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Aim. To study the effect of combined oral contraceptives (COC) with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transition. Materials and methods. Females in the menopausal transition who needed contraception were divided into two groups. Group 1 (19 patients) received COCs containing estradiol valerate/dienogest (E2V/DNG) with a dynamic dosing regimen; Group 2 (19 patients) received monophasic COCs containing 17-estradiol/nomegestrol acetate (E2/NOMAC) for 6 months. Blood pressure (BP), parameters of carbohydrate and lipid metabolism, leptin, adiponectin, C-reactive protein, uric acid, and body composition by dual-energy X-ray absorptiometry were assessed initially and after the 6 months of therapy. Results. No significant changes in weight and body composition after 6 months of COC use were found in both groups. COCs with E2V/DNG had no significant effect on BP and all assessed metabolic parameters. Females taking COCs with E2/NOMAC showed increased fasting glucose of 4.85 (0.43) and 5.30 (0.37) mmol/L (p=0.002), insulin of 4.97 (2.35) and 8.82 (4.67) U/mL (p=0.012), NOMA index of 1.06 (0.54) and 1.88 (0.75); p=0.010 compared to baseline. However, the parameters remained within the reference values. Conclusion. COCs containing estrogens identical to natural estrogens do not affect body composition and have no significant adverse effect on BP and metabolic parameters in females during the menopausal transition, indicating that the use of these agents is acceptable from the perspective of their metabolic effects in this group of patients.

Aim. To study the correlation between the features of obstetric and gynecological anamnesis with indicators of arterial stiffness in women of different age groups to assess additional risk factors for the development of cardiovascular diseases. Materials and methods. The single centre study involved women aged 18 to 65 years. The surveyed 161 women were divided into three groups: 1st group 52 young women from 18 to 30 years old; 2nd group 54 women from 31 years old to the onset of menopause; 3rd group 55 postmenopausal women. The 1 and 2nd groups included women with preserved reproductive function. All women underwent a questionnaire survey, clinical examination, determination of anthropometric data, measurement of cfPWV, determination of arterial stiffness by volume sphygmography, 24-hour blood pressure monitoring with assessment of aortic stiffness and characteristics of the central pulse wave. Results. In group 1, the early age of menarche was associated with an increase in the rate of morning rise in SBP (r=-0.46, p=0.002) and a decrease in SEVR (r=0.33, p=0.03); the use of combined oral contraceptives correlates with an increase in the Weissler coefficient PEP/ET (R=0.3, p=0.03) and amplification of pulse pressure PPA (R=0.29, p=0.04). A history of 1 or 2 pregnancies is associated with a decrease in arterial stiffness. At the same time, 3 or more pregnancies in the anamnesis create the prerequisites for the formation of arterial stiffness. The early onset of pregnancy pathologies, namely, starting from the 1st or 2nd trimester of pregnancy, is associated with a violation of the characteristics of the reflected wave at a young age and the formation of arterial stiffness in the menopausal period. History of abortions was associated with PWVao (R=0.45, p=0.002), ASI (R=0.43, p=0.002) in group 2. History of miscarriages is associated with SEVR (R=0.52, p=0.00005) and SEVR to HR75 (R=0.27, p=0.04) in the menopausal period. Conclusion. Pathology of pregnancy, three or more pregnancies in history, early age of menarche, taking combined oral contraceptives, abortions and miscarriages in history are associated with an increase in arterial stiffness in the future, which predisposes women to the development of CVD and should be taken into account for preventive purposes.

Aim. To conduct a comparative analysis of serum orexin A levels in women of different age periods with and without sleep disorder and vasomotor symptoms. To evaluate the dynamics of orexin A levels under menopausal hormone therapy. Materials and methods. The study included 50 postmenopausal women and 30 women of reproductive age with a regular menstrual cycle. Using block randomization, patients are divided into 3 groups: group 1 (main group), n=25, -STRAW+ 10 (+1b and +1c), patients with sleep disorder and vasomotor symptoms; group 2 (comparison group), n=25, STRAW+ 10 (+1b and +1c), patients with vasomotor symptoms without sleep disorder; group 3 (control group), n=30, STRAW+ 10 (-4), women of reproductive age without sleep disorder. Group 1 patients were given menopausal hormone therapy. A comparative analysis was carried out using the questionnaire for assessing menopausal symptoms severity by the Greene Scale (the Greene Climacteric Scale) and Rating Scale for subjective sleep characteristics. After 12 weeks of treatment, a control examination was performed. Results. In group 1 women, the serum orexin A levels were significantly higher compared to the women without the symptoms. The link between the orexin A levels and menopause syndrome severity was established. A significant decrease in the menopausal symptoms severity after 12 weeks of menopausal hormone therapy was shown. It was accompanied by a 1,3-fold decrease in orexin A levels. Conclusions. The obtained data indicate the possible role of orexin A and the orexin neuropeptide system in the pathogenesis of sleep disorder and vasomotor symptoms in postmenopausal women.

Aim. To analyze and systematize the available information on pathogenetic mechanisms of hormonal carcinogenesis. Materials and methods. The review includes data from foreign articles published in PubMed and Medline and national works posted on elibrary.ru over the past 20 years. Results. Currently, the term estrogen is often used in the context of hormonal carcinogenesis. According to most researchers, it should not fit into the narrow framework of receptor-mediated proliferation induced by estrogens in target tissues. The concept of estrobiome as a combination of all mechanisms providing the realization of estrogen effects should include not only hormones and native receptors themselves, but also the enzymes involved in their synthesis, estrogen metabolites, intestinal microbiota, as well as genetic and epigenetic factors. Conclusions. When analyzing cancer risk, it is necessary to comprehensively assess contributing factors and hormonal-metabolic preconditions for neoplastic process.

Aim. To formulate a position statement on the management of the menopause in women with a past history of endometriosis from the point of view of evidence-based medicine. Materials and methods. Review of domestic and foreign literature, position of IMS and EMAS. Results. The article describes the main modes snd ways of introducing MHT and their advantages. The expert position on the management of patients with a history of endometriosis during surgical and natural menopause is highlighted. Information on the prevalence and methods of treatment of postmenopausal endometriosis is given.

BACKGROUND: Obesity is a metabolic disorder that becomes epidemic. Visceral adiposity increases the risk of arterial hypertension, diabetes mellitus and other comorbidities. According to this, the main aim of obesity treatment is not only a weight loss but also a decrease of the risk of comorbidities. AIMS: to assess the efficiency and safety of sibutramine in patients with obesity and arterial hypertension, to evaluate the drug influence on epicardial fat thickness. MATERIALS AND METHODS: 57 patients aged 35-60 with obesity and arterial hypertension were included in the study. All patients at the beginning and after 7 months of follow-up underwent complex examination including anthropometric measurement, ECG, office and ambulatory blood pressure measurement, echocardiography. Patients with controlled arterial hypertension were included. During the first month of follow-up patients were given general weight loss recommendations. Then sibutramine was added. Control visits to assess efficiency and safety of drug treatment were held after 1 and 6 months of follow-up. RESULTS: Women predominated among the study participants. Visceral adiposity was approved by anthropometric measurements among all patients. Most patients had impaired left ventricle geometry: concentric remodeling or hypertrophy. During the first month of follow-up the weight loss was mild: 2 kg (less than 2%) in average. Sibutramine for 1 month the weight loss increased: 3.7 kg (more than 2%) in average. After 6 months of drug administration the weight loss of patients consisted 8.6 kg (6.2%) in average. According to echocardiography results indexed mass of LV myocardium decreased in all patients more significantly in women. Also in this group of patients significant decrease of epicardial fat thickness was revealed. Adverse events of sibutramine were revealed in 26.3% of patients. The most frequent were constipation (12.3%) and dry mouth (10.6%). The severity of symptoms persisted for 1 month and then decreased, additional therapy was not required. CONCLUSIONS: Sibutramine treatment of obesity promotes effective weight loss, influences the adipose tissue distribution, decreases the progress of associated comorbidities. Sibutramine is an effective and safe drug that can be used in patients with visceral adiposity and controlled arterial hypertension.

Modern medications for osteoporosis (bisphosphonates, denosumab, teriparatide) are well-tolerated drugs, which can significantly lower vertebral and non-vertebral fracture risk according to prospective and observational studies in up to 10-year period. Certain drugs (denosumab, teriparatide) are active only during the treatment period and do not prevent bone loss and fracture risk after discontinuation, while such protective effect is observed in bisphosphonates. Despite impressive success of continuous 10-year denosumab treatament of severe osteoporosis, some of the recently published data suggest that vertebral fracture incidence is increased after treatment discontinuation, along with multiple vertebral fracture incidence, especially in patients with previous fractures. Issues of osteoporosis treatment duration, sequential use of osteoporosis drugs and criteria for treatment discontinuation are now in focus of attention. European Medicines Agency (EMA) and European Calcified Tissue Society (ECTS) considered these issues in 2017. ЕМА considered fractures after denosumab discontinuation as a natural disease course and did not recommend any changes in product instruction. The main conclusion of ECTS is that the possibility of multiple fractures development after denosumab discontinuation exists, however, there is still not enough firm evidence, as well as effective countermeasures. Clinicians and patients should be aware of potential risk. Both EMA and ECTS suggest considering denosumab treatment or discontinuation after 5-year treatment period or possibly replacing with bisphosphonates. Recent data suggest that prolonged osteoporosis treatment can be done in accordance with the concept of treatment until target goal (for example, achievement of femoral T-score -2.0SD and higher). In our review, we focus on recent data concerning the issues stated above. This topic was also discussed on Russian Osteoporosis Association (ROA) expert meeting in Saint Petersburg on 24 may 2018, chaired by ROA president, professor Olga Lesnyak and Columbia University professor, J.P. Bilezikian. As a result, an Expert Council resolution was written and introduced in the article.

Currently, women-specific risk factors for cardiovascular diseases (CVD) are of particular importance, one of which is hypertensive disorders during pregnancy (HDP). The effect of hypertensive disorders on the formation of arterial stiffness as a predictor of CVD development remains insufficiently studied. Aim. To study the relationship of indicators of arterial stiffness, risk factors and metabolic changes with the presence of HDP in the history of women of different age groups. Materials and methods. The study included women aged 30 to 65 years, with one or more risk factors of CVD, which were divided into two groups: 1st - with preserved menstrual function and 2nd group - in the postmenopausal period with the presence or absence of HDP. All patients underwent daily blood pressure monitoring with determining the dynamics of central arterial pressure, determining the velocity of the pulse wave from the carotid to the femoral arteries, non-invasive determination of vascular stiffness indicators using the volume sphygmography method. Results. 90 women were examined. The first group consisted of 45 women (mean age 41±5.9 years); the second group - 45 women (mean age 55.3±5.8 years). In both groups, women with HDP are more likely to have burdened CVD heredity (p=0.02). In the 1st group with HDP, the average body weight and body mass index were significantly higher (p=0.02); menstrual disorders occurred more than twice as often (p=0.01) than in women without HDP. In the 2nd group with HDP abortions were more frequent (p=0.05) in history. In the 1st group with HDP, a significantly higher augmentation index AI (p=0.01); the average value of the average daily rate of the pulse wave in the aorta was also exceeded (11.7 m/s), which is 0.8 m/s higher than in women without HDP (p=0.02). Conclusion. A change in the AI and the average daily pulse wave velocity in the aorta, along with the presence of CVD risk factors and hormonal and metabolic disorders, are early markers of subclinical damage to target organs in women of reproductive age with a history of HDP.

Background. Combined oral contraceptives (COCs) are the most common method of prevention of unwanted pregnancies in women from the early reproductive period to perimenopause, therefore their impact on quality of life, sexual function and general well-being remains the subject of active discussion. Some studies revealed various manifestations of sexual dysfunction in patients receiving COCs, therefore such questions, as well as the advantages / disadvantages of individual components (their type and dose) of drugs, are of interest to the clinician. Aim. Assess mechanisms of influence of COCs on female sexual function. Materials and methods. In order to write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, elibrary, etc.) for the last 2-15 years. Relevant articles from the peer-reviewed literature were included. Results. Many studies proved a beneficial effect of estradiol valerate (E2V) which is estrogen identical to natural one in a combination with dienogest (DNG) which is 4th generation progestin in a dynamic dosing regimen on quality of life and sexual function. This beneficial effect is achieved due to combined effects of both components of the drug as well as its reception mode. Conclusion. The combination of estradiol valerate (E2V) which is estrogen identical to natural one with dienogest (DNG) which is 4th generation progestin may be the optimal method of contraception for women of any age, including the young, with decreased libido while taking other COCs.