Adenomyosis: new possibilities of therapy. Comprehensive treatment of patients with adenomyosis What is adenomyosis

Given the increasing incidence of the disease, genital endometriosis is becoming one of the leading causes of infertility M.M. Damirov, 2004. Adenomyosis is detected in 40-45% of women with unexplained primary and 50-58% with secondary infertility. V.P. Baskakov et al., 2002.

The aim of our work was the use of Roncoleukin (LLC "BIOTECH" St. Petersburg) in the complex therapy of patients with adenomyosis suffering from infertility.

88 patients with adenomyosis of reproductive age were examined and treated. The diagnosis was established during a comprehensive clinical and laboratory examination, using additional methods (hysteroscopy, separate curettage of the uterus, transvaginal ultrasound in the dynamics of the menstrual cycle).

All patients were divided into two groups: Group I (44 patients) - patients with adenomyosis who received traditional complex hormonal therapy,

II (main) group (44 patients) - patients with adenomyosis, in addition to traditional treatment, received Roncoleukin.

All patients received hormonal therapy with Nemestranom (5 mg weekly twice a week) continuously for 6 months. Additionally, patients of group II after hysteroscopy with separate curettage of the uterus on days 2, 3, 6, 9 and 11 were prescribed Roncoleukin according to the following method: 0.25 mg Roncoleukin was diluted in 2 ml of 0.9% NaCL solution, the volume was adjusted to 50 ml with the addition of 0 5 ml of a 10% solution of human albumin and, through a polypropylene catheter inserted into the uterine cavity to the bottom level, irrigated it for 6 hours with free flow of fluid through the cervical canal. At the same time, 0.5 mg of Roncoleukin, dissolved in 2 ml of water for injection, was injected subcutaneously at 0.5 ml at four points. Dynamic monitoring of patients with ultrasound guidance was carried out during the course of therapy and 12 months after its completion.

A month after the end of the course of hormonal therapy - after the restoration of menstrual function, pregnancy was planned by 16 patients of group I and 18 patients of group II who suffered from infertility, the rest of the women used a barrier method of contraception during the entire observation period.

In the first 3 months after the end of the main course of treatment, pregnancy occurred in 10 women of group II and only in 2 of group I; over the next three months, pregnancy occurred in 7 patients of group II and 4 of group I. Over the next 6 months of observation, in one remaining patient of group II, pregnancy did not occur, and in group I, 2 women did. As a result, by the end of the year of observation after the end of treatment, 8 patients of the first group and 1 patient of the second group complained of infertility. As a result, 17 patients out of 18 (94.4%) of the main (second) group realized their desire to become pregnant, and only 8 patients out of 16 (50%) (p < 0.01) who received traditional therapy.

Thus, the combined systemic and local (intrauterine) administration of a highly active immunotropic drug of recombinant IL-2 - Roncoleukin opens up new prospects in the complex therapy of adenomyosis and makes it possible to improve the results of treatment, one of the indicators of which is the restoration of reproductive function.

The term "adenomyosis" is formed from two words - "adeno", which means connection with any gland or glands, and "miosis", which characterizes a variety of inflammations. That is,adenomyosis– disease, in which the inflammatory process occurs, which arose due to a violation of the normal functioning of the glands. Abnormal processes affect the muscular layer of the uterus, therefore, adenomyosis is nothing more than one of the varieties of endometriosis.

The endometrium is the mucous layer of the uterus. When endometriosis occurs, endometrial cells penetrate into the muscular layer of the uterus. "Settling" there, endometrial tissues do not stop their normal activities, gradually growing and increasing. The entire system (the structure of the uterus) fails, hormones cease to be produced in the right amount, immunity weakens. The sites of localization of lesions of muscle tissues swell, the size of the organ increases, resulting in pain in the pelvic region. The reproductive system of a woman begins to work with disorders, that is, internal and then intragenital adenomyosis develops and gradually progresses.

Symptoms of adenomyosis

Often adenomyosis, How disease internal organs of the reproductive system of a woman is asymptomatic. This is typical mainly for the initial stages of the development of pathology. In the future, gradually increasing, the woman has such painful symptoms:

• Pain localized (usually) in the pelvic region. Observed during menstruation, as well as before and after its occurrence
• Unhealthy brown, "chocolate" discharge
• Shortening the menstrual cycle
• Abnormal changes in the shape and size of the uterus. This symptom is detected by the doctor during the examination of the patient.
• Painful intercourse (dyspareunia)

Also, 40% of patients diagnosed with adenomyosis complain of heavy discharge during menstruation. Almost half of women with internal adenomyosis suffer from moderate to severe premenstrual syndrome. Moreover, half of the patients who seek medical help in case of impossibility to become pregnant turn out to be sick with this very disease, adenomyosis.

Reasons for the development of adenomyosis

It is believed that there is a certain genetic predisposition to adenomyosis. But the disease was often noted in women whose grandparents had never been ill with it. This leads to the conclusion that the tendency to develop the disease is not necessarily inherited, but can be caused by some individual factors.

Gynecologists usually refer to such reasons as constantly arising stress surges. First of all, women who lead an overly active lifestyle fall into the risk group. These may be women running their own businesses; raising children and working at the same time; workers in an enterprise associated with heavy physical labor; girls who are fond of weightlifting.

There is also such an opinion - the excessive use of the solarium and the love of sunbathing. Becoming the object of exposure to ultraviolet rays, the body is forced to endure a number of reactions, which can result in adenomyosis or other disease pertaining to the gynecological field.

No less dangerous is the use of therapeutic mud baths. This procedure, popular in our time, should be carried out only with the permission of a gynecologist. Incorrect use of mud baths can cause a negative reaction of the body and create conditions for the development of various internal pathologies.

All uterine interventions in one way or another increase the risk of developing adenomyosis. Adenomyosis is most likely to occur if a woman has undergone surgery in the body of the uterus after a miscarriage, had abortions, she had mechanical injuries of the internal genital organs.

Today, scientists confirm only such variants of the etiology of the disease. There is no exact data on the causes leading to the development of endometrial cells outside the uterine mucosa.

Adamyan L.V.

Endometriosis remains an unresolved scientific and clinical problem, the main debatable issues of which include the following: is endometriosis always a disease; mechanisms of development and classification; genetic and immunological aspects of endometriosis; external, internal endometriosis and adenomyosis; retrocervical endometriosis; endometriosis and pelvic pain; endometriosis and adhesive process; endometriosis and infertility; diagnostic criteria; traditional and non-traditional approaches to diagnosis and treatment. Examination, treatment and monitoring of more than 1300 patients with endometriosis made it possible to determine the authors' own positions regarding the morphofunctional, endocrinological, immunological, biochemical, genetic aspects of endometriosis and to develop alternative treatment programs.

Concepts of etiopathogenesis

The definition of endometriosis as a process in which a benign growth of tissue occurs outside the uterine cavity, similar in morphological and functional properties to the endometrium, has remained unchanged over the past century. The following main theories of the occurrence of endometriosis remain a priority:

implantation theory based on the possibility of transferring the endometrium from the uterine cavity through the fallopian tubes into the abdominal cavity, described in 1921 by J.A. Sampson. There is also a possibility of endometrial translocation during surgical interventions on the uterus and dissemination of endometrial cells by the hematogenous or lymphogenous route. It is the hematogenous pathway of "metastasis" that leads to the development of rare forms of endometriosis with damage to the lungs, skin, muscles;

a metaplastic theory that explains the appearance of endometrial-like tissue by metaplasia of the mesothelium of the peritoneum and pleura, the endothelium of the lymphatic vessels, the epithelium of the tubules of the kidneys and a number of other tissues;

dysontogenetic theory, based on the possibility of disruption of embryogenesis and the development of endometrioid tissue from abnormally located rudiments of the Müllerian canal. According to the observations of the authors of the article, endometrioid lesions are often combined with congenital anomalies of the genital organs (bicornuate uterus, accessory uterine horn, which impede the normal outflow of menstrual blood).

The key moment in the development of endometriosis - the occurrence of endometrioid heterotopia - has not yet been explained by any of the theories. Undoubtedly, this requires that the endometrial cells have an increased ability to implant, and the body's defenses are insufficient to ensure the clearance of ectopic endometrial cells. The implementation of these conditions is possible under the influence of one or more factors: hormonal imbalance; unfavorable ecology; genetic predisposition; immune disorders; inflammation; mechanical injury; disorders in the systems of proteolysis, angiogenesis and iron metabolism.

Endometriosis as a genetically determined pathology is one of the newest concepts, which is based on the presence of familial forms of the disease, the frequent combination of endometriosis with malformations of the urogenital tract and other organs, as well as the features of the course of endometriosis (early onset, severe course, relapses, resistance to treatment) with hereditary forms of the disease. The authors of the article described cases of endometriosis in a mother and eight daughters (endometriosis of various localization), in a mother and two daughters (endometrioid ovarian cysts), endometriosis in twin sisters. Based on cytogenetic studies, the relationship of the HLA antigen (Human leucocyte antigen) with endometriosis, quantitative and structural changes in chromosomes in endometrial cells (increased heterozygosity of chromosome 17, aneuploidy) have been established, it has been suggested that bilateral endometrioid cysts can arise and develop independently from different clones. The detection of specific genetic markers in the future will make it possible to identify genetic predisposition, carry out prevention and diagnose preclinical stages of the disease.

The immunological aspects of endometriosis have been intensively studied since 1978. Of interest are data on the presence of changes in general and local immunity in patients with endometriosis, which play a certain role in the development and progression of the disease. Some researchers believe that endometrioid cells have such a powerful aggressive potential that they cause damage to the immune system.

The intravital phase-interference images of peritoneal fluid and peripheral blood cells obtained by the authors of the article in patients with deep infiltrative endometriosis convincingly indicate the active participation of the immune system in the pathogenesis of this disease. Most of the current studies are devoted to the role of peritoneal macrophages, cytokines, integrins, growth factors, angiogenesis and proteolysis, which favor the implantation of endometrial cells and cause pro-inflammatory changes in the peritoneal environment. production (in particular, dioxins), the occurrence of endometriosis.

Thus, the main etiopathogenetic factors of endometriosis should be considered retrograde menstruation, coelomic metaplasia, activation of embryonic residues, hematogenous and lymphogenous metastasis, genetic predisposition, iatrogenic dissemination, disorders of the proteolysis system. Risk factors for the development of endometriosis are hyperestrogenism, early menarche, heavy and prolonged menstruation, menstrual blood outflow disorders, unfavorable environment, obesity, smoking, and stress.

Terminology and classifications

Endometriosis is traditionally divided into genital and extragenital, and genital, in turn, into internal (endometriosis of the uterine body) and external (endometriosis of the cervix, vagina, perineum, retrocervical region, ovaries, fallopian tubes, peritoneum, recto-uterine cavity). "Internal endometriosis" in recent years is increasingly considered as a very special disease and is designated by the term "adenomyosis". A comparative analysis of the morphofunctional features of internal and external endometriosis allowed a number of researchers to suggest that retrocervical endometriosis is an "external" variant of adenomyosis (adenomyosis externa). There are more than 20 histological variants of external endometriosis, including: intraperitoneal or subperitoneal (vesicular - cystic or polypoid), as well as muscular fibrous, proliferative, cystic (endometrioid cysts).

Over the past 50 years, more than 10 classifications of endometriosis have been developed, none of which is recognized as universal. One of the most widely used in world practice was the classification proposed in 1979 by the American Fertility Society (since 1995 - the American Society for Reproductive Medicine) and revised in 1996, based on the calculation of the total area and depth of endometrioid heterotopias, expressed in points : stage I - minimal endometriosis (1–5 points), stage II - mild endometriosis (6–15 points), stage III - moderate endometriosis (16–40 points), stage IV - severe endometriosis (more than 40 points). The classification is not without drawbacks, the main of which is the frequent discrepancy between the stage of spread, determined by scoring, and the true severity of the disease. The authors of the article use their own clinical classifications of endometriosis of the uterine body, endometrioid ovarian cysts and retrocervical endometriosis, which provide for the allocation of four stages of the spread of endometrioid heterotopias. Undoubtedly, the true severity of the disease is determined by the clinical picture that characterizes the course of a particular variant of the disease.

Malignancy of endometriosis

For the first time, the malignant degeneration of endometriosis was reported by J.A. Sampson in 1925, having determined the pathological criteria for a malignant process in an endometrioid focus: the presence of cancerous and benign endometrioid tissue in the same organ; the occurrence of a tumor in the endometrioid tissue; complete encirclement of tumor cells by endometrioid cells.

The clinical course of malignant endometriosis is characterized by the rapid growth of the tumor, its large size, and a sharp increase in the levels of tumor markers. The prognosis of the course is unfavorable, the survival rate for non-disseminated forms is 65%, for disseminated forms - 10%. The most common variant of malignant tumors in endometrioid heterotopias is endometrioid carcinoma (about 70%). With widespread endometriosis, even after removal of the uterus and appendages, the risk of endometrioid tissue hyperplasia and malignancy of extraovarian endometriosis remains, which can be facilitated by the appointment of estrogen replacement therapy.

Extragenital endometriosis

Rare forms of endometriosis that require a special approach are extragenital foci that can exist as an independent disease or be components of a combined lesion. In 1989, Markham and Rock proposed a classification of extragenital endometriosis: class I - intestinal; class U - urinary; class L - bronchopulmonary; class O - endometriosis of other organs. Each group includes variants of the disease with or without a defect (with or without obliteration) of the affected organ, which is fundamentally important in determining treatment tactics.

Diagnostics

F. Konincks in 1994 suggested that the term "endometriosis" refer only to the anatomical substrate; and a disease associated with this substrate and manifesting certain symptoms is called "endometrioid disease." Adenomyosis is detected in histological preparations in 30% of women who have undergone a total hysterectomy. The incidence of external endometriosis is estimated to be 7–10% in the general population, reaching 50% in women with infertility and 80% in women with pelvic pain. Endometriosis most often occurs in women of reproductive age (25–40 years), often combined with uterine myoma, hyperplastic processes in the endometrium, obstructive malformations of the genital organs.

The final diagnosis of external endometriosis is possible only with direct visualization of lesions, confirmed by histological examination, which reveals at least two of the following signs: endometrial epithelium; endometrial glands; endometrial stroma; hemosiderin-containing macrophages. It should be remembered that in 25% of cases, endometrial glands and stroma are not found in the foci, and, on the contrary, in 25% of cases, morphological signs of endometriosis are found in samples of visually unchanged peritoneum. The final diagnosis of adenomyosis is also established by pathomorphological examination of the material when the following signs are detected: endometrial glands and stroma at a distance of more than 2.5 mm from the basal layer of the endometrium; reaction of myometrium in the form of hyperplasia and hypertrophy of muscle fibers; an increase in the glands and stroma surrounding the hyperplastic smooth muscle fibers of the uterus; presence of proliferative and absence of secretory changes.

The most important clinical symptoms of endometriosis, which determine indications for treatment, are pelvic pain, disruption of normal menstrual bleeding, infertility, and dysfunction of the pelvic organs. The severity and set of manifestations of the disease vary individually. A symptom characteristic of adenomyosis - menometrorrhagia and perimenstrual spotting of the "daub" type, is due to both cyclic transformations of the ectopic endometrium and a violation of the contractile function of the uterus. Pelvic pain, usually aggravated the day before and during menstruation, is typical of both external endometriosis and adenomyosis.

Complaints of dyspareunia are presented by 26-70% of patients suffering from endometriosis with a predominant lesion of the retrocervical region, sacro-uterine ligaments. This symptom is due to both obliteration of the retrouterine space with adhesions, immobilization of the lower intestines, and direct damage to the nerve fibers by endometriosis. A fairly common occurrence is the absence of pain in endometrioid cysts of considerable size. At the same time, intense pelvic pain often accompanies mild to moderate pelvic endometriosis and is presumably due to changes in prostaglandin secretion and other pro-inflammatory changes in the peritoneal environment. When assessing the severity of pain, they rely on the subjective assessment of the patient, which largely depends on her personal characteristics (psycho-emotional, socio-demographic).

Another symptom characteristic of endometriosis (in the absence of other apparent causes) is infertility, which accompanies this pathology in 46–50%. Causal relationships between these two conditions are not always clear. For certain variants of endometriosis, it has been proven that infertility is a direct consequence of such anatomical damage as adhesive deformity of the fimbriae, complete isolation of the ovaries by periovarian adhesions, damage to ovarian tissues by endometrioid cysts. The role of factors supposedly involved in the development of endometriosis or being its consequence is more controversial: violations of the ratio of hormone levels leading to inferior ovulation and / or functional inferiority of the corpus luteum, endometrium; disorders of local (increased levels of pro-inflammatory cytokines, increased suppressor/cytotoxic population of T-lymphocytes, growth factors, activity of the proteolysis system) and general (decrease in the number of T-helpers/inducers and activated T-lymphocytes, increased activity of natural killers, increased content of T-suppressors /cytotoxic cells) immunity.

One of the most important methods for diagnosing endometriosis, despite the widespread introduction of ultrasound and laparoscopy into practice, remains a bimanual gynecological examination, which makes it possible to detect, depending on the form of the disease, a tumor-like formation in the uterine appendages, an increase in the uterus and limitation of its mobility, compaction in the retrocervical region. , pain on palpation of the walls of the small pelvis and sacro-uterine ligaments. With endometriosis of the vaginal part of the cervix and vagina, on examination, endometrioid formations are visible.

Comparative studies of the effectiveness of various methods have made it possible to determine the diagnostic complex, which, with the greatest degree of accuracy, establishes the clinical and anatomical variant of endometriosis. Ultrasound is considered the optimal and generally available screening method in the algorithm for examining patients with various forms of endometriosis (endometrioid ovarian cysts, retrocervical endometriosis, adenomyosis), although it does not reveal surface implants. As the quality of diagnostics of adenomyosis using ultrasound, magnetic resonance imaging (MRI) and spiral computed tomography (SCT) improves, the use of hysterosalpingography becomes less relevant, especially since the diagnostic value of this method is limited. MRI and SCT have the greatest diagnostic value in endometrioid infiltrates of the retrocervical zone and parametrium, allowing to determine the nature of the pathological process, its localization, relationship with neighboring organs, and also to clarify the anatomical state of the entire pelvic cavity. For the diagnosis of endometriosis of the cervix, colposcopy and hysterocervicoscopy are valuable methods.

Currently, the most accurate method for diagnosing external endometriosis is laparoscopy. More than 20 types of superficial endometrioid lesions on the pelvic peritoneum have been described in the literature: red lesions, fire-like lesions, hemorrhagic vesicles, vascularized polypoid or papillary lesions, classic black lesions, white lesions, scar tissue with or without some pigmentation, atypical lesions, etc. The presence of Alain-Masters syndrome indirectly confirms the diagnosis of endometriosis (histologically - in 60-80% of cases).

Laparoscopic signs of a typical endometrioid cyst are: an ovarian cyst with a diameter of not more than 12 cm; adhesions with the lateral surface of the pelvis and / or with the posterior leaf of the broad ligament; thick chocolate content. The accuracy of diagnosing endometrioid cysts during laparoscopy reaches 98-100%. Retrocervical endometriosis is characterized by complete or partial obliteration of the retrouterine space with immobilization by adhesions and / or involvement in the infiltrative process of the walls of the rectum or sigmoid colon, infiltrate of the rectovaginal septum, distal ureters, isthmus, sacro-uterine ligaments, parametrium.

Adenomyosis, which diffusely affects the entire thickness of the uterine wall with the involvement of the serous membrane, causes a characteristic "marble" pattern and pallor of the serous cover, a uniform increase in the size of the uterus or, in focal and nodular forms, a sharp thickening of the anterior or posterior wall of the uterus, deformation of the wall with a node of adenomyosis, hyperplasia myometrium. The effectiveness of diagnosing internal endometriosis using hysteroscopy is controversial, since the visual criteria are extremely subjective, and the pathognomonic sign - the gaping of endometrioid passages with hemorrhagic discharge coming from them - is extremely rare.

Some authors suggest performing a biopsy of the myometrium during hysteroscopy, followed by a histological examination of the biopsy. The detection of various tumor markers in the blood is becoming increasingly important in the diagnosis of endometriosis and its differential diagnosis and a malignant tumor. The most accessible at present is the detection of oncoantigens CA 19-9, CEA and CA 125. The authors of the article have developed a method for their complex determination in order to monitor the course of endometriosis.

Alternative management of patients with endometriosis

Treatment of endometriosis has become the most widely discussed aspect of this problem in recent years. An indisputable position today is the impossibility of eliminating the anatomical substrate of endometriosis by any of the interventions, except for surgery, while other methods of treatment provide a reduction in the severity of symptoms of the disease and restoration of the functions of various parts of the reproductive system in a limited contingent of patients. However, surgical treatment is not always appropriate or acceptable to the patient.

As an alternative, a trial (without verification of the diagnosis) drug treatment of minimal and moderate endometriosis, or rather, the symptoms allegedly caused by this disease, can be considered. Such therapy can only be undertaken by a doctor with extensive experience in the treatment of endometriosis, provided that masses in the abdominal cavity are excluded, there are no other (non-gynecological) possible causes of symptoms, and only after a thorough examination of the patient. although it leads to a decrease in the size of the formation and the thickness of its capsule, it contradicts the principles of oncological alertness.

Despite the data of a number of authors on the rather high effectiveness of hormonal therapy in relation to the pain symptom, the advantages of its positive effect on fertility over the surgical destruction of lesions have not been proven (reported pregnancy rates are 30-60% and 37-70%, respectively), the prophylactic value in regarding the further progression of the disease is doubtful, and the cost of the course of treatment is comparable to that of laparoscopy. On the other hand, in the absence of unequivocal statistical data in favor of surgical or medical treatment of minimal-moderate endometriosis, the choice remains with the patient.

The authors of the article prefer surgical removal of lesions, the adequacy of which depends on the experience and erudition of the surgeon. In case of endometriosis accidentally detected during laparoscopy, it is necessary to remove the foci without injuring the reproductive organs. The visually determined boundaries of the endometrioid focus do not always correspond to the true degree of spread, which makes it necessary to critically evaluate the usefulness of the intervention performed. a single block with the uterus.

With endometrioid cysts, it is fundamentally important to completely remove the cyst capsule, both for reasons of oncological alertness and to prevent relapses, the frequency of which after the use of alternative methods (punctures, cyst drainage, capsule destruction by various influences) reaches 20%. With a nodular or focal-cystic form of adenomyosis, it is possible to perform reconstructive plastic surgery for young patients in the amount of resection of the myometrium affected by adenomyosis, with the obligatory restoration of the defect, warning the patient of a high risk of recurrence due to the lack of clear boundaries between the adenomyosis node and myometrium. Radical treatment of adenomyosis can only be considered total hysterectomy.

Permissible dynamic monitoring or non-aggressive symptomatic treatment of patients with adenomyosis, as well as deep infiltrative endometriosis after the diagnosis is clarified by biopsy and histological examination. Drug therapy can become a component of treatment, the main burden on which falls when the effectiveness of surgical treatment is insufficient or it is refused. A special role is given to non-steroidal anti-inflammatory drugs (prostaglandin synthetase inhibitors), as well as hormonal or antihormonal drugs, the therapeutic effect of which is based on the suppression of steroidogenesis in the ovaries, the creation of a hypoestrogenic state or anovulation.

These are hormonal contraceptives, progestogens (medroxyprogesterone), androgen derivatives (gestrinone), antigonadotropins (danazol), gonadotropin-releasing hormone (GnRH) agonists (triptorelin, buserelin); a new generation of GnRH antagonists and progestogens are currently being tested. The drug must be selected strictly individually, taking into account side effects, if possible, starting with the least aggressive. In particular, GnRH agonists should be prescribed with caution to patients with impaired functional state of the central nervous system and autonomic regulation, which can be aggravated while taking drugs of this group, danazol, although quite effective, in high daily doses (400-800 mg) it has an adverse effect on the gastrointestinal tract, and also has androgenizing and teratogenic potential.

The preoperative appointment of GnRH agonists is discussed, the supporters of which justify its expediency by reducing the size of endometriosis foci, vascularization, and the infiltrative component. From the point of view of the authors of the article, this is unjustified, since as a result of such an impact, radical removal of heterotopias due to masking of small foci, identification of the true boundaries of the lesion in infiltrative forms, and exfoliation of the sclerosed capsule of the endometrioid cyst are difficult. Therapy with GnRH agonists is indicated as the first step in the treatment of symptoms of endometriosis in non-reproductive organs in the absence of obliteration. In the presence of obliteration (partial or complete), the method of choice is an operation involving related specialists, followed by hormonal therapy.

Postoperative treatment with GnRH agonists is advisable for women of childbearing age in advanced endometriosis, in whom radical removal of endometriosis foci was not performed in the interests of maintaining reproductive potential or due to the risk of injuring vital organs, as well as in patients at high risk of recurrence or persistence of the disease. With widespread endometriosis, postoperative hormonal therapy should be combined with anti-inflammatory and spa treatment, which prolongs the remission of the pain syndrome and reduces the risk of reoperations. The principles of add-back therapy to reduce bone loss and hypoestrogenic effects in GnRH agonist therapy include: progestogens; progestogens + bisphosphonates; progestogens in low doses + estrogens.

A special place among the options for hormonal treatment is hormone replacement therapy after radical surgery performed for endometriosis (hysterectomy with or without adnexectomy). The persistence of endometriosis foci with recurrence of symptoms after radical surgical treatment is described. Taking into account the risk of both possible recurrence and malignancy of residual lesions, estrogens are recommended to be used in combination with progestogens.

Recurrence or persistence of endometriosis after treatment is one of the most discussed problems in modern gynecology, due to the unpredictability of the course of the disease. Most authors agree that in the absence of a method that provides an accurate assessment of the adequacy of the performed intervention, the removal of the entire endometrioid substrate cannot be guaranteed by any surgical technique, and even more so by drug therapy. On the other hand, recognizing the role of systemic disorders in the pathogenesis of endometriosis, one cannot deny the possibility of de novo endometriosis.

The frequency of recurrence of endometriosis varies, according to different authors, from 2% to 47%. The highest frequency of recurrence (19–45%) of retrocervical endometriosis is associated both with the difficulty of determining the true boundaries of the lesion in infiltrative forms of endometriosis, and with a conscious rejection of an aggressive approach to removing foci located near vital organs.

Thus, endometriosis is characterized by paradoxical aspects of etiopathogenesis and clinical contrasts of the course, which have not yet been explained. Indeed, with a benign nature of the disease, an aggressive course with local invasion, wide distribution and dissemination of foci is possible; minimal endometriosis is often accompanied by severe pelvic pain, and large endometrioid cysts are asymptomatic; cyclic exposure to hormones causes the development of endometriosis, while their continuous use suppresses the disease. These mysteries stimulate further deepening and expansion of both basic and clinical research in all areas of the problem of endometriosis.

Over the past quarter century, there has been a steady increase in the incidence of genital endometriosis. Currently, endometriosis is gradually moving into third place in the structure of gynecological morbidity in Russia, since about 8-15% of women of reproductive age have this pathology. Genital endometriosis is the second most common disease in women of reproductive age, causing infertility, pain, and various menstrual irregularities.

The problem of genital endometriosis is especially relevant for young women, since the disease is accompanied by significant reproductive and menstrual dysfunctions, persistent pain syndrome, dysfunction of adjacent organs, as well as a deterioration in the general condition of patients, a decrease in their ability to work. The most common localization of genital endometriosis is the defeat of the uterus - adenomyosis, whose share in the structure of this pathology is from 70 to 80%.

The purpose of our study was to improve treatment tactics in patients with adenomyosis with initial manifestations of the disease based on the correction of the results of morpho-biochemical studies.

A comprehensive clinical, morpho-biochemical study was conducted in 90 patients with adenomyosis, including 50 patients (mean age 42.6 ± 3.35 years) with a histologically verified diagnosis. The results of conservative treatment of 40 patients with adenomyosis (mean age 38.7 ± 2.71 years) were analyzed.

To clarify the diagnosis, an instrumental examination was carried out: transabdominal and transvaginal ultrasound scanning using Aloka-630 (Japan), Megas (Italy) devices and hysteroscopy using Karl Storz endoscopic equipment (Germany). Sterile solutions of sodium chloride (0.9%) and glucose (5.0%) were used as a contrast medium. After the initial examination, separate diagnostic curettage of the cervical canal and uterine cavity mucosa, followed by their histological examination, a control hysteroscopy was performed.

Histological material was processed according to the generally accepted method. Histochemical methods revealed the main substance of the connective tissue of the myometrium using alcian blue according to the method of A. Krieger-Stoyalovsky; the determination of neutral polysaccharides was carried out using the PAS reaction, the DNA of cell nuclei - according to the Felgen method, the macromolecular stability of tissue structures of the connective tissue - according to the method of K. Velikan.

The isolation of phosphoinositides (PIN) was carried out using an improved method of flow thin layer chromatography, which made it possible to determine the content of various PIN. The content of FIN in whole blood, monocytes, and lymphocytes was studied. The comparison group for determining the levels of FIN in the blood consisted of 50 healthy female donors (mean age 39.3 ± 2.45 years).

The analysis of anamnestic and clinical data, the results of a comprehensive examination (hysteroscopy, ultrasound scanning) of 40 patients with adenomyosis (mean age 38.7 ± 2.71 years) who received conservative therapy was carried out.

The most characteristic complaints of patients were established: dysmenorrhea, which was noted by 34 (86.1%) women, menorrhagia - 17 (42.5%), pre- and postmenstrual blood discharge from the genital tract - 14 (35.0%). In addition, 18 (45.0%) patients complained of pain in the lower abdomen; for pain in the pelvic area not associated with menstruation or sexual intercourse - 10 (25.0%) women; dyspareunia was noted in 13 (32.5%) patients. Every fifth woman had dysmenorrhea accompanied by headache and dizziness. Increased irritability, depressed mood, decreased performance and neurotic disorders were noted by 23 (57.5%) women. In the majority, the pain syndrome was accompanied by general weakness, anxiety, fear, excitability, emotional lability, distracted attention, memory loss, sleep disturbance and other psychoasthenic manifestations that bothered every second patient.

A gynecological examination revealed an increase in the size of the uterus, corresponding to 6-7 weeks of pregnancy - in 31 patients, in the rest of the women, the uterus was enlarged up to 8-9 weeks of pregnancy. Pathological formations in the area of ​​the uterine appendages were not found in any patient, both in two-handed and in echographic studies.

In order to clarify the clinical diagnosis, an examination was carried out using the most informative instrumental methods: ultrasound and hysteroscopy. The information content of ultrasound in the detection of adenomyosis was 77.5 ± 6.69%, hysteroscopy - 87.5 ± 5.29%.

A morpho-biochemical study was performed in 50 operated patients (mean age 42.6 ± 3.35 years) with adenomyosis verified by morphological examination. It was established that the growth of heterotopic foci was accompanied by a pronounced plethora of the myometrial microvasculature, lymphostasis, edema of the perivascular myometrial tissue, an increase in the number of tissue basophils around the foci of endometriosis, and a high content of alcian-positive glycosaminoglycans in the intercellular substance. These changes were most pronounced in II-III degrees of damage. An uneven compaction and liquefaction of the argyrophilic substance with loss of the fibrous structure around the glands located in the myometrium was found. Disturbances in the structure of the ground substance and fibrous structures of the connective tissue skeleton of the myometrium in the form of the development of baso- and picrinophilia, progressive loss of intermolecular bonds, accumulation of acidic non-sulfated glycosaminoglycans, and an increase in the number of tissue basophils are the result of emerging tissue hypoxia. The plethora of the microvasculature of the myometrium present in the samples and the accompanying edema of the perivasal spaces and pronounced lymphostasis can be considered a morphological manifestation of the latter. The pathological process, deeply infiltrating tissues, leads to ischemia of the nerves and their demyelination. The result of these processes is a change in the afferent input at the level of the segment of the spinal cord, the impulse entering the central nervous system changes steadily, which leads to a change in the sensory quality of pain and the appearance of the most painful sensations. Reflex vasospasm, which develops in response to a painful stimulus, exacerbates ischemic disorders, further enhances afferent impulses to the brain, contributing to the formation of "vicious circles" in sympathetic reflexes. In addition, the functioning foci of endometriosis themselves turn into a powerful irritant of the higher centers of regulation of sexual function, which leads to further stimulation of the proliferative activity of cells. As a result, conditions are created for the progression of the pathological process, in which the main role belongs to the violation of intracommunicative relationships in the blood-uterine tissue system. All this leads to the formation of a vicious circle, characterized by interrelated hormonal, immune, cellular disorders, which are extremely difficult to completely eliminate with hormonal drugs alone. This is evidenced by the low efficiency of therapy used in patients with this pathology.

Currently, much attention is paid to the study of arachidonic acid and its metabolites (prostaglandins and thromboxane A 2) in the processes of cell proliferation. It has been shown that prostaglandins can influence the regulation of cell proliferation and/or differentiation, especially in the endometrium. The occurrence of pain in patients with adenomyosis may be due to hyperproduction of arachidonic acid derivatives - prostaglandins. The phenomenon of sensitization to algogenic products produced during inflammation, ischemia, and immunopathological processes is associated with prostaglandins. Prostaglandin F 2α (PGF 2α) and prostaglandin E 2 (PGE 2) accumulate in the endometrium during menstruation and cause symptoms of dysmenorrhea. PGF 2α and PGE 2 are synthesized from arachidonic acid via the so-called cyclooxygenase pathway. The main source of overproduction of prostaglandins are activated mononuclear cells. We conducted a study of the content of FIN in phagocytic mononuclear cells in patients with adenomyosis, assessing their content by their presence in monocytes. The content of FIN in the blood reflects the specifics of changes in metabolic processes occurring in the body, since the participation of inositol-containing lipids in the transition of cells to uncontrolled growth and transformation has been proven. It was found that in monocytes in patients with adenomyosis, the amount of the main FIN - phosphatidylinositol (PI) was significantly reduced by 1.3 times compared with the values ​​in women of the control group. The data obtained indicate that in patients with adenomyosis, FI deficiency plays a very important role in the processes of proliferation, which means that these disorders should be corrected in the treatment of this disease.

Currently, the most effective drugs for the treatment of adenomyosis are gonadotropin-releasing hormone agonists (zoladex, decapeptyl, diferelin, buserelin acetate, buserelin-depot, etc.). At the same time, the high cost of drugs does not allow them to be widely used in clinical practice. In this regard, patients with limited financial resources are prescribed progestogens, in which norethisterone acetate appears as an active substance - norkolut (Gedeon Richter, Hungary), primolut-nor (Schering, Germany).

The study of the results of traditional hormonal therapy and the method developed by us for the treatment of adenomyosis was carried out. The 1st group of patients included 20 women (mean age 38.2 ± 2.88 years) who received only hormonal therapy (norcolut - 10 mg per day from the 5th to the 25th day of the menstrual cycle for 6 months ). In the 2nd group of patients, which included 20 patients (mean age 39.4 ± 2.97 years), complex treatment was carried out using the following drugs: norkolut (dosing regimen, as in patients of the 1st group) in combination with trental (1 tablet 3 times a day for 6 weeks), hofitol (Labor. Rosa-Phytopharma) (2-3 tablets 3 times a day before meals for 20 days) in combination with 10 sessions of low-energy laser therapy, carried out by the device RIKTA (Russia) according to the methodology developed by us (2004). A second course of laser therapy was performed after 2 months. The therapeutic efficacy of laser therapy is due to both the laser, infrared and magnetic effects of this device, as well as the specifics of the combined use of these types of energy. Hofitol is a herbal preparation with a pronounced hepato-, nephroprotective and diuretic effect, has an antioxidant effect. Treatment with this drug affects lipid metabolism and increases the production of coenzymes by hepatocytes. Due to the fact that hyperproduction of prostaglandins plays a certain role in the occurrence of pain in patients with adenomyosis, we included the non-steroidal anti-inflammatory drug Nurofen Plus (Boots Healthcare International) in the complex therapy.

Patients began taking trental and hofitol during the first cycle of treatment with a hormonal drug. Nurofen plus was prescribed 3-4 days before the onset of menstruation and during the first 3-5 days of menstruation (200-400 mg every 4 hours). The drug was taken taking into account individual tolerance. Low-energy laser therapy was performed immediately after the end of menstruation, so that the course of treatment was not interrupted and kept within the framework of one menstrual cycle.

After 6 months, when analyzing the effectiveness of therapy, it was found that the treatment was better tolerated by patients from the 2nd group. Thus, improvement in general condition, well-being, mood was noted by 5 (25.0%) patients from the 1st group and 17 (85.0%) women from the 2nd group. Such changes had a favorable psycho-emotional effect and contributed to an increase in the working capacity of patients. Sleep improved in 2 (10.0%) women from the 1st group and in 10 (50.0%) women from the 2nd group; 1 patient from the 1st group and 8 women from the 2nd group became less irritable. When comparing the dynamics of changes in the clinical symptoms of the disease, the best therapeutic effect was observed in patients from the 2nd group - in comparison with women who received traditional hormonal treatment. Thus, dysmenorrhea decreased in 11 (64.7%) patients from the 1st group and in 16 (94.1%) women from the 2nd group, and it was possible to stop it completely in 2 and 11 patients of the respective groups. Pain in the lower abdomen decreased in 4 out of 8 patients in the 1st group and in 9 out of 10 women in the 2nd group. It should be noted that patients from the 2nd group noted a decrease in the severity of the pain symptom and dysmenorrhea already in the next menstruation after laser therapy, which was carried out against the background of drug therapy. Dyspareunia decreased in 2 patients from the 1st group and in 6 women from the 2nd group. A decrease in the duration and intensity of menstrual blood loss was noted by 7 women from the 1st group and 10 women from the 2nd group. The lack of effect from the therapy, which led to surgery, was noted in 4 (20.0%) women from the 1st group and in 1 (5.0%) patient from the 2nd group, who were diagnosed with a diffuse-nodular form of adenomyosis .

Thus, the complex correction of disorders that occur in patients with adenomyosis contributes to an increase in the effectiveness of the treatment of this pathology. The inclusion of a non-steroidal anti-inflammatory drug (nurofen plus) in the complex therapy in patients with adenomyosis in patients with adenomyosis, as well as drugs that improve microcirculation, improves the effectiveness of treatment and reduces the frequency of surgical interventions by 4 times compared with patients who received traditional hormonal therapy.

Literature

1. Adamyan L. V., Kulakov V. I. Endometriosis: a guide for physicians. Moscow: Medicine, 1998. 317 p.
2. Adamyan L. V., Andreeva E. N. Genital endometriosis: etiopathogenesis, clinic, diagnosis, treatment (a manual for physicians). M., 2001.
3. Baskakov V.P., Tsvelev Yu.V., Kira E.F. Endometrioid disease. SPb., 2002. 452 p.
4. Pain syndrome / ed. V. A. Mikhailovich, Yu. D. Ignatov. L.: Medicine, 1990. 336 p.
5. Velikan K., Velikan D. Pathogenetic mechanisms of chronic diseases//Morphological bases of clinical and experimental pathology. M.: Medicine, 1972. S. 18-25.
6. Damirov M. M. Adenomyosis. M.: BINOM, 2004. 316 p.
7. Damirov M. M. Laser, cryogenic and radio wave technologies in gynecology. M.: BINOM-Press, 2004. 176 p.
8. Kriger-Stoyalovskaya A., Tustanovskaya A., Stoyalovsky K. Methodological problems of studying connective tissue in health and disease//Morphological foundations of clinical and experimental pathology. M.: Medicine, 1972. S. 74-81.
9. Peresada OA Clinic, diagnosis and treatment of endometriosis: textbook. allowance. Minsk: Belarusian Science, 2001. 275 p.
10. Radzinsky V. E., Gus A. I., Semyatov S. M., Butareva L. B. Endometriosis: educational method. allowance. M., 2001. 52 p.
11. Rukhlyada N.N. Diagnosis and treatment of overt adenomyosis. St. Petersburg: Elbi, 2004. 205 p.
12. Slyusar N. N. The role of phosphoinositides and their metabolites in oncogenesis: Dis. ... doc. honey. Sciences. SPb., 1993. 286 p.
13. Smetnik V.P., Tumilovich L.G. Non-operative gynecology: a guide for physicians. M., 1999. 592 p.
14. Strizhakov A. N., Davydov A. I. Endometriosis. Clinical and theoretical aspects. Moscow: Medicine, 1996. 330 p.

M. M. Damirov,doctor of medical sciences, professor
T. N. Poletova, Candidate of Medical Sciences
K. V. Babkov, Candidate of Medical Sciences
T. I. Kuzmina, Candidate of Medical Sciences, Associate Professor
L. G. Sozaeva, Candidate of Medical Sciences
Z. Z. Murtuzalieva

RMAPO, Moscow

Fadeeva N.I. 1, Yavorskaya S.D. 1.2 , Dolina O.V. 3, Luchnikova E.V. 2, Chubarova G.D. 4, Ilichev A.V. 4, Maldov D.G. 4

1 Altai State Medical University, Russia

2 Consultative and Diagnostic Center of Russian State Medical University, Russia

3 Altai Regional Diagnostic Center, Russia

4 Closed Joint-Stock Company "Sky LTD", Russia

Adenomyosis: new therapeutic options

Summary. An open randomized study was conducted to evaluate the efficacy and safety of Endoferin in 25 patients of reproductive age with a histologically confirmed diagnosis of adenomyosis. The presence of a diffuse form of adenomyosis II-III degree was detected in 11 (44%) cases and a diffuse-nodular form - in 14 (56%) cases. In its pure form, adenomyosis occurred in 14 (56%) cases, in combination with uterine myoma - in 9 (36%), in combination with external genital endometriosis (one patient with vaginal endometriosis, one with ovarian endometriosis) - in 2 ( 8%) cases. At the end of therapy, within 3 menstrual cycles, menorrhagia disappeared in 100% of cases, hyperpolymenorrhea - in 61%, algomenorrhea - in 53%, in every third (36%) patient the size and volume of the uterus decreased. The clinical efficacy of Endoferin in adenomyosis is confirmed by the results of an immunomorphological study of myometrial biopsies, which indicate a decrease in the prevalence of endometriotic heterotopias by 20% and the activity of adenomyosis by 40%. During treatment with Endoferin and after its completion, the level of hormones (estrogens and progesterone) were within the normal range, which indicated the absence of a depressive effect of the drug on steroidogenesis in the ovaries.

Keywords: adenomyosis, drug therapy.

summary. An open randomized trial was conducted to evaluate the efficacy and safety of Endoferin in 25 patients of reproductive age with a histologically confirmed diagnosis of adenomyosis. The presence of a diffuse form of adenomyosis of II-III degree was revealed in 11 (44%) cases and diffuse-nodal form - in 14 (56%) cases. In a pure form, adenomyosis occurred in 14 (56%) cases, in combination with uterine myoma - in 9 (36%), in combination with external genital endometriosis (one patient with endometriosis of the vagina, one with endometriosis of the ovary) - in 2 (8%) cases. At the end of therapy, during 3 menstrual cycles, menorrhagia disappeared in 100% of cases, hyperpolymenorea - in 61%, algodismenorea - in 53%, in every third (36%) patients the size and volume of alvus decreased. The clinical efficacy of Endoferin in case of adenomyosis has been confirmed by the results of immunomorphology study of myometrium biopsy specimens, which indicate a 20% decrease in the prevalence of endometriotic heterotopia and an adenomyosis activity by 40%. In the course of treatment with Endoferin and after its termination, the level of hormones (estrogens and progesterone) was within the norm, which indicated the absence of a depressive effect of the drug on steroidogenesis in ovaries.

keywords: adenomyosis, drug therapy.

Meditsinskie news. - 2017. - N5. - P. 13-15.

Adenomyosis is a benign pathological process characterized by the appearance in the myometrium of epithelial (glandular) and stromal elements of endometrioid origin. There are three degrees of distribution of adenomyosis, as well as focal, cystic and nodular forms. This disease occurs in 7-50% of women of reproductive age, is associated with a hereditary factor, combined with hormonal and immune homeostasis disorders. For patients with adenomyosis, a chronic course is characteristic, a clinic of dysmenorrhea and menorrhagia up to the development of anemia, persistent pain syndrome, which results in a deterioration in general health, a decrease in working capacity and quality of life.

Diagnosis of adenomyosis is based on clinical data and the results of ultrasound (ultrasound) with color Doppler mapping (CDC) and / or magnetic resonance imaging (MRI) of the uterus, as well as hysteroscopy performed immediately after menstruation, which makes it possible to detect endometrioid heterotopias when they are located in submucosal layer of the uterine wall. The final confirmation of the presence of adenomyosis is based on the pathomorphological examination of the organ removed during the operation, less often - with the targeted taking of a biopsy of the myometrium under hysteroscopy conditions.

Treatment of adenomyosis is a long and not always rewarding process. The main direction is empirical drug therapy (progestogens, antigonadotropins, gonadotropin-releasing hormone agonists), which has a number of serious contraindications and complications. After discontinuation of drug treatment, the risk of relapse is high, which increases the need for surgical removal of the uterus.

Thus, adenomyosis is a chronic pathology. Universal methods for the treatment of adenomyosis, a disease that is widespread in patients of reproductive age, do not exist today. Registered drugs for the treatment of adenomyosis have a number of contraindications and complications, which excludes the possibility of long-term and widespread use, and their cancellation often leads to a relapse of the disease. The search for new, effective methods for the treatment of adenomyosis, which, without disturbing the hormonal balance in the body, eliminate the typical symptoms of the disease and restore the lost reproductive function, seems to be extremely relevant.

As part of a clinical open randomized study on the efficacy and safety of endoferin (Sky LTD CJSC) in patients with endometriosis, 25 women aged 25 to 45 years were examined and treated. Criteria for inclusion in the study: reproductive age, the presence of a clinic of adenomyosis, histological confirmation of the diagnosis and voluntary consent to participate (signed informed consent). Exclusion criteria: pregnancy, drug hormone therapy 6 months before the study, severe somatic pathology.

All patients received Endoferin, which was administered intramuscularly - 1 injection per day at a dose of 0.3 mg. The course consisted of 10 injections in the first phase of the menstrual cycle for three months (a total of 30 injections).

Endoferin is a lyophilized powder for the preparation of a solution for intramuscular injection of 0.3 mg in bottles in a package No. 10. The drug Endoferin (developed by CJSC Sky LTD) is a chromatographically purified component of the bovine follicular fluid. The basis of biological whose drug action is a series of superfamily proteins TGF-?. The drug showed high efficiency in preclinical trials on induced endometriosis in female Wistar rats.

At baseline and after 20 injections of endopherin, as well as four months after the start of therapy, clinical characteristics were assessed. The level of estradiol was determined in the 1st phase of the menstrual cycle, progesterone - in the 2nd phase of the cycle, tumor marker CA-125 (an increase is typical for endometriosis). Echography of the pelvic organs, hysteroscopy with biopsy of the myometrium and its histological examination performed at the Department of Pathological Anatomy of the Altai State Medical University (Barnaul), and immunomorphological examination performed at the Research Institute of Human Morphology of the Russian Academy of Medical Sciences (Moscow) were performed.

Statistical processing of the obtained results was carried out according to the generally accepted methods of variation statistics using Microsoft Excel 2010 and Statistica 6.1 programs. The arithmetic mean (M) and standard deviation (?) were calculated. The values ​​of continuous quantities were presented as M±?. The normality of the distribution of signs was assessed by kurtosis and asymmetry. In cases of normal distribution, Student's t-test was used. The values ​​of qualitative features were presented in the form of observed frequencies and in percentages, for comparison of which nonparametric criteria were used? 2 with Yates correction for continuity and Fisher's exact test. When assessing the qualitative characteristics of two related samples (one group before and after treatment), McNemar's test was used. The level of statistical significance when testing the null hypothesis was taken as the corresponding p≤0.05.

At the time of inclusion in the study, the average age of the patients was 40.2±5.6 years. Diffuse form of adenomyosis II-III degree was detected in 11 (44%) cases, diffuse-nodular in 14 (56%). In its pure form, adenomyosis was observed in 14 (56%) patients, in combination with uterine myoma - in 9 (36%); in combination with external genital endometriosis in 2 (8%) women (one with vaginal endometriosis, the second with ovarian endometriosis). Previously, 14 (56%) patients had already received various drug treatments for adenomyosis, including 5 (20%) with releasing factor agonists (aGnRH).

When assessing the somatic status, it was found that every fifth patient had hypertension (20%) or neurocirculatory dystonia (20%), in combination with myocardial dystrophy (16%), diseases of the gastrointestinal tract - in every second (56%), urinary tract - every third (36%). Pathology associated with hormonal status disorders was found in every second patient, in the form of thyroid dysfunction - in 44% of cases, metabolic syndrome - in 20%, benign breast dysplasia - in 36%.

In most patients, the gynecological history was aggravated by factors contributing to the development and progression of adenomyosis: chronic inflammatory diseases of the pelvic organs - in 16 (64%) women, destructive interventions on the cervix - in 16 (64%), prolonged use of intrauterine contraceptives - in 9 (36%). The reproductive history was also aggravated by medical abortions (64%) and tubal pregnancy (8%).

At the start of the study, clinical manifestations of adenomyosis were established in all 25 (100%) patients: algomenorrhea - in 19 (76%), including requiring the use of analgesics in 17 (68%); hyperpolymenorrhea - in 18 (72%); meager spotting before and after menstruation - in 15 (60%). Chronic iron deficiency anemia as a consequence of heavy menstruation occurred in every fifth patient (20%).

According to ultrasound, all 25 (100%) patients had ultrasound criteria for adenomyosis, an increase in the size of the uterus and its volume. 11 (44%) women had a uterine volume less than 100 cm 3 , 14 (56%) women had more than 100 cm 3 , including 4 (16%) of them, the size of the uterus exceeded 200 cm 3 .

At the end of the course of therapy with Endoferin, hyperpolymenorrhea disappeared in 11 of 18 patients (p=0.004), in 5 (28%) patients, blood loss significantly decreased, and remained the same in only two (11%). Anemia as a consequence of hyperpolymenorrhea after the course of treatment was found only in 1 out of 5 patients who had it at the time of inclusion in the program (p=0.1).

The symptom of scanty spotting before and after menstruation, as the most characteristic of adenomyosis, was absent in all patients (100%) (p<0,001).

Painful menstruation requiring the use of analgesics was observed in 17 (68%) women. After treatment, the disappearance of the symptom was noted in 9 (53% of those who had) (p=0.01), improvement - in 8 (47% of those who had).

When comparing the results of ultrasound before and after treatment, it was revealed that the volume of the uterus decreased in 12 (48%) patients (p = 0.0001), in the remaining 13 (52%) - remained unchanged. This was regarded as a positive result, since 10 of them had a rapid growth of the uterus before the start of treatment and / or a significant increase due to the diffuse nodular form, 3 patients had a combination of adenomyosis and uterine fibroids.

According to hysteroscopy data, adenomyosis foci were visually detected before the start of treatment in 23 (92%) cases, while after the course of therapy - in 18 (72%) patients (p=0.06).

Histological and immunomorphological characteristics of myometrial biopsies in patients with adenomyosis before and after endoferin therapy are presented in the table.

Table. Histological and immunomorphological characteristics of myometrial biopsies in 25 patients with adenomyosis before and after treatment with Endoferin

Biopsy study myometrium	Before treatment			After treatment
	Adenomyosis absent, abs, (%)	Adenomyosis is		Adeno- miosis from- missing,abs, (%)	Adenomyosis is
		active, abs, (%)	inactive, abs, (%)		active, abs, (%)	inactive, abs, (%)
Histological
Immunomorphological

At the end of the course of therapy, according to the histological examination of myometrial biopsies, adenomyosis was absent in 48% of women (p=0.0001), the rest had a decrease in endometrioid heterotopias by 20%. According to the immunomorphological study, the activity of adenomyosis decreased by 40% (p=0.1) (figure).

During the treatment with endoferin and after its completion, the level of sex hormones (estradiol and progesterone) in all 25 patients was within the normative limits, which indicated the absence of a depressive effect of the drug on steroidogenesis in the ovaries. In addition, the disappearance and reduction of symptoms of adenomyosis was combined in 5 cases with the normalization of the initially elevated level of the CA-125 tumor marker (p=0.01).

During the study, against the background of intramuscular administration of the drug Endoferin, the following side effects were recorded: weight gain (44%); increased libido (28%); the appearance of a taste (metallic, bitter) with the introduction of the drug (20%).

Conclusions:

1. The effectiveness of therapy for adenomyosis with Endoferin during 3 menstrual cycles leads to:

a) clinical disappearance of menorrhagia in 100% of cases, hyperpolymenorrhea - in 61%, algomenorrhea - in 53% of cases;

b) stabilization of the size of the uterus with its initially rapid growth in 52% of cases, a decrease in the size of the uterus - in 36% of cases;

c) a decrease in the prevalence of endometriotic heterotopias, according to the histology of endometrial biopsy, in every fifth patient (20%).

2. The course of treatment of adenomyosis with Endoferin for 3 menstrual cycles (10 injections per cycle) in women of reproductive age is not accompanied by inhibition of steroidogenesis in the ovaries and contributes to the normalization of the initially elevated level of the CA-125 tumor marker.

3. The demonstrated clinical efficacy of Endoferin in the treatment of endometriosis (adenomyosis) in the absence of its negative effect on ovarian function, as well as the insignificance of side effects in its use, allow us to recommend this drug for the treatment of patients of reproductive age with diffuse and diffuse nodular forms of adenomyosis.

L I T E R A T U R A

1. Adamyan L.V., Andreeva E.N., Apolikhina I.A., Bezhenar V.F. and others. Endometriosis: diagnosis, treatment and rehabilitation: Clinical recommendations. - M., 2014.

2. Adamyan L.V., Kulyakov V.I., Andreeva E.N. Endometriosis: A Guide for Physicians. - M., 2006. - 411 p.

3. Vanin A.F., Zairatyants O.V., Serezhenkov V.A. and others // Problems of reproduction. - 2009. - V.15, No. 5. - P.52-58.

4. Kulakov V.I., Manukhin I.B., Savelyeva G.M. Gynecology. National leadership. - M., 2007. - 794 p.

5. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis // Fertil. Steril. - 2008. - Vol.90, Suppl. 3.-S260-S269.

6. Mounsey A.L., Wilgus A., Slawson D.C.// Fm. fam. Phys. - 2006. - Vol.74. - P.594-600.

Medical news. - 2017. - No. 5. - S. 13-15.

Attention! The article is addressed to medical specialists. Reprinting this article or its fragments on the Internet without a hyperlink to the original source is considered a copyright infringement.