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0COMPREHENSIVE TREATMENT OF UTERINE FIBROIDS IN WOMEN OF LATE
REPRODUCTIVE PERIOD Asabaeva A.A.1, Isamiddinova E.I.2, Omar M.I.3
1Asabaeva Ainura Alibekovna - obstetrician-gynecologist, assistant, DEPARTMENT OF SMU 2Isamiddinova Elnura Isamiddinkyzy - resident doctor, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY № 2, ASTANA MEDICAL UNIVERSITY NJS, ASTANA,
3Omar Munozhat Isamidinovna - obstetrician-gynecologist, STATE-OWNED ENTERPRISE AT THE TURKESTAN CITY CENTRAL HOSPITAL OF THE HEALTH DEPARTMENT OF
THE TURKESTAN REGION, TURKESTAN, REPUBLIC OF KAZAKHSTAN
Abstract: the article analyzes uterine fibroids are one of the most common benign diseases of the female genital organs. According to various data, up to 50-70% of surgical interventions are performed for uterine fibroids in gynecological hospitals in Russia, of which 60.9-95.5% are radical operations, including at reproductive age (24-26.8%). The average age of patients undergoing hysterectomy for uterine fibroids is 40± 3.4 years in more than 90%. 600,000 hysterectomies are performed annually in the United States of America, of which 60% are due to uterine fibroids. In the European Union, about 300,000 surgical operations for uterine fibroids are performed annually, including approximately 230,000 hysterectomies. If it was previously believed that uterine fibroids are detected in about 25% of women over 30 years old, then recent large-scale autopsy studies with a cut interval every 2 mm indicate the possibility of its spread among women of childbearing age up to 80%. Keywords: uterine, fibroids, operations, female.
UDC 618.1.089
Surgical removal is still the main method of treating uterine fibroids, most often myomectomy or uterine extirpation are used, depending on the age and reproductive plans of the patient. Today, drug therapy is not widespread and is used as symptomatic therapy for small fibroids or preoperative preparation.
The study of the role of apoptosis and proliferation processes in the genesis of hyperproliferative diseases such as uterine fibroids, adenomyosis and endometrial hyperplastic processes represents a new direction in the study of their pathogenesis. The study of the morphological features of uterine fibroids, the severity of proliferative activity, and the features of vascularization will reveal some new pathogenetic mechanisms of uterine fibroids. This is especially important for effective therapy of combined uterine pathology.
The purpose of the study
Improving the effectiveness of treatment of patients with uterine fibroids of late reproductive age using selective progesterone receptor modulators, ulipristal acetate as preoperative preparation.
Research objectives
1. To give a complete clinical and laboratory characterization of women of the late reproductive period with uterine fibroids.
2. To compare the effectiveness and safety of various preoperative preparation regimens for women of the late reproductive period with uterine fibroids.
3. Evaluate side effects and adverse events when using various types of conservative therapy
Materials and methods of research
The current study included 215 patients with uterine fibroids who were hospitalized from 2017 to 2019. In all cases, the diagnosis of uterine fibroids was confirmed histologically. 145 case histories were analyzed retrospectively, and 70 were analyzed prospectively. The age of the examined patients ranged from 35 to 45 years. 60 patients received hormone therapy as a preoperative preparation.The data of ten patients who preferred surgery without prior hormonal treatment were used as a comparison group.Subsequently, all underwent myomectomy or hysterectomy according to indications. The patients were fully informed about all the known advantages, disadvantages and differences between treatment options.Prior to hormonal treatment, patients of all groups underwent a pipel biopsy of the endometrium or separate diagnostic curettage under the control of hysteroscopy in order to exclude hyperplastic processes of the endometrium. Treatment began during the first 4 days of menstruation.Inclusion criteria: late reproductive age (35-45 years); presence of a uterine fibroid node > 3 cm in size (according to vaginal ultrasound and MRI); presence of typical symptoms associated with fibroids (menorrhagia - RVC score >100, signs of pressure in the pelvis, posthemorrhagic anemia - hemoglobin level < 100 g/l or lower). Exclusion criteria: the total size of the uterus exceeding the 16th week of pregnancy; the presence of a history of surgical operations on the uterus; indications in the history of hormone replacement therapy and hormonal contraception or other hormonal treatment during the last month before the start of the
study; pelvic inflammatory diseases; atypical endometrial hyperplasia; malignant neoplasms; severe, chronic extragenital pathology; refusal of patients to participate in the study. All patients signed an informed consent form.
The study included a preoperative standard examination of patients with an interval of once a month for 3 months, as well as postoperative monitoring of basic laboratory parameters (general blood test, general urine test, biochemical blood test, hemostasiogram, LH, FSH, prolactin, estradiol), gynecological examination, transvaginal and transabdominal ultrasound with Dopplerography. All patients taking SMRP as a preoperative preparation underwent MRI of the pelvic organs before the start of treatment and at week 13.
The criteria for evaluating the effectiveness included the volume of blood loss, changes in the size of the uterus and myomatous nodes compared with baseline indicators (based on ultrasound data conducted every 4 weeks and pelvic MRI data obtained before and after treatment), the symptoms of uterine fibroids and adverse events of the therapy were also evaluated. Hemoglobin levels were measured at each visit. The performance criteria were evaluated every 4 weeks.
The severity of the pain syndrome was assessed using the "Visual Analog Pain Scale" (VAS). Pain intensity: 1-2 points - mild pain; 3-4 points - moderate pain; 5-6 - moderate pain; 7-8 - severe; 9-10 - unbearable pain.
The safety assessment criterion was evidence of the superiority of the side effect profile of ulipristal acetate compared with buserelin acetate in terms of serum estradiol levels at week 13 and the percentage of patients with moderate or severe hot flashes during treatment. The frequency and severity of adverse events (according to spontaneous reports or identified through general questions) were recorded in special forms at each visit.
The thickness of the endometrium and the condition of the ovaries were evaluated by ultrasound before starting treatment, as well as at 5, 9 and 13 weeks.
The duration of the operation was defined by us as the time interval between the beginning of the surgical incision and the application of the last suture to the surgical wound. Statistical processing of the obtained data was carried out using Windows 10 and MS Excel 2010 and Statistica 8 programs. The reliability of differences in the groups was determined by the Student's t-criterion, the differences were considered reliable at p<0.05. Correlations were evaluated by Spearman's rank correlation method.
The results of the study and their discussion
The analysis of the examination results of 215 patients showed that the age of patients ranged from 35 to 45 years, the average age was 40.2 ± 1.8 years. During a general examination of all the women we examined, there were no pronounced deviations from the norm. The constitutional constitution of most patients was correct. An assessment of the lifestyle revealed its active nature in more than half of the patients. The BMI of the examined patients up to 26 was detected in 19.1% of women, within the average values of 26-30 - in 140 women, which was 65.1%, and 15.8% of the examined had a BMI of more than 30.
When assessing the somatic status of the examined women, we found that diseases of the gastrointestinal tract and hepatobiliary complex were the most common in the structure of extragenital pathology, which amounted to 31.7% of observations. Cardiovascular pathology was found in 7.3% of women, mainly including hypertension 2st.
Diseases of the urinary system were also found in 13% of cases and respiratory diseases were detected in 16.7% of women. Diabetes mellitus was noted by 1.3% of the surveyed women.
Analyzing the anamnestic data, we revealed the presence of adverse factors causing tumor growth. The most frequent of them were: chronic inflammatory diseases of the pelvic organs (in 30% of cases), absence of childbirth and lactation in the anamnesis (in 12 % of cases), indication of abortion in the anamnesis (in 16% of cases), the presence of cysts and ovarian cysts (in 12 % of cases).
According to the literature, early onset of menstruation increases the risk of uterine fibroids. Early onset of the menstrual cycle can increase the number of cell divisions that occur in the myometrium during the reproductive period, which leads to an increased risk of mutations in genes that control myometrial proliferation. In more than half of the patients in our study, the age of menarche was 11-13 years - 127 observations (59 %). 37 (17,3 %) The patients noted the early onset of menstruation; 51 (23.7 %) patients were over 14 years old. The predominant number of patients had menarche on time.
There is also evidence of an increase in the incidence of uterine fibroids with age, which has been demonstrated in epidemiological studies. According to various sources, a rapid increase in the frequency of diagnosis of uterine fibroids is observed in women after the age of 40. An obvious increase in the incidence of uterine fibroids in the late reproductive period may represent the accumulated growth of fibroids over 20-30 years of stimulation with estrogen and progesterone. A decrease in the size of uterine fibroids in postmenopausal women may be due to the lack of hormonal stimulation after menopause. According to our study, the average age of the patients was 40.2 ± 1.8 years and did not significantly differ from the average statistical indicators in the population (p<0.05), which is consistent with the data of domestic and foreign literature. According to the results of our study, both schemes of preoperative conservative therapy contributed to a decrease in the size of the maximum size of myomatous nodes. At week 13, the average decrease was 23.9% in the group receiving 5 mg ulipristal and 11.25% in the group receiving buserelin acetate. The size range of the largest nodes in the
ulipristal group was 8% - 68%, and in the aGnRG group - 5% - 35%. There were 4 cases of node migration and 3 cases of node size increase in the group of uliprystal acetate.
An analysis of the data obtained during our study shows that the most frequent indications for surgical treatment were: recurrent cyclic and acyclic bleeding, leading to varying degrees of anemia (80%), persistent pain syndrome (55%) and impaired function of organs adjacent to the uterus (16%). Thus, when analyzing the volume, timing of operations and blood loss, it can be concluded that the preparation of ulipristal with acetate creates conditions for organ-preserving operations, minimizing the volume of surgical intervention. Improved vision during surgery due to reduced bleeding, which helps to reduce the duration of the operation. The results of our study are confirmed by the data of foreign authors, who also noted this fact. Thus, the molecular biological mechanisms of suppressing the growth and size reduction of leiomyomas under the influence of the new selective modulator PR ulipristal consist in a decrease in the proliferative and mitotic activity of tumor cells in combination with the induction of their apoptosis and impaired extracellular matrix production, as well as a decrease in their degree of hypertrophy. The detected tendency to increase the expression of RH by tumor cells is probably a compensatory process. The preservation of a high level of expression of Bc1-2 in combination with a slight increase in the expression of Bax with pronounced induction of apoptosis suggests the influence of ulipristal on various ways of its regulation.
References
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2. Adamyan L.V., Sonova M.M., Shamugiya N.M. The experience of using selective progesterone receptor modulators in the treatment of uterine fibroids (literature review) // Problems of reproduction. - 2016. - No. 4. - pp. 34-38.
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