Estrogen drugs used in the treatment of tumors

Rating of phytoestrogens: choosing the best

Sooner or later, every woman begins to think about menopause, and these thoughts are far from joyful. The new condition causes rejection not so much as a reminder of age, but rather due to unpleasant symptoms that seriously affect the quality of life. These are sudden hot flashes, mood swings, sudden weight gain, insomnia.

Of course, today there are ways to alleviate the symptoms of menopause and maintain hormonal levels. The two most common are taking hormonal drugs or taking phytoestrogens. What to choose?

Phytoestrogens or hormones?

45% of women take hormonal medications during menopause. This therapy is called replacement therapy: small doses of hormones (progesterone, estrogen) enter the body, which compensate for the lack of its own. By restoring hormonal balance, the symptoms of menopause become less pronounced.

However, hormones have quite serious side effects. Therefore, hormones can be taken for 3-5 years, and menopause lasts on average 7-10 years. In addition, such therapy is contraindicated in some fairly common diseases. For example, it is not recommended for women with varicose veins, since taking hormones further increases blood clotting and increases the risk of thrombosis. Hormone replacement therapy is not suitable for women with endometriosis, uterine fibroids, or breast tumors, since the condition will worsen due to an increase in estrogen concentration. Taking hormones can trigger breast cancer if there is a hereditary predisposition.

An alternative to hormones are phytoestrogens. These are non-hormonal plant components that can partially replace the female body’s own hormones. They are indicated both in the early stages of menopause and after menopause with mild or moderate symptoms of menopause.

Herbal components have a very gentle effect on the body - they are 1000–1500 times weaker than hormonal drugs. This is more of a plus than a minus. Phytoestrogens can be taken for a long time; they have no side effects or contraindications, like hormonal drugs.

Sex hormone preparations and their analogues

Home Medical Encyclopedia Medicines Medicines used to treat malignant neoplasms

See also diethylstilbestrol, methylandrostenediol, methyltestosterone, thyroidin, levothyroxine sodium, hydrocortisone, betamethasone, cortisone, methylprednisolone, solu-medrol, depomedrol, prednisolone, triamcinolone, clomiphene citrate, sinestrol, testosterone propionate, “tetrasterone” solution in oil for injection ects, testenate.

MEDROTESTRONA PROPIONATE (Medrotestroni propionas)

Synonyms: Methyldihydrotestosterone propionate, Mesterone, Dgostapolon, Masteril, Permastil, Propionas, Emdisterone.

Pharmachologic effect. Its structure and action are similar to testosterone propionate; has an antitumor effect, but has a higher anabolic (increasing protein synthesis) and lower androgenic activity (an effect similar to that of male sex hormones).

Indications for use. Breast cancer, even with an advanced process with metastases (new tumors that have appeared in other organs and tissues as a result of the transfer of cancer cells with blood or lymph from the primary breast tumor). The drug is prescribed to patients with a preserved menstrual cycle at the start of treatment or during menopause up to 5 years (the second phase of menopause, which occurs after the last menstruation and is characterized by a decrease in the secretion of female sex hormones and the reverse development of the genital organs); patients whose ovarian function (the process of formation of eggs in the ovaries) was previously suppressed by irradiation of the ovaries, androgen drugs (drugs of male sex hormones), or who have undergone oophorectomy (removal of the ovaries).

Method of administration and dose. Intramuscularly daily during the period of active metastasis (the appearance of new tumors in other organs and tissues due to the transfer of cancer cells with blood or lymph from the primary tumor) 0.1 g, during remission (temporary weakening or disappearance of the manifestations of the disease) - 0.05 g. Treatment is long-term: for the prevention of relapses (reappearance of signs of the disease) and metastases after mastectomy (surgical removal of the mammary gland) - 2-3 years, in case of an advanced process (stage IV) - throughout life.

Side effect. Hypercalcemia (increased calcium content in the blood) and hypercalciuria (increased calcium content in the urine), acute parenchymal hepatitis (inflammation of liver tissue), accompanied by jaundice (yellowing of the skin and mucous membranes of the eyeballs), cardiac dysfunction, virilization phenomena (appearance in women male traits / deepening of the voice, development of muscles, etc. / under the influence of male sex hormones).

Contraindications. Acute liver and kidney diseases, acute diseases of the cardiovascular system (myocardial infarction, severe hypertension /persistent rise in blood pressure/), terminal stage of the disease (the state of the body preceding death).

Release form. 5% oil solution in ampoules of 1 ml in a package of 6 pieces.

Storage conditions. List B. In a dry place at room temperature.

PROLOTESTON (Prolotestonum)

Pharmachologic effect. Proloteston is a prolonged (long-acting) dosage form of medrotestron; the inclusion of medrotestron nylon and enanth esters in the drug ensures slow absorption when administered intramuscularly and effectiveness after a single injection for approximately 15 days.

Indications for use. Indications for use are the same as for medrotestron propionate (advanced stages of breast cancer).

Method of administration and dose. 0.35-0.7 g (1-2 ml of 35% solution) is administered deeply intramuscularly once every 2 weeks. During a long time.

Side effects and contraindications. The same as when using medrotestron propionate.

Release form. 35% oil solution in ampoules of 1 ml (0.35 g of prolotestone in 1 ml).

Storage conditions. List B. Under normal conditions.

OMNADREN

Pharmachologic effect. The drug has androgenic (similar to the action of male sex hormones) activity. Contains testosterone esters with varying rates of absorption and excretion. Due to the selection of appropriate proportions of individual components, it is possible to maintain the androgenic effect of testosterone for about 4 weeks with a single injection. Exogenous (introduced into the body from the outside) testosterone in men stimulates the development and function of the gonads (genital organs), the development of the external genitalia, prostate gland, seminal vesicles, as well as secondary sexual characteristics (height, deep voice, beard and mustache growth). In the female body, testosterone exhibits an antagonistic (opposite) effect in relation to estrogens (female sex hormones), which is important in the treatment of fibroids (benign tumors of the muscular layer of the uterus), endomstriosis (appeared in various organs of tissue areas similar in structure to the inner lining of the uterus, and undergoing cyclical changes according to the menstrual cycle), breast cancer. It has an anabolizing (promoting protein formation) effect in women and men.

Indications for use. In women, functional bleeding due to hyperestrogenism (increased levels of female sex hormones - estrogens in the blood), uterine fibroids, endometriosis, menopausal syndrome (together with estrogens), premenstrual tension syndrome, late metastatic (with the spread of the tumor to other organs and tissues due to the transfer of cancerous cells with blood and lymph from the primary tumor) forms of breast cancer. In men - lack of puberty, decreased fertility (oligospermia - decreased volume of sperm released /less than 1 ml/), androgen deficiency (male sex hormones) and underdevelopment of the genital organs, menopausal syndrome, impotence.

Method of administration and dose. The contents of 1 ampoule are usually administered intramuscularly every 4 weeks.

Side effect. Acne (acne), gynecomastia (enlarged mammary glands in men), swelling, increased sensitivity and allergic skin reactions, frequent erections, symptoms of hypercalcemia (increased calcium levels in the blood). Pain, itching, and redness may appear at the injection site. Violation of spermatogenesis (the process of formation of male germ cells - sperm) and sperm maturation. Bleeding from the birth canal. Increased libido (sexual desire). Thrombophlebitis (inflammation of the vein wall with blockage), cholestatic (associated with stagnation of bile in the bile ducts) jaundice, increased levels of aminotransferases (enzymes).

Contraindications. Pregnancy. Suspicion or detection of a prostate tumor. Hypercalcemia, heart failure, liver and kidney failure. Do not use in asthenized (weakened) patients and elderly men, in boys before the onset of puberty.

Release form. 1 ampoule contains: testosterone propionate - 0.03 g, testosterone phenylpropionate - 0.06 g, testosterone isocapronate - 0.06 g, testosterone capronate -0.1 g, benzyl alcohol -0.05 g, injection oil - up to Iml . Packaging of 1 and 5 ampoules.

Storage conditions. List B. In a cool, dark place.

Estrogen drugs

POLYESTRADIOL PHOSPHATE

Synonyms: Estradurine.

Pharmachologic effect. Polyestradiol phosphate is a water-soluble high-molecular polyester consisting of phosphoric acid and 17-beta-estradiol, prolonged (long-term) action for parenteral (bypassing the digestive tract) administration. The estrogenic hormone estradiol released as a result of hydrolysis (the female sex hormone that causes the development of female genital organs, secondary sexual characteristics, and also promotes the proliferation / growth / of the endometrium - the inner layer of the uterus) has a constant high concentration in the plasma, while a decrease in the level of testosterone (male sex hormone) by 80-90% of the initial values.

Indications for use. The drug has a strong and long-lasting estrogenic (similar to the action of female sex hormones) effect. Used for adenoma (benign prostate tumor) and prostate cancer.

Due to its prolonged (long-term) action, it is used for maintenance therapy after the use of phosphastrol and other fast-acting drugs. In women, it is used as replacement therapy (introduction into the body of substances;!, the natural formation of which is reduced or stopped) in case of insufficiency of estrogens (female sex hormones produced by the ovaries and the adrenal cortex; causing the development of female genital organs, secondary sexual characteristics, and also promoting endometrial proliferation) and

climacteric syndrome (deterioration of health during menopause).

Method of administration and dose. Injected deeply intramuscularly. The drug is dissolved immediately before injection. For prostate cancer, 80-160-320 mg is prescribed once a month for 2-3 months, then the dose is reduced to 40-80 mg per month. For hypertrophy (increase in volume) of the prostate gland, 40-80 mg is administered once a month. Treatment is carried out for a long time. During treatment, the content of estrogens (female sex hormones) in the urine is periodically determined and, depending on the results, the dose and frequency of administration are adjusted.

For replacement therapy, 40 mg is prescribed once a month, for menopause (only polyestradiol phosphate 40) - 20-40 mg.

Treatment should be discontinued at least 6 weeks before surgery, associated with an increased risk of thromboembolism (blockage of blood vessels with a blood clot), as well as during a period of prolonged immobilization (immobilization), if migraine-like headaches appear, sudden blurred vision (suspicion of thrombosis /blockage/ of the retinal veins), the development of thrombophlebitis (inflammation of the vein wall with blockage) or thromboembolism, cholestatic (associated with stagnation of bile in the bile ducts) hepatitis, increased blood pressure.

Side effect. In men - gynecomastia (enlarged breasts in men) and decreased libido (sex drive) or potency. Rarely - thromboembolism, increased blood pressure, sodium and water retention, nausea, vomiting, headache, depression (state): allergic reactions

to mepivacaine: skin rash, broncho-obstructive syndrome (bronchial obstruction), anaphylactic shock (immediate allergic reaction).

Contraindications. Severe liver dysfunction, thromboembolic syndrome, active thrombophlebitis, prolonged immobilization, Dubin-Johnson syndrome (a hereditary liver disease characterized by a moderate increase in bilirubin levels in the blood), sickle cell anemia (a hereditary disease characterized by increased breakdown of sickle-shaped red blood cells, and the presence in them of functionally defective hemoglobin (oxygen carrier), Rotor syndrome (a hereditary liver disease characterized by a moderate increase in bound bilirubin in the blood), increased sensitivity to the components of the drug. In women - pregnancy, breastfeeding, menorrhagia (uterine bleeding) of unspecified genesis (origin), estrogen-dependent tumors, endometriosis (the appearance in various organs of tissue areas similar in structure to the inner lining of the uterus and subject to cyclic changes according to the menstrual cycle), instructions in anamnesis (medical history) for jaundice and otosclerosis (progressive hearing loss and tinnitus) that developed during pregnancy.

The drug should be prescribed with extreme caution to patients with chronic heart and renal failure, arterial hypertension (high blood pressure), epilepsy, migraine, liver dysfunction, porphyria (hereditary disease associated with impaired porphyrin metabolism), otosclerosis, cerebrovascular accident, coronary artery disease hearts; patients with a history of thromboembolic syndrome and thrombophlebitis.

Release form. Polyestradiol phosphate 40 and 80 in bottles in a package of 1 piece with the addition of water for injection in ampoules of 2 ml. 1 bottle of polyestradiol phosphate 40 contains polyestradiol phosphate 0.04 g, mepivacaine 0.005 g, nicotinamide (Vit.PP) 0.025 g, as well as sodium hydroxide, sodium phosphate and sodium chloride. 1 bottle of polyestradiol phosphate 80 contains polyestradiol phosphate 0.08 g, mepivicaine 0.005 g, nicotinamide 0.04 g, as well as sodium hydroxide, sodium phosphate and sodium chloride.

Storage conditions. In a place protected from light.

FOSFESTROL (Phosphoestrolum)

Synonyms: Honvan, Citonal, Diphostilbene, Phospho-stibene, Stibostatin, Stilphostrol, Honvol, etc.

Pharmachologic effect. Fosfestrol was synthesized with the aim of creating an estrogenic drug (an analogue of female sex hormones) with selective antitumor activity, namely, so that it was inactive during circulation in the blood, but upon penetration into the tumor tissue of the prostate gland, it decomposed under the influence of the phosphatase enzyme contained in it (activity which is increased in tumor cells) with the release of diethylstilbestrol, which has a cytostatic (preventing cell growth) effect. Thus, fosfestrol can be considered as a prodrug that performs a “transport” function, i.e., delivering the active substance to the tumor tissue.

Indications for use. Fosfestrol is used to treat prostate cancer, including cases with metastases (new tumors in other organs and tissues that appear as a result of the transfer of cancer cells in the blood or lymph from the primary tumor). It is considered a specific agent that acts in all stages of cancer of this localization, sensitive to estrogen drugs. For estrogen-resistant forms of tumor (forms of malignant tumors that cannot be treated with female sex hormones), fosfestrol is ineffective.

OnaiuG applications and doses. Fosfestrol is used intravenously in the form of a 6% solution and orally in the form of tablets.

There are different schemes for using fosfestrol. Typically, treatment begins with daily intravenous administration of 1.2 g (4 ampoules of 0.3 g). Administer slowly or dropwise, diluted in a 5% glucose solution (with the patient lying down), for 10 days, then 0.3 g (1 ampoule per day) for 10-20 days. In special cases, the drug is used daily for a long time. For weakened patients, people with heart failure, impaired liver and kidney function, the drug begins to be administered in smaller doses - 0.6 g (2 ampoules of 0.3 g) per day for 10 days, then 0.3 g (1 ampoule) in a day. Reducing the dose of fosfestrol should be carried out under the control of clinical and biochemical parameters; the level of acid phosphatase in the blood serum should be determined.

If intravenous administration is not possible, fosfestrol is prescribed orally in the form of tablets (before meals with a small amount of liquid). Take 3-4 tablets (0.1 g per tablet) 3 times a day. In case of development of dyspepsia (digestive disorders), it is recommended to hold the tablets behind the neck or under the tongue until completely dissolved. For maintenance therapy, 1-2 tablets are prescribed 3 times a day, then 1 tablet 2 times a day (no less). Maintenance therapy can be carried out with injections of fosfestrol 0.3 g 4-3-2-1 times a week (under the control of clinical and biochemical parameters). You can also carry out maintenance therapy by prescribing prolonged (long-acting) estrogen drugs (polyestradiol phosphate injections) or oral (by mouth) antiandrogens (see Flutamide).

Fosfestrol solutions should not be mixed with infusion solutions containing calcium or magnesium salts.

Side effect. Treatment with fosfestrol is usually well tolerated by patients. At the beginning of treatment, nausea, vomiting, and deterioration in general condition are sometimes observed; these phenomena disappear during further treatment. Itching and pain may occur in the anus and genitals, and less commonly in the face and neck. In these cases, antihistamines can be used. During treatment, pain may occur in the area where metastatic nodes are located (places where new tumors appear in the form of nodes in other organs and tissues due to the transfer of cancer cells with blood or lymph from the primary tumor). It is also possible to reduce blood clotting with hemorrhagic phenomena (bleeding). Feminization phenomena may be observed (gynecomastia - enlargement of the mammary glands in men).

Contraindications. The drug is contraindicated in cases of reduced blood clotting, a tendency to hemorrhages (bleeding), and severe liver damage. To prevent a decrease in blood clotting, it is recommended to inject a calcium chloride solution into a vein.

Release forms. 6% solution in ampoules of 5 ml; tablets of 0.1 g in a package of 30 pieces.

Storage conditions. List B. In a place protected from light.

CHLORTRIANIZEN (Chlortrianisenum)

Synonyms: Chlorotrianizen, Chlorotrisin, Chlortri-anisestrol, Hormonizen, Merbentul, Metas, Hormonisen, Trianisoesgrol.

Pharmachologic effect. Synthetic estrogen (synthetic analogue of female sex hormones). When administered, inugry has a longer lasting effect than other estrogens; has minimal feminizing properties (the ability to cause the appearance of female secondary sexual characteristics in men - enlargement of the mammary glands, deposition of fat on the thighs, etc.).

Indications for use. Prostate cancer.

Method of administration and dose. Orally 0.012 g 2-3 times a day. Treatment is carried out for a long time. For metastases (new tumors that have appeared in other organs and tissues as a result of the transfer of cancer cells with blood or lymph from the primary tumor), prednisolone is additionally prescribed.

Side effect. Sometimes swelling and pain in the mammary glands, which quickly disappear.

Contraindications. Acute and chronic liver diseases.

Release form. Tablets of 0.012 g in a package of 12 pieces.

Storage conditions. List B. In a place protected from light.

Estracyt

Synonyms: Estramustine phosphate, Emcyt.

Pharmachologic effect. It is an estrogen (an analogue of female sex hormones) and a cytotoxic (cell-damaging) agent that is effective against prostate cancer. It has antigonadotropic (aimed at preventing the hormonal function of the gonads) properties. At the usual dosage it does not cause severe suppression of hematopoiesis.

Indications for use. Used for prostate cancer in an advanced stage and when hormonal therapy is ineffective.

Method of administration and dose. Prescribed orally and intravenously. Take orally 1 hour before meals or 2 hours later

after meals, 2-3 capsules (280 mg per capsule) 2 times a day. Drink with water. At the same time, you should not take milk, dairy products or medications containing calcium.

If there is no effect within 3-4 weeks. treatment is stopped. You can start treatment with intravenous injections of 0.3 g (300 mg) daily for 3 weeks. followed by taking 2-3 capsules 2 times a day or injecting 0.3 g into a vein 2 times a week. It should be injected into the vein slowly, over 3-5 minutes (to avoid phlebitis /inflammation of the vein).

You can administer the estracite solution as an infusion (no more than 3 hours). To do this, dissolve the contents of the ampoule in 8 ml of solvent, shaking slightly, but not allowing foaming, then dilute in 250 ml of 5% glucose solution. The use of isotonic sodium chloride solution for this purpose is not allowed. After intravenous administration of estracite, a small amount of 5% glucose solution should be injected (without removing the needle).

Side effect. When using estracite, nausea, vomiting, diarrhea (diarrhea), leukopenia (low levels of leukocytes in the blood), and in rare cases, allergic reactions, pain in the heart area may occur. Thromboembolism (blockage of a vessel with a blood clot), gynecomastia (enlargement of the mammary glands in men) are possible.

Contraindications. The drug is contraindicated in acute diseases of the liver and heart, thrombophlebitis (inflammation of the veins with their blockage).

Release forms. Capsules of 0.28 g (280 mg) in bottles of 100 capsules; 1.5% solution in ampoules of 10 ml (150 mg per ampoule) and 3% solution in ampoules of 10 ml (300 mg per ampoule) in a package of 10 ampoules with the addition of 10 ampoules of solvent.

Storage conditions. At a temperature not higher than +25 °C.

Progestin drugs

Gestonorone caproat

Synonyms: Depostat, Primostat, Gestoporona caproate, etc.

Pharmachologic effect. It is close to oxyprogesterone caproate and has prolonged gestagenic activity (long-term action, similar to the action of hormones of the corpus luteum of the ovary).

It is believed that the mechanism of action of the drug in adenoma (benign tumor) of the prostate gland is associated with inhibition at the cellular level of the stimulating effect of testosterone metabolites (metabolic products) on tumor development.

Indications for use. The drug is used for prostate adenoma, mainly in patients with contraindications to surgical treatment. In addition, the drug is used for cancer (carcinoma) of the endometrium (inner lining of the uterus) and breast cancer.

Method of administration and dose. Administer 200 mg intramuscularly once a week. Before administration, the solution in the ampoule is heated to body temperature. When treating men, a 2-3 month course is recommended; if symptoms recur, the course of treatment is repeated. Women are given the drug for a long time.

When treating adenoma, it is necessary to monitor renal function.

Side effect. When using the drug, men may develop gynecomastia (enlarged mammary glands) and impaired potency (sexual activity). In some cases, short-term shortness of breath may occur immediately after intramuscular injection. The drug should be used with caution in patients suffering from

chronic liver diseases, as well as in patients with diabetes (monitor liver function and carbohydrate metabolism). Caution should be exercised in case of bronchial asthma, epilepsy, migraine.

Contraindications. Malignant liver tumors (if they are not caused by metastases / transfer of cancer cells with blood or lymph from the primary tumor / endometrial or breast tumors), including a history (previous), pregnancy, breastfeeding. History of pregnancy herpes (viral skin lesions suffered during a previous pregnancy).

Release form. 10% solution in oil (with the addition of benzyl benzoate) in ampoules of 2 ml (200 mg per ampoule) in a package of 5 ampoules.

Storage conditions. In a place protected from light.

MEDROXYPROGESTERONE ACETATE

Synonyms: Depoprova for use in oncology, Provera for use in oncology, Farlutal, Onko-Provera, Provera 100, Clinovir, Depcorlutin, Depo-Alfacort, Depo-Klinovi, Depo-Promon, Farmolut, Gestopuran, Luteodione, Methylgesten, Neolut, Nidaxin , Normobion, Prodafem, Promon-E, Verok, Sedometril, Vadesin, etc.

Pharmachologic effect. The drug has a progestin (similar to the action of the female sex hormone progesterone) effect and is devoid of androgenic (similar to the action of male sex hormones) and estrogenic (similar to the action of female sex hormones - estrogens) activity. In high doses, it has an antitumor effect in hormone-sensitive malignancies. It has a pyrogenic (increasing body temperature) effect, and in large doses it has corticosteroid (similar to the action of adrenal hormones) activity.

Indications for use. Hormone-dependent forms of recurrent (recurring) breast cancer in women in menopause (the second phase of menopause) as palliative (not aimed at treating the underlying disease, but at alleviating the patient’s condition) treatment; recurrent and/or metastatic (accompanied by the appearance of new tumors in other organs and tissues that have developed as a result of the transfer of cancer cells with blood or lymph from the primary tumor) endometrial cancer (the inner lining of the uterus) as an additional and/or palliative treatment; recurrent and/or metastatic kidney cancer as additional and/or palliative treatment.

Method of administration and dose. The drug is used orally or intramuscularly.

Tablets are prescribed orally for endometrial and kidney cancer from 200 to 600 mg per day, for breast cancer - from 400 to 1200 mg per day. The effect is usually observed after 8-10 weeks. from the start of treatment.

The drug is used intramuscularly as follows. For endometrial cancer and kidney cancer, the initial doses of the drug are 500-1000 mg per week. If the patient's condition improves over several weeks or a month and the condition stabilizes, then maintenance therapy is prescribed at a dose of 500 mg per week.

For breast cancer, the drug is prescribed at an initial dose of 500 mg per day for 28 days. Then maintenance doses of 500 mg are used 2 times a week. Treatment is continued until the patient responds to treatment.

The results of drug therapy for hormonal breast cancer can appear even after 8-10 weeks from the start of treatment.

As the disease progresses, medroxyprogesterone acetate therapy is discontinued.

Side effect. Allergic reactions in the form of urticaria, rash, and in isolated cases, anaphylactoid reactions (immediate allergic reactions). Thromboembolism (blockage of a vessel with a blood clot), thrombophlebitis (inflammation of the vein wall with blockage); nervousness, insomnia, weakness, depression (state of depression), dizziness, headache; nausea. Changes in the nature of discharge from the genital tract, sensitivity of the mammary glands and galactorrhea (milk leakage outside the period of breastfeeding). Pyrogenic reactions (increase in body temperature). With long-term use of high doses of the drug, it is possible

development of the Itsenko-Cushing symptom complex (obesity, accompanied by decreased sexual function, increased bone fragility due to increased release of adrenocorticotropic hormone from the pituitary gland).

When using a suspension, compactions and sterile abscesses (formation of limited cavities filled with pus, without the addition of bacterial pathogens of purulent infection) at the injection site are possible.

Contraindications. Hypersensitivity to medroxyprogesterone or other components of the drug. Pregnancy.

Release forms. Tablets 100; 200; 250; 500 mg (0.1; 0.2; 0.25; 0.5 g); oral suspension containing 500 mg in 1 ml; suspension for intramuscular injection in bottles of 3.3 ml (500 mg or 150 mg per 1 ml) and 6.7 ml (1000 mg).

Storage conditions. In a dry place, protected from light.

OXYPROGESTERONE CAPRON (Oxyprogesteronicaproas)

Synonyms: Germofort, Kaposten, Gormofort, Depolit, Delalitin, Extralitin, Hydroxyprogesterone, Caproate, etc.

Pharmachologic effect. The drug has a progestin (similar to the action of the female sex hormone progesterone) effect and is devoid of androgenic (similar to the action of male sex hormones) and estrogenic (similar to the action of female sex hormones - estrogens) activity. In high doses, it has an antitumor effect in hormone-sensitive malignant neoplasms.

Indications for use. Used in the treatment of patients with uterine cancer, breast cancer and some other malignant tumors.

Method of administration and dose. A 25% solution of 3-4 ml is administered intramuscularly daily or every other day for a long period (30-300 days).

If crystals form in the ampoule, the ampoule is heated in a boiling bath while shaking. If the crystals disappear and the solution becomes transparent, and when cooled to +36-+38 °C the crystals do not fall out again, the solution is suitable for use.

Side effects and contraindications.

Release form. 12.5% ​​(0.125 g) and 25% (0.25 g) solution of oxyprogesterone capronate in oil in ampoules containing 1 ml.

Storage conditions. List B. In a place protected from light. Ampoules are stored at a temperature not lower than 0 °C.

When should you start taking phytoestrogens?

Menopause is a difficult period in a woman’s life, so it is advisable to prepare for it. It is important to understand that it is impossible to delay the onset of menopause, but you can, firstly, avoid its onset before a genetically determined period, and secondly, you can soften the onset of menopause and make its manifestations invisible. In the early stages of menopause or even before its onset, you can already take phytoestrogens.

But strictly speaking, you can take phytoestrogens at any stage of menopause, as soon as you feel its manifestations: hot flashes, increased appetite, decreased libido, vaginal dryness, sleep disturbances, emotional swings.

By the way, women often confuse the concepts of “menopause” and “menopause” and use them as synonyms. But in medicine, these terms are differentiated: menopause is only one stage of menopause. To make it easier for you to understand what awaits you during menopause, here are brief characteristics of all stages:

1. Premenopause . This is the name of the first stage, which occurs at the age of 40–45 years. At this time, the intensity of the cycle changes, it first becomes shorter, then longer, then loses regularity. Between menstruation, discharge appears that was not there before. Perimenopause affects your mood - it can change from good to bad and vice versa in an instant. Sleep is disturbed, weight begins to increase. This is the beginning of hormonal changes.

2. Menopause . This stage begins at 50–53 years, but it can occur much earlier (at 40–45 years) or much later (from 55 years). You can talk about menopause only after a year has passed since your last menstruation. During menopause, estrogen levels drop sharply, FSH concentration increases, and ovarian function declines. Due to dramatic changes in hormonal balance, symptoms at this stage become more severe than during perimenopause. These are severe hot flashes, decreased libido, sagging skin, and vaginal dryness. Her mood also suffers - the woman becomes irritable and reacts sharply even to minor problems. Due to the fact that the body lacks estrogen, the functioning of the cardiovascular system worsens and the risk of stroke and heart attack increases.

3. Postmenopause . It begins after menopause, that is, after 12 months of no periods. The body gradually rebuilds and adapts to the new ratio of hormones. At this time, the symptoms of menopause become less pronounced. However, there may be periods when symptoms seem to return with renewed vigor. During this period, there is a danger of the so-called delayed consequences of menopause: the risk of osteoporosis is higher, as bones lose density, and there is a high probability of developing diabetes, heart attack, and stroke. If a woman took hormonal drugs at previous stages, now it is advisable to reduce their dosage and gradually stop taking them, since the undesirable manifestations of their use (dementia, deterioration of cognitive abilities) are stronger than the expected benefits. Therefore, at this stage, it is recommended to take phytoestrogens even for those women who have previously resorted to hormonal therapy.

So how do phytoestrogens work? What exactly does their help with menopause consist of?

Treatment of pathological menopause in women

In recent years, women's life expectancy has been increasing rapidly. Currently, the average age of menopause is 49 ± 0.5 years, therefore, every woman spends approximately 1/3 of her life in a state of hypoestrogenism. In some cases, menopause acquires the features and signs of a pathological process. Women suffering from pathological manifestations of menopause seek help from various specialists - a neurologist, cardiologist, endocrinologist, psychiatrist, etc. In Russia, only 1–2% of women receive modern therapy. According to statistics, drugs from the group of hormone replacement therapy (HRT) are used by only 20 million out of 470 million.

As follows from Table 1, less than half of women in various countries of the world receive adequate therapy. It is extremely rare for patients with pathological menopause to be prescribed individual complex treatment. More than 80% of practicing doctors are poorly versed in the treatment of pathological menopause. Currently, doctors have a large arsenal of tools at their disposal to correct the complications of a hypoestrogenic condition. However, the health status of women depends on the correct choice of tactics, start time, duration of therapy and a number of other factors. Taking into account all of the above, we decided to analyze the indications and contraindications for pathogenetic therapy with HRT drugs and outline the principles of treatment of pathological manifestations of menopause in women.

Manifestations of pathological menopause in women, developing against the background of changes in hormonal status, are polymorphic in nature and relate to various areas of practical medicine - therapy, cardiology, urology, neurology, traumatology, etc.

Hormonal markers, or criteria, of menopause are:

• decreased estradiol levels;
• high level of FSH;
• LH/FSH index < 1;
• estradiol/estrone index < 1;
• relative hyperandrogenism;
• increase in LH levels;
• increase in androgen/estrogen ratio ≤ 1;
• decrease in inhibin levels.

For a long time, it was generally accepted that the main target organs for sex hormones were the uterus and mammary glands, i.e., the so-called reproductive targets. However, thanks to advances in basic science, new types of receptors have been identified. Thus, in addition to reproductive target organs, humans also have non-reproductive ones.

Target organs and localization of sex hormone receptors

Reproductive organs:

• genitals;
• hypothalamus;
• pituitary;
• mammary gland.

Non-reproductive organs:

• brain;
• the cardiovascular system;
• musculoskeletal system;
• urethra and bladder;
• skin and hair;
• colon;
• liver, etc.

The most significant complications and manifestations of a hypoestrogenic state that affect a woman’s quality of life include: menopausal syndrome, urogenital changes, degenerative processes in the skin and its appendages, atherosclerosis and its complications, metabolic disorders, osteoporosis, Alzheimer’s disease, etc.

The time of manifestation and the severity of the main symptoms and pathological conditions are subject to significant individual fluctuations. However, despite this, certain patterns are visible in the sequence of their manifestations, presented in Table 2.

Currently, the most effective method of treating menopausal disorders is HRT with estrogen-containing drugs. The entire range of treatment and preventive measures can be divided into two types:

• non-drug effects - diet therapy, exercise therapy, physiotherapy, reflexology, psychotherapy, auto-training and herbal medicine;
• drug therapy - pathogenetic and symptomatic.

Non-drug prevention and correction of complications of pathological menopause in women

In the prevention and treatment of complications of menopause, proper nutrition and lifestyle changes play an important role:

• sleep at least 8 hours at night;
• walks in the fresh air for at least 1–1.5 hours;
• a set of general strengthening exercises and hardening;
• giving up bad habits - smoking and drinking alcohol.

Diet therapy

A set of dietary recommendations is aimed at preventing late metabolic disorders, which include atherosclerosis and its complications, osteoporosis and obesity. Dietary recommendations include:

• compliance with the diet, split 5-6 meals a day;
• last meal no later than 18:00;
• daily calorie intake of food is not > 2000–2200 kcal (however, when the level and intensity of physical activity changes, this indicator must be adjusted); limiting consumption or completely avoiding easily digestible carbohydrates;
• a diet low in animal fats;
• eating foods high in calcium (for women under 50 years old - 1000 mg/day; for postmenopausal women - 1500 mg/day; for postmenopausal women receiving HRT with estrogens - 1000 mg/day);
• taking “natural vitamins” and fiber-rich foods daily.

Psychotherapy

In order to prevent complications and treat menopause in women, psychotherapy and teaching patients the basics of auto-training are used. These events help to form in women an optimistic attitude towards the transition period - menopause and to realize the reversible nature of most of the phenomena observed in them.

Physiotherapy

In addition to the above, it should be noted the positive possibilities of physiotherapeutic correction of many complications of menopause in women. The arsenal of modern physiotherapeutic means is quite wide. The most commonly used physiotherapeutic agents belonging to the group of “natural” can be divided into the following categories:

• climatotherapy - it is optimal for a woman to stay in her “own” climate zone;
• aerotherapy is air treatment, the most accessible is walking in the fresh air; in the absence of contraindications, it is possible to increase the intensity of the load before running. It is also possible to carry out light-air baths (optimal air temperature is not lower than 18°C ​​and wind speed is not more than 5 m/s);
• heliotherapy, or insolation - before prescribing this type of therapy, it is necessary to exclude the following pathologies: diseases of the cardiovascular system, thyrotoxicosis, large tumors, etc. It is advisable to start with exposure to the sun for 5-7 minutes and increase the duration of procedures to 45 minutes - in morning time, before 10 or after 17 hours.

The second group of physiotherapeutic measures includes physical and chemical influences. I would like to dwell in more detail on just some of them.

1. If vegetative symptoms predominate during the pathological development of menopause in women, it is recommended:
   manual massage;
2. electrophoresis of aminophylline on the “collar” area;
3. galvanization of the cervical-facial area, etc.
4. If complaints of a psycho-emotional nature predominate, the following measures are advisable:
   endonasal galvanization;
5. circular shower;
6. electrosleep, etc.
7. If you are prone to arterial hypertension, the following procedures are indicated:
   electrosleep;
8. galvanization or bromine electrophoresis;
9. galvanic anode collar or magnesium electrophoresis;
10. electrophoresis with β-adrenergic blocking drugs, etc.

Physiotherapy

An important role is played by the use of complexes or individual exercises that can be used during all periods of menopause and senium:

• walking, especially in combination with aerotherapy;
• running (in the absence of contraindications);
• a set of breathing exercises;
• exercises aimed at relaxing both general and individual muscles;
• complex training of the pelvic and detrusor muscles;
• exercises aimed at strengthening the muscle corset and preventing osteoporosis, etc.

Drug correction and prevention of pathological manifestations of pathological menopause in women

Taking into account the pathogenetic features and mechanisms of development of the main complications of menopause, i.e. hypoestrogenism, drug therapy in women can be divided into pathogenetic and symptomatic. The first category includes hormone replacement therapy. Currently, there is a wide range of drugs in this group on the Russian market, differing in the method of administration, main active ingredient, dosage, chemical structure and other parameters.

For HRT, various estrogen preparations are used, which include natural or synthetic estrogens. To treat the manifestations of menopause, as a rule, natural estrogens and their agonists are used. Table 3 shows some of the types of estrogens used for HRT.

The main purpose of using HRT is to replace, using pharmacological agents, the hormonal function of the ovaries in women experiencing a deficiency of sex hormones. It is important to achieve such levels of hormones in the blood that would ensure improvement of the present condition, prevention of late metabolic disorders, and at the same time the negative impact on target organs - the endometrium and mammary glands - would be minimal.

Indications for starting HRT in women are early manifestation of menopause (up to 40 years), a burdened medical history (especially cardiovascular pathologies, osteoporosis, Alzheimer's disease), primary or secondary hypogonadism in women, condition after oophorectomy, urogenital disorders, early vasomotor symptoms menopausal syndrome, migraine, obesity, etc.

Absolute and relative contraindications for prescribing HRT drugs

Absolute contraindications for HRT: pregnancy, bleeding from the genital tract of unknown etiology, acute hepatitis, acute deep vein thrombosis, acute thromboembolic diseases, some tumors of the genital organs and mammary glands, meningioma.

Relative contraindications to HRT: uterine fibroids, endometriosis, migraine, history of venous thrombosis or embolism, familial hypertriglyceridemia, cholelithiasis, epilepsy, family history of breast cancer, ovarian cancer.

Contraindications for the use of estrogens: history of breast cancer, endometrial cancer, pathologies accompanied by liver dysfunction, porphyria, estrogen-dependent tumors, decompensation of diabetes mellitus.

Before prescribing HRT drugs, the patient should be carefully monitored. Mandatory examinations include:

• blood pressure control;
• determination of levels - glycemia, lipoproteins, FSH, E2 in blood serum, TSH, T3 and T4, indicators of the blood coagulation system;
• gynecological examination;
• Ultrasound of the reproductive organs of the pelvis with determination of the thickness of the endometrium;
• palpation of the mammary glands and mamographic examination.

In some cases it is also necessary to:

• ECG study;
• consultation with an endocrinologist, neurologist, cardiologist, phlebologist, etc.

Currently, the domestic pharmaceutical market offers drugs used for HRT of different composition, route of administration and dose of the active substance. The figure shows the main routes of administration of drugs used for HRT.

Taking into account the physiological characteristics of the female body, HRT drugs should be used differently during different periods of menopause; Thus, when deciding on the choice of the type of drug and treatment regimen, it is necessary to determine the condition of the uterus (if it is absent, it is important to find out the reasons for the hysterectomy) and the phase of menopause. During periods of pre- and early menopause, drugs in this group restore the menstrual cycle, which, among other things, has a beneficial effect on the woman’s condition; The most physiological is the use of three-phase drugs. During periods of “late menopause,” in contrast to premenopause, when stimulation of the secretory hormonal function of the ovaries is justified, the fundamental condition should be the preservation of age-related homeostasis.

It is also necessary to determine the dominant manifestations of pathological menopause - vegetative, cardiac, urogenital, or others.

Currently, there are the following main modes of use of HRT:

• monotherapy with estrogens (Proginova, Divigel, Ovestin, Estrofem, Premarin, Klimara, etc.) or progestogens (Duphaston, MPA, etc.);
• combination therapy (estrogens and progestogens) in a cyclic mode (Divina, Klimen, Klimonorm, Trisequence, Climodien, etc.);
• monophasic combination therapy (estrogens and progestogens) in a continuous mode (cliogest, etc.);
• use of other drugs (Livial, Gynodian-depot, etc.).

Currently, in our country, drugs for transdermal administration of the active substance, HRT, are increasingly being used. In practice, there are two ways to administer estrogen-containing drugs parenterally through intact skin: applying a hypoalcoholic gel or using a transdermal patch or controlled-release estradiol sticker. However, transdermal forms are monocomponent drugs. When using these drugs in women with an intact uterus, the use of progestogens is necessary. Currently, both scientists and clinicians have come to the conclusion that the duration of use of HRT should be on average 5–7 years, since this is the optimal period not only and not so much for achieving a positive result (relief of existing pathological manifestations of menopause) therapy, but also for the prevention of more serious complications of pathological menopause.

When using HRT drugs, it is necessary to monitor the levels of estradiol and FSH after 3 months, and then every 6 months; Pelvic ultrasound and mammography should be performed annually; analysis of coagulation system indicators is performed every 6 months, etc.

The overall positive effect of the use of HRT: reduction in vegetative-emotional manifestations of menopause (noted in 90–95% of patients), reduction in pathological urogenital manifestations (in 85% of women), reduction in the risk of hip fractures by 50% and vertebral fractures by 60–70%, reduction in the incidence of myocardial infarction (in 35–50% of patients), reduction in the incidence of Alzheimer’s disease by 30–60%.

Considering the undoubted advantages of HRT therapy, it is also necessary to keep in mind its negative aspects. The advantages of HRT include: pathogenetically determined effects, rapid regression of symptoms, ease of use, therapeutic and preventive effects, complex intersystem effects. Among the disadvantages of HRT: a large list of contraindications, complex intersystem effects, the need to gradually reduce the dose of the estrogen component of the drug when discontinuing treatment, high price, and a negative attitude towards the use of HRT among doctors and patients.

In this regard, the question naturally arises about the need to use alternative methods for correcting complications of pathological menopause.

Drugs for symptomatic therapy can be considered as an alternative treatment for the pathological manifestations of menopause. First of all, these include phytoestrogens. These are natural substances that are part of plants and have estrogenic or antiestrogenic effects. Currently, there are three main classes of phytoestrogens:

• isoflavins (genistein, daidzein);
• lignans (enterolactone, enterodiol);
• coumestans (coumestrals).

These substances are included in a number of pharmacological preparations, including homeopathic ones.

Taking into account the main symptoms, according to the direction of action, drugs can be divided into the following groups:

• drugs for correcting the main manifestations of menopausal syndrome - homeopathic drugs Klimakt-Hel, Klimaktoplan, Remens, etc.;
• sedatives - novo-passit, bellaspon, grandoxin, etc.;
• antihypertensive drugs - concor, nebilet, moexipril, etc.;
• lipid-lowering drugs - Zocor, etc.;
• urological drugs - driptan, etc.;
• medicines for the correction of bone-metabolic disorders - miacalcic, fosomax, alpha D3-Teva;
• restoratives and preparations for vitamin therapy, etc.

To summarize, it should be emphasized once again that patients with pathological manifestations of menopause can complain to a variety of specialists - a cardiologist, neurologist, endocrinologist, etc. Therefore, doctors of all specialties should have a good knowledge of the clinic and modern methods of correcting the manifestations of pathological menopause in women. This will undoubtedly help improve a woman’s quality of life, and will also reduce the incidence of morbidity and mortality from such socially significant pathologies as myocardial infarction, Alzheimer’s disease, osteoporosis, etc.

E. V. Doskina, Candidate of Medical Sciences RMAPO, Moscow

Phytoestrogens: to whom and why?

As we have already found out, phytoestrogens are substances of plant origin, the structure of which is similar to the structure of estrogens. Although plant estrogens are weaker than real hormones, they are able to bind to receptors with which estrogens interact. In this way, the deficiency of hormones in those organs in the regulation of which estrogens are involved is compensated.

However, phytoestrogens do not copy the action of hormones, since they do not act on all receptors. For example, phytoestrogens cannot restore reproductive function. But they can easily cope with many manifestations of menopause.

So, what benefits do phytoestrogens bring during menopause?

• Reduces the number, frequency and severity of hot flashes.
• They stimulate collagen production, which moisturizes the skin, makes it more elastic, and slows down its aging.
• Eliminate dryness in the vagina, maintain the condition of all mucous membranes.
• Stabilizes emotional state.
• Improve calcium metabolism, prevent calcium leaching from bones.
• They improve the condition of blood vessels, which is the prevention of late stroke in the later stages of menopause.

Studies that analyzed the condition of women living in China and Japan have proven that in women living in these countries, the manifestations of hormonal imbalance are smoothed out, and many of them have not even encountered hot flashes. In addition, the risk of breast cancer after 55 years is lower than in European women. Scientists believe that this situation is due to diet: in Asia they consume a lot of food rich in phytoestrogens, in particular, soy is one of the main products.

Estradiol is one of the main female sex hormones and plays a key role in the functioning of the reproductive system. The main source of estrogen in a woman’s body is theca cells of the antral follicles, in which estradiol is synthesized from androgens (androstenedione and testosterone) under the action of the aromatase enzyme. The main target of estrogens is the organs of the reproductive system: the uterus, ovaries, vagina, fallopian tubes and mammary glands.

Assisted reproduction methods, widely used in clinical practice in recent decades, can increase the likelihood of pregnancy largely due to the use of drugs that stimulate the growth of many follicles, as a result of which the level of estradiol in a woman’s body significantly increases. In this case, implantation and development of the embryo occur against the background of pronounced hyperestrogenism, in other words, even without the administration of exogenous estradiol preparations during ART, hyperestrogenism occurs, the effect of which on embryogenesis and the health of the unborn child has not been sufficiently studied. The same applies to artificial hyperestrogenism, which is created as a result of the widespread administration of estrogen drugs to many patients in ART programs.

Oocyte donation occupies a special place in the treatment of infertility using ART methods. Preparation of the endometrium for pregnancy in recipients of donor oocytes with non-functioning or removed ovaries is impossible without the use of estradiol drugs, which cause endometrial proliferation and support pregnancy in the early stages.

Over the past decades, vast experience has been gained in prescribing estrogen drugs to prepare for pregnancy and maintain it in the early stages. At the same time, not a single instruction for the use of estradiol drugs registered both in Russia and abroad contains indications such as preparation of the endometrium in ART programs and support of the luteal phase and early stages of pregnancy. Indications for the use of estradiol valerate and estradiol hemihydrate are limited to hormone replacement therapy (HRT) for menopausal disorders, involutive changes in the skin and genitourinary tract, and depressive states during the menopause. Indications also include symptoms of estrogen deficiency in women of any age due to natural menopause or sterilization, as well as the prevention of postmenopausal osteoporosis.

Moreover, all instructions for the use of estrogen preparations indicate that pregnancy is a contraindication and should be the reason for immediate cessation of therapy. At the same time, the instructions for the drugs Divigel and Proginova contain information that epidemiological studies have not demonstrated the presence of a teratogenic or fetotoxic effect when exposed to estrogens on the fetus.

Thus, on the one hand, the question arises about the safety of prescribing estrogens in the early stages of pregnancy and in preparation for the transfer of embryos, including thawed ones, against the background of HRT. On the other hand, there is widespread clinical practice of using estrogens before and during pregnancy simply because there is no alternative to them, and the necessity and effectiveness of their use are not questioned. At the same time, side effects are not described, either due to their absence, or because experts are afraid of being criticized for using estrogens for obviously prohibited indications.

The purpose of this article is to systematize the accumulated knowledge on the safety and advisability of using estrogens using the example of patients in the ART program, who are a frequent subject and a convenient model for their study.

The influence of estradiol levels on the outcome of IVF

The main factor ensuring a high pregnancy rate in an IVF program is the ability of the ovaries to respond to stimulation with adequate growth of several follicles containing oocytes capable of fertilization. Stimulation of the ovaries with FSH drugs leads to a significant increase in the concentration of serum estradiol and in some cases provokes the development of ovarian hyperstimulation syndrome (OHSS), a severe iatrogenic complication that is potentially dangerous to a woman’s health. There are conflicting data in the literature regarding the effect of hyperestrogenism on the likelihood of pregnancy and successful progression of pregnancy [1–7].

In a study by T. Gelety and R. Buyalos [1], the possible adverse effect of estradiol on embryo implantation was studied in groups of women with peak estradiol concentrations of more than 5000 pg/ml and less than 3500 pg/ml. The group of women with high estradiol levels received significantly more oocytes, while the fertilization rate was lower than in the control group. The implantation and pregnancy rates were statistically significantly higher in the high estradiol group, and the miscarriage rate did not differ between the high and low estradiol groups. T. Papageorgiou et al. [2] analyzed the outcomes of 905 IVF cycles depending on the level of estradiol on the 5th day of stimulation and on the day of human chorionic gonadotropin (hCG) administration. The number of oocytes and embryos obtained and the pregnancy rate were significantly higher in the group of women with high estradiol levels.

C. Chen et al. [3] studied the relationship between the peak concentration of estradiol and the outcome of 697 IVF cycles when embryos were transferred on the 3rd and 5th days of development and did not reveal the adverse effects of estrogens. A. Blazar et al. [4] showed that the likelihood of pregnancy is higher in patients with high estradiol concentrations on the day of hCG administration.

In a systematic review examining the association between estradiol levels on the day of hCG administration and pregnancy in long-term IVF protocols, I. Kosmas et al. [5] included 9 retrospective studies. Three studies (191 cases) revealed a positive correlation, five (1875) did not establish a significant relationship, and two studies (1286) found an adverse effect. The authors concluded that the existing evidence is insufficient to support or refute the hypothesis of a possible effect of estradiol concentrations on IVF outcome.

In a retrospective study by C. Wu et al. [6] studied the frequency of fertilization, implantation and pregnancy in groups of patients with different concentrations of estradiol (274 cycles in total). The frequency of fertilization and cleavage did not differ between groups, the implantation rate and pregnancy rate were statistically insignificantly lower in the group of patients with estradiol levels above 5000 pg/ml.

Another retrospective analysis of 1123 IVF cycles performed by G. Kong et al. [7], showed that the level of estradiol correlates with the number of oocytes and good quality embryos obtained. There was no statistically significant effect of estradiol on oocyte maturity, fertilization rate and overall pregnancy rate, while the rate of implantation and development of OHSS was statistically significantly higher, and the rate of pregnancy loss was lower in the group with high estradiol levels.

Thus, most studies do not confirm the adverse effect of high estradiol levels on the incidence and progression of pregnancy.

Oocyte donation programs against the background of HRT as a model for assessing the effect of estrogens on IVF outcomes, pregnancy and child health

The effect of taking estrogen drugs on the course of pregnancy and the health of children can be assessed by studying the outcomes of pregnancies and births in IVF programs with donor oocytes in women with removed or non-functioning ovaries. Exogenous estrogens, taken transdermally, orally, or vaginally, are the only source of estradiol in these patients. Most specialists have no doubt about the need to imitate the natural balance of sex hormones by prescribing exogenous preparations of estrogen and progesterone to maintain early pregnancy in oocyte donation programs.

G. Sheffer-Mimouni et al. [8] studied the outcomes of 134 singleton deliveries in recipients of donor oocytes. The frequency of congenital malformations was 2.2%, i.e., did not exceed the general population. The authors drew attention to the high frequency (43%) of bleeding in the first trimester of pregnancy, which in most cases could be stopped by additional prescription of estrogen drugs.

S. Krieg et al. [9] compared the outcomes of 78 pregnancies after IVF with donor oocytes and 108 pregnancies after IVF with autologous oocytes. The incidence of preterm birth, preeclampsia, gestational diabetes and placental pathology, as well as fetal weight at birth, did not differ between groups and did not depend on maternal age.

In 2012, D. Stoop et al. [10] conducted a study of couples matched for age, ethnicity, parity and number of fetuses, and examined the outcomes of 205 pregnancies after oocyte donation and 205 pregnancies after ICSI with autologous oocytes. There were no differences between the groups in terms of term of delivery, fetal weight, body length, head circumference and Apgar status of the newborns. However, in the oocyte donation group, an increased risk of gestational hypertension and bleeding in the first trimester of pregnancy was found, which can be explained by suboptimal concentrations of sex hormones, since doses within the framework of maintenance HRT are selected empirically.

Thus, the need and effectiveness of the use of estrogens during pregnancy occurring in the oocyte donation program is beyond doubt, however, measures must be taken into account and promptly taken to prevent pregnancy complications.

Support of the luteal phase in the stimulation cycle for IVF

The change in estradiol concentration during controlled stimulation of superovulation reflects the response of the ovaries to the administration of gonadotropin drugs and correlates with the number of growing follicles and the degree of their maturity. Some ART clinics use hormonal monitoring of follicle growth, and the level of estradiol per follicle with a diameter of more than 12-14 mm is a criterion for assigning an hCG trigger for the final maturation of follicles. At the same time, according to D. Kyrou et al. [11] the concentration of estradiol on the day of hCG administration is itself a weak prognostic criterion for the outcome of an IVF cycle.

A number of studies have examined the effect of estradiol levels and the dynamics of its decrease in the luteal phase of the cycle on the pregnancy rate in an IVF program. S. Friedler et al. [12] studied the effect of a decrease in estradiol levels in the mid-luteal phase compared to its level on the day of hCG administration on the outcome of IVF in 100 patients under 38 years of age with normal and excessive ovarian response to stimulation. On average, by the middle of the luteal phase, the level of estradiol decreased by 95% of the initial level, while the average level of estradiol and the degree of its decrease did not differ in cycles with a positive (pregnancy) and negative outcome. The rate of pregnancy per transfer was highest in the group with estradiol levels on the day of hCG administration from 5000 to 8000 pg/ml and in the group with the highest estradiol levels (from 200 to 600 pg/ml) in the mid-luteal phase. The frequency of spontaneous miscarriages was statistically insignificantly higher in the group of patients with an excessive response to stimulation and a decrease in estradiol concentrations in the luteal phase of the cycle by more than 98%. The multivariate analysis conducted by the authors rejects the hypothesis of a possible adverse effect of supraphysiological doses of estradiol on the day of hCG administration, as well as its sharp decrease in the luteal phase on the pregnancy rate.

L. Kondapalli et al. [13] in a retrospective study studied the relationship between the level of estradiol on the day of hCG administration and 12 hours after hCG administration, the pregnancy rate and the rate of live birth in 1712 cycles of the first IVF attempt in patients aged 21-45 years. Estradiol levels increased at 12 hours by more than 10% in 1065 (62.2%) cycles, remained unchanged in 525 (30.7%) cycles, and decreased by more than 10% in 122 (7.1%) cycles. Estradiol levels on the day of hCG administration did not differ between groups, while pregnancy and delivery rates were significantly lower in groups where estradiol levels decreased (aOR 0.53, 95% CI 0.33–0.84, p

=0.007 and 0.40, 95% CI: 0.22–0.71;
p
= 0.002, respectively) or remained unchanged (aOR: 0.73; 95% CI: 0.57–0.94;
p
= 0.013 and 0.74; 95% CI: 0.56–0.97;
p
= 0.032 respectively). The authors propose using this criterion to predict pregnancy after IVF.

The hormonal profile of the luteal phase of the cycle of stimulation of superovulation with gonadotropin preparations differs from that in the luteal phase of the natural cycle by a higher concentration of progesterone and estradiol, a shortening of the plateau period and a pronounced decrease on the 7-10th day after the introduction of the ovulation trigger [14]. It is believed that ovarian stimulation results in the formation of many luteal cysts that are unable to produce adequate progesterone. It has been proven that the administration of progesterone drugs after embryo transfer significantly increases the pregnancy rate. Researchers have different opinions regarding the need to take estradiol medications.

A systematic review and meta-analysis conducted in 2008 by T. Gelbaya et al. [15], did not reveal any benefits of additional administration of estradiol regarding the incidence of pregnancy. At the same time, the authors refer to the limitations and heterogeneity of the available data.

In 2011, M. van der Linden et al. published a meta-analysis in the Cochrane database, which included 9 studies and 1571 IVF cycles [16–24]. The authors assessed the effect of taking estradiol in the luteal phase of the stimulated cycle on the likelihood of pregnancy, the incidence of OHSS, miscarriages and childbirth, depending on the route of drug administration (oral, transdermal or vaginal) and stimulation protocol (with GnRH agonists or antagonists). Only one study examined live birth rates and found no difference between the progesterone alone and progesterone plus estradiol groups. There were no differences in the rate of progressive pregnancy (OR 1.00, 95% CI 0.77-1.31) and the rate of miscarriage (OR 1.01, 95% CI 0.70-1.45) in the groups of women taking only progesterone and progesterone together with estradiol. According to 7 studies, the incidence of clinical pregnancy did not differ with the additional administration of estradiol. However, subgroup analysis with different routes of drug administration revealed an increased incidence of clinical pregnancy in the subgroup of women taking progesterone + transdermal estradiol compared with women taking progesterone alone (OR 0.50, 95% CI 0.31–0.82) [14 ].

In this regard, N. Huang et al. in 2015, they conducted a new meta-analysis that included 15 randomized controlled trials and examined the outcomes of 2406 IVF cycles [16–19, 21, 22, 26–34]. The relative probability of pregnancy in the groups of women taking estradiol + progesterone, compared with women taking progesterone only, was 1.18 (95% CI 0.98-1.41; p

=0.07) for oral administration, 1.07 (95% CI 0.59-1.93;
p
=0.83) for vaginal administration and 1.81 (95% CI 0.53-6.17;
p
=0.35) for transdermal forms. Pregnancy rates were not statistically significantly higher in the groups of women taking 2, 4, and 6 mg oral estradiol compared with women taking progesterone alone (38.6% vs. 35.0%; 38.3% vs. 37.3% and 48.3% versus 44.0%). There were also no differences between subgroups in the incidence of spontaneous miscarriage and ectopic pregnancy [25].

Thus, the additional administration of oral forms of estradiol in a dose of 2 to 6 mg in the luteal phase of the cycle slightly increases the likelihood of pregnancy in an IVF program, while the combination of progesterone with a transdermal form of estradiol significantly increases the frequency of pregnancy.

Support of luteal phase estrogen drugs and the risk of bleeding in an IVF cycle

In studies studying the effect of various drugs on the outcome of an IVF program, parameters such as clinical or progressing pregnancy and live birth are most often studied. At the same time, there are a number of intermediate outcomes that are no less important for the doctor and the patient. For example, in a prospective randomized study by S. Kwon et al. [35] showed that taking 4 mg of estradiol valerate in the luteal phase of the stimulated cycle does not affect the pregnancy rate, but statistically significantly increases the implantation rate (22.2% versus 13.3%; p

=0.035) and reduces the frequency of bleeding (7.4% vs. 27.8%;
p
=0.010), which is a cause of anxiety for both the doctor and the patient expecting a positive result.

Support of estrogen preparations for the luteal phase of the IVF cycle in patients with insufficient ovarian response to stimulation

It is well known that there is a directly proportional relationship between the number of oocytes and embryos obtained and the pregnancy rate in an IVF cycle. In women with an insufficient ovarian response to stimulation (3 follicles or less, according to the Bologna criteria), the frequency of cycle cancellations significantly increases and the likelihood of pregnancy decreases [36].

M. Aghahosseini et al. [37] were the first to conduct a randomized controlled study of the effect of taking estrogen preparations (4 mg orally) in the luteal phase of an IVF cycle in 118 patients over 37 years of age who had 5 or fewer oocytes obtained. The authors found no differences in implantation and pregnancy rates between groups, which were extremely low in this cohort of patients (9.5% vs. 8.2% and 13.2% vs. 10.9%, respectively).

In a prospective randomized study, F. Kutlusoy et al. [38] studied the effect of additional intake of estradiol hemihydrate in the luteal phase of the cycle in patients who responded to stimulation with the growth of 6 or fewer follicles or from whom 5 or fewer oocytes were obtained. Patients of group 1 ( n

=33) to support the luteal phase, only 9% gel with progesterone was prescribed vaginally, in the 2nd group (
n
=27) an additional 2 mg of estradiol was prescribed orally, in the 3rd group (
n
=35) - 6 mg of estradiol. The incidence of clinical pregnancy (12.1, 37.0 and 25.7%) and the frequency of childbirth (12.1, 37.0 and 22.9%) were significantly higher in groups 2 and 3 compared with 1st group.

The authors conclude that taking estrogen medications may increase the likelihood of embryo implantation in an IVF program in patients with an insufficient ovarian response to stimulation.

Transfer of thawed embryos against the background of HRT

Artificial preparation of the endometrium for the transfer of thawed embryos with estradiol and progesterone preparations is widely used in clinical practice both in patients with an ovulatory menstrual cycle and in women with anovulation.

It has been established that taking 2 to 6 mg of estradiol daily, starting from the 1st-3rd day of the menstrual cycle, in 90-96% of cases leads to suppression of the growth of the dominant follicle, blocks the release of LH and allows you to choose the date of transfer of thawed embryos at random [39, 40].

In some cases, to completely suppress the growth of follicles, GnRH drugs are additionally prescribed starting from the middle of the luteal phase of the previous menstrual cycle. One of the disadvantages of this approach is the need to constantly take high doses of estradiol and progesterone drugs during pregnancy, at least until 8 weeks. However, this option of preparing for the transfer is the only possible one in patients with persistent or sporadic anovulation.

J. Queenan et al. [41] studied the outcomes of 199 cycles of preparation for transfer using HRT drugs without pituitary desensitization. In 8 (4%) of 199 cycles, growth of the dominant follicle with a diameter of more than 16 mm was observed; in none of these cases was an LH peak detected. In the work of X. Yang et al. [42], the outcomes of 173 cycles of transfer of thawed blastocysts against the background of HRT were analyzed depending on the presence of a dominant follicle and ovulation. In 128 cases there was no growth of the dominant follicle, in 29 cases the follicle increased in diameter, but there was no ovulation, in 14 cases ovulation occurred. The pregnancy rate in these groups was 66, 71 and 61%, respectively, the miscarriage rate was significantly higher in the latter group compared to groups 1 and 2 (37.5% versus 8% and 5%, respectively). In other words, suppression of ovulation with estradiol drugs turned out to be necessary and sufficient for the successful transfer of thawed embryos.

At the same time, A. Simon et al. [40] compared the outcomes of 53 transfers of thawed embryos against the background of HRT and 53 cycles against the background of HRT with pituitary desensitization. Not a single case of growth of a dominant follicle was identified. Endometrial thickness on the day progesterone was started (10±1.6 mm vs. 11±1.6 mm), pregnancy rate (21.1% vs. 26.4%), and implantation rate (9% vs. 9.5%) did not differed between groups.

In a retrospective study by V. Morozov et al. [43] found that endometrial thickness was higher during natural cycle (VC) transfer (9.95 mm vs. 8.89 mm; p

<0.001), and the mean estradiol level was lower (103.8 pg/ml vs. 526.1 pg/ml;
p
<0.001) compared with HRT.
The pregnancy rate was also higher after transfer of thawed embryos to the EC (36.76% vs. 22.99%; p
= 0.0298).

In 2008, T. Ghobara and P. Vandekerckhove [44] analyzed 7 randomized controlled trials, which included 1120 women who underwent transfer of thawed embryos in the EC, against the background of HRT (including pituitary desensitization) and after ovarian stimulation. The authors found that the likelihood of live birth was statistically significantly lower in the group of women taking HRT against the background of pituitary desensitization compared with HRT without desensitization (OR 0.38, 95% CI 0.17-0.84; p

=0.02). There were no differences in the outcomes of cryotransfers in the EC compared with HRT without desensitization, and no differences in outcomes between cycles stimulated with clomiphene citrate and hMG drugs compared with HRT. The authors concluded that there are no advantages to different protocols for preparing thawed embryos for transfer.

C. Givens et al. [45] conducted a large retrospective study of 1677 cycles of thawed embryo transfer in 1205 patients. The birth rate did not differ between the groups where thawed embryos were transferred in a modified EC and against the background of HRT in patients who underwent IVF with their own oocytes (28.4% versus 29.4%, respectively) and with donor oocytes (25.6% versus 26. 9%).

J. Konc et al. [46] also did not reveal significant differences between the outcomes of transfers of thawed embryos to the EC, against the background of ovarian stimulation and against the background of HRT, while the pregnancy rate was higher in the group of transfers to the EC.

In a large retrospective cohort study, Y. Zheng et al. [47] studied the outcomes of 5414 cycles of transfer of thawed embryos: 2216 transfers to the EC, 1180 “semi-natural” cycles, where estradiol drugs were prescribed from the 10-12th day of the menstrual cycle, and 2022 transfers against the background of HRT, where estrogen intake was started from 1-12 days. 4th day of the cycle. The implantation rate was significantly higher in the HRT group compared with the EC and half-EC groups (29.3% vs. 21.5% and 25.6%; p

=0.01), as well as the pregnancy rate (48.7% vs. 42.7% and 36.1%;
p
=0.01). The authors concluded that HRT significantly increases the likelihood of pregnancy after transfer of thawed embryos.

In 2013, E. Groenewoud et al. [48] ​​conducted a meta-analysis of 20 studies examining the effectiveness of different methods of preparing the endometrium for transfer of thawed embryos, of which 13 studies were retrospective. There were no differences in the pregnancy rate and the rate of live birth after transfers in the EC, modified EC, against the background of HRT and HRT with pituitary desensitization. Since most of the studies studied had a retrospective design and studied different cohorts of patients, the authors concluded that a prospective randomized multicenter study was necessary [49].

Thus, the results of most studies indicate high pregnancy rates and live birth rates after the transfer of thawed embryos against the background of HRT with estradiol and progesterone. This method of preparing for transfer is a convenient and effective alternative to natural cycle transfer.

Is it necessary to prescribe additional estrogens to patients with thin endometrium?

An equally pressing and not fully resolved problem is the insufficient thickness of the endometrium, which is associated with implantation failures and miscarriage after IVF. Most researchers agree that pregnancy rates are significantly reduced when endometrial thickness is less than 7 mm on the day of embryo transfer. A number of studies have noted a positive linear relationship between endometrial thickness and pregnancy rate [50, 51]. However, the literature describes cases of the onset and successful progression of pregnancy with an endometrial thickness of 3-4 mm [52-54].

The growth of the endometrium in the follicular phase of the cycle occurs under the influence of estradiol, which produces the dominant follicle, i.e. this process is estrogen-dependent. There is a direct correlation between the diameter of the dominant follicle and the thickness of the endometrium. At the same time, in some patients the endometrium remains thin even in ovarian stimulation cycles against the background of the growth of many follicles and high concentrations of estradiol. In such cases, a mandatory study is diagnostic hysteroscopy, which often reveals concomitant pathology of the endometrium: intrauterine synechiae or chronic endometritis. Impaired endometrial receptivity leads to its “insensitivity” to hormonal signals and relative resistance to estradiol drugs.

L. Detti et al. [55] studied the effect of estradiol concentrations during ovarian stimulation on endometrial thickness and pregnancy outcomes in 102 patients in an IVF program. The authors did not find a significant relationship between the peak concentration of estradiol and endometrial thickness. In patients with an endometrium less than 9.8 mm, the risk of miscarriage was significantly increased.

One of the main prognostic factors for the likelihood of pregnancy today remains the quality of the resulting embryo and its implantation potential. Therefore, to adequately assess the isolated influence of the uterine factor on the probability of pregnancy, L. Dain et al. [56] studied the outcomes of 737 IVF cycles with donor oocytes. Clinical pregnancy rates and delivery rates did not differ between groups of women with endometrial thickness less than 7 mm and more than 10 mm. The birth rate was highest in the group of women with an endometrial thickness of 8-10 mm. The clinical pregnancy rate, miscarriage rate and live birth rate in the group of women with an endometrial thickness of 6 mm or less were 29.6, 9.3 and 16.7%, respectively.

For the same purpose, J. Gingold et al. [57] studied the influence of endometrial thickness and structure on the outcomes of transfers of fresh and thawed euploid embryos after preimplantation genetic diagnosis. The authors found no relationship between implantation rate, clinical pregnancy rate, and endometrial thickness on the day of embryo transfer.

A systematic review and meta-analysis on the effect of endometrial thickness on pregnancy rates in an IVF program was published by A. Kasius et al. [51] in 2014. The analysis included 22 studies and outcomes of 10,724 IVF cycles, of which only 260 (2.4%) cycles had endometrial thickness of 7 mm or less. There was a trend towards a decrease in the incidence of progressive pregnancy and the rate of live births (OR 0.38 (95% CI 0.09-1.5), as well as a significant decrease in the incidence of clinical pregnancy (OR 0.42; 95% CI 0.27 -0.67) in women with endometrial thickness 7 mm and below. However, due to the low predictive value of this criterion (positive predictive value 77%, negative predictive value - 48%), the authors do not recommend using endometrial thickness to decide on freezing all embryos, cancellation of transfer and refusal of IVF treatment.

B. Demir et al. [58] compared IVF outcomes in women with an endometrial thickness of 8 mm or less who took ( n

=57) and did not take (
n
=60) 4 mg estradiol orally daily starting from the day of hCG administration. There were no statistically significant differences in endometrial thickness on the day of embryo transfer (9.6±2.9 mm versus 10.3±2.4 mm), clinical pregnancy rate (28.1% versus 23.3%), and implantation rate (16% vs. 10.4%) and miscarriage rates (21% vs. 31.6%). The authors considered it inappropriate to prescribe estradiol drugs to patients with an endometrial thickness of 8 mm or less on the day of hCG administration.

Considering the direct relationship between endometrial thickness and estradiol concentration in most patients, H. Jung and H. Roh H. [59] conducted a prospective randomized study of additional administration of 4 mg estradiol orally starting from the 3rd day of the cycle on the outcome of the IVF program and found a statistically significant increase pregnancy rates (48.3% vs. 25.9%) and implantation rates (26% vs. 10%) in the group of women taking estradiol compared with the group of women not taking estradiol. M. Shen et al. [60] described a case of successful treatment of a patient with multiple unsuccessful IVF attempts and thin endometrium using long-term use of estrogen drugs.

Thus, the results of many studies indicate that the problem of insufficient readiness of the endometrium for embryo implantation in patients with infertility and miscarriage is not always associated with estrogen deficiency, while additional use of estradiol drugs can increase the pregnancy rate in such women.

Estrogen priming

One of the reasons for the poor response is considered to be an increase in FSH concentration, since it leads to the growth of antral follicles, the appearance of larger follicles at the beginning of stimulation and, accordingly, an asynchronous response of the follicles to stimulation with FSH drugs.

A promising solution to the problem of insufficient ovarian response to stimulation is “estrogen priming” - the administration of estrogen drugs in the luteal phase of the cycle preceding stimulation to reduce FSH levels. This tactic was first proposed by R. Fanchin et al. [61] in 2003. The authors showed that after oral administration of 4 mg estradiol from the 20th day of the previous menstrual cycle until the 1st day of the next cycle, the level of FSH statistically significantly decreases, the average diameter of the follicles and the average volume of the ovaries decreases by 3-3. th day of the cycle. The theoretical basis for this effect is the negative feedback between the levels of FSH and estradiol in the luteal phase of the cycle. The administration of estradiol preparations leads to the formation of a more homogeneous cohort of antral follicles in size and a more synchronous response to stimulation.

GnRH antagonists act in the same way when prescribed 3-4 days before the start of the cycle or from the 1st to 3rd day of the cycle. R. Fanchin et al. [62] in 2004 showed that a single administration of 3 mg of cetrorelix acetate on the 25th day of the cycle leads to a statistically significant decrease in FSH levels and a decrease in the average diameter of the follicles on the 3rd day of the next cycle.

M. Hill et al. [63] in a retrospective study examined the effectiveness of estrogen priming in a cohort of 57 patients with unsatisfactory results of previous IVF attempts (5 or fewer oocytes received, poor quality of oocytes or embryos, lack of response to stimulation) or a predicted insufficient response to stimulation (FSH more than 12 IU/ l, number of antral follicles 5 or less) compared with 228 patients in the control group who received the same stimulation protocol without estrogen priming. The mean number of good quality oocytes and embryos obtained did not differ between groups. No statistically significant differences were found in the rates of implantation, clinical pregnancy, spontaneous miscarriages, and live births among patients who received and did not receive estrogen priming.

A retrospective study of 155 IVF cycles with stimulation according to an antagonist protocol in patients with a previous insufficient response to stimulation (less than 5 oocytes received) was conducted by E. Chang et al. [64]. In 86 cycles, 4 mg estradiol valerate was prescribed, starting from the 21st day of the previous cycle until the 3rd day of the stimulation cycle (28 cycles) or until the day of hCG administration (58 cycles); in 69 cycles, estrogen priming was not prescribed. The rate of cycle cancellation was significantly lower in the estrogen priming group (15.1% vs. 37.7%; p

<0.01), and the number of oocytes obtained was statistically significantly higher (4.5±2.9 versus 3.2±1.9;
p
<0.01).
There were no differences in the embryological parameters of the subgroups receiving estradiol before the 3rd day of the cycle and before the day of hCG administration, while in the latter subgroup the rate of progressive pregnancy was slightly higher (27.1% versus 20%; p
= 0.357).

In 2013, X. Chang et al. [65] conducted a meta-analysis of 7 studies examining estrogen priming. The analysis included 450 estrogen priming cycles and 606 control cycles. The authors concluded that when using estrogen priming, the duration of stimulation, the total number of oocytes obtained and the number of mature oocytes increases, and the frequency of interrupted ART cycles decreases. There were no differences in pregnancy rates, although there was a trend toward an increase: OR 1.22 (0.89–1.68).

Another meta-analysis was published by K. Reynolds et al. [66] in 2013. It included 8 studies: 7 retrospective and 1 randomized controlled trial. All studies used an antagonist stimulation protocol. In 6 studies, estrogen priming was administered concomitantly with a GnRH antagonist drug; 6 studies used an estradiol patch and 2 gave oral estradiol. A total of 468 cycles with estrogen priming and 621 cycles without priming were analyzed. The rate of ART cycle cancellation in group 1 was significantly lower, and the rate of clinical pregnancy was higher when using estrogen priming. There were no differences in the number of oocytes and embryos obtained between the groups. Noteworthy is the heterogeneity of the criteria for underestimation.

What phytoestrogens are there?

There are 3 classes of phytoestrogens:

1. Kumestans - there are a lot of them in products that can hardly be called familiar to Russian people (sprouted seeds of clover, alfalfa).

2. Lignans – found in peanuts, brown rice, flax seeds.

3. Isoflavones are the safest and most studied phytoestrogens. There are a lot of them in soybeans.

It is isoflavones that are abundant in tofu, soy milk and meat - these are the products that form the basis of the diet of women in China and Japan. However, normalization of hormonal levels is not the only merit of isoflavones. They also lower “bad” cholesterol and reduce the risk of heart and vascular diseases. To preserve your health, you need to get from 25 to 50 mg of isoflavones per day (this is equal to 0.5–1 liter of soy milk).

The content of phytoestrogens varies in different foods. To get the required dose of phytoestrogens, you need to eat foods with plant components in sufficient quantities and do this regularly. Residents of Asia do not need to do anything for this - their diet is already rich in phytoestrogens. But what about those who don’t eat soy or tofu every day? Not everyone can radically change their diet.

A more convenient solution is preparations with phytoestrogens.

Basics of treatment with antitumor drugs - estrogens

All antitumor drugs, including estrogen drugs, are prescribed only by an experienced oncologist.

The use of antitumor drugs is also under the strict supervision of a physician. This is due to the high toxicity of cancer treatments, as well as the high risk of interaction with other drugs or food.

Estrogen preparations are used in the form of oil solutions intramuscularly. The duration of estrogen treatment is determined by the doctor depending on the form and severity of the disease.

Criteria for choosing products with phytoestrogens

Of course, if you go to a pharmacy and ask for some product with phytoestrogens, you will be offered many options. How to choose the right one? To begin with, keep in mind that you need to take phytoestrogens in a course, which means you should approach your choice as responsibly as possible. It is very important to evaluate the effectiveness of the complex, its cost-effectiveness (whether you can afford to buy it for several months or even years). We analyzed these criteria and compared several popular drugs.