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Endometriosis affects 10% of all women of reproductive age, i.e. 190 million patients. Ukraine currently does not gather statistics on the incidence of endometriosis, but, at a rough estimate, this number is approximately 280 thousand women and the real number may be higher. Endometriosis has known significant social, medical and economic impact. Therefore, Ukrainian leading specialists in obstetrics and gynecology focus on new treatments for endometriosis, given current scientific data and the needs of patients. The given resolution and algorithms for treatment for endometriosis are the common stand of leading specialists in gynecology in our country and were developed on the basis of modern domestic and foreign data and current clinical guidelines. This resolution aims to improve clinical approaches to the routine practice of treatment for endometriosis. The constant increase in the incidence of endometriosis and its management characteristics allows to conduct an extensive study of the effectiveness and safety profile of various progestogens. In recent years, a number of further evidence have appeared regarding dydrogesterone treatment for endometriosis. New data on the effectiveness of dydrogesterone offer another hormone-based treatment for endometriosis, which is extremely important given the need for long-term and individualized treatment for endometriosis. The Europ ean Society of Human Reproduction and Embryology (ESHRE) states that the degree of pain relief in endometriosis is the same for all hormone-based treatments, but the safety and tolerability profiles of different medicinal products differ, which must be considered. According to the obtained data on the effectiveness and metabolic safety profile of various progestogens and during the discussion, algorithms for dydrogesterone-based treatment for endometriosis were proposed.

Research objectives: to evaluate the activity of apoptosis and proliferation mechanisms of eutopic endometrium in patients with adenomyosis who had a history of papillary thyroid carcinoma (PTC). Materials and methods. 63 women of reproductive age were examined: group I – 31 patients with adenomyosis and PTC in history, group II – 32 patients with adenomyosis and normal thyroid status. The intensity of pelvic pain was assessed using a visual analog scale in all women. The material for morphological research was obtained with Pipelle biopsy of the endometrium in the secretory phase of the menstrual cycle. A morphological study was performed on 30 biopsies of eutopic endometrium (15 samples from patients of group I and 15 samples from patients of group II). An immunohistochemical study was performed using monoclonal antibodies to cell-specific markers Bcl-2 (DAKO, clone 124) and Ki-67 (DAKO, clone MIB-1). Results. High expression of Bcl-2 was detected in the endometrial glandular epithelial cells (EGECs) in 70% and 62.5% of samples in group I and II respectively (р > 0.05), the number of Bcl-2-positive cells was significantly higher in samples from group I (80.0 ± 13.1% versus 60.0 ± 15.2% in group І and ІІ respectively, р < 0.05). In endometrial stromal cells (ESCs) high expression of Bcl-2 was detected in 90% and 100% of samples from group I and II respectively (р > 0.05), no significant difference in the number of positive cells was found between groups (18.9 ± 12.2% and 12.6 ± 9.1% in group І and ІІ respectively, р > 0.05). Expression of Ki-67 was detected in the EGECs in 70% and 62.5% (р > 0.05) of samples in group І and ІІ respectively and in the ESCs in 100% of samples from groups I and II respectively. The immunocytochemical Ki-67 labelling index was much more prominent in group I (45.0 ± 11.4% versus 25.8 ± 16.7% EGECs (р < 0.05); 26.5 ± 10.2% versus 16.3 ± 8.9% ESCs (р < 0.05) for group I and II respectively). Conclusions. Altered proliferation of the eutopic endometrium with marked resistance to apoptosis was found in reproductive aged female with adenomyosis and PTC in history, that is can be considered as a marker of the aggressiveness of the disease course in this cohort of patients.

Research objectives: to evaluate the effect of vitamin D supplementation (Olidetrim) in the complex anti-relapse therapy of bacterial vaginosis (BV) in women of reproductive age. Materials and methods. The study included 63 women of reproductive age with BV and with a level of 25-hydroxyvitamin D below 75 nmol/l, who were divided into groups: the main group included 32 women who were prescribed standard therapy (metronidazole 500 mg twice a day for 7 days) and cholecalciferol (Olidetrim) 4000 IU/day with subsequent continuation of its intake in a dose 2000 IU/day for up to 6 months; the comparison group included 31 women, who were not intake vitamin D preparation during the standard therapy and during the next 6 months of observation. After treatment, women provided completed questionnaires and self-collected vaginal swabs 1, 3, and 6 months after beginning of the study or before BV relapse. Evaluation of Gram-stained smears was carried out by microscopy according to Hay/Ison criteria, where BV corresponded to type III. The level of 25-hydroxyvitamin D in blood serum was determined by the chemiluminescent immunoassay method before the start of the study and at 3 and 6 months of follow-up. The primary endpoint was BV recurrence at any post-treatment interval; the patients were offered a second treatment in this case. Results. Vitamin D deficiency at the beginning of the study was detected in 12 (37.5%) patients of the main group and in 13 (41.94%) women of the comparison group, an insufficient level – in 20 (62.5%) patients of the main group and in 58.06% women of the comparison group. Patients complained of pathological vaginal discharge, itching, burning and dyspareunia lasting from 1 week to 2 months. At the seven-day course of basic BV therapy all participants noted the normalization of discharge and the absence of vaginal discomfort. Positive dynamics were also observed according to the gynecological examination. One month after the treatment, 4 (12.5%) participants of the main and 6 (19.36%) women of the comparison group noted the recovery of symptoms. Absence of BV recurrence after 3 months was noted by 25 (78.12%) women of the main group and 16 (51.61%) women of the comparison group (p = 0.054), that was confirmed by the laboratory tests. At the same time, the level of 25-hydroxyvitamin D in the main group increased by 43.37% (p = 0.05), and in the comparison group it did not differ from the initial level. There were no complaints in 24 (75.0%) patients after 6 months, however, a laboratory-confirmed normal state of the vaginal microbiome was observed in 22 (70.96%) participants of the main group and in 14 (45.16%, p = 0.07) women of the comparison group. Continuation of vitamin D intake at a dose of 2000 IU/day for the next 3 months demonstrated maintenance of the 25-hydroxyvitamin D level within normal values (81.7 ± 6.23 nmol/l in the main group vs. 38.51 ± 5.43 nmol/l in comparison group, p = 0.05). Conclusions. A decrease in the frequency of BV recurrences in women during support a normal level of vitamin D was found, which allows recommending the inclusion of cholecalciferol supplementation (Olidetrim) in the standard treatment. In patients with recurrent BV a long-term monitoring of the serum level of vitamin D is advisable in order to timely prescribe supplementation.

Research objective: to examine the incidence of asymptomatic and recurrent bacterial vaginosis (BV) in Ukrainian women and to evaluate diagnostic and treatment strategies for the disease control. Materials and methods. This study lasted from January to March 2021 and included 277 doctors of women's clinics, gynecological hospitals and oncology centers from all regions of Ukraine. Information was provided on 12 896 patients between of 18 and 59 ages with BV. Results. Analysis of data from 12 896 questionnaires allowed us to determine that women from 18 to 35 years of age (62.6%) were the most frequently consulted about BV. Only 58.72% patients with BV reported about abnormal vaginal discharge as the reason for visit, while 41.24% of the respondents reported other reasons. Questionnaire analysis of patients with vaginal discharge revealed scant symptoms of the disease: only 62.67% complained about the change of discharge character; 38.49% and 36.35% of examinees pointed to the vaginal itching and unpleasant odor, respectively; 19.89% of patients were troubled by dysuric symptoms and 15.10% of patients mentioned dyspareunia. In the list of submitted questionnaires, 59.92% of patients indicated an additional examination to identify the causes of vaginitis by the PCR method (urogenital scraping). According to its results, Gardnerella vaginalis was detected in diagnostically significant concentrations in 71.49% of patients, Atopobium vaginae was found in 11.32% of cases, Mobiluncus spp. was detected in 19.96% of patients and Trichomonas vaginalis was found in 13.12% of patients. Candida colonization was diagnosed in 62.07%, with Candida albicans in 48,52% cases and non-albicans forms in 13,55% of patients. In the treatment of BV priority was given to the vaginal forms of the most compliant therapy regimens: 2 times a day for 3 days or once a day for 7 days, depending on the clinical situation. Some patients opted for a long course of treatment for recurrent infections, choosing the combination metronidazole 750 mg / miconazole 200 mg 1 suppository once a day for 5 days for 12 months. Conclusion. Diagnosis of BV in Ukraine continues to be based on clinical conditions and requires a unified algorithm that will be based on current clinical guidelines and dictated by national protocols for management. High mycotic colonization (62,07%) in BV makes it expedient to use combined agents (metronidazole 750 mg / miconazole 200 mg tioconazole/tinidazole) both as etiotropic and empirical therapy and especially if there are clinical conditions that may can cause BV (before surgical interventions, after antibiotic therapy, in endocrine pathology, etc.).

Dysmenorrhoea and intermenstrual pelvic pain are the most common symptoms of clinical manifestations of adenomyosis, which significantly impair the quality of women’s life. Adequate and long-term pain correction and alternative therapeutic approaches became extremely important for patients with adenomyosis during the COVID-19 pandemic. Research objective: to examine the clinical efficacy of nitric oxide donor (L-arginine) in the complex treatment of pelvic pain syndrome associated with adenomyosis. Materials and methods. The study included 63 women diagnosed with adenomyosis. Patients were divided into 2 groups by simple randomization: I (D) group (n = 31) received dydrogesterone 30 mg from 5 to 25 days of the menstrual cycle, II (D+T) group (n = 32) in addition to dydrogesterone received a nitric oxide donor L-arginine (Тivortin) according to the scheme. Pelvic pain was assessed before treatment with a Visual Analogue Scale and a McGill Pain Questionnaire, and an assessment of the overall pain impact on women's well-being was based on the SF-36 Health Status Survey. The effectiveness of pelvic pain therapy was assessed after the first and third months of treatment, as well as three months after the end of therapy with the above methods. Results. Researchers achieved a therapeutic effect in the treatment of chronic pelvic pain in both study groups, but in group II (D + T) after 3 months of treatment there was a significant reduction in pelvic pain, while patients of the standard therapy group have prolonged progestogen intake. There was a further improvement in the clinical condition in group I (D) after 6 months of follow-up, as well as no recurrence of pain in group II (D + T). Conclusions. The results of study demonstrate a significant effect of Tivortin as part of complex therapy on the rate of achievement and duration of therapeutic effect in the treatment of pelvic pain associated with adenomyosis.

Adenomyosis is characterized by polymorphism of clinical manifestations and is the cause of chronic pelvic pain associated with endometriosis in 53–80% of cases. Heavy dysmenorrhea in adenomyosis is a key factor that reduces the quality of life and, moreover chronic pain reduces stress resistance and launches the rehabilitation cytokines cascade, which causes exacerbation of endometriosis. Formation of painful syndrome with adenomyosis may be due to: changes in neurohumoral regulation, stimulation of nerves and blood vessels growth and myometrium inflammatory remodeling against the background of circulatory disorders and vascular sclerosis. These processes lead to violation of neuroimmune relationships that determine the increase in the number and sensitivity of nociceptors against the background of the chronic immuno-inflammatory process in endometrials and myometry. Experimental studies have shown that the supraspinal role of the nitric oxide (NO) is to indirect mechanical nociceptive reflexes. The dose-dependent L-arginine role in the pain syndrome formation also was shown; it was found that small doses of L-arginine lead to the activation of nNO-synthase and analgesic effect. Large doses are activated by cotorphine synthase to form a dipeptide of cortorphine (L-tyrosine-L-arginine), which induces the met-enkephalin release and analgesic effect. Individual studies have demonstrated a decrease in the symptoms of urinary pain syndrome during L-arginine treatment, which made it possible to include it into the European Association of Urologists recommendations on the chronic pelvic pain treatment in 2017. Clinical comparative study (2013) of the NO donator (L-arginine) effectiveness in the treatment of endometriosis-associated intermenstrual pelvic pain and dysmenorrhea showed a high efficiency of a 3-month course of combination therapy (dienogest 2 mg + Tivortin 4.2 g). Supplement of basic therapy by NO donator (L-аrginine) has shown a faster reaching the clinical effect on reducing endometriosis-associated symptoms and sustainable maintenance of the result achieved. The multifaceted pharmacological effects of L-arginine directly affect a number of essential factors for the adenomyosis development and progression, which allows using this drug in clinical practice.