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Context: No prospective epidemiologic studies have examined associations between use of oral contraceptives (OCs) or menopausal hormone therapy (MHT) and risk of pituitary adenoma in women. Objective: Our aim was to determine the association between use of OC and MHT and risk of pituitary adenoma in two separate datasets. Methods: We evaluated the association of OC/MHT with risk of pituitary adenoma in the Nurses’ Health Study and Nurses’ Health Study II by computing multivariable-adjusted hazard ratios (MVHR) of pituitary adenoma by OC/MHT use using Cox proportional hazards models. Simultaneously, we carried out a matched case-control study using an institutional data repository to compute multivariable-adjusted odds ratios (MVOR) of pituitary adenoma by OC/MHT use. Results: In the cohort analysis, during 6 668 019 person-years, 331 participants reported a diagnosis of pituitary adenoma. Compared to never-users, neither past (MVHR = 1.05; 95% CI, 0.80-1.36) nor current OC use (MVHR = 0.72; 95% CI, 0.40-1.32) was associated with risk. For MHT, compared to never-users, both past (MVHR = 2.00; 95% CI, 1.50-2.68) and current use (MVHR = 1.80; 95% CI, 1.27-2.55) were associated with pituitary adenoma risk, as was longer duration (MVHR = 2.06; 95% CI, 1.42-2.99 comparing more than 5 years of use to never, P trend = .002). Results were similar in lagged analyses, when stratified by body mass index, and among those with recent health care use. In the case-control analysis, we included 5469 cases. Risk of pituitary adenoma was increased with ever use of MHT (MVOR = 1.57; 95% CI, 1.35-1.83) and OC (MVOR = 1.27; 95% CI, 1.14-1.42) compared to never. Conclusion: Compared to never use, current and past MHT use and longer duration of MHT use were positively associated with higher risk of pituitary adenoma in 2 independent data sets. OC use was not associated with risk in the prospective cohort analysis and was associated with only mildly increased risk in the case-control analysis. [ABSTRACT FROM AUTHOR]

Objective: Menopausal status impacts risk for many health outcomes. However, factors including hysterectomy without oophorectomy and Menopausal Hormone Therapy (MHT) can mask menopause, affecting reliability of self-reported menopausal status in surveys. We describe a step-by-step algorithm for classifying menopausal status using: directly self-reported menopausal status; MHT use; hysterectomy; oophorectomy; intervention timing; and attained age. We illustrate this approach using the Australian 45 and Up Study cohort (142,973 women aged ≥ 45 years). Results: We derived a detailed seven-category menopausal status, able to be further consolidated into four categories ("pre-menopause"/"peri-menopause"/"post-menopause"/"unknown") accounting for participants' ages. 48.3% of women had potentially menopause-masking interventions. Overall, 93,107 (65.1%), 9076 (6.4%), 17,930 (12.5%) and 22,860 (16.0%) women had a directly self-reported "post-menopause", "peri-menopause", "pre-menopause" and "not sure"/missing status, respectively. 61,464 women with directly self-reported "post-menopause" status were assigned a "natural menopause" detailed derived status (menopause without MHT use/hysterectomy/oophorectomy). By accounting for participants' ages, 105,817 (74.0%) women were assigned a "post-menopause" consolidated derived status, including 15,009 of 22,860 women with "not sure"/missing directly self-reported status. Conversely, 3178 of women with directly self-reported "post-menopause" status were assigned "unknown" consolidated derived status. This algorithm is likely to improve the accuracy and reliability of studies examining outcomes impacted by menopausal status. [ABSTRACT FROM AUTHOR]

The effect of MHT on cardiovascular disease (CVD) risk among women with prediabetes or type 2 diabetes (PreDM or T2DM) is unclear. We examined the association between ever or early use MHT and CVD risk in postmenopausal women with PreDM or T2DM, and the potential modifying effect of race. 2,917 postmenopausal women with PreDM or T2DM were pooled from 3 prospective CVD cohorts (the Atherosclerosis Risk in Communities, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study). Ever (yes vs no) or early use of MHT (MHT initiated ≤5 vs > 5 years since menopause), and their associations with ischemic stroke, coronary heart disease (CHD), and atherosclerotic cardiovascular disease (ASCVD) were assessed using Cox proportional hazards models. During a median follow-up of 15 years, 264 stroke, 484 CHD, and 659 ASCVD events were observed. In fully adjusted models, ever use of MHT was associated with reduced risk of stroke (hazard ratio 0.86, 95% CI 0.76–0.98), CHD (0.85, 0.74–0.98), and ASCVD (0.83, 0.73–0.95) in white women with PreDM or T2DM. Early use of MHT was associated with reduced risk of stroke (0.82, 0.72–0.95), CHD (0.85, 0.74–0.98), and ASCVD (0.82, 0.70–0.96) in the white group. No risk reduction with ever or early use of MHT was found for black women with PreDM or T2DM. MHT is associated with statistically reduced CVD risk among white but not black women with PreDM or DM. Race is an effect modifier in the association between MHT use and CVD. [Display omitted] • The effect of menopausal hormone therapy (MHT) on cardiovascular disease (CVD) in women with type 2 diabetes (T2DM) is unclear. • Pooled analysis showed ever or early use of MHT was associated with reduced CVD risk in women with pre-diabetes or T2DM. • Race may be an effect modifier to this association with the result evident in White women with pre-diabetes or T2DM. [ABSTRACT FROM AUTHOR]

Administration of menopausal hormone therapy (MHT) in patients with genital endometriosis (GE) is a controversial issue requiring a patient-personalized approach. Current principles for MHT selection and prescription in patients with anamnestic endometriosis are presented, which are based on the guidelines of the International Menopause Society (IMS), The European Menopause and Andropause Society, local and foreign publications retrieved from electronic data bases PubMed, Cyberleninka. The data of our study on observing 724 patients with GE treated with diverse MHT types were presented and analyzed (428 women in perimenopausal period, 296 in postmenopausal period). Patients with endometriosis in perimenopausal and postmenopausal periods showed more prominent manifestations of climacteric and post-ovariectomy syndromes, as well as high risk of reduced bone mineral density (BMD) due to repeated surgery on the ovaries and preceding long-term “antiestrogen therapy”. Custom-compounded MHT based on components combinations, dosage and administration route provides a significantly improved quality of life for patients with endometriosis, prevents loss of BMD and reduces risk of cardiovascular diseases. Using low and ultra-low dose estrogen bioidentical to natural substances in this patient group minimizes a risk of disease recurrence.

Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in ‘special situations,’ such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.

Hormone therapy is recommended for relief from hot flashes or night sweats in women younger than age 60 years or those who entered menopause within 10 years of seeking treatment. Hormone therapy also can reduce bone loss and the risk of fractures; offer a potential cardioprotective benefit; and alleviate the genitourinary symptoms of menopause, including dysfunction of the bladder and irritation of the vagina and vulva. For women with early menopause without contraindications, hormone therapy is recommended until at least the average age of natural menopause. Observational studies suggest that the risk of thromboembolism and stroke is lower with transdermal therapy than with oral hormone therapy. Compounded bioidentical hormone therapies that have not been approved by the Food and Drug Administration are not recommended owing to safety concerns. Hormone therapy is not recommended for primary or secondary prevention of coronary heart disease or dementia. Nonhormone therapies that have been shown to reduce hot flashes include low-dose selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors, gabapentinoids, weight loss, hypnosis, and cognitive behavioral therapy. For women with only genitourinary symptoms, local vaginal hormone therapies are recommended. The treatment is not without its risks, including concerns about cognitive decline and breast cancer. More research is warranted, to determine the long-term benefits and risks of menopausal hormone therapy, to gauge the effects of prolonged use in women initiating therapy close to menopause, to inform the timing of and approach to hormone therapy discontinuation, and to answer additional unknowns. As scientists work to address these questions, technology can help identify women likely to benefit from hormone therapy. The MenoPro mobile app, backed by the North American Menopause Society, provides a free algorithm to flag the strongest candidates.

On September 11–12, 2020, in Kyiv hosted the International Women's Health Summit “From Menarche to Menopause” with the participation of leading foreign and domestic experts in the field of obstetrics and gynecology. The event was devoted to such topical topics as miscarriage, infertility, menstrual irregularities, menopausal hormone therapy (MHT). The current concern in clinical practice is not overuse of MHT, but it underutilization, and the fact that only a small number of women with impaired quality of life through menopausal symptoms receive treatment, despite that they perfectly fit the patient's profile for such therapy. All types of MHT are characterized by following effects: a positive effect on the cardiovascular system if MHT was start before 60 ages or in the first 10 years after menopause onset; the mortality rate from all causes is not increased in patients on MHT. The “ideal” MHT should relieve vasomotor symptoms, influence urogenital symptoms, prevent fractures and bone loss, protect the cardiovascular system and endometrium, and should not increase the risks of breast cancer, deep vein thrombosis and pulmonary embolism. Estradiol + dydrogesterone (Femoston®) scheme fits perfectly into these criteria. Femoston® is an oral MHT preparation that is effective in relieving symptoms of estrogen deficiency with a proven safety profile on the cardiovascular system and breast. This drug helps to reduce the manifestations of symptoms of estrogen deficiency, increase bone mineral density, and has a positive effect on metabolic processes. Numerous studies have shown that combination of estradiol + dydrogesterone is not only highly effective against menopausal symptoms, but also extremely important features, in particular, a proven safety profile for breast cancer.

Advances in HIV care over the last 30 years have transformed a virtually fatal condition into a chronic, manageable one. Antiretroviral therapy (ART) has dramatically changed the outlook for people living with HIV so that most individuals with well controlled disease have a normal life expectancy. As result of this increase in life expectancy, one-third of women living with HIV are of menopausal age.Adding to the shift in age distribution, rates of new HIV diagnosis are increasing in the over 50-year age group, likely the result of a combination of low condom use and perception of transmission risk and in women, an increased risk of HIV acquisition due to the mucosal disruption that accompanies vaginal atrophy.Many women living with HIV are unprepared for menopause, have a high prevalence of somatic, urogenital and psychological symptomatology and low rates of menopausal hormone therapy (MHT) use. Many women experience enormous frustration shuttling between their general practitioner and HIV care provider trying to have their needs met, as few HIV physicians have training in menopause medicine and primary care physicians are wary of managing women living with HIV, in part, because of fears about potential drug-drug interactions (DDIs) between MHT and ART.Several data gaps exist with regard to the relationship between HIV and the menopause, including whether the risk of HIV transmission is increased in virally-suppressed women with vaginal atrophy, whether or not menopause amplifies the effects of HIV on cardiovascular, psychological and bone health, as well as the safety and efficacy of MHT in women living with HIV.Menopausal women living with HIV deserve high quality individualised menopause care that is tailored to their needs. More research is needed in the field of HIV and menopause, primarily on cardiovascular disease and bone health outcomes as well as symptom control, and strategies to reduce HIV acquisition, encourage testing, and maintain older women in care in order to inform optimal clinical management.

Menopause signifies permanent cessation of ovarian function and the end of a woman's reproductive potential. Menopausal transition plays a major role in many symptoms common in middle age and may contribute to chronic conditions and disorders of aging. An evidence-based plan of care improves outcomes, enhancing quality of life. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the prevalence of menopausal symptoms, and the use of menopausal hormone therapy (MHT) and nonconventional methods of alleviating menopausal symptoms and their health benefits in peri- and postmenopausal women. A sample of 349 peri-or postmenopausal women were studied, all of whom had experienced menopausal symptoms. A pre-tested questionnaire was used to assess the kinds of menopausal symptoms experienced, the types of therapies used, and the health benefits of using MHT or alternative therapies (AT). The mean age of peri- and postmenopausal women was 49.55 (±2.51) and 61.32 (±6.77) years, respectively. The most common symptoms in both groups of peri- and postmenopausal women related to mental health. Altogether 45% of women used MHT and 27.8% AT. Those using MHT reported significant benefits in their sexual life (p < 0.001), whereas those using AT reported significant benefits of better sexual life (p < 0.001), skin condition (p < 0.001), and physical activity (p < 0.05). This study indicated that the most common symptoms connected with the menopausal transition were mental ailments. In order to prevent them, the women more frequently applied MHT in comparison to alternative methods, with postmenopausal women using MHT more often than perimenopausal women. Satisfaction was found with both conventional and alternative treatments for the relief of menopausal symptoms. [ABSTRACT FROM AUTHOR]

Adult-type ovarian granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available. We evaluated the effect of parity and postmenopausal hormone therapy (HT) use on the risk of AGCT in a population-based case-control setting. We identified all women diagnosed with AGCT during 1994–2015 (n = 505) from the Finnish Cancer Registry. For each case, five controls matched for age were selected from the National Population Registry, which also provided data on parity and ages at deliveries. Information on postmenopausal HT by different regimens (estradiol-only, sequential estrogen-progestin and continuous estrogen-progestin) was obtained from nationwide Prescription Register. The association between parity, ages at deliveries, HT use, and AGCT incidence was evaluated by odds ratios (ORs) using a conditional logistic regression model and stratified by age at index date (<55 years or ≥ 55 years). Parity and age at first or last delivery had no significant effect on AGCT risk. Systemic postmenopausal HT had been used by 20.4% of women who were later diagnosed with AGCT. The risk for subsequent AGCT was significantly decreased among users of estradiol-only therapy for at least five years (OR 0.28; 95% confidence interval 0.08–0.94) and continuous estradiol-progestin therapy for 6 months to 5 years (0.23; 0.08–0.71). Unlike in epithelial ovarian cancer, AGCT development is not clearly associated with parity, and users of postmenopausal HT do not seem to carry an excess risk for AGCT formation. • Adult-type granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available • AGCT development is not clearly associated with parity or age at deliveries • Use of postmenopausal hormone therapy does not increase the risk for subsequent AGCT [ABSTRACT FROM AUTHOR]

This study aimed to explore Australian health-care providers' knowledge of menopause and its consequences, and their views about menopause-related health care. This was a cross-sectional qualitative study of Australian general practitioners (GPs), gynecologists (GYs) and pharmacists (PHs). Recruitment was ultimately achieved through professional networks and cold calling. There were equal numbers of GPs, GYs and PHs, and equal numbers of males and females in each group. All participants demonstrated sound understanding of menopause and its consequences. A strong theme was recognition of high usage of complementary and alternative medicines (CAMs) by women for menopausal symptoms. Most participants highlighted lack of efficacy evidence for most CAMs, but the majority of GPs and PHs considered CAMs to 'have a role'. Most supported menopausal hormone therapy (MHT) when symptoms impaired quality of life. Limitations to comprehensive care included knowledge gaps and lack of time. Australian health-care providers appeared knowledgeable about menopause, but uncertain about its management. MHT prescription appeared limited to women with severe symptoms despite lifestyle modification and a trial of CAMs. The upskilling of clinicians providing care for women at midlife, with respect to the indications for and prescribing of MHT, urgently needs to be addressed. [ABSTRACT FROM AUTHOR]

The article provides an overview of the possible causes of bleeding from the genital tract in peri- and postmenopausal women. The correct approach to patients with abnormal uterine bleeding during menopausal hormone therapy is described. A modern analysis of data on the diagnosis and treatment of postmenopausal vaginal bleeding against the background of menopausal hormone therapy was carried out. The modern possibilities of endometrial diagnostics and treatment are shown.

Modern mankind, through the development of medicine and using its scientifically grounded innovations has learned to prolong human life. In Ukraine as in the whole world there is a tendency to increase in life expectancy. Since aging is a natural physiological process, a person from time immemorial has been preoccupied with the search for the so-called “Philosophy Stone” is a substance that prevents aging. This article analyzes data from scientific publications on modern aspects of the problems associated with aging of the female body. It has been proven that aging and anti-aging processes substantiate the individualization of modern approaches to the correction of pre- and perimenopause complications. The general strategy for maintaining of women’s health in peri- and postmenopause according to the International Menopause Society includes menopausal hormone therapy, taking into accounts the therapy goals and individual risk factors. Despite all the desire to give a modern definition of aging, it is currently not possible, therefore in this literature review an attempt is made to analyze the known strategies of premature aging to develop the potential for prolonging active life. In any case, the doctor needs to correlate the benefits and risks of menopausal hormone therapy, taking into account individual risk factors and select appropriate rehabilitation methods aimed at “improving the female face” of the classic image of old age. Since the role of estrogen deficiency in the formation of perimenopausal complications and especially premature aging, is not questioned, anti-aging strategies should be considered a pathogenetically justified method of treating vasomotor, psychosomatic symptoms and sleep disorders, as well as a method of preventing metabolic syndrome. It should be remembered that hormone therapy has a number of limitations and contraindications, which is an incentive for every doctor to contribute to prolongation of the active and healthy life of women 40+ and 50+ years old. Creation of a conceptual model for overcoming the complications of reproductive aging and especially cardiovascular events, osteoporosis, cerebrovascular pathology based on the identification of risk factors will allow to develop the protective anti-aging therapy not only to prolong a woman's life, but also to improve its quality

Aim: to develop individualized options for correcting sex steroid deficiency in early postmenopausal patients with uterine leiomyoma.Materials and Methods. 180 postmenopausal patients with uterine leiomyoma were examined. To correct menopausal manifestations, patients were prescribed: Group 1 (n = 60) – low-dose drug estradiol 1 mg/drospirenone 2 mg, Group 2 (n = 60) – ultra-low-dose drug estradiol 0.5 mg/drospirenone 0.25 mg, Group 3 (n = 60) – patients refused to take menopausal hormone therapy (MHT). Clinical and anamnestic, laboratory and instrumental examination was carried out by assessing vasomotor and genitourinary symptoms. Special attention was paid to ultrasound examination of the pelvic organs with Dopplerometry of the intratumoral vessels.Results. The vasomotor manifestations of menopausal syndrome in postmenopausal patients with uterine leiomyoma were effectively relieved with drug containing 17β-estradiol/drospirenone, regardless of component dosage (RR = 0.25). The size of nodes in uterine leiomyoma type 2–6 according to classification of The International Federation of Obstetricians and Gynecologists (FIGO) as well as Dopplerometry data in the uterine artery in postmenopausal women showed no changes after 9-month use of 17β-estradiol/drospirenone. In Group 1, increased vascularization intensity (RR = 1.4) and decreased peripheral vascular resistance in intranodular vessels were revealed in 6 % patients.Conclusion. The use of MHT drugs at varying component doses did not enlarge size of leiomyoma nodes nor affected hemodynamic parameters in the uterine arteries during 6-month-treatment. However, while prolonging MHT duration, it increased vascularization of myoma nodes assessed by measuring intranodular blood flow, increased vascularization and decreased resistance index after administering low-dose vs. ultra-low-dose MHT therapy that should be taken into account upon planning therapeutic regimen and its timeframe.

Introduction. Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy. Aim. To search a molecular predictive marker of the effectiveness of OS treatment. Materials and methods. The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood. Results. Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy. Conclusion. The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.

In this review we summarize current data on prevalence, etiology and pathogenesis resulting in premature ovarian insufficiency (POI). In particular, genetic, autoimmune, metabolic, iatrogenic disorders as well as unfavorable impact of environmental factors represent key pathogenetic mechanisms underlying POI development. Clinical picture of this disease is mainly manifested by oligo- and amenorrhea as well as genitourinary menopausal syndrome (GUMS). Special attention is paid to a link between such clinical signs and psychosocial discomfort not being a life-threatening condition but still able to markedly lower quality of woman’s life and considered as a comorbidity with type 2 diabetes mellitus, osteoporosis and cardiovascular diseases. Hormone replacement therapy (HRT) serves as the first-line therapeutic approach for treating POI, which is performed according to the principles similar to those used to perform menopausal hormone therapy (MHT) in case of natural menopause that should be continued until reaching at least the average age for the onset of menopause. Topical estriol therapy eliminates GUMS symptoms, which in turn positively affects sexual function and woman’s psychosocial status and contributes to improved quality of life. The data from recent studies examining topical estriol therapy in POI demonstrated high efficacy and safety. Finally, we also discuss diverse strategies to support reproductive function in women with POI.

Aim. To review scientific publications on clinical effectiveness and potential application of phytoestrogens (PE) in the treatment of climacteric syndrome.Materials and methods. The PRISMA approach was used. The systematic search was performed in three electronic scientific databases: Cochrane library, PubMed/MEDLINE, and eLIBRARY.ru. The publications were also manually searched for in the reference lists of the relevant articles.Results. The filters were used to select 79 publications; 26 of them were included in the final review. The main method of treatment for the manifestations of the climacteric syndrome is menopausal hormonal therapy (MHT). One of the alternative methods for the control of its symptoms is the application of phytoestrogens (PE), primarily, isoflavones, lignans, and coumestans. Active metabolites of PE are expressed under the influence of gut microflora that is different in various groups of women, which can determine the differences in the effectiveness. Taking into account multidirectional character of the studies as well as numerous publications of low quality, it is still impossible to come to the final conclusion on the effectiveness of PE-containing food supplements (FS) when it comes to a decrease in the occurrence rate and expression of such symptoms as hot flushes, night sweats, and cognitive deterioration. The conclusions on the prevention of cardio-vascular diseases are not definite either.Conclusions. The review showed that scientists could not come to the conclusion on the effectiveness and safety of PE-containing FS. Probably, the most prospective means of the control of climacteric syndrome are FS that contain isoflavones of red clover and soy in the maximum effective concentration. Considering free access to such FS on the market, they must meet high safety requirements.

About 10% of the world's populations are menopausal women. This period coincides with the most active social and professional activities of almost every woman. In addition to typical manifestations, this age stage is characterized by menopausal metabolic syndrome, which is caused by estrogen deficiency and is found in 35–49% of women in older age groups. Modern approaches to the treatment and prevention of menopausal disorders include following principles: lifestyle changes, menopausal hormone therapy (MHT), non-hormonal therapy (drugs with hormone-like effects, phytoestrogens, selective modulators of estrogen receptors, β-alanine, sedatives, tranquilizers, and antidepressants), non-drug correction methods. According to the International Menopause Society recommendations (2016), MHT is a gold standard for prevention and treatment of menopausal disorders. However, the choice of MHT as a therapeutic standard is not always unambiguous and acceptable, because hormone therapy is associated with a number of side effects. In addition, there are a number of absolute contraindications for MHT. Therefore, the task of a gynecologist is to choose personalized (individual) therapy for menopausal disorders for each patient. Factors that must be considered when choosing between MHT and non-hormonal drugs include: severity and duration of menopause syndrome, presence of absolute and relative contraindications for MHT, patient’s desire, tolerance of the chosen method. Phytoestrogens (selective modulators of plant-derived estrogen receptors, which are structurally similar to endogenous estrogens) are well-researched among the means of non-hormonal therapy of menopausal patients. Due to their weak estrogenic action, they reduce the severity of menopausal syndrome without affecting the proliferative processes in the endometrium. Phytoestrogens are used by gynecologists in many countries for mild climacteric complaints and/or if there are absolute contraindications for MHT. One of these drugs is Climona® that is contains biologically active components of plant origin (hop cones, cimicifuga root, dioscorea root, vitamin D, α-lipoic acid), which have been shown to be effective in decrease of menopause manifestations and reducing menopausal metabolic syndrome

Purpose. To compare the influence of Cimicifuga racemosa extract (CR, Ze 450) and menopausal hormone therapy (MHT) on metabolic parameters and body weight in symptomatic menopausal women. Methods. In this monocentric retrospective cohort study, women over 40 years old with a first consultation between 2009 and 2016 were screened. Included in the final analysis were women treated with either MHT or CR and having at least one follow-up consultation. Metabolic serum parameters (lipids, glucose, insulin, and HOMA-IR), body weight, and menopausal symptoms (Menopause Rating Scale (MRS)-II) were the main outcome measures. Statistical analysis by uni- and multi-variable linear mixed-effects regression models assuming a linear effect of time. Results. 174 women were included in the final analysis (CR n = 32, MHT n = 142). There was no difference between the groups regarding baseline characteristics (age, BMI, serum metabolic parameters, hormones, and blood pressure) and total MRS-II score, while reproductive stage differed significantly with more postmenopausal women treated with CR (83%) than MHT (55%) (p = 0.038). Median follow-up time was 12 months. In both groups, metabolic serum parameters and body weight did not change over the follow-up period, while total and MRS-II subscores improved. Conclusion. Menopausal symptoms improved significantly in both groups (MHT and CR), while serum metabolic parameters and body weight did not change in MHT- or CR-treated women.

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.

The article presents the modern view on pathogenetic mechanisms of the cholelithiasis development in women, illustrated by clinical observations. Gender-associated risk factors for cholelithiasis are pregnancy and childbirth, female sex hormones administration and polycystic ovary syndrome. The gallstone disease risk factors in women taking hormonal oral contraceptives and menopausal hormone therapy are hereditary predisposition, impaired lipid, carbohydrate metabolism and functional gallbladder disorders. Patients at high risk of developing cholelithiasis are recommended to perform a gallbladder ultrasound examination before and during hormonal therapy. The ursodeoxycholic acid treatment is safe, effective and compatible with female sex hormone administration in patients with detected biliary sludge.

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.

Relevance. As the prevention and treatment of diseases improves, the average life expectancy of the population increases. For many of our contemporaries, a third of their lives are postmenopausal. Menopause-related health problems are increasingly common and require the attention of healthcare professionals. Aim. To raise awareness of gynecologists, urologists and other specialists about the medico-social significance of the problems of women in the menopausal period based on the analysis of literature sources and analysis of clinical cases. Materials and methods. To write this review, a search was carried out for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) over the past 20 years. The review included articles from the peer-reviewed literature. An analysis of 2 clinical cases with comorbid pathology in menopausal patients is presented. Results. The review presents data on age-related physiological changes and quality of life in menopausal women. The analysis of 2 clinical cases of the appointment of menopausal hormone therapy in patients with comorbid diseases was carried out. Conclusions. The importance of awareness of outpatient doctors in the diagnosis and management tactics of patients with comorbid diseases in menopause is emphasized.

Climacteric is a physiological transition period in a woman’s life during which the reproductive system involutive processes against the age-related changes are dominated in the body, and characterized by reduction of menstrual and generative function due to genetically programmed cessation of ovarian function. There are 4 periods of menopause: menopausal transition period, menopause, perimenopause and menopause. This document provides an overview of existing diagnosis and treatment methods of menopausal disorders in women, proposed algorithms for diagnosis and treatment of this disease to prevent heart diseases, osteoporosis and improve the quality of ukrainian women life. No need for hormonal laboratory research to diagnosis of perimenopause and menopause for most healthy women aged over 45 with the following features: vasomotor symptoms on a background of irregular menstruation in perimenopause; absence of menstruation for the last 12 months or appearance of menopausal symptoms after hysterectomy at menopause. The most common symptoms of menopause are vasomotor symptoms (hot flashes, night sweats, palpitations, labile blood pressure); psychological (emotional lability, depression, anxiety, irritability, sleep disturbances, poor memory and concentration); general physical symptoms (asthenia, headache, pain in muscles and joints, skin discomfort); urogenital and sexual (vaginal itching, burning, dryness and dyspareunia, frequent and urgent urination, decreased libido). The only pathogenetically effective method for the correction of menopausal disorders is menopausal hormone therapy. For this therapy are used natural estrogen (17β-estradiol, estradiol valerate, estriol) in combination with progestins (dydrogesterone) or androgens. It is possible parenteral (injections), transdermal, vaginal and oral hormone introduction. To correct the climacteric syndrome, urogenital disorders are used short courses of menopausal hormone therapy (for 1–5 years). For the prevention and treatment of osteoporosis menopausal hormone therapy lasts over 3 years if necessary, in combination with a bisphosphonate.

On November 8–9, 2019 in Tbilisi (Georgia) the I International Forum of Menopause Experts initiated by the Association of Gynecologists-Endocrinologists of Ukraine was held. Expert working group included leading specialists in the field of obstetrics and gynecology in Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Uzbekistan and Ukraine. Experts presented data of their countries on the status of menopause management, experience in solving problems of this period of life. During medical counseling women should pay special attention to the timely start of therapy, explaining the benefits and risks of menopausal hormone therapy (MHT), identifying age-dependent risks and ways to overcome them. MHT is the most effective and pathogenetically substantiated method for the correction of menopausal disorders today. The goal of MHT is to partially compensate for the deficiency of sex hormones using minimally optimal doses that can improve the general condition of women and ensure the prevention of late metabolic disorders and osteoporosis. Individualization of MHT depends on the patient's age and menopausal status. For each stage of woman's reproductive aging according to the STRAW+10 a balanced decision is required on the choice of the regimen and dosage of the combined MHT with therapeutically effective low-dosage forms. It is recommended to start MHT mainly in perimenopause or in early postmenopause, but with menopause duration no more than 10 years. It is necessary to evaluate the thickness of the endometrium using transvaginal sonography before therapy. In perimenopause it is preferable to start MHT in a combined cyclic regimen with a lower dose of estrogen. In postmenopausal women it is preferable to start with a lower dose of estrogen and use a continuous combined dosage regimen of estrogen and gestagen. It is proposed a continuous assessment of the fractures risks to effectively prevent the osteoporosis in women in the postmenopausal period. An annual basic examination is necessary throughout the entire period of MHT use: measurement of weight, waist circumference and blood pressure level, gynecological examination, cytological examination of a cervical smear according to Papanicolaou, ultrasound of the pelvic organs with determination of the endometrium thickness and structure, mammography.

Context: The decrease in serum estrogens after menopause is associated with a shift from a gynoid to an android adipose tissue (AT) distribution. Menopausal hormone therapy (HT) mitigates this change and accompanying metabolic dysfunction, but its effects on AT sex steroid metabolism have not been characterized., Objective: We studied effects of HT on subcutaneous and visceral AT estrogen and androgen concentrations and metabolism in postmenopausal women., Design, Setting, Patients, and Interventions: Serum and subcutaneous and visceral AT from 63 postmenopausal women with (n=50) and without (n=13) per oral HT were analyzed for estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and serum estrone sulfate using liquid chromatography-tandem mass spectrometry. Steroid sulfatase activity was measured using radiolabeled precursors. mRNA expression of genes encoding sex steroid-metabolizing enzymes and receptors was performed using real-time reverse transcription quantitative polymerase chain reaction., Results: HT users had 4- to 7-fold higher concentrations of estrone and estradiol in subcutaneous and visceral AT, and 30% lower testosterone in visceral AT compared to non-users. Estrogen-to-androgen ratios were 4- to 12-fold higher in AT of users compared to non-users of HT. In visceral AT, estrogen-to-androgen ratios increased with HT estradiol dose. AT to serum ratios of estrone and estradiol remained high in HT users., Conclusions: Higher local estrogen to androgen ratios and high AT to serum ratios of estrogen concentrations in HT users suggest that HT may significantly influence intracrine sex steroid metabolism in AT, and these local changes could be involved in the preventive effect of HT on menopause-associated abdominal adiposity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies., Methods: We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures., Results: Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume., Discussion: HC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies., Highlights: Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese nine cities' tertiary Grade A hospital and systematically describe the medication treatment patterns in women with OP., Methods: Prescription information for female OP patients in nine cities (Beijing, Shanghai, Guangzhou, Hangzhou, Tianjin, Zhengzhou, Chengdu, Shenyang, Harbin) was extracted from the Hospital Prescription Analysis Collaboration Project Database of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. Statistical analysis was conducted to evaluate demographic characteristics and medication treatment patterns., Results: A total of 669,505 prescriptions for medication treatment of female OP patients were included in this study. The majority of patients were aged 60 to 99 years (69.79 %) followed by 50 to 59 years (18.81 %) and 40 to 49 years (6.69 %). Geographically, the highest concentration of patients was in North China (Beijing, Tianjin) (43.05 %) followed by East China (Shanghai, Hangzhou) (31.43 %). The top three prescribed medications were active vitamin D and its analogs (40.78 %), calcium supplements (32.51 %), and bisphosphonates (18.75 %). The prescription frequency of menopausal hormone therapy (MHT) was 0.31 %. The proportion of female OP patients receiving monotherapy and two drug combinations therapy is equivalent (about 37 %)., Conclusion: The diagnosis and treatment of female OP patients in China showed regional variations. The most commonly prescribed medications for this population were calcitriol, calcium carbonate with vitamin D3, and alendronate sodium with vitamin D3. The use of MHT was relatively limited., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Context: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases., Objective: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women., Methods: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders., Results: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99)., Conclusion: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea.Methods: A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002-2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan-Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose-response relationship.Results: The median follow-up was 79.6 of months. Kaplan-Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691-0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577-0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605-1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547-0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064).Conclusions: The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose-response relationship in a population-based cohort study. [ABSTRACT FROM AUTHOR]

Background: Exogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO: CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods. Methods: Embase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the 'positive', 'negative' or 'neutral' effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive. Results: We identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli. Conclusion: Our findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The application of menopausal hormone therapy (MHT) is generally restricted most likely due to limited prescriptions by doctors. Fear of cancer risk may be a critical factor. We investigated the views of Chinese obstetricians and gynecologists on the relationship between hormone therapy and cancer risk. Methods: A self-administered web-based nationwide cross-sectional questionnaire. Results: In total, 5243 medical workers responded to the questionnaire (response rate 94.5%); 4995 were certified obstetricians and gynecologists. Most were aged 36–55 years (70.9%), had > 10 years of working experience (68.5%), and worked at tertiary (34.8%) and secondary hospitals (49.1%); 70% of the clinicians were aware of the endometrial cancer risk caused by estrogen, and 20% considered progestogen to cause the same risk. Regarding breast cancer, while 67.9 and 74.8% of the clinicians viewed natural and synthetic estrogens as risk factors, respectively, only 41.7% identified the carcinogenic effect of progestins as higher than that of progesterone (26.7%). Approximately 75% of the participants believed synthetic estrogens and progestins constituted a risk for ovarian cancer (higher than the percentages for their natural counterparts); 13.0–21.1% of the respondents were worried about choriocarcinoma due to hormone treatment. Finally, 86.8% of obstetricians and gynecologists claimed to have poor knowledge regarding this field. Conclusion: Misconceptions and a lack of knowledge in this regard may result in the fear of cancer and could be the underlying causes of limited MHT prescriptions. We believe that scientific research, continued education, and the media all have roles to play in changing preconceived ideas regarding MHT prescriptions. [ABSTRACT FROM AUTHOR]

Successful aging includes good health and low levels of disability. To that end, primary prevention is far better than managing subsequent organ damage. When medication is needed to prevent or manage disease, the preferred choice should be associated with the greatest benefits and fewest adverse effects. Cardiovascular diseases are the leading cause of morbidity and mortality in postmenopausal women worldwide. Considering disease-adjusted life years, other leading causes are chronic obstructive pulmonary disease, diabetes mellitus, dementias, hearing loss, cancers of the breast, lung and bowel, osteoporosis, fractures and falls, depression, osteoarthritis, refractive errors of the eye and non-diabetic chronic kidney disease. This review explores the global prevalence of these diseases in women aged 50 years and older, and medications commonly used for them, and contrasts the effects of menopausal hormone therapy (MHT) with others. When initiated early, there is good evidence for MHT benefit in all-cause mortality and primary prevention of cardiovascular disease, diabetes and osteoporosis; fair evidence for benefit in dementias, depression and osteoarthritis; limited evidence for benefit in chronic obstructive pulmonary disease, hearing loss, non-diabetic chronic kidney disease and colorectal cancer; null effects on lung cancer and refractive errors; and varied effects on breast cancer and stroke. Relative benefits and adverse effects of other medications warrant consideration. [ABSTRACT FROM AUTHOR]

The most common treatment for menopausal syndrome is menopausal hormone therapy (MHT), however, the safety of MHT, due to the risk of developing and recurrent breast cancer (BC), is still a matter of debate. The review presents the results of randomized cohort studies of this issue. It has been shown that MHT increases the risk of developing breast cancer and disease recurrence after treatment. The risk of breast cancer developing in women receiving MHT depends on body mass index (BMI), duration of hormone use, and dose of drugs, and is greater in thin women compared with women with increased BMI, and also greater in estrogen–progestin combined MHT users compared with estrogen-only users. It was found that hormone-dependent forms of cancer developed more often in women using MHT, but by the time of diagnosis, the disease was found in more advanced stages and metastases in lymph nodes were found more often when compared with patients who did not use MHT. Risk of breast cancer recurrence is less with low doses of vaginal estrogen. An alternative option for the relief of menopausal disorders in breast cancer patients during and after treatment is using of pineal gland hormone melatonin, since, along with its anti-aging properties, it is able to suppress cancer at the stages of initiation, progression, and metastasis and has the ability to reduce the toxic effects of anticancer drugs simultaneously increasing their effectiveness. [ABSTRACT FROM AUTHOR]

Physical inactivity, high postmenopausal body mass index, alcohol consumption and use of menopausal hormone therapy are established risk factors for breast cancer. Less is known about whether these factors influence the risk of progression of benign and premalignant breast lesions to invasive breast cancer. This registry‐based cohort study was based on women with a precancerous lesion who were followed for breast cancer. The cohort consisted of 11 270 women with a benign lesion, 972 women with hyperplasia with atypia and 2379 women with carcinoma in situ diagnosed and treated after participation in BreastScreen Norway, 2006‐2016. Information on breast cancer risk factors was collected by a questionnaire administered with the invitation letter. Cox regression analysis was used to estimate the association between breast cancer and physical activity, body mass index, alcohol consumption, tobacco smoking and menopausal hormone therapy, adjusted for age. During follow‐up, 274 women with a benign lesion, 34 women with hyperplasia with atypia and 118 women with carcinoma in situ were diagnosed with invasive breast cancer. We observed an increased risk of breast cancer associated with use of menopausal hormone therapy for women with a benign or premalignant lesion. Alcohol consumption and tobacco smoking showed suggestive increased risk of breast cancer among women with a benign lesion. We were only to a limited degree able to identify associations between modifiable risk factors of breast cancer and the disease among women with a precancerous lesion, and a larger study is needed to confirm or refute associations. What's new? Whether established lifestyle risk factors for breast cancer, such as physical inactivity, use of hormone therapy (HT), and alcohol consumption, fuel cancer development in women with benign or premalignant breast lesions remains uncertain. In this investigation, increased risk of breast cancer development was observed among women with benign breast lesions who used menopausal HT. HT was not significantly linked to premalignant lesions. Likewise, only suggestive associations were detected for alcohol intake, smoking, and physical inactivity in women with benign or premalignant lesions. The findings warrant further study to better understand the impact of lifestyle factors on prior breast lesions. [ABSTRACT FROM AUTHOR]

BackgroundExogenous sex steroids within hormonal contraception and menopausal hormone therapy (MHT) have been used for family planning and management of menopausal symptoms, without consideration of their effects on the vaginal microbiota. This is largely because their use predates our understanding of the importance of the vaginal microbiome on human health. We conducted a systematic review (PROSPERO: CRD42018107730) to determine the influence of exogenous sex steroids, stratified by oestrogen-containing or progestin-only types of contraception, and MHT on the vaginal microbiome, as measured by molecular methods.MethodsEmbase, PubMed and Medline were searched for relevant literature published through to December 1st 2020. Eligible studies reported on the effect of specific exogenous sex steroids on the vaginal microbiome using a molecular method. Data regarding the ‘positive’, ‘negative’ or ‘neutral’ effect of each type of contraceptive or MHT on the vaginal microbiome was extracted and summarised. A positive effect reflected sex steroid exposure that was associated with increased abundance of lactobacilli, a change to, or maintenance of, an optimal vaginal microbiota composition, or a decrease in bacterial diversity (specifically reflecting a low-diversity optimal microbiota state), relative to the control group. An exogenous sex steroid was designated as having a negative effect on the vaginal microbiome if it resulted in opposing effects (i.e. loss of lactobacilli, a non-optimal microbiota state). When no significant change was found, this was considered neutral/inconclusive.ResultsWe identified 29 manuscripts reporting on the effect of exogenous sex steroids on the vaginal microbiome; 25 investigating hormonal contraceptives, and 4 investigating MHT. Oestrogen-containing contraception, particularly reflecting the combined oestrogen and progestin-containing contraceptive pill, had a positive effect on the composition of the vaginal microbiota. Progestin-only contraception, particularly reflecting depo-medroxyprogesterone acetate, had mixed effects on the microbiota. Among post-menopausal women using MHT, exogenous oestrogen applied topically was associated with increased prevalence of lactobacilli.ConclusionOur findings suggest that oestrogen-containing compounds may promote an optimal vaginal microbiota, which could have clinical applications. The impact of progestin-only contraceptives on the vaginal microbiota is less clear; more data is needed to determine how progestin-only contraceptives contribute to adverse reproductive and sexual health outcomes.

Menopausal hormone therapy (MHT) was widely used to treat menopause-related symptoms in menopausal women. However, MHT therapies were controversial with the increased risk of breast cancer because of different estrogen and progestogen combinations, and the molecular basis behind this phenomenon is currently not understood. To address this issue, we identified differentially expressed genes (DEGs) between the estrogen plus progestogens treatment (EPT) and estrogen treatment (ET) using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data. As a result, a total of 96 upregulated DEGs were first identified. Seven DEGs related to the cell cycle (CCNE2, CDCA5, RAD51, TCF19, KNTC1, MCM10, and NEIL3) were validated by RT-qPCR. Specifically, these seven DEGs were increased in EPT compared to ET (p < 0.05) and had higher expression levels in breast cancer than adjacent normal tissues (p < 0.05). Next, we found that estrogen receptor (ER)-positive breast cancer patients with a higher CNNE2 expression have a shorter overall survival time (p < 0.05), while this effect was not observed in the other six DEGs (p > 0.05). Interestingly, the molecular docking results showed that CCNE2 might bind to 17β-estradiol (−6.791 kcal/mol), progesterone (−6.847 kcal/mol), and medroxyprogesterone acetate (−6.314 kcal/mol) with a relatively strong binding affinity, respectively. Importantly, CNNE2 protein level could be upregulated with EPT and attenuated by estrogen receptor antagonist, acolbifene and had interactions with cancer driver genes (AKT1 and KRAS) and high mutation frequency gene (TP53 and PTEN) in breast cancer patients. In conclusion, the current study showed that CCNE2, CDCA5, RAD51, TCF19, KNTC1, MCM10, and NEIL3 might contribute to EPT-related tumorigenesis in breast cancer, with CCNE2 might be a sensitive risk indicator of breast cancer risk in women using MHT.

Objective: to evaluate the awareness of pharmaceutical specialists on the pharmacotherapy of climacteric syndrome based on survey results.Material and methods. The authors analyzed 394 surveys of pharmaceutical specialists in Saint-Petersburg. The survey consisted of 13 questions, covered the personal characteristics of the participants (age, education, professional experience) and their knowledge about special medicines and food supplements to control climacteric symptoms, indications, and contraindications.Results. The results showed that pharmaceutical specialists saw the difference between combined oral contraceptives and menopausal hormone therapy, but they do not know about the protective cardiovascular effects of menopausal hormone therapy. Most specialists consider menopausal hormone therapy more effective than phytoestrogens, but they have no idea how it works. For most of them, there is hardly any difference between various classes of phytoestrogens. In their opinion, medical representatives and scientific conferences are the main providers of medical information.Conclusion. The analysis of the level of awareness of pharmaceutical specialists about the pharmacotherapy of menopausal syndrome based on the results of the survey revealed insufficient knowledge among pharmacy workers on a number of fundamental issues. Therefore, it is necessary to develop methodological recommendations on menopausal hormone therapy preparations and phytoestrogens-based drugs for pharmaceutical specialists who act as an important intermediate between a doctor and a patient.

Objectives: The purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association. Methods: Baseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Free, bioavailable, and total serum levels of reproductive hormones were measured through liquid chromatography/tandem mass spectrometry. For genotyping of UGT1A1 (rs10928303), UGT1A4 (rs10929301, rs11673726), UGT1A6 (rs1105879, rs2070959, rs6759892), UGT1A8 (rs10167119), UGT2B7 (rs7439366), and SULT1A1 (rs9282861, rs1968752), mass spectrometry based on multiplex methods and TaqMan assays were performed. Adjusted linear models were fit to assess the associations between SNPs and blood hormones using age, body mass index (BMI), and MHT as covariates. Results: The mean age was 59.8 years, and the mean BMI was 25.1 kg/m². Past or recent use of MHT was reported by 41.2% of the participants. SNPs in SULT1A1 (rs1968752 and rs9282861) and UGT1A4 (rs11673726) genes were significantly associated with estrone levels, whereas SNPs in UGT1A6 (rs6759892) and UGT1A8 (rs10167119) genes were significantly associated with bioavailable estradiol levels. Conclusions: There was no evidence that MHT use modified the association between SNPs and sex-steroid hormone levels; however, further studies are needed to establish the potential clinical significance of UGT1A4 (rs11673726), UGT1A6 (rs6759892), and UGT1A8 (rs10167119) SNPs and the modulation of hormone levels in postmenopausal women. [ABSTRACT FROM AUTHOR]

Since the introduction of menopausal hormone therapy (MHT) in the 1940s, randomized clinical trials and observational studies have been performed to determine the benefits and risks of MHT. However, MHT therapeutic impact remains under debate as multiple factors including genetic biomarkers and medical history contribute to inter-individual variations in neurodegenerative diseases. Herein, we review the characteristics of women who participated in clinical studies and methodological approaches for study analyses to assess the critical variables influencing an association between MHT and risk of neurodegenerative diseases. Outcomes of the review indicated that: (1) observational studies assessed outcomes of MHT in symptomatic women whereas MHT clinical trials were conducted in asymptomatic postmenopausal women not treated for menopausal symptoms, (2) in asymptomatic postmenopausal women, late MHT intervention was of no benefit, (3) different MHT treatments and regimens between observational studies and clinical trials may impact outcomes, and (4) observational studies may provide greater predictive validity for long-term neurological health outcomes as MHT was introduced in symptomatic women and administered over a long period of time. Going forward, achieving precision hormone therapy will require a priori identification of symptomatic women appropriate for MHT and the type and dose of MHT appropriate for their genetic profile and health risks. [ABSTRACT FROM AUTHOR]

Objectives: An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture.Methods: Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD).Results: Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group.Conclusions: MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture. [ABSTRACT FROM AUTHOR]

The menopause transition arises mainly from a decline in ovarian function characterized by a decrease in levels of ovarian estrogens (estradiol) and progesterone in women. Menopausal hormone therapy (MHT) has been used to counteract menopause-associated symptoms in postmenopausal women. With the development of advanced brain imaging methods, understanding MHT-related effects on brain structures and functions could help advance our understanding of the biological consequence of MHT-related effects on behavior, thereby contributing to developing new strategies for optimizing brain health during the menopause transition. This review focuses on the human research related to the impact of MHT on structural and functional organization of the prefrontal cortex in postmenopausal women. Although such MHT-related effects on brain structures and functions have only begun to be understood, it may be useful to examine present findings to identify areas for future research. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44–0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59–0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02–1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06–2.44) in older women, but no association was shown for all-cause mortality. Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear. [ABSTRACT FROM AUTHOR]

The objective of this project is to create eligibility criteria for the use of menopausal hormone therapy (MHT) similar to those established for contraceptive methods. A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by patients with medical conditions based on the best available evidence. The project protocol, which was registered in the Open Science Framework platform (DOI 10.17605/OSF.IO/J6WBC), will be conducted in two phases. As a first step we will conduct a series of systematic reviews on the safety of MHT, addressing eight clinical questions. The findings of these systematic reviews will help to inform a structured process in which a panel of experts will define the eligibility criteria according to a specific framework, which will facilitate the discussion and development process. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, will be defined. This will provide health professionals with a powerful decision-making tool that can be used in the management of menopausal symptoms. [ABSTRACT FROM AUTHOR]

Background The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n–3 (ɷ-3) PUFA concentrations are unknown. Objective We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n–3 PUFA concentrations. Methods Postmenopausal women (ages 50–79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65–79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n  = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n  = 610). RBC n–3 and n–6 (ɷ-6) PUFAs were quantified. Results Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n–3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n–6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged. Conclusions HT increased RBC concentrations of the terminal n–3 and n–6 PUFAs (DHA and DPA n–6). These findings are consistent with an estrogen-induced increase in DHA and DPA n–6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory. [ABSTRACT FROM AUTHOR]