Endometriosis (endometriosis disease)

Endometriosis is a benign condition in which functioning endometrial tissue is implanted outside the uterine cavity. Symptoms of endometriosis depend on the localization of endometriotic foci and can be as follows: dysmenorrhea, dyspareunia, infertility, dysuric disorders and pain during defecation.

The diagnosis of endometriosis is established on the basis of a biopsy obtained by laparoscopy. Treatment includes the appointment of anti-inflammatory drugs, drugs to suppress ovarian function and suppress the growth of the endometrium. In severe cases, if a child is not scheduled to be born, a hysterectomy with removal of the ovaries is performed.

[1], [2], [3], [4], [5]

Epidemiology

In the structure of gynecological diseases, endometriosis occupies the third place after inflammatory diseases of genital organs and uterine myomas. It is diagnosed in 2-10% of women who first turned to a gynecologist and 30% of patients who need gynecological operations. When using laparoscopy, the foci of endometriosis are revealed in 20-50% of women suffering from infertility of an unknown genesis.

[6], [7], [8], [9], [10], [11], [12], [13], [14], [15]

Causes of the endometriosis

At present there is no clearly formulated theory of the occurrence of endometrioid heterotopia. The basic concepts of the onset of endometriosis (endometriosis):

• Embryonic ("congenital" form).
• Metaplastic.
• Endometrial (translocation).

Most researchers believe that endometriosis develops as a result of transplantation of viable endometrial cells thrown through the fallopian tubes during menstruation into the abdominal cavity. Their engraftment and growth of the foci of endometriosis occur when the immunological status of the organism changes.

The development of endometriosis (endometriosis disease) is determined by a number of pathogenetic factors.

Leading pathogenetic factors:

• Hormonal disorders.
• Dysfunction of the immune system and the perverted biological response of endometrial cells to sex hormones.
• Constitutionally hereditary (genetic) predisposition.
• Insufficiency of the body's antioxidant system.
• Prolonged tension of protective-adaptive reactions and reduction of nonspecific resistance of the organism.

Additional pathogenetic factors:

• Violations of menstrual function (with the appearance of menarche).
• Inflammatory diseases of the internal genitalia, leading to anovulation or deficiency of the function of the yellow body.
• Dysfunction of the liver and pancreas.
• Retrograde wave of uterine contraction from the neck to the bottom during menstruation.
• Surgical interventions, including cesarean sections and frequent abortions, operations on the uterus and appendages of the uterus, diagnostic curettage of the uterus.
• Prolonged use of intrauterine contraceptives.
• Stressful situations.
• Deterioration of the ecological situation.

As the disease progresses and in the process of treatment, the significance of pathogenetic factors may change.

[16], [17]

Pathogenesis

The most widely spread hypothesis is the transport of endometrial cells from the uterine cavity and implantation of them in other organs. Retrograde flow of menstrual tissue through the fallopian tubes can facilitate the transport of endometrial cells intraabdominal; the lymphatic and circulatory systems can also facilitate the transport of the endometrium to distant areas (eg, the pleural cavity).

There is a hypothesis of coelomic metaplasia: the transformation of coelomic epithelium into gland resembling the endometrium.

Microscopically, the endometriosis consists of glands and stroma, identical to the endometrium. These tissues contain estrogens and progesterone receptors and thus grow, differentiate and bleed in response to hormonal changes during the menstrual cycle.

Endometriosis is more common in first-degree relatives of patients with endometriosis. It is assumed that heredity is a risk factor for the development of this disease. The increase in endometriosis is observed in nulliparous, mild-toothed, as well as in women with a shortened menstrual cycle (<27 days), with prolonged menstruation (> 8 days) and in patients with malformations of the Mullerian duct.

Endometriosis occurs in about 10-15% of women aged 25-44 with active menstruation. The average age of patients with endometriosis is 27 years, but this disease can also occur in adolescents.

Approximately 25-50% of infertile women suffer from endometriosis. In patients with severe forms of the disease, with the presence of adhesive process of the pelvic organs and violation of the anatomy of the pelvic organs, the probability of infertility is high, because the mechanisms of the capture of the egg and tube transport deteriorate. Some patients with minimal manifestations of endometriosis and normal anatomy of the pelvic organs also suffer infertility. These patients may be reduced fertility due to disruption of the luteal phase of the cycle or the presence of luteinization syndrome of the neovulatory follicle; the production of peritoneal prostaglandins increases or peritoneal macrophagal activity increases (leading to phagocytosis), or the endometrium is unresponsive.

Potential protective factors are multiple pregnancies, the use of microdosed oral contraceptives (in continuous or cyclic mode), regular gymnastics (especially if started at the age of 15 years and with a duration of 7 hours per week).

Endometriosis is usually limited to the peritoneal or serous surfaces of the abdominal organs, most often by the ovaries, wide ligaments, utero-intestinal space and sacroculent ligaments. Less common is endometriosis on the serous surface of the small and large intestine, ureters, bladder, vagina, cervix, in the area of postoperative scars, pleura and pericardium. Bleeding from peritoneal endometriotic foci contributes to the development of the inflammatory process, accompanied by the deposition of fibrin, the formation of adhesions. All this leads to anatomical violations of the pelvic organs and abdominal cavity.

[18], [19], [20], [21], [22], [23], [24],

Symptoms of the endometriosis

Correctly evaluated complaints, detailed history and analysis of objective examination data in patients with endometriosis (endometriosis) allow the doctor to make a preliminary diagnosis and develop the correct algorithm for differential diagnostic search.

Symptoms of endometriosis

Complaints. Among a large number of complaints leading in patients with endometriosis are:

Pain. The degree of pain syndrome depends on:

• localization and prevalence of the process;
• degree of destruction of endometriosis of the peritoneum of the small pelvis, intestines, organs of the urinary system;
• duration of the disease.

In the initial period, the pain is cyclical. As the progression of endometriosis, the cyclicity of pain is disturbed, they become permanent and debilitating, their intensity increases. Then the pelvic pain becomes chronic; accentuates, disability or disability. In such cases, it should be considered that the patient developed a persistent pain syndrome. Pain can be permanent, irradiate to the lumbar region, sacrum, coccyx, anus, crotch. The relationship between the intensity of the pain syndrome and the severity of endometriosis is not established.

[25]

Menstrual dysfunction

The nature of violations of menstrual function largely depends on the location of the foci of endometriosis, the degree of damage to the genitals and pelvic organs. The most frequent are:

• Progressive algodismorrhoea (with intrauterine endometriosis with lesion of the isthmus, ovarian endometriosis, pelvic peritoneum, sacro-uterine ligaments, endocervical endometriosis with lesion of pararectal tissue and rectum wall).
• Menometrorrhagia (with intrauterine endometriosis and adenomyosis in combination with uterine myoma).
• Blood smearing before and after menstruation, contact bleeding: discharge (with endometriosis of the vagina, cervix, cervical canal, endometriosis of the ovaries and adenomyosis of the uterus).
• Irregular menstruation (with the combination of endometriosis of the ovaries with sclerokistozom).

Violation of the function of the pelvic organs

Dysfunction of the bladder or rectum (hematuria, bloating, stool retention, blood stench in the stool) with endometriosis (endometriosis) of these organs.

Impaired reproductive function

Infertility: primary, secondary, miscarriage. It is established that 30-40% of women with endometriosis suffer infertility.

History of the disease. In the history of the disease, it is necessary to find out when the patient's first treatment was to the doctor, with what it was associated (pain, menstrual dysfunction, infertility, impaired function of adjacent organs), what changes were found.

Results of instrumental research and treatment. Particular attention should be paid to the use of hormonal drugs (name, duration of use, tolerability), their effect on the nature of changes in menstrual function (cyclicity, duration, soreness). The use of immunomodulators, physiobalneotherapy (type, duration of treatment, effect) and other methods of treatment.

Family history and heredity. Violations of menstrual and generative functions in the immediate family, as well as the presence of endometriosis in them, allows us to assume the genetic conditionality of these diseases.

Postponed diseases. First of all, it is necessary to find out the transferred gynecological diseases (acute and chronic adnexitis), obstetric and gynecological operations, during which the uterine cavity was opened (conservative myomectomy, reconstructive plastic surgery for the development of the uterus, cesarean section, suturing perforations on the uterus, ectopic pregnancy, etc.). Particular attention should be paid to operations on the cervix (diathermy surgical, cryosurgical manipulations). If there is an indication in the medical history of an operation on the ovaries, the extent of the intervention and the result of the histological examination of the removed preparation should be clarified.

Extragenital diseases of attention deserve liver diseases, acute and chronic infectious diseases (frequent exacerbations, indicating the failure of the immune system),

Menstrual function. The age of the onset of menarche, regularity, duration and morbidity (time of appearance, localization, duration, irradiation) are monthly. It is necessary to determine the nature of the discharge from the genital tract before and after menstruation. Abundant and prolonged menstruation, which have the character of meno- and metrorrhagia, are characteristic of adenomyosis or uterine myoma.

Genital function. In the presence of pregnancies, it is necessary to find out their course and outcome, complications during pregnancy and the birth act (weakness of labor, bleeding in the consecutive and early postpartum periods, etc.). If the patient suffers from infertility, then its duration, the results of the study (GAS, laparoscopy, etc.) should be determined.

Symptoms of endometriosis with different implant locations

Localization	Symptoms
Genital organs	Dysmenorrhea Pain in the lower abdomen and in the pelvic area Infertility Irregularity of menstruation Pain in the lumbosacral region
Gastrointestinal tract	Tenesmus and rectal bleeding associated with the menstrual cycle Diarrhea, colon obstruction
urinary system	Hematuria and pain associated with the menstrual cycle Ureteral obstruction
Surgical scars, navel	Pain and bleeding associated with the menstrual cycle
Lungs	Hemoptysis associated with the menstrual cycle

Stages

Determining the stages of the disease helps doctors formulate a treatment plan and evaluate the response to therapy. According to the American Society of Reproductive Medicine, endometriosis can be classified by stages: I - minimal, II - easy, III - moderate, IV - severe. The classification is based on the number, location and depth of implantation and the presence of loose or dense adhesions.

Another classification system is based on the presence of pelvic pain. The degree of pain threshold assessment is different, therefore existing classification systems need to be improved.

Symptoms of endometriosis (endometriosis) depend largely on the localization of endometrioid heterotopia.

Classification of staging of endometriosis (endometriosis disease) [Zem K]

• Stage I - Foci of endometriosis in the small pelvis and on the vaginal part of the cervix less than 5 mm in size. Both fallopian tubes mobile and passable.
• Stage II - Foci of endometriosis in the small pelvis more than 5 mm, blood in the douglas space, foci of endometriosis in the bladder, peritubar and periovarial adhesions, pronounced ampullar stenosis or phimosis.
• Stage III - Foci of endometriosis in the uterus, fallopian tubes, "chocolate" cysts in the ovaries, infiltration in the area of sacro-uterine ligaments and wide ligaments.
• Stage IV - Extragenital endometrioid foci in the abdominal cavity and in the bladder (cystoscopy), in the lungs and on the skin

Depending on the localization of endometrioid heterotopies, there are:

• genital endometriosis (lesion of genital organs: uterus, vagina, ovaries, peritoneum of rectum-uterine and vesicle-uterine space, perineum);
• extragenital endometriosis (development of pathological process in other organs and systems: rectum, appendix, small and large intestine, hernial sac, lungs, pleural cavity, skin, navel, limbs, eyes, lymph nodes, central nervous system, etc.).

Classification of endometriosis of the American Fertility Society (R-AFS, 1985).

• Small forms: stage I (1-5 points).
• Light forms: stage II (6-15 points).
• Moderate forms: stage III (16-40 points). Multiple implants, endometrioid cysts with a diameter of less than 2 cm, a small number of adhesions.
• Heavy forms: stage IV (more than 40 points). Endometrioid cysts with a diameter of more than 2 cm, expressed adhesions of the fallopian tubes and ovaries, obstruction of the fallopian tubes, intestinal and / or urinary tract damage.

Adenomyosis can be diffuse and focal (nodular).

Classification of adenomyosis (internal endometriosis) of a diffuse form (Kulakov VI, Adamyan LV, 1998):

• Stage I - the pathological process is limited to the submucosal membrane of the uterus.
• Stage II - the pathological process passes to the muscle layers.
• Stage III - the spread of the pathological process to the entire thickness of the muscular wall of the uterus to its serous cover.
• Stage IV - involvement in the pathological process, in addition to the uterus, parietal peritoneum of the pelvis and adjacent organs.

Classification of endometrioid cysts of the ovaries

• Stage I - small point endometrioid formations on the surface of the ovaries, peritoneum of the rectum-uterine space without the formation of cystic cavities.
• Stage II is an endometrial cyst of one of the ovaries with a size of no more than 5-6 cm with small endometrioid inclusions on the peritoneum of the pelvis. Minor adhesive process in the area of the uterine appendages without intestinal involvement.
• Stage III - endometrioid cysts of both ovaries. Endometrioid heterotopia of small size on the serous cover of the uterus, fallopian tubes and on the parietal peritoneum of the small pelvis. Pronounced adhesion process in the appendages of the uterus with partial involvement of the intestine.
• Stage IV - bilateral endometrioid cysts of large ovaries (more than 6 cm) with the transition of the pathological process to neighboring organs - the bladder, rectum and sigmoid colon. A widespread adhesion process.

Classification of endometriosis of the rectovaginal septum.

• Stage I - endometriotic foci are located within rectovaginal tissue.
• Stage II - germination of endometrioid tissue in the cervix and vaginal wall with the formation of small cysts.
• Stage III - the spread of the pathological process to the sacro-uterine ligaments and the serous cover of the rectum.
• Stage IV - involvement in the pathological process of the rectal mucosa, the spread of the process to the peritoneum of the rectum-uterine space with the formation of an adhesive process in the region of the uterine appendages.

[26], [27], [28], [29], [30]

Diagnostics of the endometriosis

The diagnosis is based on the typical symptoms of the disease. The diagnosis should be confirmed by biopsy, which is performed with laparoscopy, sometimes by laparotomy, vaginal examination, sigmoidoscopy or cystoscopy. When diagnosing endometriosis in the biopsy material, the intrauterine glands and stroma should be determined. Endometriosis has the following macroscopic signs: the presence of transparent, red, brown, black implants whose dimensions vary during the menstrual cycle; the most typical area of endometriosis is the pelvic peritoneum, on which the punctuation of red, blue or purple-brown grains larger than 5 mm is determined.

Endometrioid passages can be detected using ultrasonography, passage of barium through the intestine, intravenous urography, CT and MRI, but the data obtained are not definite and adequate for the diagnosis. At the present level, serological studies of markers of endometriosis (for example, serological cancer antigen 125 [> 35 units / ml], antiendometrioid antibodies), which can help in the diagnosis, are conducted, but these data need further processing. Women who have endometriosis must always be screened for infertility.

Objective examination of patients

Given the cyclical changes in the patients' condition, the increase in manifestations of endometriosis (endometriosis disease) in the second phase of the menstrual cycle, it is advisable to conduct an objective examination of patients in this period.

Inspection. Growth, body weight, body type and constitution. Coloring of the skin. Presence and condition of scars on the anterior abdominal wall, condition of the umbilical ring. The form and degree of development of mammary glands.

Gynecological examination for the detection of endometrioid heterotopies is advisable to be carried out in the second phase of the menstrual cycle 3-5 days before the expected monthly periods. The examination begins with examination of the perineum (scars, infiltrates, ulceration, etc.).

When examining the vagina, attention should be paid to the area of the posterior fornix (polyposis overgrowth, infiltration). When examining the cervix, areas suspected of endometriosis (nodular or small-cystic growths that are clearly visible on the eve or during the menstrual period) can be identified. When palpation of the uterus is determined by its shape, size, mobility, soreness, it is necessary to assess the state of the isthmus (infiltration, soreness in the lesion of its endometriosis disease) and the posterior vaginal vault (infiltration in endometriosis). When palpation of the appendages of the uterus, their magnitude, mobility, soreness, consistency is determined. The condition of the sacro-uterine ligaments is assessed (thickened, strained, painful when affected by endometriotic heterotopia).

Gynecological examination is one of the most important methods of diagnosing endometriosis.

• It is necessary to carefully examine the vulva, vagina and cervix to detect any signs of endometriosis. When examining the vaginal part of the cervix, endometrial foci of varying size and shape are seen (from small-to-small cysts to 0.7-0.8 cm in diameter, of different colors).
• In the isthmus of the uterus, there is a densification, enlargement, soreness, in the posterior vaginal vault - infiltration of tissues, adhesive changes. When palpation is determined by thickening, tension and soreness of the sacro-uterine ligaments.
• In nodal adenomyosis, the uterus is of normal size or slightly enlarged with dense painful nodes in the region of the bottom, body or corners. Before menstruation and during it, the size of the nodes increases somewhat, the uterus softens, and soreness increases sharply. With diffuse adenomyosis, the size of the uterus reaches 5-8 weeks of pregnancy and more. A clear relationship between the size of the uterus and the phases of the menstrual cycle is noted.
• With endometriosis of the ovaries, painful, immobile, dense, enlarged ovaries or a conglomerate of the appendages of the uterus are palpable from one or both sides. Dimensions and soreness of the conglomerate of the appendages of the uterus vary depending on the phases of the cycle. Endometrioid cysts are defined as painful tumor-like formations of ovoid form, of various sizes (on average 6-8 cm), of a tautoelastic consistency, limitedly mobile, located laterally and posteriorly from the uterus.
• Endometriosis rectovaginal septum with vaginal (or vaginal-rectal) study is established when a dense, painful formation is detected, with an uneven surface 0.8-1 cm or more (up to 4-5 cm) on the posterior surface of the uterus of the uterus. The node is surrounded by dense painful infiltration, extending to the anterior wall of the rectum and the posterior vaginal vault.

Colposcopy. It is spent to all patients. In this study, foci of ectometriosis on the cervix can be identified.

[31], [32], [33], [34], [35], [36]

Tests of functional diagnostics

For endometriosis disease, a monophasic (no ovulation) curve of rectal temperature or a slow rise in temperature in phase II are characteristic, indicating that the function of the corpus luteum is inadequate. It is also possible to have a two-phase curve that indicates ovulation.

Radiation methods of research

X-ray methods. Hysterosalpingography is more expedient in the I phase of the menstrual cycle. Although adenomyosis is characterized by the presence of contiguous tissues, this sign is not permanent. Excretory urography reveals the involvement of the urinary tract (ureters, bladder) in the process.

Irrigoscopy is performed if there is a suspicion of endometriosis spreading to the lower parts of the large intestine. In this case, narrowing of the gut lumen or its deformation is determined. Filling defects have even and clear contours.

X-ray examination of the chest is performed with suspicion of the thoracic forms of endometriosis (lungs, pleura, diaphragm). Radiographic examination of the lumbar spine is performed during differential diagnosis.

Ultrasound examination. The method allows to establish the presence of endometrioid cysts of the ovaries. Characteristic uneven consistency of the contents of the cyst, a close relationship with the uterus. The posterior endometriosis is presented in the form of a homogeneous dense infiltrate, the day before or during menstruation - cellular structure. Although adenomyosis is characterized by a low level of the myometrium structure, this characteristic is not constant.

Computed tomography and magnetic resonance imaging. The methods contribute to the determination of not only the explicit localizations of heterotopies, but also of smaller foci of the lesion of the sexual sphere. MRI is one of the most accurate methods for establishing the localization of foci of endometriosis (endometriosis disease) by the difference in the density of the tissues studied.

Invasive methods for the diagnosis of endometriosis (endometriosis)

Laparoscopy. The method is the most informative for the diagnosis of genital endometriosis. "Small forms" of endometriosis are defined as eyes with a diameter of 1-5 mm, which rise above the surface of the peritoneum, bright red, dark brown in color. The most frequent localization of endometrioid heterotopia is the peritoneum, which covers the sacro-uterine ligaments and the rectal-uterine cavity. Endometrioid cysts are defined as rounded formations with a thick capsule, dark brown contents, with extensive spikes. The permeability of the pipes is determined by introducing a colorant through the uterus.

Hysteroscopy. If there is a suspicion of endometriosis of the uterus (adenomyosis), hysteroscopy is carried out in phase I of the cycle. In this case, against the background of a thin mucous membrane, the mouth of the endometrioid passages can be seen rounded, oval and slit, dark red or bluish, from which blood flows.

Histomorphological studies

Any parts of the removed organ are subjected to the investigation in order to verify and detect pathomorphological studies characteristic of endometriosis.

Differential diagnosis

Differential diagnosis of genital endometriosis is performed with:

• myoma of the uterus;
• chronic endometritis;
• hyperplastic processes of the endometrium;
• ovarian tumors;
• metroflebitom;
• malignant neoplasms of the genitals;
• tubo-ovarian formations of inflammatory etiology.

Treatment of the endometriosis

The goal of endometriosis treatment is removal of foci of endometriosis, relief of clinical symptoms, restoration of reproductive function.

Indications for hospitalization

• Severe pain syndrome, not stopping the introduction of drugs.
• Rupture of the endometrioid cyst.
• Metrorrhagia associated with adenomyosis.
• Planned surgical treatment.

With the prevalent forms of the disease and the high risk of recurrence, a modern approach to the treatment of endometriosis patients is the combination of a surgical method and hormonal therapy.

When choosing a method for treating endometriosis, the following factors should be considered:

• age;
• attitude towards reproductive function;
• oschesmatic condition and transferred diseases;
• personality characteristics, psychosomatic status (profile);
• localization, prevalence and severity of the course (anatomical and morphological changes, such as: inflammatory, cicatrical-adhesive processes, endometrial hyperplasia, destructive changes in the ovaries and uterus, etc.).

The main methods of treatment of endometriosis are:

1. Surgery.
2. Conservative treatment, including hormonal and auxiliary (syndrome) therapy.
3. Combined treatment (surgical and conservative).

Surgery

The volume of surgical treatment for endometriosis is determined by its clinical form and stage of the pathological process.

Indication for the operation:

• Endometrioid cysts (endometriomas).
• Internal endometriosis (adenomyosis of the uterus), accompanied by heavy bleeding and anemization.
• Inefficiency of hormonal treatment, intolerance to hormonal drugs.
• Endometriosis of postoperative scars, navel, perineum.
• Continuing stenosis of the lumen of the intestine or ureters, despite the removal or reduction of pain under the influence of conservative treatment.
• The combination of endometriosis with anomalies of the genitals (endometriosis of the accessory horn).
• Combination of uterine fibroids, subject to surgical treatment, with some localizations of endometriosis (isthmus of the uterus, zadachachechnogo, etc.).
• Endometriosis (endometriosis disease) in patients with oncological diseases, for which surgical, radiation treatment and / or chemotherapy was performed (ovarian cancer, thyroid cancer, stomach cancer, colon cancer, etc.); a little differently with the carcinoma of the breast. With this localization, zoladex can be used to treat endometriosis.
• Combination of endometriosis and infertility, when pregnancy does not occur within 2 years. The operation is performed in a savings volume.
• The presence of somatic pathology, excluding the possibility of prolonged hormonal therapy (cholelithiasis, urolithiasis, thyrotoxicosis, hypertensive disease with a crisis current).
• Combination of endometriosis with nephroptosis requiring surgical correction, or Allen-Masters syndrome.

Endometriosis of the moderate and severe course is treated most effectively with ablation or excision of as many endometriosis sites as possible, while the reproductive potential remains. Indications for surgical treatment are the presence of limited outgrowths of endometriosis, significant adhesions in the pelvic area, obstruction of the fallopian tubes, the presence of debilitating pain in the pelvis and the patient's desire to maintain reproductive function.

Endometriosis is also treated with microsurgical methods to prevent adhesion. Laparoscopy is used to remove lesions; peritoneal or ovarian endometrioid heterotopy can be removed by electrocautery or vaporization and excision with a laser. After this treatment, fertility is restored in 40-70% and inversely proportional to the severity of endometriosis. If the resection is not complete, then the appointment of oral contraceptives or GnRH agonists may increase the fertility rate. Laparoscopic resection of sacro-uterine ligaments with electrocautery or laser excision can reduce pelvic pain. Some patients need to perform presecral nevrectomy.

Hysterectomy is performed by patients who have endometriosis and pelvic pains of a debilitating nature, and to patients who have performed the function of procreation. After removal of the uterus and both ovaries in the postoperative period, estrogens can be prescribed or, if a significant amount of endometrioid tissue is preserved, the appointment of estrogens can be delayed by 46 months; During this interval, suppressive drugs are necessary. Together with estrogens, prolonged progestin can be prescribed (for example, medroxyprogesterone acetate 2.5 mg orally once a day), because pure estrogen can lead to overgrowth and hyperplasia of the residual endometrial tissue and to endometrial cancer.

Conservative (hormonal and auxiliary) treatment

The goal of hormonal therapy is the development of atrophic changes in the tissue of endometrioid heterotopia. However, hormonal therapy does not eliminate the morphological substrate of endometriosis, but has an indirect effect on it; This explains the symptomatic and clinical effect of therapy.

The choice of drugs and methods for their use depend on the age of the patient, the location and extent of endometriosis, the tolerability of drugs, the presence of concomitant gynecological and somatic pathology.

Gonadotropin-releasing hormone agonists:

• Buserelin in the form of depot forms in / m at 3.75 mg once in 28 days or Buserelin in the form of a spray at a dose of 150 mcg in each nostril 3 times a day from the 2nd day of the menstrual cycle;
• goserelin n / a 3.6 mg once every 28 days;
• tryptorelin (in the form of depot forms) IM in 3.75 mg once in 28 days; Gonadotropin-releasing hormone agonists are the drugs of choice in the treatment of endometriosis. The duration of therapy is 3-6 months.

When there are pronounced side effects associated with the development of hypoestrogenic effect (hot flushes, increased sweating, palpitations, nervousness, urogenital disorders, etc.), the return therapy with drugs for hormone replacement therapy (for example, tibolone, 1 tablet per day in continuous mode for 3-6 months).

• Dalteprin sodium is administered orally for 1 capsule (100 or 200 mg) 3 or 4 times a day (daily dose of 400-800 mg) for 3-6 months, less than 12 months.
• Gestrinone is administered orally 2.5 mg twice a week for 6 months.
• COCs are prescribed from the 1st to the 21st day of the menstrual cycle or continuously, the course is 6-12 months.

Progestogens:

• medroxyprogesterone acetate orally 30 mg / day or IM 150 mg of the deposited substance every 2 weeks for 6-9 months;
• dydrogesterone orally 10-20-30 mg / day for 6-9 months.

For the hormonal treatment of endometriosis, the following groups of drugs are currently used:

• combined estrogen-gestagen preparations (silage marvelon, etc.);
• progestins (Dyufaston, Depo-Provera, 17-OPK);
• antigestagens (gestrion);
• antigonadotropins (danazol, danogen);
• GnRH agonists (zoladex, buserelin, decapeptil);
• antiestrogens (tamoxifen, zitozonium);
• anabolic steroids (non-working, retabolil).

When choosing a drug and the method of hormonal therapy should take into account:

• Age of the patient. In the active reproductive age (up to 35 years) the advantage should be given to progestins, then combined estrogen-progestin drugs, anabolic steroids; the use of androgens should be minimal. At the age of over 35 years, in the absence of contraindications it is permissible to use a variety of drugs.
• Concomitant symptoms and syndromes: hyperpolymenorrhea, viril syndrome, overweight.
• The condition of the reproductive system: concomitant diseases (eg mammary glands), in which contraindications to prescription of drugs may occur.
• Profession. The gestagenic properties of progestins can cause voice changes (speakers, singer, actresses, teachers, etc.).
• Background hormonal profile: the level of gonadotropins and sex steroids in the blood serum or their metabolites in the urine.
• The period of the therapy: before the surgical stage and in the postoperative period.
• Activity of the manifestation of clinical forms of endometriosis.
• The necessary mode of administration (continuously or cyclically) of drugs (for hormonal contraceptives and gestagens).

The presence or absence of contraindications to the use of hormonal drugs in conservative therapy, which are:

• Polyvalent allergy.
• Hypersensitivity to specific drugs.
• Thrombosis, thromboembolic processes, chronic thrombophlebitis, hypercoagulable syndrome.
• Pregnancy, lactation.
• Combination of endometriosis with uterine myoma *.
• Diseases of the mammary glands **.
• Porphyria.
• Diseases of the liver (cirrhosis, acute and chronic hepatitis, Rotor syndrome, Dubin-Johnson syndrome, cholestatic jaundice).
• Diseases of the blood (leukopenia, thrombocytopenia, hypercalcemia).
• Bleeding unclear etiology from the genital tract.

* Exception for monophasic estrogen-progestogen drugs.

** Exception for gestagens.

• Herpes, jaundice of pregnant women in anamnesis, otosclerosis, severe itching. .
• Dysplasia of the epithelium of the cervix and cervical canal.
• Tumors of the uterine appendages.
• Kidney disease in the stage of decompensation of their function (including urolithiasis).
• Diabetes.
• Hypertensive disease (stage II-B).
• Diseases of the organs of vision (glaucoma).
• Organic diseases of the central nervous system and manic-depressive conditions (severe depression).
• Malignant tumors of any localization.

Carrying out hormonal therapy is aimed at creating the effect of "imaginary pregnancy" or "therapeutic amenorrhea". The onset of pregnancy in the treatment of endometriosis is an indication for the abolition of hormonal drugs and the implementation of measures aimed at its preservation. During hormonal therapy, prevention of liver, digestive tract and kidney damage should be carried out. Control tests at least 1 time in 3 months.

The criteria for the effectiveness of the therapy are:

• the dynamics of clinical manifestations of endometriosis;
• results of histological examination.

Endometriosis is being treated with non-steroidal anti-inflammatory drugs. Differentiated treatment should be carried out individually, taking into account the age of the patient, the symptoms of the disease, the desire to maintain reproductive function. The drugs of choice are the means for suppressing ovarian function, growth and activity of endometriosis. Effective conservative surgical resection of as many endometrioid sprouts as possible; sparing operations are performed and preparations are prescribed. In severe cases, preparations for suppressing ovarian function and suppressing the growth of endometrial tissue are oral contraceptives used in a continuous mode, agonists of GnRH and danazol. GnRH agonists temporarily suppress the production of estrogens, but treatment should last no more than 6 months, because longer use can lead to loss of bone mass. If the treatment lasts more than 4-6 months, daily administration of low-dose oral contraceptives is added to this therapy. Danazol is a synthetic androgen and antigonadotropin, inhibits ovulation. However, the androgenic adverse effects of the drug limit its use. After administration of danazol or GnRH agonists, oral contraceptives are administered in a cyclic or continuous fashion; they can also slow the progression of the disease and provide a contraceptive effect for women who do not wish to become pregnant in the future. After pharmacotherapy of patients who suffer from endometriosis, fertility rates are restored in 40-60%. Whether the reproductive function improves in the treatment of minimal or mild endometriosis is unclear.

[37], [38], [39]

Auxiliary (syndromic) treatment

Conducting syndromic treatment of endometriosis is aimed at reducing pain, blood loss, etc. And includes the use of funds:

• non-steroidal anti-inflammatory (prostaglandin inhibitors);
• immunocorrection (levomizol, timogen, tsikloferon);
• antioxidant therapy (HBO, tocopherol acetate, etc.);
• desensitizing therapy (sodium thiosulfate);
• correction of psychosomatic and neurotic disorders (radon, iodine-bromine baths);
• treatment of concomitant diseases.

[40], [41], [42], [43]

Combined treatment

The idea that endometriosis patients are subject to predominantly radical surgical treatment, which has existed for decades, has been replaced by a trend toward combined therapy of this contingent of patients. This tactic implies the operative treatment (according to indications) on the principles of minimizing surgical trauma in combination with hormonal correction and various types of auxiliary therapy.

The leading role in combined therapy of genital endometriosis belongs to surgical treatment. At the first stage, endosurgical interventions are performed, with laparoscopy allowing for objective selection of patients for laparotomy at earlier stages of affection of neighboring organs, removal of the most affected areas, cryodestruction of the remote infiltration bed and small foci of endometriosis.

After performing the surgery for endometriosis (especially organ-preserving, non-radical, as well as in a common process and combined form), adjuvant hormone-modulating therapy is indicated for 6-12 months. The choice of hormonal drugs and the duration of treatment after the operation should be differentiated for each patient, taking into account the prevalence of the disease, concomitant somatic pathology, the state of the immune system.

[44], [45], [46]

Rehabilitation

• Conducting general restorative therapy (physiotherapy exercises, multivitamins, calcium preparations).
• The overwhelming majority of patients after the operation are required to be carried out for 6-12 months. Anti-relapse therapy, especially when performing them in a savings volume. Treatment is carried out with the mandatory inclusion of hormonal drugs and immunomodulators. The latter are especially needed after extensive operations for common genital and extragenital endometriosis, when the secondary immune system deficit is expressed significantly. Hormonal therapy is indicated after bilateral ovariectomy, if the radical removal of extragenital endometriosis failed. It is established that hormonal treatment, appointed immediately after the operation, significantly improves the results of treatment and reduces the frequency of recurrence of the disease. Clinical recovery occurs in 8 times more often in the case of hormone therapy immediately after surgical removal of endometriosis.
• The appointment and conduct of an anti-relapse course of treatment with progestins (dyufaston, norkolut, non-vellon, etc.) is recommended after exposure to factors contributing to exacerbation of the disease (abortions, diathermosurgical manipulations on the cervix, exacerbation of inflammatory diseases, etc.).
• Physical factors without significant thermal component (drug electrophoresis, ultrasound, magnetophores, diadynamic currents, etc.) are prescribed for the purpose of carrying out resorptive and anti-inflammatory therapy, preventing "adhesions".
• After removing endometriosis foci by surgical means or suppressing their activity with hormonal drugs, resort factors (radon and iodine-bromine waters) should be used to eliminate psychoneurological manifestations, cicatricial and infiltrative tissue changes, and to normalize the function of the gastrointestinal tract.
• Treatment of pronounced neurological manifestations in patients with endometriosis disease allows not only to eliminate the lesions of the peripheral nervous system, but also to prevent the development of neurotic-like conditions. Therapy should be purposeful in view of the identified neurologic syndromes. The use of physical and resort factors, tranquilizers, analgesics, psychotherapy, acupuncture allows faster elimination of neurological disorders.

Forecast

The success of surgical intervention to restore reproductive function depends on the prevalence of endometriosis: the effectiveness of treatment at stage I of the disease is 60%, with the prevalent endometriosis - 30%. Relapses of the disease within 5 years after surgical treatment develop in 19% of patients.

With the use of hormonal therapy, 70-90% of women note a reduction in pain and a decrease in the intensity of menstrual bleeding. The frequency of recurrence of endometriosis one year after the course of therapy is 15-60%, the frequency of pregnancy is 20-70%, depending on the group of drugs.