Gynecology

Endometrial hyperplasia (EH) is a spectrum of morphological changes in the endometrium characterized by the proliferation of glands and an increase in the gland-stromal ratio. The relevance of this disease is due to its high prevalence (10–55%). The clinical significance of EH is related to the increased risk of endometrioid cancer. One of the leading causes of EH is absolute or relative hyperestrogenism and progesterone deficiency that does not eliminate the proliferative effect of estrogens. The risk group for EH includes women with early menarche, late menopause, infertility, anovulation, polycystic ovary syndrome, obesity, type 2 diabetes mellitus, hypertension, Lynch syndrome, estrogen-producing ovarian tumors, as well as those receiving estrogen monotherapy or tamoxifen. Most leading experts believe that therapy should include surgery followed by drug therapy aimed at eliminating risk factors to reduce the risk of EH recurrence. Despite numerous research findings demonstrating the benefits of a particular treatment modality and the consequent presence of these modalities in clinical guidelines, the potential benefits of alternative therapies are still being discussed. This issue requires further study and the selection of optimal treatment regimens for patients with EH.

Rheumatoid arthritis is one of the most common and severe autoimmune diseases. The prevalence of rheumatoid arthritis among adults in different geographical areas of the world ranges from 0.5 to 2%. The prevalence of juvenile rheumatoid arthritis is approximately 6 per 10 thousand children. The disease occurs 2 times more often in girls than in boys. Some studies have demonstrated a possible effect of high cumulative doses of methotrexate on ovarian function in patients with systemic lupus erythematosus, but further studies are needed to confirm this effect. The analysis of literature data allowed us to identify prognostically significant factors in the development of autoimmune ovarian failure in patients of reproductive age with rheumatic pathology, and to note the fact that there is missing information about the state of the reproductive system in female patients with juvenile arthritis.

Aim. To analyze the relationship between the expression of proteomic markers [estrogen (ER) and progesterone (PR) receptors, LIF, FOXA1, FOXA2] of endometrial receptivity and indicators of the levels of sex steroids [estradiol (E₂) and progesterone (P)] in the peripheral blood during the “implantation window” in women with a history of reproductive dysfunction with “thin” endometrium (TE) and evaluate their significance for the therapeutic effect of using estradiol drugs.

Materials and methods. The prospective cohort comparative study was conducted. The main group included 52 patients with TE (<7 mm according to ultrasound on preovulatory days), the comparison group consisted of 62 women with normal endometrial thickness (≥7 mm according to ultrasound), women of both groups with reproductive dysfunctions of unknown reason; the control group included 16 healthy women. Aspiration biopsy of the endometrium was performed on the 6–8 days after ovulation (LH +6–8), as well as venipuncture to obtain a sample of peripheral blood to determine the E₂, P levels. A combined histological and immunohistochemical study of endometrial samples was performed (ER, PR, LIF, FOXA1, FOXA2). The therapeutic effects of estradiol drugs were assessed in a cohort of women from the main group with TE (n=16 out of 26, those who have not changed their reproductive plans).

Results. All women had ovulatory values of progesterone [P≥16.1 nmol/l (LH +6–8)] and normoestrogenemia in the blood (p>0.05). According to the results of the correlation analysis, there were no associations between the E₂, P levels and the value of M-echo, and no relationships were found between the E₂, P levels and the expression of ER, PR, LIF, FOX-proteins. It was revealed that there are significant positive relationships between M-echo and FOXA2 expression in the endometrium (r=0.422; p<0.001). Conditional threshold values for the ER, PR expression (LH +6–8) were determined, the excess of which is associated with abnormal expression of LIF, FOX-proteins: for PR in the glands – 105 and 285, for ER in glands – 145, for ER in the stroma – 155. It was found that usual doses of estradiol drugs (1–1.5 mg/day) are capable of increasing endometrial proliferation in women with TE, provided that the expression of ER, PR, LIF, FOX-proteins in their endometrium is similar to healthy women. Increased doses of estradiol drugs (4 mg/day) in women with TE had a significant effect in the form of an increase M-echo value and/or pregnancy in cases where the endometrial expression of LIF, FOX-proteins was comparable with healthy women, even in the presence of hormone-receptor interactions in the endometrium that are different from healthy women. Spontaneous pregnancy in participants of the main group with hypoplastic endometrium in our study occurred in 5 women in whom the expression characteristics of FOXA1 and/or FOXA2 in the endometrium were comparable to healthy women.

Conclusion. TE is not the only marker of an imbalance of proteomic molecules, but it determines a greater likelihood of impaired expression of ER, PR, LIF, FOX-proteins in the endometrium. In women with an unclear reason of fertility disorders, it is necessary to conduct an in-depth examination of endometrial samples. Characteristics of endometrial expression ER, PR, LIF, FOX-proteins and the usefulness of hormone-receptor interactions in the TE in women with a history of reproductive disorders can be markers for predicting the effectiveness of the use of exogenous estradiol drugs in women in order to enhance endometrial proliferation with an initially low M-echo.

Aim. To evaluate the clinical efficacy of complex antioxidant therapy (CAT) in the treatment of patients with pelvic varicose veins (PVV).

Materials and methods. Patients with PVV (n=150) were divided into groups 1 and 2 of 75 subjects; the groups were comparable. Treatment in both groups included standard therapy with one of the venotropic agents (60 days). Patients of group 1 additionally received CAT for 30 days (1 course), in total 3 courses with 2-month intervals.

Results. When assessing the parameters of the lipoperoxidation system (antioxidant protection) in group 1 during CAT combined with standard venotropic therapy, there was a statistically significant decrease in the levels of lipid hydroperoxides (p<0.0001), diene conjugates (p=0.001), malonic dialdehyde (p<0.0001), an increase in the levels of catalase (p<0.0001), superoxide dismutase (p<0.0001), glutathione peroxidase (p<0.0001), glutathione reductase (p<0.0001), glutathione-S-transferase (p=0.002) and the reduced glutathione content (p=0.032) compared to levels before treatment. The above group showed a decrease in the diameter of the pelvic varicose veins: internal iliac (p<0.001), ovarian (p<0.0001) and arcuate (p<0.001), an increase in their blood flow velocity (p=0.003, 0.041, and 0.040, respectively), a decrease in the duration of retrograde flow to 0.3 cm. There was a decrease in pelvic pain (p<0.0001), dysmenorrhea (p=0.024), dyspareunia (p=0.037), the frequency of irregular menstruation (p=0.031), an improvement in quality of life (p=0.047), pregnancy rate (p=0.013), the number of live births (p=0.004), and the duration of remission (p=0.047).

Conclusion. The use of a combination of antioxidants superoxide dismutase 250 mg 2 times a day, acetyl-glutathione at 100 mg 2 times a day, and astaxanthin 400 mg/day for 30 days in 3 courses with 2-month intervals combined with venotropic therapy can significantly improve the treatment outcomes of patients with PVV.

Background. Colpoptosis combined with stress urinary incontinence is one of the most common conditions in postmenopausal women. Menopause is also associated with the risk of genitourinary syndrome due to estrogen deficiency. Despite the variety of options for surgical correction of genital prolapse and urinary incontinence, there is no universal technique. The use of vaginal approach in pelvic floor surgery is associated with several controversies regarding the rates of recurrence and mesh-associated complications. Studies of the state of the endothelium in menopause have demonstrated a close relationship between age-related features and the frequency of adverse clinical outcomes, which requires an optimal intervention not only on the hormonal status but also on the microcirculatory system.

Aim. To improve the principles of complex treatment of pelvic organ prolapse and genitourinary syndrome in postmenopausal patients.

Materials and methods. The study included 48 postmenopausal patients with genital prolapse of stage II and above according to the POP-Q classification. All patients received continuous menopausal hormone therapy (MHT) with a combined estrogen-progestogen agent. The patients in group 1 (n=24) received MHT according to clinical guidelines for managing patients with genitourinary syndrome. The patients in group 2 (n=24), in addition to MHT, received sulodexide containing glucurono-2-amino-2-deoxyglucoglucan sulfate before the intended surgical treatment and for 30 days after surgery. Correction of colpocystocele, proctocele and stress urinary incontinence was performed using anterior and posterior colporrhaphy, perineoplasty, and urethral sling placement in case of stress urinary incontinence.

Results. Six months after surgical treatment, signs of genital prolapse recurrence were detected in 3 patients (12.5%) in group 1, and 1 patient (4.2%) showed signs of mesh-associated complications (implant extrusion) after urethral sling placement. In group 2, only 4.2% of patients (n=1) showed signs of recurrence of stage II cystocele. All patients who underwent urethral sling surgery reported improved urinary incontinence (n=10). During complex therapy, 3 months after surgery, a more significant improvement of endothelial dysfunction markers was noted in group 2 patients (homocysteine level in group 1 after treatment was 12.27±0.34, in group 2 – 8.34±0.24).

Conclusions. Combination therapy of genitourinary syndrome and genital prolapse using MHT, endotheliotropic drugs and vaginal surgical approach in postmenopausal patients contributes to effective and safe treatment associated with minimal risk of complications and recurrence rate. Endothelial dysfunction correction is an essential step in planning surgical intervention in menopausal patients, which contributes to improving tissue repair in the postoperative period.

Aim. To evaluate the effectiveness of combined pelvic organ prolapse correction using the proposed modification of laparoscopic promontofixation of the uterus and vaginal walls using a mesh graft in women of reproductive age.

Materials and methods. A prospective non-randomized study included 41 women of reproductive age (up to 49 years) with grade II–IV symptomatic combined pelvic organ prolapse. The main group (n=19) included women who underwent surgery using the proposed original method (invention patent No. RU2795649C1 dated October 27, 2022), the control group (n=22) included women who underwent conventional laparoscopic promontofixation of the uterus and vaginal walls and vaginal plasty with local tissues. The duration of surgery, intraoperative blood loss, anatomical result, effect on symptoms and sexual function were assessed using the Pelvic Floor Distress Inventory (PFDI-20), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12).

Results. The duration of surgery and intraoperative blood loss were significantly lower in the main group (p=0.043 and p<0.001, respectively). Anatomical success was achieved in both groups and persisted throughout the follow-up period (without statistically significant differences). Analysis of the PFDI-20 questionnaire responses showed a significant improvement in both groups with no statistically significant differences. Analysis of the PISQ-12 questionnaire data showed a significant improvement in the quality of sexual life in both groups; however, after a year of follow-up, patients of the main group had a significantly better quality of sexual life (p<0.05).

Conclusion. The surgical correction of combined pelvic organ prolapse using the proposed method demonstrated a good anatomical result, a decrease in intraoperative blood loss and duration of surgery, as well as an improvement in sexual function in women of reproductive age.

Background. Side effects of endocrine therapy with tamoxifen (TAM) reduce the quality of life of patients with breast cancer (BC) and adversely affect treatment compliance. Against the background of treatment of BC with TAM, the risk of developing endometrial hyperplasia (EH) increases. At the moment, algorithms for monitoring patients receiving TAM by an obstetrician-gynecologist have not been developed and approved. There are also divergent opinions of experts regarding the diagnosis and management of patients in the detection of EH. This article presents the results of the final stage of the study in 2017–2022 – a survey study. The purpose of this study was to assess adherence to endocrine therapy and satisfaction with observation by a gynecologist of women with BC after 5 years of observation and their relationship with the identified early associated polymorphisms of the CYP2D6, CYP3A5, CYP2C9 and ABCB1 genes.

Materials and methods. 54 patients with BC, out of 120 who had previously passed the first pharmacogenetic stage of the study, were interviewed with specially designed questionnaire. Due to the small sample size, delta percentages (∆%) were used in each comparison group with a difference threshold of 5%. To assess associations with the studied genetic polymorphisms, previously obtained significant associations of adverse drug reactions with pharmacogenetics in the same patients were used.

Results. The prevalence of all adverse drug reactions (ADRs), with the exception of EH, was higher in the group of patients who canceled TAM. Over 5 years of follow-up, 57.4% of patients were regularly observed by an obstetrician-gynecologist, 42.59% of patients visited a gynecologist less than once a year. Of all the respondents, 53.7% of patients are satisfied with the regularity and quality of dispensary observation by an oncologist, 33.33% of patients are satisfied with the regularity and quality of dispensary observation by an obstetrician-gynecologist. All studied ADRs (EH, hot flashes, asthenia, bone pain and dyspepsia) associated with various genetic polymorphisms, prevailed in the group of patients who stopped taking TAM due to drug intolerance (∆%: 25.72, 6.97, 4.81, 6.97 and 24.52 respectively) compared with the TAM-group.

Conclusion. The results obtained confirm the role of the studied genetic polymorphisms in the development of ADRs of TAM, but only systemic (hot flashes, asthenia, bone pain and dyspepsia). With regard to endometrial hyperplasia, no significant differences were obtained, which requires more extensive studies.