Adenomyosis scientific articles. Modern problems of science and education. Terminology and classifications

Adenomyosis - symptoms and treatment

What is adenomyosis? We will discuss the causes, diagnosis and treatment methods in the article by Dr. A. Yu. Klimanov, a gynecologist with 17 years of experience.

Definition of disease. Causes of the disease

Adenomyosis -a type of endometriosis- pathology in which the uterine layer of the endometrium grows beyond the mucous membrane of the uterus (ovaries, fallopian tubes, organs of the urinary, respiratory and digestive systems). This form of the disease is characterized by damage to the myometrium of the uterine cavity by endometrial cells. However, adenomyosis should be considered not only together with endometriosis, but also as an independent nosological entity.

At the moment, the incidence of adenomyosis has increased significantly in the population and in terms of prevalence is on the same level as adnexitis (inflammation of the ovaries, fallopian tubes) and (tumor).

As with many other gynecological diseases, surgical intrauterine interventions (abortion, diagnostic curettage, resection of polyps without hysteroscopy control) can become triggers for the development of adenomyosis. During these procedures, damage to the basal lamina separating the endometrium from the myometrium may occur, resulting in invasion (infection) of endometrial cells into the thickness of the uterine wall. Complicated childbirth, long-term use of intrauterine contraceptive devices (spirals), dysfunctional uterine bleeding should also be considered a risk group.

It is worth noting a number of reasons that negatively affect the state of the reproductive system: age of menarche (too early or too late onset of the first menstrual bleeding), late defloration (rupture of the hymen), long-term use of COCs and other hormonal drugs, age (presence of hormonal activity), obesity .

Factors associated with high risks of developing adenomyosis:

• general condition of the woman (decreased immune forces of the body, burdened allergy history (tolerance to allergens); recurrent infectious diseases, chronic processes, arterial hypertension (increased blood pressure), physical inactivity - sedentary lifestyle)
• an unfavorable social environment in which a woman is exposed to severe stress;
• bad environmental situation.

In patients whose close relatives suffered from adenomyosis, endometriosis and tumor-like formations of the reproductive system, the likelihood of adenomyosis occurring is much higher. Congenital adenomyosis cannot be ruled out due to disturbances during intrauterine development.

If you notice similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!

Symptoms of adenomyosis

The most typical clinical symptom of adenomyosis will be a change in the nature of menstruation: increased duration (more than seven days), increased profuseness and pain, the presence of clots. The development of adenomyosis is also indicated by intermenstrual bleeding and spotting in the middle of the cycle. Often, patients experience the appearance of scanty brownish discharge for several days before and after the menstrual cycle.

A distinctive feature of such patients is the severe course of premenstrual syndrome. In addition, menstruation is always accompanied by pain that occurs in the lead-up and subsides in the first two days after its onset. In many ways, the intensity and nature of pain is determined by the localization and extent of spread of foci of adenomyosis. Irradiation (spread of pain symptoms) into the perineum is caused by the formation of foci in the isthmus of the uterus. Pain in the groin area indicates the presence of foci of adenomyosis in the uterus in the area of ​​the uterine angle. Often women complain of sharp pain and discomfort during sexual intercourse.

Patients suffering from adenomyosis are emotionally labile (unreasonable mood swings occur), and often note excessive irritability, the spontaneous appearance of frequent headaches, flashing spots before the eyes, and dizziness.

A significant number of patients seen by a reproductologist for infertility or miscarriage were diagnosed with adenomyosis.

The clinical picture of adenomyosis can be blurred and does not always correspond to the degree of prevalence and severity of the disease.

Pathogenesis of adenomyosis

Adenomyosis refers to hormone-dependent pathologies, but to give an unambiguous answer to the question: “What actually leads to adenomyosis?” at the moment science cannot. There are a number of theories explaining the pathogenesis of this disease.

One of the hypotheses highlights hyperestrogenism, which leads to increased proliferation (reproduction) of cells, which in turn is the cause of hyperplastic changes in the endometrium. Adenomyosis is often combined with endometrial hyperplasia, which indirectly confirms the theory. Among other things, it often occurs in combination with uterine fibroids (benign neoplasm). This indicates some similarity in the pathogenetic aspects of these pathologies. Hyperestrogenism enhances the growth of cells in the basal layer of the endometrium, as a result of which its permeability and penetration of epithelial cells into the muscle tissue increases.

Inflammatory diseases have a direct connection with an increased incidence of adenomyosis.

Today, many researchers are studying the theory of the development of endometrioid heterotopias (outside the uterine cavity) from elements of the endometrium and its displacement into the thickness of the uterus.

Classification and stages of development of adenomyosis

The classification of adenomyosis is based on morphological characteristics, as well as the degree of depth of myometrial damage. Based on this, four forms of adenomyosis can be distinguished:

• focal – local adenomyotic foci are formed in the underlying tissues by endometrial cells;
• nodal– endometrial cells located in the myometrium, which in their shape resemble nodules (adenomyomas). The connective tissue formed due to inflammation surrounds numerous nodes filled with blood;
• diffuse– endometrial cells do not form obvious nodes or lesions;
• mixed– a combination of nodular and diffuse adenomyosis.

By penetration depth The endometrium is divided into:

• 1st degree – only the submucosal layer is involved;
• 2nd degree – the muscle layer is affected by no more than half;
• 3rd degree – damage to more than half of the muscle layer;
• Grade 4 – total damage to the muscle layer; adjacent organs and tissues may be involved in the process.

Complications of adenomyosis

Most women who have been diagnosed with adenomyosis are monitored for infertility, which occurs due to the formation of adhesions in the fallopian tubes, which impede or prevent the passage of the egg into the uterus. The anamnesis of such patients, as a rule, reveals the absence of pregnancy for a long time with regular sexual activity without contraception, or the anamnesis is aggravated by multiple spontaneous miscarriages. This occurs due to a change in the condition of the endometrium, which complicates the process of egg implantation, in combination with developing inflammation and an increase in the tone of the muscle layer.

One of the most serious complications of adenomyosis is iron deficiency anemia, which develops as a result of heavy discharge during menstruation and bleeding from the uterine cavity in the middle of the cycle. Women often attribute the clinical manifestations of this disease to fatigue: severe weakness, drowsiness, not related to the number of hours spent sleeping, increased fatigue; Shortness of breath may increase, frequent colds, pallor of the skin and mucous membranes are noted. However, these symptoms should not be underestimated. Failure to see a doctor in a timely manner can lead to serious consequences, such as the development of sideropenic syndrome, manifested not only by brittle hair and nails in the early stages, but as the disease progresses - paresthesia (a feeling of numbness and “pins and needles” in the limbs), muscle weakness, dyspeptic and dysuric disorders (digestion and urination disorders). Constant dizziness and repeated fainting indicate worsening severity of the disease and the need for emergency etiotropic treatment!

Long, heavy menstrual cycles, accompanied by severe pain and previous severe premenstrual syndrome, have a detrimental effect on the psycho-emotional state of the patient, and her resistance to stress decreases. Subsequently, this can lead to the development of neurosis-like and depressive conditions.

In addition, adenomyosis creates problems for women both socially (intensive discharge during menstruation forces them to reduce physical activity and temporarily give up favorite activities) and intimately: sexual intercourse becomes painful and their frequency decreases.

Diagnosis of adenomyosis

Sometimes adenomyosis can be asymptomatic or with mild clinical symptoms, so it is necessary to carefully carry out a set of diagnostic measures, including:

• collection of complaints and medical history;
• gynecological examination on a special chair;
• additional instrumental and laboratory research methods.

During an examination in a gynecological chair, the doctor can detect changes in the shape, structure, and size of the uterus. The examination should be carried out 3-4 days before the date of expected menstruation.

Uterine tuberosity and tumor-like formations may indicate the presence of adenomyosis in nodular form; an enlarged, spherical shape of the uterus indicates the prevalence of a diffuse process. Sometimes adenomyosis is a pathology combined with fibroids; in such situations, the symptoms of adenomyosis remain classic. The exception is the size of the uterus at the end of the menstrual cycle: it does not become smaller and is proportional to the fibroids. The combination of the above symptoms with the presence of intense, painful and prolonged menstruation in the patient allows a preliminary diagnosis of “adenomyosis” to be made.

Ultrasound scanning with a transvaginal sensor provides the most informative data on pathology. For a more accurate diagnosis, the study should also be carried out shortly before the start of menstruation. However, the reliability of ultrasound examination is significantly reduced in the diffuse form of adenomyosis. In such cases, it is advisable to use a modern endoscopic method for diagnosing intrauterine pathologies - hysteroscopy. Often during the procedure, if adenomyosis is suspected, other abnormalities are identified and eliminated that could not be visualized during ultrasound - polyps in the uterus, hyperplastic changes in the endometrium, uterine fibroids.

If difficulties arise in differential diagnosis, MRI is used. The advantages of this method are non-invasiveness (penetration into the body without damaging the skin) and the accuracy of the data obtained, as well as obtaining a clear three-dimensional image, which eliminates the possibility of diagnostic errors.

For timely detection and prevention of anemia and inflammatory processes, it is necessary to perform:

• complete blood count with leukocyte formula, general urine test;
• hormonal studies - CA125 (allows you to assess the severity of the disease and the effectiveness of the therapy).

Incorrect diagnosis of adenomyosis is fraught with the danger of prescribing severe and aggressive therapy.

Treatment of adenomyosis

The patient’s age, the prevalence and localization of the disease, its severity and form, as well as the presence of concomitant somatic diseases in the patient determine the treatment tactics (conservative or surgical).

Surgical treatment of adenomyosis can be organ-preserving or radical. The latter method includes an operation such as hysterectomy - removal of the uterus, which is the operation of choice in patients of the older age group with the progression of the disease , combination with other pathologies of the uterus, ineffectiveness of the therapy. Despite numerous data According to published sources, clinical practice shows that organ-preserving operations do not exclude relapses of the disease. High efficiency of excision of foci of adenomyosis with suturing of the uterus is achieved in rare cystic forms of the disease.

When adenomyosis is detected in young patients, it is necessary to preserve reproductive function. Combined hormonal contraceptives are used as first-line drugs (they are prescribed for a long time). The use of norsteroid derivatives is also practiced. Anti-inflammatory treatment is carried out, vitamins and medications are prescribed, the effect of which is aimed at reducing pain, as well as measures that help improve immunity.

If necessary, patients with severe degrees of adenomyosis, against which neurosis-like and depressive conditions develop, are recommended to consult a psychologist and conduct psychotherapy. For severe depression - transcranial brain stimulation (using magnetic pulses).

Forecast. Prevention

Adenomyosis is difficult to treat, and surgery often solves the problem only temporarily. This is why prevention of adenomyosis is incredibly important.

Of course, timely detection of the disease plays a significant role, so it is important to pay attention to the state of your health, regularly visit a gynecologist, and perform an ultrasound examination of the pelvic organs.

The set of measures aimed at preventing the development of adenomyosis can include:

• limiting excessive physical activity leading to fatigue;
• reducing the time spent in the solarium and in the open sun;
• reducing the impact of stress factors.

Normalization of the work and rest regime also has a beneficial effect on the general condition of life.

With proper attitude towards your health, the risks of developing not only adenomyosis, but also associated pathologies are reduced.

Uterine adenomyosis has become one of the commercial diagnoses. Almost every second woman is diagnosed with it, especially one ultrasound. The worst thing is that treatment is prescribed “from the end,” that is, either surgery or the use of gonadotropin-releasing hormone agonists, which cause artificial menopause. For young women planning a pregnancy, this approach is simply not acceptable.

Adenomyosis was previously considered a manifestation of endometriosis, which develops inside the walls of the uterus. However, in 1991, after a thorough analysis of numerous data, a new classification of damage to the walls of the uterus by endometrioid tissue was proposed. In most cases, uterine adenomyosis is not diagnosed, so the frequency of uterine lesions is most often judged after examining surgically removed uteruses for various reasons. According to some data, adenomyosis was found in 9-30% of such cases, according to others, up to 70% of women who had their uterus removed had adenomyosis. The average age of women who develop adenomyosis is 30 years or older, and they are usually women who have given birth. Most often, foci of adenomyosis are found along the posterior wall of the uterus (this wall has a rich blood supply).

The main signs of adenomyosis are painful, heavy menstruation, and sometimes chronic pain in the pelvis. Often such heavy periods cannot be treated with hormonal therapy or removal of the endometrium by curettage. Evidence that adenomyosis may be a cause of infertility is very controversial, but endometrial maturation and detachment may be impaired, which in turn may prevent proper implantation of the fertilized egg.

Adenomyosis can be diagnosed using a vaginal ultrasound, or MRI. Hysterosalpingography and transabdominal ultrasound are often not informative in making this diagnosis. The uterus may be slightly enlarged, but its contours will not change. However, it is practically impossible to differentiate foci of adenomyosis from small fibromatous foci using ultrasound. Enlarged endometrial glands, especially before menstruation, are also mistakenly mistaken for foci of adenomyosis by many doctors.

Until recently, the only treatment for adenomyosis was removal of the uterus, which was associated with increased mortality in such patients.
Modern medicine makes it possible to treat adenomyosis with synthetic estrogens, gonadotropin-releasing hormone agonists and a number of other drugs. Uterine artery embolization is a new type of surgical treatment that allows you to preserve the uterus and reduce the amount of blood lost during menstruation.

The topic of endometriosis-adenomyosis will be discussed in more detail in the book “Encyclopedia of Women's Health.”

The term "adenomyosis" is formed from two words - "adeno", which means a connection with any gland or glands, and "miosis", which characterizes a variety of inflammations. That is,adenomyosis– disease, in which an inflammatory process occurs due to a disruption in 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 lining layer of the uterus. When endometriosis occurs, endometrial cells penetrate the muscular layer of the uterus. “Settled” there, endometrial tissues do not stop their normal activities, gradually growing and enlarging. The entire system (uterine structure) fails, hormones are no longer produced in the required quantities, and the immune system weakens. The localized areas of muscle tissue damage swell, the size of the organ increases, resulting in pain in the pelvic area. The woman’s reproductive system begins to work with disturbances, that is, internal and then intragenital adenomyosis develops and gradually progresses.

Symptoms of adenomyosis

Often adenomyosis, How disease internal organs of the woman’s reproductive system is asymptomatic. This is typical mainly for the initial stages of development of the pathology. Subsequently, gradually increasing, the woman experiences the following painful symptoms:

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

Also, 40% of patients who have been diagnosed with adenomyosis complain of heavy discharge during menstruation. Almost half of women with internal adenomyosis experience moderate or severe premenstrual syndrome. Moreover, half of the patients who seek medical help if they are unable to get pregnant turn out to be sick with this very disease, adenomyosis.

Causes of adenomyosis development

It is believed that there is a certain genetic predisposition to adenomyosis. But the disease was often observed in women whose ancestors never had it. It follows that the tendency to develop the disease is not necessarily inherited, but can be caused by some individual factors.

Gynecologists usually include constantly occurring stress overexertion as such reasons. Women who lead an overly active lifestyle are primarily at risk. These could be women running their own businesses; raising children and working at the same time; workers in an enterprise involving heavy physical labor; girls who are fond of weightlifting.

There is also such an opinion - excessive use of solariums and love of sunbathing. When exposed to ultraviolet rays, the body is forced to endure a number of reactions, which can result in adenomyosis or other disease related to the gynecological field.

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

All uterine interventions in one way or another increase the risk of developing adenomyosis. The most likely occurrence of adenomyosis will be if a woman has undergone surgery in the body of the uterus after a miscarriage, had an abortion, or had mechanical injuries to the internal genital organs.

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

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 effectiveness and safety of the drug Endoferin in 25 patients of reproductive age with a histologically confirmed diagnosis of adenomyosis. The presence of a diffuse form of adenomyosis of degree II-III 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 fibroids - 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 effectiveness 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 normal limits, 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 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, medicamentous 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 spread 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, and is combined with disorders of hormonal and immune homeostasis. Patients with adenomyosis are characterized by a chronic course, a clinical picture of dysmenorrhea and menorrhagia up to the development of anemia, persistent pain syndrome, the consequence of which is a deterioration in general health, a decrease in performance and quality of life.

Diagnosis of adenomyosis is based on clinical data and the results of ultrasound examination (US) 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 a pathomorphological examination of the organ removed during surgery, less often - by taking a targeted biopsy of the myometrium under hysteroscopy.

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. There are no universal methods for treating adenomyosis, a disease that is widespread in patients of reproductive age. 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 withdrawal often leads to relapse of the disease. The search for new, effective methods for treating adenomyosis, allowing, without disturbing the hormonal balance in the body, eliminating the typical symptoms of the disease and restoring lost reproductive function, seems extremely relevant.

As part of a clinical open randomized study on the effectiveness and safety of endoferin (Sky LTD) 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 clinical adenomyosis, histological confirmation of the diagnosis and voluntary consent to participate (informed consent was signed). Exclusion criteria: pregnancy, drug hormone therapy 6 months before the study, severe somatic pathology.

All patients received the drug 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 (30 injections in total).

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

Clinical characteristics were assessed at baseline and after 20 injections of endoferin, as well as four months after the start of therapy. The level of estradiol was determined in the 1st phase of the menstrual cycle, progesterone in the 2nd phase of the cycle, and tumor marker CA-125 (an increase is typical for endometriosis). An echography of the pelvic organs, hysteroscopy with a biopsy of the myometrium and its histological examination performed at the Department of Pathological Anatomy of the Altai State Medical University (Barnaul), and an immunomorphological study 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 using generally accepted methods of variation statistics using Microsoft Excel 2010 and Statistica 6.1. The arithmetic mean (M) and standard deviation (?) were calculated. The values ​​of continuous quantities were presented as М±?. The normality of the distribution of characteristics was assessed by kurtosis and skewness. In cases of normal distribution, Student's t-test was used. The values ​​of qualitative characteristics were presented as observed frequencies and percentages, for comparison of which nonparametric tests were used? 2 with Yates' continuity correction and Fisher's exact test. When assessing the qualitative characteristics of two related samples (one group before and after treatment), the McNemar criterion was used. The level of statistical significance when testing the null hypothesis was taken at 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. The diffuse form of adenomyosis of II-III degree was detected in 11 (44%) cases, diffuse nodular in 14 (56%). Adenomyosis in its pure form was observed in 14 (56%) patients, in combination with uterine fibroids - 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 (GnRH agonists).

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 imbalances was identified in every second patient, in the form of thyroid dysfunction - in 44% of cases, metabolic syndrome - in 20%, benign mammary dysplasia - in 36%.

In most patients, the gynecological history was burdened 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%), long-term use of intrauterine contraceptives - in 9 (36%). The reproductive history was also aggravated by medical abortions (64%) and tubal pregnancies (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%); scanty bleeding 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 data, 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 of less than 100 cm 3, 14 (56%) had more than 100 cm 3, including 4 (16%) of them whose uterine size exceeded 200 cm 3.

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

The symptom of scanty bleeding before and after menstruation, as the most characteristic symptom 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 it) (p = 0.01), improvement - in 8 (47% of those who had it).

When comparing ultrasound results 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%) it remained unchanged. This was regarded as a positive result, since 10 of them had rapid growth of the uterus before treatment and/or significant enlargement due to a diffuse nodular form; in 3 patients a combination of adenomyosis and uterine fibroids was detected.

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

Histological and immunomorphological characteristics of myometrial biopsies from 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

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

During treatment with endoferin and after its completion, the level of sex hormones (estradiol and progesterone) in all 25 patients was within normal limits, which indicated the absence of a depressive effect of the drug on steroidogenesis in the ovaries. In addition, the disappearance and reduction of adenomyosis symptoms 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, the following side effects were recorded against the background of intramuscular administration of the drug Endoferin: weight gain (44%); increased libido (28%); the appearance of a taste (metallic, bitter) when administering the drug (20%).

Conclusions:

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

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

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

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

2. Carrying out a course of treatment of adenomyosis with the drug 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 helps to normalize the initially elevated level of tumor marker CA-125.

3. The demonstrated clinical effectiveness 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 when using it, allows us to recommend this drug for the treatment of patients of reproductive age with diffuse and diffuse nodular forms of adenomyosis.

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

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Taking into account 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 in 50-58% with secondary infertility. V.P. Baskakov et al., 2002.

The purpose of our work was the use of Roncoleukin (BIOTECH LLC, 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 through a comprehensive clinical and laboratory examination, using additional methods (hysteroscopy, separate uterine curettage, ultrasound examination using the transvaginal technique 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 who received Roncoleukin in addition to traditional treatment.

All patients received hormonal therapy with nemestran (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 of 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 level of the fundus, 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, 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, 16 patients of group I and 18 patients of group II who suffered from infertility planned pregnancy; the remaining women used a barrier method of contraception throughout the entire observation period.

In the first 3 months after the end of the main course of treatment, pregnancy occurred in 10 women in group II and only in 2 in group I; over the next three months, pregnancy occurred in 7 patients in group II and 4 in group I. Over the next 6 months of observation, pregnancy never occurred in the one remaining patient in group II, while in group I pregnancy occurred in 2 women. 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 had complaints of infertility. As a result, 17 patients from 18 (94.4%) of the main (second) group realized their desire to become pregnant, and only 8 patients from 16 (50%) (p0.01) who received traditional therapy.

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