Method of treating benign hyperplastic processes of female reproductive system

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely obstetrics and gynaecology, and may be used for treating benign hyperplastic processes of the female reproductive system. That is ensured by the introduction of gonadotropin-releasing hormone agonist for 6 months once monthly in a combination with the oral administration of the preparation for hormonal replacement therapy. It is preceded by specifying the initial metabolic, vegetative and gynaecologic status of the patient which along with an age group provides a basis to assess an adequacy of initiating hormonal add-back therapy. If the patient belongs to the age group of under 40 years of age, and in case of observing additional burdening of the metabolic and vegetative status, the introduction of gonadotropin-releasing hormone agonist with no hormonal add-back therapy prescribed. For the purpose of preventing potential negative symptoms, it is combined with underlying prescription of a complex of phytoestrogens and vitamins with required intake of calcium and vitamin D3. Each injection of gonadotropin-releasing hormone agonist, starting with the second one, is followed by clinical assessment of hypestrogenism symptoms and blood chemistry analysis, and if observing hypestrogenism symptoms, additional hormonal add-back therapy is prescribed. If the patient appears to belong to the age of 40 years old and more, and in case of observing the presence of burdened metabolic and vegetative status regardless of the age group, 2 years after the first injection of gonadotropin-releasing hormone agonist, hormonal add-back therapy is started. When selecting the preparation included in the hormonal add-back therapy regimen: there are differentiated: if the patient belongs to a younger group under 35 years of age, a therapeutic add-back preparation is presented by a combine oral contraceptive containing ethinyl estradiol 30 mg and dienogest 2 mg in each tablet. The oral contraceptive is prescribed 1 tablet a day in the continuous regimen which is recommended to be used after termination of the therapeutic course with gonadotropin-releasing hormone agonist if pregnancy prevention is required. If the patient belongs to the age group of 35 years and older, a therapeutic hormonal add-back preparation is presented by a preparation for hormonal replacement therapy containing micronised 17-p estradiol 1 mg and dydrogesterone 5 mg or a preparation containing drospirenone 2 mg instead of dydrogesterone in each tablet 1 tablet a day in the continuous regimen. An initial or underlying tendency to increase of blood pressure, a combined preparation for hormonal replacement therapy containing drospirenone is prescribed. The therapeutic course is followed by recommended administration of the preparation of hormonal replacement therapy if the patient belongs to the age group of 50 years and older in the continuous regimen.

EFFECT: method enables providing an evident therapeutic effect that is manifested in stable elimination of estrogenic deficiency symptoms accompanying gonadotropin-releasing hormone agonist therapy with preserved clinical effectiveness and improved patient's quality of life.

2 ex

 

The invention relates to medicine, namely to gynecology, and can be used in gynecology for the treatment of benign hyperplastic processes, such as uterine fibroids, genital endometriosis, endometrial hyperplastic processes in women of reproductive and perimenopausal period.

Over the past decade has significantly increased incidence of hyperplastic processes of the reproductive system in women. Uterine fibroids occur in a population at 25-35% of women mainly late reproductive and premenopausal age (Valeeva E.M., 2004). Endometriosis affects 5-10% of the population of women of reproductive age (Eskenazi Century, N. Warner, 1997). The prevalence of endometrial hyperplastic processes increases with age, ranging from 6% among women of reproductive age with a variety of reproductive health to 15-20% or more among women in perimenopause (Chernukha, 1999, rose, dis.).

One of the urgent problems of modern gynecology is the choice of adequate therapy in this group of patients, since there is a high frequency of poor treatment outcome and, as a consequence, the further progression of the process, up to malignancy.

The modern approach to the conservative treatment of hyperplastic processes W is nskoi reproductive system conforms to currently accepted concepts in accordance with which they are based on a system hyperestrogenemia and violation of the local balance of hormones, growth factors and immune response (L.V. Adamyan, Tkachenko E.R., S.I. Kiselev, Gaidarova AH Modern methods of diagnostics and treatment of hyperplastic processes and tumors of the uterus. Practical gynecology (clinical lecture).

Modern methods of conservative treatment hyperplasticity processes aimed at the suppression of hyperestrogenemia with simultaneous effects on local tissue processes and preserving the reproductive potential of women.

There is a method of treatment of hyperplastic processes of the female reproductive system in which to suppress excess estrogen influences to use drugs such as steroids origin - progestins, as well as combined oral contraceptives (Manual endocrine gynecology. Edited Emiliou, 1997).

However, the treatment of hyperplastic processes of the reproductive system drugs steroid of origin has a common drawback: with a relatively high efficiency of the treatment of endometrial hyperplasia and endometriosis and their effect on uterine fibroids and benign proliferation of breast unpredictable, and therefore their use is limited.

There is a method of treatment of hyperplastic% is saw of the female reproductive system agonists of gonadotropin-releasing hormone (GnRH), causing artificial reversible menopause and affect local processes of proliferation and apoptosis (Tikhomirov A.L., Lubnin D.M. Pathogenetic rationale for the use of agonists and GnRH agonists in the treatment of combined gynecological pathology. Questions of gynecology, obstetrics and Perinatology, 2006; 5:1:82-87).

The treatment regimen includes intramuscular or subcutaneous administration of the agonist neurokinin 1 every 28 to 30 days within 6 months.

A-GnRH, forming postmenopausal hormonal status, resolve proliferative processes in the foci of endometriosis and hyperplastic endometrium, simultaneously stabilize the growth of myoma nodes and lead to their reduction.

The disadvantage of this method are the side effects associated with hypoestrogenia and formation of postmenopausal hormonal status. Symptoms of oestrogen deficiency can significantly impair the quality of life of women, manifesting vasomotor disturbances, mood changes, worsening of sleep, lower efficiency. No less serious complication of therapy is the loss of bone mineral density (Sagsveen M.). In the end, more than half of women stop taking inrg due to tides and other vasomotor disorders and doctors reduce the duration of a course of treatment, for fear of reducing mineralolproduckte bone.

Recently, to mitigate adverse effects associated with hypoestrogenia use the so-called "therapy cover", namely, that on the background of treatment with agonists of gonadotropin-releasing hormone administered drugs sex hormones - or progestins progestins in combination with low doses of estrogen, which helps to reduce side reactions agonists of GnRH, without affecting their efficiency.

There is a method of treatment of hyperplastic processes of the female reproductive system through the introduction of GnRH agonists in combination with a progestin-tibolona (T. Agorastos, Vaitsi V., Paschopoulos M. et al. Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia. Maturitas 2004; 48: 125-132).

The method of treatment involves intramuscular injection of agonist neurokinin of leuprolide acetate at a dose of 3.75 mg 1 every 28-30 days for 6 months while receiving tibolona 2.5 mg daily in tablet form.

However, this method is limited in application because of the lack of effectiveness of cupping a progestin tibolone vasomotor symptoms, adverse metabolic reactions, as well as the high cost of therapy.

As the closest analogue of the adopted method for the treatment of hyperplastic processes of the female reproductive system through the introduction of GnRH agonists - leiprorelina acetate is a dose of 3.75 mg intramuscularly together with drugs for hormone replacement therapy conjugated estrogens and medroxyprogesterone acetate, oral input (Homstein M.D., Surrey E.S., Weisberg G.W., L.A. Casino Leuprolide acetate Depot and hormonal add-back in endometriosis: a 12-month study. Obstet Gynecol 1998; 91: 16-24).

Medroxyprogesterone acetate (MPA) has demonstrated effectiveness in reducing vasomotor symptoms.

However, with regard to the protection of bone tissue was observed lack of effect (Cedars M, Lu K, Meldrum DR, Judd HL. Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate. Obstet Gynecol 1990; 75:641-5).

Therapy agonist neurokinin - leiprorelina - acetate in combination with medroxyprogesterone acetate does not prevent the negative effects of agonists of gonadotropin-releasing hormone on the metabolism and does not provide protection against cardio-vascular system.

In addition, after the adverse results of the WHI study (Initiative on women's health The Women's Health Initiative), obtained by using the combination of conjugated estrogens and medroxyprogesterone acetate in women in the postmenopausal period, the use of these drugs in Europe and in Russia is limited.

In this regard, the search for better ways of hormonal cover therapy in women with drug menopause modeled after receiving GnRH agonists, remains relevant and necessary.

The objective of the invention is to provide a method of treatment, the Oia hyperplastic processes of the female reproductive system, allows you to get a pronounced and persistent therapeutic effect, on the background of reduction of symptoms and complications hypoestrogyny with medication menopause and improve the quality of life of patients.

The invention consists in that in the method of treatment of benign hyperplastic processes of the female reproductive system, including the introduction into the organism of agonist neurokinin within 6 months 1 per month in combination with oral drug for hormone replacement therapy, pre-install the original metabolic, autonomic, and gynecological status of the patient, the condition of which, together with its affiliation to a particular age group are taking for the basis for determining the appropriateness of initiation of hormone therapy cover, and facilities of the patient to the age group up to 40 years and no additional encumbrances metabolic and autonomic status introduction agonist neurokinin conduct without hormonal therapy of the cover against which to prevent possible negative symptoms, designate the complex of phytoestrogens and vitamins with mandatory drug calcium and vitamin D3after each injection of an agonist of gonadotropin-releasing hormone from the second, conduct a clinical assessment of symptom is in hypoestrogyny and analysis of biochemical indicators in the blood and in the case of the onset of symptoms hypoestrogyny additionally prescribe hormonal therapy cover when the facilities of the patient to the age group 40 years and older, and in the presence of encumbrances metabolic and autonomic status, regardless of age group 2 weeks after the first injection of agonist neurokinin begin hormone therapy cover, the choice of the drug included in the scheme of hormonal therapy cover, perform differentially: the facilities of the patient to a young age group up to 35 years as drug therapy cover prescribed combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienoguesta in each tablet, 1 tablet per day in continuous mode, which is recommended to continue taking after completion of the course of treatment with agonist neurokinin if necessary, protection against pregnancy, toiletries patients in the age group 35 years and older as of the hormonal drug therapy cover prescribe the drug for hormone replacement therapy containing 1 mg of micronized 17β-estradiol and 5 mg dydrogesterone, or preparation containing 2 mg of drospirenone instead of dydrogesterone each tablet 1 tablet a day, in the continuous mode, when the source or appeared on treatment trends for high blood pressure prescribed in combination the drug for hormone replacement therapy, containing drospirenone, after the course of treatment recommended to continue taking the drug for hormone replacement therapy in facilities of the patient to the age group 50 years and older in the continuous mode.

The use of the invention allows to obtain the following technical result.

The method allows to obtain a pronounced therapeutic effect, which is manifested in persistent symptoms of oestrogen deficiency arising on a background of treatment with agonists of gonadotropin-releasing hormone, while maintaining the effectiveness of this treatment of hyperplastic processes of the reproductive system (genital endometriosis, endometrial hyperplasia, and uterine fibroids), both in isolation and in combination, which ultimately improves the quality of life.

The method improves superensemble treatment with agonists of gonadotropin-releasing hormone and helps to extend their use to the recommended 6-month course of treatment.

The method provides for a differentiated selection of therapy cover and time of its beginning, depending on the initial status of the patient and characteristics of portability, the first injection of the agonist of gonadotropin-releasing hormone.

The method allows to reduce the symptoms and complications of hypoestrogenism, improve carbohydrate and fat metabolism, to achieve stability in blood pressure, that is here to reduce the risk of cardiovascular diseases, associated with age and estrogen deficiency, as well as to minimize vasomotor symptoms.

The method takes into account the need for continued prevention of the recurrence of hyperplastic processes of the reproductive system after completion of the course the introduction of GnRH agonists in patients who are not planning pregnancy, drugs, used as a cover therapy during treatment with GnRH agonists.

The technical result is achieved due to the developed by the authors of the new technology. The authors first established pathogenic diversity of the formation of symptoms of oestrogen deficiency against medical menopause depending on the initial status of patients.

Features of the organism's reaction to treatment with agonists of gonadotropin-releasing hormone are determined by the patient's age, functional status, her reproductive system (early reproduction, late reproduction, perimenopause), status, metabolic and autonomic status: the initial endocrine-metabolic syndrome and autonomic dysfunction.

The authors found that regardless of the characteristics of the underlying disease (uterine fibroids, endometrial hyperplasia, genital endometriosis), women under the age of 40 years with normal baseline indicators endocr the NGO-metabolic and autonomic status tolerate treatment with agonists of gonadotropin-releasing hormone and do not need supplemental hormones. Minor vegetative symptoms and temporary decrease in mineral bone density in these patients can be compensated by the appointment of phytoestrogens, vitamins and minerals.

The authors also identified risk factors for adverse reactions to therapy with agonists of gonadotropin-releasing hormone on the basis of which and depending on the age and functional status of the reproductive system developed differentiated application of hormonal preparations as a cover therapy.

Given the high risk of recurrence of hyperplastic processes of the reproductive system, the developed technology enables the prolongation of course antiproliferative secondary prevention immediately after the introduction of GnRH agonists, the same drugs that were injected into the body as a cover therapy that provides relapse prevention.

The drug hormone therapy cover two weeks after the beginning of injection of the agonist of gonadotropin-releasing hormone is associated with the mechanism of action agnrs. After his first injection, first within the first 7 days the content of sex hormones increases (physiological response), then after 2-3 weeks is a long blockade of secretion and GnRH, which is characterized hypoestrogenemia symptoms.

sleduushee monthly introduction supports low level of sex hormones, in conjunction with other mechanisms administered drugs provides synergies and prolonged therapeutic effect of their actions.

Drugs developed by the authors in the scheme of hormonal therapy cover selected optimally effective for each age group in the research process and statistical processing of the obtained data.

The method is as follows.

The patient with hyperplastic processes of the reproductive system, with indications for GnRH agonists, before therapy inrg survey conducted to assess the autonomic nervous system (the questionnaire to identify autonomic changes), indicators of fat and carbohydrate metabolism (glucose, total cholesterol, lipoprotein cholesterol, triglycerides).

Setting the initial metabolic, autonomic, and gynecological status of the patient, the condition of which, together with its affiliation to a particular age group, the main parameters of activity data and personal history is taken for a basis to determine the feasibility of initiation of hormone therapy cover.

Regardless of the source of the data - metabolic, autonomic, and gynecological status and age group of the patient is prescribed care the agonists of GnRH by intramuscular or subcutaneous injection, for example, leiprorelina acetate 3.75 mg 1 every 28 to 30 days within 6 months.

When the facilities of the patient to the age group up to 40 years and no additional encumbrances metabolic and autonomic status introduction agonist neurokinin spend without hormonal therapy cover.

To prevent possible negative symptoms of the patient, a member of the group, designate a complex of phytoestrogens and vitamins with mandatory drug calcium and vitamin D3.

After each injection of an agonist of gonadotropin-releasing hormone from the second, conduct a clinical assessment of the symptoms hypoestrogyny and indicators of biochemical analysis of blood. In case of occurrence of a symptom hypoestrogyny - vasomotor complaints, in breach of quality of life, or persistent high blood pressure of 140/90 mm Hg or more or dyslipidemia appoint additional hormonal therapy cover.

When the facilities of the patient to the age group 40 years and older, and if there are encumbrances on autonomic and metabolic status, regardless of age group 2 weeks after the first injection of agonist neurokinin prescribe hormonal therapy cover.

The choice of the drug included in the scheme of hormonal therapy cover, produce differentiated.

If p is indigesti patient to a young age group up to 35 years as drug therapy cover prescribed combined oral contraceptive, containing 30 mcg ethinyl estradiol and 2 mg dienoguesta in each tablet. Combined oral contraceptive administered in a continuous mode 1 tablet in day.

When the facilities of the patient to the age group 35 years and older as of the hormonal drug therapy cover prescribe the drug for hormone replacement therapy containing 1 mg of micronized 17β-estradiol and 5 mg dydrogesterone, or preparation containing 2 mg of drospirenone instead of dydrogesterone in each tablet.

Drug for hormone replacement therapy is administered in a continuous mode 1 tablet in day.

When the source or appeared on treatment trends for high blood pressure prescribed combination drug for hormone replacement therapy containing drospirenone.

After the end of treatment agonist neurokinin recommend continued taking the drug for hormone replacement therapy in facilities of the patient to the age group of 50 years and more, in a continuous mode.

Combined oral contraceptive may be recommended to continue with toiletries patient to a young age group up to 35 years if necessary, protection from pregnancy in standard mode 21+7 or in continuous mode, the desire of the women.

Way passed clinical trials in City clinical hospital №72 City of Moscow and gynecological hospital No. 5 in Moscow on women aged 17-52 years. The total number of surveyed volunteers was 90 people, including 50 from combined patologia hyperplastic processes of the reproductive system (uterus, genital endometriosis, endometrial hyperplastic processes) and 40 with endometriosis. All patients were treated by the proposed method with regard to gynecological, metabolic and autonomic status and age group (in accordance with the invention).

In 90% of treated patients noted a pronounced therapeutic effect, which consists in reducing the severity of hyperplastic processes of endometrial hyperplasia, sizes myomatous nodes, the absence of clinical symptoms and recurrence of hyperplastic processes of the reproductive system in a long time.

Clinical trials and observations demonstrated improved tolerability of treatment with agonists of gonadotropin-releasing hormone, which allowed to extend their use to the recommended 6-month course and achieve a pronounced therapeutic effect.

The possibility of planning long-term treatment programs hyperplastic PR the processes of the reproductive system, including endometriosis, a disease characterized by a high recurrence rate. The combination of GnRH agonists with combined oral contraceptives potentially beneficial from the standpoint of the increase therapeutic effects. At the same time low dose of levonorgestrel in a combined oral contraceptive can eliminate the side effects and to prevent the development of complications hypoestrogyny patients related to the young age group, and, as a consequence, to improve the quality of life. Extension of hormonal contraceptive after the end of therapy agonist neurokinin provides reliable contraception and prevention of relapses hyperplastic process up to the moment when a woman decides to plan pregnancy.

Using the proposed method of treatment combined and isolated hyperplastic process of the reproductive system helped to avoid surgery and to achieve a positive result of conservative therapy with good tolerability.

Clinical example 1

Patient OPU, 50 years history No. 1842.

The diagnosis of dysfunctional uterine bleeding in perimenopausal; simple hyperplasia, endometrial; uterine myoma of the small sizes with interstitielle-subserosal location of the node; iron deficiency ane the Oia mild.

With the original metabolic, autonomic, and gynecological status.

Complaints received at a bleeding from the genital tract within 2 weeks, weakness, dizziness, irregular menstruation over the 2 years that could occur during a delay menstruation hot flashes.

History: uterine fibroids was first diagnosed at the age of 40, during the observations noted a slight increase of the dominant node and the appearance of the second small node fibroids. In 45 years about bleeding that developed after a 10-day delay menstruation, underwent a separate diagnostic curettage under control hysteroscopy. The result of histological research: simple (glandular) hyperplasia of the endometrium. After surgery received treatment dydrogesterone (20 mg/day) 15-day cycles in conventional luteal phase of the menstrual cycle (3 cycles). After treatment menstrual cycle returned to normal, regular menstruation was observed up to 48 years. With 48 years noted progressive delay menstruation from 2 to 10 months during the 10-month delay in 49 years began to complain of hot flushes. However, this long delay ended in spontaneous menstruation, shortly before which the hot flashes themselves disappeared. Next menstruation again came staderini, until after the next 3-week delay is not started bleeding, not stopped despite the use of hemostatic means and which was the reason for hospitalization.

Objectively: the patient is in satisfactory condition. Build normotimicescoe, the female type. Height 172 cm, weight 70 kg, Pulse 88 beats./min, BP 110/80 mm Hg. Pale skin, clean. Peripheral edema no. The breast is developed normally, palpation diffusely sealed, pathological lesions and discharge from the nipple is not detected. When the General inspection of the signs of pathology of internal genital organs are not detected.

Gynecological examination: cervix visually not changed (routine cytological examination conducted 6 months prior to treatment, pathology was not detected); the body of the uterus is enlarged and deformed by the front wall myoma node size is about 3 cm, palpation dense, mobile, painless. Appendages on both sides are not defined, their painless. Discharge from the genital tract blood in moderation.

Given the prolonged bleeding in the perimenopausal patient age, hysteroscopy and separate diagnostic curettage. Visual inspection of the uterine cavity of deformation is not found, histological the second report on results of research scraping of the endometrium - "simple hyperplasia".

The results of clinical laboratory tests: HB - 102 g/l, the remaining indicators clinical analysis of blood within normal limits. In the biochemical analysis of blood, mostly without pathology, there are minor changes in the lipid spectrum: total cholesterol - 6.2 mmol/l, TG - 1.2 mmol/l, LDL-C of 4.1 mmol/l, HDL-C - 1,85 mmol/L.

Mammography: fibrocystic breast disease, the recommended control through the year. Ultrasound of the pelvic organs: two myomatous node size of 3.1 cm and 1.2 cm, the uterus is not deformed. The reflection from the endometrium linear (one day after curettage). In ovaries isolated follicles.

Assess the source of the metabolic status of the patient: the lack of excess weight, changes in lipid profile in the direction of hyperlipidemia; vegetative status: the presence of occasional hot flushes; gynecological status: combined gynecological pathology - fibroids and hyperplastic process of the endometrium.

Considering the age group of the patient is older than 40 years, and aggravated metabolic and autonomic status assigned to the treatment by the proposed method, including intramuscular agonist neurokinin - leiprorelina acetate (lyukrin depot) - 6 injection 1 injection 3.75 mg in 30 days with hormone therapy, Prakriti is.

Two weeks from the first injection leiprorelina acetate, the patient started taking the drug for hormone replacement therapy - etostone 1/5 containing 1 mg of micronized 17β-estradiol and 5 mg dydrogesterone 1 tablet per day together with calcium D3Nycomed-Forte 1 tablet 2 times a day in order to relieve menopausal symptoms and prevention of loss of bone mineral density. By the 15th day of therapy the effects of menopausal syndrome decreased significantly. Control clinical examination during the course of therapy showed a decrease in the size of myoma nodes while maintaining consistently good overall health.

Examination after the last injection leiprorelina acetate showed positive dynamics of the underlying disease course. According to ultrasound the size of the dominant myoma node decreased to 1.5 cm, the second node does not appear. The reflection from the endometrium linear. In the right ovary is determined by a single follicle in the left follicles are not rendered. Hormone replacement therapy is continued by femoston 1/5. For the 6 months follow up feeling good, growth of fibroids and negative dynamics of fibrocystic mastopathy by ultrasound is not observed.

From the presented clinical example is IDNO, that the use of the proposed method of combined treatment of hyperplastic process of the reproductive system allows you to avoid surgery and to achieve a positive result conservative therapy with good tolerability. Relief of menopausal symptoms femoston allowed to extend the treatment to the required 6 injections. During this time occurred the depletion of follicular ovarian reserve, which created the opportunity to continue receiving femoston as hormone replacement therapy.

Clinical example 2

Patient EIS, 31 year history No. 6985 appealed with complaints of lower abdominal pain right side pain in the lower abdomen of the pull of nature, of varying intensity, radiating to the buttock, groin, constant, but increasing for several days before and during menstruation.

Pre-installed original metabolic, autonomic, and gynecological status.

History: menstruation for 12 years, was installed immediately, 5-6 days 28-29 days, regular, moderate, painful. Sex life of 20 years, married, regular. Protected from pregnancy by using barrier methods (male condom). Pregnancies - 3. Childbirth is 1 in 24. The pregnancy ended in childbirth, was uneventful. Induced abortion - 2, 25 and 2 years. The second abortion complicated acute endometritis, oophoritis, concerning which received treatment in hospital. Gynecological diseases: cervical ectopia, laser coagulation in 25 years. Chronic oophoritis with 27 years (Exodus postabortion acute inflammatory process).

Abdominal pain periodically disturbed for several years, but began to grow, to become constant and disrupt the everyday physical and social activity with 27 years after a previous inflammatory process. The pain intensity was regarded as exacerbation of chronic oophoritis, about which the patient twice received antibiotic therapy without effect. After the 2nd course of antibiotic therapy was prescribed course of physiotherapy, which has caused increased pain. It was further recommended the use of nonsteroidal anti-inflammatory drugs, against which the pain has decreased slightly. Shortly after the end of medication, symptoms of pain resumed.

When inspecting the condition is satisfactory. The shape of female type, height 165 cm, weight-53 kg heart rate of 78 beats per minute, BP 120/70 mm Hg. The skin is clean. Mammary gland: effects of mastitis (observed in mammologist about fibrocystic mastopathy). Signs of diseases of internal organs not in the manifest.

Gynecological examination: external genitals are developed correctly. Vaginal mucosa is normal pink color, without pathological changes. The cervix has a cylindrical shape, with no apparent pathology. The body of the uterus is rejected to the right is a medium sized, dense, painless, somewhat limited in mobility due to adhesions. The appendages on the left is not clearly defined, and the field in spinach sensitive when viewed from the right is palpated increased to 4 cm ovarian sensitive during the inspection. There is tenderness to palpation in the region of Sacro-uterine ligaments and the walls of the pelvis.

Ultrasound of the pelvic organs: the size of the uterus within age norms, the structure is not modified, M-echo - 6 mm (7th day of the menstrual cycle), visually corresponds to the proliferative phase, the volume of the left ovary 7.4 cm3with follicles maximum diameter of 8 mm, in the right ovary is defined cystic formation 2.7 cm in diameter, heterogeneous echostructure (endometrioid cyst?).

Physical examination of the pathology it is not revealed.

Laparoscopy: detected peritoneal endometriosis and endometrioma right ovary. Made surgical intervention in the amount of resection of right ovary, laser coagulation of endometrioid heterotopy. The histological conclusion research re the projected ovarian tissue confirmed the diagnosis of endometrioma.

Clinical diagnosis of external genital endometriosis III-IV degree, endometrioma right ovary, adhesions in the pelvis.

Taking into account peculiarities of pathogenesis of endometriosis patient treatment by the proposed method for the prevention of relapse. Given the absence of encumbrances on metabolic and autonomic status and age group of the patient to 40 years assigned intramuscular injection of agonist neurokinin - leiprorelina acetate (lyukrin depot): 1 injection injection 3.75 mg once a 30 days course of 6 injections without hormonal therapy cover.

To prevent possible negative symptoms of the patient, a member of the group assigned - phytoestrogen (Estravil) and vitamins with mandatory drug calcium and vitamin D3(Calcium D3Nycomed).

After the 3rd injection when interviewing the patient complained of worsening of the General condition, weakness, constantly depressed mood, lack of libido, hair loss on the head, rare hot flushes. The patient started hormone therapy cover in the form of low-dose combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienoguesta (j), in continuous mode. In patients receiving Janina the patient's condition has improved during the month.

After the last inye the tion of agonist neurokinin clinical and ultrasound examination, not showing signs of recurrence of endometriosis. With the patient interviewed about her reproductive plans. In the conversation, the patient reported that he is not planning pregnancy within the next year. Given this circumstance, and that combined oral contraceptive with dienoguesta has its own therapeutic potential in the prevention of relapse of endometriosis, it was decided to continue taking Janina with contraceptive and therapeutic purposes in standard mode, the 21-day cycles with 7-day intervals. Within 4 months of monitoring the health of the patient is good, no complaints, signs of recurrence of endometriosis is not revealed.

A method of treating benign hyperplastic processes of the female reproductive system, including the introduction into the organism of agonist neurokinin within 6 months 1 per month in combination with oral drug for hormone replacement therapy, wherein the pre-set initial metabolic, autonomic, and gynecological status of the patient, the condition of which, together with its affiliation to a particular age group are taking for the basis for determining the appropriateness of initiation of hormone therapy cover, and set the patient's age, grouped 40 years and no additional encumbrances metabolic and autonomic status, introduction agonist neurokinin spend without hormonal therapy cover, against which to prevent possible negative symptoms, designate the complex of phytoestrogens and vitamins with mandatory drug calcium and vitamin D3after each injection of an agonist of gonadotropin-releasing hormone from the second, conduct a clinical assessment of the symptoms hypoestrogyny and analysis of biochemical indicators in the blood and in the case of the onset of symptoms hypoestrogyny additionally prescribe hormonal therapy, shelter, toiletries patients in the age group 40 years and older, and in the presence of encumbrances metabolic and autonomic status, regardless of age group 2 weeks after the first injection of agonist neurokinin begin hormone therapy cover, while the choice of the drug included in the scheme of hormonal therapy cover, carry out differentiation: when facilities patient to a young age group up to 35 years old as drug therapy cover prescribed combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienoguesta in each tablet, 1 tablet per day in continuous mode, which is recommended to continue receiving after treatment with agonist neurokinin when is neobhodimosti protection against pregnancy, when the facilities of the patient to the age group 35 years and older as of the hormonal drug therapy cover prescribe the drug for hormone replacement therapy containing 1 mg of micronized 17β-estradiol and 5 mg dydrogesterone or preparation containing 2 mg of drospirenone instead of dydrogesterone each tablet 1 tablet a day, in the continuous mode, when the source or appeared on treatment trends for high blood pressure prescribed combination drug for hormone replacement therapy containing drospirenone, after the course of treatment recommended to continue taking the drug for hormone replacement therapy in facilities of the patient to the age group of 50 years and over in the continuous mode.



 

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FIELD: veterinary medicine.

SUBSTANCE: method includes injection of the preparation "FSH-super" and the preparation of prostaglandin F2α. On the day of artificial insemination the cows-donors are additionally injected with homeopathic preparation "Ovariovit" at the dose of 4.9-5.1 ml per head in a single dose.

EFFECT: method enables to obtain a greater number of embryos and to improve their quality.

5 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to gynecology, and can be used for syndrome of ovary hyperstimulation, as well as for its prevention in a subject who is under treatment against infertility with gonadotropic hormone. For this purpose composition, which contains quinagolide in pharmaceutically acceptable carrier, is introduced to patient.

EFFECT: introduction of quinagolide, in contrast to other dophamine agonists, ensures high therapeutic efficiency in considerably smaller doses and is quickly excreted from organism, which reduces risk of toxicity for mother and fetus.

16 cl, 3 tbl, 6 ex, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to administration of formula (I) described new triazole derivatives as greline-like ligands of growth hormone secretion stimulating receptors (GHSS receptors) that can be effective in treatment or prevention of GHSS receptors mediated physiological and/or pathophysiological conditions in mammals, preferentially in humans. Formula (I): where R1 is chosen from a group including hydrogen atom, (C1-C12)alkyl phenyl, naphthyl, (C5-C14)phenyl(C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; R2 is chosen from a group including (C1-C12)alkyl, phenyl, naphthyl, (C5-C14)phenyl (C1-C12)alkyl, indolylalkyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -Cl, -Br, -I, -NO2, (C1-C12)alkyl, phenyl, naphthyl, -O-(C1-C12)alkyl; one of radicals R3 and R4 represents hydrogen atom, and other radical are chosen from a group including hydrogen atom, phenyl, naphthyl, indolylalkyl; R5 is chosen from a group including hydrogen atom, phenyl, naphthyl, -CO-(C3-C8)cycloalkyl, -CO-phenyl, -CO-(C5-C7)heteroaryl containing 1, 2 nitrogen atoms, -CO-(C3-C7)heteroaryl(C1-C4)alkyl containing 1, 2 nitrogen atoms, -CO-(C5-C6)heterocyclyl containing 1, 2 nitrogen or oxygen atoms, -CO-C*(R9R10)-NH2, -CO-CH2-C*(R9R10)-NH2, -CO-C*(R9R10)-CH2-NH2, phenylsulfonyl which can contain up to 3 substitutes independently chosen from a group including halogen, -F, -CI, -Br, -I, -N3, -CN, -NR7R8, -OH, -NO2, (C1-C4)alkyl; R6 represents hydrogen atom; R7 and R8 represent hydrogen atom; R9 and R10 are independently chosen from a group including hydrogen atom and (C1-C4)alkyl; m relates to 0, 1 or 2, and preferentially 0; and * means carbon atom in a R or S configurations, if it is chiralene.

EFFECT: invention refers to GHSS receptors antagonists and agonists which can be used for modulation of these receptors and are effective in treatment of said conditions, particularly growth impairment, cachexia, short-term, intermediate and/or long-term energy balance control; short-term, intermediate and/or long-term food intake control (stimulation and/or suppression); adipogenesis, adiposity and/or obesity; body weight growth and/or reduction in mammals.

22 cl, 6 tbl, 15 ex, 46 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to the tetrahydroquinolin derivatives with the common formula (I) or their pharmaceutically acceptable salts, where R1 and R2 are H or Me; R3 is H, hydroxy or (1-4C)alkoxi; R4 is H, OH, (1-4C)alkoxi; R5 is OH, (1-4C)alkoxi or R7; provided the R4 is H, then R5 differs from OH or (1-4C)alkoxi; R6 is (2-5C)heteroaryl, not necessarily substituted with one or more substitutes, selected from (1-4C)alkyla, bromine or chlorine; (6C)aryl, not necessarily substituted with one or more substitutes, selected from (1-4C)alkyla, (1-4)C-alkoxi, bromine, chlorine, phenyl or (1-4C) (di)alkylamino; (3-8C)cycloalkyl, (2-6C)heterocycloalkyl or (1-6C)-alkyl; R7 is amino, (di)(1-4C)alkylamino, (6C)arylcarbonylamino, (2-5C)heteroarylcarbonylamino, (2-5C)heteroaryl-carbonylokxi, R8-(2-4C)alkoxi, R9-methylamino or R9-methoxi; R8 is amino, (1-4C)alkoxi, (di)(1-4C)-alkylamino, (2-6C)-heterocycloalkyl, (2-6C)heterocycloalkylcarbonylamino or (1-4C)-alkoxicarbonylamino; and R9 is aminocarbonyl, (di)(1-4C)alkylaminocarbonyl, (2-5C)heteroaryl or (6C)aryl. The invention also relates to the pharmaceutical composition which contains the said derivatives, and to the application of the derivatives in fertility modulating.

EFFECT: novel tetrahydroquinolin derivatives with follicle-stimulating hormone receptors modulating activity are obtained.

15 cl, 51 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to the tetrahydroquinolin derivatives with the common formula (I) , or their pharmaceutically acceptable salts, where R1 and R2 are H, Me; R3 is (2-6C)-hetercycloalkyl(1-4C)alkyl, (2-5C)heteroaryl(1-4C)alkyl, (6C)aryl(1-4C)-alkyl, (2-6C)hetercycloalkylcarbonylamino(2-4C)alkyl, R5-(2-4C)alkyl or R5-carbonyl(1-4C)alkyl; R4 is (2-5C)heteroaryl (6C)aryl, not necessarily substituted with one or more substitutes selected from bromine, chlorine, nitro, phenyl, (1-4C)alkyl, trufluoromethyl, (1-4C)alkoxi or (1-4C)alkylamino; or (2-6C)hetercycloalkyl; R5 is (di (1-4C)alkylamino, (1-4C)alkoxi, amio, hydroxy, (6C)arylamino, (di)(3-4C)alkenylamino, (2-5C)heteroaryl(1-4C)alkylamino, (6C)aryl(1-4C)alkylamino, (di)[(1-4C)alkoxi(2-4C)alkyl]amino, (di)[(1-4C)alkylamino2-4C)alkyl]amino, (di)[amino(2-4C)alkyl]amino or (di)[hydroxy(2-4C)alkyl]amino. The invention also relates to the pharmaceutical composition based on the compound with formula (I) and to the application of the compound with the formula (I).

EFFECT: novel tetrahydroquinolin derivatives with follicle-stimulating hormone receptors modulating activity are obtained.

10 cl, 44 ex

FIELD: veterinary medicine.

SUBSTANCE: method includes injection of the preparation "FSH-super" and the preparation of prostaglandin F2α. On the day of artificial insemination the cows-donors are additionally injected with homeopathic preparation "Ovariovit" at the dose of 4.9-5.1 ml per head in a single dose.

EFFECT: method enables to obtain a greater number of embryos and to improve their quality.

5 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to urology, and can be used for treating relative sterility in varicocele. That is ensured by preoperative testicle Doppler sonography (size and volume), evaluation of spermogram and hormonal status (blood plasma testosterone concentration). It is followed by calculation of a testicle atrophy index (TAI), and if the testicle atrophy index exceeds 22 % in normal testosteronemia, and if the testicle atrophy index exceeds 15% in hypertestosteronemia, the Mannar subinguinal microsurgical varicocelectomy is required. The patients not showing any improvements of the spermogram values within 12 months after varicocelectomy are additionally prescribed with a hormone-stimulating therapy by human chorionic gonadotropin preparations.

EFFECT: method allows higher clinical effectiveness and lower drug-induced body burden due to an adequate choice of a therapeutic approach consisting in proved prescription of the hormone-stimulating therapy.

5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmacology, and represents a water-based composition of human follicle-stimulating hormone (HFSH) containing a therapeutically effective amount of the HFSH and glycine, methionine, a nonionic surface active agent and a phosphate buffer as stabilisers, and the amount of glycine is 0.1 to 10% (wt/vl), the amount of methionine is 0.01 to 2.0 % (wt/vl), the amount of the nonionic surface active agent is 0.001 to 0.02% (wt/vl), and the nonionic surface active agent is specified in a group consisting of a polysorbate nonionic surface active agent, a poloxamer nonionic surface active agent or combinations of those, and the phosphate buffer has salt concentration 1mM to 50 mM and pH 6.5 to 7.5.

EFFECT: invention provides maintained long-term HFSH stability.

5 cl, 4 ex, 7 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to gynecology, and deals with extracorporal fertilisation. After induction of superovulation for puncture of follicle into vagina cavity introduced is heated to body temperature tubular element with ball-like tip, which has guide canal on axis for puncture-biopsy needle. By means of it respective side of posterior vaginal fornix is pressed into abdominal cavity for maximally possible distance. Ovary is moved with side of mature follicles to contact of selected mature follicle with posterior fornix wall. Follicle centre is superposed with axis of tubular element canal, follicle is fixed in said state, distance from place of puncture of vaginal mucous membrane from the side of its cavity to follicle centre is determined and needle is moved out of the canal for said distance. After that follicular fluid is aspirated.

EFFECT: method ensures targeted puncturing of follicle centre, which results in reduction of traumaticity and increase of extracorporal fertilisation efficiency.

1 ex

FIELD: medicine.

SUBSTANCE: efficiency of claimed method is ensured by physiological syndrome characteristic for women during ovulation.

EFFECT: application of LH (luteinising hormone) for treatment of libido absence or low libido and/or difficulty of achievement of orgasm in women.

3 cl

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology, precisely to cellular biology and experimental oncology and can be used for development of new methods aimed at antitumorigenesis. Human chorionic gonadotropin (HCG) is used for stimulation of pathological process and disorganisation of cell carcinoma culture of throat Hep-2.

EFFECT: invention allows effecting turmoral Hep-2 cell lines, excluding lymphocytic mediation, as well as hormone effect through the specific receptors with having signs of tumor degradation in the condition of cell culture.

2 dwg, 2 tbl, 2 ex

FIELD: medicine; gynecology.

SUBSTANCE: method includes abdominovaginal exposure from 5-7th day of menstrual period. Exposure is carried out with variable pulsating magnetic field generated by apparatus "Polus-2" at maximum intensity, frequency 50 Hz in intermittent duty. Duration of procedure is 20 minutes. Exposure is carried out daily, 3 times a day with interval between procedures not less than 2 hours. Method is noninvasive, improves implantation potential of endometrium due to blood circulation improvement in uterus arteries, and provides multilayer structure in endometrium.

EFFECT: higher incidence of pregnancy in patients with previous failures in extracorporal fertilisation.

3 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns pharmaceutical compositions containing FSH and hCG in different quantities and sustaining folliculogenesis and follicle maturation without ovary hyperstimulation. The invention enables flexible ovulation stimulation, gradual adjustment of FSH and hCG quantities depending on folliculogenesis stage, thus sustaining more successful and safe ovulation without ovary hyperstimulation, and higher success percentage.

EFFECT: reduced composition cost and risk of complications.

21 cl, 3 tbl, 1 dwg

FIELD: chemical and pharmaceutical industry, oncology, immunology.

SUBSTANCE: invention relates to correction of cancer-dependent immunodeficit in Pliss lymphosarcoma, namely normalizing of CD4+ T-lymphocyte level in rat peripheral blood by using chorial gonadotropin.

EFFECT: new agent for normalizing of CD4+ T-lymphocyte level in rat peripheral blood.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves administering Thyroxin at a dose of 50 mg/day in a combination with Metformin at a dose of 500 mg/day, Detralex at a dose of 800 mg/day within a month before forthcoming operation to patients. Low molecular weight heparin is subcutaneously introduced two hours before surgical intervention. Hydroxyethylized starch infusion is carried out at a dose of 0.5-1.0 ml/kg during operation. Low molecular weight heparin is subcutaneously introduced 7 days long after the surgical intervention.

EFFECT: enhanced effectiveness of treatment; prevented thrombogenetic complications and hemodynamic instability; improved metabolic processes in blood platelets, blood vessel walls; decreased thrombophilic orientations of hemostasis system.

2 tbl

FIELD: medicine.

SUBSTANCE: toxic action of cadmium is experimentally simulated by the daily subcutaneous introduction of a cadmium sulphate solution 0.3 mg/kg on a metal basis wherein a unit of the solution 1 ml is equal to cadmium 0.3 mg. A preventive agent is presented by Aquadetrim introduced in animals once a day daily through a probe into a stomach in dose 25000 IU/kg 1 hour before the subcutaneous introduction of the sulphate solution.

EFFECT: effective reduction of toxic action of cadmium on the body that has been shown by the functional renal state.

2 dwg, 5 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: toxic action of cadmium is experimentally simulated by the daily subcutaneous introduction of a cadmium sulphate solution 0.3 mg/kg on a metal basis wherein a unit of the solution 1 ml is equal to cadmium 0.3 mg. A preventive agent is presented by Aquadetrim 25000 IU/kg and 10% calcium chloride 1.5 ml/ kg of body weight. Said preparations are introduced simultaneously daily through a probe in a stomach once a day for 30 days. For the following 30 days, said preparations are introduced daily 1 hour before the subcutaneous injection of cadmium sulphate.

EFFECT: effective reduction of toxic action of cadmium on the body, particularly nephropathic action ensured by changed calcium hemostasis.

2 dwg, 5 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology and can be applied for external treatment of psoriatic onychodystrophy. For this purpose mixture of gel tisol and ointment daivonex is applied on nidus of affection in ratio 1:2 with following keeping under adhesive plaster during 8-10 h two times per day. Course of treatment constitutes not less than 14 days.

EFFECT: method ensures reduction of treatment terms and duration of remission and obtaining high therapeutic effect.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: ADMA-like gestosis model is experimentally reproduced in laboratory pregnant Wistar rats by the daily intraperitoneal introduction of L-nitro-arginine-methyl ester 25 mg/kg for 7 days. The endothelial dysfunction is corrected by the vitamine-mineral preparation 'Complivit Trimestrum Trimester 3' which with underlying simulation is introduced intragastrically in a dose of 0.084 tablet/kg/day for 7 days.

EFFECT: method provides effective endothelial dysfunction correction in pregnant females ensured by an endothelioprotective effect of vitamins under specified experimental conditions and dosages.

1 ex

FIELD: medicine.

SUBSTANCE: method involves the introduction of lead acetate with underlying experimental hypercalcemia. Hypercalcemia is created by using the preparation Aquadetrim introduced in animals once a day daily through a probe into a stomach in dose 3000 IU/100 g for 30 days. In 14 days from the beginning of the experiment, it is combined with the subcutaneous introduction of lead acetate 40 mg/kg at a metal basis for 16 days.

EFFECT: reduced toxic action, including on kidneys with the controlled blood calcium content and the required toxic lead dose in experiment.

2 dwg, 5 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: ADMA-like gestosis model is experimentally reproduced in laboratory pregnant rats by introducing NO-synthase inhibitor L-NAME. It is combined with the pathology correction by the 7-day daily intragastric introduction of the vitamin-mineral preparation 'Complivit Trimestrum Trimester 3' 0.084 tab/kg/day.

EFFECT: method provides the manifested correction of placental microcirculation disorder ensured by endothelial protective effect of the preparation in the proper dosages.

1 ex

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