Abnormal uterine bleeding (AMB). Definition

dysfunctional uterine bleeding - bleeding due to pathology of endocrine regulation, not associated with organic causes, most often occurring in connection with anovulatory cycles (90% of DMC). Provided that at least 2 years have passed since menarche, regular menstrual cycles with heavy bleeding lasting more than 10 days are classified as DMC; menstrual cycle less than 21 days and irregular menstrual cycle. As a rule, DMK is accompanied by anemia.

Frequency -14-18% of all gynecological diseases. Predominant age: 50% of cases - older than 45 years (premenopausal and menopausal periods), 20% - adolescence (menarche).

Etiology:

- Smearing discharge in the middle of the cycle - a consequence of a decrease in estrogen production after ovulation;

 Frequent menstruation is a consequence of the shortening of the follicular phase, due to inadequate feedback from the hypothalamic-pituitary system;

 Shortening of the luteal phase - premenstrual spotting or polymenorrhea due to a premature decrease in progesterone secretion; the result of insufficiency of the functions of the corpus luteum;

- Prolonged activity of the corpus luteum - a consequence of the constant production of progesterone, which leads to a lengthening of the cycle or prolonged bleeding;

- Anovulation - excessive production of estrogens, not associated with the menstrual cycle, not accompanied by cyclic production of LH or secretion of progesterone by the corpus luteum;

- Other causes - damage to the uterus, leiomyoma, carcinoma, vaginal infections, foreign bodies, ectopic pregnancy, hydatidiform mole, endocrine disorders (especially dysfunction thyroid gland), blood dyscrasia. Pathomorphology. Depends on the cause of DMC. Histopathological examination of endometrial preparations is mandatory.

Protocol code:

Abbreviations used in the protocol:

DUB - dysfunctional uterine bleeding

LH - luteinizing hormone

CNS - central nervous system

Ultrasound - ultrasonography

ECG - electrocardiography

Protocol development date: April 2013

Protocol Users: obstetrician-gynecologists

Clinical picture

Symptoms, course

Diagnostic criteria: bloody issues from the genital tract, anemia.

Complaints on bloody discharge from the genital tract, weakness, malaise

Physical examination: pale, haggard face, pointed nose, pale blue nails, anemic skin, tachycardia, sudden drop blood pressure, readiness for hemorrhagic shock.

Diagnostics

The list of basic and additional diagnostic measures:

Main diagnostic measures:

Complete blood count (6 parameters)– counting of blood cells detection of anemia

Determination of the clotting time of capillary blood

General urine analysis

Coagulogram (prothrombin time, fibrinogen, thrombin time, aPTT, plasma fibrinolytic activity, hematocrit)- the state of the blood coagulation system

Determination of total protein- blood biochemistry

Determination of glucose- blood biochemistry

Determination of bilirubin- state of liver function

Creatinine determination- state of the urinary system

Pap smear testing for gonorrhea, trichomoniasis, and yeast- degree of cleanliness of the vagina

Ultrasound of the female genital organs– detection of volumetric formations of the pelvic organs

ECG- the state of the cardiovascular system

Anesthesiologist's consultation— identification of the degree of anesthetic risk

Consultation of a general practitioner– detection of extragenital pathology

histological examination of scrapings– tissue research

Additional diagnostic measures:

Immunoradiometric determination of triiodothyronine, thyroxine or antibodies to thyroglobulin

Thyroid ultrasound- to rule out thyroid disease

ELISA - HBsAg- Order of the Ministry of Health of the Republic of Kazakhstan No. 404 dated 15.08.97

Blood test for HIV- Order of the Ministry of Health of the Republic of Kazakhstan No. 575 dated 11.07.02

Immunoradiometric determination of cortisol, estradiol, progesterone or testosterone- hormonal status

Immunoradiometric determination of thyroid-stimulating hormone- hormonal status

Oncogynecologist consultation– exclusion of oncopathology

Minimum examination before hospitalization:

 Wasserman reaction, HIV;

 Determination of blood group and Rh factor, the presence of antibodies;

 Complete blood count (6 parameters);

- General analysis of urine;

- Examination of smears for gonorrhea, trichomoniasis and yeast fungus;

- Ultrasound of the pelvic organs.

Differential Diagnosis

Differential Diagnosis:

• decubital ulcer;
• abortion;
• trophoblastic disease.

Treatment

Treatment goals: stop bleeding from the uterus and vagina, normalize the menstrual cycle.

Treatment tactics: All methods of treatment are divided into conservative and surgical:

• Hysteroscopy and curettage of the uterine cavity diagnostic;
• Antianemic therapy;
• Hormone therapy.

Non-drug treatment: —

Medical treatment:

Clinical tactics:

This is a diagnosis of exclusion, referring to patients in whom organic causes of hemorrhages are not detected by conventional clinical and paraclinical methods. The basic rule in conducting therapy is to proceed from the principle systems approach to this problem: the need to restore the disturbed cyclic regulation of the sexual cycle with the help of a complex effect on the woman's body as a whole, with an emphasis on individual primary or most affected links. When conducting treatment, it is necessary to comply with the following fundamental accounting provisions:

1) the nature of menstrual irregularities and the level of damage in the hypothalamus - pituitary gland - ovaries - uterus;

2) age of the patient;

3) the duration of the disease and the duration of bleeding, the severity of anemia;

4) the presence of concomitant extragenital diseases;

5) the period of the expected menstrual cycle.

Every woman is familiar with bloody discharge from the genital tract. They appear regularly and last for several days. Monthly bleeding from the uterus is observed in all healthy women of childbearing age, that is, capable of bearing children. This phenomenon is considered the norm (menstruation). However, there are also abnormal uterine bleeding. They occur when disturbances occur in the body. Most often, such bleeding occurs due to gynecological diseases. In most cases, they are dangerous, as they can have serious consequences.

Definition of abnormal uterine bleeding

Abnormal uterine bleeding is a condition in which there is a tear in the vascular wall of the body or cervix. It is not associated with the menstrual cycle, that is, it appears independently of it. Bleeding may occur frequently. In this case, they occur between periods. Sometimes, abnormal uterine bleeding occurs rarely, such as once every few months or years. Also, this definition is suitable for long periods lasting more than 7 days. In addition, it is considered abnormal from 200 ml for the entire period of "critical days". This problem can occur at any age. Including adolescents, as well as among women who are in the menopause period.

Abnormal uterine bleeding: causes

The reasons for the appearance of blood from the genital tract can be different. However, this symptom is always a reason for urgent medical attention. medical care. Often, abnormal uterine bleeding occurs due to oncological pathologies or diseases that precede them. Due to the fact that this problem is one of the reasons for the removal reproductive organ, it is important to identify the cause in time and eliminate it. There are 5 groups of pathologies due to which bleeding may occur. Among them:

1. Diseases of the uterus. Among them: inflammatory processes, ectopic pregnancy or the threat of termination, fibroids, polyps, endometriosis, tuberculosis, cancer, etc.
2. Pathologies associated with the secretion of hormones by the ovaries. These include: cysts, oncological processes of the appendages, early puberty. Also, bleeding can occur due to dysfunction of the thyroid gland, stressful situations, taking contraceptives.
3. Pathology of the blood (thrombocytopenia), liver or kidneys.
4. iatrogenic causes. Bleeding caused by surgery on the uterus or ovaries, the introduction of the IUD. In addition, iatrogenic causes include the use of anticoagulants and other drugs.
5. Their etiology is not completely clear. These bleedings are not associated with diseases of the genital organs and are not caused by other listed reasons. It is believed that they occur due to a violation of hormonal regulation in the brain.

The mechanism of development of bleeding from the genital tract

The pathogenesis of abnormal bleeding depends on what kind of cause they were caused. The mechanism of development in endometriosis, polyps and oncological processes is similar. In all these cases, it is not the uterus itself that bleeds, but pathological elements that have their own vessels (myomatous nodes, tumor tissue). Ectopic pregnancy can proceed as an abortion or rupture of the tube. Last option is very dangerous for a woman's life, as it causes massive intra-abdominal bleeding. Inflammatory processes in the uterine cavity cause tearing of the endometrial vessels. In violation of the hormonal function of the ovaries or the brain, changes occur in the menstrual cycle. As a result, there may be several ovulations instead of one, or, on the contrary, a complete absence. The same mechanism has the use of oral contraceptives. can cause mechanical damage to the organ, thereby leading to bleeding. In some cases, the cause cannot be established, so the development mechanism also remains unknown.

Abnormal uterine bleeding: classification in gynecology

There are a number of criteria according to which uterine bleeding is classified. These include the cause, frequency, period of the menstrual cycle, as well as the amount of fluid lost (mild, moderate and severe). By etiology, there are: uterine, ovarian, iatrogenic and dysfunctional bleeding. DMCs differ in nature. Among them:

1. Anovulatory uterine bleeding. They are also called single-phase DMC. They arise due to short-term persistence or atresia of the follicles.
2. Ovulatory (2-phase) DMC. These include hyper- or hypofunction of the corpus luteum. Most often, this is an abnormal uterine bleeding of the reproductive period.
3. Polymenorrhea. Blood loss occurs more frequently than once every 20 days.
4. Promenorrhea. The cycle is not broken, but the "critical days" last more than 7 days.
5. Metrorrhagia. This type of disorders is characterized by irregular bleeding, without a certain interval. They are not related to the menstrual cycle.

Symptoms of uterine bleeding

In most cases, it is impossible to immediately determine the cause of the appearance of blood from the genital tract, since the symptoms are almost the same for all DMC. These include pain in the lower abdomen, dizziness and weakness. Also, with constant blood loss, there is a decrease in blood pressure and pallor of the skin. In order to distinguish DMC among themselves, it is necessary to calculate: how many days it lasts, in what volume, and also set the interval. To do this, it is recommended to mark each menstruation in a special calendar. Abnormal uterine bleeding is characterized by a duration of more than 7 days and an interval of less than 3 weeks. Women of childbearing age usually experience menometrorrhagia. In menopause, bleeding is profuse, prolonged. The interval is 6-8 weeks.

Diagnosis of bleeding from the uterus

To detect abnormal uterine bleeding, it is important to monitor your menstrual cycle and visit your gynecologist periodically. If this diagnosis is still confirmed, it is necessary to be examined. For this, general urine and blood tests (anemia), a smear from the vagina and cervix are taken, and a gynecological examination is performed. It is also necessary to do an ultrasound of the pelvic organs. It allows you to determine the presence of inflammation, cysts, polyps and other processes. In addition, it is important to take tests for hormones. This applies not only to estrogens, but also to gonadotropins.

What is dangerous bleeding from the uterus

Abnormal bleeding from the uterus is a rather dangerous symptom. This symptom may indicate a disturbed pregnancy, tumors and other pathologies. Massive bleeding leads not only to the loss of the uterus, but even to death. They are found in diseases such as ectopic pregnancy, torsion of the tumor stem or myomatous node, ovarian apoplexy. These conditions require immediate surgical attention. Slight short-term bleeding is not so terrible. However, their reasons may be different. They can lead to malignancy of the polyp or fibroids, infertility. Therefore, examination is extremely important for a woman of any age.

How to treat uterine bleeding?

Treatment of abnormal uterine bleeding should begin immediately. First of all, hemostatic therapy is necessary. This applies to heavy bleeding. An ice pack is applied to the area of ​​\u200b\u200bthe uterus, or an erythrocyte mass is injected intravenously. Also produce surgery(most often the removal of one of the appendages). With mild bleeding, conservative therapy is prescribed. It depends on the cause of DMC. Most of the time it's hormonal. medicines(drugs "Jess", "Yarina") and hemostatic drugs (solution "Dicinon", tablets "Calcium Gluconate", "Ascorutin").

Abnormal uterine bleeding

The urgency of the problem.

Classification of menstrual disorders.

Etiology.

Diagnostic criteria for NMC.

Tactics, principles of conservative and surgical treatment.

Prevention, rehabilitation.

In the basis of primary and secondary violations of the menstrual cycle, the main role belongs to hypothalamic factors, according to the scheme: puberty is the process of establishing the rhythm of luliberin secretion from its complete absence (in the premenarche) followed by a gradual increase in the frequency and amplitude of impulses until the rhythm of an adult woman is established. IN initial stage the level of RG-HT secretion is insufficient for the onset of menarche, then for ovulation, and later for the formation of a full-fledged corpus luteum. Secondary forms of menstrual disorders in women, proceeding according to the type of corpus luteum insufficiency, anovulation, oligomenorrhea, amenorrhea, are considered as stages of one pathological process, the manifestations of which depend on the secretion of luliberin (Leyendecker G., 1983). In maintaining the rhythm of HT secretion, the leading role belongs to estradiol and progesterone.

Thus, the synthesis of gonadotropins (GT) is controlled by hypothalamic GnRH and peripheral ovarian steroids by the mechanism of positive and negative feedback. An example of negative feedback is an increase in FSH release at the beginning of the menstrual cycle in response to a decrease in estradiol levels. Under the influence of FSH, the growth and maturation of the follicle occurs: proliferation of granulosa cells; synthesis of LH receptors on the surface of granulosa cells; synthesis of aromatases involved in the metabolism of androgens into estrogens; promoting ovulation in conjunction with LH. Under the influence of LH, androgens are synthesized in the theca cells of the follicle; the synthesis of estradiol in the granulosa cells of the dominant follicle; stimulation of ovulation; synthesis of progesterone in luteinized granulosa cells. Ovulation occurs when the maximum level of estradiol in the preovulatory follicle is reached, which, by a positive feedback mechanism, stimulates the preovulatory release of LH and FSH by the pituitary gland. Ovulation occurs 10-12 hours after the LH peak or 24-36 hours after the estradiol peak. After ovulation, granulosa cells undergo luteinization with the formation of a corpus luteum, under the influence of LH secreting progesterone.

Structural formation of the corpus luteum is completed by the 7th day after ovulation, during this period there is a continuous increase in the concentration of sex hormones in the blood.

After ovulation in the II phase of the cycle, there is an increase in the concentration of progesterone in the blood compared to the basal level (4-5th day of the menstrual cycle) by 10 times. To diagnose disorders of reproductive function, the concentration of hormones in the blood is determined in the II phase of the cycle: progesterone and estradiol, the combined action of these hormones ensures the preparation of the endometrium for implantation of the blastocyst; sex steroid-binding globulins (PSSH), the synthesis of which occurs in the liver under the influence of insulin, testosterone and estradiol. Albumins are involved in the binding of sex steroids. The immunological method for studying blood hormones is based on the determination of active forms of steroid hormones that are not associated with proteins.

Anomalies of the menstrual function is the most common form of violations of the reproductive system.

Abnormal uterine bleeding (AMB) - it is customary to call any bloody uterine discharge outside of menstruation or pathological menstrual bleeding (more than 7-8 days in duration more than 80 ml in terms of blood loss for the entire period of menstruation).

AUB can be symptoms of a variety of pathologies reproductive system or somatic diseases. Most often, uterine bleeding is a clinical manifestation of the following diseases and conditions:

Pregnancy (uterine and ectopic, as well as trophoblastic disease).

Uterine fibroids (submucosal or interstitial fibroids with centripetal nodule growth).

Oncological diseases (cancer of the uterus).

Inflammatory diseases of the genital organs (endometritis).

Hyperplastic processes (polyps of the endometrium and endocervix).

Endometriosis (adeiomyosis, external genital endometriosis)

The use of contraceptives (IUDs).

Endocrinopathy (chronic anovulation syndrome - PCOS)

Somatic diseases (liver diseases).

10. Blood diseases, including coagulopathy (thrombocytopenia, thrombocytopathy, von Willebrand disease, leukemia).

11. Dysfunctional uterine bleeding.

Dysfunctional uterine bleeding (DUB) - violations of menstrual function, manifested by uterine bleeding (menorrhagia, metrorrhagia), in which there are no pronounced changes in the genitals. Their pathogenesis is based on functional disorders of the hypothalamic-pituitary regulation of the menstrual cycle, as a result of which the rhythm and level of hormone secretion changes, anovulation and a violation of the cyclic transformations of the endometrium are formed.

Thus, DMC is based on a violation of the rhythm and production of gonadotropic hormones and ovarian hormones. DMC is always accompanied by morphological changes in the uterus.

DMK is always a diagnosis of exclusion

In the general structure of gynecological diseases, DMK is 15-20%. Most cases of DUB occur 5-10 years before menopause or after menarche, when the reproductive system is in an unstable state.

Menstrual function is regulated by the cerebral cortex, suprahypothalamic structures, hypothalamus, pituitary gland, ovaries, uterus. This is a complex system with double feedback, for its normal functioning, the coordinated work of all links is necessary.

The main point in the mechanism of functioning of the endocrine system that regulates the menstrual cycle is ovulation, most DMCs occur against the background of anovulation.

DMC is the most common pathology of the menstrual function, is characterized by a recurrent course, leads to impaired reproductive function, the development of hyperplastic processes in the uterus and mammary glands. Recurrent DMC leads to a decrease in social activity and a deterioration in the quality of life of a woman, accompanied by mental (neurosis, depression, sleep disturbance) and physiological abnormalities (headaches, weakness, dizziness due to anemia).

DMK is a polyetiological disease, which is special type response of the reproductive system to the impact of damaging factors.

Uterine bleeding, depending on the age of the woman, are distinguished:

1. Juvenile or pubertal bleeding - in girls during puberty.

2. Premenopausal bleeding at the age of 40-45 years.

3. Menopausal - 45-47 years;

4. Postmenopausal - bleeding in menopausal women a year or more after menopause, most common cause are uterine tumors.

According to the state of menstrual function:

menorrhagia

Metrorrhagia

Menometrorrhagia

Etiology and pathogenesis of DMK complex and multifaceted.

Causes of DMC:

psychogenic factors and stress

mental and physical fatigue

acute and chronic intoxications and occupational hazards

inflammatory processes of the small pelvis

dysfunction of the endocrine glands.

In pathogenesis uterine bleeding involved the following mechanisms:

1. violation of the contractile activity of the uterus with myoma, endometriosis, inflammatory diseases;

disorders in the vascular supply of the endometrium, the causes of which may be endometrial hyperplastic processes, hormonal disorders;

violation of thrombus formation in patients with defects in the hemostasis system, especially in the microcirculatory-platelet link, with the formation of a smaller number of blood clots, compared with normal endometrium, and also as a result of activation of the fibrinolytic system;

Violation of the regeneration of the endometrium with a decrease in the hormonal activity of the ovaries or due to intrauterine causes.

There are 2 large groups of uterine bleeding:

Ovulatory ( caused by a drop in progesterone . Depending on the changes in the ovaries, the following 3 types of DMC are distinguished:

A. Shortening the first phase of the cycle;

b. Shortening of the second phase of the cycle - hypoluteinism;

V. Lengthening of the second phase of the cycle - hyperluteinism.

Anovulatory uterine bleeding caused by a drop in estrogen ( follicular persistence and follicular atresia) .

Uterine bleeding always occurs against the background of a decline in the level of steroid hormones.

Clinic for ovulatory uterine bleeding:

maybe bleeding leading to anemia;

there may be spotting before menstruation;

spotting after menstruation;

there may be spotting in the middle of the cycle;

miscarriage and infertility.

Presentation Description Abnormal Uterine Bleeding: Modern Treatment Approaches and Slides

Abnormal uterine bleeding: modern approaches treatment and prevention obstetrician-gynecologist of the 1st category, Ph.D. n. , Assistant of the Department of Obstetrics and Gynecology No. 1 ONMed. O. M. Kalanzhov

ABNORMAL UTERINE BLEEDING (AUB) is any uterine bleeding that does not meet the parameters of normal menstruation in a woman of reproductive age. NB! AUB includes only bleeding from the body and cervix, but not from the vagina and vulva. Washington (2005) - revision of the term "DMK" . With the support of WHO, FIGO, ASRM, ACOG, RCOG, ECOG introduced understandable in various countries, medical schools, clinical guidelines and textbooks, the comprehensive term "ABNORMAL UTERINE BLEEDING" (AUB). Dysfunctional uterine bleeding (DUB) is abnormal bleeding from the uterus that is not related to systemic diseases, organic pathology of the pelvic organs or complications of pregnancy.

CHARACTERISTICS OF THE MENTAL CYCLE characteristic regularity (days) frequency (days) duration (days) volume of blood loss norm regular ± 5 24 -38 4.5 -8 normal (80.0 -120.0 ml) deviation variant 1 (polymenorrhea) more than ± 20 8 excess deviation variant 2 (opsomenorrhea) absent > 38< 4, 5 сниженный

Hypothalamus Pituitary gland (anterior lobe) Ovaries Gonadotropic releasing hormones (GN. RG) Gonadotropic hormones (FSH, LH) Uterus Endometrial cyclic changes. Regulation of the menstrual cycle Steroid hormones (E, Pg, A, inhibin)

The frequency of occurrence of AUB in the structure of gynecological diseases, taking into account the age gradation of women: 1. Juvenile uterine bleeding - 10% 2. AUB in active reproductive age - 25 -30% 3. AUB in late reproductive age - 35 -55% 4. AUB in postmenopause − 55 -60%

AMC classification based on etiological factor(Malcolm Murno − XIX Congress of FIGO) 1. AUB due to uterine pathology: endometrial dysfunction (ovulatory bleeding, chronic endometritis); diseases of the uterine body (uterine fibroids, endometrial polyp, adenomyosis, endometrial hyperplastic processes, endometrial cancer, endometritis, genital TVS, arteriovenous anomaly of the uterus); diseases of the cervix (cervical endometriosis, endocervix polyp, cervical cancer, atrophic cervicitis, uterine fibroids - cervical variant); associated with pregnancy (spontaneous abortion, placental polyp, trophoblastic disease, disturbed ectopic pregnancy).

Classification of AUB based on etiological factor (Malcolm Murno - XIX Congress of FIGO) 2. AUB not associated with uterine pathology: anovulatory bleeding (at puberty or perimenopause, polycystic ovaries, thyroid dysfunction, hyperprolactinemia, stress, eating disorders); diseases of the uterine appendages (bleeding after ovarian resection, ovariectomy); on the background hormone therapy(COCs, progestins, HRT).

Classification of AUB based on the etiological factor (Malcolm Murno - XIX Congress of FIGO) 3. AUB due to systemic pathology: (diseases of the blood system, liver, kidneys, nervous system). 4. AUB associated with iatrogenic factors: (resection, electro- or cryosurgery of the endometrium; bleeding from the biopsy area of ​​the cervix, taking anticoagulants). 5. AUB of unknown etiology.

AUB of a functional nature 2. Associated with ovarian dysfunction 1. Not associated with organic or systemic pathology OMT Anovulatory bleeding Ovulatory bleeding Estrogen bleeding Gestagen bleeding Breakthrough bleeding Withdrawal bleeding - absolute hyperestrogenism (follicle persistence) - profuse acute bleeding - relative hyperestrogenism (follicle atresia) - prolonged blood smearing - bilateral oophorectomy - withdrawal of estrogen preparations - irradiation of mature follicles - high progesterone / estrogen ratio (reception of prolonged gestagens, low-dose COCs with low estrogen levels) - a sharp decrease in progesterone levels (normal menstruation, withdrawal of progesterone - a test for amenorrhea )

Anovulatory estrogenic breakthrough bleeding Hyperestrogenic anovulation FOLLICLE PERSISTENCE One or more follicles reach a certain stage of maturity, but ovulation does not occur and no corpus luteum is formed. Progesterone is not synthesized. The follicle exists from several days to several months, producing a significant amount of estrogen. High level estrogen levels (absolute hyperestrogenism) + Progesterone deficiency Hypoestrogenic anovulation FOLLICULAL ATRESIATION With follicle atresia, estrogens are produced for a long time, but in a relatively small amount Low (below normal), but constant estrogen levels (relative hyperestrogenism) + Progesterone deficiency

Ovulatory AUB Shortening of the 2nd phase of MC, according to basal body temperature (< 10 дней) Уменьшение параметров желтого тела, по данным УЗИ, на 21 -23 день МЦ 1. Недостаточность лютеиновой фазы (НЛФ) Уменьшение концентрации прогестерона и эстрогена на 7 -8 день после овуляции Недолгосрочное и минимальное действие гестагенов 2. Недостаточная секреторная трансформация эндометрия Скудные кровянистые выделения, возникающие за 7 -10 дней до предполагаемой менструации Обильные кровотечения на фоне укороченного (реже удлиненного) МЦ 3. Неадекватное отторжение эндометрия

Diagnosis of AUB Confirmation of the presence of bleeding based on the assessment of the validity of complaints of metrorrhagia (Jansen's method) Stage 1 Conducting a differential diagnostic search and establishing the diagnosis of AUB: - history (somatic history, menstrual history, exclusion of EGP and coagulopathy); - assessment of thyroid function; - examination in mirrors, cytological examination cervix, ultrasound of the pelvic organs, hysteroscopy, endometrial GI (exclusion of organic pathology of OMT) 2nd stage Establishment of the clinical and pathogenetic variant of AUB 3rd stage

Clinical and pathogenetic variants of AUB Parameters Ovulation Anovulation NLF Hypoestrogenic (relative hyperestrogenism) Hyperestrogenic (absolute hyperestrogenism) MC characteristics regular irregular MC duration (days) 22-30 35 Endometrial thickness on days 21-23 MC (mm)< 10 14 Максимальный диаметр фолликула (мм) 16 -18 25 Уровень прогестерона на 21 -23 день МЦ (нмоль/л) 15 -20 < 15 Уровень эстрадиола на 21 -23 день МЦ (пг/мл) 51 -300 301 Histological examination endometrium Defective secretory transformation Atrophic or proliferative changes Hyperplastic processes

Treatment of AUB Hippocrates: "You can't treat until you've made a diagnosis" NB! Treatment of various clinical and pathogenetic variants of AUB should be strictly individual. Stage I - stop bleeding (HEMOSTASIS) Stage II - anti-relapse therapy and its tasks: 1. restoration of the HHA system 2. restoration of ovulation 3. restoration of sex steroid hormone deficiency

Stage I - stop bleeding (HEMOSTASIS) hemostasis 3. Surgical hemostasis 2. Hormonal hemostasis 1. Non-hormonal hemostasis

Stage I - stop bleeding (NON-HORMONAL HEMOSTASIS) antifibrinolytic drugs (plasminogen - plasmin) NSAIDs (inhibit PG synthetase, balance PG F 2 a / E 2)

Stage I - stop bleeding (HORMONE HEMOSTASIS) gestagens BUT ... !!! the effect is achieved more slowly (3-5 tab / d - until hemostasis, dose reduction by 1 tab - every 3 days, the total duration of admission is at least 10 days, the abolition of gestagens, after MP bleeding - the formation of a new MC) monophasic COCs (4 -6 tab/d - before hemostasis, 3 tab/d - 3 days, 2 tab/d - 3 days, 1 tab/d - up to 21 days)

Stage I - stop bleeding (SURGICAL HEMOSTASIS) - hysteroscopy - FDV of the cervical canal and uterine cavity METHOD OF CHOICE IN PATIENTS: PUBERTY (life-threatening profuse uterine bleeding, secondary anemia - hemoglobin 70 g / l and below, endometrial polyp according to ultrasound) LATE REPRODUCTIVE AGE OF THE CLIMACTERIC PERIOD!!! DAMAGE TO UTERINE RECEPTORS - HORMONE-RESISTANT BUA

Stage II - anti-relapse therapy of AUA Principles of therapy for AUA Pathogenetic approach - anovulatory, AUA - ovulatory AUA Accounting for risk factors for the occurrence of progestogen intolerance syndrome Identification, accounting endocrine diseases and metabolic disorders. reproductive intentions

Combined oral contraceptives (COCs) (monophasic) Therapeutic effect in AUB: decreased ovarian hormonal activity; suppression of endometrial growth; Undesirable effects: suppression of secretion of gonadotropins

Gestagens Therapeutic effect in AUB: Progestogenic effect on the endometrium Stopping estrogen-induced endometrial growth Stabilization of endometrial vascularization and stopping uncontrolled vascular growth Initiation of the coagulation cascade Hemostatic and antifibrinolytic effect Inhibition of the activity of matrix metalloproteinases Undesirable effects: systemic effects of progestogens and their metabolites on the woman's body - intolerance syndrome gestagens

IUD - LNG Therapeutic effect in AUB: reversible severe suppression of endometrial growth, up to amenorrhea Undesirable effects: intermenstrual bleeding ovarian cysts

AGONISTS - Mr. WG Therapeutic effect in AUB: decreased sensitivity of adenohypophysis receptors to Gn. RG - decrease in the synthesis of gonadotropins by the pituitary gland - hypoestrogenism Undesirable effects: drug-induced menopause (hot flashes, hypertension, dyspareunia, osteoporosis) high cost of drugs

Gestagens Available for patients Simple control of the therapeutic effect Effective timely correction of therapy at any stage of treatment Acceptable for long-term use

Long-term use of progestogen (dydrogesterone) is possible due to: 1. Maximum binding by progesterone receptors 2. Selective antiestrogenic activity in relation to the endometrium 3. Non-hepatotoxic No mutagenic, teratogenic and carcinogenic potential

Progestogen intolerance syndrome Psychopathological disorders Metabolic disorders Physical manifestations Anxiety Irritability Aggression Panic attacks Depression Disorders of attention Forgetfulness Mood lability Lethargy Excess weight Lipid metabolism disorders Glucose/insulin disorders Acne Seborrhea Flatulence Edema Dizziness Headaches Mastalgia

Morphological transformation of the endometrium while taking progestogens Dydrogester on Progesterone 100% - the optimal level of the morphological state of the endometrium in the secretory phase * Without progesterone Norethisterone Levonogestr ate MPA !!! in women of reproductive age.

Pathogenetic approaches to anti-relapse therapy of AUB Order No. 582 of the Ministry of Health of Ukraine COC in cyclic mode (for contraception) HRT (minimum estrogen level and adequate progesterone content) Anovulatory hypoestrogenic AUB (follicle atresia) Selective gestagens (dydrogesterone) in cyclic mode from the 11th to the 25th day of MC (10-20 mg/day) for 3-6 months days) for 3-6 months With pronounced hyperproliferative processes of the endometrium - selective progestogens from the 5th to the 25th day of MC (10-20 mg / day) for 3-6 months Ovulatory AUA against the background of NLF

Pathogenetic approaches to anti-relapse therapy of AUB Order No. 582 of the Ministry of Health of Ukraine COCs in a cyclic mode Selective gestagens (dydrogesterone) in a cyclic mode from the 11th to the 25th day of MC (10-20 mg / day) for 3-6 months Juvenile uterine bleeding Selective gestagens (dydrogesterone) in a cyclic mode from the 11th to the 25th day of MC (20 mg / day) for 3-6 months Constant monitoring is preferable !!! Navy, agonists - Mr. WG (uterine fibroids, adenomyosis) Contraindications to the use of gestagens (TE diseases, gastrointestinal diseases in the acute stage, severe varicose veins) AUB in the premenopausal period > 45 years LDV in order to exclude the organic pathology of AUB in postmenopause

No effect from conservative therapy AMC Surgical treatment: 1. Endoscopic technologies (Nd: YAG laser thermal and cryoablation, radio wave ablation and, if necessary, endometrial resection) 2. Hysterectomy 3. Panhysterectomy

Efficiency of adequate, pathogenetically substantiated therapy of AUB 1. Restoration of normal MC 2. Implementation of the patient's reproductive plans 3. Prevention of endometrial hyperplastic processes 4. Prevention of major surgical interventions

NB! Treatment of AUB associated with progesterone deficiency should be pathogenetically justified. The method of treatment of AUB is highly effective both in therapy and in the prevention of this pathology.

N.M. PODZOLKOVA, MD, Professor, V.A. DANSHINA, Russian medical Academy postgraduate education of the Ministry of Health of Russia, Moscow

Abnormal uterine bleeding has a significant negative impact on the quality of life of patients, has significant economic consequences for both the patients themselves and the healthcare system as a whole. Examination and management of women of reproductive age with abnormal uterine bleeding is difficult due to the lack of standardized methods for identifying and classifying potential causes. Currently, there are no unified approaches to the examination and treatment of such patients, inadequate therapy can lead to the development of complications, and unreasonable surgical treatment can lead to a complex of somatic problems and an increase in economic costs.

Abnormal uterine bleeding (AMB) is a collective term various kinds menstrual irregularities characteristic of the puberty, reproductive and perimenopausal periods of a woman's life. This group of conditions accounts for up to 20% of all visits to the gynecologist's office.

AUBs cause a significant number of missed work days and school hours, and have significant economic consequences for the patients themselves. For a woman with heavy periods, the loss of ability to work results in a loss of approximately $1,692 per year.

International studies show that only every fifth patient with AUB turns to a doctor for help. Based on this, it is difficult to estimate the total costs associated with the diagnosis and treatment of AUB. Most women are believed to self-administer non-steroidal anti-inflammatory drugs (NSAIDs) and over-the-counter hemostatic drugs. The direct cost to insurance companies associated with AMK is approximately US$1 billion per year.

A number of authors note a significant negative impact of AUB on a woman's quality of life, arguing that chronic menstrual irregularities are associated with anger, fear, unmotivated anxiety and aggression. In a study by Chapa (2009), 40% of 100 women with symptoms of menorrhagia had a restriction of daily and social activities, sexual abstinence, and a decrease in interest in participating in recreational activities. Evidence from other studies suggests that AUB is correlated with low socioeconomic status, lack of employment, abdominal pain, and psychological distress.

In addition to the direct negative impact on the quality of life, AUB can lead to the development of various complications, in particular, menorrhagia is the most common cause iron deficiency anemia in developed countries.

In order to understand the pathogenesis of AUB, it is necessary to briefly dwell on the processes of regulation of the menstrual cycle and folliculogenesis in healthy women of reproductive age.

There are five levels of regulation of the menstrual cycle: 1st - target organs, 2nd - ovaries, 3rd - pituitary gland, 4th hypothalamus and 5th - the highest - areas of the brain that have connections with hypothalamus and affecting its function, including the neocortex. The patterns of functioning of the reproductive system are shown in Figure 1.

The role of extrahypothalamic structures of the brain, including the cortex big brain, consists in the synthesis by neurons of neurotransmitters and neuromodulators, such as acetylcholine, catecholamines, serotonin, dopamine and histamine, which have a regulatory effect on the hypophysiotropic functions of the hypothalamus.

The hypothalamus, due to the synthesis of gonadoliberins (GL) and prolactin-inhibiting factor in the arcuate and paraventricular nuclei, has a direct effect on the pituitary gland. The synthesis of gonadotropin-releasing factors is influenced by:

Neurotransmitters and neurotransmitters of extrahypothalamic structures of the CNS - direct stimulation and suppression;
- autogegulation of GL secretion - ultrashort feedback;
- tropic hormones of the pituitary gland - short feedback;
- sex steroid hormones - long feedback.

In the adenohypophysis, various substances are synthesized, including hormones that are directly involved in the regulation of the reproductive system: LH, FSH and prolactin. The level of tonic secretion of tropic hormones is mainly influenced by the circoral release of GL, i.e., the hypothalamus, and cyclic secretion is regulated mainly by the mechanism of negative and positive feedback, therefore, depends on the effect of steroids on the pituitary gland.

In the ovaries, the synthesis of steroid hormones occurs, as well as the maturation and release of gametes and the formation of the corpus luteum. The main hormone-synthesizing ovarian tissues include theca and granulosa, which contain a complete set of enzymes that allow the synthesis of all 3 classes of sex steroids: androgens, estrogens and progesterone.

As a result of complex embryonic processes of differentiation, migration and cell division, by the time a girl is born, according to various authors, from 300 thousand to 2 million primordial follicles are present in her ovaries. By menarche, the number of follicles decreases to 200-400 thousand, of which about 400 later become a source of egg formation.

The mechanism of the follicle exit from the primordial stage has not yet been deciphered, it occurs throughout the entire prepubertal, pubertal, reproductive and premenopausal periods, this process depends on the hormonal status of the body. It is not interrupted during pregnancy and lactation, during anovulation, when taking hormonal contraceptives, etc. Once it starts growing and goes through the hormone-independent, hormone-sensitive and hormone-dependent stages of growth, the follicle either reaches ovulation or undergoes atresia.

The hormone-independent phase lasts about 3 months. until the development of approximately 8 layers of granulosa cells in the premordial follicle and occurs in the absence of nutrition from the vessels. The processes occurring in the follicles do not depend on circulating hormones, the regulation is carried out due to local factors.

In the hormone-sensitive growth phase, which lasts about 70 days, as the granulosa layer thickens, the preantral follicle becomes moderately sensitive to FSH. During this period, a significant change in the morphology and functioning of the oocyte occurs: the zona pellucida appears, and the theca sensitive to LH is rapidly formed from the surrounding stroma.

After the antral follicle reaches 2 mm in diameter, it is able to grow only under the influence of a high concentration of FSH - the hormone-dependent phase begins. In each menstrual cycle, more than one follicle enters the hormone-dependent phase, but the so-called. the cohort from which the dominant follicle is selected, the rest undergo atresia. In the granulosis of the dominant follicle, receptors for FSH appear, under the influence of which the production of estradiol constantly increases with the formation of a preovulatory peak. At the end of the follicular phase of the menstrual cycle, luteinization of granulosa cells occurs, receptors for LH are synthesized.

The main events of the follicular phase of the menstrual cycle are the growth of a cohort of follicles, including one dominant follicle (rarely two), and atresia of all follicles in the cohort, except for the dominant one.

The successive change in the peaks of the concentration of estradiol and LH with FSH leads to ovulation - the rupture of the follicle and the release of the egg from the ovarian hillock.

In the second phase of the menstrual cycle, an increase in the mass of the corpus luteum occurs with an increase in vascularization under the influence of tonic secretion of LH, more progesterone and estradiol are synthesized. In the absence of fertilization of the egg, inevitable luteolysis occurs, leading to the elimination of the FSH and LH block and the onset of a new menstrual cycle.

In the endometrium during a normal menstrual cycle, 3 phases are distinguished:

The phase of desquamation, when, under the influence of a decrease in the concentration of steroid hormones in the absence of fertilization, ischemic changes occur and rejection of the functional layer of the endometrium by 2/3 due to a decrease in the lumen and twisting of the spiral arteries;
- the proliferative phase, which begins in the first days of the menstrual cycle, layering on the desquamation phase. There is a restoration of the lost functional layer of the endometrium due to an increase in cells, the uterine glands are formed.
- the secretory phase, which begins after ovulation under the influence of progesterone, the mitotic activity of the endometrium decreases, the uterine glands branch out, and begin to produce a secret.

The harmony of the processes occurring in the menstrual cycle is carried out due to the usefulness of gonadotropic stimulation, adequate functioning of the ovaries, synchronous interaction of the peripheral and central links of regulation - reverse afferentation.

The main causes of dysregulation of the reproductive system are: stress, a sharp and / or significant decrease in body weight, increased physical exercise, reception medicines that affect the synthesis, metabolism, reception and reuptake of neurotransmitters and neuromodulators, functional hyperprolactinemia, increased synthesis of inhibin by ovarian tissue, as well as impaired metabolism of growth factors and prostaglandins by ovarian tissue.

Stress-induced changes in the function of the hypothalamic-pituitary-ovarian system persist for a long time after the end of exposure to the stress factor. In short-stressed primates, menstrual cycles remained ovulatory, but there was a decrease in peak LH and progesterone levels by 51.6% when the stress began in the follicular phase and by 30.9% when the luteal phase began. phases. Menstrual irregularities persisted for 3-4 cycles after the end of stress, which coincides with persistence advanced level cortisol. Obviously, the existence and adequate functioning of the corpus luteum is the most vulnerable phase of the menstrual cycle.

It has been proven that the same menstrual irregularity can be caused by various causes, and the same cause can lead to the formation of various syndromes of menstrual irregularity. With long-term existence pathological process all links of regulation are gradually involved in it, up to a change in the dominant factor of pathogenesis, and clinical picture may change.

Examination and management of women of reproductive age with abnormal uterine bleeding is difficult due to the lack of standardized methods for identifying and classifying potential causes of AUB and the confusion of the applied nomenclature. Therefore, in 2009 a new classification of pathological uterine bleeding in the reproductive period was introduced. The causes of uterine bleeding were divided into organic (PALM), determined by objective visual examination and characterized by structural changes, and functional (COEIN), not associated with structural changes, unclassified pathologies (N) were singled out in a separate category (Table 1).

AUB was divided into acute and chronic (bleeding from the uterine cavity, different in volume, duration and frequency from menstruation and present for 6 months, usually not requiring immediate medical intervention). Acute AUB is an episode of severe bleeding that requires immediate medical intervention to prevent further blood loss, which may develop with or without a history of existing chronic AUB.

According to the recommendations of the FIGO expert group, patients with acute AUB should have a general laboratory examination ( general analysis blood group and Rh factor, pregnancy test), assessment of the hemostasis system (total thromboplastin time, prothrombin time, APTT, fibrinogen), as well as the determination of von Willebrand factor. It can be assumed that 13% of women with AUB have systemic hemostasis disorders, most often von Willebrand disease. It is not yet clear how often these disorders cause or contribute to AUB and how often they are asymptomatic or with minimal biochemical abnormalities, but it is clear that they are often missed by doctors in the examination plan to identify the causes of AUB. Careful history taking with 90% sensitivity makes it possible to identify systemic disorders of hemostasis (Table 2).

Removal of the endometrium during curettage of the walls of the uterine cavity is not required by all patients of the reproductive period with AUB. It is advisable in patients with several factors predisposing to the development of atypical endometrial hyperplasia and carcinoma (obesity or overweight, hypertension, metabolic syndrome, etc.). When determining indications for separate diagnostic curettage, a combination of personal and genetic risk factors, M-echo assessment on TV ultrasound should be taken into account. It is believed that curettage of the walls of the uterine cavity is indicated for all patients of the late reproductive period (over 45 years).

In a woman with a family history colorectal cancer the lifetime risk of endometrial cancer is up to 60%, with a median age at diagnosis of 48-50 years. Screening for endometrial cancer is now part of the approach to managing patients with AUB. First of all, this applies to women of late reproductive and perimenopausal periods. Various techniques can be used to remove the endometrium, the main thing is that an adequate tissue sample is obtained, which will make it possible to conclude that there are no signs of malignant growth.

Given the high likelihood of AUB in chlamydial infection, it is advisable to exclude chlamydial endometritis (PCR endometrial biopsy).

In patients with AUB, the incidence of endometrial hyperplasia is 2-10% and can reach up to 15% in women with recurrent menorrhagia during the menopausal transition. Progression from hyperplasia to endometrial cancer occurs in 3-23% of cases within 13 years, with a frequency of 5% for endometrial hyperplasia and carcinoma. Individual risk factors are: weight ≥ 90 kg, age ≥ 45 years, history of infertility, no history of childbirth, and family history of colon cancer.

The listed diagnostic measures will allow us to suggest the cause of AUB, assess the severity of the patient's condition, and determine the sequence and direction of therapeutic effects.

Total cost of AUB treatment in women requiring surgical intervention are about $40,000. Additional treatment costs equate to $2,291 per patient per year (95% CI, $1,847–$2,752). The database (NHS Hospital Episode Statistics) of the UK (2010--2011) includes 36,129 episodes of AUB, for which specialist consultations were held. Hospitalized patients spent 21,148 bed days in hospitals, an annual cost to the NHS of £5.3-7.4m. Art., based on the range of the cost of a bed-day from 250 to 350 f. Art. respectively. Most experts believe that in countries with effective national guidelines, savings in the treatment of patients with AUB can be achieved primarily by reducing the number of hysterectomies.

The global approach to treating women of reproductive age with chronic AUB is to prevent possible complications. Based on this, the need for anti-relapse treatment of AUB is obvious, the main task of which is the regulation of the menstrual cycle to minimize blood loss and prevent excessive stimulation of the endometrium by estrogens. In the reproductive period, it is possible to use three main methods of treating acute AUB:

Non-hormonal with the use of antifibrinolytics (tranexamic acid) or NSAIDs;
- hormonal hemostasis - use combined hormonal contraceptives (oral and parenteral, mainly containing analogues of natural estrogens), progestogens, including as part of the intrauterine releasing system Mirena, gonadotropin releasing hormone agonists;
- surgical hemostasis - removal of altered tissue with or without visual control, followed by a morphological study of endometrial fragments. TO surgical methods stopping acute AUB is resorted to in cases of patient instability, the presence of a contraindication or the ineffectiveness of conservative methods.

Prevention algorithm and drug treatment BUN at reproductive age is shown in Figure 2.

One of the combined oral contraceptives used to treat abnormal uterine bleeding is Qlaira. This is the first product with natural estradiol, identical to natural, including the combination of estradiol valerate with dienogest. Dienogest, which is part of the drug, has pronounced antiproliferative pharmacological properties. The high therapeutic efficacy of Qlaira against AMK has been confirmed in international randomized placebo-controlled trials. An analysis of data from three multicenter clinical studies conducted in Europe and North America, in which 2,266 women took part, showed that the use of Qlaira was accompanied by a significant reduction in menstrual blood loss and a shortening of the duration of withdrawal bleeding. The drug is 15.5 times superior to placebo in the number of women who are completely cured of AUB (42.0 vs. 2.7%, p< 0,0001), и в 4,9 раза -- по динамике уменьшения кровопотери (76,2 против 15,5%, p < 0,0001) . Его эффективность составляет 76,2%, при этом therapeutic effect in women with heavy and / or prolonged menstrual bleeding, it is achieved in the first months of treatment and continues throughout the application, regardless of the initial volume of blood loss.

Thus, the relevance of studying the etiology and pathogenesis of AUB in women of reproductive age is obvious. Currently, there are no unified approaches to the examination and treatment of such patients, inadequate therapy can lead to the development of complications, and unreasonable surgical treatment can lead to a complex of somatic problems and an increase in economic costs.

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