What is the proliferative phase. Forms of deviation of the structure of the endometrium from the norm

The inner layer of the uterus is called the endometrium. This tissue has a complex structural structure and a very important role. The reproductive functions of the body depend on the condition of the mucous membrane.

Every month throughout the cycle, the density, structure and size of the inner layer of the uterus changes. The proliferation phase is the very first stage of the natural transformations of the mucous membrane that begin. It is accompanied by active cell division and proliferation of the uterine layer.

Endometrial condition proliferative type directly depends on the intensity of fission. Disturbances in this process lead to abnormal thickening of the resulting tissues. Too many cells have a negative impact on health and contribute to the development of serious diseases. Most often, when examined in women, glandular endometrial hyperplasia is detected. There are other, more dangerous diagnoses and conditions that require emergency medical attention.

For successful fertilization and a trouble-free pregnancy, cyclic changes in the uterus must correspond to normal values. In cases where an atypical structure of the endometrium is observed, pathological deviations are possible.

It is very difficult to find out about the unhealthy state of the uterine mucosa by symptoms and external manifestations. Doctors will help with this, but to make it easier to understand what endometrial proliferation is and how tissue proliferation affects health, it is necessary to understand the features of cyclical changes.

The endometrium consists of functional and basal layers. The latter consists of tightly adjacent cellular particles penetrated by numerous blood vessels. Its main function is to restore the functional layer, which, if fertilization fails, peels off and is excreted with the blood.

The uterus cleanses itself after menstruation, and the mucous membrane during this period has a smooth, thin, even structure.

The standard menstrual cycle is usually divided into 3 stages:

Proliferation.
Secretion.
Bleeding (menstruation).

At each of these stages there is a certain one. We recommend reading our article for more detailed information.

In this order of natural changes, proliferation comes first. The phase begins approximately on the 5th day of the cycle after the end of menstruation and lasts 14 days. During this period, cellular structures multiply through active division, which leads to tissue proliferation. The inner layer of the uterus can increase up to 16 mm. This is the normal structure of the endometrial layer of the proliferative type. This thickening helps to attach the embryo to the villi of the uterine layer, after which ovulation occurs, and the uterine mucosa enters the secretion phase in the endometrium.

If conception has occurred, the corpus luteum is implanted into the uterus. If a pregnancy fails, the embryo stops functioning, hormone levels decrease, and menstruation begins.

Normally, the stages of the cycle follow each other in exactly this sequence, but sometimes failures occur in this process. For various reasons, proliferation may not stop, that is, after 2 weeks, cell division will continue uncontrollably and the endometrium will grow. Too dense and thick inner layer of the uterus often leads to problems with conception and the development of serious diseases.

Proliferative diseases

Intensive growth of the uterine layer during the proliferative phase occurs under the influence of hormones. Any disruption in this system prolongs the period of cell division activity. An excess of new tissue causes uterine cancer and the development of benign tumors. Background pathologies can provoke the occurrence of diseases. Among them:

endometritis;
cervical endometriosis;
adenomatosis;
uterine fibroids;
uterine cysts and polyps;

Hyperactive cell division is observed in women with identified endocrine disorders, diabetes mellitus and hypertension. The condition and structure of the uterine mucosa are negatively affected by abortion, curettage, excess weight, and abuse of hormonal contraceptives.

Hyperplasia is most often diagnosed against the background of hormonal problems. The disease is accompanied by abnormal growth of the endometrial layer and has no age restrictions. The most dangerous periods are puberty And . In women under 35 years of age, the disease is rarely detected, since hormonal levels at this age are stable.

Endometrial hyperplasia has clinical signs: the cycle is disrupted, uterine bleeding is observed, and constant pain appears in the abdominal area. The danger of the disease is that the reverse development of the mucosa is disturbed. The size of the overgrown endometrium does not decrease. This leads to infertility, anemia, and cancer.

Depending on how effectively the late and early stages of proliferation occur, endometrial hyperplasia can be atypical and glandular.

Glandular hyperplasia of the endometrium

High activity of proliferative processes and intensive cell division increases the volume and structure of the uterine mucosa. With pathological growth and thickening of glandular tissues, doctors diagnose glandular hyperplasia. The main reason development of the disease are hormonal disorders.

There are no typical symptoms. The symptoms that appear are characteristic of many gynecological diseases. Most women's complaints are related to conditions during menstruation and after menstruation. The cycle changes and is different from previous ones. Heavy bleeding is painful and contains clots. Often discharge occurs outside the cycle, which leads to anemia. Serious blood loss causes weakness, dizziness and weight loss.

The peculiarity of this form of endometrial hyperplasia is that the newly formed particles do not divide. The pathology rarely transforms into a malignant tumor. Nevertheless, this type of disease is characterized by indomitable growth and loss of function typical of tumor formations.

Atypical

Refers to intrauterine diseases that are associated with hypoplastic processes of the endometrium. The disease is mainly detected in women after 45 years of age. In every third out of 100, the pathology develops into a malignant tumor.

In most cases, this type of hyperplasia develops due to hormonal disruptions that activate proliferation. Uncontrolled division of cells with a disrupted structure leads to the growth of the uterine layer. In atypical hyperplasia, there is no secretory phase, as the size and thickness of the endometrium continues to grow. This leads to long, painful and heavy periods.

Severe atypia is a dangerous condition of the endometrium. Not only does active cell proliferation occur, the structure and structure of the nuclear epithelium changes.

Atypical hyperplasia can develop in the basal, functional, and simultaneously in both layers of the mucosa. Last option is considered the most severe, since there is a high probability of developing cancer.

Phases of endometrial proliferation

It is usually difficult for women to understand what the phases of endometrial proliferation are and how a violation of the sequence of stages is associated with health. Knowledge about the structure of the endometrium helps to understand the issue.

The mucosa consists of a ground substance, a glandular layer, connective tissue (stroma) and numerous blood vessels. From about the 5th day of the cycle, when proliferation begins, the structure of each of the components changes. The entire period lasts about 2 weeks and is divided into 3 phases: early, middle, late. Each stage of proliferation manifests itself differently and takes a certain time. The correct sequence is considered the norm. If at least one of the phases is absent or there is a malfunction in its course, the likelihood of pathologies developing in the lining inside the uterus is very high.

Early

The early stage of proliferation is days 1-7 of the cycle. The mucous membrane of the uterus during this period begins to gradually change and is characterized by the following structural transformations of tissue:

the endometrium is lined with a cylindrical epithelial layer;
blood vessels are straight;
glands are dense, thin, straight;
cell nuclei have a rich red color and an oval shape;
stroma oblong, spindle-shaped.
the thickness of the endometrium in the early polyferative phase is 2–3 mm.

Average

The middle stage of the proliferative endometrium is the shortest, usually on the 8th–10th day of the menstrual cycle. The shape of the uterus changes, noticeable changes occur in the shape and structure of other elements of the mucosa:

the epithelial layer is lined with cylindrical cells;
the kernels are pale;
the glands are elongated and curved;
connective tissue loose structure;
the thickness of the endometrium continues to grow and reaches 6–7 mm.

Late

On days 11–14 of the cycle (late stage), the cells inside the vagina increase in volume and swell. Significant changes occur in the uterine lining:

the epithelial layer is high and multilayered;
some of the glands elongate and have a wavy shape;
the vascular network is tortuous;
cell nuclei increase in size and have rounded shape;
the thickness of the endometrium in the late proliferative phase reaches 9–13 mm.

All listed stages are closely related to the secretion phase and must correspond to normal values.

Causes of uterine cancer

Cancer of the uterus is one of the most dangerous pathologies of the proliferative period. In the early stages, this type of disease is asymptomatic. The first signs of the disease include copious mucous discharge. Over time, signs such as pain in the lower abdomen, uterine bleeding with endometrial fragments, frequent urge to urinate, and weakness appear.

The incidence of cancer increases with the onset of anovulatory cycles, characteristic of people over 45 years of age. During premenopause, the ovaries still produce follicles, but they rarely mature. Ovulation does not occur, and accordingly, the corpus luteum does not form. This leads to hormonal imbalance - the most common reason formation of cancerous tumors.

At risk are women who have not had pregnancy or childbirth, as well as those with identified obesity, diabetes mellitus, metabolic and endocrine disorders. Background diseases that provoke cancer of the reproductive organ are polyps in the uterus, endometrial hyperplasia, fibroids, and polycystic ovaries.

Diagnosis of oncology is complicated by the condition of the uterine wall in case of cancerous lesions. The endometrium becomes loose, the fibers are located in different directions, and the muscle tissue is weakened. The boundaries of the uterus are blurred, polypoid growths are noticeable.

Regardless of the stage of the pathological process, endometrial cancer is detected by ultrasound. To determine the presence of metastases and the location of the tumor, hysteroscopy is used. In addition, the woman is recommended to undergo a biopsy, x-ray and a series of tests (urine, blood, hemostasis study).

Timely diagnosis makes it possible to confirm or exclude the growth of a tumor, its nature, size, type and degree of spread to neighboring organs.

Treatment of the disease

Treatment of cancer pathology of the uterine body is prescribed individually, depending on the stage and form of the disease, as well as age and general condition women.

Conservative therapy is used only in the initial stages. Women of reproductive age with diagnosed stage 1–2 disease undergo hormonal therapy. During the course of treatment, you need to regularly take tests. This is how doctors monitor the state of the cell nucleus, changes in the structure of the uterine mucosa and the dynamics of the development of the disease.

The most effective method is considered to be removal of the affected uterus (partial or complete). To eliminate single pathological cells after surgery, a course of radiation or chemical therapy is prescribed. In cases of rapid growth of the endometrium and rapid growth of a cancerous tumor, doctors remove the reproductive organ, ovaries and appendages.

With early diagnosis and timely treatment, any of the therapeutic methods gives positive results and increases the chances of recovery.

The endometrium is the mucous layer that lines the inside of the uterus. Its functions include ensuring implantation and development of the embryo. In addition, the menstrual cycle depends on the changes occurring in it.

One of the important processes occurring in a woman’s body is endometrial proliferation. Disturbances in this mechanism cause the development of pathology in the reproductive system. The proliferative endometrium marks the first phase of the cycle, that is, the stage that occurs after the end of menstruation. During this stage, endometrial cells begin to actively divide and grow.

Proliferation concept

Proliferation is the active process of cell division in a tissue or organ. As a result of menstruation, the mucous membranes of the uterus become very thin due to the fact that the cells that make up the functional layer are rejected. This is what determines the process of proliferation, since cell division renews the thinned functional layer.

However, proliferative endometrium does not always indicate the normal functioning of the woman’s reproductive system. Sometimes it can occur in the event of pathology development, when cells divide too actively, thickening the mucous layer of the uterus.

Causes

As mentioned above, the natural cause of proliferative endometrium- end of the menstrual cycle. The rejected cells of the uterine mucosa are excreted from the body along with the blood, thereby thinning the mucous layer. Before the next cycle occurs, the endometrium needs to restore this functional area of the mucosa through the process of division.

Pathological proliferation occurs as a result of excessive stimulation of cells by estrogen. Consequently, when the mucous layer is restored, endometrial division does not stop and the walls of the uterus thicken, which can lead to the development of bleeding.

Process phases

There are three phases of proliferation (with its normal course):

Early phase. It occurs during the first week of the menstrual cycle and at this time epithelial cells, as well as stromal cells, can be found on the mucous layer.
Middle phase. This stage begins on the 8th day of the cycle and ends on the 10th. During this period, the glands enlarge, the stroma swells and loosens, and the cells of the epithelial tissue stretch.
Late phase. The proliferation process stops on the 14th day from the beginning of the cycle. At this stage, the mucous membrane and all glands are completely restored.

Diseases

The process of intensive division of endometrial cells can fail, as a result of which cells appear in excess of the required number. These newly formed “building” materials can combine and lead to the development of tumors such as proliferative endometrial hyperplasia.

It is a consequence of hormonal imbalance in monthly cycle. Hyperplasia is a proliferation of endometrial and stromal glands and can be of two types: glandular and atypical.

Types of hyperplasia

The development of such an anomaly occurs mainly in women at menopausal age. The main reason is most often a large number of estrogens, which affect endometrial cells, activating their excessive division. With the development of this disease, some fragments of the proliferative endometrium acquire a very dense structure. In particularly affected areas, the compaction can reach 1.5 cm in thickness. In addition, the formation of proliferative type polyps on the endometrium located in the organ cavity is possible.

This type of hyperplasia is considered a precancerous condition and is most often found in women during menopause or in old age. In young girls, this pathology is diagnosed very rarely.

Atypical hyperplasia is considered to be a pronounced proliferation of the endometrium, which has adenomatous sources located in the branching of the glands. Examining scrapings from the uterus, one can detect a large number of tubular epithelial cells. These cells can have both large and small nuclei, and in some they can be stretched. In this case, the tubular epithelium can be either in groups or separately. The analysis also shows the presence of lipids on the walls of the uterus; their presence is an important factor in making a diagnosis.

Transition from atypical glandular hyperplasia to cancer occurs in 3 women out of 100. This type of hyperplasia is similar to endometrial proliferation during a normal monthly cycle, however, during the development of the disease, there are no decidual tissue cells on the uterine mucosa. Sometimes the process of atypical hyperplasia can be reversed, however, this is only possible under the influence of hormones.

Symptoms

With the development of proliferative endometrial hyperplasia, the following symptoms are observed:

The menstrual functions of the uterus are disrupted, manifested by bleeding.
There is a deviation in the menstrual cycle, in the form of intense cyclic and prolonged bleeding.
Metrorrhagia develops - unsystematic and non-cyclical bleeding of varying intensity and duration.
Bleeding occurs between periods or after their delays.
Breakthrough bleeding with the release of clots is observed.
The constant occurrence of bleeding provokes the development of anemia, malaise, weakness and frequent dizziness.
An anovulatory cycle occurs, which can cause infertility.

Diagnostics

Due to the similarity of the clinical picture of glandular hyperplasia with other pathologies diagnostic measures are of great importance.

Diagnosis of endometrial hyperplasia of the proliferative type is carried out using the following methods:

Studying the patient's history and complaints related to the time of onset of bleeding, its duration and frequency. Accompanying symptoms are also studied.
Analysis of obstetric and gynecological information which include heredity, pregnancy, contraceptive methods used, past illnesses(not only gynecological), operations, diseases transmitted through sexual contact, etc.
Analysis of information about the beginning of the menstrual cycle (patient’s age), its regularity, duration, pain and profuseness.
Conducting a bimanual vaginal examination by a gynecologist.
Gynecological smear collection and microscopy.
Prescription of transvaginal ultrasound, which determines the thickness of the uterine mucosa and the presence of proliferative endometrial polyps.
Determination using ultrasound of the need for an endometrial biopsy to make a diagnosis.
Carrying out separate curettage using a hysteroscope, which scrapes or completely removes the pathological endometrium.
Histological examination of scrapings to determine the type of hyperplasia.

Treatment methods

Therapy for glandular hyperplasia is carried out various methods. It can be either operative or conservative.

Surgical treatment of pathology of the proliferative type of the endometrium involves complete removal of areas that have undergone deformation:

The cells affected by the pathology are scraped out from the uterine cavity.
Surgical intervention using hysteroscopy.

Surgical intervention is provided in the following cases:

the patient’s age allows her to perform the reproductive function of the body;
the woman is “on the threshold” of menopause;
in cases of heavy bleeding;
after detection of a proliferative type on the endometrium

The materials obtained as a result of curettage are sent for histological analysis. Based on its results and in the absence of other diseases, the doctor may prescribe conservative therapy.

Conservative treatment

This therapy involves certain methods of influencing pathology. Hormone therapy:

Oral hormonal hormones are prescribed combined contraceptives, which should be taken for 6 months.
A woman takes pure gestagens (progesterone preparations), which help reduce the body's secretion of sex hormones. These medications should be taken for 3-6 months.
A gestagen-containing intrauterine device is installed, which affects endometrial cells in the body of the uterus. The validity period of such a spiral is up to 5 years.
Prescribing hormones intended for women over 35 years of age, which also have a positive effect on treatment.

Therapy aimed at general strengthening of the body:

Taking complexes of vitamins and minerals.
Taking iron supplements.
Purpose sedatives.
Carrying out physiotherapeutic procedures (electrophoresis, acupuncture, etc.).

In addition, to improve the general condition of overweight patients, a therapeutic diet is developed, as well as measures aimed at physically strengthening the body.

Preventive actions

Measures to prevent the development of proliferative endometrial hyperplasia may be as follows:

regular examination by a gynecologist (twice a year);
taking preparatory courses during pregnancy;
selection of suitable contraceptives;
Immediately consult a doctor if any disturbances in the functioning of the pelvic organs occur.
giving up smoking, alcohol and other bad habits;
regular feasible physical activity;
healthy eating;
careful monitoring of personal hygiene;
taking hormonal medications only after consultation with a specialist;
avoid abortion procedures by using necessary means contraception;
take place annually full examination body and if a deviation from the norm is detected, immediately consult a doctor.

To avoid relapses of proliferative type endometrial hyperplasia, it is necessary:

regularly consult with a gynecologist;
undergo examinations by a gynecologist-endocrinologist;
consult with a specialist when choosing methods of contraception;
lead healthy image life.

Forecasts

The prognosis for the development and treatment of endometrial proliferative gland hyperplasia directly depends on the timely detection and treatment of the pathology. By consulting a doctor in the early stages of the disease, a woman has a high chance of being completely cured.

However, one of the most serious complications hyperplasia can become infertility. The reason for this is a hormonal imbalance, leading to the disappearance of ovulation. Timely diagnosis of the disease and effective therapy will help to avoid this.

Very often there are cases of recurrence of this disease. Therefore, a woman needs to regularly visit a gynecologist for an examination and follow all his recommendations.

Every month, a woman’s body undergoes changes associated with hormonal cyclic fluctuations. One of the manifestations of such changes is menstrual bleeding. But this is only the visible part complex mechanism aimed at maintaining a woman’s reproductive function. It is very important that the mucous layer of the uterus - the endometrium - has a normal thickness throughout the entire cycle. What thickness of the endometrium before, during and after menstruation is considered normal?

What happens in the female body every month?

The normal menstrual cycle consists of three phases: proliferation, secretion, desquamation (menstruation). During each of them, changes occur in the ovaries and endometrium, caused by fluctuations in hormones (estrogen, progesterone, pituitary hormones). Therefore, on different days of the cycle, as well as during menstruation, the thickness of the endometrial layer changes.

For example, the thickness of the endometrium before menstruation is much greater than in the first days after it. The usual duration of the menstrual cycle is 28 days, during which time the uterine lining should completely recover.

Changes in the endometrium in the proliferation phase

The proliferation phase consists of early, middle and late stages. At the early stage of the proliferation phase, immediately after menstruation, the endometrium should be no more than 2-3 mm. During this period, at the beginning of the menstrual cycle, endometrial regeneration begins thanks to the cells of the basal layer. Visually, the uterine mucosa at this stage is thin, pale pink, with isolated small hemorrhages.

The middle stage begins on the 4th day of the menstrual cycle. Happening gradual increase endometrial thickness, on the 7th day after menstruation it is 6-7 mm. The duration of this period is up to 5 days.

At a late stage, the normal thickness of the endometrium is 8-9 mm. This stage lasts three days. At this stage, the uterine mucosa loses its uniform structure. It becomes folded, and areas of thickening of certain zones are observed. For example, the endometrium is somewhat denser and thicker in the fundus and on the posterior wall of the uterus, and slightly thinner on its anterior surface. This is due to the preparation of the mucosa for implantation ovum.

This video presents detailed information about the course of menstruation:

What changes in the endometrium occur during the secretion phase?

This phase is also divided into early, middle and late stages. It begins 2-4 days after ovulation. Does this phenomenon affect the thickness of the endometrium? At the early stage of secretion, the endometrium has a thickness of at least 10 and maximum 13 mm. The changes are primarily related to increased production progesterone by the corpus luteum of the ovary. The mucous membrane increases even more significantly than in the proliferation phase, by 3-5 mm, becomes swollen, and acquires a yellowish tint. Its structure becomes homogeneous and does not change until the onset of menstruation.

The middle stage lasts from the 18th to the 24th day of the menstrual cycle and is characterized by the most pronounced secretory changes in the mucous membrane. At this point, the normal thickness of the endometrium is a maximum of 15 mm in diameter. The inner layer of the uterus becomes as dense as possible. When performing an ultrasound during this period, you can notice an echo-negative strip at the border of the myometrium and endometrium - the so-called rejection zone. This zone reaches its maximum before menstruation. Visually, the endometrium is swollen and, due to folding, can acquire a polypoid appearance.

What changes occur in the late stage of secretion? Its duration is from 3 to 4 days, it precedes menstrual bleeding, and usually occurs on the 25th day of the monthly cycle. If a woman is not pregnant, then involution of the corpus luteum occurs. Due to the reduced production of progesterone, pronounced trophic disorders occur in the endometrium. When performing an ultrasound during this period, the heterogeneity of the endometrium is clearly visible, with areas of dark spots, zones vascular disorders. This picture is caused by vascular reactions occurring in the endometrium, leading to thrombosis, hemorrhage, and necrosis of mucosal areas. The rejection zone on ultrasound becomes even more distinct, its thickness is 2-4 mm. On the eve of menstruation, the capillaries in the layers of the endometrium become even more dilated and spirally convoluted.

Their tortuosity becomes so pronounced that it leads to thrombosis and subsequent necrosis of mucosal areas. These changes are called "anatomical" menstruation. Immediately before menstruation, the thickness of the endometrium reaches 18 mm.

What happens in the desquamation phase?

During this period, the functional layer of the endometrium is rejected. This process begins on the 28-29th day of the menstrual cycle. The duration of this period is 5-6 days. There may be deviations from the norm for one or two days. The functional layer looks like areas of necrotic tissue; during menstruation, the endometrium is completely rejected in 1-2 days.

At various diseases In the uterus, there may be a slow rejection of areas of the mucous membrane, this affects the intensity of menstruation and its duration. Sometimes during menstruation there is very heavy bleeding.

If the bleeding intensifies, you should consult a gynecologist. This should be especially remembered during the first menstruation after a miscarriage, as this may mean that particles of the fertilized egg remain in the uterus.

Additional information about menstruation is provided in the video:

Does menstruation always start on time?

Sometimes there are situations when the onset of menstruation occurs untimely. If pregnancy is excluded, then this phenomenon is called delayed menstruation. The main reason for this condition is a hormonal imbalance in the body. Some experts consider the norm to be delayed for a healthy woman up to 2 times a year. They can be quite common for teenage girls who have not yet established their menstrual cycle.

Factors that may lead to this condition:

Chronic stress. It can provoke a violation of the production of pituitary hormones.
Overweight or, conversely, a sharp weight loss. In women who lose weight rapidly, menstruation may disappear.
Insufficient intake of vitamins and nutrients. This can happen with a passion for weight loss diets.
Significant physical activity. They can lead to a decrease in the production of sex hormones.
Gynecological diseases. Inflammatory diseases in the ovaries lead to disruption of hormone production.
Diseases of the endocrine organs. For example, menstrual irregularities often occur with thyroid pathology.
Operations on the uterus. Often a delay in menstruation occurs after an abortion.
After spontaneous abortion. In some cases, curettage of the uterine cavity is additionally performed. After a miscarriage, the endometrium does not have time to recover, and more late onset menses.
Reception hormonal contraceptives. After their cancellation, menstruation may occur later than 28 days.

The average delay is most often up to 7 days. If your period is delayed by more than 14 days, you must be tested again to determine if you are pregnant.

If there are no periods for a long time, 6 months or more, they talk about amenorrhea. This phenomenon occurs in women during menopause, rarely after an abortion, when the basal layer of the endometrium was damaged. In any case, if the normal menstrual cycle is disrupted, you should consult a gynecologist. This will allow timely detection of the disease and begin its treatment.

The endometrium of the proliferative type is an intensive growth of the mucous uterine layer, occurring against the background of hyperplastic processes caused by excessive division of the cellular structures of the endometrium. With this pathology, gynecological diseases develop and reproductive function is disrupted. When faced with the concept of proliferative endometrium, it is necessary to understand what this means.

Endometrium - what is it? This term refers to the mucous layer lining the inner uterine surface. This layer is complex structural structure, which includes the following fragments:

glandular epithelial layer;
main substance;
stroma;
blood vessels.

The endometrium performs important functions in the female body. It is the mucous uterine layer that is responsible for the attachment of the fertilized egg and the onset of a successful pregnancy. After conception, the endometrial blood vessels provide the fetus with oxygen and essential nutrients.

Proliferation of the endometrium promotes the growth of the vascular bed for normal blood supply to the embryo and the formation of the placenta. During the menstrual cycle, a number of cyclic changes occur in the uterus, divided into the following successive stages:

Endometrium in the proliferation phase - characterized by intensive growth due to the proliferation of cellular structures through their active division. In the proliferation phase, the endometrium grows, which can be either a completely normal physiological phenomenon, part of the menstrual cycle, or a sign of dangerous pathological processes.
Secretion phase - at this stage, the endometrial layer is prepared for the menstrual phase.
Menstrual phase, endometrial desquamation - desquamation, rejection of the overgrown endometrial layer and its removal from the body with menstrual blood.

To adequately assess the cyclic changes of the endometrium and the extent to which its condition corresponds to the norm, it is necessary to take into account factors such as the duration of the menstrual cycle, the stages of proliferation and the secretive period, the presence or absence of dysfunctional uterine bleeding.

Phases of endometrial proliferation

The process of endometrial proliferation includes several successive stages, which corresponds to the concept of normality. The absence of one of the phases or failures in its course may mean the development of a pathological process. The entire period takes two weeks. During this cycle, follicles mature, stimulating the secretion of the hormone estrogen, under the influence of which the endometrial uterine layer grows.

The following stages of the proliferation phase are distinguished:

Early - lasts from 1 to 7 days of the menstrual cycle. At the early stage of the phase, the uterine mucosa changes. Epithelial cells are present on the endometrium. Blood arteries practically do not twist, and stromal cells have a specific shape that resembles a spindle.
The middle phase is a short phase, occurring between the 8th and 10th days of the menstrual cycle. The endometrial layer is characterized by the formation of certain cellular structures formed during indirect division.
The late stage lasts from 11 to 14 days of the cycle. The endometrium is covered with convoluted glands, the epithelium is multilayered, the cell nuclei are round in shape and large in size.

The stages listed above must meet the established norm criteria, and they are also inextricably linked with the secretory phase.

Phases of endometrial secretion

The secretory endometrium is dense and smooth. Secretory transformation of the endometrium begins immediately after completion of the proliferation stage.

Experts distinguish the following stages of secretion of the endometrial layer:

Early stage - observed from 15 to 18 days of the menstrual cycle. At this stage, secretion is very weakly expressed, the process is just beginning to develop.
The middle stage of the secretion phase occurs from 21 to 23 days of the cycle. This phase is characterized by increased secretion. A slight suppression of the process is noted only at the end of the stage.
Late - for the late stage of the secretion phase, suppression of secretory function is typical, which reaches its peak at the onset of menstruation itself, after which the process of reverse development of the endometrial uterine layer begins. The late phase is observed in the period from 24-28 days of the menstrual cycle.

Proliferative diseases

Proliferative endometrial diseases - what does this mean? Typically, the secretory type endometrium poses virtually no threats to a woman’s health. But the mucous uterine layer during the proliferative phase grows intensively under the influence of certain hormones. This condition carries potential danger in terms of the development of diseases caused by pathological, increased division of cellular structures. The risks of developing tumors, both benign and malignant, increase. Among the main pathologies of the proliferative type, doctors identify the following:

Hyperplasia- pathological proliferation of the uterine endometrial layer.

This disease is manifested by such clinical signs as:

menstrual irregularities,
uterine bleeding,
pain syndrome.

With hyperplasia, the reverse development of the endometrium is disrupted, the risks of infertility increase, reproductive dysfunction and anemia develop (against the background of heavy blood loss). The likelihood of malignant degeneration of endometrial tissue and the development of cancer also increases significantly.

Endometritis- inflammatory processes localized in the area of the mucous uterine endometrial layer.

This pathology manifests itself:

uterine bleeding,
heavy, painful menstruation,
vaginal discharge of a purulent-bloody nature,
aching painful sensations,localized in the lower abdomen,
painful intimate contacts.

Endometritis also negatively affects the reproductive functions of the female body, provoking the development of complications such as problems with conception, placental insufficiency, the threat of miscarriages and spontaneous termination of pregnancy in the early stages.

Uterine cancer- one of the most dangerous pathologies developing in the proliferative period of the cycle.

To the greatest extent given malignant disease Patients over 50 years of age are susceptible. The disease manifests itself as active exophytic growth simultaneously with concomitant infiltrating germination into muscle tissue. The danger of this type of oncology lies in its practically asymptomatic course, especially in the early stages of the pathological process.

The first clinical sign is leucorrhoea - vaginal discharge of a mucous nature, but, unfortunately, most women do not pay special attention to this.

Clinical symptoms such as:

uterine bleeding,
pain localized in the lower abdomen,
increased urge to urinate,
bloody vaginal discharge,
general weakness and increased fatigue.

Doctors note that most proliferative diseases develop against the background of hormonal and gynecological disorders. The main provoking factors include endocrine disorders, diabetes mellitus, uterine fibroids, endometriosis, hypertension, and excess body weight.

In the high-risk group, gynecologists include women who have undergone abortions, miscarriages, curettage, surgical interventions on the organs of the reproductive system, and who abuse hormonal contraceptives.

For warning and timely detection For such diseases, you need to monitor your health, and be examined by a gynecologist at least 2 times a year for the purpose of prevention.

The danger of suppressing proliferation

Inhibition of proliferative processes in the endometrial layer is a fairly common phenomenon, characteristic of the menopause and the decline of ovarian functions.

In patients of reproductive age, this pathology is fraught with the development of hypoplasia and dysmenorrhea. During processes of a hypoplastic nature, thinning of the mucous uterine layer occurs, as a result of which the fertilized egg cannot attach normally to the wall of the uterus, and pregnancy does not occur. The disease develops against the background of hormonal disorders and requires adequate, timely medical care.

Proliferative endometrium - a growing mucous uterine layer, can be a manifestation of the norm or a sign of dangerous pathologies. Proliferation is characteristic of the female body. During menstruation, the endometrial layer is shed, after which it is gradually restored through active cell division.

For patients with reproductive disorders, it is important to take into account the stage of endometrial development when conducting diagnostic examinations, since different periods indicators may differ significantly.

Early stage of the proliferation phase. In this phase of the menstrual cycle, the mucous membrane can be traced in the form of a narrow echo-positive strip (“traces of the endometrium”) of a homogeneous structure, 2-3 mm thick, located centrally.

Colpocytology. The cells are large, light-colored, with medium-sized nuclei. Moderate folding of cell edges. The number of eosinophilic and basophilic cells is approximately the same. Cells are placed in groups. There are few leukocytes.

Endometrial histology. The surface of the mucous membrane is covered with flattened columnar epithelium, which has a cubic shape. The endometrium is thin, there is no division of the functional layer into zones. The glands look like straight or somewhat winding tubes with a narrow lumen. In cross sections they have a round or oval shape. The epithelium of the glandular crypts is prismatic, the nuclei are oval, located at the base, and stain well. The cytoplasm is basophilic, homogeneous. The apical edge of the epithelial cells is smooth and clearly defined. On its surface, using electron microscopy, long microvilli are identified, which contribute to an increase in the surface of the cell. The stroma consists of spindle-shaped or stellate reticular cells with delicate processes. There is little cytoplasm. It is barely noticeable around the nuclei. In stromal cells, as in epithelial cells, single mitoses appear.

Hysteroscopy. In this phase of the menstrual cycle (up to the 7th day of the cycle), the endometrium is thin, smooth, pale pink in color, small hemorrhages are visible in some areas, and isolated areas of the endometrium are visible in a pale pink color that have not been rejected. The eyes of the fallopian tubes are clearly visible.

Middle proliferation phase. The middle stage of the proliferation phase lasts from 4-5 to 8-9 days after menstruation. The thickness of the endometrium continues to increase to 6-7 mm, its structure is homogeneous or with a zone increased density in the center there is a zone of contact between the functional layers of the upper and lower walls.

Colpocytology. A large number of eosinophilic cells (up to 60%). Cells are placed scatteredly. There are few leukocytes.

Endometrial histology. The endometrium is thin, there is no separation of the functional layer. The surface of the mucous membrane is covered with high prismatic epithelium. The glands are somewhat tortuous. The nuclei of epithelial cells are locally located on different levels, numerous mitoses are observed in them. Compared to the early phase of proliferation, the nuclei are enlarged, less intensely colored, and some of them contain small nucleoli. From the 8th day of the menstrual cycle, a layer containing acidic mucoids forms on the apical surface of epithelial cells. Alkaline phosphatase activity increases. The stroma is swollen, loosened, in connective tissues a narrow strip of cytoplasm is visible. The number of mitoses increases. The stromal vessels are single, with thin walls.

Hysteroscopy. In the middle stage of the proliferation phase, the endometrium gradually thickens, becomes pale pink, and no vessels are visible.

Late stage of proliferation. In the late stage of the proliferation phase (lasts approximately 3 days), the thickness of the functional layer reaches 8-9 mm, the shape of the endometrium is usually teardrop-shaped, the central echo-positive line remains unchanged throughout the first phase of the menstrual cycle. Against a general echo-negative background, it is possible to distinguish short, very narrow echo-positive layers of low and medium density, which reflect the delicate fibrous structure of the endometrium.

Colpocytology. The smear contains predominantly eosinophilic superficial cells (70%), few basophilic ones. In the cytoplasm of eosinophilic cells there is granularity, the nuclei are small and pyknotic. There are few leukocytes. Characterized by a large amount of mucus.

Endometrial histology. There is some thickening of the functional layer, but there is no division into zones. The surface of the endometrium is covered with tall columnar epithelium. The glands are more tortuous, sometimes corkscrew-like. Their lumen is somewhat expanded, the epithelium of the glands is high, prismatic. The apical edges of the cells are smooth and distinct. As a result of intensive division and increase in the number of epithelial cells, the nuclei are at different levels. They are enlarged, still oval, and contain small nucleoli. Closer to the 14th day of the menstrual cycle, you can see a large number of cells containing glycogen. The activity of alkaline phosphatase in the epithelium of the glands reaches its highest level. The nuclei of connective tissue cells are larger, rounded, less intensely colored, and an even more noticeable halo of cytoplasm appears around them. The spiral arteries that grow from the basal layer at this time already reach the surface of the endometrium. They are still slightly tortuous. Under the microscope, only one or two adjacent peripheral vessels are determined.

Psteroscopy. In the late phase of proliferation, certain areas of the endometrium appear as thickened folds. It is important to note that if menstrual cycle proceeds normally, then in the proliferation phase the endometrium can have different thicknesses, depending on the location - thickened in the days and posterior wall of the uterus, thinner on the anterior wall and in the lower third part of the uterine body.

Early stage of the secretion phase. In this phase of the menstrual cycle (2-4 days after ovulation), the thickness of the endometrium reaches 10-13 mm. After ovulation, due to secretory changes (the result of the production of progesterone by the menstrual corpus luteum of the ovary), the structure of the endometrium becomes homogeneous again until the onset of menstruation. During this period, the thickness of the endometrium increases faster than in the first phase (by 3-5 mm).

Colpocytology. Characteristic deformed cells are wavy, with curved edges, as if folded in half; the cells are located in dense clusters, layers. The cell nuclei are small and pyknotic. The number of basophilic cells increases.

Histology of the endometrium. The thickness of the endometrium increases moderately compared to the proliferation phase. The glands become more tortuous, their lumen is expanded. The most characteristic sign of the secretion phase, in particular its early stage, is the appearance of subnuclear vacuoles in the epithelium of the glands. Glycogen granules become large, cell nuclei move from the basal to the central sections (indicating that ovulation has occurred). The nuclei are pushed aside by vacuoles into central departments the cells are initially at different levels, but on day 3 after ovulation (day 17 of the cycle), the nuclei, which lie above large vacuoles, are located at the same level. On the 18th day of the cycle, in some cells glycogen granules move to the apical sections of the cells, as if bypassing the nucleus. As a result of this, the nuclei again descend down to the base of the cell, and glycogen granules are located above them, which are located in the apical parts of the cells. The kernels are more rounded. There are no mitoses in them. The cytoplasm of the cells is basophilic. Acid mucoids continue to appear in their apical sections, while alkaline phosphatase activity decreases. The endometrial stroma is slightly swollen. Spiral arteries are tortuous.

Hysteroscopy. In this phase of the menstrual cycle, the endometrium is swollen, thickened, and forms folds, especially in the upper third of the uterine body. The color of the endometrium becomes yellowish.

Middle stage of secretion phase. Duration middle stage the second phase is from 4 to 6-7 days, which corresponds to days 18-24 of the menstrual cycle. During this period, the greatest severity of secretory changes in the endometrium is observed. Echographically, this is manifested by a thickening of the endometrium by another 1-2 mm, the diameter of which reaches 12-15 mm, and its even greater density. At the border of the endometrium and myometrium, a rejection zone begins to form in the form of an echo-negative, clearly defined rim, the severity of which reaches its maximum before menstruation.

Colpocytology. Characteristic folding of cells, curved edges, accumulation of cells in groups, the number of cells with pyknotic nuclei decreases. The number of leukocytes increases moderately.

Endometrial histology. The functional layer becomes higher. It is clearly divided into deep and superficial parts. The deep layer is spongy. It contains highly developed glands and a small amount of stroma. The surface layer is compact, it contains less tortuous glands and many connective tissue cells. On the 19th day of the menstrual cycle, most of the nuclei are located in the basal part of the epithelial cells. All kernels are round and light. The apical section of the epithelial cells becomes dome-shaped, glycogen accumulates here and begins to be released into the lumen of the glands by apocrine secretion. The lumen of the glands expands, their walls gradually become more folded. The epithelium of the glands is single-row, with basally located nuclei. As a result of intense secretion, the cells become low, their apical edges are vaguely expressed, as if with teeth. Alkaline phosphatase completely disappears. In the lumen of the glands there is a secret that contains glycogen and acidic mucopolysaccharides. On day 23, the secretion of the glands ends. A perivascular decidual reaction of the endometrial stroma appears, then the decidual reaction becomes diffuse, especially in superficial sections compact layer. The connective tissue cells of the compact layer around the vessels become large, round and polygonal in shape. Glycogen appears in their cytoplasm. Islands of predecidual cells are formed. A reliable indicator of the middle stage of the secretion phase, which indicates a high concentration of progesterone, are changes in the spiral arteries. Spiral arteries are sharply tortuous, form “skeins”, they can be found not only in the spongy, but also in the superficial parts of the compact layer. Until the 23rd day of the menstrual cycle, the tangles of the spiral arteries are most clearly expressed. Insufficient development of “coils” of spiral arteries in the endometrium of the secretory phase is characterized as a manifestation of weak function of the corpus luteum and insufficient preparation of the endometrium for implantation. The structure of the endometrium of the secretory phase, the middle stage (days 22-23 of the cycle), can be observed with prolonged and increased hormonal function of the menstrual corpus luteum - persistence of the corpus luteum, and in the early stages of pregnancy - during the first days after implantation, with intrauterine pregnancy outside the implantation zone ; with progressive ectopic pregnancy evenly in all parts of the mucous membrane of the uterine body.

Hysteroscopy. In the middle phase of the secretion stage, the hysteroscopic picture of the endometrium does not differ significantly from that in the early phase of this stage. Often, the folds of the endometrium acquire a polypoid shape. If the distal end of the hysteroscope is placed tightly to the endometrium, the glandular ducts can be seen.

Late stage of the secretion phase. Late stage of the second phase of the menstrual cycle (lasts 3-4 days). In the endometrium, pronounced trophic disorders occur due to a decrease in the concentration of progesterone. Echographic changes in the endometrium associated with polymorphic vascular reactions in the form of hyperemia, spasms and thrombosis with the development of hemorrhages, necrosis and other dystrophic changes, a slight heterogeneity (spotting) of the mucosa appears due to the appearance of small areas (dark "spots" - zones of vascular disorders), becomes clearly visible the rim of the rejection zone (2-4 mm), and the three-layer structure of the mucosa characteristic of the proliferative phase is transformed into a homogeneous tissue. There are cases when echo-negative zones of the endometrial thickness in the preovulatory period are mistakenly assessed by ultrasound as pathological changes.

Colpocytology. The cells are large, pale-colored, foamy, basophilic, without inclusions in the cytoplasm, the contours of the cells are indistinct and blurry.

Endometrial histology. The folding of the gland walls is enhanced, it has a dust-like shape on the longitudinal sections, and a star-like shape on the transverse sections. The nuclei of some epithelial gland cells are pyknotic. The stroma of the functional layer is wrinkled. Predecidual cells are close together and located around the spiral vessels diffusely throughout the compact layer. Among the predecidual cells there are small cells with dark nuclei - endometrial granular cells, which are transformed from connective tissue cells. On the 26-27th day of the menstrual cycle, in the superficial areas of the compact layer, lacunar expansion of capillaries into the stroma is observed. In the premenstrual period, spiralization becomes so pronounced that blood circulation slows down and stasis and thrombosis occur. A day before the onset of menstrual bleeding, a state of the endometrium occurs, which Schroeder called “anatomical menstruation.” At this time, you can find not only dilated and congested blood vessels, but also spasm and thrombosis, as well as small hemorrhages, edema, and leukocyte infiltration of the stroma.

Psteroscopy. In the late phase of the secretion stage, the endometrium acquires a reddish tint. Due to the pronounced thickening and folding of the mucosa, the eyes of the fallopian tubes cannot always be seen. Just before menstruation, the appearance of the endometrium can be mistakenly interpreted as endometrial pathology (polypoid hyperplasia). Therefore, the time of hysteroscopy must be recorded for the pathologist.

Bleeding phase (desquamation). During menstrual bleeding, due to a violation of the integrity of the endometrium due to its rejection, the presence of hemorrhages and blood clots in the uterine cavity, the echographic picture changes during the days of menstruation as parts of the endometrium with menstrual blood are discharged. At the beginning of menstruation, the rejection zone is still visible, although not entirely. The structure of the endometrium is heterogeneous. Gradually, the distance between the walls of the uterus decreases and before the end of menstruation they “close” with each other.

Colpocytology. The smear contains foamy basophilic cells with large nuclei. A large number of erythrocytes, leukocytes, endometrial cells, and histocytes are also found.

Endometrial histology(28-29 days). Tissue necrosis and autolysis develop. This process begins from the superficial layers of the endometrium and is flammable in nature. As a result of vasodilation, which occurs after a prolonged spasm, a significant amount of blood enters the endometrial tissue. This leads to rupture of blood vessels and detachment of necrotic sections of the functional layer of the endometrium.

Morphological signs characteristic of the endometrium of the menstrual phase are: the presence of tissue permeated with hemorrhages, areas of necrosis, leukocyte infiltration, a partially preserved area of the endometrium, as well as tangles of spiral arteries.

Hysteroscopy. In the first 2-3 days of menstruation, the uterine cavity is filled with a large number of endometrial scraps from pale pink to dark purple, especially in the upper third. At the bottom and middle third The endometrium of the uterine cavity is thin, pale pink, with pinpoint hemorrhages and areas of old hemorrhages. If the menstrual cycle was full, then already before the second day of menstruation there is almost complete rejection of the uterine mucosa, only in certain areas of it small fragments of the mucous membrane are detected.

Regeneration(3-4 days of the cycle). After rejection of the necrotic functional layer, regeneration of the endometrium from the tissues of the basal layer is observed. Epithelization of the wound surface occurs due to the marginal glands of the basal layer, from which epithelial cells move in all directions onto the wound surface and close the defect. Under normal conditions menstrual bleeding under conditions of a normal two-phase cycle, the entire wound surface is epithelialized on the 4th day of the cycle.

Hysteroscopy. During the regeneration stage, against a pink background with areas of hyperemia of the mucosa, small hemorrhages are visible in some areas, and isolated areas of the endometrium of a pale pink color may be encountered. As the endometrium regenerates, areas of hyperemia disappear, changing color to pale pink. The angles of the uterus are clearly visible.

Cyclic changes in the lining of the uterus (endometrium). Proliferation phase. secretion phase. Menstruation.

Cyclic changes in the lining of the uterus (endometrium). The endometrium consists of the following layers.

1. Basal layer. which is not rejected during menstruation. From its cells during the menstrual cycle, a layer of the endometrium is formed.

2. Surface layer. consisting of compact epithelial cells that line the uterine cavity.

3. Intermediate, or spongy, layer .

Rice. 2.15. Cyclic changes in the organs of the reproductive system during the menstrual cycle.

I - gonadotropic regulation of ovarian function;

PDH - anterior pituitary gland;

III - cyclic changes in the endometrium;

IV - cytology of the vaginal epithelium;

V - basal temperature;

VI - tension of cervical mucus.

The last two layers constitute the functional layer, which undergoes major cyclic changes during the menstrual cycle and is shed during menstruation.

In phase 1 of the menstrual cycle, the endometrium is thin layer, consisting of glands and stroma. The following main phases of changes in the endometrium during the cycle are distinguished;

1) proliferation phase ;

2) secretion phase ;

3) menstruation .

Proliferation phase. As the secretion of estradiol by growing ovarian follicles increases, the endometrium undergoes proliferative changes. There is an active proliferation of cells in the basal layer. A new superficial loose layer with elongated tubular glands is formed. This layer quickly thickens 4-5 times. Tubular glands, lined with columnar epithelium, elongate.

Secretion phase. In the luteal phase of the ovarian cycle, under the influence of progesterone, the tortuosity of the glands increases, and their lumen gradually expands. The stromal cells, increasing in volume, move closer to each other. The secretion of the glands increases. In the lumen of the glands are found copious amounts secret. Depending on the intensity of secretion, the glands either remain highly convoluted or take on a sawtooth shape. There is increased vascularization of the stroma. There are early, middle and late phases of secretion.

Menstruation. This is the rejection of the functional layer of the endometrium. The subtle mechanisms underlying the occurrence and process of menstruation are unknown. It has been established that the endocrine basis for the onset of menstruation is a pronounced decrease in the levels of progesterone and estradiol due to regression of the corpus luteum.

There are the following main local mechanisms involved in menstruation:

1) change in the tone of spiral arterioles;

2) changes in the mechanisms of hemostasis in the uterus;

3) changes in the lysosomal function of endometrial cells;

4) regeneration of the endometrium.

Rice. 2.13. The content of hormones in blood plasma during the menstrual cycle.

It is established that the beginning menses preceded by intense narrowing of the spiral arterioles, leading to ischemia and desquamation of the endometrium.

During menstrual cycle the content of lysosomes in endometrial cells changes. Lysosomes contain enzymes, some of which are involved in the synthesis of prostaglandins. In response to a decrease in progesterone levels, the secretion of these enzymes increases.

Endometrial regeneration observed from the very beginning of menstruation. By the end of the 24th hour of menstruation, 2/3 of the functional layer of the endometrium is rejected. The basal layer contains epithelial stromal cells, which are the basis for endometrial regeneration, which is usually completely completed by the 5th Day of the cycle. In parallel, angiogenesis is completed with the restoration of the integrity of ruptured arterioles, veins and capillaries.

Changes in the ovaries and uterus occur under the influence of the two-phase activity of the systems regulating menstrual function: the cerebral cortex, the hypothalamus, the pituitary gland. Thus, there are 5 main links in the female reproductive system: cerebral cortex, hypothalamus, pituitary gland, ovary, uterus (Fig. 2.14). The interconnection of all parts of the reproductive system is ensured by the presence in them of receptors for both sex and gonadotropic hormones.

Normal endometrial histology

Cyclic changes in the endometrium under the influence of steroid hormones

Mucous membrane of the fundus and body of the uterus morphologically the same type. In women of the reproductive period it consists of two layers:

Basal layer 1 – 1.5 cm thick, located on the inner layer of the myometrium, the reaction to hormonal effects is weak and inconsistent. The stroma is dense, consists of connective tissue cells, and is rich in argyrophilic and thin collagen fibers.

The endometrial glands are narrow, the epithelium of the glands is cylindrical, single-row, the nuclei are oval, intensely stained. The height varies depending on the functional state of the endometrium from 6 mm after menstruation to 20 mm at the end of the proliferation phase; The shape of the cells, the location of the nucleus in them, the outline of the apical edge, etc. also change.

Among the columnar epithelial cells, large vesicular cells adjacent to the basement membrane can be found. These are the so-called clear cells or “vesicle cells,” which are immature cells of the ciliated epithelium. These cells can be found in all phases of the menstrual cycle, but their greatest number is observed in the middle of the cycle. The appearance of these cells is stimulated by estrogens. In the atrophic endometrium, clear cells are never detected. There are also gland epithelial cells in a state of mitosis - the early stage of prophase and wandering cells (histiocytes and large lymphocytes) penetrating through the basement membrane into the epithelium.

In the first half of the cycle, additional elements may be found in the basal layer - true lymphatic follicles, which differ from inflammatory infiltrates by the presence of a germinal center of the follicle and the absence of focal perivascular and/or periglandular, diffuse infiltrate of lymphocytes and plasma cells, other signs of inflammation, as well as clinical manifestations the last one. In children's and senile endometrium, lymphatic follicles are absent. The vessels of the basal layer are not sensitive to hormones and do not undergo cyclic transformations.

Functional layer. The thickness varies depending on the day of the menstrual cycle: from 1 mm at the beginning of the proliferation phase, to 8 mm at the end of the secretion phase. It is highly sensitive to sex steroids, under the influence of which it undergoes morphofunctional and structural changes throughout each menstrual cycle.

The mesh-fibrous structures of the stroma of the functional layer at the beginning of the proliferation phase until the 8th day of the cycle contain single delicate argyrophilic fibers; before ovulation, their number quickly increases and they become thicker. In the secretion phase, under the influence of endometrial edema, the fibers move apart, but remain densely located around the glands and vessels.

Under normal conditions, gland branching does not occur. In the secretion phase, additional elements are most clearly indicated in the functional layer - a deep spongy layer, where the glands are more closely located, and a superficial - compact one, in which the cytogenic stroma predominates.

The surface epithelium in the proliferation phase is morphologically and functionally similar to the epithelium of the glands. However, with the beginning of the secretion stage, biochemical changes occur in it that cause easier adhesion of the blastocyst to the endometrium and subsequent implantation.

At the beginning of the menstrual cycle, the stromal cells are spindle-shaped, indifferent, and there is very little cytoplasm. By the end of the secretion phase, part of the cells, under the influence of the hormone of the corpus luteum of menstruation, increases and changes into predecidual (the most correct name), pseudodecidual, decidua-like. Cells that develop under the influence of hormones of the corpus luteum of pregnancy are called decidual.

The second part decreases, and endometrial granular cells containing high molecular weight peptides like relaxin are formed from them. In addition, single lymphocytes (in the absence of inflammation), histiocytes, mast cells (more in the secretion phase) are located here.

The vessels of the functional layer are highly sensitive to hormones and undergo cyclic transformations. The layer has capillaries, which in the premenstrual period form sinusoids and spiral arteries; in the proliferation phase, they are poorly tortuous and do not reach the surface of the endometrium. In the secretion phase, they lengthen (the height of the endometrium to the length of the spiral vessel is 1:15), become more convoluted and spiral into balls. The greatest development is achieved under the influence of hormones of the corpus luteum of pregnancy.

If the functional layer is not rejected and the endometrial tissue undergoes regressive changes, then the tangles of spiral vessels remain even after the disappearance of other signs of the luteal effect. Their presence is a valuable morphological sign of the endometrium, which is in a state of complete reverse development from the secretory phase of the cycle, as well as after a violation of pregnancy. early date– uterine or ectopic.

Innervation. The use of modern histochemical methods for detecting catecholamines and cholinesterase has made it possible to detect nerve fibers in the basal and functional layers of the endometrium that are distributed throughout the endometrium, accompany the vessels, but do not reach the surface epithelium and glandular epithelium. The number of fibers and the content of mediators in them changes throughout the cycle: in the endometrium, the proliferation phase is dominated by adrenergic influences, and in the secretion phase, cholinergic influences predominate.

Endometrium of the uterine isthmus reacts to ovarian hormones much weaker and later than the endometrium of the uterine body, and sometimes does not respond at all. The mucous membrane of the isthmus has a few glands that run in an oblique direction and often form cyst-like extensions. The epithelium of the glands is low cylindrical, elongated dark nuclei almost completely fill the cell. Mucus is secreted only into the lumen of the glands, but is not contained intracellularly, which is typical for the cervical epithelium. The stroma is dense. In the secretory phase of the cycle, the stroma is slightly loosened, and sometimes a weakly expressed decidual transformation is observed in it. During menstruation, only the superficial epithelium of the mucous membrane is rejected.

In underdeveloped uteruses, the mucous membrane, which has the structural and functional characteristics of the isthmic part of the uterus, lines the walls of the lower and middle parts body of the uterus. In some underdeveloped uteruses, only in its upper third is normal endometrium found, capable of responding according to the phases of the cycle. Such endometrial abnormalities are observed mainly in hypoplastic and infantile uteruses, as well as in uterus arcuatus and uterus duplex.

Clinical and diagnostic value: localization of the endometrium of the isthmic type in the body of the uterus is manifested by the sterility of the woman. In the event of pregnancy, implantation in a defective endometrium leads to deep ingrowth of villi into the underlying myometrium and to the occurrence of one of the most severe obstetric pathologies - placenta increta.

The mucous membrane of the cervical canal. Has no glands. The surface is lined with a single-row high cylindrical epithelium with basally located small hyperchromic nuclei. Epithelial cells intensively secrete intracellular mucus, which impregnates the cytoplasm - the difference between the epithelium of the cervical canal and the epithelium of the isthmus and body of the uterus. Under the cylindrical cervical epithelium there may be small rounded cells - reserve (subepithelial) cells. These cells can transform into both cylindrical cervical epithelium and stratified squamous, which is observed in endometrial hyperplasia and cancer.

In the proliferation phase, the nuclei of the cylindrical epithelium are located basally, in the secretion phase - mainly in the central sections. Also, during the phase with secretion, the number of reserve cells increases.

The unchanged dense mucosa of the cervical canal is not captured during curettage. Pieces of loosened mucous membrane come across only with its inflammatory and hyperplastic changes. Scrapings very often reveal polyps of the cervical canal crushed by a curette or not damaged by it.

Morphological and functional changes in the endometrium

during the ovulatory menstrual cycle.

The menstrual cycle refers to the period of time from the 1st day of the previous menstruation to the 1st day of the next. A woman's menstrual cycle is determined by rhythmically repeating changes in the ovaries (ovarian cycle) and in the uterus (uterine cycle). The uterine cycle is directly dependent on the ovaries and is characterized by regular changes in the endometrium.

At the beginning of each menstrual cycle, several follicles simultaneously mature in both ovaries, but the process of maturation of one of them proceeds somewhat more intensively. Such a follicle moves to the surface of the ovary. When fully mature, the thinned wall of the follicle breaks, the egg is ejected outside the ovary and enters the funnel of the tube. This process of releasing an egg is called ovulation. After ovulation, usually occurring on days 13-16 of the menstrual cycle, the follicle differentiates into the corpus luteum. Its cavity collapses, granulosa cells turn into luteal cells.

In the first half of the menstrual cycle, the ovary produces an increasing amount of predominantly estrogenic hormones. Under their influence, the proliferation of all tissue elements of the functional layer of the endometrium occurs - the proliferation phase, the folliculin phase. It ends around day 14 in a 28-day menstrual cycle. At this time, ovulation occurs in the ovary and the subsequent formation of the menstrual corpus luteum. The corpus luteum secretes a large amount of progesterone, under the influence of which morphological and functional changes occur in the endometrium prepared by estrogens, which are characteristic of the secretion phase - the luteal phase. It is characterized by the presence of secretory function of the glands, predecidual reaction of the stroma and the formation of spirally convoluted vessels. The transformation of the endometrium of the proliferation phase into the secretion phase is called differentiation or transformation.

If fertilization of the egg and implantation of the blastocyst did not occur, then at the end of the menstrual cycle, the menstrual corpus luteum regresses and dies, which leads to a drop in the titer of ovarian hormones that support the blood supply of the endometrium. In this regard, angiospasm, hypoxia of endometrial tissues, necrosis and menstrual rejection of the mucous membrane occur.

Classification of the phases of the menstrual cycle (according to Witt, 1963)

This classification most closely matches modern ideas about changes in the endometrium in certain phases of the cycle. It can be used in practical work.

Proliferation phase
Early stage – 5-7 days
Middle stage – 8-10 days
Late stage – 10-14 days
Secretion phase
Early stage (first signs of secretory transformations) – 15-18 days
Middle stage (most pronounced secretion) – 19-23 days
Late stage (beginning regression) – 24-25 days
Regression accompanied by ischemia – 26-27 days
Bleeding phase (menstruation)
Desquamation – 28-2 days
Regeneration – 3-4 days

When assessing the changes occurring in the endometrium according to the days of the menstrual cycle, it is necessary to take into account: the duration of the cycle in a given woman (except for the most common 28-day cycle, there are 21-, 30- and 35-day cycles) and the fact that ovulation during a normal menstrual cycle may occur between days 13 and 16 of the cycle. Therefore, depending on the time of ovulation, the structure of the endometrium at one or another stage of the secretion phase changes slightly within 2-3 days.

Proliferation phase

Lasts on average 14 days. It can be lengthened or shortened within about 3 days. Changes occur in the endometrium, occurring mainly under the influence of an ever-increasing amount of estrogenic hormones that are produced by the growing and maturing follicle.

Early phase of proliferation (5 – 7 days).
The glands are straight or slightly curved with a round or oval outline in cross section. The epithelium of the glands is single-row, low, cylindrical. The nuclei are oval, located at the base of the cell. The cytoplasm is basophilic, homogeneous. Individual mitoses.

Stroma. Fusiform or stellate reticular cells to the tender shoots. There is very little cytoplasm, the nuclei are large, they fill almost the entire cell. Random mitoses.
The middle phase of proliferation (8 - 10 days).
The glands are elongated, slightly convoluted. The nuclei are located in places on various levels, more enlarged, less stained, some have small nucleoli. There are many mitoses in the nuclei.

The stroma is swollen and loosened. In cells, a narrow border of the cytoplasm is more distinguishable. The number of mitoses increases.
Late phase of proliferation (11 - 14 days)
The glands are significantly convoluted, corkscrew-shaped, the lumen is dilated. The nuclei of the epithelium of the glands are at different levels, enlarged, contain nucleoli. The epithelium is multirowed, but not multilayered! In single epithelial cells there are small subnuclear vacuoles (they contain glycogen).

The stroma is juicy, the nuclei of connective tissue cells are larger and rounded. In cells, the cytoplasm is even more visible. Few mitoses. The spiral arteries growing from the basal layer reach the surface of the endometrium are slightly tortuous.

Diagnostic value. Endometrial structures corresponding to the proliferation phase, observed under physiological conditions in the first half of the 2-phase menstrual cycle, may reflect hormonal disorders if they are detected in the second half of the cycle (this may indicate an anovulatory, single-phase cycle or an abnormal, prolonged proliferation phase with delayed ovulation in a two-phase cycle), with glandular endometrial hyperplasia in various parts of the hyperplastic uterine mucosa and with dysfunctional uterine bleeding in women at any age.

Secretion phase

The physiological phase of secretion, directly related to the hormonal activity of the menstrual corpus luteum, lasts 14 ± 1 days. Shortening or lengthening the secretion phase by more than 2 days in women during the reproductive period is considered functionally pathological. Such cycles turn out to be sterile.

Biphasic cycles, in which the secretory phase ranges from 9 to 16 days, are often observed at the beginning and end of the reproductive period

The day of ovulation can be determined by changes in the endometrium, which consistently reflect first increasing and then decreasing function of the corpus luteum. During the 1st week of the secretion phase, the day of ovulation occurs is diagnosed by changes in the epithelium of the eelosis; in the 2nd week, this day can most accurately be determined by the state of the endometrial stromal cells.

Early stage (15-18 days)
On the 1st day after ovulation (15th day of the cycle), microscopic signs of the effect of progesterone on the endometrium are not yet detected. They appear only after 36–48 hours, i.e. on the 2nd day after ovulation (on the 16th day of the cycle).

The glands are more convoluted, their lumen is expanded; in the epithelium of the glands - subnuclear vacuoles containing glycogen - a characteristic feature of the early stage of the secretion phase. Subnuclear vacuoles in the epithelium of the glands after ovulation become much larger and are found in all epithelial cells. The nuclei, pushed aside by the vacuoles into the central sections of the cells, are initially at different levels, but on the 3rd day after ovulation (17th day of the cycle), the nuclei lying above the large vacuoles are located at the same level.

On the 4th day after ovulation (18th day of the cycle), in some cells the vacuoles partially move from the basal part past the nucleus to the apical part of the cell, where glycogen also moves. The nuclei again find themselves at different levels, descending to the basal part of the cells. The shape of the nuclei changes to a more round one. The cytoplasm of cells is basophilic. In the apical sections, acidic mucoids are detected, and the activity of alkaline phosphatase decreases. There are no mitoses in the epithelium of the glands.

The stroma is juicy and loose. At the beginning of the early stage of the secretion phase in surface layers In the mucous membrane, focal hemorrhages are sometimes observed that occurred during ovulation and are associated with a short-term decrease in estrogen levels.

Diagnostic value. The structure of the endometrium at the early stage of the secretion phase reflects hormonal disorders, if observed in the last days of the menstrual cycle - with a delayed onset of ovulation, during bleeding with shortened incomplete periods. two-phase cycles, during acyclic dysfunctional uterine bleeding. It has been noted that bleeding from the postovulatory endometrium is especially often observed in women during menopause.

Subnuclear vacuoles in the epithelium of the endometrial glands are not always a sign indicating that ovulation has occurred and the secretory function of the corpus luteum has begun. They may also occur:
under the influence of progesterone of the corpus luteum
in menopausal women as a result of the use of testosterone after preliminary preparation with estrogen hormones
in the glands of mixed hypoplastic endometrium with dysfunctional uterine bleeding in women of any age, including menopause. In such cases, the appearance of subnuclear vacuoles may be associated with adrenal hormones.
as a result non-hormonal treatment disorders of menstrual function, during novocaine blockade superior cervical sympathetic ganglia, electrical stimulation of the cervix, etc.

If the appearance of subnuclear vacuoles is not associated with ovulation, they are contained in some cells of individual glands or in a group of endometrial glands. The vacuoles themselves are often small.

The endometrium, in which subnuclear vacuolization is the result of ovulation and the function of the corpus luteum, is primarily characterized by the configuration of the glands: they are tortuous, dilated, usually of the same type and regularly distributed in the stroma. Vacuoles are large, have the same size, and are found in all glands and in every epithelial cell.

Middle stage of the secretion phase (19-23 days)
In the middle stage, under the influence of hormones of the corpus luteum, which reaches its highest function, secretory transformations of endometrial tissue are most pronounced. The functional layer becomes higher. It is clearly divided into deep and superficial. The deep layer contains highly developed glands and a small amount of stroma. The surface layer is compact; it contains less convoluted glands and many connective tissue cells.

In the glands on day 5 after ovulation (day 19 of the cycle), most of the nuclei are again located in the basal part of the epithelial cells. All nuclei are round, very light, vesicle-like (this type of nuclei is a characteristic feature that distinguishes the endometrium of the 5th day after ovulation from the endometrium of the 2nd day, when the epithelial nuclei are oval and darkly colored). The apical section of the epithelial cells becomes dome-shaped, glycogen accumulates here, moved from the basal sections of the cells and now begins to be released into the lumen of the glands by apocrine secretion.

On the 6th, 7th and 8th day after ovulation (20, 21, 22nd day of the cycle), the lumens of the glands expand, the walls become more folded. The epithelium of the glands is single-row, with basally located nuclei. As a result of intense secretion, the cells become low, their apical edges are vaguely defined, as if jagged. Alkaline phosphatase completely disappears. In the lumen of the glands there is a secret containing glycogen and acidic mucopolysaccharides. On the 9th day after ovulation (23rd day of the cycle), the secretion of the glands ends.

In the stroma on the 6th, 7th day after ovulation (20, 21st day of the cycle), a perivascular decidual reaction appears. The connective tissue cells of the compact layer around the vessels become larger and acquire rounded and polygonal shapes. Glycogen appears in their cytoplasm. Islands of predecidual cells are formed.

Later, the predecidual transformation of cells spreads more diffusely throughout the compact layer, mainly in its superficial parts. The degree of development of predecidual cells varies individually.

Vessels. The spiral arteries are sharply tortuous and form “tangles”. At this time, they are found both in the deep parts of the functional layer and in the superficial parts of the compact layer. The veins are dilated. The presence of convoluted spiral arteries in the functional layer of the endometrium is one of the most reliable signs determining the luteal effect.

From the 9th day after ovulation (23rd day of the cycle), stromal edema decreases, as a result of which the tangles of spiral arteries, as well as the surrounding predecidual cells, are more clearly visible.

During the middle stage of secretion, implantation of the blastocyst occurs. The best conditions for implantation are the structure and functional state endometrium on days 20-22 of the 28-day menstrual cycle.
Late stage of the secretion phase (24 – 27 days)
From the 10th day after ovulation (on the 24th day of the cycle), due to the onset of regression of the corpus luteum and a decrease in the concentration of hormones produced by it, the trophism of the endometrium is disrupted and degenerative changes gradually increase in it. On days 24-25 of the cycle, initial signs of regression are morphologically observed in the endometrium; on days 26-27 this process is accompanied by ischemia. In this case, first of all, the juiciness of the tissue decreases, which leads to wrinkling of the stroma of the functional layer. Its height during this period is 60-80% of the maximum height that was in the middle of the secretion phase. Due to tissue wrinkling, the folding of the glands increases; they acquire pronounced star-shaped outlines on transverse sections and sawtooth on longitudinal ones. The nuclei of some epithelial cellular glands are pyknotic.

Stroma. At the beginning of the late stage of the secretion phase, the predecidual cells come closer together and are more clearly defined not only around the spiral vessels, but also diffusely throughout the compact layer. Among the predecidual cells, endometrial granular cells are clearly visible. Long time these cells were mistaken for leukocytes, which began to infiltrate the compact layer several days before the onset of menstruation. However later research It has been established that leukocytes penetrate the endometrium immediately before menstruation, when the already altered vascular walls become sufficiently permeable.

From the granules of granular cells in the late stage of the secretion phase, relaxin is released, which promotes the melting of the argyrophilic fibers of the functional layer, thus preparing the menstrual rejection of the mucous membrane.

On days 26-27 of the cycle, lacunar expansion of capillaries and focal hemorrhages into the stroma are observed in the superficial layers of the compact layer. Due to the melting of the fibrous structures, areas of separation of the cells of the stroma and the epithelium of the glands appear.

The state of the endometrium, thus prepared for disintegration and rejection, is called “anatomical menstruation.” This condition of the endometrium is detected one day before the onset of clinical menstruation.

Bleeding phase

During menstruation, processes of desquamation and regeneration occur in the endometrium.

Desquamation (28-2nd day of the cycle).
It is generally accepted that in the implementation of menstruation important role play changes in the spiral arterioles. Before menstruation, due to the regression of the corpus luteum that occurred at the end of the secretion phase, and then its death and a sharp decline in hormones, structural regressive changes increase in the endometrial tissue: hypoxia and those circulatory disorders that were caused by prolonged spasm of the arteries (stasis, blood clots, fragility and permeability vascular wall, hemorrhage into the stroma, leukocyte infiltration). As a result, the twisting of the spiral arterioles becomes even more pronounced, blood circulation in them slows down, and then, after a long spasm, vasodilation occurs, as a result of which a significant amount of blood enters the endometrial tissue. This leads to the formation of small and then more extensive hemorrhages in the endometrium, rupture of blood vessels, and rejection - desquamation - of necrotic sections of the functional layer of the endometrium, i.e. to menstrual bleeding.

Causes of uterine bleeding during menstruation:
decline in the level of gestagens and estrogens in peripheral blood plasma
vascular changes, including increased permeability of vascular walls
circulatory disorders and concomitant destructive changes in the endometrium
release of relaxin by endometrial granulocytes and melting of argyrophilic fibers
leukocyte infiltration of the compact layer stroma
the occurrence of focal hemorrhages and necrosis
increased protein content and fibrinolytic enzymes in endometrial tissue

A morphological sign characteristic of the endometrium of the menstrual phase is the presence of collapsed stellate-shaped glands and tangles of spiral arteries in the disintegrating tissue riddled with hemorrhages. On the 1st day of menstruation, in the compact layer, among the areas of hemorrhage, separate groups of predecidual cells can still be distinguished. Menstrual blood also contains tiny particles of the endometrium that retain viability and the ability to implant. Direct evidence of this is the occurrence of cervical endometriosis when leaking menstrual blood enters the surface of granulation tissue after diathermocoagulation of the cervix.

Fibrinolysis of menstrual blood is caused by the rapid destruction of fibrinogen by enzymes released during the breakdown of the mucous membrane, which prevents the clotting of menstrual blood.

Diagnostic value. Morphological changes in the endometrium, beginning to desquamate, can be mistakenly taken for manifestations of endometritis developing during the secretory phase of the cycle. However, in acute endometritis, a thick leukocyte infiltrate of the stroma also destroys the glands: leukocytes, penetrating the epithelium, accumulate in the lumens of the glands. For chronic endometritis characterized by focal infiltrates consisting of lymphocytes and plasma cells.

Regeneration (3-4 days of the cycle).
During the menstrual phase, only individual sections of the functional layer of the endometrium are rejected (according to the observations of Prof. Vikhlyaeva). Even before the complete rejection of the functional layer of the endometrium (in the first three days of the menstrual cycle), epithelization of the wound surface of the basal layer has already begun. On the 4th day, epithelization of the wound surface ends. It is believed that epithelialization can occur by the proliferation of epithelium from each gland of the basal layer of the endometrium, or by the proliferation of glandular epithelium from areas of the functional layer preserved from the previous menstrual cycle. Simultaneously with the epithelization of the surface of the basal layer, the development of the functional layer of the endometrium begins, its thickening occurs due to the coordinated growth of all elements of the basal layer, and the mucous membrane of the uterine body enters an early stage of proliferation.

The division of the menstrual cycle into proliferative and secretory phases is arbitrary, because a high level of proliferation remains in the epithelium of the glands and stroma in the early phase of secretion. Only the appearance of progesterone in the blood high concentration by the 4th day after ovulation leads to a sharp suppression of proliferative activity in the endometrium.

Violation of the relationship between estradiol and progesterone leads to the development of pathological proliferation in the endometrium in the form of various forms of endometrial hyperplasia.

In the structure of gynecological morbidity endometriosis takes 3rd place after inflammatory processes and uterine fibroids, affecting up to 50% of women with preserved menstrual function. Endometriosis leads to functional and structural changes in the reproductive system, often negatively affecting psycho-emotional state women, significantly reducing the quality of life.

Currently, many clinicians indicate that endometriotic lesions occur at any age, regardless of ethnicity and socioeconomic conditions. Epidemiological studies indicate that in 90 - 99% of patients, endometriotic lesions are detected between the ages of 20 and 50 years, most often during the reproductive period.

- these are growths, similar in structure to the uterine mucosa, outside the usual localization of the endometrium. According to modern ideas about the nature of endometriosis, this disease should be considered as a pathological process with a chronic, relapsing course. Endometriosis forms and develops against the background of disrupted immune, molecular genetic and hormonal relationships in the female body. The endometriotic substrate has signs of autonomous growth and disturbances in the proliferative activity of cells. Endometriosis can be localized both in the body of the uterus (adenomyosis, or internal endometriosis) and outside the uterus (external endometriosis).

Regardless of the location and size of endometriotic lesions, histologically endometriosis is characterized by benign proliferation of glandular epithelium, reminiscent of functioning glands of the endometrial stroma. However, the ratio of glandular epithelium and stroma in endometrioid heterotopias of different locations is not the same.

In recent years, an opinion has been expressed that “internal endometriosis of the uterus” should be considered a completely independent disease, denoting it with the term “adenomyosis” and not “endometriosis” (Haney A. F. 1991). It is emphasized that the clinical picture, diagnosis, prevention, and treatment methods for adenomyosis have significant features. In addition, adenomyosis cannot result from “retrograde menstruation” through the fallopian tubes, as the most accepted implantation theory states. Adenomyosis develops from the basal layer of the endometrium, which takes into account the translocation hypothesis of the occurrence of uterine endometriosis.

Over the past half century, more than 10 different classifications of endometriosis have been proposed.

Currently, the most common classification is the American Fertility Society, revised in 1985, which is based on the assessment of laparoscopic findings.

Classification of common forms of genital endometriosis according to A. I. Ishchenko (1993)

By stages

Stage I: peritoneal implantation with small peritoneal defects and endometrioid lesions.

Stage II: endometriosis of the uterine appendages with endometrioid foci or ovarian cysts, with the development of multiple adhesions around the fallopian tubes and ovaries, the formation of endometrioid infiltrates on the pelvic peritoneum.

Stage III: spread of the endometrioid process to the cellular spaces starting behind the cervical tissue and neighboring organs:

IIIa: damage to the serous cover of a neighboring organ or involvement of an extraperitoneally located organ in the endometrioid infiltrate (distal colon, small intestine, appendix, bladder, ureters);

IIIb: damage to the muscle layer of a neighboring organ with deformation of its wall, but without obstruction of the lumen;

IIIc: damage to the entire thickness of the wall of a neighboring organ with obstruction of the lumen, damage to paravaginal and pararectal tissue, parametrium with the formation of the structure of the ureter.

Stage IV: dissemination of foci of endometriosis throughout the pelvic peritoneum, serous covering of the pelvis and peritoneal cavity, ascites or multiple lesions of neighboring organs and cellular spaces of the pelvis.

According to the degree of damage to the uterus

1. The lesion reaches the muscular layer of the uterus.

2. Damage to more than half of the muscle layer.

3. Damage to the entire thickness of the uterine wall.

Distant foci of endometriosis:

- in a postoperative scar;

- in the navel;

- in the intestines (not adjacent to the genitals);

- in the lungs, etc.

In the domestic literature, a clinical classification of adenomyosis is proposed, distinguishing 4 stages of the spread of endometrioid invasion. She considers diffuse myometrial damage depending on the depth of penetration of endometriotic tissue.

Stage I: the pathological process is limited to the submucosa of the uterine body.

Stage II: the pathological process extends to the middle thickness of the uterine body.

Stage III: the entire muscular layer of the uterus up to its serous layer is involved in the pathological process.

Stage IV: involvement in the pathological process, in addition to the uterus, the parietal peritoneum of the small pelvis and neighboring organs.

At the same time, the classification does not apply to the nodular form of the disease.

There is no consensus regarding the classification of retrocervical endometriosis. Retrocervical endometriosis in the domestic literature is considered as a variant of external genital endometriosis and is classified into 4 stages of spread to surrounding tissues and organs.

Stage I: localization of endometriotic lesions within the rectovaginal tissue.

Stage II: endometriosis grows into the cervix and vaginal wall with the formation of small cysts.

Stage III: spread of the pathological process to the uterosacral ligaments and serous covering of the rectum.

Stage IV: involvement of the rectal mucosa in the pathological process with the formation of an adhesive process in the area of the uterine appendages, obliterating the utero-rectal space.

Endometriosis of retrocervical tissue (infiltrative form) is extremely rare as an independent localization, usually combined with endometriosis of the pelvic peritoneum, ovaries or adenomyosis, often involving the intestines and urinary tract in the process.

It is obvious that the accumulation of new information about the etiology and pathogenesis of endometriosis, clinical, structural, functional, immunological, biological, genetic variants of this disease will allow us to propose new classifications.

Basic theories of the development of endometriosis

The variety of localizations of endometriosis has led to a large number of hypotheses about its origin. Significant amount concepts try to explain the emergence and development of this disease from various positions. Key statements:

— origin of the pathological substrate from the endometrium (implantation, lymphogenous, hematogenous, iatrogenic dissemination);

— metaplasia of the epithelium (peritoneum);

— disturbance of embryogenesis with abnormal remains;

- disruption of hormonal homeostasis;

- changes in immune balance;

— features of intercellular interaction.

Numerous experimental and clinical studies prove and confirm this or that position, depending on the point of view of the author. However, most researchers tend to agree that endometriosis is a disease with a relapsing course.

Implantation (translocation) theory of endometriosis development

The most widespread is the implantation theory of the occurrence of endometriosis, first proposed by J. F. Sampson in 1921. The author suggested that the formation of foci of endometriosis occurs as a result of retrograde reflux of viable endometrial cells into the abdominal cavity, rejected during menstruation, and their further implantation on the peritoneum and surrounding organs ( subject to patency of the fallopian tubes).

Accordingly, the introduction of endometrial particles through various routes into the pelvic cavity is considered a critical moment in the development of endometriosis. One of the obvious options for such a drift is surgical procedures, including diagnostic curettage, obstetric and gynecological operations associated with the opening of the uterine cavity and surgical trauma of the uterine mucosa. The iatrogenic moment of the development of the disease has been sufficiently proven by a retrospective analysis of the etiology of endometriosis in women who underwent certain operations.

Of considerable interest is the possibility of metastasis of endometriosis in the blood and lymphatic vessels. This type of dissemination of endometrial particles is considered one of the most important causes of known variants of extragenital endometriosis, such as endometriosis of the lungs, skin, muscles. The spread of viable endometrial cells along the lymphatic pathways is a common occurrence, as evidenced by the fairly frequent detection of significant foci of endometriosis in the lumen of the lymphatic vessels and nodes.

Metaplastic theory of the origin of endometriosis

This theory reflects the most controversial issue in the pathogenesis of the disease and was proposed by N.N. Ivanov (1897), R. Meyer (1903).

Proponents of this theory believe that embryonic cellular elements located between the mature cells of the serous covering of the pelvis can transform into the epithelium of the uterine tube type. In other words, lesions of endometriosis can arise from multipotent peritoneal mesothelial cells. In the occurrence of endometriosis, the so-called Müllerian potential of the mesothelium, which is associated with the concept of the “secondary Müllerian system” proposed by Lauchlan, is important. The author used this concept to designate epithelial changes of the Müllerian type (including endometrioid lesions) outside the derivatives of the Müllerian system, metaplastic processes and benign proliferations (epithelium and mesenchyme), which can be observed on the surface of the ovaries or directly under their surface, in the pelvic peritoneum, omentum , retroperitoneal lymph nodes and other organs.

The Müllerian potential of the pelvic mesothelium and adjacent stroma is associated with their close relationship in embryonic period to the Müllerian system, which is formed by intussusception of the primary coelom. The intraembryonic part of the primary coelom, its derivatives (pleura, pericardium, peritoneum, superficial epithelium of the ovary) and the Müllerian system (fallopian tubes, spruce and cervix) are of close embryonic origin. Tissues formed from coelomic epithelium and adjacent mesenchyme (“secondary Müllerian system”) are capable of differentiating into Müllerian-type epithelium and stroma.

This point of view about the origin of endometriosis is not widely accepted because it does not have strict scientific evidence.

Dysontogenetic (embryonic) theory of endometriosis

The embryonic theory of the origin of endometriosis suggests its development from the remnants of the Müllerian ducts and primary kidney. This assumption was developed at the end of the 19th century and continues to be accepted by some contemporaries. To confirm the dysontogenetic hypothesis, researchers cite cases of combination of endometriosis with congenital anomalies reproductive system, gastrointestinal tract.

Hormonal disorders and endometriosis

Literature data indicate the dependence of the development of endometrioid structures on hormonal status, disturbances in the content and ratio of steroid hormones. For the occurrence of endometriosis, the characteristics of the activity of the hypothalamic-pituitary-ovarian system are primarily important.

In patients with endometriosis, chaotic peak emissions of follicle-stimulating (FSH) and luteinizing (LH) hormones occur, a decrease in the basal level of progesterone is observed, and many have hyperprolactinemia and impaired androgenic function of the adrenal cortex.

A number of studies have noted that unovulated follicle syndrome (LUF syndrome) contributes to the occurrence of endometriosis. Thus, in women with this syndrome, the concentrations of 17-β-estradiol and progesterone in the peritoneal fluid after ovulation were significantly lower than in healthy women. At the same time, other works point to the opposite hormonal fluctuations with LUF syndrome. A high level of progesterone in the first days of menstruation is considered a factor promoting the survival of viable endometrial cells, which is confirmed by experimental data obtained on castrated animals.

One way or another, in patients with genital endometriosis, a high incidence of LFU syndrome is noted while maintaining the external parameters of the ovulatory menstrual cycle (two-phase basal temperature, sufficient progesterone levels in the middle of the luteal phase, secretory changes in the endometrium).

An indirect role in the development of endometriotic lesions is attributed to dysfunction of the thyroid gland. Deviations from the physiological secretion of thyroid hormones, which are estrogen modulators at the cellular level, can contribute to the progression of disorders of histo- and organogenesis of hormone-sensitive structures and the formation of endometriosis.

When examining patients with endometriosis, local morphological changes in the ovaries were also revealed, especially when the ovaries themselves were affected. It has been shown that outside the zones of endometriotic lesions, the ovaries have signs of oocyte degeneration, cystic and fibrous atresia of the follicles, stromal thecamatosis, and follicular cysts. Some authors believe that this is due to the effect on the ovaries toxic agents inflammation, for example prostaglandins, the content of which increases with endometriosis.

However, it should be noted that dysfunction of the hypothalamus-pituitary-ovarian system, like other disorders, cannot be considered an indispensable companion to endometriosis and is often not detected in many patients.

Immunological theory of the origin of endometriosis

Disruption of immune homeostasis in endometriosis was suggested by M. Jonesco and C. Popesco in 1975. The authors believed that endometrial cells, entering the blood and other organs, represent autoantigens. Proliferation of endometrioid cells in other tissues is possible as a result of increased levels of estrogenic hormones, which stimulate the secretion of corticosteroids. The latter, in turn, being depressants, suppress local cellular and humoral immunity, thereby providing favorable conditions for invasion and development of viable endometrial cells.

Further studies revealed anti-endometrial autoantibodies in patients with endometriosis. Thus, IgG and IgA antibodies to ovarian and endometrial tissues were identified, which were determined in blood serum, in vaginal and cervical secretions.

When studying the immune status of patients with endometriosis, a correlation was revealed between the frequency of detection of antibodies and the stage of spread of endometriosis. Numerous studies reliably prove that endometriosis develops against the background of a disturbed immune balance, namely T - cellular immunodeficiency, inhibition of T-suppressor function, activation of delayed-type hypersensitivity, decreased activity of T-lymphocytes with simultaneous activation of the B-lymphocyte system and decreased function of natural killer (NK) cells.

In endometriosis, a congenital decrease in the function of the immune system - NK cells - has also been found. The natural cytotoxicity of lymphocytes was discovered relatively recently, in the late 70s, but very soon the enormous importance of this reaction for maintaining physiological homeostasis became clear. NK cells - effectors of natural cytotoxicity - perform the function of the first defense in the immune surveillance system in the body. They are directly involved in the elimination of transformed and tumor cells, virus-infected cells, and those modified by other agents.

Such a leading role of NK cells definitely indicates that it is the deficiency of the activity of these cells that can determine the implantation and development of endometrial particles brought into the abdominal cavity. In turn, the development of endometriosis foci increases the production of immunosuppressive agents, which determine a further decrease in the activity of NK cells, deterioration of immune control and the progression of endometriosis.

Thus, in patients with endometriotic lesions, general signs of immunodeficiency and autoimmunization are observed, leading to weakening of immune control, which create conditions for implantation and development of functional endometrial foci outside their normal localization.

Features of intercellular interactions in endometriosis

Researchers continue to search for the causes of implantation and further development endometrial elements in the pelvic tissues.

Although retrograde flow of menstrual blood is likely common, not all women develop endometriosis. In some observations, the prevalence of endometrioid lesions is minimal and the process may remain asymptomatic; in others, endometriosis spreads throughout the entire pelvic cavity and becomes the cause of various complaints. Moreover, in some cases of endometriosis, self-healing is possible, while in other cases the disease stubbornly recurs, despite intensive care. A number of authors believe that cases of “mild” endometriosis should not be considered a disease requiring special treatment. In their opinion, this is a physiological phenomenon associated with the regular retrograde reflux of menstrual blood. However, it is not clear what serves as the boundary between this condition and endometriosis as a disease.

These problems are currently the focus of study. It is obvious that, in addition to the general signs of immunodeficiency and autoimmunization, there are some other factors (perhaps a combination of them) that determine the perception of endometrial particles from the pelvic peritoneum, which creates conditions for the implantation of these particles, instead of recognizing them as foreign and contribute to their destruction.

In recent years, sufficient data have been obtained confirming the leading role of genetic factors in the occurrence of endometriosis, as well as clarifying the significance of dysfunction of the immune and reproductive systems in the development of this pathology.

Based on genealogical analysis and determination of genetic and biochemical markers, the following patterns were identified:

— genetic factors play a significant role in the development of endometriosis;

— there is a reliable connection between certain genetic factors and the anatomical localization of endometrioid lesions;

— based on the expression of biochemical genetic markers, it is possible to determine the presence or absence of a predisposition to endometriosis or an already developed disease.

Accordingly, in endometriosis, cell dysfunction is associated with the expression of defective genes as a result of mutation. The observed familial cases of the disease indicate the possibility of the involvement of complex genetic defects, presumably affecting several genes, in the pathogenesis of endometriosis. It is likely that one or more gene defects are responsible for predisposition to the development of endometriosis. This predisposition alone may be sufficient, or the participation of environmental factors may also be required.

Studies indicating the genetic determination of immune disorders that initiate the development of endometriosis deserve significant attention.

Cellular and humoral immunity in endometriosis are identified with HLA antigens.

It can be assumed that endometriosis is hereditarily determined by genes associated with certain antigens of the HLA system, namely HA, A10, B5, B27.

Of course, it is impossible to explain the entire variety of clinical and morphological manifestations of endometriosis only by a primary genetically determined immune defect. Character matters too local violations tissue homeostasis directly in the pelvic area. These processes attract the attention of researchers, and analysis of the results constantly expands knowledge about the mechanisms of control of tissue proliferation, inflammatory and dystrophic reactions.

A significant place is given to macrophages that directly respond to the presence of foreign elements. Macrophages “move” red blood cells, damaged tissue fragments and, possibly, endometrial cells that enter the abdominal cavity.

It has been established that with endometriosis, the total number and activity of peritoneal macrophages increase.

A relationship has been noted between the severity of endometriosis and the macrophage reaction of the peritoneal fluid, and an increase in the content of macrophages in the foci of endometriosis has been proven.

On present stage Of interest is the concept put forward by W.P. Damowski et al. (1988), subsequently slightly modified by R.W. Shaw (1993):

- retrograde movement of endometrioid fragments during menstruation occurs in all women;

— rejection or implantation of these fragments depends on the function of the immune system;

- endometriosis reflects a deficiency of the immune system, which is inherited;

— immune deficiency can be both qualitative and quantitative, leading to endometriosis;

- the production of autoantibodies is a reaction to ectopic endometrium and it, in turn, can contribute to infertility in endometriosis.

This hypothesis is essentially a combination of implantation and immunological theories. This concept states that endometrioid fragments move through the fallopian tubes in all women. IN abdominal cavity they are redistributed by the immune system, represented mainly by peritoneal macrophages. Endometriosis can develop when the peritoneal distribution system becomes congested due to increasing retrograde movement of endometriotic elements. Endometriosis also occurs when the peritoneal distribution system is defective or imperfect. Ectopic endometrial proliferation results in the formation of autoantibodies.

It has been shown that, in addition to phagocytic activity, peritoneal macrophages regulate local processes related to reproduction by releasing prostaglandins, hydrolytic enzymes, proteases, cytokines, and growth actors that initiate tissue damage.

In recent years, considerable attention has been paid to studying the role of prostaglandins in endometriosis. Potential sources of prostaglandin production in the abdominal cavity are the peritoneum and macrophages. In addition, there is passive diffusion of prostaglandins from organs located in the abdominal cavity and release by the ovaries during follicle rupture during ovulation. As a result of research, the important role of prostaglandins in the pathogenesis of endometriosis has been established.

An increase in the concentration of prostaglandins in a woman’s blood plasma predisposes to the formation of the disease, affecting the cytoproliferative activity and differentiation of endometriotic tissue cells. Prostaglandins may stimulate endometrial growth and manifest the main clinical symptoms - dysmenorrhea and infertility.

Prostaglandins and immunocomplexes are not the only physiological regulators of intercellular interaction. Other factors that determine the fate of ectopic endometrial tissue are cytokines and growth factors.

In addition to cells of the immune system, other cells are capable of secreting similar signaling molecules, which have come to be called cytokines. Cytokines are peptide mediators that promote cell interaction. Certain material has been accumulated on the role of cytokines that provide favorable conditions for the introduction and development of viable endometrial elements. The biological potential of cytokines is to regulate the interaction of macrophages with tissue elements, formation of foci of inflammation and immunomodulation. In fact, cytokines are universal regulators of inflammation processes. It is known that different cell populations are capable of secreting the same cytokines. Macrophages, B cells, and some subsets of T lymphocytes produce a similar array of cytokines. Obviously, activation of a certain group of cells leads to the synthesis of a set of cytokines and the induction of functions associated with them.

With endometriosis in the peritoneal fluid, the concentration of such cytokines as interleukin-1, interleukin-6, the main producers of which are macrophages, increases. A correlation was noted between the level of interleukin-1 and the stage of spread of endometriosis. Cytokines accumulated during local activation of macrophages close the feedback loop, which ensures the involvement of new mediators in the process. In addition, interleukin-1 is believed to have a number of properties that may be associated with endometriosis. Thus, interleukin-1 induces the synthesis of prostaglandins, stimulates the proliferation of fibroblasts, the accumulation of collagen and the formation of fibrinogen. e. Processes that may contribute to the formation of adhesions and fibrosis associated with endometriosis. It also stimulates B cell proliferation and the induction of autoantibodies. It has been established that, along with sex hormones and cytokines, growth factors are important regulators of cell proliferation and differentiation.

These factors are produced by non-specialized cells present in all tissues and have endocrine, paracrine, autocrine, and intracrine effects. Of particular interest from the point of view of the pathogenesis of endometriosis deserves one of the modes of action of growth factors, called intracrine interaction. Growth factors are not secreted and do not require surface receptors to mediate their activity. They remain inside the cell and act directly as intracellular messengers, regulating cellular functions. There are epdermal, platelet, insulin-like and other growth factors.

The release of growth factors complements the effect of other active agents, promoting not only proliferation, but also degenerative changes in tissues. The process of accumulation of growth factors and cytokines is facilitated by the fact that they are also produced in tissue cells attacked by macrophages, primarily in epithelial cells, ibroblasts, etc.

In endometriosis, increased expression of tumor necrosis factor α (TNF-α) has been found in peritoneal fluid. The importance of epidermal growth factor in the process of proliferation of endometrial cells is assessed as a possible activator of the proliferative features of fibroblasts and epithelial cells.

It is interesting to note that when endometriosis is modeled experimentally, its development is closely related to the accumulation of heterotopias of epidermal growth factor, insulin-like growth factor and TNF-a in the tissue. At the same time, these growth factors influence the development of adhesions. This seems very important for understanding the pathomechanisms of endometriosis, the spread of which is closely related to the proliferation of heterotopic elements and the proliferation of connective tissue.

Thus, it can be assumed that the cells of endometriotic lesions are directly involved in the processes of proliferation and further spread of the pathological process.

In addition to growth factors, cellular proliferation is also controlled by proto-oncogenes, since conversion to cellular oncogenes and changes in their expression or activation caused by mutations, translocations and amplifications lead to changes in cellular growth. These molecules of intercellular interaction are considered as one of the promising tissue markers of proliferative activity in a wide range of various pathological processes, including tumor ones.

Cellular oncogenes encode the synthesis of proteins called oncoproteins, or oncoproteins. It should be noted that all known oncoproteins are involved in the transmission of mitogenetic signals from cell membrane to the nucleus to certain cell genes. This means that most growth factors and other cytokines can interact with oncoproteins to some extent.

Studying the content and functional activity of one of the oncoproteins that transmits growth signals to DNA - c-myc, we noted a certain pattern of its expression in endometriotic lesions. Foci of adenomyosis, endometrioid cysts and endometrioid ovarian cancer are characterized by high expression of c-myc, which increases sharply in malignant tumor, which can be used for their differential diagnosis.

Consequently, the accumulation of the c-myc oncoprotein in the cells of endometriosis foci can lead to increased binding of growth factors that are synthesized by the endometrioid cells themselves, which stimulates the growth of pathological formation by an autocrine mechanism.

Genes have been found in the cell genome that, on the contrary, inhibit cell proliferation and have an anti-oncogenic effect. Loss of such genes by a cell can lead to the development of cancer. The most studied anti-oncogenes are p53 and Rb (retinoblastoma gene). The suppressor gene p53 was named a molecule in 1995. Regulation of cell proliferative activity by p53 is carried out by inducing or not inducing apoptosis.

Apoptosis is the genetically programmed death of cells in a living organism. Impaired apoptosis is important for carcinogenesis at all stages. At the initiation stage, mutated cells can die as a result of apoptosis, and the tumor does not develop. At the promotion stages, the growth of tumor cells is also limited by apoptosis.

Activation of the unchanged form of p53 against the background of the activity of cellular oncogenes c-myc and C-fos leads tumor cells to death as a result of apoptosis, which occurs spontaneously in the tumor and can be enhanced by exposure to radiation and chemicals.

Mutations or inactivation of p53 by other means against the background of increased expression of oncoproteins (oncogenes) - c-myc, c-fos, c-bcl, on the contrary, result in increased cell proliferation with possible malignant transformation.

Complex interactions between the oncoproteins c-myc, c-fos, c-bcl and the antioncogenes p53 and Rb mediate the balance between proliferation and apoptosis.

The essence of the process of cell apoptosis is as follows:

— cells that should be included in the self-destruction program express genes that induce the process of apoptosis and, accordingly, specific proteins are produced (“death domains”);

— activation of endonucleases occurs, which fragments DNA and the nucleus;

- the cell nucleus and the cell itself disintegrate into apoptotic bodies, which are surrounded by a membrane. The contents of the cell do not enter the surrounding space and there is no reaction (including inflammatory);

- a cell undergoing apoptosis separates from a number of neighboring cells and is engulfed by macrophages or utilized by neighboring cells. The whole process takes from a few minutes to 1-3 hours.

Inhibitors of apoptosis are the bcl-2 family of oncogenes. Oncogenes of this family encode specific proteins (BCL-2). By blocking apoptosis, they promote the survival of those cells that should self-destruct, but survive.

Increased expression of genes-inhibitors of apoptosis and inducers of proliferation enhances the proliferative activity of biologically inappropriate cells, gives them increased resistance, extraordinary survival, resistance to self-destruction.

Apoptosis-inducing genes include Fas/Apo1, tumor necrosis factor (TNF), natural (wild) type p-53, which repairs DNA. P-53 prolongs the presynaptic phase (G1). If the cell does not have time to undergo repair during this time, apoptosis is induced and the cell is eliminated. Inhibitors of apoptosis (except for genes of the bcl-2 family) are increased production of gonadotropic hormones (FSH and LH), their disordered secretion, accumulation of somatic cell mutation factors, aging of the body, metabolic disorders (oxidative stress), etc.

The process of proliferation is diametrically opposed to apoptosis. Proliferation is activated by the Ki-67 genes encoding a nuclear protein involved in mitotic cell division, as well as the c-myc gene, which regulates the entry of a cell from the G1 (presynthetic) phase into the S (synthetic) phase.

Increased expression of the c-myc gene preserves (increases) the proliferative activity of the cell, disrupting (slowing down) cell differentiation. Unregulated c-myc expression may lead to tumorigenesis.

The mechanism of apoptosis was developed in the process of evolutionary development with the advent of multicellular organisms and intercellular regulation of individual cell functions and is deeply physiological, as it is aimed at preserving the genetically specified number of cells, stabilizing the boundaries of closely adjacent tissues (endometrium-myometrium), preventing the accumulation and transfer of pathologically altered DNA into other cells in the process of mitotic division.

Suppression of apoptosis leads to the occurrence of hyperplastic, proliferative and tumor diseases.

Regulators of apoptosis, acting at the level of the whole organism, are hormones. The action of hormones at the cellular and molecular level is mediated by cytokines, interleukins, scaffolding factors, genes and specific oncoproteins.

The onset of enlometriosis is associated only with the presence of the menstrual cycle, during which endometrial cells express genes that induce and inhibit apoptosis. During the proliferation phase and early secretion apoptosis is low, which has a deep physiological meaning. In the late stage of proliferation, the expression of the apoptosis inhibitor (bcl-2 inhibitor gene) is maximally reduced, which enhances the apoptotic self-destruction of virus-infected, damaged, biologically inappropriate endometrial cells, including those with high proliferative potential. Apoptosis, how physiological process, is protective in nature.

Studying the role of apoptosis and proliferation in the genesis of internal endometriosis allowed us to draw the following conclusions:

— in foci of endometriosis and hyperplastic endometrium there is low apoptosis and high proliferative activity of cells;

— the source of areas of endometriosis can be cells of hyperplastic endometrium. Histochemical studies confirm the data on the predominance of proliferating type epithelium in the foci of endometriosis and hyperplastic endometrium compared with unchanged endometrium in patients with adenomyosis and in healthy women;

- the unusual survival of ectopic endometrial cells is due to their high proliferative potential, as well as the fact that they were not eliminated by the genetic program of self-destruction as inappropriate;

- in the pathogenesis of adenomyosis and endometrial hyperplasia, high expression of genes - inhibitors of apoptosis, namely bcl-2, plays a role;

— high proliferative potential of foci of internal endometriosis is due to the intense expression of proliferation inducers Ki-67 and c-myc;

- low apoptosis, high proliferative potential, as well as a violation of the relationship between the processes of proliferation and apoptosis, determine the ability of ectopic cells of hyperplastic endometrium to autonomous growth, which reduces dependence on hormonal influences, as the cells switch to auto- and paracrine mechanisms of regulation;

— the imbalance of molecular genetic indicators of proliferation and apoptosis processes (absolutely low apoptosis and high proliferative activity) in the foci of endometriosis and hyperplastic endometrium has been proven.

Low apoptosis and increased proliferative activity of hyperplastic endometrial cells apparently accompany the process of their movement to other tissues and organs, since such a cell clone has an altered plasmolemma, which contributes to easier migration through basement membranes and extracellular matrix. It is possible that, as a metastatic embolus, hyperplastic endometrial cells have a protective fibrin coating that protects them from elimination by cells of the immune system. It is possible that the protective coating reduces the number of hormone receptors in ectopic foci of endometriosis.

Thus, current information on the molecular genetic features of various types of endometriotic lesions allows us to consider endometriosis as chronic illness with signs of autonomous growth of heterotopias, with a violation biological activity endometrial cells. Autonomous growth of endometriosis foci means a lack of control over the proliferation and differentiation of heterotopia cells by the woman’s body. This does not mean that endometrioid cells are in proliferative chaos. Endometrioid cells switch to itra-, auto- and paracrine mechanisms for regulating their growth, which is expressed in the loss of contact inhibition and the acquisition of “immortality”. Thus, it is known that foci of endometriosis become direct producers of growth factors, growth factor receptors, cytokines, and oncogenes in the absence of expression of the p53 suppressor gene, initiating imbalances in the organs and tissues of the abdominal cavity, exacerbating the existing immunodeficiency. Consequently, we can assume the formation of a persistent vicious circle of pathological processes that contribute to the engraftment of new particles of endometrioid tissue, the spread of existing ectopia, and the formation of deeply invasive and widespread forms of endometriosis.

Morphofunctional characteristics of endometriosis

Endometriosis is a benign pathological process characterized by the proliferation of tissue similar in structure and function to the endometrium.

Endometrioid heterotopias have a distinct ability to penetrate organ tissue, reaching blood and lymphatic vessels, and also disseminate.

Tissue infiltration with subsequent destruction occurs as a result of the proliferation of the stromal component of endometrioid heterotopias. The ratio of glandular epithelium and stroma in foci of endometriosis of different locations is not the same. It has been reliably established that in heterotopias developing in the myometrium (adenomyosis) and rectovaginal septum, the stromal component predominates. At the same time, no specific pattern has been observed in the relationship between the epithelial and stromal components in endometriosis of the ovaries, peritoneum, and ligamentous apparatus of the uterus.

Histological diagnosis of endometriosis is based on the identification of columnar epithelium and subepithelial stroma, which are similar to similar components of the uterine mucosa.

According to the classification of J.F. Brosens (1993), there are 3 types of histological structure of endometrioid lesions:

- mucous (with liquid contents), presented in the form of endometrioid cysts or superficial lesions of the ovary;

- peritoneal, which is diagnosed microscopically by active endometrioid foci (red, glandular or vesicular, growing deep into the tissue, black, folded and regressing - white, fibrous), which are more often detected in reproductive age;

- nodular - an adenoma localized between smooth muscle fibers and fibrous tissue, usually detected in the ligamentous apparatus of the uterus and the rectovaginal septum.

Many authors associate the characteristics of the clinical manifestations of the disease with the depth of germination of endometrioid implants into the underlying tissues (myometrium, peritoneum, ovaries, parametrium, intestinal walls, bladder, etc.).

Deep endometriosis is considered to be lesions that infiltrate the affected tissue to a depth of 5 mm or more. Deeply infiltrating endometriosis is diagnosed in 20-50% of patients.

P.R. Konincks (1994) distinguishes 3 types of deep endometriosis, considering it and endometrioid ovarian cysts to be the final stage of the development of the disease:

- type 1 - cone-shaped endometriosis lesion, which does not violate the anatomy of the pelvis;

- type 2 - deep localization of the lesion with extensive surrounding adhesions and disruption of the anatomy of the pelvis;

- type 3 - deep endometriosis with significant spread over the surface of the peritoneum.

Numerous studies indicate features of the morphological structure of various localizations of endometriosis:

— variability in the ratio of the epithelial component and stroma of endometriosis foci;

— discrepancy between the morphological picture of the endometrium and endometrioid lesions;

- mitotic activity (secretory activity) of ectopic endometriosis, which does not correlate with the morphological characteristics of the endometrium;

— polymorphism of the glandular component of the endometriosis lesion (high frequency of detection of epithelium in endometrioid implants in the same patient, corresponding to different forms of the menstrual cycle);

— diversity of vascularization of the stroma of endometrioid heterotopias.

The composition and quantity of stroma have a certain significance for the cyclic changes of the epithelium in foci of endometriosis. Epithelial proliferation is impossible without the stromal component. It is in the stroma that the program of epithelial cytodifferentiation and functional activity of tissues is contained. A sufficient amount of stroma with a predominance of fibroblasts and numerous vessels contributes to the cyclic restructuring of the glandular epithelium in endometrioid heterotopias. Foci of endometriosis without signs of functional activity (flattened atrophic epithelium) are characterized by an insignificant content of the stromal component and weak vascularization.

It has been established that many endometrioid heterotopias lack a sufficient number of estrogen and progesterone receptors. This is evidenced by the data obtained by many authors on a significant decrease in the content of estrogen-, progesterone- and androgen-binding receptors in endometriotic lesions of various locations in comparison with the endometrium.

The results of studies of the activity of steroid reception in foci of endometriosis in patients treated and not treated with hormonal therapy are further confirmation that the effect of hormones on cellular elements is secondary and is determined by the proliferative potential and differentiation of the cell itself. Accordingly, it was found that the average level of estrogen- and progesterone-binding receptors in heterotopias of various localizations practically does not differ in treated and untreated patients with endometriosis, but depends mainly on the localization of the pathological focus. The level of reception of the studied tissues showed a decrease in receptor activity as the endometriotic lesion moves away from the uterus.

The results of the study made it possible to establish an obvious correlation between the hormonal sensitivity of endometriotic lesions and the receptor activity of the organ or tissue where they arose.

Thus, the influence of hormones on the cellular elements of endometriosis foci is not direct, but indirectly through the activation of growth factors and other substances of the paracrine system.

Literature data indicate that the most common concomitant pathological process with endometriosis, especially with adenomyosis, is uterine fibroids. The combination of adenomyosis with endometriosis of other genital organs, mainly the ovaries, is also common occurrence and is diagnosed in 25.2 - 40% of patients.

Pathological transformation of the endometrium is diagnosed in 31.8-35% of cases in combination with internal endometriosis. Pathological transformation of the endometrium is characterized by polyps against the background of an unchanged uterine mucosa (56%), as well as a combination of endometrial polyps with types of hyperplasia (44%).

It is important to emphasize that endometrial hyperplasia is such a common occurrence that it may not have a cause-and-effect relationship with endometriosis, but only be combined with this pathology.

The high frequency of hyperplastic processes in the ovaries with adenomyosis, which are observed 2 times more often than in the endometrium, deserves some attention. A direct relationship has been noted between the frequency of hyperplastic processes in the ovaries and the spread of endometriosis in the uterine wall. In this regard, it is recommended that before starting hormonal therapy, laparoscopy with ovarian biopsy is performed and, if severe hyperplasia or a tumor process is detected, appropriate treatment adjustments are made.

The above allows us to make fairly substantiated statements:

- long-term hormone therapy can only temporarily improve the patient’s quality of life, but is not able to provide regression of the disease and can hardly be considered as radical method treatment of endometriosis;

— surgical treatment becomes especially important, but it requires removal of all endometriosis implants in the pelvis.

Oncological aspects of endometriosis

The oncological aspect of endometriosis remains one of the most significant and controversial. The subject of discussion is quite contradictory information about the frequency of malignant transformation of endometriosis. Many researchers point to a high incidence of malignancy in endometriosis - 11-12%. According to another point of view, malignancy of endometriosis is extremely rare. No one denies the ability of endometriotic lesions to undergo malignant transformation. Neoplasms arising from endometrioid foci can be divided into ovarian and extraovarian. The most common (in more than 75% of all described cases) are ovarian tumors, usually limited to the ovary. The second most common location is the rectovaginal localization of neoplasms of endometriotic origin, followed by the uterus, fallopian tubes, rectum and bladder.

The oncological aspects of endometriosis raise a logical question: what is the risk of carcinoma in patients with endometriosis? A number of gynecological oncologists are of the opinion that patients with endometriosis should be classified as a high-risk group for ovarian, endometrial, and breast cancer. Proponents of the concept of “potentially low-grade endometriosis” believe that the malignancy of endometriosis should not be exaggerated. Such a statement probably confirms the extremely rare observation of malignant degeneration of endometriosis of the cervix, fallopian tubes, vagina, and retrocervical region.

Among the oncological aspects of endometriosis, it is necessary to highlight the malignant transformation of ovarian endometriosis. The importance of the position in this issue is due to the responsibility in choosing a method of treatment for patients with the initial stages of endometriosis. Since foci of endometriosis have a high proliferative potential and autonomous growth, the totality of modern data on the pathogenesis of the disease allows us to consider the surgical method of treating endometriosis to be pathogenetically substantiated.

The most common malignant neoplasm of endometrioid origin is endometrioid carcinoma, which occurs in approximately 70% of cases of endometrioid ovarian cancer and in 66% of cases of extraovarian localization.

Thus, in patients with advanced forms of the disease, the risk of malignancy of endometriosis should be taken into account.

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