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Meditsinskiy sovet = Medical Council

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No 15 (2023)
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REPRODUCTIVE HEALTH AND ART

12-25 507
Abstract

Introduction. The relevance of studying the mechanisms underlying the development of adenomyosis is determined not only by its high prevalence reaching 40% among reproductive aged women, but also by its association with unexplained infertility (60%), as well as woman’s quality of life impairment.

Aim. To enhance efficiency of therapy after surgical treatment of endometriosis and minimize the risk of disease recurrence.

Materials and methods. In a cohort prospective comparative study conducted on the basis of the gynecological department of the Inozemtsev City Clinical Hospital, 80 patients of reproductive age who underwent organ-preserving treatment for external genital endometriosis and nodular adenomyosis were included. Dienogest (Zafrilla) was prescribed to 65 patients at a dose of 2 mg/day (1 tablet) from day 2 after surgical treatment continuously for 6 months, taking into account contraindications to its use, 15 patients refused to take the drug in the postoperative period, and made up the control group.

Results. The results of the study showed that after surgical treatment of external genital endometriosis and the nodular form of adenomyosis and the appointment of suppressive therapy with Zafrilla, after 3 months, the intensity of the pain syndrome was transformed according to the VAS, NRS, B&B scales by one step, and after 6 months it decreased to a slight (p < 0.05), which contributed to the improvement of the quality of life of patients based on the EHP-30 questionnaire. The long-term results of the study allow us to recommend the drug Zafrilla, with high compliance, good tolerance, a favorable safety profile, in order to reduce pain, the intensity of menstrual flow, and prevent recurrence of the disease based on 24 months of observation.

Conclusion. An integrated approach to the treatment of external genital endometriosis and nodular adenomyosis, including surgical treatment and suppressive therapy with Zafrilla, made it possible to realize reproductive function in 48% of patients. Taking dienogest for 24 weeks provided effective relief of pain, alleviated the symptoms of the disease, as well as improved the quality of life and realized reproductive plans.

27-37 320
Abstract

Introduction. Machine learning (ML) applied to data analysis allows to more accurately and targetedly determine the most significant correctable and non-correctable predictors of onset of pregnancy in assisted reproductive technology (ART) programs in patients of different age groups. Analysis of data using various techniques and comparison of results obtained via two models will determine the most significant factors for onset of pregnancy in the ART program.

Aim. To determine the most significant clinical and embryological predictors of onset of pregnancy using standard regression analysis and a decision tree algorithm to predict pregnancy in the ART program.

Materials and methods. A total of 1,021 married couples were included in the retrospective study. The study analysed clinical and laboratory test findings and stimulated cycle parameters depending on the effectiveness of the ART program. A regression analysis was carried out and a decision tree algorithm was built using the Gini criterion to determine the most significant factors.

Results. We identified “general” signs that require further validation on other models, including ML: the presence/absence of a history of pregnancies, stimulated cycle parameters (oocyte cumulus complex, number of metaphase II (MII) oocytes, number of zygotes), spermogram indicators on the day of puncture, number of high and good quality embryos, as well as the embryo grading.

Conclusion. rFSH (follitropin-alpha, Gonal-f) gives a significant result in two of the five available age groups, follitropin-beta, corifollitropin alfa – in one of the five groups only. Building a model that includes not only the couple’s medical history data, but also molecular markers using machine learning methods will not only allow us to most accurately determine the most promising groups of patients for in vitro fertilization (IVF) programs, but also increase the efficiency of ART programs by selecting the highest quality embryo to be transferred.

39-42 413
Abstract

The vulva and vagina are a unique anatomical region, which anatomy and physiology changes throughout a woman's life. The most noticeable changes are hormone-mediated and are associated with the onset of puberty, menstrual cycle, pregnancy and menopause. The microbiome changes over time due to various factors, such as hormones, which leads to a change in pH. Various hygiene practices and habits also have a huge impact on the microflora of the vulva and vagina, and therefore on a woman’s health. Today, the market offers a huge number of care and hygiene products designed for the genital area of women. But, unfortunately, information about their correct use and safety of use is limited. For example, various health behaviours, such as vaginal douching and pubic hair removal are still widely used, although there is some evidence of their negative impacts on the health of the vulva and vagina. Despite the abundance of specialized intimate hygiene products, the use of general care products that are not intended for the genital area and therefore can cause irritation, itching and other unpleasant effects is reported. Foreign guidelines for intimate female hygiene practices resolve itself to recommendations of daily vulva cleansing with a gentle hypoallergenic liquid wash. There is a need to increase women's awareness about rational choice of feminine hygiene products and disorders of the vulva and vagina to improve their intimate health.

45-51 278
Abstract

Introduction. Cervical intraepithelial neoplasias that have been recognized as a precursor of squamous cell carcinoma are subject to active detection for the purpose of eradication. Human papillomavirus (HPV) exposure of women is the major risk factor for carcinogenesis, which is a necessary part for the formation of a pre-tumour and malignant phenotype. Cervical intraepithelial neoplasias that precede the development of squamous cell carcinoma should be actively detected and treated early. The identification of patients with HPV is an important part of subsequent therapies. Inosine pranobex is used as one of the components of the treatment of HPV-associated diseases.

Aim. To study the role of various diagnostic methods in patients with benign and neoplastic cervical processes.

Materials and methods. The study included 311 women who were 21–64 years old. Colposcopy, cytological examination, HPV testing, preliminary biopsy, cervical excise with histological evaluation of tissue sampling were carried out.

Results. HPV 16 was more often detected in a malignant tumour and CIN 3; HPV type 31 and 33 were more often detected in CIN 2 and CIN 3; HPV type 18 was detected in almost all patient with CIN, and malignant and benign neoplastic disorders in preliminary biopsy, that was not typical of results of the excision. In excision CIN 1 were confirmed in 17.07%, CIN 2 in 31.88%, CIN 3 in 66.67%. Preliminary results of benign process in 6.67% turned out to be CIN 1, and in 6.67% – CIN 2, that confirms the need for a comprehensive evaluation. Studies of prevalence of various types of HPV showed that the established sequence of recommended tests, which consists of extended colposcopy, cytology and identification of HPV types, if necessary, does not always correspond to the biopsy results and histological findings on cervical excision specimens. According to our sources, the final result can be determined after excision procedure of cervical tissue and histological examination of the tissue obtained.

Conclusion. No strong correlations between examination methods and cervical pathology have been revealed. The final diagnosis is made after cervical biopsy. High prevalence of different types of HPV raises the question of need for complex therapy with inclusion the inosine pranobex.

53-56 541
Abstract

Introduction. Anemia is a major health problem worldwide, increasing the risks of low birth weight, preterm birth, perinatal mortality, stillbirth, postpartum hemorrhage, and maternal mortality. Replenishing iron deficiency at the stage of preconceptional preparation reduces the incidence of IDA and can reduce the incidence of pregnancy complications and improve perinatal outcomes.

Aim. To evaluate the effectiveness of ferrous sulfate 80 mg and its potential to replenish iron deficiency in women with infertility before using assisted reproductive technologies (ART).

Materials and methods. A prospective clinical longitudinal study was conducted from May to September 2023 at LLC Health Clinic, Moscow. The study included women (n = 34) at the stage of pregnancy planning by IVF with a diagnosed iron deficiency. Iron deficiency was established in accordance with the following criteria: decrease in serum ferritin level less than 30 μg/l, serum iron level less than 15 μmol/l.

Results. After 12 weeks of taking ferrous sulfate, the average hemoglobin level increased from 112.3 ± 6.5 (101–119) g/l to 118.5 ± 6.5 (110–133) g/l (W-Wilcoxon 9300 test, p = 0.003), mean serum iron level from 15.4 ± 4.0 (5.7–22.5) μmol/l to 34.8 ± 7.1 (20.1–46.7) μmol/l (Wilcoxon W test 602.0, p < 0.001), mean ferritin level from 8.2 ± 3.1 (4.5–17.0) μg/ml to 37.6 ± 6.7 (30.6–52.6) μg/ml (Wilcoxon W test 595.0, p < 0.001).

Conclusions. Timely examination of patients for iron deficiency and iron deficiency anemia at the stage of preconceptional preparation makes it possible to prescribe an effective correction, thereby helping to reduce the risks of complications of pregnancy and childbirth.

58-64 381
Abstract

Anti-Mullerian hormone (AMH) is well known as one of the key factors in reproductive development and the formation of sexual characteristics in the embryonic period in both sexes. In women, AMH is produced by granulosa cells of the preantral and early antral follicles of the ovaries and is a key biochemical marker of ovarian reserve. Recently, the role of AMH and its transmembrane receptor AMHRII as possible pathogenetic links in a number of gynecological diseases has been actively studied. The ability of AMH to cause regression of the Müllerian duct in male embryos suggests its inhibitory role for a number of benign and malignant gynecological tumors, as well as endometriosis. In this connection, active scientific research in this direction is currently underway. A number of studies have shown that AMH causes apoptosis of human endometrial stromal cells and endometriosis cells in vitro, and is also involved in the development of autophagy processes in endometriosis. The above studies demonstrate the important role of AMH in cell apoptosis in endometriosis, and indicate its therapeutic potential for a wide range of gynecological diseases. It is important to note that AMH, as a representativemember of the TGF-β superfamily, has high affinity and specificity for the AMHRII receptor, which. This fact makes further study of the function of AMH and AMHRII relevant both for assessing their effectinfluence on the processes of folliculogenesis, and reproductive aging processes, and for developing new targeting targeted therapy strategies therapy for a wide range of gynecological diseases, including endometriosis.

65-70 353
Abstract

Endometriosis is a disease characterized by a benign growth of tissue identical to the endometrium outside the uterine cavity with an accompanying inflammatory process. The exact prevalence of external genital endometriosis (EGE) is unknown. According to some data, the prevalence varies from 2% to 10% among the general female population and up to 50% among women with established infertility. Currently, there is no single theory that could fully explain the causes and mechanisms of the development of the disease. The etiopathogenesis of endometriosis is widely discussed and remains uncertain. The main clinical markers of the disease are chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. The progressive and recurrent course of EGE with a significant deterioration in the quality of life of women is the main motivation for the scientific community in the search for radical therapeutic methods. The main goal of therapy is to reduce pain, correct reproductive dysfunction, prevent / slow down the occurrence of such long-term consequences associated with endometriosis, such as fibrosis, adhesions and malignant transformation. Available advanced technologies aimed at establishing and studying the pathophysiology of endometriosis have made it possible to optimize therapeutic strategies. However, many controversial issues still arise in routine clinical practice. This article will provide an overview of the general basic concept of disease pathogenesis and highlight the role of hormonal treatment (dienogest) in women with endometriosis.

72-81 397
Abstract

Introduction. Delayed diagnosis and treatment of endometriosis lead to impaired quality of life and pain chronification in young female patients.

Aim. To study indicators of quality of life, anxiety, depression and pain syndrome in adolescents with peritoneal endometriosis (PE) over a one-year period of conservative therapy.

Materials and methods. A total of 45 girls aged 13 to 17 years with a confirmed diagnosis of PE were enrolled in a prospective longitudinal study. Pain syndrome (VAS, McGill Pain Questionnaire), anxiety-depressive symptoms (Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI)), quality of life indicators (SF-36) were assessed before and after one year of treatment in female patients (dienogest administered continuously, NSAIDs and drotaverine for immediate pain relief only).

Results. One year of therapy resulted in a significant decrease in the severity of dysmenorrhea and chronic pelvic pain, gastrointestinal symptoms and dysuria, daily activity and productivity impairment (p < 0.001) in girls with PE. In addition, the study demonstrated decreased indicators of anxiety and depressive disorders (BDI depression, HADS anxiety and depression, STAI reactive and personal anxiety (p < 0.001)) and an improvement in quality-of-life indicators (physical and psychological component, average index (p < 0.001)). There was a declining trend in blood hormone and inflammation test results within the reference range during treatment. The estradiol level has been shown to be a risk factor for high levels of affective disorder symptoms in adolescents with PE: STAI reactive anxiety (p = 0.046), HADS anxiety and depression (p = 0.044 and 0.033, respectively).

Conclusion. The one-year therapy of PE in adolescents (dienogest administered continuously, a combination of NSAIDs and drotaverine in pain syndrome only) was associated with significantly improved quality of life, decreased severity of anxietydepressive disorders and pain, which confirms the need to start therapy when symptoms of the disease begin to show them-selves in adolescence.

INFECTIONS

83-93 303
Abstract

Introduction. The article describes the experience of treating patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using a variant of complex local therapy with drugs containing sertaconazole nitrate and benzyl-dimethyl-[3-(myristoylamino) propyl] ammonium chloride monohydrate.

Aim. To evaluate the efficacy of local therapy in patients with recurrent vulvovaginal candidosis with underlying mixed non-specific vaginal dysbiosis.

Materials and methods. A prospective open randomized clinical trial to evaluate the outcomes of treatment with drugs containing sertaconazole nitrate at a dose of 300 mg (Flucovag®, vaginal suppositories, two times with an interval of 7 days) and benzyl-dimethyl-[3-(myristoylamino)propyl] ammonium chloride monohydrate at a dose of 15 mg (Miramistin® vaginal suppositories once a day at bedtime for 10 days) in women with mixed nonspecific infectious vaginal diseases with underlying recurrent vulvovaginal candidosis (n = 68) was conducted. Methods: vaginal microbiota evaluation with AmpliPrime® Florocenosis/Bacterial vaginosis-FL PCR (NextBio LLC, Russian Federation), vaginal pH, Hay/Ison scoring criteria, antimycotic sensitivity evaluation against Candida spp. (NCCLS standards).

Results and discussion. This kind of local complex therapy in patients with recurrent vulvovaginal candidosis combined with mixed vaginal dysbiosis using drugs containing sertaconazole nitrate (Flucovag®) and benzyl-dimethyl[3-(myristoylamino) propyl]ammonium chloride monohydrate (Miramistin®), followed by probiotic contamination showed high clinical (94.1 ± 2.3%) and microbiological (81.9 ± 2.1%) efficacy combined with safety and satisfactory compliance.

Conclusion. A comprehensive approach to the treatment of mixed nonspecific vaginal dysbiosis with underlying recurrent vulvovaginal candidosis showed high clinical efficacy and satisfactory compliance.

PRE- AND POSTMENOPAUSE

94-103 264
Abstract

Metabolic disorders that are progressive in nature most significantly influence the health of postmenopausal women. Osteoporosis and cardiovascular diseases are the most important long-term consequences and seriously affect the menopausal women’s quality of life. Hot flashes, a sudden feeling of heat or burning that begins in the face, neck, upper chest or back regions, is a common reason to see a doctor. Sometimes, hot flashes are accompanied by redness of the skin, red blotches, or rapid heartbeat. In some cases, rises in local skin temperature are observed. The above symptoms are the result of impaired functioning of thermosensitive neurons in the hypothalamic region. Menopausal hormone therapy is the gold standard for pharmacotherapy of various menopausal symptoms. However, it has different absolute and relative contraindications, as well as patients’ refusal of treatment mainly due to hormone phobia, that have resulted in a situation where 30% of menopausal women take hormone replacement therapy and only 15% continue to take it for a long period. Patients often insist on a natural approach to symptom relief and need evidence-based information about different hormonal and non-hormonal treatment options. Concerns about potential side effects of the hormone replacement therapy resulted in increased interest rates for phytoestrogens to manage menopausal symptoms. A rational fixed dose combination of phytoestrogens and micronutrients is a well-tolerated alternative preparation to support the health of perimenopausal women, which can be used with virtually no restrictions.

104-110 6234
Abstract

Introduction. Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the mainstay of the management for relieving pain syndrome in osteoarthritis (OA). NSAIDs are characterized by an individual reaction to medication, as well as a quite high frequency of gastrointestinal side effects. The issue of the disadvantages and advantages of a particular group of NSAIDs is still open.

Aim. To evaluate the safety and efficacy of Meloxicam at a dose of 15 mg/day as compared with Nimesulide and placebo in postmenopausal women with an inflammatory phenotype of OA.

Results and discussion. The frequency of all adverse events was comparable among the group of patients receiving meloxicam (40.0%), and lower than in the nimesulide group (48.0%), but higher than in the placebo group. A decrease in pain syndrome was observed as early as at 2 weeks of treatment in the group of patients receiving meloxicam. A significant decrease in WOMAC scores (overall result, pain syndrome, stiffness, function) was observed in the group of patients receiving meloxicam, and in the group of patients receiving nimesulide, after 3 weeks of treatment. meloxicam and nimesulide demonstrated high efficacy at 3 weeks compared with the initial VAS scores. The placebo group showed no efficacy.

Conclusion. The frequency of all adverse events was lower while taking meloxicam as compared to nimesulide. Our results substantiate the concept to prescribe meloxicam at a dose 15 mg once daily for the treatment of pain and stiffness in post-menopausal women with OA.

111-116 331
Abstract

Genitourinary menopausal syndrome is still a widespread problem that significantly affects the quality of life in postmenopause. The cause of this state is hypoestrogenism that is associated with menopause and the following change in the vaginal microflora due to the elimination of lactobacilli. The disturbance of the vulval and vaginal microflora provides risks for the invasion of pathogenic microorganisms, and the deficiency of sex hormones is associated with atrophy of the epithelium of the urogenital tract. An analysis of published clinical studies using a combination of L. acidophilus and 0.03 mg estriol (Gynoflor® E) in postmenopausal women with vulvovaginal atrophy, breast cancer survivors, in postmenopausal women with breast cancer on aromatase inhibitors was performed. Treatment with a combination of L. acidophilus and 0.03 mg of estriol (Gynoflor® E) can be evaluated as safe without risk of endometrial effects or other systemic effects. Local estrogen therapy in postmenopausal women can restore the vaginal epithelium, and a useful lactobacillus flora is needed to prevent urogenital infections. Local application of estriol is preferable, as it causes a local proliferative response and has no stimulating effect on the endometrium. This method of therapy may also be considered for hormone-sensitive women with breast cancer on aromatase inhibitors. However, today, there are not enough clinically validated studies proving the absolute safety of this treatment method among breast cancer women. The effect of this therapy is achieved due to the synergistic action of estriol and lactobacilli.

119-124 513
Abstract

The menopause in a woman’s life is one of the most significant events indicating the large-scale changes in the hypothalamus-pituitary-ovarian axis function. Gonadal steroid hormones are actively involved in the central nervous system (CNS) growth, differentiation, physiology and ageing processes. Sleep provides restoration of the central nervous system, and also contributes to memory consolidation. Sleep influences the two primary effector systems, the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), which in turn regulate adaptive and innate immune responses. During sleep, blood levels of cortisol, adrenaline and norepinephrine drop, whereas the levels of neurotransmitters such as growth hormone, prolactin and melatonin show a steep increase. We get more and more facts showing the role of sleep in the processes of immunogenesis and metabolism, in particular fat metabolism. A systematic modern literature analysis on the prevalence and structure of sleep disturbances in women during pre-, peri- and postmenopause was carried out. The results of individual studies revealing the relationship between sleep disturbances and hormone levels including levels of sex steroids are presented. A review of current scientific evidence shows conclusively that the neuroendocrine system significantly determines the sleep quality. Sleep disturbances associated with RLS, COAC are highly prevalent, especially among postmenopausal women, due to declining ovarian function and deficiency of sex steroids. The results of conducted studies support the continued study and analysis of the relationships between gender, neuroendocrine factors, sleep disorders and the search for effective methods for their treatment. SonNorm Duo containing melatonin, peppermint leaf oil, and motherwort herb extract is one of the drugs used to manage sleep disturbances. SonNorm Duo is an adaptogenic sedative drug that is indicated for sleep disturbances, circadian rhythm sleep-wake disorders associated with rapid travel across multiple time zones.

126-133 378
Abstract

After the end of the reproductive period, women spend a third of their lives in menopause. During this period, they experience a range of predictable symptoms and conditions associated with changing levels of sex hormones and aging of the body. The menopausal transition precedes menopause by several years and is usually characterized by irregular menstrual cycles, hot flashes and night sweats. After menopause, genitourinary symptoms predominate, including vulvovaginal atrophy and dryness and complaints associated with urinary disturbances: increased urinary frequency, urgency, and nocturia. Menopausal hormone therapy is effective for vasomotor and genitourinary symptoms, but it is associated with the development of cardiovascular risks, cognitive impairment, depression, and a number of side effects. An alternative in the therapy of menopausal symptoms can be the prescription of biologically active supplement Happyclim®. The complex composition of the drug effectively fills the lack of its own estrogen in the female body. The preparation Happyclim® contains phytoestrogens (soy isoflavones, flavonoids) and auxiliary components (magnesium and B vitamins, vitamin C, extract of medicinal melissa), which with high efficiency affect the woman’s body during menopausal transition, alleviating the symptoms of menopause and improving the quality of life. This article presents a cross-section of the literature on the use of phytoestrogens and the dietary supplement Happyclim® during the perimenopausal transition to delay the administration of menopausal hormone therapy.

134-143 309
Abstract

Introduction. The problem of early manifestations of menopausal syndrome is due to the high prevalence among postmenopausal women, a wide range of clinical manifestations, a sharp decrease in the quality of life, not always sufficient effectiveness of menopausal hormone therapy (MHT) in the presence of restrictions on its use.

The aim. To evaluate the dynamics of clinical manifestations of menopausal syndrome and to determine the pathogenetic effects of vitamin D preparation when used in combination with menopausal hormone therapy in women of early postmenopausal age with menopausal syndrome.

Materials and methods. 154 women were examined, of which 81 were characterized by the presence of clinical manifestations of menopausal syndrome. All women with menopausal syndrome received menopausal hormone therapy with estradiol and didrogesterone drug for 6 months, while 39 women additionally also took the vitamin D drug. Before and after therapy in patients with menopausal syndrome, the prevalence of symptoms of the Green scale was assessed. Concentrations of 25(OH) D, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were determined in the blood serum of all women.

Results and discussion. The use of MHT by women with menopausal syndrome leads to a decrease in the frequency of registration of a number of symptoms of the Green scale (p < 0.05). At the same time, a decrease in the frequency of registration of individual complaints is found only in the group of women who, along with MYT, received a vitamin D preparation (p < 0.05). Taking the vitamin D preparation is accompanied by an increase in its initially reduced serum concentrations to normal values (p < 0.001). The addition of cholecalciferol to the complex therapy of menopausal syndrome ensures the normalization of RANKL levels by reducing its production in the dynamics of treatment (p < 0.05) A decrease in the concentration of RANKL in response to the complex intake of a hormonal drug and cholecalciferol caused higher OPG/RANKL index values in the basic group by the end of therapy than in women of the comparison group (p < 0.01).

Conclusions. The obtained effects of vitamin D preparation when prescribed in combination with menopausal hormone therapy (reduction of the frequency of symptoms of menopausal syndrome, reduction of initially elevated levels of RANKL) indicate the expediency of its use in the treatment of early manifestations of menopausal syndrome.



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ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)