positive effect on lipid metabolism, manifested by an increase in the level of high density lipoproteins and a decrease in the level of low density lipoproteins. Along with this, the drug does not have a pronounced effect on protein synthesis in the liver.

     Among oral drugs for HRT, doctors (especially in Europe) most often prescribe drugs containing estradiol valerate, a prodrug of endogenous 17-beta-estradiol. At a dose of 12 mg of estradiol, valerate for oral administration as monotherapy or in combination with gestagens showed high efficacy in the treatment of menopausal disorders (drugs Klimodien, Klimen, Klimonorm, CycloProginova, Proginova, Divina, Divitren, Indivina).

     However, preparations containing micronized 17-beta-estradiol (Femoston 2/10, Femoston 1/5) are no less popular.

   • conjugated estrogens [show] .

     The composition of conjugated equiestrogens obtained from the urine of pregnant mares includes a mixture of sodium sulfates, estrone sulfate (they make up about 50%). Most of the other components of hormones or their metabolites are specific to horses - these are equilin sulfate - 25% and alphadihydroequilin sulfate - 15%. The remaining 15% are inactive estrogen sulfates. Equilin has a high activity; it is deposited in adipose tissue and continues to act even after the drug is discontinued.

     Horse urine estrogens and their synthesized analogues have a more dramatic effect on the synthesis of the renin substrate and hormone-binding globulins compared to estradiol valerate.

     An equally significant factor is the biological half-life of the drug. Horse urine estrogens are not metabolized in the liver and other organs, while estradiol is rapidly metabolized with a half-life of 90 minutes. This explains the very slow excretion of equilin from the body, which is evidenced by the persistence of its elevated level in the blood serum, noted even three months after the cessation of therapy.

   • Micronized forms of estradiol.
2. PREPARATIONS FOR INTRAMUSCULAR INTRODUCTION [show]

   For parenteral administration, there are preparations of estradiol for subcutaneous administration (the classic form - depot - the drug Ginodian Depot, which is administered once a month).

   • Estradiol valerate.
3. PREPARATIONS FOR INTRAVAGINAL INTRODUCTION
4. PREPARATIONS FOR TRANSDERMAL INTRODUCTION [show]

   The most physiological way to create the desired concentration of estrogens in the blood of women should be recognized as the transdermal route of administration of estradiol, for which skin patches and gel preparations were developed. The Klimara patch is applied once a week and provides a constant level of estradiol in the blood. Divigel and Estrogel gel is used once a day. The pharmacokinetics of estradiol during its transdermal administration differs from that which occurs after its oral administration. This difference lies primarily in the exclusion of extensive initial metabolism of estradiol in the liver and a significantly lower effect on the liver. With transdermal administration, estradiol is less converted to estrone, which, after oral administration of estradiol preparations, exceeds the level of the latter in blood plasma. In addition, after oral administration of estrogens, they undergo hepatic recirculation to a large extent. As a result, when using a patch or gel, the estrone / estradiol ratio in the blood is close to normal and the effect of the primary passage of estradiol through the liver disappears, but the hormone's beneficial effect on vasomotor symptoms and protection of bone tissue from osteoporosis remain. Transdermal estradiol, compared with oral, has about 2 times less effect on lipid metabolism in the liver; does not increase the level of sexsteroid-binding globulin in serum and cholesterol in bile.

   Gel for external use 1 g of gel contains: estradiol 1.0 mg, excipients q.s. up to 1.0 g DIVIGEL is a 0.1% alcohol-based gel, the active ingredient of which is estradiol hemihydrate. Divigel is packaged in aluminum foil sachets containing 0.5 mg or 1.0 mg of estradiol, which corresponds to 0.5 g or 1.0 g of gel. The package contains 28 sachets. Pharmacotherapeutic group Replacement hormone therapy. Pharmacodynamics Pharmacodynamics and clinical efficacy of Divigel is similar to oral estrogens. Pharmacokinetics When the gel is applied to the skin, estradiol penetrates directly into the circulatory system, which avoids the first stage of hepatic metabolism. For this reason, fluctuations in plasma estrogen concentration when using Divigel are much less pronounced than when using oral estrogens. Transdermal application of estradiol at a dose of 1.5 mg (1.5 g of Divigel) creates a plasma concentration of approximately 340 pmol / l, which corresponds to the level of the early follicle stage in premenopausal women. During treatment with Divigel, the estradiol/estrone ratio remains at 0.7; whereas with oral estrogen it usually drops to less than 0.2. Metabolism and excretion of transdermal estradiol occurs in the same way as natural estrogens. Indications for use Divigel is prescribed for the treatment of menopausal syndrome associated with natural or artificial menopause, which developed as a result of surgical intervention, as well as for the prevention of osteoporosis. Divigel should be used strictly according to the doctor's prescription. Contraindications Pregnancy and lactation. Severe thromboembolic disorders or acute thrombophlebitis. Uterine bleeding of unknown etiology. C-strogen-dependent cancer (breast, ovary or uterus). Severe liver disease, Dubin-Johnson syndrome, Rotor syndrome. Hypersensitivity to the constituent components of the drug. Dosage and administration Divigel is intended for long-term or cyclic treatment. Doses are selected by the doctor, taking into account the individual characteristics of patients (from 0.5 to 1.5 g per day, which corresponds to 0.5-1.5 mg of estradiol per day, in the future the dose can be adjusted). Usually, treatment begins with the appointment of 1 mg of estradiol (1.0 g of gel) per day. Patients with an "intact" uterus during treatment with Divigel are recommended to prescribe a progestogen, for example, medroxyprogesterone acetate, norethisterone, norethisterone acetate or dydrogestron for 10-12 days in each cycle. In patients in the postmenopausal period, the duration of the cycle can be increased up to 3 months. The dose of Divigel is applied once a day to the skin of the lower part of the anterior abdominal wall, or alternately to the right or left buttocks. The application area is equal in size to 1-2 palms. Divigel should not be applied to the mammary glands, face, genital area, as well as to irritated skin. After applying the drug, wait a few minutes until the gel dries. Accidental contact of Divigel with eyes should be avoided. Wash your hands immediately after applying the gel. If the patient has forgotten to apply the gel, this should be done as soon as possible, but no later than within 12 hours from the time the drug was applied as scheduled. If more than 12 hours have passed, then the application of Divigel should be postponed until the next time. With irregular use of the drug, menstrual-like uterine bleeding of a “breakthrough” may occur. Before starting therapy with Divigel, you should undergo a thorough medical examination and visit a gynecologist at least once a year during treatment. Under special supervision should be patients suffering from endometriosis, endometrial hyperplasia, diseases of the cardiovascular system, as well as cerebrovascular disorders, arterial hypertension, a history of thromboembolism, lipid metabolism disorders, renal failure, breast cancer in history or family history. During treatment with estrogens, as well as during pregnancy, some diseases may worsen. These include: migraines and severe headaches, benign breast tumors, liver dysfunction, cholestasis, cholelithiasis, porphyria, uterine fibroids, diabetes mellitus, epilepsy, bronchial asthma, otosclerosis, multiple sclerosis. Such patients should be under the supervision of a physician if they are treated with Divigel. drug interaction There is no data on the possible cross-interaction of Divigel with other drugs. Side effect Side effects are usually mild and very rarely lead to discontinuation of treatment. If they are nevertheless noted, then usually only in the first months of treatment. Sometimes observed: engorgement of the mammary glands, headaches, swelling, violation of the regularity of menstruation. Overdose As a rule, estrogens are well tolerated even at very high doses. Possible signs of an overdose are the symptoms listed in the "Side Effects" section. Their treatment is symptomatic. Shelf life 3 years. The drug should not be used later than the date indicated on the package. Store at room temperature out of the reach of children. The drug is registered in the Russian Federation. Literature 1. Hirvonen et al. Transdermal estradiol gel in the treatment of the climacterium: a comparison with oral therapy. Br J of Ob and Gyn 1997, Vol 104; Suppl. 16:19-25. 2. Karjalainen et al. Metabolic changes induced by oral estrogen and transdermatjfylktradiol gel therapy. Br J of Ob and Gyn 1997, Vol 104; Suppl. 16:38-43. 3. Hirvonen et al. Effects of transdermal oestrogen therapy in postmenopausal women: a comparative study of an oestradiol gel and an oestradiol delivering patch. Br J of Ob and Gyn 1997, Vol 104; Suppl. 16:26-31. 4. Marketing research 1995, Data on tiles, Orion Pharma. 5. JArvinen et al. Steady-state pharmacokinetics of oestradiol gel in postmenopausal women: effects of application area and washing. Br J of Ob and Gyn 1997, Vol 104; Suppl. 16:14-18.

   

   • Estradiol.

Existing data on the pharmacological properties of various estrogens indicate the preference for using drugs containing estradiol for the purposes of HRT.

For 2/3 of all women, the optimal doses of estrogens are 2 mg of estradiol (oral) and 50 mcg of estradiol (transdermal). However, in each case, during HRT, women should be examined in the clinic to adjust these doses. In women after 65 years of age, there is a decrease in renal and especially hepatic clearance of hormones, which requires special care in prescribing estrogens in high doses.

There is evidence that lower doses of estradiol (25 mcg/day) may be sufficient to prevent osteoporosis.

Currently, there are data indicating the presence of pronounced differences in the effect of conjugated and natural estrogens on the cardiovascular system and the hemostasis system. In the work of C.E. Bonduki et al. (1998) compared conjugated estrogens (oral 0.625 mg/day, continuous) and 17-beta-estradiol (transdermal 50 µg/day) in menopausal women. All women took medroxyprogesterone acetate (orally 5 mg/day) for 14 days every month. It was found that conjugated estrogens, unlike estradiol, cause a statistically significant decrease in plasma antithrombin III after 3, 6, 9 and 12 months after the start of therapy. At the same time, both types of estrogen did not affect prothrombin time, factor V, fibrinogen, platelet count, and euglobulin lysis time. For 12 months, no thromboembolic complications occurred among the study participants. According to these results, conjugated estrogens reduce the level of antithrombin III, while HRT with 17-beta-estradiol does not affect this indicator. The level of antithrombin III is of key importance in the development of myocardial infarction and thromboembolism.

Antithrombin III deficiency can be congenital or acquired. The lack of ability of conjugated estrogens to have a protective effect in women with myocardial infarction may be due precisely to their effect on the content of antithrombin III in the blood. Therefore, natural estrogens are preferred over oral conjugated estrogens when prescribing HRT to patients with risk factors for thrombosis.

In this regard, it should be noted that the historical increase in the use of conjugated estrogens in the United States until recent years cannot be considered the best and recommended in all cases. These obvious facts could not be discussed if statements in favor of the use of conjugated estrogens did not appear in the literature, based only on their wide use in the USA and the existence of a sufficiently large number of studies of their properties. In addition, one cannot agree with the statements about the best properties among the gestagens that are part of various combinations of HRT, medroxyprogesterone acetate in relation to their effect on lipid metabolism. Existing data show that among the gestagens on the market, along with progesterone, there are both its derivatives - 20-alpha- and 20-beta-dihydrosterone, 17-alpha-hydroxyprogesterone, and 19-nortestosterone derivatives, the use of which allows you to get the desired effect. .

Hydroxyprogesterone derivatives (C21-gestagens) are chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, dydrogesterone, etc., and 19-nortestosterone derivatives are norethisterone acetate, norgestrel, levonorgestrel, norgestimate, dienogest, etc.

The choice of a drug from the group of combined estrogen-progestin drugs is due to the period of age-related hormonal changes in a woman.

Specially designed to increase the effectiveness of hormone replacement therapy and prophylactic use, taking into account the requirements of maximum drug safety. This drug, featuring an optimal ratio of hormones, not only has a positive effect on the lipid profile, but also contributes to the rapid reduction of menopausal symptoms. It has not only a preventive, but also a therapeutic effect on osteoporosis.

Klimonorm is highly effective in atrophic disorders of the genitourinary system and skin atrophic disorders, as well as for the treatment of psycho-somatic disorders: irritability, depression, sleep disorders, forgetfulness. Klimonorm is well tolerated: more than 93% of all women taking Klimonorm note only positive changes in their well-being (Czekanowski R. et al., 1995).

Klimonorm is a combination of estradiol valerate (2 mg) and levonorgestrel (0.15 mg), providing the following benefits of this drug:

• rapid and effective reduction in the severity of menopausal symptoms;
• prevention and treatment of postmenopausal osteoporosis;
• maintaining the positive effect of estrogen on the atherogenic index;
• antiatrophogenic properties of levonorgestrel have a positive effect on changes in the mucous membranes of the genitourinary system and weakness of the sphincters;
• while taking Klimonorm, the cycle is well controlled and no phenomena of endometrial hyperplasia were noted.

Klimonorm should be considered the drug of choice for the purposes of HRT during pre- and perimenopause in most women with osteoporosis, psychosomatic disorders, atrophic changes in the mucous membranes of the genitourinary system, hypercholesterolemia, hypertriglyceridemia, with a high risk of developing colon cancer, Alzheimer's disease.

The dose of levonorgestrel included in Klimonorm provides good cycle control, sufficient protection of the endometrium from the hyperplastic effect of estrogens and at the same time maintaining the beneficial effect of estrogen on lipid metabolism, the cardiovascular system, prevention and treatment of osteoporosis.

It has been shown that the use of Klimonorm in women aged 40 to 74 years for 12 months leads to an increase in the density of spongy and cortical bone tissue by 7 and 12%, respectively (Hempel, Wisser, 1994). The mineral density of the lumbar vertebrae in women aged 43 to 63 years with the use of Klimonorm for 12 and 24 months increases from 1.0 to 2.0 and 3.8 g / cm 2, respectively. Treatment with Klimonorm for 1 year in premenopausal women with ovaries removed is accompanied by a restoration to a normal level of bone mineral density and markers of bone metabolism. In this parameter, Klimonorm is superior to Femoston. Additional androgenic activity of levonorgestrel, apparently, is also very significant for the formation of a state of mental comfort. If Klimonorm eliminates or reduces the symptoms of depression, then Femoston in 510% of patients increases the symptoms of depressive mood, which requires interruption of therapy.

An important advantage of levonorgestrel as a progestogen is its almost 100% bioavailability, which ensures the stability of its effects, the severity of which practically does not depend on the nature of the woman's diet, the presence of gastrointestinal diseases and the activity of the hepatic system that metabolizes xenobiotics during their primary passage. Note that the bioavailability of dydrogesterone is only 28%, and its effects are therefore subject to marked differences, both interindividual and interindividual.

In addition, it should be noted that cyclic (with a seven-day break) taking Klimonorm provides excellent cycle control and a low frequency of intermenstrual bleeding. Femoston, used in continuous mode, in this regard, controls the cycle less, which may be due to the lower progestogenic activity of dydrogesterone compared to levonorgestrel. If, when taking Klimonorm, the regularity of menstrual bleeding is observed in 92% of all cycles and the number of cases of intermenstrual bleeding is 0.6%, then when using Femoston, these values ​​are 85 and 4.39.8%, respectively. At the same time, the nature and regularity of menstrual bleeding reflect the state of the endometrium and the risk of developing its hyperplasia. Therefore, the use of Klimonorm from the point of view of preventing possible hyperplastic changes in the endometrium is preferable to Femoston.

It should be noted that Klimonorm has a pronounced activity in relation to the treatment of menopausal syndrome. When analyzing its action in 116 women, a decrease in the Kupperm index from 28.38 to 5.47 was revealed for 6 months (after 3 months it decreased to 11.6) with no effect on blood pressure and body weight (Czekanowski R. et al ., 1995).

At the same time, it should be noted that Klimonorm compares favorably with preparations containing other 19-nortestosterone derivatives (norethisterone) with more pronounced androgenic properties as a progestogen. Norethisterone acetate (1 mg) counteracts the positive effect of estrogens on HDL-cholesterol levels and, in addition, may increase low-density lipoprotein levels, thereby increasing the risk of cardiovascular disease.

For women who need additional protection against hyperplastic processes in the endometrium, it is better to prescribe Cyclo-Proginova, in which the activity of the progestogen component (norgestrel) is 2 times higher compared to Klimonorm.

Combined estrogen-gestagenic drug. The action is due to the estrogen and progestogen components that make up the drug. The estrogenic component - estradiol is a substance of natural origin and after entering the body quickly turns into estradiol, which is identical to the hormone produced by the ovaries and has its own effects: it activates the proliferation of the epithelium of the organs of the reproductive system, including the regeneration and growth of the endometrium in the first phase of the menstrual cycle, the preparation of the endometrium for action progesterone, increased libido in the middle of the cycle, affects the metabolism of fats, proteins, carbohydrates and electrolytes, stimulates the production of globulins by the liver that bind sex hormones, renin, TG and blood clotting factors. Due to participation in the implementation of positive and negative feedback in the hypothalamic-pituitary-ovarian system, estradiol is also able to cause moderately pronounced central effects. It plays an important role in the development of bone tissue and the formation of bone structure.

The second component of the drug Cyclo-Proginova is an active synthetic progestogen - norgestrel, which is superior in strength to the natural hormone of the corpus luteum progesterone. Promotes the transition of the uterine mucosa from the proliferation stage to the secretory phase. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes, stimulates the development of the terminal elements of the mammary glands. It blocks the secretion of hypothalamic LH and FSH release factors, inhibits the formation of gonadotropic hormones, inhibits ovulation, and has slight androgenic properties.

Klimen is a combined preparation containing the natural estrogen estradiol (in the form of valerate) and the synthetic progestogen with antiandrogenic effect cyproterone (in the form of acetate). Estradiol, which is part of Klimen, compensates for the estrogen deficiency that occurs during natural menopause and after surgical removal of the ovaries (surgical menopause), eliminates menopausal disorders, improves blood lipid profile and provides prevention of osteoporosis. Cyproterone is a synthetic progestogen that protects the endometrium from hyperplasia, preventing the development of cancer of the uterine mucosa.

In addition, cyproterone is a strong antiandrogen, blocks testosterone receptors and prevents the effect of male sex hormones on target organs. Cyproterone enhances the beneficial effect of estradiol on the blood lipid profile. Due to the antiandrogenic effect, Klimen eliminates or reduces such manifestations of hyperandrogenism in women as excessive facial hair growth ("lady's mustache"), acne (blackheads), hair loss on the head.

Klimen prevents the formation of male-type obesity in women (accumulation of fat in the waist and abdomen) and the development of metabolic disorders. When taking Klimen during a 7-day break, a regular menstrual-like reaction is observed, and therefore the drug is recommended for premenopausal women.

It is a combined, modern, low-dose hormonal drug, the therapeutic effects of which are due to estradiol and dydrogesterone included in the composition.

Currently, three varieties of Femoston are produced - Femoston 1/10, Femoston 2/10 and Femoston 1/5 (Konti). All three varieties are produced in a single dosage form - tablets for oral administration (28 tablets per pack), and differ from each other only in the dosage of the active ingredients. The numbers in the name of the drug indicate the content of the hormone in mg: the first is the content of estradiol, the second is dydrogesterone.

All varieties of Femoston have the same therapeutic effect, and various dosages of active hormones allow you to choose the optimal drug for each woman, which is best suited for her.

Indications for use for all three varieties of Femoston (1/10, 2/10 and 1/5) are the same:

1. Hormone replacement therapy of natural or artificial (surgical) menopause in women, manifested by hot flashes, sweating, palpitations, sleep disturbances, excitability, nervousness, vaginal dryness and other symptoms of estrogen deficiency. Femoston 1/10 and 2/10 can be used six months after the last menstruation, and Femoston 1/5 - only a year later;
2. Prevention of osteoporosis and increased fragility of bones in women during menopause with intolerance to other drugs intended to maintain normal bone mineralization, prevent calcium deficiency and treat this pathology.

Femoston is not indicated for the treatment of infertility, however, in practice, some gynecologists prescribe it to women who have problems conceiving to increase the growth of the endometrium, which significantly increases the likelihood of implantation of a fertilized egg and pregnancy. In such situations, doctors use the pharmacological properties of the drug to achieve a certain effect in conditions that are not an indication for use. A similar practice of off-label prescriptions exists all over the world and is called off-label prescriptions.

Femoston compensates for the deficiency of sex hormones in a woman's body, thereby eliminating various disorders (vegetative, psycho-emotional) and sexual disorders, and also prevents the development of osteoporosis.

Estradiol, which is part of Femoston, is identical to the natural one, which is normally produced by the ovaries of a woman. That is why it replenishes the estrogen deficiency in the body and provides smoothness, elasticity and slow aging of the skin, slows down hair loss, eliminates dry mucous membranes and discomfort during intercourse, and also prevents atherosclerosis and osteoporosis. In addition, estradiol eliminates such manifestations of the menopausal syndrome as hot flashes, sweating, sleep disturbance, excitability, dizziness, headaches, atrophy of the skin and mucous membranes, etc.

Dydrogesterone is a progesterone hormone that reduces the risk of endometrial hyperplasia or cancer. This progesterone hormone does not have any other effects, and was introduced into Femoston specifically to level the risk of hyperplasia and endometrial cancer, which is increased due to the use of estradiol.

In the postmenopausal period, drugs intended for continuous use should be used. Of these, Climodien has additional benefits associated with good tolerability, since dienogest, which is part of it, has moderate antiandrogenic activity and optimal pharmacokinetics.

Contains 2 mg of estradiol valerate and 2 mg of dienogest per tablet. The first component is well known and described, the second is new and should be described in more detail. Dienogest combined in one molecule with almost 100% bioavailability the properties of modern 19-norprogestagens and progesterone derivatives. Dienogest - 17-alpha-cyanomethyl-17-beta-hydroxy-estra-4.9(10) diene-3-one (C 20 H 25 NO 2) - differs from other norethisterone derivatives in that it contains a 17-cyanomethyl group (-CH 2 CM) instead of the 17 (alpha)-ethynyl group. As a result, the size of the molecule, its hydrophobic properties and polarity changed, which, in turn, affected the absorption, distribution and metabolism of the compound and gave dienogest, as a hybrid gestagen, a unique spectrum of effects.

The progestogenic activity of dienogest is especially high due to the presence of a double bond in position 9. Since dienogest has no affinity for plasma globulins, approximately 90% of its total amount is bound to albumin, and it is in a free state in fairly high concentrations.

Dienogest is metabolized through several pathways - mainly by hydroxylation, but also by hydrogenation, conjugation and aromatization into completely inactive metabolites. Unlike other nortestosterone derivatives that contain an ethynyl group, dienogest does not inhibit the activity of enzymes containing cytochrome P450. Due to this, dienogest does not affect the metabolic activity of the liver, which is its undoubted advantage.

The half-life of dienogest in the terminal phase is quite short compared to other progestogens, similar to that of norethisterone acetate and ranges between 6.5 and 12.0 hours. This makes it convenient to use it daily in a single dose. However, unlike other progestogens, the accumulation of dienogest with daily oral administration is negligible. Compared to other oral progestogens, dienogest has a high renal excretion/fecal ratio (6.7:1). About 87% of the administered dose of dienogest is eliminated after 5 days (mostly in the urine in the first 24 hours).

As a result of the fact that mainly metabolites are found in the urine, and unchanged dienogest is detected in small quantities, a sufficiently high amount of unchanged substance remains in the blood plasma until elimination.

The lack of androgenic properties of dienogest makes it the drug of choice for use in combination with estrogens in continuous hormone replacement therapy.

In studies on molecular models, it was shown that, unlike other 19-norprogestins, dienogest not only did not have androgenic activity, but became the first 19-norprogestogen, which has a certain antiandrogenic activity. Unlike most nortestosterone derivatives (eg, levonorgestrel and norethinodrone), dienogest does not compete with testosterone for binding to sex steroid-binding globulin and therefore does not increase the free fractions of endogenous testosterone.

Since the estrogenic component of hormone replacement therapy stimulates the synthesis of this globulin in the liver, a progestogen with partially androgenic activity can counteract this effect. Unlike most nortestosterone derivatives, which reduce plasma globulin, dienogest does not affect the estrogen-induced increase in its level. Therefore, the use of Climodien leads to a decrease in the level of free testosterone in serum.

It has been shown that dienogest is also able to alter the biosynthesis of endogenous steroids. In vitro studies have shown that it reduces the synthesis of ovarian steroids by inhibiting the activity of 3-beta-hydroxysteroid dehydrogenase. Moreover, dienogest, like progesterone, has been found to locally reduce the conversion of testosterone to its more active form, dihydrotestosterone, by inhibiting 5-alpha reductase by a competitive mechanism in the skin.

Dienogest is well tolerated and has a low incidence of side effects. In contrast to the estrogen-dependent increase in renin levels during the control cycle, no increase in renin was observed with dienogest.

In addition, dienogest causes less platelet aggregation than medroxyprogesterone acetate, and also has an antiproliferative effect on breast cancer cells.

Thus, dienogest is a strong oral progestogen that is ideal for combined use with estradiol valerate in Climodien hormone replacement therapy. Its chemical structure determines the combination of the positive properties of 19-norprogestins with those of C21-progestogens (Table 2).

Table 2. Pharmacokinetic and pharmacodynamic properties of dienogest

Properties and characteristics	19-Nor-progestogens	C21-Pro-gesta- genes	Dieno-gest
High bioavailability when taken per os	+	+
Short plasma half-life	+	+
Strong progestogenic effect on the endometrium	+	+
Absence of toxic and genotoxic effects	+	+
Low antigonadotropic activity		+	+
Antiandrogenic activity		+	+
Antiproliferative Effects		+	+
Relatively low skin penetration		+	+
Except for progesterone receptors, does not bind to any other steroid receptors			+
Does not bind to specific steroid-binding transport proteins			+
No adverse effects on the liver			+
A significant part of the steroid in the free state in plasma			+
In combination with estradiol valerate, weak accumulation with daily intake			+

Climodien effectively relieves the manifestations and symptoms of menopause associated with a decrease in hormone levels after menopause. The Kupperm index on when taking Climodien decreased from 17.9 to 3.8 for 48 weeks, improved verbal and visual memory, eliminated insomnia and breathing disorders during sleep. Compared with estradiol valerate monotherapy, the combination of estradiol valerate with dienogest had a more pronounced positive effect on atrophic changes in the urogenital tract, manifested by vaginal dryness, dysuria, frequent urge to urinate, etc.

Taking Climodien was accompanied by favorable changes in lipid metabolism, which, firstly, are useful for preventing atherosclerosis, and, secondly, contribute to the redistribution of fat according to the female type, making the figure more feminine.

Specific markers of bone metabolism (alkaline phosphatase, pyridinoline, deoxypyridinoline) when taking Climodien changed in a characteristic way, indicating inhibition of osteoclast activity and a pronounced suppression of bone resorption, which indicates a decrease in the risk of osteoporosis.

The description of the pharmacological properties of Climodien will be incomplete if we do not note its ability to increase the content of endogenous mediators mediating vasodilation in postmenopausal women - cGMP, serotonin, prostacyclin, relaxin, which makes it possible to attribute this drug to drugs with vasorelaxant activity that can improve blood circulation.

The use of Climodien leads to atrophic changes in the endometrium in 90.8% of women, and therefore prevents the development of endometrial hyperplasia. Bloody discharge, which is relatively common in the first months of therapy, decreases with increasing duration of treatment. The frequency of adverse and side effects is similar in the treatment of postmenopausal women with other similar drugs. At the same time, there was no adverse effect on chemical laboratory parameters, which is especially important, on hemostasis and carbohydrate metabolism.

Thus, we can conclude that for postmenopausal women, the drug of choice for a continuous combined regimen of hormone replacement therapy is Climodien, which, meeting all the necessary standards of efficacy and tolerability, helps to maintain femininity after menopause.

• provides quick and effective relief of menopausal symptoms;
• provides reliable "protection" of the endometrium and better control of breakthrough bleeding, compared with Kliogest, without reducing the beneficial effects of estrogen;
• contains a dienogestprogestogenic component that does not bind to sex steroid-binding globulin, as a result of which endogenous steroids testosterone and cortisol are not displaced from their binding sites with transport proteins;
• lowers testosterone levels in women;
• contains dienogest, which has a partial antiandrogenic effect;
• according to the study of indicators of bone metabolism, it exhibits an inhibitory effect of estradiol on bone resorption. Dienogest does not counteract this effect of estradiol;
• according to the results of the study of endothelial markers during the treatment period, there is a vasodilating effect of estradiol and nitric oxide on the vasculature;
• does not have an adverse effect on the lipid profile;
• does not change blood pressure values, coagulation factors or body weight;
• improves mood, cognitive function, eliminates insomnia and normalizes sleep in patients with its disorders, if they are associated with menopause.

Climodiene is a highly effective, well-tolerated and easy-to-use combination hormone replacement therapy that is designed for long-term use. It stops all manifestations of menopausal syndrome and causes amenorrhea after 6 months from the start of administration.

Climodien is indicated for continuous combined treatment of menopausal disorders in postmenopausal women. Additional benefits of Climodien include the antiandrogenic properties of its progestogen, dienogest.

Of great interest today is the emergence of a new monophasic combination drug Pauzogest for the treatment of postmenopausal patients.

Pauzogest is the drug of choice for long-term treatment of women who are more than a year postmenopausal and who prefer HRT without periodic bleeding.

Pauzogest is a combination of estrogen and progesterone. One tablet of Pauzogest contains 2 mg of estradiol (2.07 mg as estradiol hemihydrate) and 1 mg of norethisterone acetate. The drug is available in a package - 1 or 3 blisters of 28 tablets. The tablets are film-coated. The daily dose is 1 tablet and is taken daily in continuous mode. The drug compensates for the lack of female sex hormones in the postmenopausal period. Pauzogest relieves vegetative-vascular, psycho-emotional and other menopausal estrogen-dependent symptoms in the postmenopausal period, prevents bone loss and osteoporosis. The combination of estrogen with progestogen allows you to protect the endometrium from hyperplasia and at the same time prevent unwanted bleeding. The active substances of the drug are well absorbed when taken orally and are actively metabolized in the intestinal mucosa and when passing through the liver.

Similarly to endogenous estradiol, exogenous estradiol hemihydrate, which is part of Pauzogest, affects a number of processes in the reproductive system, the hypothalamic-pituitary system and other organs; it stimulates bone mineralization.

Taking estradiol hemihydrate once a day provides a stable constant concentration of the drug in the blood. It is excreted completely within 72 hours after entering the body, mainly with urine, in the form of metabolites and, partially, unchanged.

Recent studies have shown that the role of the progestogen component in HRT is not limited to protecting the endometrium. Gestagens can weaken or enhance some of the effects of estradiol, for example, in relation to the cardiovascular and skeletal systems, and also have their own biological effects, in particular, a psychotropic effect. Side effects and tolerability of the drug for HRT are also largely determined by the progestogen component. The properties of the progestogen component in the composition of continuous combination therapy are especially important, since the duration of administration and the total dose of the progestogen in this regimen is greater than in cyclic regimens.

Norethisterone acetate, which is part of Pauzogest, belongs to testosterone derivatives (C19 progestogens). In addition to the general property of derivatives of C21 progestogens and C19 progestogens to cause transformation of the endometrium, norethisterone acetate has various additional "characteristics" that determine their use in therapeutic practice. It has a pronounced antiestrogenic effect, reducing the concentration of estrogen receptors in target organs and inhibiting the action of estrogen at the molecular level ("down-regulation"). On the other hand, moderately pronounced mineralocorticoid activity of norethisterone acetate can be successfully used in the treatment of menopausal syndrome in women with primary chronic adrenal insufficiency, and androgenic activity can be used both to achieve a positive anabolic effect and to compensate for androgen deficiency in menopause, leading to a decrease in sexual desire.

A number of undesirable effects of norethisterone acetate appear during its passage through the liver and, most likely, are due to the presence of the same residual androgenic activity. Oral administration of norethisterone acetate prevents the estrogen-dependent synthesis of lipoprotein apoproteins in the liver and therefore reduces the beneficial effect of estradiol on the blood lipid profile, as well as impairs glucose tolerance and increases blood insulin levels.

Norethisterone acetate is well absorbed when taken orally. It is excreted mainly in the urine. With the simultaneous administration of estradiol hemihydrate, the characteristics of norethisterone acetate do not change.

Thus, Pauzogest has a positive effect on all peri- and postmenopausal symptoms. Clinical evidence suggests that Pauzogest reduces bone loss, is the prevention of bone loss in postmenopausal women, thereby reducing the risk of fractures caused by osteoporosis. The proliferation of the endometrium, which occurs under the influence of estrogen, is effectively inhibited by the continuous intake of norethisterone acetate. This minimizes the risk of developing hyperplasia and endometrial cancer. Most women do not experience uterine bleeding while taking Pauzogest in monophasic mode, which is preferable for postmenopausal patients. Long-term use of Pauzogest (less than 5 years) does not increase the risk of developing breast cancer. The drug is well tolerated. Side effects include breast engorgement, mild nausea, rarely headache, and peripheral edema.

Thus, the results of many clinical studies indicate that the arsenal of means for postmenopausal HRT has been replenished with another worthy drug with high efficacy, safety, good tolerability, acceptability and ease of use.

Conclusion

When choosing a drug for HRT in women, it is necessary to consider:

• age and weight of patients
• features of the anamnesis
• relative risk and contraindications for use

oral preparations	It is best taken by women with atrophic skin changes, hypercholesterolemia, it is possible to use women who smoke and women with a high risk of developing colon cancer.
Transdermal preparations	It is preferable to use in women with diseases of the gastrointestinal tract, gallbladder, diabetes, hypertriglyceridemia and possibly in women after cholecystectomy.
Estrogen monotherapy	Indicated for women with a hysterectomy and possibly older women suffering from vascular disease of the heart or Alzheimer's disease.
Combination estrogen-gestagen therapy	It is indicated for women with an unremoved uterus, as well as for women with a removed uterus with a history of hypertriglyceridemia or endometriosis.

The choice of HRT regimen depends on the severity of the climacteric syndrome and its period.

• In perimenopause, it is preferable to use two-phase combined preparations in a cyclic mode.
• In postmenopause, it is advisable to constantly use a combination of estrogen with a progestogen; since at this age in women, as a rule, insulin resistance is increased and hypercholesterolemia is observed, it is better for them to use Climodien, the only drug for continuous use that contains a progestogen with antiandrogenic activity.

If you weigh everything correctly, then not prescribing hormone therapy is much more dangerous, he believes. Svetlana K alinchenko, professor, doctor of medical sciences, head of the department of endocrinology, FPK MR RUDN University.

Svetlana Chechilova, AiF:​ I remember that we did the first article with you about male impotence. And today you are engaged in women's issues?

Svetlana Kalinchenko: Indeed, in the beginning, my colleagues and I enthusiastically tackled hormonal balance in men in their prime and beyond. We set a criterion: a healthy man is a person without obesity, with a waist less than 93 cm, he does not suffer from nocturia (does not wake up at night from the urge to go to the toilet), does not experience problems with sleep, does not complain of erectile dysfunction ...

We quickly learned how to make men healthy. But, when the ability to have sex returned to them, their families began to collapse.

- Men began to leave from the same age to the young?

That's exactly what happened. And we understood that next to a healthy man there should be a healthy woman. What does his cousin look like? Obesity, waist more than 80 cm, folds sagging on the back and sides, she sleeps badly, urine leaks during dancing and sneezing, sexual intimacy is not happy ...

But give her estrogens, vitamin D (in fact, it is the most important fat-burning hormone) and testosterone, which are responsible for the quantity and quality of muscle mass, bladder tone and libido, and the problems are solved. Before us is again a beautiful, youthful woman who is still interesting to her partner. A woman's sexuality is much more complex than a man's. Not every woman experiences and should experience an orgasm, but if she once liked the caresses, touches of her partner, she should keep these feelings.

- There are many versions of why a person grows old. Which one do you share?

It seems to me that the endocrine theory of aging is correct, its author is our compatriot Vladimir Dilman. We begin to get sick and grow old, when with age all the glands begin to work with reduced activity and there is a drop in the production of important energy hormones of the thyroid gland, growth hormone, adrenal hormones, sex ...

A century ago, the average life expectancy was 49 years, and today in civilized countries - 80. Thanks to the achievements of medicine, we reach the age of ill health and live in a state of illness for a significant part of our lives. We began to live up to the main disease - deficiency of sex hormones.

- That is, you think that if our body receives a sufficient amount of hormones, then old age can be canceled?

Yes. Decreased production of sex hormones is a key moment of aging. Our life is divided into two periods. First - there are plenty of sex hormones, the body can easily and simply cope with most diseases. The second - after the onset of a deficiency of sex hormones, when diseases become progressive in nature, their irreversible course goes on. Things should be called by their proper names: menopause in women and androgen deficiency in men is an unnatural condition. And any pathological condition must be treated. If the lack of sex hormones is eliminated in time, how many problems can be avoided! Prevent osteoporosis (if the diagnosis is made, alas, the treatment is late), prevent diabetes, obesity, Alzheimer's disease from developing ...

- And how, then, to explain that today diabetes, stroke, heart attack have become younger?

Because very young people eat up obesity, and the bad hormone leptin is formed in adipose tissue. It leads to a decrease in the production of sex hormones. Leptin secretion only increases with age. Obese men and women have a hormonal deficiency early, they age prematurely.

- But many women enter menopause without feeling any problems.

Believe me, there is no healthy menopause. If today a 45-year-old woman has no complaints about her health, about menopausal hot flashes, she does not have excess weight, then all the same, in ten years, illnesses will catch up with her. Women enter menopause in different ways.

Someone feels a lack of estrogen, someone lacks testosterone or vitamin D. Outwardly, this can be seen even with the naked eye. Estrogens are hormones responsible for beauty, so a woman with their deficiency develops wrinkles early. And her peer with a lack of testosterone gains weight, social activity disappears, and sexuality decreases. She is still beautiful, but she does not want to use her attractiveness at all.

Here is my patient's story. Her fate is very common for Russia: at the age of 38, her uterus was removed, but the doctors did not prescribe HRT, because she did not complain about anything. The years went by. The family broke up, the husband left for another woman. Nevertheless, she takes care of herself, practices yoga.

At 42, I finally prescribe HRT to her, but she again goes to other doctors who simply intimidate her: “Look how beautiful you are, you will still be fine, and hormones will trigger obesity and cancer.” At that time, she still had a lot of testosterone, so she did not gain weight, she did not suffer from hot flashes. But very soon the moment came when testosterone began to decline, and the woman's libido disappeared. Then she came back to me. Total - 5 years of inactivity.

Old age has come to the woman, she has no desire to visit, she does not need sex. Wrinkles appeared on the back (the so-called lambrequins), cellulite on the hips, the skin on the arms sagged - there are all signs of a lack of testosterone.

Hormones are vital for hysterectomized women Tens of thousands of post-hysterectomy women who are in menopause die prematurely because they refuse estrogen therapy, years of research confirms. In the 1990s, about 90% of women aged 50 or older who had a hysterectomy took estrogen, and it lasted 4 to 5 years. Doctors noticed that estrogen reduced the risk of osteoporosis and heart disease in these patients. But in 2002, data began to come in about a high incidence of side effects on the background of HRT. As a result, over the next 1.5 years, many doctors stopped prescribing estrogen to postmenopausal women. Recently, researchers at Yale University set out to quantify the number of premature deaths that occurred among women aged 50-59 years who had a hysterectomy after they stopped taking estrogen. Doctors were horrified: over the past 10 years, 48,000 women have died, this study result is published in the American Journal of Public Health.

- Is there any other evidence of age-related endocrine disorders in the body?

Signs of elevated insulin levels can be seen: the skin turns dark - pigmentation is visible on the elbows, neck. Insulin is a bad hormone, it stimulates cell division and triggers malignant neoplasms. When there is a decrease in the production of sex hormones and vitamin D, there is an increase in insulin. But the body does not feel it, so-called insulin resistance develops. Dermatologists of the 19th century knew that serious diseases of the heart and blood vessels, the threat of oncology, were hidden behind the dark staining of the skin, but these were rare cases. Because at that time, only a few people lived to a deficiency of sex hormones and insulin resistance. And there was no vitamin D deficiency at all.

People spent a lot of time in the air, the skin under the influence of ultraviolet synthesized a sufficient amount of vitamin D - this hormone is part of the secretory secretions of the skin. Today, dark elbows are much more common.

When is it necessary to prescribe hormone replacement therapy?

As soon as there was a deficiency, because every day, month, year, lived without hormones, deals an irreversible blow. Atherosclerosis, which has started, can no longer be stopped. HRT, appointed late, will slow down the progression, but it does not guarantee getting rid of the disease. In order not to miss the moment, it is necessary to pass a test to determine not only ovulation, but also the follicle-stimulating hormone, which is produced in the pituitary gland. When a woman's estrogen levels are low, she may still be menstruating, but that doesn't mean she has enough hormones. Therefore, the International Menopause Society recommends that women, starting at age 35, determine the level of follicle-stimulating hormone. And when it rises, it's time to start HRT. This is the concept of the XXI century - preventive medicine. In the world, the deficiency of sex hormones and vitamin D has learned not only to determine and replenish, but also to prevent - to take the necessary steps in advance.

Many women associate estrogen intake with the occurrence of breast cancer, which claims many lives.

There are many fallacies in this statement. In fact, breast cancer is the cause of death in 4% of cases. The leading cause of premature death is cardiovascular disease, which, as I have already explained, is triggered by insulin resistance. And it does not happen without hormonal disorders. That is, if there is arterial hypertension, then you need to look for what is missing: vitamin D, estrogens, gestagens, testosterone ...

As for breast cancer itself, by the time doctors detect it on a mammogram, the disease is over a decade old. Cancer develops very slowly. If suddenly a woman who missed estrogen-sensitive cancer on the mammography window (and today it is a contraindication to HRT), still receives hormones, then the drugs will only help to reveal the existing oncology. She will find herself sooner. And this should be treated well.

- Pretty bold statement. It seems to me that most doctors with this point of view are unlikely to agree.

Alas. But there is such an oncologist-mammologist Chingiz Mustafin, who fully shares my opinion. By the way, here's the real story. The famous writer Lyudmila Ulitskaya was diagnosed with breast cancer. She writes that she took HRT for 10 years: "The hormones gave me youth, beauty, but they also caused cancer." Ulitskaya is wrong. Hormone therapy only showed her cancer, which means it helped the writer: the neoplasm was discovered on time, they had an operation right there in Israel, Ulitskaya continues to live and write new books.

But if she had not taken HRT, then the cancer would still have manifested itself, but it is not known when. Probably, oncology would have been detected at a different stage. Would an operation help?

But, probably, modern hormones, which are delivered directly to the organ that needs them, reduce the risk of side effects?

Certainly. New low-dose and highly selective drugs are aimed clearly at the target. Doctors for 8 years observed 80 thousand women who received HRT. If the therapy included estrogens, then osteoporosis and oncology did not occur. The risk of cancer was manifested only in women who received the old gestagens. Today there are already unique gestagens, metabolically neutral, they do not lead to obesity and at the same time do not lower testosterone if a woman does not have an excess of it. New treatment regimens have also been developed. If a woman has her uterus removed, pure estrogen should be given to her.

If a woman is no longer menstruating, she should receive both estrogen and progestogen all the time. If a woman is still in the premenopausal period and she periodically has periods, then she needs to take estrogen for 14 days first, and estrogen with progestogen for the next 14 days ...

- Oh, how difficult it is! ..

The selection of HRT is not an easy intellectual task, a woman cannot choose therapy for herself. This is only possible for a very competent doctor. Unfortunately, there are very few of them in Russia. Today, many of our gynecologists still believe that testosterone is a male hormone. And in Europe, patches, gels, testosterone injections have been created for women.

Our doctors, overcome by hormone phobia, do not prescribe HRT to patients also because they do not have their own experience in using this therapy. And in Sweden, for example, in 2011, 87% of gynecologists of the appropriate age received HRT, which is why they prescribed it to more than half of the country's women. Fears pass when a person gains his own experience. And how many of our doctors have tried hormones? counted units. Result: today, as 15 years ago, less than 1% of Russian women receive HRT.

You should know it

2 secrets from Dr. Kalinchenko 1) Osteoporosis is terrible with fractures. But even a person with osteoporosis will not have a fracture until he falls. Therefore, today foreign doctors do not prescribe drugs that cause dizziness to patients. Unfortunately, Russian doctors still prescribe these drugs to patients. 2) Vitamin D cannot be obtained by drinking fish oil. It is a misconception that the required dose can be obtained from food. Vitamin D needs to be supplemented.

- It seems to me that doctors are afraid of hormones, because they burned themselves on the previous contraceptives.

Indeed, all the bad information about hormones was obtained after the use of old contraceptives - excessive doses of estrogens and progestogens. Modern HRT is safe because it only makes up for what is missing. And the more serious health problems a woman has, the more she needs hormones.

I came across dermatological diseases that no one can cure. But, surprisingly, even psoriasis goes away if the patient receives sex hormones and vitamin D.

- Do the patients themselves ask for HRT? After all, they must have read about foreign practice.

Women are poorly informed about HRT. I have been taking hormones myself since the 90s. And I can count on my fingers the rare patients who have since come to me for advice about taking HRT.

- Probably, the rest go to a beauty salon for youth, and not to a gynecologist.

In fact, a good beautician will tell you that you can’t hide your age with Botox alone. We need sex hormones. And cosmetologists, not gynecologists, remain leaders in prescribing HRT. Because as soon as the sex hormones go away, all the numerous procedures that are offered in the salons cease to help. Believe me, Madonna does not look so good because she had plastic surgery. She receives hormone therapy - estrogens, progestogens, testosterone and vitamin D.

Catad_tema Menopausal syndrome and hormone replacement therapy - articles

Modern pharmacological market of hormone replacement therapy drugs

A wide selection of drugs for HRT in the Russian pharmaceutical market makes it possible to rationally use and select the necessary drug in each case. Before prescribing HRT and during treatment, a gynecologist's examination, ultrasound of the genitals, examination of the mammary glands, oncocytology, Pipel endometrial biopsy, measurement of blood pressure, height, body weight, examination of the hemostasis system and blood lipid spectrum, blood sugar, general urine analysis are necessary. Contraindications for HRT are: history and current thromboembolic complications, malignant tumors of the endometrium, uterus, breast, severe forms of liver dysfunction and severe diabetes mellitus, vaginal bleeding of unknown etiology. In the first months of HRT treatment, soreness of the mammary glands can be observed, in rare cases, nausea, headache, swelling and some other side effects, usually of a transient nature, and do not require discontinuation of the drug. With the appearance of unusually strong or frequent headaches, visual or hearing impairments, the first signs of thrombosis, the appearance of jaundice or epileptic seizures, as well as the onset of pregnancy, HRT preparations should be discontinued and an appropriate examination should be carried out.

Menopause - the period of the last menstruation, established retrospectively after 12 months of their absence. The age at which natural menopause develops is 45-55 years. However, menopause can occur earlier: after surgery, radiation exposure, etc. Menopause is characterized by estrogen deficiency, which contributes to a sharp increase in the risk of occurrence and progression of various dysfunctional conditions. The clinical symptoms of menopausal disorders depend on the age of the woman and the variant of the onset of menopause; hereditary, environmental factors and the somatic state by the menopause period play an important role in the development of clinical symptoms.

Menopause divides menopause into 2 phases: premenopause (before menopause) and postmenopause (after menopause). The feasibility of conducting HRT in women with the help of steroid sex hormones in the pre- and post-menopausal period is undeniable. However, its effectiveness and safety depend on the individual characteristics of the woman and the correct choice of the drug. The range of hormonal preparations is constantly expanding, as is the scope of indications for their use.

Most epidemiological studies have found that more than 80% of women suffer from certain disorders in the menopause (table 1), but only 10-15% of them seek medical help.

Table 1
The most common menopausal complaints in women aged 45-54 years

As a rule, ovarian dysfunction begins at a relatively early age. As a result, many women, for more than a third of their lives, are forced to endure manifestations of estrogen deficiency, which often overshadows their lives. In almost 90% of women, the estrogen deficiency that accompanies menopause negatively affects their physical condition and leads to an increase in their biological age.

Currently, women have the opportunity to live through the menopause without pathological manifestations or any changes in their lifestyle, remaining young, energetic, sexy and attractive thanks to a number of drugs being introduced into medical practice in the Russian Federation. Treatment and prevention of menopausal disorders includes the use of drugs of sex hormones and non-hormonal agents. A specific hormonal drug should be selected by a doctor, taking into account age characteristics and the concentration of hormones in the blood.

It is generally accepted in the world to use conjugated estrogens, estradiol acetate and valerate, 17-b-estradiol, estriol, estriol succinate and cyproterone acetate for HRT. In the USA, conjugated estrogens are widely used, in European countries - estradiol acetate and valerate. Unlike synthetic ones, the listed estrogens do not have a pronounced effect on the liver, coagulation factors, carbohydrate metabolism, etc., their positive effect on the cardiovascular system is noted. The cyclic addition of progestogens to esgrogens for 10-12-14 days is mandatory, which avoids endometrial hyperplasia.

PHARMACOECONOMICS OF HRT

Pharmacoeconomic studies show that long-term use of HRT is more effective in terms of treatment costs than symptomatic treatment of individual manifestations of menopause. Surveys of Japanese women have shown that HRT is more effective in managing menopause than traditional oriental medicine and methods. Horisberber et al. (1993) compared different regimens for the symptomatic treatment of menopause. The authors showed that the most economically advantageous is the use of oral estrogens, which leads to the complete elimination of pathological symptoms. Of the transdermal forms, estradiol gel turned out to be the cheapest and most convenient, which cannot be said about the transdermal patch.

Most pharmacoeconomic assessments assume that menopausal symptoms only indirectly affect the cost of treatment due to their impact on quality of life. However, it has been shown that the use of HRT avoids more than a quarter of all medical prescriptions made to women in the pre- and postmenopausal period.

WOMEN'S READINESS TO RECEIVE HRT

To achieve the full positive effect of HRT, including the prevention of osteoporosis and cardiovascular disease, long-term treatment (about 10 years) is necessary. However, 5-50% of women stop taking HRT drugs during the first year of treatment, with the main reason for women not taking therapy being the reluctance to return to monthly bleeding, and the doctor's attitude to HRT is crucial. To obtain the maximum effect from HRT, it is necessary to seek the consent of patients to conduct this type of therapy. Receiving HRT should be preceded by a careful selection of drugs, taking into account the individual requirements of women.

If you do not want to return to the monthly menstrual cycle, women can choose HRT, in which bleeding is observed once every three months. Transdermal therapy may also provide an acceptable bleeding rate.

DESCRIPTION OF INDIVIDUAL DRUGS

Conjugated equine estrogens are obtained from the urine of pregnant mares. They include a mixture: estrone sulfate - 25% and specific equine estrogens: equine sulfate - 25% and dihydroequilin - 15%.

Preparations containing conjugated estrogens include:

Premarin (USA) - 0.625 mg, 20, 40, 60 pieces per pack. The usual dose for cyclic use is 0.625-1.25 mg per day. Alternate reception for 3 weeks with a break of 1 week. In the presence of menstrual-like bleeding, the reception is started from the 5th day of the menstrual cycle, and from the 15th to the 25th day, any progestogen preparation is additionally prescribed.

Hormoplex (Yugoslavia) - dragee 1.25 mg, 20 pcs in a box. It is a mixture of conjugated estrogens (mainly estrone and equilin sulfates). The recommended daily dose is 1.25 mg, for 20 or 29 days with breaks of 7 days.

Estrofeminal (Germany) - capsules containing 0.3, 0.6 or 1.25 mg of conjugated estrogens. Intended for cyclic treatment at a dose of 0.6-1.25 mg for 21 days with a break of 7 days.

Natural estrogens, depending on the route of administration, are divided into 2 groups: for oral use and parenteral. HRT preparations containing estrogen and progestin are widely used in the world. These include drugs of monophasic, biphasic and triphasic types.

Biphasic type drugs for HRT supplied to the Russian pharmaceutical market include:

Divina (Finland) - calendar pack with 21 tablets: 11 white tablets contain 2 mg estradiol valerate and 10 blue tablets, consisting of 2 mg estradiol valerate and 10 mg medroxyprogesterone acetate. The dosing regimen of this drug, as well as other drugs of the two-phase type, is as follows: 1 tablet daily, starting from the 5th day of the cycle and further along the calendar scale, then a break of 7 days is taken.

Klimonorm (Germany) - a calendar package with 21 tablets: 9 yellow tablets containing 2 mg of estradiol valerate and 12 turquoise tablets, which include 2 mg of estradiol valerate and 0.15 mg of levonorgestrel.

Klimen (Germany) - a calendar package with 21 tablets, of which 11 white tablets contain 2 mg of estradiol valerate, and 10 pink tablets contain 2 mg of estradiol valerag and 1 mg of cyproterone acetate.

Cyclo-progynova (Germany) - a calendar package with 21 tablets, of which 11 white tablets contain 2 mg of estradiol valerate, and 10 light brown tablets contain 2 mg of estradiol valerate and 0.5 mg of norgestrel.

Femoston (Germany) - a calendar package with 28 tablets, of which 14 orange tablets contain 2 mg of estradiol, and 14 yellow tablets contain 2 mg of estradiol and 10 mg of digidogesterone. The drug compensates for the deficiency of sex hormones in a woman's body, relieves menopausal symptoms during natural menopause, after surgical removal of the ovaries. Also, the drug is used for the treatment and prevention of osteoporosis in postmenopausal women.

The drug affects lipid metabolism to a much greater extent than other drugs for HRT, normalizes lipid metabolism, significantly reduces the risk of atherosclerosis and other diseases of the cardiovascular system. Femoston does not affect carbohydrate metabolism. Even with prolonged therapy, the drug does not cause thrombosis or thromboembolic disorders. Causes an adequate secretory phase of the endometrium. It improves the quality of life of patients by reducing the number of complaints and objectively detectable menopausal symptoms. Femoston is the base drug for HRT in the presence of diseases of the cardiovascular system.

Divitren (Finland) - a modified drug, a calendar package with 91 tablets: 70 white tablets contain 2 mg of estradiol valerate, 14 blue tablets contain 2 mg of estradiol valerate and 20 mg of progesterone acetate and 7 yellow tablets without active substance (placebo) . The drug is taken continuously, menstrual bleeding occurs only once every three months.

Three-phase preparations for HRT on the pharmacological market of the Russian Federation are represented by Trisequens and Trisequens-forte (Novo Nordisk, Denmark), containing estradiol and norethisterone acetate, which ensure the intake of estradiol throughout the 28 days of the cycle. Due to this, the woman does not experience the recurrence of menopausal symptoms such as hot flashes and night sweats during the menstrual phase of the cycle.

Trisequens - tablets of 28 pieces per pack in the form of a calendar disc: 12 blue tablets containing 2 mg of estradiol, 10 white tablets - 2 mg of estradiol and 1 mg of norethisterone acetate and 6 red tablets - estradiol 1 mg.

Trisequens forte - retard tablets of 28 pieces per pack: 12 yellow tablets - 4 mg of estradiol, 10 white tablets - 4 mg of estradiol and 1 mg of norethisterone acetate and 6 red tablets - 1 mg of estradiol.

Monophasic drugs are more often used in postmenopausal women, and it is recommended to start treatment no earlier than a year after menopause, in a continuous mode, because. they do not cause endometrial proliferation. The absence of menstrual bleeding with these drugs makes them more acceptable to postmenopausal patients. These are drugs such as:

Kliogest (Novo Nordisk, Denmark) - 28 tablets per pack. 1 tablet contains 1 mg of estradiol and 2 mg of norethisterone acetate. This drug also has a beneficial effect on the blood lipid spectrum: it reduces the level of total cholesterol and LDL cholesterol by approximately 20%, without significantly affecting the concentration of HDL cholesterol, and at the same time it is highly effective for the prevention of osteoporosis.

Livial (Netherlands) - in the package of 28 white tablets, consisting of 2.5 mg of tibolone. This drug has estrogenic, progestogenic and weak androgenic activity, relieves menopausal symptoms and helps maintain bone integrity.

Monocomponent preparations for oral administration include:

Proginova (Germany) - calendar package with 21 white dragees, each of which contains 2 mg of estradiol valerate.

Estrofem (Novo Nordisk, Denmark) - blue tablets of 2 mg, 28 pieces per pack.

Estrofem forte - yellow tablets 4 mg, 28 pieces per pack.

With parenteral administration of drugs, the primary metabolism of estrogens in the liver is excluded, therefore, smaller doses of the drug are required to achieve a therapeutic effect compared to drugs for oral use. With parenteral use of natural estrogens, various routes of administration are used: intramuscular, cutaneous, transdermal and subcutaneous. The use of ointments, suppositories, tablets with estriol allows you to achieve a local effect in urogenital disorders.

The combined preparation of HRT for intramuscular administration was developed and supplied to the Russian Federation from Germany - this is Ginodian-Depot, 1 ml of which contains 200 mg of prasterone enanthate and 4 mg of estradiol valerate in an oil solution. The drug is administered intramuscularly, 1 ml every 4 weeks.

Percutaneous and cutaneous routes of administration of estradiol into the body are possible with the use of the following drugs:

Estraderm TTS (Switzerland) - active substance: 17-b estradiol. The transdermal therapeutic system is a patch with a contact surface of 5, 10 and 20 cm 2 and a nominal amount of released estradiol of 25, 50 and 100 μg/day, respectively. Plaster 6 pieces per pack. The patch is applied to a clean and dry area of ​​​​the back, abdomen, buttocks or thighs, the places of applications are alternated. Treatment begins with a dose of 50 mcg, the dose is further adjusted depending on the severity of the clinical effect. For maintenance therapy, a patch containing 25 μg of the active substance is usually used. The drug is used cyclically, the treatment is supplemented with gestagens. In the case of hysterectomy, the drug is prescribed continuously.

Klimara (Germany) - is a transdermal therapeutic system in the form of a patch consisting of 3 layers: a translucent polyethylene film, an acrylic area with an adhesive surface containing estriol, a protective polyester tape. The patch with an area of ​​12.5 cm 2 contains 3.9 mg of estradiol. The package contains 4 and 12 pieces.

Klimara-forte (Germany) - a similar patch with an area of ​​​​25 cm 2 contains 7.8 mg of estradiol, in a package of 4 and 12 pieces.

Menorest (USA-Germany) is a transdermal patch containing 17-b-estradiol. Release form: menorest-25, menorest-50, menorest-75, menorest-100. Release per day, respectively, 25, 50, 75, 100 mcg. The dosing regimen is similar when using Estraderm TTS.

Estrogel (Finland) - skin gel containing 0.6-1 mg of estradiol, 80 mg in tubes with a measuring spatula. The gel is applied to any part of the skin (with the exception of the genitals and mammary glands), on the largest possible area. It is used in a continuous or cyclic mode, the dose is set individually, the treatment is supplemented with gestagenic preparations.

Divigel (Finland) - dermal gel containing 500 mcg of estradiol hemihydrate in 1 sachet, 25 sachets per pack. Dosing regimen is similar to estrogel.

For the treatment of local urogenital disorders, the drug Ovestin (Netherlands) is used, which is oral tablets of 30 pieces per pack, containing 1 or 2 mg of estriol; vaginal cream in tubes of 15 g; vaginal suppositories 0.5 mg estriol.

These drugs are indicated for atrophy of the mucous membrane of the lower urinary tract due to estrogen deficiency, for pre- and postoperative treatment in the postmenopausal period during vaginal operations, as well as for diagnostic purposes with unclear results of a vaginal smear.

CONCLUSION

A wide selection of drugs for HRT in the Russian pharmaceutical market makes it possible to rationally use and select the necessary drug in each case. However, it should be remembered that before prescribing HRT and during treatment, a gynecologist's examination, ultrasound of the genitals, examination of the mammary glands, oncocytology, Paypel endometrial biopsy (Paipel Cornier - Pharma med, Canada), measurement of blood pressure, height, body weight, examination of the system hemostasis and lipid spectrum of blood, blood sugar, urinalysis. The first examination by a gynecologist a month after the start of hormone therapy, then after 3 months for 1 year, then 2 times a year.

Contraindications for HRT are: history and current thromboembolic complications, malignant tumors of the endometrium, uterus, breast, severe forms of liver dysfunction and severe diabetes mellitus, vaginal bleeding of unknown etiology.

It should be borne in mind that in the first months of treatment, soreness of the mammary glands, in rare cases, nausea, headache, swelling and some other side effects may be observed. These symptoms are usually transient and do not require discontinuation of the drug. However, with the appearance of unusually severe, migraine-like or frequent headaches, with visual or hearing impairments, the first signs of thrombosis, the appearance of jaundice or epileptic seizures, the onset of pregnancy, HRT preparations should be discontinued and an appropriate examination should be carried out.

LITERATURE

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THE MODERN PHARMACOLOGICAL MARKET DRUGS of SUBSTITUTIVE HORMONAL THERAPY (SHT)

Syzov D.J., Gurevich K.G., Popkov S.A.
Moscow State University of Medicine and Dentistry

The wide choice of drugs for SHT in the Russian pharmaceutical market enables of rational application and selection of a necessary drug in each concrete case. Before assignment SHT and during treatment the masses of a body, research of the system of a hemostasis and lipide spectrum of a blood, contents of saccharum in a blood, bulk analysis of urine are necessary gunecology survey, research of lactic Ferri lactases, oncocutology, Paypel biopsy of endometrium, measurement a HELL, body height.