The basis for the prevention of cancer is the correction of initial epigenetic disorders in the cell, i.e. implementation of pathological genome reversion. Convincing evidence has accumulated to support the potential antitumor activity of compounds derived from cruciferous vegetables of the genus Brassicaceae. Indole-3-carbinol and 3,3'-diindolylmethane (DIM) have been investigated for their use as chemopreventive agents. DIM is formed in the acidic environment of the stomach as a result of dimerization of indole-3-carbinol monomers. Currently, it is impossible to identify a specific vector of influence of DIM at the molecular level. In this review, we summarize the pleiotropic effects of DIM aimed at correcting reversible epigenetic changes in tumor cells. Emphasis will be placed on the major cellular and molecular events that are effectively modulated by DIM. The main profile of DIM competencies concerns the management of intracellular signal transmission and correction of initial molecular genetic changes at the level of key participants in signaling pathways (NF-κB/Wnt/Akt/mTOR) leading to the development of cancer. The ability of DIM to differentially modulate tumor cell apoptosis has been observed in preclinical studies. It has been suggested that using DIM it is possible to increase the effectiveness of chemotherapeutic compounds with different molecular targets, thereby increasing chemosensitization. DIM has entered phase III clinical trials, with preliminary results confirming its promise both as a stand-alone drug and in combination with other components of anticancer therapy. Establishing the range of epigenetic control of DIM molecular and genetic changes in various cancers will allow optimization of therapeutic epigenetics approaches.

Background. An unfavorable bleeding pattern is a common reason for refusing to continue hormonal contraception. Aim. To evaluate the characteristics of uterine bleeding when using a new combined oral contraceptive (COC) containing estetrol and drospirenone (Esteretta®). Materials and methods. A multicenter observational study included 1402 females aged 18–49 who received Esteretta® for 6 cycles. The frequency, duration, and severity of withdrawal bleeding, as well as the frequency of unpredictable bleeding, were assessed. Results. The rate of regular withdrawal bleeding was 100%. The proportion of women with heavy menstruation/withdrawal bleeding decreased from 29.6 to 10.07% (p0.0001). The duration of regular withdrawal bleeding was significantly reduced (p=0.008). The incidence of unpredictable bleeding during COC use decreased from 4.57 to 3.29% (p=0.05). Satisfactory cycle control was observed in 87.43% of women. 2.5% of participants refused to continue using COCs. Conclusion. Esteretta® provides a high rate of regular withdrawal bleeding and a low rate of unpredictable bleeding. Given the optimal safety profile, this drug may be the first choice for contraception in sexually active women who are not planning a pregnancy.

Aim. To evaluate comprehensively the quality of life (QoL) of patients with pelvic organ prolapse (POP) who have indications for reconstructive surgery (RS) and determine the optimal tools for QoL assessment as part of preoperative screening. Materials and methods. The study included 860 patients hospitalized for RS at the Saint-Petersburg State University Hospital. The following validated questionnaires were used to assess QoL: the RAND SF-36 (general QoL questionnaire and specialized questionnaires), in particular the P-QoL (QoL Pelvic Organ Dysfunction Questionnaire in POP), the PFDI-20 (Pelvic Organ Dysfunction Questionnaire), the ICIQ-SF (Stress Incontinence Questionnaire), the PISQ-12 (PTD Sexual Dysfunction Questionnaire), the HADS (Hospital Anxiety and Depression Scale). Lower abdominal and lower back pain was assessed using a Visual Analog Scale. Results. Significant QoL reduction was found in most patients, including in physical and psycho-emotional aspects. Among the patients, there were no women with a high level of physical and mental health components. The indicators of vitality, general health, role-physical, and emotional functioning were more significantly reduced. More than 1/3 of women had borderline or increased levels of anxiety, and 1/4 had high levels of depression. Notably, the P-QoL questionnaire was used for the first time in the russian population of patients with POP. It identifies general health perceptions, the impact of prolapse on life, role, physical, social and personal limitations, emotions, sleep/energy, and symptom severity. Based on the study, optimal tools for preoperative screening and monitoring the state of patients after surgery are proposed. Conclusion. The population of women with POP with indications for RS is heterogeneous in terms of the severity of physical and psychosocial functioning impairment and the degree of impact of pelvic organ prolapse symptoms. The following questionnaires can be considered as optimal tools for assessing QoL and symptom burden in patients with POP as part of preoperative screening: P-QoL to assess the decrease of various QoL aspects, PFDI-20 to determine the severity of specific pelvic organ dysfunction symptoms, HADS to identify the level of anxiety and depression.

Background. The high mortality rate from ovarian cancer is largely due to the asymptomatic course of the disease. The signs of malignant and borderline ovarian tumors are similar to the manifestations of benign lesions, which determines the relevance of developing additional examination procedures and searching for new cancer markers that will distinguish benign and malignant processes. Aim. To build stable blood lipid panels for differentiation of healthy women, patients with benign (BOT) and malignant (MOT) ovarian tumors. Materials and methods. The search for markers for clustering of molecular profiles of blood samples of patients of the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology with BOT (cystadenoma – n=30, endometrioid cyst – n=56, teratoma – n=21), with MOT (borderline tumor – n=28, ovarian cancer of low malignancy – n=16, ovarian cancer of high malignancy – n=59) and volunteers of the group control (n=19) using discriminant analysis of orthogonal projections to hidden structures with an established threshold of importance of the variable VIP1 (OPLS) and the method of projections to hidden structures (PLS-PLS – it is a technology of multidimensional statistical analysis used to reduce the dimension of the feature space with minimal loss of useful information; VIP importance threshold 1) and other statistical tools. Samples’ molecular profile was complete by species, which were identificated by nuclear magnetic resonance and high-perfomance liquid chromatography-mass spectrometry. The analysis of the involvement of compounds that are potential markers of malignant processes in metabolic pathways was carried out. Results. Based on the OPLS and PLS methods, as a result of pairwise and multiclass comparisons, respectively, sets of lipids were identified that can be considered as markers of malignant and benign neoplasms. The overlap of the obtained panels with databases of metabolic pathways was studied, in particular, it was shown that all markers (except glucose) obtained by PLS for differentiation of healthy patients, patients with BOT or with MOT are involved in the transport of small molecules, glucose and lactate are involved in the “TCA Cycle” pathway “Nutrient Utilization and Invasiveness of Ovarian Cancer”. Triglycerides TG 16:0_16:0_18:1, TG 16:0_18:0_18:1, TG 16:0_18:1_18:1, TG 18:0_18:1_18:1, TG 18:0_18:1_18:2 and lactate are involved in the “HIF1A and PPARG regulation of glycolysis” pathway, and The HIF1A and PPARG genes are associated with the development of tumors. Metabolites CE 20:4, TG 16:0_16:0_18:1, TG 16:0_18:0_18:1, TG 16:0_18:1_18:1, TG 18:0_18:1_18:1, TG 18:0_18:1_18:2 are included in the pathways of energy metabolism, and LPC 16:0, PC 16:0_20:3, PC 16:0_20:4 is involved in the path of “Choline metabolism in cancer”. Graphs of the correlation interaction of markers that allow solving classification problems with an unambiguous interpretation of the results are constructed, which makes it possible to assert the prospects of using these panels for further creation of classification models. Conclusion. It is shown that lipids from the developed panels are involved in metabolic pathways associated with the development of tumor diseases and can be used for further validation of diagnostic models based on advanced machine learning methods. The introduction of the achievements of postgenomic research has the potential to increase the diagnostic value of the applied methods of differentiation of benign and malignant proliferative processes, as well as to supplement the available data on the processes of carcinogenesis in the ovaries. Thus, the analysis of the molecular profile of blood by mass spectrometry is a minimally invasive potentially effective diagnostic method.

Aim. To analyze the dynamics of the incidence and prevalence of uterine fibroids (UF) in the population of women in the Sverdlovsk region (SR) and the municipality of Yekaterinburg. Materials and methods. A study was conducted on the incidence and prevalence of UF in rural and urban women aged 18 years and over in 2016–2022. The data from Table No. 3000 of the Federal Statistical Observation Form No. 12 “Information on the number of diseases registered in patients living in the service area of a medical organization” were analyzed. When calculating the indicators, the average annual number of women aged 18 years and over in 2016–2022 was used, the values were expressed in 0/0000. Results. It was found that the incidence of UF in SR was 149.11 0/0000, in the city – 130.89 0/0000 in 2016. There was an increase in the incidence of UF in the SR and the city by 1.93 and 1.96 times in 2019, respectively, compared with 2016 (p0.001). The average growth rate (AGR) of incidence in the SR and the city was 24.6 and 25.2% respectively, and had a pronounced growth dynamics in 2016–2019. The prevalence of UF in SR was 735.8 0/0000, in the city – 650.74 0/0000 in 2016. Subsequently, the dynamics of the increase in prevalence, similar to the incidence, was observed. The prevalence rate in the region was 15.5%, in the city – 11.6% in 2016–2019. There was a decrease in the incidence of UF in SR (p=0.014) and the city (p0.001) in 2020–2022. The AFR had a negative value: -3.4 and -7.9%. The prevalence of UF corresponded to a moderate trend, taking into account the positive values of AFR: 1.3% in SR and 2.3% in the city. Conclusion. The prevalence of UF in SR and the city of Yekaterinburg in the pre-pandemic period (2017–2019) was characterized by a marked increase compared to the initial 2016 year. During the pandemic, there was a slight dynamics in the city and stagnation of the indicator in the SR due to a pronounced decrease in incidence.

Background. Epithelial-mesenchymal transition (EMT) is a conserved mechanism in the process of morphogenesis and organogenesis. EMT provides cells with migratory and invasive properties, which is a necessary condition for the formation of endometrioid heterotopias. Aim. To confirm the presence of EMT features in different types of endometriosis. Materials and methods. During a period of five years (2012–2017) we analyzed 43 cases of extragenital endometriosis: appendix (3 case), colon (5 cases), ileum (1 case), abdominal scar endometriosis after caesarean section (24 cases), and inguinal hernia (10 cases). The material was processed according to histological and immunohistochemical technique using monoclonal E-cadherin and polyclonal Vimentin antibodies to assess local invasiveness. Results. In peritoneal endometriosis, the ratio of E-cadherin to Vimentin expression was 10.3, in the colon = 9.1, in the appendix 8.6, in the ileum 5.5, in the hernial sac 4.2. Thus, in diffuse infiltrative forms of endometriosis, the lesion phenotype is characterized by low expression of E-cadherin, while expression of Vimentin is at a high level (p0.05). Conclusion. The results of our study confirmed involvement of the epithelial-mesenchymal transition process in the pathogenesis of extragenital endometriosis lesions, on the one hand, and they certify its invasive potential in these localizations, on the other hand.

Endometriosis affects about 10% of women of reproductive age and can negatively impact their quality of life (QoL). Due to the heterogeneity of symptoms or even their absence, early diagnosis is difficult. Therefore, it is necessary to comprehensively assess the patient's complaints, including a thorough review of medical history, the results of imaging studies, and risk factors for endometriosis. Early diagnosis enables preemptive treatment and avoids surgical intervention. The article presents data on managing patients with endometriosis in outpatient settings, describing methods for non-invasive imaging diagnosis of endometriosis. Current options of pharmacotherapy aimed at controlling the development of the disease and improving the QoL of patients in the long term are addressed. Timely initiated drug treatment improves the QoL of patients, in some cases, leads to a regression of the lesions, and improves the prognosis for the reproductive function. A shift in focus to clinical diagnosis, combined with non-invasive imaging, shortens the time between the first consultation and the final diagnosis. According to the current view of Russian and international professional societies, therapy should be long-term; therefore, selecting treatment with predictable responses and monitoring the course of the disease is necessary.

The frequency of abdominal delivery in the world is steadily rising. Since the latter is associated with a lot of complications compared with vaginal delivery, the increase in the proportion of deliveries in women with a uterine scar through the natural birth canal is an important strategic goal of the obstetrics and gynecology community. In addition, it is established that every second patient after a cesarean section develops a defect in the scar area, which is often accompanied by various disorders of the menstrual cycle (in 25,5% of cases – abnormal uterine bleeding) and can cause secondary infertility. Both assessment of the risk of scar failure at the stage of preconceptional preparation and timely detection and treatment of isthmocele symptoms are still serious challenges facing obstetricians and gynecologists. Clinical guidelines devoted to the cesarean scar defect problem have not yet been developed. This review presents the quintessence of modern data on possible risk factors, clinical manifestations with a detailed consideration of pathophysiological mechanisms, diagnostic tools and correction methods of symptomatic isthmocele and uterine scar defect with a detailed description of indications and a comparative assessment of their effectiveness in order to standardize approaches to the diagnosis and treatment of these pathological conditions.

Aim. To determine local features of lipoperoxidation processes, antioxidant defense, state of matrix metalloproteinases in chronic endometritis. Materials and methods. Eighty women aged 29.33±6.71 (min-max [24–36]) with histologically and immunohistochemically confirmed chronic endometritis and a history of reproductive losses were examined (group 1). The control group consisted of 30 patients without chronic endometritis confirmed by the results of a histochemical study and no history of reproductive losses, suffering from infertility of tubal-peritoneal origin at the age of 30.11±6.9 years (min-max [24–37]; group 2). All 130 patients underwent transvaginal echography of the pelvic organs, and histological and immunohistochemical examination of endometrial samples was performed. The activity of lipid peroxidation factors was analyzed: primary, secondary and final products of lipid peroxidation in heptane and isopropanolol fractions of uterine cavity aspirate, enzymes of the antioxidant system: superoxide dismutase, catalase, glutathione peroxidase, deoxyribonuclease I (DNase), by spectrophotometric method, remodeling factors – matrix metalloproteinases MMP-2, -9 by flow fluorimetry. Results. In patients of group 1, according to transvaginal echography of the pelvic organs, M-echo was 6.29±1.22 mm, in group 2 – 9.10±1.15 mm. In chronic endometritis, disruption of pro-oxidant and activity of antioxidant factors in the endometrium in women with chronic endometritis and a history of reproductive losses. In the heptane fraction of the phenolic extract, the concentration of primary products of lipid peroxidation (diene conjugates) was 12.98% higher than in the control, the content of secondary products of lipid peroxidation (ketodienes) was higher by 15.45%, conjugated trienes by 18.67% higher than the values in the control group, which indicates increased lipid peroxidation of endometrial cell membranes during CE. In the isopropanol phase, the products of lipid peroxidation of phospholipid acyl residues are detected. In the isopropanol fraction of the lipid extract, the amount of diene conjugates was higher, ketodienes by 24.32% and conjugated trienes by 26.14%. An increase in the activity of the enzymes superoxide dismutase by 23.98%, catalase by 14.34%, glutathione peroxidase by 12.39%, and DNase by 2.9 times was recorded compared to the indicators of group 2. Conclusion. Chronic endometritis is accompanied by changes in the system of pro-oxidant and antioxidant factors, the content of tissue remodeling products. The pathogenetic changes underlying oxidative stress in the endometrium may be increased leukocyte infiltration, imbalance of primary, secondary and end products of lipid peroxidation, enzymes superoxide dismutase, catalase, glutathione peroxidase, deoxyribonuclease I (DNase), expression of matrix metalloproteinases-2, -9.

The concept of the demographic policy of the Russian Federation is to increase the birth rate, preserve citizens' health, and increase life expectancy. One of the priority areas is the reproductive health of women. The pleiotropic effect of the components of combined hormonal drugs is successfully used in clinical practice by obstetricians-gynecologists not only for contraception but also for conditions requiring prophylaxis and drug therapy. Estrogens have a protective effect on the reproductive and extragenital organs; however, evidence of the effect of estrogen-containing drugs on breast tissue and hemostasis remains debatable. We analyzed the data published in the international databases PubMed, Google Scholar, and MEDLINE (search depth – 5 years). Estetrol (E4) is a native fetal estrogen produced by the fetal liver during pregnancy. The key difference from other estrogens is its highly selective and differentiated effect on various tissues and its unique antiproliferative properties. The review presents the results of studies on estrogenic and antiestrogenic effects of E4 and the combination of E4 with progestogen (Esteretta drug product approved in Russia), with particular attention paid to the oncoprotective effect of E4. Research data suggest that E4 may have different effects on breast epithelial cells and breast cancer cells compared to other estrogens. Clinical data indicate that E4 has a more selective pharmacological profile compared to other estrogens, which is reflected in a low estrogenic effect on the liver, including the production of sex hormone binding globulin, hemostasis parameters, and lipid profile.