The main causes of abnormal uterine bleeding. Review of dysfunctional uterine bleeding: what it is, what to do

N.M. PODZOLKOVA, Doctor of Medical Sciences, Professor, V.A. DANSHINA, Russian Medical Academy of 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 and has significant economic consequences both for the patients themselves and for the health care system as a whole. The evaluation 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 uniform approaches to the examination and treatment of such patients; inadequate therapy can lead to the development of complications, and unjustified surgical treatment can lead to a complex of somatic problems and increased economic costs.

Abnormal uterine bleeding (AUB) is a collective concept various types menstrual cycle disorders characteristic of the pubertal, 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.

AUB are the cause significant amount missed work days and school days have significant economic consequences for the patients themselves. A woman with heavy menstruation disability results in a loss of approximately $1,692 per year.

International studies show that only every fifth patient with AUB seeks help from a doctor. Based on this, it is difficult to estimate the total costs associated with the diagnosis and treatment of AUB. It is believed that most women self-administer nonsteroidal anti-inflammatory drugs (NSAIDs) and over-the-counter hemostatic agents. Direct costs to insurance companies associated with AMCs are approximately $1 billion per year.

A number of authors note the 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 reported limitations in daily and social activities, sexual abstinence, and decreased interest in participating in recreational activities. Data from other studies show that AUB correlates with low socioeconomic status, lack of employment, abdominal pain, and psychological distress.

In addition to direct negative influence on the quality of life, AUB can lead to the development of various complications, in particular, menorrhagia is the most common cause of 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 - 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 presented in Figure 1.

The role of extrahypothalamic brain structures, including the cerebral cortex, is 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, through the synthesis of gonadoliberins (GL) and prolactin-inhibiting factor in the arcuate and paraventricular nuclei, has direct action to the pituitary gland. The synthesis of gonadotropin-releasing factors is influenced by:

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

Synthesis takes place in the adenohypophysis various substances, 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 influenced mainly by the circhoral release of GL, i.e., the hypothalamus, and cyclic secretion is regulated mainly by a negative and positive feedback mechanism, and 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 tissues of the ovary include theca and granulosa, which contain a full 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, her ovaries contain, according to various authors, from 300 thousand to 2 million primordial follicles. By menarche, the number of follicles decreases to 200-400 thousand, of which about 400 subsequently become the source of egg formation.

The mechanism for the exit of the follicle 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 the period of anovulation, when taking hormonal contraceptives, etc. Once it begins to grow 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 vascular nutrition. The processes occurring in the follicles do not depend on circulating hormones; regulation is carried out due to local factors.

During 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, quickly forms from the surrounding stroma.

After the antral follicle reaches 2 mm in diameter, it is able to grow only under the influence of high concentration FSH - the hormone-dependent phase begins. In each menstrual cycle, not one follicle enters the hormone-dependent phase, but the so-called. cohort from which the dominant follicle is selected, the rest undergo atresia. In the granulosa 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, and 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 of the cohort except the dominant one.

Consecutive changes in the concentration peaks of estradiol and LH with FSH lead to ovulation - rupture of the follicle and release of the egg from the oviductal mound.

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, and more progesterone and estradiol are synthesized. In the absence of fertilization of the egg, inevitable luteolysis occurs, leading to the elimination of the block of FSH and LH and the onset of a new menstrual cycle.

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

The desquamation phase, when, under the influence of a decrease in the concentration of steroid hormones in the absence of fertilization, ischemic changes and rejection of the functional layer of the endometrium occur by 2/3 due to a decrease in the lumen and twisting of the spiral arteries;
- proliferative phase, which begins in the first days of the menstrual cycle, layering on the desquamation phase. The lost functional layer of the endometrium is restored due to the increase in cells, and 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 and begin to produce secretions.

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

The main causes of dysregulation of the reproductive system are: stress, sudden and/or significant decrease in body weight, increased physical activity, intake medicines, affecting 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.

Changes in the function of the hypothalamic-pituitary-ovarian system caused by stress persist long after the end of exposure to the stress factor. In primates exposed to short-term stress, menstrual cycles remained ovulatory, but there was a 51.6% reduction in peak LH and progesterone levels when stress began in the follicular phase and by 30.9% in the luteal phase. phases. Menstrual irregularities persisted for 3-4 cycles after the end of stress, which coincides with the persistence of elevated cortisol levels. 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 cycle disorder can be caused by for various reasons, and the same reason can lead to the formation various syndromes menstrual irregularities. 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 the clinical picture may change.

The 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 nomenclature used. Therefore, in 2009 it was introduced new classification pathological uterine bleeding during the reproductive period. 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 allocated as a separate category (Table 1).

AUB were divided into acute and chronic (bleeding from the uterine cavity, differing in volume, duration and frequency from menstruation and present for 6 months, usually not requiring immediate medical intervention). Acute AUB is an episode of significant bleeding requiring immediate medical intervention to prevent further blood loss, which can occur with or without a history of existing chronic AUB.

According to the recommendations of the FIGO expert group, patients with acute AUB should undergo a general laboratory examination ( general analysis blood, blood type and Rh factor, pregnancy test), assessment of the hemostatic system (total thromboplastin time, prothrombin time, APTT, fibrinogen), as well as determination of von Willebrand factor. It can be assumed that 13% of women with AUB have systemic disorders hemostasis, 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 physicians in testing for causes of AUB. A thorough medical history can reveal systemic hemostatic disorders with 90% sensitivity (Table 2).

Removal of the endometrium during curettage of the walls of the uterine cavity is not required for all patients reproductive period with AMK. It is advisable in patients who have several factors predisposing to the development of atypical endometrial hyperplasia and carcinoma (obesity or overweight body, hypertension, metabolic syndrome, etc.). When determining the indications for separate diagnostic curettage, a combination of personal and genetic risk factors and M-echo assessment with 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 old).

A woman with family history For colorectal cancer, the lifetime risk of endometrial cancer is up to 60%, with an average age at diagnosis of 48-50 years. Screening for endometrial cancer is now part of the management approach to patients with AUB. This primarily applies to women of the 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 allow us to conclude that there are no signs of malignant growth.

Considering high probability occurrence of AUB during chlamydial infection, it is advisable to exclude chlamydial endometritis (PCR of 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 of hyperplasia to endometrial cancer occurs in 3-23% of cases over 13 years, with a rate of 5% for hyperplasia and endometrial carcinoma. Selected risk factors include: weight ≥ 90 kg, age ≥ 45 years, history of infertility, previous birth history, 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 interventions.

The total cost of treating AUB in women requiring surgery is approximately $40,000. Additional treatment costs equate to $2,291 per patient per year (95% CI, $1,847-$2,752). The UK NHS Hospital Episode Statistics database (2010-2011) includes 36,129 episodes of AUB for which specialist consultations were carried out. Hospitalized patients spent 21,148 bed days in hospital, representing an annual cost to the NHS of £5.3 million to £7.4 million. 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 leadership savings in the treatment of patients with AUB can be achieved primarily by reducing the number of hysterectomies.

The global approach to the treatment of 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 to regulate the menstrual cycle to minimize the amount of blood loss and prevent excessive stimulation of the endometrium by estrogen. During the reproductive period, it is possible to use three main methods of treating acute AUB:

Non-hormonal using 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 Mirena intrauterine releasing system, gonadotropin releasing hormone agonists;
- surgical hemostasis - removal of altered tissue with or without visual control, followed by morphological study endometrial fragments. Surgical methods of stopping acute AUB are used in cases of patient instability, contraindications, or ineffectiveness of conservative methods.

Prevention algorithm and drug treatment AMK in reproductive age presented in Figure 2.

One of the combined oral contraceptives used to treat abnormal uterine bleeding is Qlaira. This is the first drug with natural estradiol, identical to natural, including a combination of estradiol valerate with dienogest. Dienogest, which is part of the drug, has pronounced antiproliferative properties. pharmacological properties. The high therapeutic efficacy of Qlaira against AUB has been confirmed in international randomized placebo-controlled studies. An analysis of data from three multicenter clinical trials conducted in Europe and North America, which included 2,266 women, 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 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 use, 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 uniform approaches to the examination and treatment of such patients; inadequate therapy can lead to the development of complications, and unjustified surgical treatment can lead to a complex of somatic problems and increased economic costs.

Literature

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The gynecologist is often faced with the task of diagnosis and treatment (AMC). Complaints about abnormal uterine bleeding (AUB) account for more than a third of all complaints made during a visit to a gynecologist. The fact that half of the indications for hysterectomy in the United States are abnormal uterine bleeding (AUB) indicates how serious this problem can be.

Inability to detect any histological pathology in 20% of specimens removed during hysterectomy indicates that the cause of such bleeding may be potentially treatable hormonal or medical conditions.

Every gynecologist should strive to find the most appropriate, cost-effective and successful method of treating uterine bleeding (UB). Accurate diagnosis and adequate treatment depend on knowledge of the most likely causes of uterine bleeding (UB). and the most common symptoms that express them.

Anomalous(AUB) is a general term used to describe uterine bleeding that goes beyond the parameters of normal menstruation in women of childbearing age. Abnormal uterine bleeding (AUB) does not include bleeding if its source is located below the uterus (for example, bleeding from the vagina and vulva).

Usually to abnormal uterine bleeding(AUB) refers to bleeding originating from the cervix or fundus of the uterus, and since they are clinically difficult to distinguish, both options must be taken into account in case of uterine bleeding. Pathological bleeding may also occur in childhood and after menopause.

What is meant by normal menstruation, is somewhat subjective, and often differs from one woman to another, and even more so from one culture to another. Despite this, normal menstruation (eumenorrhea) is considered to be uterine bleeding after ovulation cycles, occurring every 21-35 days, lasting for 3-7 days and not being excessive.

The total volume of blood loss for normal menstrual period is no more than 80 ml, although the exact volume is difficult to determine clinically due to the high content in menstrual flow rejected endometrial layer. Normal menstruation does not cause serious pain and does not require the patient to change a sanitary pad or tampon more than once an hour. There are no visible clots in normal menstrual flow. Therefore, abnormal uterine bleeding (AUB) is any uterine bleeding that goes beyond the above parameters.

For description abnormal uterine bleeding(AMC) often use the following terms.
Dysmenorrhea is painful menstruation.
Polymenorrhea - frequent menstruation at intervals of less than 21 days.
Menorrhagia - excessive menstrual bleeding: the volume of discharge is more than 80 ml, the duration is more than 7 days. At the same time, regular ovulatory cycles are maintained.
Metrorrhagia is menstruation with irregular intervals between them.
Menometrorrhagia - menstruation with irregular intervals between them, excessive in volume of discharge and/or duration.

Oligomenorrhea - menstruation occurring less than 9 times a year (that is, with an average interval of more than 40 days).
Hypomenorrhea - menstruation, insufficient (scanty) in terms of the volume of discharge or its duration.
Intermenstrual bleeding is uterine bleeding between obvious periods.
Amenorrhea is the absence of menstruation for at least 6 months, or only three menstrual cycles per year.
Postmenopausal uterine bleeding is uterine bleeding 12 months after the cessation of menstrual cycles.

Such classification of abnormal uterine bleeding(AUB) can be helpful in establishing its cause and diagnosis. However, due to the existing differences in the presentation of abnormal uterine bleeding (AUB) and the frequent existence of multiple causes, the clinical picture of AUB alone is not sufficient to exclude a number of common diseases.

Dysfunctional uterine bleeding- an outdated diagnostic term. Dysfunctional uterine bleeding is a traditional term used to describe excessive uterine bleeding when uterine pathology cannot be identified. However, a deeper understanding of the issue of pathological uterine bleeding and the advent of improved diagnostic methods have made this term obsolete.

In most cases uterine bleeding, not associated with uterine pathology, are associated with for the following reasons:
chronic anovulation (PCOS and related conditions);
use of hormonal drugs (for example, contraceptives, HRT);
hemostasis disorders (for example, von Willebrand disease).

In many cases that in the past would have been classified as dysfunctional uterine bleeding, modern medicine, using new diagnostic methods, identifies uterine and systemic disorders of the following categories:
causing anovulation (for example, hypothyroidism);
caused by anovulation (in particular hyperplasia or cancer);
accompanying bleeding during anovulation, but can be either associated with abnormal uterine bleeding (AUB) or unrelated (for example, leiomyoma).

From a clinical point of view, treatment will always be more effective if it can be determined cause of uterine bleeding(MK). Because grouping different cases of uterine bleeding (UB) into one ill-defined group does not contribute to the diagnostic and treatment processes, the American Consensus Panel recently announced that the term “dysfunctional uterine bleeding” no longer appears to be necessary for clinical medicine.

E. B. Rudakova, A. A. Luzin, S. I. Mozgovoy

In recent years, there has been an increase in the frequency of uterine bleeding, which may be due to an increase in the total number of menstrual cycles in modern women throughout life, as well as with increasing intergenetic interval. In Russia, menstrual irregularities, manifested by bleeding, are in second place among gynecological problems associated with sending women to hospital. Every year, one third of visits to a gynecologist in the USA and Great Britain are associated with abnormal uterine bleeding (AUB). In reproductive age, this is the most common indication for emergency hospitalization, in addition, AUB is an indication for 300,000 hysterectomies performed annually in the United States, and in a third of cases, the anatomical causes of uterine bleeding are not identified. The highest frequency of uterine bleeding is observed in the next 5-10 years after menarche and 5-10 years before the upcoming menopause.

It is generally accepted that the main form of functioning of the reproductive system according to the mature fertile type is the ovulatory, adequately hormonally provided menstrual cycle. The menstrual cycle is a manifestation of a complex biological process in a woman’s body, characterized by cyclical changes in the function of the reproductive, endocrine, cardiovascular, nervous and other systems. The reproductive system, in turn, is a supersystem, the functional state of which is determined by the reverse afferentation of its constituent subsystems. A prospective study based on the analysis of 275,947 menstrual cycles found that the average duration of the menstrual cycle at the age of 20 years was 28.9 ± 2.8 days, at the age of 40 years - 26.8 ± 2.0 days. Based on the criteria for a normal menstrual cycle, the diagnosis of AUB is made when the duration of bleeding increases for more than 7 days, blood loss exceeds 80 ml, and the cyclicity of bleeding is disrupted. In one fifth of women, the average menstrual blood loss exceeds 60 ml, its value can vary by 40% from cycle to cycle.

The frequently used term AUB refers to all cyclic and acyclic bleeding from the uterus, regardless of its origin. The term “dysfunctional uterine bleeding” is no less often used in the literature, defining it as bleeding from the endometrium not associated with pregnancy, organic diseases of the uterus and systemic disorders. A number of publications in recent years have been devoted to the problem of unifying international terminology on issues of uterine bleeding.

Depending on the nature of the violations, there are various symptoms AMK:

• hypermenorrhea (menorrhagia) - excessive (more than 80 ml) or prolonged menstruation (more than 7 days) with a regular interval of 21-35 days;
• metrorrhagia - irregular, intermenstrual bleeding;
• menometrorrhagia - irregular, prolonged uterine bleeding;
• polymenorrhea - frequent menstruation with an interval of less than 21 days.

The most accepted classifications are those based on the genesis of bleeding, taking into account the characteristics of hormonal levels and the age of their onset: organic, dysfunctional, iatrogenic. In terms of age, juvenile bleeding, bleeding of reproductive age, peri- and postmenopause are distinguished. Bleeding in the juvenile period and perimenopause is anovulatory in nature. In this case, the occurrence of anovulation in the juvenile period is due to the immaturity of the hypothalamic-pituitary system, the absence of a formed circhoral rhythm of luliberin, and in perimenopause - a decrease in ovarian function.

The heterogeneity of the group of patients with AUB is explained by a wide range of causes of bleeding. During reproductive age, about 25% of uterine bleeding is due to organic causes, the rest are a consequence of functional disorders in the hypothalamus-pituitary-ovarian system (dysfunctional uterine bleeding - DUB). The main cause of DUB is chronic anovulation, which occurs in 55-82% within 2 years after menarche, in 20% within 5 years. Although the presence of an ovulatory cycle also does not exclude DMC, as, for example, with Halban syndrome - persistence of the corpus luteum, manifested as amenorrhea after 6-8 weeks of menstrual irregularities. According to E. G. Chernukh, ovulatory bleeding is often observed against the background of organic pathology, and anovulatory bleeding often has a substrate in the form of hyperplastic endometrium.

The ratio of common and rare causes of AUB in different age periods shown in. Organic causes of abnormal uterine bleeding are: pathology of the uterus (trauma, foreign body of the uterine cavity, chronic and acute endometritis, inflammatory diseases of the pelvic organs, uterine tumors, adenomyosis, endometrial polyps), ovaries (hormone-producing tumors), coagulopathies, medications (anticoagulants, tricyclic antidepressants, serotonin reuptake inhibitors, tamoxifen, contraceptives), somatic diseases (Cushing's syndrome, diabetes mellitus, systemic lupus erythematosus, Crohn's disease, and so on).

The inflammatory genesis of AUB is sometimes not given due attention, but according to a number of authors, the frequency of chronic endometritis in reproductive age can reach 80-90%, varying in the structure of intrauterine pathology in the range of 0.2-66.3%. Moreover, based on our comprehensive microbiological studies, the frequency of pathogen detection in the endometrium of patients with AUB is 42.1%, and the frequency of chronic endometritis in this group of patients is 31.5%.

The mechanisms of AUB development also remain not entirely clear. In addition to the classic “hormonal” concept of menstrual (uterine) bleeding by Markee (1940), there is an “inflammatory” hypothesis by Finn (1986). According to it, menstrual (uterine) bleeding is a sign that an “infection has been detected” in the endometrium. The hypothesis was based on certain changes in the endometrium in the late secretion phase: tissue edema, migration of leukocytes and the presence of decidual cells with signs of tissue fibroblasts.

L. A. Salamonsen et. al. (2002) put forward a different concept, according to which menstrual (uterine) bleeding is an active process under the control of matrix metalloproteinases and dependent on their activity. The fall in progesterone concentration in the late secretory phase is key point, changing the balance of metalloproteinase inhibitors - matrix metalloproteinases (MMPs) towards the latter. These proteolytic enzymes (MMP-1, MMP-3, MMP-9) degrade the extracellular matrix and promote shedding of the upper two-thirds of the endometrium. Proinflammatory cytokines (IL-1, IL-8, TNF-alpha) are indirectly involved in this process, influencing the processes of angiogenesis, endometrial remodeling and attraction of leukocytes, which in turn also produce MMPs.

The occurrence of uterine bleeding is determined not only by the level of sex steroid hormones, but also by the local production of other biologically active molecules: prostaglandins (PGs), cytokines, growth factors. A shift in the ratio between the endometrial content of the vasoconstrictor PG F2a and the vasodilator PG E2 may be one of the causes of ovulatory DUB, while an increase in the concentration of prostaglandins with a decrease in progesterone levels may increase blood loss during menstruation.

The endometrium expresses angiogenesis inducers and most angiogenesis blocking factors. It has been suggested that impaired angiogenesis may be a cause of AUB. For example, increased levels of estrogen induce the synthesis of vascular endothelial growth factor (VEGF), which promotes angiogenesis in the endometrium, as well as nitric oxide (endothelial relaxing factor), which affects excess menstrual blood loss. Endometrial endothelins are powerful vasoconstrictors; a lack of their production can increase the duration of bleeding and thus contribute to the occurrence of menorrhagia.

Estrogens also stimulate fibrinolysis, and progesterone inhibits this process by increasing the concentration of fibrinolysis inhibitors. Excessive activation of the fibrinolytic system can disrupt the balance of the hemostatic system, leading to uterine bleeding. Normally, primary hemostasis in the endometrium is achieved not only through the formation of small blood clots in the spiral arterioles, but also through their spasm.

About 19-28% of patients of reproductive age hospitalized for AUB have disturbances in the hemostatic system. Approximately 80-85% of inherited disorders in the hemostatic system are associated with hemophilia A (factor VIII deficiency), von Willebrand disease and hemophilia B (factor IX deficiency). Approximately 15% of congenital disorders of hemostasis are associated with deficiency of fibrinogen, prothrombin, factors V, VII, X, XI, XIII, as well as combined deficiency of factors V and VIII. About 20-30% of patients in this category with AUB of the menorrhagia type have platelet disorders. Bleeding caused by pathology of the hemostatic system is characterized by disturbances in the form of menorrhagia, starting from the period of menarche, accompanied by a decrease in hemoglobin levels, the presence of a characteristic history (hemorrhages and postoperative bleeding) and family predisposition.

The diagnostic algorithm for AUB is widely covered in Russian and foreign literature(). Although, due to the heterogeneity of the causes of AUB, the list of diagnostic procedures differs.

Morphological verification of the cause of AUB is quite complex, since the material obtained during therapeutic and diagnostic curettage of the endometrium may be inadequate for the interpretation, for example, of signs of chronic endometritis or glandular hyperplasia due to the presence of numerous artificial changes caused by tissue destruction and massive amounts of blood in the material .

Verification during subsequent research may have its own characteristics with consideration of such issues as the preferred period of the ovarian-menstrual cycle for collecting diagnostic material, interpretation of morphological findings taking into account gynecological history, taking hormonal drugs, and is the subject of clinical and morphological comparisons.

An experienced doctor, even by the nature of menstrual dysfunction, can guess its genesis. For example, the regularity of bleeding, the presence of premenstrual syndrome and dysmenorrhea suggest the presence of ovulation. Heavy, irregular and painless menstrual bleeding, especially in the middle of the reproductive period, suggests an ovulation disorder. In any case, it is necessary to exclude organic causes of uterine bleeding. Thus, the presence of anteponing, postponing scanty discharge“rusty” character (against the background cyclical pain associated with the cycle) suggests the presence of adenomyosis. Hypermenorrhea is often one of the symptoms of endometrial polyp or submucous uterine fibroids. Uterine bleeding against the background of follicular atresia is prolonged, not abundant and occurs after 6-8 weeks of delayed mensis. Against the background of persistence of the follicle, bleeding is usually profuse, with clots, occurring after delayed mensis.

The principles of therapy for uterine bleeding are built in accordance with the reasons that cause them, as well as the degree of blood loss, the patient’s condition and have two main goals: stopping bleeding and preventing its recurrence.

There is a therapeutic approach based on the tactics of managing uterine bleeding depending on hematocrit and blood hemoglobin. Thus, in the case of mild anemia and the established fact of anovulation, the following is indicated: antianemic therapy, antifibrinolytic and nonsteroidal anti-inflammatory drugs (NSAIDs); Hormonal drugs are used for moderate to severe anemia. In the latter case, the use of surgical hemostasis is also indicated.

With heavy or prolonged mensis, 50-250 mg of iron is released into the blood. The need for iron in these women increases 2.5-3 times. This amount of iron is not absorbed even with a high content of it in food. In this case, both replenishment of latent iron deficiency and treatment of iron deficiency therapy are carried out exclusively with iron preparations. A multicentre randomized trial (Mahomed, 2004; NICE level of evidence - 1) involving 5449 pregnant and gynecological patients of reproductive age with iron deficiency anemia found that combined oral iron and folic acid supplementation was more effective than monotherapy. Deficiency of folic acid and cyanocobalamin, often observed in posthemorrhagic anemia, leads to disruption of DNA synthesis in the hematopoietic organs, and their inclusion in medications increases the active absorption of iron in the intestine, its further utilization, as well as the release of additional amounts of transferrin and ferritin. These drugs include the complex antianemic drug Ferro-Folgamma, containing 100 mg of anhydrous iron (II) sulfate, 5 mg of folic acid, 10 mcg of cyanocobalamin and 100 mg of ascorbic acid. The active components of Ferro-Folgamma are in a special neutral shell, which ensures their absorption mainly in upper section small intestine. The absence of local irritation on the gastric mucosa contributes to good tolerability of the drug by gastrointestinal tract. As part of the treatment of uterine bleeding, a positive effect of using Ferro-Folgamma was noted. In particular, after 4-5 weeks of treatment, hemoglobin levels and other indicators of general hemostasis were restored in 87.6-90.1% of patients with JMC who initially had mild or moderate anemia.

Within complex therapy NSAIDs are used that block prostaglandin synthetase and allow a 30-50% reduction in the volume of blood lost.

If there is no effect from symptomatic hemostatic therapy, hormonal hemostasis is performed using estrogens, progestogens or combined estrogen-progestogen drugs. A number of studies have demonstrated the effectiveness of using synthetic transdermal estrogens and intravenous administration of equilins for hormonal hemostasis.

The therapy complex should include antifibrinolytic drugs that inhibit the conversion of plasminogen to plasmin, for example, tranexamic acid. Tranexamic acid is given at 20-25 mg/kg every 6-8 hours, but not more than 1.5 g per course. The use of drugs in this group for DUB leads to a reduction in menstrual blood loss by approximately 45-60%.

There are publications in foreign and domestic literature about the successful intranasal use of desmopressin (1-deamino-8-D-vasopressin acetate) as part of the complex therapy of patients with AUB. Desmopressin is a synthetic analogue of the antidiuretic hormone of the posterior lobe of the pituitary gland (vasopressin). Desmopressin increases the plasma concentration of factor VIII and von Willebrand factor by 2-6 times and indirectly affects platelets.

After stopping the bleeding, either therapy is carried out for the identified organic pathology, or therapy is aimed at forming a regular menstrual cycle. In this case, oral contraceptives and progestogens are used in the contraceptive mode. Therapy with combined estrogen-progestin drugs is usually carried out for 3-6 months, after which regular menstruation may spontaneously resume.

In the case of recurrent bleeding or lack of effect from conservative therapy, the rationality of the conservative treatment performed, namely the adequacy of the dose and regimen of medications, should be established, as well as the degree of adherence to therapy should be determined. In the case of a true lack of effect from conservative treatment, the issue of surgical treatment is decided. In this case, along with traditional ones (hysterectomy, panhysterectomy), endoscopic techniques are successfully used: Nd-YAG laser ablation (method efficiency: 88-93% - normalization of the menstrual cycle, amenorrhea was obtained in 55.4-74%), diathermic loop ( loop)-resection and diathermic rollerball-ablation. These methods have a number of advantages over hysterectomy: less often postoperative complications, shorter recovery time and lower cost of treatment. Destruction of the endometrium requires subsequent dynamic monitoring with transvaginal echographic monitoring of the condition of the pelvic organs.

Adequate treatment of AUB can not only improve the quality of life of patients, but in some cases solve their reproductive problems.

For questions regarding literature, please contact the editor.

E. B. Rudakova, Doctor of Medical Sciences, Professor
A. A. Luzin
S. I. Mozgovoy, Candidate of Medical Sciences, Associate Professor
GU VPO Omsk State Medical Academy, Omsk

Abnormal uterine bleeding (AUB)

0 RUB

This is bleeding that differs from normal menstruation in duration and volume of blood loss and/or frequency. Normally, the duration of the menstrual cycle varies from 24 to 38 days, the duration of menstrual bleeding is 4-8 days, total blood loss ranges from 40 to 80 ml. In reproductive age, BUN is 10 - 30%, in perimenopause it reaches 50%.

AUB are one of the main causes iron deficiency anemia, reduce the performance and quality of life of women. AUB ranks second among the reasons for hospitalization of women in gynecological hospitals and serves as an indication for 2/3 of hysterectomies and endometrial ablations.

Causes

The causes of AUB have age-related characteristics. In young girls, AUB is more often associated with hereditary disorders of the hemostatic system and infections. Approximately 20% of adolescents and 10% of women of reproductive age with heavy menstruation have blood diseases (coagulopathies), such as von Willebrand disease, thrombocytopenia, and less commonly, acute leukemia, and liver disease.

In reproductive age, the causes of AUB include organic disorders of the endo- and myometrium (submucous uterine fibroids, adenomyosis, polyps, hyperplasia and endometrial cancer), as well as inorganic pathology (disorders of the blood coagulation system, intrauterine devices, chronic endometritis, ovulatory dysfunction, taking medications drugs - some antibiotics, antidepressants, tamoxifen, corticosteroids). In many cases, the cause is endocrinopathies and neuropsychic stress (for example, polycystic ovary syndrome, hypothyroidism, hyperprolactinemia, obesity, anorexia, sudden loss weights or extreme sports training). Breakthrough bleeding while taking hormonal drugs is more often observed in women who smoke, which is associated with a decrease in the levels of steroids in the bloodstream due to increased metabolism in the liver.

In perimenopause, AUB occurs against the background of anovulation and various organic pathologies of the uterus. With age, the likelihood of malignant lesions of the endo- and myometrium increases.

Clinical manifestations

Depending on the nature of the disorders, various symptoms of AUB are distinguished:

Irregular, prolonged uterine bleeding (menometrorrhagia);

Excessive (more than 80 ml) or prolonged menstruation (more than 8 days) with a regular interval of 24-38 days (menorrhagia (hypermenorrhea);

Irregular, intermenstrual bleeding from the uterus, usually (often not intense) (metrorrhagia);

Frequent menstruation less than 24 days apart (polymenorrhea)

Diagnosis of abnormal uterine bleeding

Examination by a gynecologist-endocrinologist, assessment of patient complaints. Many women misinterpret the amount of blood loss during menstruation. For example, 50% of women with normal menstrual blood loss complain of increased bleeding. In order to clarify the presence of AUB, the patient is asked the following questions:

A laboratory examination is necessary to determine the presence of anemia and hemostasis pathology. Transvaginal ultrasound of the pelvic organs is considered as a 1st line diagnostic procedure for assessing the condition of the endometrium. Sonohysterography has high diagnostic significance; it is performed when transvaginal ultrasound is insufficiently informative to clarify focal intrauterine pathology. Hysteroscopy and endometrial biopsy continue to be considered as the “gold” standard for diagnosing intrauterine pathology, primarily to exclude precancerous lesions and endometrial cancer. Recommended for suspected endometrial pathology, presence of risk factors for uterine cancer (obesity, PCOS, diabetes mellitus, family history of colon cancer), in patients with AUB after 40 years.

MRI is recommended if there is multiple fibroids uterus to clarify the topography of nodes before planned myomectomy, embolization uterine arteries, FUS ablation, as well as in cases of suspected adenomyosis or in cases of poor visualization of the uterine cavity to assess the condition of the endometrium.

Treatment methods for abnormal uterine bleeding

Treatment of AUB at the Center for Obstetrics, Gynecology and Perinatology named after. IN AND. Kulakov of the Ministry of Health of Russia is carried out on the basis of modern international and Russian clinical recommendations, in the development of which researchers took an active part Department of Gynecological Endocrinology. The principles of treatment for AUB pursue 2 main goals: stopping bleeding and preventing its relapse. In each specific case, upon appointment drug therapy Not only the effectiveness of the drugs is taken into account, but also possible side effects, the woman’s age, interest in pregnancy or contraception. For AUB not associated with organic pathology, non-surgical treatment methods are used.