Hormones along with chemotherapy simultaneous reception. Hormone therapy in oncology. Hormone therapy for uterine cancer in Israel

With the further progress of developed capitalism on the territory of Russia, a woman is increasingly faced with the need to maintain an attractive appearance and sexual activity right up to the grave.

It has long been known that since the onset of menopause, the level of estrogen providing:

• not only fertility,
• but also an acceptable state of the cardiovascular,
• musculoskeletal systems,
• skin and its appendages,
• mucous membranes and teeth

falls catastrophically.

The only hope of an aging lady some thirty years ago was the fat layer, due to which the last estrogen, estrone, was formed from androgens through metabolism through steroids. However, rapidly changing fashion brought to the catwalks, and then to the streets, a population of slender women, more reminiscent of drag queens and ingénue-pipis than heroine mothers and hard workers.

In pursuit of slim figure women somehow forgot about what a heart attack at fifty and osteoporosis at seventy are. Fortunately, gynecologists with the latest achievements pharmaceutical industry in the field of hormone replacement therapy. From about the beginning of the nineties, this direction, standing at the junction of gynecology and endocrinology, began to be considered a panacea for all women's misfortunes, from early menopause to femoral neck fractures.

However, even at the dawn of the popularization of hormones, in order to keep a woman flourishing, sound demands were made not to prescribe drugs to everyone indiscriminately, but to make an acceptable sample, separating women with high risks of oncogynecology and directly protecting them from the realization of risks.

Hence the moral: every vegetable has its time

Aging - although natural, is by no means the most pleasant episode in the life of every person. It brings with it such changes that do not always set the lady on positive tone and often quite the opposite. Therefore, with menopause, drugs and medications are often simply necessary to take.

Another question is how safe and effective they will be. It is precisely the balance between these two parameters that is the biggest problem of modern pharmaceutical industry and practical medicine: neither shooting a sparrow from a cannon, nor chasing an elephant with a slipper is impractical, and sometimes even very harmful.

Hormone replacement therapy in women today is very ambiguously evaluated and prescribed:

• Only in women without risk of breast, ovarian, endometrial cancer.
• If there are risks, but they were not noticed, the development of breast or ovarian cancer will be highly likely, especially if there is a zero stage of these cancers.
• Only in women with minimal risk thrombotic complications, therefore better in non-smokers with a normal body mass index.
• It is better to start in the first ten years from the last menstruation and not to start in women over 60. At least the effectiveness in younger women is much higher.
• Mostly patches from a combination of a small dose of estradiol with micronized progesterone.
• To reduce vaginal atrophy, local estrogen suppositories can be used.
• The benefits in the main areas (osteoporosis, ischemic changes in the myocardium) do not compete with safer drugs or are not completely proven, to put it mildly.
• Almost all ongoing studies have certain errors that make it difficult to draw unambiguous conclusions about the predominance of the benefits of substitution therapy over its risks.
• Any prescription of therapy should be strictly individual and take into account the specifics of the situation of a particular woman, for whom not only an examination before prescribing drugs is mandatory, but also ongoing follow-up for the entire duration of treatment.
• Domestic serious randomized trials with their own conclusions have not been conducted, national recommendations are based on international recommendations.

The further into the forest, the more firewood. With the accumulation of clinical experience with the practical use of hormone replacement, it became clear that women with initially low risks of breast cancer or uterine mucosa are not always safe, taking some categories of "pills of eternal youth."

How is the situation today, and on whose side is the truth: adherents of hormones or their opponents, let's try to figure it out here and now.

Combined hormonal agents

As hormone replacement therapy in menopause, combined hormonal agents and pure estrogens. Which drug will be recommended by the doctor depends on many factors. These include:

• patient's age,
• presence of contraindications
• body mass,
• severity of climacteric symptoms,
• concomitant extragenital pathology.

Klimonorm

One package contains 21 tablets. The first 9 yellow tablets contain an estrogenic component - estradiol valerate at a dosage of 2 mg. The remaining 12 tablets are brown in color and include estradiol valerate 2 mg and levonorgestrel 150 mcg.

The hormonal agent must be taken 1 tablet daily for 3 weeks, at the end of the package, a 7-day break should be taken, during which menstrual discharge will begin. In the case of a preserved menstrual cycle, tablets are taken from the 5th day, with irregular menstruation - on any day with the condition of excluding pregnancy.

The estrogen component eliminates negative psycho-emotional and autonomic symptoms. Common ones include: sleep disorders, hyperhidrosis, hot flashes, vaginal dryness, emotional lability, and others. The gestagenic component prevents the occurrence of hyperplastic processes and endometrial cancer.

Femoston 2/10

This drug is available as Femoston 1/5, Femoston 1/10 and Femoston 2/10. The listed types of funds differ in the content of estrogen and progestogen components. Femosten 2/10 contains 14 pink and 14 yellow tablets (28 pieces in total in a package).

Pink tablets contain only the estrogenic component in the form of estradiol hemihydrate in an amount of 2 mg. The yellow tablets consist of 2 mg estradiol and 10 mg dydrogesterone. Femoston must be taken daily for 4 weeks, without interruption. After the end of the package, you should start a new one.

Angelique

The blister contains 28 tablets. Each tablet contains estrogen and progestogen components. The estrogenic component is represented by estradiol hemihydrate at a dose of 1 mg, the progestogen component is drospirenone at a dose of 2 mg. Tablets should be taken daily, without observing a weekly break. After the end of the package, the reception of the next one begins.

pausegest

The blister contains 28 tablets, each contains estradiol in an amount of 2 mg and norethisterone acetate in a dose of 1 mg. Tablets begin to drink from the 5th day of the cycle with preserved menstruation and on any day with irregular periods. The drug is taken constantly, without observing a 7-day break.

Cyclo-Proginova

There are 21 tablets in a blister. The first 11 white tablets contain only the estrogenic component - estradiol valerate at a dosage of 2 mg. The next 10 light brown tablets consist of estrogenic and progestogen components: estradiol in the amount of 2 mg and norgestrel in a dosage of 0.15 mg. Cyclo-Proginova should be taken daily for 3 weeks. Then it is necessary to observe a week break, during which menstrual-like bleeding will begin.

Divigel

The drug is available in the form of a 0.1% concentration gel, which is used for external use. One sachet of Divigel contains estradiol hemihydrate in the amount of 0.5 mg or 1 mg. The drug must be applied to clean skin once a day. Recommended places for rubbing the gel:

• lower abdomen,
• small of the back,
• shoulders, forearms,
• buttocks.

The area of ​​application of the gel should be 1 - 2 palms. Recommended daily change of skin areas for rubbing Divigel. It is not allowed to apply the drug to the skin of the face, mammary glands, labia and irritated areas.

menorest

Produced in the form of a gel in a tube with a dispenser, the main active ingredient of which is estradiol. The mechanism of action and method of application are similar to Divigel.

Klimara

The drug is a transdermal therapeutic system. Produced in the form of a patch measuring 12.5x12.5 cm, which must be glued to the skin. The composition of this anti-menopausal agent includes estradiol hemihydrate in the amount of 3.9 mg. The patch is attached to the skin for 7 days, at the end of the week period, the previous patch is peeled off and a new one is attached. Recommended places for application of Climara are the gluteal and paravertebral regions.

Ovestin is available in tablets, vaginal suppositories, and as a cream for vaginal use. The most commonly prescribed form of the drug is vaginal suppositories. The composition of one suppository includes micronized estriol in the amount of 500 mcg. Candles are administered intravaginally daily, without interruption. The main role of the drug is to replenish estrogen deficiency in menopausal and postmenopausal periods.

estrogel

The drug is available in the form of a gel for external use in tubes with a dispenser. The tube contains 80 gr. gel, in one dose - 1.5 mg of estradiol. The main action is the elimination of the lack of estrogens in menopause and postmenopause. The rules for applying the gel are the same as for Divigel.

Advantages and disadvantages of using different forms of preparations. Click to enlarge.

Hormonal background

For a woman, the basic sex hormones can be considered estrogens, progestins and, paradoxically, androgens.

In a rough approximation, all these categories can be characterized as follows:

• estrogens are female hormones
• progesterone - pregnancy hormone
• androgens - sexuality.

estradiol, estriol, estrone are steroid hormones produced by the ovaries. It is also possible to synthesize them outside the reproductive system: the adrenal cortex, adipose tissue, bones. Their precursors are androgens (for estradiol - testosterone, and for estrone - androstenedione). In terms of effectiveness, estrone is inferior to estradiol and replaces it after menopause. These hormones are effective stimulators of the following processes:

• maturation of the uterus, vagina, fallopian tubes, mammary glands, growth and ossification of the long bones of the limbs, development of secondary sexual characteristics (hair growth along female type, pigmentation of the nipples and genital organs), proliferation of the epithelium of the vaginal and uterine mucosa, secretion of vaginal mucus, endometrial rejection during uterine bleeding.
• An excess of hormones leads to partial keratinization and desquamation of the vaginal lining, proliferation of the endometrium.
• Estrogens prevent absorption bone tissue, promote the production of blood coagulation elements and transport proteins, reduce the level of free cholesterol and low-density lipoproteins, reducing the risk of atherosclerosis, increase the level of the hormone in the blood thyroid gland, thyroxine,
• adjust receptors to the level of progestins,
• provoke edema due to the transition of fluid from the vessel into the intercellular spaces against the background of sodium retention in the tissues.

Progestins

mainly provide the onset of pregnancy and its development. They are secreted by the adrenal cortex, the corpus luteum of the ovaries, and during gestation - by the placenta. Also, these steroids are called gestagens.

• In non-pregnant women, they balance estrogens, preventing hyperplastic and cystic changes in the uterine mucosa.
• In girls, they help the maturation of the mammary glands, and in adult women they prevent breast hyperplasia and mastopathy.
• Under their influence, the contractility of the uterus and fallopian tubes decreases, their susceptibility to substances that enhance muscle tension(oxytocin, vasopressin, serotonin, histamine). Due to this, progestins reduce the pain of menstruation and have an anti-inflammatory effect.
• Reduce the sensitivity of tissues to androgens and are androgen antagonists, inhibiting the synthesis of active testosterone.
• A decrease in progestin levels determines the presence and severity of premenstrual syndrome.

Androgens, testosterone, in the first place, literally fifteen years ago, were accused of all mortal sins and were considered only harbingers in the female body:

• obesity
• acne
• increased hairiness
• hyperandrogenism was automatically equal to polycystic ovaries, and it was prescribed to deal with it by all available means.

However, as the accumulation practical experience it turned out that:

• a decrease in androgens automatically reduces the level of collagen in tissues, including the pelvic floor
• worsens muscle tone and leads not only to the loss of a tightened appearance women, but
• problems with urinary incontinence and
• excess weight gain.

Also, women with androgen deficiency clearly have a drop in sexual desire and are more likely to have an uneasy relationship with orgasm. Androgens are synthesized in the adrenal cortex and ovaries and are represented by testosterone (free and bound), androstenedione, DHEA, DHEA-C.

• Their level gradually begins to fall in women after 30 years.
• With natural aging, spasmodic falls, they do not give.
• A sharp decrease in testosterone is observed in women against the background of artificial menopause (after surgical removal of the ovaries).

climacteric

The concept of climax is known to almost everyone. Almost always in everyday life, the term has an irritable-tragic or even abusive connotation. However, it is worth understanding that the processes of age-related restructuring are completely natural events, which normally should not become a sentence or signify a dead end in life. Therefore, the term menopause is more correct, when against the background age-related changes processes of involution begin to dominate. In general, menopause can be divided into the following periods:

• Menopausal transition (on average, after 40-45 years) - when not every cycle is accompanied by the maturation of the egg, the duration of the cycles changes, they are called “confused”. There is a decrease in the production of follicle-stimulating hormone, estradiol, anti-Mullerian hormone and inhibin B. Against the background of delays, psychological stress, flushing of the skin, urogenital signs of estrogen deficiency may already begin to appear.
• Menopause is usually referred to as the last menstruation. Since the ovaries are turned off, after her menstruation no longer goes. This event is set retrospectively, after a year of absence menstrual bleeding. The timing of the onset of menopause is individual, but there is also an “average temperature in the hospital”: in women under 40, menopause is considered premature, early - up to 45, timely from 46 to 54, late - after 55.
• Perimenopause refers to menopause and the 12 months after it.
• Postmenopause is the period after. All the various manifestations of menopause are more often associated with early postmenopause, which lasts 5-8 years. In the late part of postmenopause, there is a pronounced physical aging of organs and tissues, which prevails over autonomic disorders or psycho-emotional stress.

What do you have to fight

perimenopause

can respond in a woman's body as episodes advanced level estrogen and lack of egg maturation (uterine bleeding, breast engorgement, migraine), and manifestations of estrogen deficiency. The latter can be divided into several groups:

• psychological difficulties: irritability, neurotypization, depression, sleep disturbances, performance decline,
• vasomotor phenomena: increased sweating, hot flashes,
• genitourinary disorders: vaginal dryness, itching, burning, increased urination.

Postmenopause

gives the same symptoms due to lack of estrogen. Later they are supplemented and replaced:

• metabolic abnormalities: accumulation of abdominal fat, a drop in the body's susceptibility to its own insulin, which can result in type 2 diabetes.
• cardiovascular: an increase in the level of atherosclerosis factors ( total cholesterol, low density lipoproteins), dysfunction of the vascular endothelium,
• musculoskeletal: accelerated resorption of bone mass, leading to osteoporosis,
• atrophic processes in the vulva and vagina, urinary incontinence, urination disorders, inflammation of the bladder.

Menopausal hormone therapy

Treatment hormonal drugs in women with menopause, they have the task of replacing deficient estrogens, balancing them with progestins in order to avoid hyperplastic and oncological processes in the endometrium and mammary gland. When choosing dosages, they proceed from the principle of minimum sufficiency, in which the hormones would work, but would not have side effects.

The purpose of the appointment is to improve the quality of life of a woman and prevent late metabolic disorders.

This is very important points, since the arguments of supporters and opponents of substitutes for natural female hormones are based on the assessment of the benefits and harms of synthetic hormones, as well as the achievement or non-achievement of the goals of such therapy.

The principles of therapy are the appointment in women under 60 years of age, despite the fact that the last unstimulated menstruation was in the lady no earlier than ten years ago. Combinations of estrogens with progestins are preferred, with low estrogen doses consistent with those of young women in the endometrial proliferating phase. Therapy should be started only after obtaining informed consent from the patient, confirming that she is familiar with all the features of the proposed treatment and is aware of its pros and cons.

When to start

Hormone replacement therapy preparations are indicated for:

• vasomotor disorders with mood changes,
• sleep disorders,
• signs of atrophy of the genitourinary system,
• sexual dysfunction,
• premature and early menopause,
• after removal of the ovaries,
• with a low quality of life against the background of menopause, including those caused by pain in the muscles and joints,
• prevention and treatment of osteoporosis.

Let's make a reservation right away that basically this is how Russian gynecologists look at the problem. Why this reservation, we will consider a little lower.

Domestic recommendations, with some delay, are formed on the basis of the opinions of the International Society for Menopause, whose recommendations in the 2016 edition list almost the same, but already supplemented items, each of which is supported by a level of evidence, as well as the recommendations of the American Association of Clinical Endocrinologists in 2017, which emphasize precisely on the proven safety of certain variants of gestagens, combinations and forms of drugs.

• According to them, tactics for women during the menopausal transition and for older age categories will differ.
• Appointments should be strictly individual and take into account all manifestations, the need for prevention, the presence of concomitant pathologies and family history, the results of studies, as well as the expectations of the patient.
• Hormonal support is only part of a general strategy to normalize a woman's lifestyle, including diet, rational physical exercise, rejection of bad habits.
• Replacement therapy should not be initiated unless there are clear signs of estrogen deficiency or physical consequences this deficit.
• A patient receiving therapy is invited to a gynecologist for a preventive examination at least once a year.
• Women whose natural or postoperative menopause occurs before age 45 have a higher risk of osteoporosis, cardiovascular disease, and dementia. Therefore, for them, therapy should be carried out at least until the average age of menopause.
• The issue of continuing therapy is decided individually, taking into account the benefits and risks for a particular patient, without critical age restrictions.
• Treatment should be at the lowest effective dosage.

Contraindications

In the presence of at least one of the following conditions, even if there are indications for replacement therapy, no one prescribes hormones:

• bleeding from the genital tract, the cause of which is not clear,
• breast oncology,
• endometrial cancer,
• acute deep vein thrombosis or thromboembolism,
• acute hepatitis,
• allergic reactions to drugs.

Estrogens are not indicated for:

• hormone dependent breast cancer
• endometrial cancer, including in the past,
• hepatocellular insufficiency,
• porphyria.

Progestins

• in case of meningioma

The use of these funds may be unsafe in the presence of:

• uterine fibroids,
• ovarian cancer in the past
• endometriosis,
• venous thrombosis or embolism in the past,
• epilepsy,
• migraine,
• cholelithiasis.

Application Variations

Among the routes of administration of replacement hormones are known: tableted through the mouth, injectable, transdermal, local.

Table: Pros and cons of different administration of hormonal drugs.

Pros:	Minuses:
Estrogen tablets
Just accept. A lot of experience has been accumulated in the application. The drugs are inexpensive. A lot of them. Can go in combination with progestin in one tablet.	Due to the different absorbability, an increased dose of the substance is required. Reduced absorption against the background of diseases of the stomach or intestines. Not indicated for lactase deficiency. Influence the synthesis of proteins by the liver. More contain less effective estrone than estradiol.
Skin gel
Easy to apply. The dose of estradiol is optimally low. The ratio of estradiol and estrone is physiological. Not metabolized in the liver.	Must be applied daily. More than pills. Suction may vary. Progesterone cannot be added to the gel. Less effectively affect the lipid spectrum.
skin patch
Low content of estradiol. Does not affect the liver. Estrogen can be combined with progesterone. There are forms with different dosages. You can quickly stop treatment.	Suction fluctuates. It does not stick well if it is humid or hot. Estradiol in the blood begins to decrease over time.
Injections
May be prescribed for the ineffectiveness of tablets. It is possible to prescribe in patients with arterial hypertension, disorders of carbohydrate metabolism, pathologies of the gastrointestinal tract, migraines. Provide fast and lossless delivery active substance into the body.	Complications from soft tissue injuries during injections are possible.

There are different tactics for different groups of patients.

One drug containing estrogen or progestin.

• Estrogen monotherapy is indicated after hysterectomy. In the course of estradiol, estradiolavalerate, estriol in a discontinuous course or continuously. Possible tablets, patches, gels, vaginal suppositories or tablets, injections.
• Isolated gestagen is prescribed in the menopausal transition or perimenopause in the form of progesterone or dydrogesterone in tablets to correct cycles and treat hyperplastic processes.

Combination of estrogen with progestin

• In intermittent or continuous cyclic mode (provided there are no endometrial pathologies) - usually practiced during the menopausal transition and perimenopause.
• For postmenopausal women, a continuous combination of estrogen and progestin is more commonly chosen.

At the end of December 2017, a conference of gynecologists was held in Lipetsk, where one of the central places was occupied by the issue of hormone replacement therapy in postmenopause. V.E. Balan, MD, Professor, President of the Russian Association for Menopause, voiced the preferred directions of substitution therapy.

Preference should be given to transdermal estrogens in combination with a progestin, preferably micronized progesterone. Compliance with these conditions reduces the risk of thrombotic complications. In addition, progesterone not only protects the endometrium, but also has an anti-anxiety effect, helping to improve sleep. The optimal dosage is 0.75 mg of transdermal estradiol per 100 mg of progesterone. For perimenopausal women, the same drugs are recommended at a ratio of 1.5 mg per 200.

Women with premature ovarian failure (premature menopause)

having higher risks for strokes, heart attacks, dementia, osteoporosis and sexual dysfunctions, should receive more high doses estrogen.

• At the same time, combined oral contraceptives can be used in them until the time of the middle onset of menopause, but transdermal combinations of estradiol and progesterone are preferred.
• For women with low sexual attraction(especially against the background of the removed ovaries), it is possible to use testosterone in the form of gels or patches. Since specific female preparations have not been developed, the same agents are used as in men, but at lower dosages.
• Against the background of therapy, there are cases of the onset of ovulation, that is, pregnancy is not excluded, so drugs for replacement therapy cannot be considered contraceptives at the same time.

Pros and cons of HRT

Assessing the ratio of the risks of complications from sex hormone therapy and their benefits in combating the symptoms of a deficiency of these hormones, it is worth analyzing each item of the alleged profit and harm separately, referring to serious clinical researches with a decent representative sample.

Breast cancer on the background of substitution therapy: oncophobia or reality?

• A lot of noise has been made lately by the British Medical Journal, which previously distinguished itself in heavy legal battles with the Americans about the safety and dosing regimen of statins and came out of these clashes very, very worthily. In early December 2017, the journal published data from almost a decade of research in Denmark, which analyzed the stories of about 1.8 million women from 15 to 49 years old who used different variations of modern hormonal contraceptives(combinations of estrogens and progestins). The conclusions were disappointing: the risk of invasive breast cancer in women who received combined contraceptives exists, and it is higher than in those who abstain from such therapy. The risk increases with the duration of contraception. Among those who use this method of contraception for a year, the drugs give one extra case of cancer in 7690 women, that is, the absolute increase in risk is small.
• Expert statistics presented by the president of the Russian Menopause Association that only every 25 women in the world die of breast cancer, and cardiovascular episodes are the most common cause of death, are so-so consolation.
• The WHI study shows hope that estrogen-progestin combination begins to significantly increase the risk of breast cancer no earlier than after five years of use, stimulating the growth of pre-existing tumors (including poorly diagnosed zero and first stages).
• However, the International Menopause Society also notes the ambiguity of the effects of replacement hormones on breast cancer risks. The risks are higher, the higher the body mass index of the lady, and the less active lifestyle she leads.
• According to the same society, the risks are less when using transdermal or oral forms of estradiol in combination with micronized progesterone (versus its synthetic variants).
• Thus, hormone replacement therapy after 50 increases the risk of progestin joining estrogen. A larger safety profile shows micronized progesterone. At the same time, the risk of recurrence in women who have previously had breast cancer does not allow them to prescribe replacement therapy.
• To reduce the risks, women with a low initial risk of breast cancer should be selected for replacement therapy, and annual mammograms should be performed against the background of ongoing therapy.

Thrombotic episodes and coagulopathy

• This is, first of all, the risk of strokes, myocardial infarctions, deep vein thrombosis and pulmonary embolism. Based on WHI results.
• In early postmenopausal women, this is the most common type of estrogen complication and increases as women age. However, with initially low risks in young people, it is low.
• Transcutaneous estrogens in combination with progesterone are relatively safe (data from less than ten studies).
• The frequency of deep vein thrombosis and PE is approximately 2 cases per 1000 women per year.
• According to the WHI, the risk of PE is less than in normal pregnancies: +6 cases per 10,000 with combination therapy and +4 cases per 10,000 with estrogen monotherapy in women 50-59 years old.
• The prognosis is worse in those who are obese and have had previous episodes of thrombosis.
• These complications are more common in the first year of therapy.

However, it should be noted that the WHI study was aimed more at identifying the long-term effects of replacement therapy for women who have passed more than 10 years after menopause. The study also used only one type of progestin and one type of estrogen. It is more suitable for testing hypotheses, and cannot be considered flawless with the maximum level of evidence.

The risk of stroke is higher in women whose therapy was started after the age of 60, while we are talking about an ischemic disorder cerebral circulation. At the same time, there is a dependence on oral long-term intake of estrogens (data from the WHI and the Cochrane study).

Oncogynecology is represented by cancer of the endometrium, cervix and ovaries

• Endometrial hyperplasia has a direct relationship with the intake of isolated estrogens. At the same time, the addition of progestin reduces the risk of uterine neoplasms (data from the PEPI study). However, the EPIC study, on the contrary, noted an increase in endometrial lesions during combination therapy, although the analysis of these data attributed the results to the probably lower adherence of the studied women to therapy. For the time being, the International Menopause Society has suggested that micronized progesterone at a dose of 200 mg per day for 2 weeks in the case of sequential therapy and 100 mg per day when combined with estrogen for continuous use is considered safe for the uterus.
• An analysis of 52 studies confirmed that hormone replacement therapy increased the risk of ovarian cancer by about 1.4 times, even if it was used for less than 5 years. For those who have at least a blueprint in this area, these are serious risks. An interesting fact is that early signs of ovarian cancer that have not yet been confirmed can be masked as manifestations of menopause, and it is for them that hormone therapy can be prescribed, which will undoubtedly lead to their progress and accelerate tumor growth. However, there are currently no experimental data in this direction. So far, we have agreed that there is no confirmed data on the relationship between the use of replacement hormones and ovarian cancer, since all 52 studies differed at least by some errors.
• Cervical cancer today is associated with the human papillomavirus. The role of estrogens in its development is poorly understood. Long-term cohort studies have found no association between the two. But at the same time, cancer risks were assessed in countries where regular cytological studies make it possible to timely detect cancer of this localization in women even before menopause. Data from the WHI and HERS studies were evaluated.
• Cancer of the liver and lung has not been associated with hormones, there is little information on stomach cancer, and there are suspicions that it is reduced during hormone therapy, as is colorectal cancer.

Expected benefit

Pathologies of the heart and blood vessels

This is the main cause of disability and mortality in postmenopausal women. It is noted that the use of statins and aspirin does not have the same effect as in men. Weight loss, the fight against diabetes, arterial hypertension should come first. Estrogen therapy may have a protective effect on the cardiovascular system when approaching the time of menopause and negatively affect the heart and blood vessels if its onset is delayed by more than 10 years from the last menstruation. According to the WHI, women 50-59 years of age were less likely to experience heart attacks during therapy, and there was a benefit in relation to the development of coronary heart disease, provided that therapy was started before 60 years of age. An observational study in Finland confirmed that estradiol preparations (with or without progestin) reduced coronary mortality.

The largest studies in this area were DOPS, ELITE and KEEPS. The first, Danish study, mainly focused on osteoporosis, incidentally noted a reduction in coronary deaths and hospitalizations for myocardial infarction among women with recent menopause who received estradiol and norethisterone or went without therapy for 10 years, and then were followed up for another 16 years. .

In the second, earlier and later prescription of tableted estradiol was evaluated (in women up to 6 years after menopause and later than 10 years). The study confirmed that early initiation of replacement therapy is important for the condition of the coronary vessels.

The third compared conjugated equine estrogens with placebo and transdermal estradiol, finding no significant difference in vascular health in relatively young healthy women over 4 years.

Urogenycology is the second direction, the correction of which is expected from the appointment of estrogen

• Unfortunately, as many as three large studies have shown that systemic estrogen use not only exacerbates existing urinary incontinence, but also contributes to new episodes. stress incontinence. This circumstance can greatly impair the quality of life. The latest mathematic analysis conducted by the Cochrane Group noted that only oral preparations have such an effect, and local estrogens seem to reduce these manifestations. As an added benefit, estrogens have been shown to reduce the risk of recurrent urinary tract infections.
• With regard to atrophic changes in the vaginal mucosa and urinary tract, here estrogens were at their best, reducing dryness and discomfort. At the same time, the advantage remained with local vaginal preparations.

Bone thinning (postmenopausal osteoporosis)

This is a large area, the fight against which is dedicated to a lot of effort and time of doctors of various specialties. Its most terrible consequences are fractures, including those of the femoral neck, which rapidly disable a woman, significantly reducing her quality of life. But even without fractures, loss of bone density is accompanied by chronic pain syndrome in the spine, joints, muscles and ligaments, which I would like to avoid.

No matter how nightingales gynecologists are filled with the topic of the benefits of estrogens for maintaining bone mass and preventing osteoporosis, even international organization on menopause in 2016, whose recommendations are essentially written off domestic protocols for replacement therapy, vaguely wrote that estrogens are the most appropriate option for preventing fractures in early postmenopause, but the choice of osteoporosis therapy should be based on a balance of effectiveness and costs.

Rheumatologists are even more categorical in this respect. Thus, selective estrogen receptor modulators (raloxifene) have not been shown to be effective in preventing fractures and cannot be considered the drugs of choice for the management of osteoporosis, giving way to bisphosphonates. Also, the prevention of osteoporotic changes is given to combinations of calcium and vitamin D3.

• Thus, estrogens are able to inhibit bone loss, but their oral forms have been mainly studied in this direction, the safety of which in relation to oncology is somewhat doubtful.
• Data on a decrease in the number of fractures on the background of replacement therapy have not been received, that is, today estrogens in terms of preventing and eliminating the severe consequences of osteoporosis are inferior to safer and more effective drugs.

Such treatment is recommended: a) for patients with massive lesions of regional lymph nodes(histologically proven invasion of three or four nodes of one of the collectors or metastases were found simultaneously in several groups of nodes, such as axillary and parasternal or subclavian, etc.); b) patients who are in the premenopausal period and menopause. Hormone therapy in young women, especially those under 30, and in old age(over 70 years of age) is not recommended. The latter is associated more with the risk of complications when using hormonal drugs than with low sensitivity to them.

As shown above, with multiple metastases in the lymph nodes found in the preparation after mastectomy, in more than half of the patients the tumor is a disseminated process, so hormone therapy is considered necessary. medical event aimed at combating carcinoma and tumor foci in distant organs. Although the mechanism of action of hormones is still unclear, the detection of specific hormone receptors in tumor cells suggests the possibility of their direct inhibition along with changes in the central regulatory systems during prolonged exposure to synthetic hormonal drugs. True, if latent dissemination of the tumor is suspected, chemotherapy is preferred, however, as experience has shown, the combination of chemotherapeutic and hormonal drugs leads to better long-term results due not only to mutual potentiation, but also to the anabolic effects of hormones, which to a certain extent remove the immunosuppressive effects of chemotherapy.

Hormone therapy for primary breast cancer usually begins with a bilateral oophorectomy, which allows both classical and non-classical estrogens to be removed from the body. Removal of the ovaries is especially indicated for patients of the pathogenetic group III (hypertensive-adrenal, see p. 36), it is less beneficial in patients of the pathogenetic group II (ovarian) and is not indicated for patients of groups I (young) and IV ("senile" form of cancer) groups. The literature provides numerous data on the correlation between adrenal steroidogenesis, in particular, an increase in the level of cortisol, an increase in the secretion of ACTH, an increase in the content of the metabolic and the appearance of cancer metastases (Deshpande, 1977). Long-term administration of corticosteroids is widely used to suppress adrenal function after oophorectomy. In other cases, after ovariectomy, androgenic hormones are used, which have a predominantly peripheral effect. The therapeutic effect of androgens is not strictly related to masculinization. The duration of administration cannot be estimated. For young women (up to 40 years of age), drugs are administered for several years after oophorectomy. Androgens are contraindicated in patients with a chromatin-negative characteristic of the tumor due to the worsening of the results by more than 2 times (Bavli Ya. L., Neishtadt E. L., 1968), therefore, most specialists prefer to carry out corticosteroid therapy after oophorectomy.

Experience has shown that the implementation of ovariectomy and hormone therapy after mastectomy causes a delay in the development of metastases only in the first 2 years of follow-up (table 11). In subsequent years, the results of treatment of this group of patients differ little from the results in the group of patients who did not receive hormone therapy.

Table 11. The frequency of occurrence of relapses and distant metastases in advanced form of primary cancer (4 or more metastatically affected axillary nodes detected during mastectomy) in patients in the premenopausal period and early menopause (randomized trial of 311 patients; Ravdin et al., 1970)

Endocrinological control after ovariectomy and hormonal therapy in patients with primary operable breast cancer is very difficult, since a significant part of patients before treatment do not reveal significant differences in the content of gonadotropins, prolactin, 17-p-estradiol, total estrogens, cholesterol, glucose, alkaline phosphatase and other biochemical components compared with healthy women. True, the concentration of estrogens and prolactin is significantly higher in patients in the premenopausal period than in the postmenopausal period (Malarkey et al., 1977). After ovariectomy, there is a significant increase in the level of non-classical phenol steroids (by 20%), a decrease in the level of excretion of classical estrogens and an increase in the content of 17-ketosteroids due to an increase in the activity of the adrenal glands.

The decrease in the content of phenol steroids and the normalization of the ratio of the concentrations of various estrogen fractions, which are further achieved under the influence of androgens or corticosteroids, are important for assessing the effect of hormonal drugs, but cannot serve as a criterion for the usefulness of treatment, since there is no parallelism between clinical course disease and endocrinological parameters (Stoll, 1977). It should be emphasized that there is a consensus on the advantages of surgical removal of the ovaries over radiation castration with additional hormone therapy for operable forms of breast cancer. Firstly, oophorectomy makes it possible to achieve a decrease in estrogenic activity in a shorter time, since the main source of the latter is the theca tissue and follicular ovarian cysts. Secondly, during laparotomy it is possible to clarify whether there is a metastatic lesion of the liver, retroperitoneal nodes and the ovaries themselves, the invasion of which by the tumor is observed in 3-15% and 5-9% of patients with stage III cancer, respectively. Finally, practice shows that the abandonment of the ovaries significantly reduces the therapeutic effect of the subsequent use of androgens and corticosteroids, and in some women leads to an increase in the level of gonadotropins under the influence of corticosteroids. The use of the latter to suppress adrenal function after radiation castration is not only ineffective, but also unsafe.

The detection of steroid hormone receptors in tumor cells (they can be found in almost 2/3 of patients, more often in premenopausal and menopausal women) is also an indication for targeted hormone therapy, although this is not enough to predict a favorable response to treatment. The absence of receptors, in particular estrogen (ER), in a primary breast tumor can be combined with earlier and more frequent occurrence of local recurrences and metastases, regardless of other prognostic factors (tumor size, its location, metastases in regional lymph nodes, the patient's age, the use of additional hormonal or chemotherapy). For example, according to Knaight et al. (1977), out of 145 patients with primary breast cancer, ER in the tumor was absent in 54; of the latter, 18 (34%) had metastases within 18 months of mastectomy compared with 13 of 91 patients (14%) who had ER. In patients with metastases in regional nodes in the absence of ER, the interval between mastectomy and the appearance of distant metastases was half as long. Biggest difference was observed in patients younger than 50 years (35 and 8%, respectively). There are reliable observations indicating that not only ER in carcinomas of patients in the postmenopausal period are much more common than in the premenopausal period, but their content in tumors is 2-4 times higher. The latter is explained by endogenous estrogens, "occupying" receptors and thereby preventing the addition of exogenous estradiol (Yeltsina N.V., 1978). In addition, the concentration of ER varies from 5 to 2000 femtomol per 1 mg of protein (in menopause, an ER concentration of 0.15 femtomol per 1 mg of dry mass of the tumor is considered negative, more than 0.25 is positive, and in patients who have undergone ovariectomy, less than 0, 4 - negative, more than 0.75 - positive).

Assessing the role of various hormonal receptors still encounters numerous difficulties, not only because of defects in the technique for their detection, but also because of the unclear data on their activity. There are a number of key factors to consider. For example, to understand the interaction between a tumor cell and a hormone, it is important to evaluate the totality of biosynthetic elements, nuclear translocation. Seasonal biological fluctuations in the amount of ER and their dependence on the menstrual cycle were revealed. It is still difficult to make a final conclusion about the role of ER and PR (progestin receptors). Nevertheless, treatment with physiologically inactive antiestrogen drugs (nonsteroidal antihormones) that directly affect the tumor cell and do not affect the central mechanisms of hormone genesis is already being successfully developed. According to Leis (1977), the use after mastectomy of one of the antiestrogenic drugs - tamoxifen (nafoxidine, clomiphene are also used) at a dose of 10 mg 2 times a day (first month), 10 mg 3 times a day (second and third months) and 10 mg 2 times a day (fourth month) upon detection of ER and PR in patients of premenopausal and menopausal age with a tumor classified as stage III (T3N2M0), led in 90% of patients to a relapse-free course in the first 2 years after mastectomy. Sufficient efficacy of antiestrogen therapy in the treatment of cancer metastases has been proven, according to Stoll (1977), which has a great future.

Attempts are being made to create compounds that have both cytostatic and antisteroidal properties (similar drugs are already used, for example, estramustine phosphate, prednimustine).

Thus, indications for additional hormone therapy after mastectomy are based on the following principles:
1. Indications for oophorectomy followed by androgen and (or) corticosteroid therapy are:
a) local spread of the tumor (diameter 5 cm or more, infiltrative character, fast growth, inflammatory changes, ulcerations) and multiple lesions of regional lymph nodes (3 nodes or more with histological examination after mastectomy)
b) predominantly premenopausal period and menopause;
c) chromatin-positive (detection of Barr bodies in more than 20% of 500 tumor cells) characteristic of the primary node or "metastases in the lymph nodes.
2. There are the following indications for the use of estrogens and progestins:
a) the presence of ER and PR in tumor cells in patients in the premenopausal period and menopause;
b) deep menopause (over 5 years, preferably over 10 years);
As mentioned above, in all cases, additional hormone therapy should be combined with the introduction of chemotherapeutic drugs.

Hormones(Greek, hormaino to set in motion, induce) - biologically active substances that are the most important regulators of metabolism and body functions. They are formed in the secretory cells of the endocrine glands and some other tissues and are released into the blood and lymph. Features of hormones are that they are formed by specialized cells, are released into the circulating body fluids, have a high specific biological activity, act on organs and tissues located far from the place of hormone synthesis (distance action). Previously, it was believed that a substance can be called a true hormone if it has all of the listed properties, but hormones have now been discovered that manifest their action at the site of synthesis.

The effect of hormones on metabolism and energy is carried out mainly through a change in the activity of certain enzymes, and hormones either directly affect their synthesis, or the synthesis of other substances involved in a particular enzymatic process. The action of hormones can be inhibited by equal compounds, which are sometimes called antihormones.

The flow of hormones into the blood is regulated primarily by nervous system using chemical signals from the hypothalamus (neurohumoral regulation). These signals are "served" by hypothalamic neurohormones and, in response to them, so-called triple hormones are formed in the pituitary gland, which determine the synthesis and release into the blood of the hormone from the corresponding endocrine gland.

An increase in the blood content of any hormone in comparison with the physiological norm causes inhibition of the formation of the corresponding releasing factor by the hypothalamus, which entails a decrease in the amount of tropic hormone synthesized in the pituitary gland, and as a result, a decrease in the release of this hormone into the bloodstream until its concentration in the blood.

A decrease in the blood concentration of any hormone, on the contrary, stimulates the synthesis of the corresponding releasing factor and ultimately causes the release of an additional amount of the hormone into the bloodstream until its concentration in the blood reaches the physiological norm.

This is the negative feedback mechanism that dynamically supports the most complex system of neurohumoral regulation of body functions within physiological limits. The intensity of hormone synthesis also depends on the content in the body of a substance whose metabolism is controlled by this hormone: the higher, for example, the content of glucose in the blood, the more insulin is released into the bloodstream to normalize its concentration in the blood; insufficient intake of sodium salts causes an increase in the secretion of the hormone aldosterone, which ensures sodium retention in the body, and so on.

The release of any hormone into the bloodstream changes during the day: most often it is higher in the morning and lower in the evening, more hormones are released in the winter months than in the summer. The content of most hormones in the blood also depends on gender and age. Pregnancy, puberty and menopause are also characterized by a change in the concentration of hormones in the blood. A persistent violation of the synthesis of hormones in the direction of an increase or decrease in comparison with the norm is the cause of serious diseases, such as acromegaly, diabetes mellitus, diffuse toxic goiter, etc.

Many hormones, natural or artificially synthesized, are used in medicine as medicines (see below Hormonal preparations, Hormone therapy).

hormone therapy(hormone[s] + Greek, therapeia treatment) - treatment of various diseases with hormonal drugs.

With endocrine diseases hormone therapy is aimed at normalizing the hormonal status and metabolic processes that are disturbed as a result of insufficient or excessive function of the endocrine glands. In non-endocrine diseases, the role of hormone therapy lies in the specific effect on individual stages of the development of the disease.

Hormone therapy in endocrine diseases. Depending on the functional state the corresponding endocrine gland conventionally distinguish between replacement, stimulating and inhibitory, or blocking, hormone therapy.

Hormone replacement therapy is used for endocrine diseases characterized by complete loss or a significant decrease in the function of the gland (or glands) of internal secretion, in order to eliminate the deficiency of the corresponding hormones (or one hormone) in the body. The patient is prescribed drugs of these hormones or their analogues, for example, dehydrotachysterol - an analogue of parathyroidin or anabolic steroids - analogues of androgens (Anabolic agents). Hormone replacement therapy is effective only during the period of use of hormones or appropriate hormonal preparations, since it does not eliminate the causes of the disease. As a rule, hormone replacement therapy is lifelong. Such is the treatment of diabetes mellitus with insulin (see Diabetes mellitus), glucocorticoid hormones and their drugs for Addison's disease, thyroid hormones (thyroidin, etc.) for hypothyroidism, sex hormones for primary hypogonadism, and so on. The initial and maintenance dose of the hormonal drug is selected individually under strict clinical control with the obligatory consideration of the functional state of the patient's body. daily dose the drug is distributed taking into account physiological fluctuations in the flow of the corresponding hormone into the bloodstream.

Stimulating hormone therapy is used when it is necessary to increase the insufficient functional activity of the endocrine gland or to assess its functional reserves. For this purpose, hormones of the anterior pituitary gland and hypothalamic neurohormones are used. Long-term, or course, stimulating hormone therapy is used quite rarely, mainly for the treatment of secondary hypogonadism. A variety of stimulating hormone therapy is the intermittent administration of hormonal drugs. This type of hormone therapy is used to stimulate hypoplastic adrenal glands along with the administration of ACTH or its synthetic analogue, synacthen, in patients who have received glucocorticoid hormones daily for a long time, after unilateral adrenalectomy, etc.

Inhibitory (blocking) hormone therapy is used to treat absolute or relative hyperfunction of the endocrine gland or in complex treatment hormonally dependent tumors. The blockade of the pathological influence of a hormone that enters the body in excess can be carried out both directly by suppressing the function of the gland, and by administering a hormone whose action is opposite to that of a hormone that enters the body in excess. However, the possibilities of inhibitory hormone therapy are usually limited in comparison with operational methods treatment and radiation therapy.

Hormone therapy for non-endocrine diseases refers to pathogenetic therapy, as it allows you to influence some of the mechanisms of the development of the disease. Most of all, hormone therapy of this kind uses hormones of the adrenal cortex - glucocorticoids, which have a wide range of therapeutic effects and can affect the activity of enzyme systems and cellular metabolism. Anabolic steroids and sex hormones occupy an important place in hormone therapy for non-endocrine diseases.

Hormone therapy in children requires special attention, since the appointment of any hormonal drug entails inhibition of the function of the corresponding endocrine gland, the morphological and physiological development of which ends on average by the age of 25. Based on this, children are prescribed (if absolutely necessary) hormones with a short biological half-life (hydrocortisone, prednisolone). It is better for a child to take hormones in the morning. Special care is required when prescribing insulin to children. The appearance of sugar in the urine is not always diabetes. Many pathological conditions mimic the clinical picture of diabetes mellitus, but not all are due to insulin deficiency (renal diabetes). Correction of such metabolic disorders in a hospital excludes the use of hormonal drugs. Anabolic hormones can be prescribed to children after infectious diseases, with some endocrine diseases, but they are contraindicated in diseases of an infectious-allergic nature (glomerulonephritis, rheumatism, collagenoses, etc.).

All hormonal preparations for children can only be prescribed by a doctor. Hormone therapy in children is carried out under constant monitoring: it is necessary to carefully monitor changes in body weight, the state of the gastrointestinal tract. When prednisolone is used, the concentration of calcium and glucose in the blood is systematically determined, whether the growth of hair on the body has increased, whether there are signs arterial hypertension, abdominal syndrome, adrenal insufficiency.

Hormonal drugs - medicines containing natural hormones or their synthetic substitutes. Most hormonal preparations containing natural hormones (corticotropin, thyrotropin, insulin, etc.) are obtained from animal tissues and subjected to biological standardization.

According to the chemical structure, preparations of natural hormones include:

To substances of a protein and polypeptide structure, for example, preparations of hormones of the pituitary gland, parathyroid and pancreas, calcitonin;

To derivatives of amino acids, for example, preparations of thyroid hormones (with the exception of calcitonin);

To steroid compounds, for example, preparations of hormones of the adrenal cortex and gonads.

Synthetic hormone replacements may have a different chemical structure than the corresponding natural hormones. Some groups of hormonal drugs have special group names; for example,

Hormonal drugs that have the properties of the male sex hormone are referred to as androgens,

Hormonal preparations that exhibit the properties of follicular hormones - like estrogens,

Hormonal preparations with the properties of the corpus luteum hormone - like gestagens.

Preparations of hormones of the adrenal cortex are called corticosteroids.

Hormonal preparations are used for diseases associated with insufficient production of the corresponding hormones in the patient's body (insulin - in diabetes mellitus, triiodothyronine - in myxedema, sex hormone preparations - in hypofunction of the sex glands, etc.). Such therapy is substitution and is carried out for a long time, sometimes throughout the life of the patient. Some hormonal drugs are used for diseases not associated with hormonal deficiency. For example, glucocorticoid drugs are prescribed as anti-inflammatory and antiallergic drugs, mineralocorticoids - for myasthenia gravis.

In diseases caused by excessive production of any hormones, antagonists of the corresponding hormones are prescribed. For example, for the treatment of hyperthyroidism, antithyroid drugs are used, and for acromegaly, drugs that suppress the production of growth hormone (bromocriptine, etc.) are used. In some cases, mutual antagonism of hormonal drugs is used. So, with tumors dependent on the production of estrogens (breast cancer in women of mature age), androgenic drugs are used; with fibrous osteodystrophy, which develops as a result of excessive production of parathyroid hormone, calcitonin preparations. To suppress the production of gonadotropic hormones in order to prevent pregnancy, contraceptives containing estrogens and gestagens are used.

The use of hormonal drugs may be accompanied by side effects : glucocorticoids can cause ulceration of the gastric mucosa and duodenum, osteoporosis; thyroid hormone preparations - weight loss, cardiac arrhythmias; insulin - an excessive decrease in blood sugar levels (hypoglycemia), etc. Hormone preparations, the production of which is regulated by the corresponding pituitary hormones, inhibit the production of the patient's own hormones according to the principle of negative feedback. So, glucocorticoid drugs suppress the production of ACTH and, as a result, with prolonged use, they can inhibit the functions of the adrenal cortex, which leads to a decrease in the release of natural glucocorticoids from them.

Medicinal plants: goji

Be healthy!

Unfortunately, disappointing statistics indicate that the number of breast cancer patients has increased significantly. Therefore, it is worth knowing which procedures are suitable, as well as the possible consequences of hormone therapy for breast cancer. But let's start in order.

Definition of an ailment

Breast/mammary cancer, or the more scientific medical name, carcinoma, is nothing more than a malignant neoplasm in the glandular tissue. The disease can begin its development, both in the male and in the female body, despite the misconception of many. Let not a large percentage - 1% - but such a possibility exists. To date, this disease unfortunately, it is gaining momentum and acquiring the status of a scourge of the population.

Attention! This disease is very common in Europe, and very rare in Japan.

It is worth mentioning the age at which the disease manifests itself statistically more often: in women - from 45 years old, in men - from 62 years old. The peak age for both men and women is 65 years.

Interesting! Although the treatment is very difficult, there has been a recent trend in developed countries to increase the number of patients who have recovered. This is primarily due to timely diagnosis and examination.

Treatment with hormone therapy

Based on numerous studies in the field of this disease, it has been established that its manifestation in most cases is due to some disturbances in the functioning of the systems responsible for the production of hormones. It is these failures that lead, first to education, and then to growth. malignant tumors. So, the procedure of hormone therapy for breast cancer is aimed at replacing the wrong hormones. Applies in cases:

• when breast cancer is hormone-dependent (has a positive reaction to certain hormones);
• when the disease recurs and it comes back.

Based on blocking special preparations, those hormones that the patient's body produces on its own. This limits the effect of these hormones on the tissues of the body. Hormone therapy for breast cancer is a systematic approach to the treatment of the disease, and works better in combination with other methods - surgery, radiation and. The main task of such hormonal treatment, is the avoidance of re-return pathology. On the this moment hormone treatment, as an independent method, is not used.

Note! The procedure has been one of the most successful remedies in the fight against breast cancer for over a hundred years.

Drugs and their mechanism of action

The effectiveness of the treatment is due to the fact that the drugs, affecting the hormones that the female body produces, suppress their influence, and thereby reduce the action of cancer cells, further killing them altogether. Considering that up to 75% of all breast cancers arise precisely because of a malfunction of the hormonal systems (cancer cells have receptors for sensitivity to female hormones- estrogen and progesterone), then this treatment is very effective.

The determination of the number of such receptors is carried out using a biopsy. As a result, there are the following analytical conclusions:

• 75 percent of tumors are diagnosed with ERC + (estrogen receptors), which makes it possible to resort to hormone therapy;
• 65 percent are PR+ (progesterone receptors). Therapy is also possible;
• 25 percent are diagnosed as “hormonally negative”, which makes it impossible to use hormone therapy for breast cancer due to an insufficient number of receptors;
• if the rules for storing the sample were not followed, or its quantity was too small, it is possible to conclude that the hormonal status has not been clarified.

Important! Until 2005, one known drug was tamoxifen. In the future, other substances-inhibitors, for example, Aromasin, began to be used.

Types of treatment

The main types of treatment with hormonal drugs include prophylactic, neoadjuvant and therapeutic methods. The first is carried out after the main procedures (for example, surgery), the second - before, to reduce the tumor and the third - when the operation is not possible, aimed at reducing the focus or its complete elimination.

These methods differ from each other primarily by the purpose for which they are used. So, there are blocking, elimination or reduction of action. Each of them has its positive aspects and negative consequences. It is possible to determine which method to choose only by taking into account a number of factors, ranging from the hormonal status of the tumor to the stage of menopause.

Side effects

Undoubtedly, there are side effects of hormone therapy for breast cancer, since this is a direct effect on one of the most important systems of the female body. However, their effect is not as great as is commonly thought.

The choice in this situation is relative and completely independent. In any case, agreeing or refusing hormonal intervention will have its pros and cons. The only thing is to properly study the issue and know what you might encounter.

If you study the reviews of doctors and patients about hormone therapy for breast cancer, it becomes clear that the results and consequences depend on a number of factors - primarily on the drug. These effects can last different time- from short-term effects to quite serious ones.

As mentioned above, the effect of the drug and its consequences may be different, but common ones can be distinguished:

• mood swings, depression;
• weight gain, swelling;
• untimely arrival of menopause;
• throwing into the heat;
• dryness of the vagina.

The actions of hormone therapy are very individual, so after going through all the diagnostic examinations, you should consult a doctor and determine all possible consequences. However, it is important to carefully weigh the pros and cons, leaning more towards the final deliverance from a terrible disease.

In women for the prevention and correction pathological disorders associated with menopause, various non-drug, drug and hormonal agents are used.

Over the past 15-20 years, specific hormone replacement therapy for menopause (HRT) has become widespread. Despite the fact that for a very long time there were discussions in which an ambiguous opinion was expressed on this issue, the frequency of its use reached 20-25%.

Hormone therapy - pros and cons

The negative attitude of individual scientists and practitioners is justified by the following statements:

• the danger of interference in the "fine" system of hormonal regulation;
• inability to develop correct treatment regimens;
• interference with the natural aging processes of the body;
• the impossibility of accurate dosing of hormones depending on the needs of the body;
• side effects of hormone therapy in the form of the possibility of developing malignant tumors, cardiovascular diseases and vascular thrombosis;
• the lack of reliable data on the effectiveness of the prevention and treatment of late complications of menopause.

Mechanisms of hormonal regulation

Preservation of the constancy of the internal environment of the body and the possibility of its adequate functioning as a whole is provided by a self-regulating hormonal system of direct and feedback. It exists between all systems, organs and tissues - the cerebral cortex, nervous system, endocrine glands, etc.

The frequency and duration of the menstrual cycle, the onset are regulated by the hypothalamic-pituitary-ovarian system. The functioning of its individual links, the main of which are the hypothalamic structures of the brain, is also based on the principle of direct and feedback between each other and with the body as a whole.

The hypothalamus constantly releases gonadotropin-releasing hormone (GnRH) in a certain pulsed mode, which stimulates the synthesis and secretion of the anterior pituitary gland of follicle-stimulating and luteinizing hormones (FSH and LH)). Under the influence of the latter, the ovaries (mainly) produce sex hormones - estrogens, androgens and progestins (gestagens).

An increase or decrease in the level of hormones of one link, which is also influenced by both external and internal factors, respectively, entails an increase or decrease in the concentration of hormones produced by the endocrine glands of other links, and vice versa. This is the general meaning of the feed-and-feedback mechanism.

Rationale for the need to use HRT

Menopause is a physiological transitional stage in a woman's life, characterized by involutive changes in the body and the extinction of the hormonal function of the reproductive system. In accordance with the classification of 1999, during menopause, starting from 39-45 years and lasting up to 70-75 years, there are four phases - premenopause, postmenopause and perimenopause.

The main trigger in the development of menopause is the age-related depletion of the follicular apparatus and the hormonal function of the ovaries, as well as changes in the nervous tissue of the brain, which leads to a decrease in the production of progesterone and then estrogen by the ovaries, and to a decrease in the sensitivity of the hypothalamus to them, and hence to a decrease in synthesis of GnRg.

At the same time, in accordance with the principle of the feedback mechanism, in response to this decrease in hormones in order to stimulate their production, the pituitary gland “responds” with an increase in FSH and LH. Thanks to this “boosting” of the ovaries, the normal concentration of sex hormones in the blood is maintained, but already with a tense function of the pituitary gland and an increase in the content of hormones synthesized by it in the blood, which is manifested in blood tests.

However, over time, estrogen becomes insufficient for the corresponding reaction of the pituitary gland, and this compensatory mechanism is gradually depleted. All these changes lead to dysfunction of other endocrine glands, hormonal imbalance in the body with manifestation in the form of various syndromes and symptoms, the main of which are:

• climacteric syndrome occurring in premenopause in 37% of women, in 40% - during menopause, in 20% - 1 year after its onset and in 2% - 5 years after its onset; climacteric syndrome is manifested by a sudden feeling of hot flashes and sweating (in 50-80%), bouts of chills, psycho-emotional instability and unstable blood pressure (often elevated), heart palpitations, numbness of the fingers, tingling and pain in the heart area, memory impairment and sleep disturbances , depression, headache other symptoms;
• genitourinary disorders - decreased sexual activity, dryness of the vaginal mucosa, accompanied by burning, itching and dyspareunia, pain when urinating, urinary incontinence;
• dystrophic changes in the skin and its appendages - diffuse alopecia, dry skin and increased fragility of nails, deepening of skin wrinkles and folds;
• metabolic disturbances, manifested by an increase in body weight with a decrease in appetite, fluid retention in the tissues with the appearance of pastosity of the face and swelling of the legs, a decrease in glucose tolerance, etc.
• late manifestations - a decrease in bone mineral density and the development of osteoporosis, hypertension and coronary heart disease, Alzheimer's disease, etc.

Thus, against the background of age-related changes in many women (37-70%), all phases of the menopause may be accompanied by one or another dominant complex pathological symptoms and syndromes of varying severity and severity. They are caused by a deficiency of sex hormones with a corresponding significant and steady increase in the production of gonadotropic hormones of the anterior pituitary - luteinizing (LH) and follicle-stimulating (FSH).

Hormone replacement therapy for menopause, taking into account the mechanisms of its development, is a pathogenetically substantiated method that allows preventing, eliminating or significantly reducing dysfunction of organs and systems and reducing the risk of developing serious illnesses associated with deficiency of sex hormones.

Hormone therapy drugs for menopause

The main principles of HRT are:

1. Use only drugs similar to natural hormones.
2. The use of low dosages that correspond to the concentration of endogenous estradiol in young women up to 5-7 days of the menstrual cycle, that is, in the proliferative phase.
3. The use of estrogens and progestogens in various combinations, which allows to exclude the processes of endometrial hyperplasia.
4. In cases of postoperative absence of the uterus, the possibility of using only estrogens in intermittent or continuous courses.
5. The minimum duration of hormone therapy for the prevention and treatment of coronary heart disease and osteoporosis should be 5-7 years.

The main component of preparations for HRT are estrogens, and the addition of gestagens is carried out in order to prevent hyperplastic processes in the uterine mucosa and control its condition.

Tablets for replacement therapy for menopause contain the following groups of estrogens:

• synthetic, which are constituents - ethinylestradiol and diethylstilbestrol;
• conjugated or micronized forms (for better absorption in the digestive tract) of the natural hormones estriol, estradiol and estrone; these include micronized 17-beta-estradiol, which is part of drugs such as Clicogest, Femoston, Estrofen and Trisequens;
• ether derivatives - estriol succinate, estrone sulfate and estradiol valerate, which are components of the preparations Klimen, Klimonorm, Divina, Proginova and Cycloproginova;
• natural conjugated estrogens and their mixture, as well as ether derivatives in Hormoplex and Premarin preparations.

For parenteral (cutaneous) use in the presence of severe diseases of the liver and pancreas, migraine attacks, arterial hypertension of more than 170 mm Hg, gels (Estrazhel, Divigel) and patches (Klimara) containing estradiol are used. When using them and an intact (preserved) uterus with appendages, it is necessary to add progesterone preparations ("Utrozhestan", "Dufaston").

Substitution therapy preparations containing gestagens

Gestagens are produced with varying degrees activity and have a negative effect on carbohydrate and lipid metabolism. Therefore, they are used in the minimum sufficient dosages necessary for the regulation secretory function endometrium. These include:

• dydrogesterone (Dufaston, Femoston), which does not have metabolic and androgenic effects;
• norethisterone acetate (Norkolut) with androgenic effect - recommended for osteoporosis;
• Livial or Tibolon, which are close in structure to Norkolut and are considered the most effective drugs in the prevention and treatment of osteoporosis;
• Diane-35, Androkur, Klimen containing cyproterone acetate, which has an antiandrogenic effect.

Combined replacement therapy preparations, which include estrogens and progestogens, include Triaklim, Klimonorm, Angelik, Ovestin, and others.

Modes of taking hormonal drugs

Various modes and schemes of hormonal therapy for menopause have been developed, which are used to eliminate early and late consequences associated with insufficiency or absence of hormonal ovarian function. The main recommended schemes are:

1. Short-term, aimed at preventing menopausal syndrome - hot flashes, psycho-emotional disorders, urogenital disorders, etc. The duration of treatment according to the short-term scheme is from three months to six months with the possibility of repeating courses.
2. Long-term - for 5-7 years or more. Its goal is the prevention of late disorders, which include osteoporosis, Alzheimer's disease (the risk of its development is reduced by 30%), heart and vascular diseases.

There are three modes of taking tablets:

• monotherapy with estrogenic or progestogen agents in a cyclic or continuous mode;
• biphasic and triphasic estrogen-progestogen preparations in cyclic or continuous mode;
• combination of estrogens with androgens.

Hormone therapy for surgical menopause

It depends on the volume of the surgical intervention and the age of the woman:

1. After removal of the ovaries and a preserved uterus in women under 51, it is recommended to take 2 mg of estradiol in a cyclic regimen with 1 mg of cyprateron or 0.15 mg of levonorgestrel, or 10 mg of medroxyprogesterone, or 10 mg of dydrogesterone, or 1 mg of estradiol with dydrogesterone 10 mg.
2. Under the same conditions, but in women aged 51 and older, as well as after high supravaginal amputation of the uterus with appendages - in a monophasic regimen, taking estradiol 2 mg with norethisterone 1 mg, or medroxyprogesterone 2.5 or 5 mg, or diagnostics according to 2 mg, or drosirenone 2 mg, or estradiol 1 mg with dydrosterone 5 mg. In addition, it is possible to use Tibolone (belongs to the drugs of the STEAR group) at 2.5 mg per day.
3. After surgical treatment with the risk of relapse - taking monophasic estradiol with dienogest 2 mg or estradiol 1 mg with dydrogesterone 5 mg, or STEAR therapy.

Side effects of HRT and contraindications to its use

Possible side effects of hormone therapy for menopause:

• engorgement and soreness in the mammary glands, the development of tumors in them;
• increased appetite, nausea, abdominal pain, biliary dyskinesia;
• pastosity of the face and legs due to fluid retention in the body, weight gain;
• dryness of the mucous membrane of the vagina or an increase in cervical mucus, uterine irregular and menstrual bleeding;
• migraine pain, increased fatigue and general weakness;
• spasms in the muscles of the lower extremities;
• the occurrence of acne and seborrhea;
• thrombosis and thromboembolism.

The main contraindications to hormonal therapy for menopause are as follows:

1. Malignant neoplasms of the mammary glands or internal genital organs in history.
2. Bleeding from the uterus of unknown origin.
3. Severe diabetes.
4. Hepato-renal insufficiency.
5. Increased blood clotting, a tendency to thrombosis and thromboembolism.
6. Violation of lipid metabolism (possibly external use of hormones).
7. The presence of or (contraindication to the use of estrogen monotherapy).
8. Hypersensitivity to the drugs used.
9. The development or worsening of the course of diseases such as, autoimmune diseases connective tissue, rheumatism, epilepsy, bronchial asthma.

Timely and adequately used and individually selected hormone replacement therapy can prevent serious changes in a woman's body during menopause, improve not only her physical, but also her mental state, and significantly improve the level of quality.