Systematic review of neurokinin-3 receptor antagonists for the management of vasomotor symptoms of menopause.

IMPORTANCE: Vasomotor symptoms (VMS) affect many postmenopausal persons and impact sleep and quality of life. OBJECTIVE: This systematic review examines the literature describing the safety and efficacy of neurokinin-3 receptor antagonists approved and in development for postmenopausal persons with VMS. EVIDENCE REVIEW: A search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted using the search terms and permutations of neurokinin-3 receptor antagonist, elinzanetant, fezolinetant, and osanetant. Inclusion criteria of reporting on efficacy or safety of fezolinetant, elinzanetant, or osanetant; studies in participants identifying as female; full record in English; and primary literature were applied. Abstract-only records were excluded. Extracted data were synthesized to allow comparison of reported study characteristics, efficacy outcomes, and safety events. Eligible records were evaluated for risk of bias via the Cochrane Risk of Bias 2 tool for randomized studies and the Grading of Recommendations Assessment, Development and Evaluation system was used. This study was neither funded nor registered. FINDINGS: The search returned 191 records; 186 were screened after deduplication. Inclusion criteria were met by six randomized controlled trials (RCT), four reported on fezolinetant, and two reported on elinzanetant. One record was a post hoc analysis of a fezolinetant RCT. An additional study was identified outside the database search. Three fezolinetant RCT demonstrated a reduction in VMS frequency/severity, improvement in Menopause-Specific Quality of Life scores, and improvement in sleep quality at weeks 4 and 12 compared with placebo without serious adverse events. The two RCT on elinzanetant also showed improvements in VMS frequency and severity. All eight records evaluated safety through treatment-emergent adverse events; the most common adverse events were COVID-19, headache, somnolence, and gastrointestinal. Each record evaluated had a low risk of bias. There is a strong certainty of evidence as per the Grading of Recommendations Assessment, Development and Evaluation system. CONCLUSIONS AND RELEVANCE: Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS.

Vasomotor symptoms and cardiovascular health: findings from the SWAN and the MsHeart/MsBrain studies.

Vasomotor symptoms (VMS) are often considered the classic menopausal symptom and are experienced by most women during the menopause transition. VMS are well established to be associated with decrements in quality of life during the menopause. More recent research also links VMS to poorer cardiovascular health. This review summarizes key insights about links between VMS and cardiovascular disease (CVD) risk that come from the Study of Women's Health Across the Nation (SWAN), a longitudinal epidemiologic cohort study of the menopause transition, as well as from the MsHeart/MsBrain studies, clinical studies that leverage vascular imaging and brain imaging as well as wearable technologies that provide objective indicators of VMS. Using a range of methodologies and extensive consideration of confounders, these studies have shown that frequent and/or persistent VMS are associated with adverse CVD risk factor profiles, poorer underlying peripheral vascular and cerebrovascular health, and elevated risk for clinical CVD events. Collectively, the SWAN and MsHeart/MsBrain studies form complementary epidemiologic and clinical studies that point to the importance of VMS to women's cardiovascular health during the menopause transition and beyond.

Evaluación del impacto, los patrones de tratamiento y las percepciones de pacientes y clínicos de los síntomas vasomotores moderado-graves asociados a la menopausia en España / Analysis of the impact, patterns of care, and perspectives of patients and physicians about moderate-to-severe menopausal vasomotor symptoms in Spain

Introducción: La menopausia puede originar distintos síntomas, siendo los vasomotores especialmente prevalentes y molestos. Este trabajo pretende conocer su impacto y los patrones/percepciones sobre el tratamiento en España, para lo que se han analizado las opiniones de clínicos y pacientes con síntomas vasomotores moderado-graves (SVM-MG). Métodos: Estudio transversal descriptivo de la subpoblación española del Programa de Enfermedades Específicas de Adelphi-VMS™. Médicos de atención primaria y de Ginecología y Obstetricia seleccionaron las pacientes. Estas fueron invitadas a rellenar una encuesta y los cuestionarios MENQOL y WPAI:SHP. Los datos se han presentado como porcentaje o media±desviación estándar. Resultados: Un total de 32 médicos de Atención Primaria y Ginecología y Obstetricia completaron los formularios de registro para 241 mujeres, de las cuales 143 experimentaban SVM-MG. A pesar del impacto global reportado en el trabajo (24,84%±17,49 presentismo) y en la calidad de vida (3,37±1,52 MENQOL), solo el 53,85% de las mujeres eran tratadas. El tratamiento hormonal de la menopausia era el más prescrito (77,92%), seguido de los inhibidores de la recaptación de serotonina (32,47%). El 59% de los clínicos estaba muy o completamente satisfecho con el tratamiento hormonal de la menopausia, mientras que solo el 19% lo estaba con los inhibidores de la recaptación de serotonina. Pacientes y especialistas indicaron un nivel de satisfacción inferior al 38% en el control de los SVM. Conclusiones: Los SVM-MG asociados a la menopausia tienen un importante impacto sobre la calidad de vida. Una mayor sensibilización en su manejo y mejores opciones terapéuticas contribuirían significativamente a mejorar la salud y bienestar de la mujer durante el climaterio.(AU)

Introduction: Menopause generates different symptoms, among which vasomotor symptoms are especially prevalent and bothersome. The aim of this work was to determine their impact and the treatment patterns and perceptions in Spain by analyzing the opinions of physicians and patients with moderate-to-severe vasomotor symptoms (MS-VMS). Methods: Descriptive cross-sectional study of the Spanish subpopulation from the Adelphi-VMS™ Disease-Specific Program. Primary Care and Gynecology and Obstetrics physicians selected the patients. These patients were invited to complete a survey and the MENQOL and WPAI:SHP questionnaires. Data are presented as percentage or mean±standard deviation. Results: Overall 32 Primary Care and Gynecology and Obstetrics physicians participated in the study, enrolling 241 women, of whom 143 experienced MS-VMS. Despite the reported impact on global work (24.84%±17.49 presentism) and quality of life (3.37±1.52 MENQOL score), only 53.85% of women with MS-VMS were treated. Menopausal hormone treatment was the most prescribed (77.92%), followed by serotonin reuptake inhibitors (32.47%). Fifty-nine percent of clinicians were very or completely satisfied with hormone treatment, whereas only 19% had this level of satisfaction with selective serotonin reuptake inhibitors. Less than 38% of patients and physicians were satisfied with the control of VMS. Conclusions: Menopause-associated MS-VMS have an important impact on quality of life. Increased awareness about their management and better therapeutic options would significantly contribute to improving women's health and well-being during their climacteric period.(AU)

Fezolinetant: un nuevo tratamiento en estudio para la menopausia / Fezolinetant: A new treatment being studied for menopause

La menopausia es el cese fisiológico de la menstruación que puede presentarse en las mujeres entre los 42 y 58 años con una sintomatología diversa. La clínica más frecuente es la vasomotora, que puede afectar en gran medida a la calidad de vida de las mujeres. Tradicionalmente se ha usado la terapia hormonal sustitutiva, que se considera el tratamiento más efectivo. Sin embargo, existe una serie de contraindicaciones por las que se debe plantear el uso de una terapia no hormonal. Actualmente estas opciones son subóptimas en efectividad y tolerancia, por lo que se está investigando acerca de nuevos tratamientos como el fezolinetant, un antagonista del receptor de neuroquinina 3. Para dilucidar dichas investigaciones se ha realizado una búsqueda bibliográfica en las principales bases de datos. Aunque aún queda por establecer su seguridad y efectos a largo plazo, la terapia con fezolinetant parece ser prometedora en pacientes en las que no se puede usar terapia hormonal. Disminuye la sintomatología vasomotora moderada o grave desde el primer día de tratamiento de manera estadísticamente significativa al compararla con placebo y con otros tratamientos no hormonales, con un buen perfil de tolerancia y escasos efectos secundarios. Sin embargo, este medicamento aún se encuentra en ensayos de fase III, por lo que se necesita continuar con su estudio.(AU)

Menopause is the physiological cessation of menstruation that can occur in women between 42 and 58 years of age with diverse symptoms. The most common clinic is vasomotor, which can greatly affect the quality of life of women. Traditionally, hormone replacement therapy has been used and is considered the most effective treatment. However, there are contraindications for which the use of non-hormonal therapy should be considered. Nowadays, these options are suboptimal in terms of effectiveness and tolerance, which is why research is being carried out on new treatments such as fezolinetant, a neurokinin 3 receptor antagonist. To elucidate these investigations a bibliographic search has been carried out in the main databases. Although its safety and long-term effects remain to be established, fezolinetant looks promising in patients for whom hormonal therapy cannot be used. It decreases statistically significant the moderate or severe vasomotor symptoms from the first day of treatment when compared with placebo and with other non-hormonal treatments with a good tolerance profile and few side effects. However, this drug is still in phase III trials, so it needs to continue with its study.(AU)

Global view of vasomotor symptoms and sleep disturbance in menopause: a systematic review.

Studies have shown racial/ethnic differences in the prevalence of vasomotor symptoms (VMS), sleep disturbance and VMS treatment in menopause. To assess the reproducibility of these differences, we systematically reviewed observational studies, published in 2000-2021, reporting the prevalence/incidence of VMS, sleep disturbance or treatment use in menopausal women stratified by race/ethnicity. We screened 3799 records from PubMed and Embase and included 27 papers (19 studies). No incidence data were found. Prevalence data varied widely, but some common patterns emerged. In all five studies comparing VMS between Black women and White, Hispanic and/or East Asian women, the prevalence was highest in Black women and lowest in East Asian women. The prevalence of sleep disturbance overall was compared among Black, White and East Asian women in two study populations, and was highest in White women in both papers. Sleep disturbance was more common than VMS in East Asian women. In all four studies comparing hormone therapy use between White women and Black and/or East Asian women, treatment use was more common in White women. These results highlight the need for individualized counseling and treatment, outreach to under-served minorities, and standardized definitions and outcome measures for VMS and sleep disturbance for future studies.

Association between vasomotor symptom frequency and weight gain in the Study of Women's Health Across the Nation.

OBJECTIVE: The menopause transition is associated with weight gain in women. We examined whether changes in vasomotor symptom (VMS) frequency precede weight changes. METHODS: This longitudinal retrospective analysis included data from the multisite, multiethnic Study of Women's Health Across the Nation. Women in premenopause or perimenopause aged 42 to 52 years at baseline self-reported VMS frequency (hot flashes/night sweats) and sleep problems at up to 10 annual visits. Menopause status, weight, body mass index, and waist circumference were compared across visits. The primary objective was to measure the association between VMS frequency and weight gain using a lagged approach with first-difference regression models. Secondary objectives were to statistically quantify mediation by sleep problems and moderation by menopause status and explore the association between cumulative, 10-year VMS exposure and long-term weight gain. RESULTS: The primary analysis sample included 2,361 participants (12,030 visits; 1995-2008). Increased VMS frequency across visits was associated with subsequently increased weight (0.24 kg), body mass index (0.08 kg/m 2 ), and waist circumference (0.20 cm). Cumulative exposure to a high frequency of VMS (≥6 d/2 wk) over 10 consecutive annual visits was associated with increases in weight measures, including a 3.0-cm increase in waist circumference. Contemporaneous sleep problems mediated no more than 27% of waist circumference increases. Menopause status was not a consistent moderator. CONCLUSIONS: This study demonstrates that increases in VMS, onset of a high frequency of VMS, and persistent VMS symptoms over time may precede weight gain in women.

Association of Migraine and Vasomotor Symptoms.

OBJECTIVE: To further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women. PATIENTS AND METHODS: We conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women's clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors. RESULTS: Of 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002). CONCLUSION: This large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms.

Vasomotor symptoms and risk of cardiovascular disease in peri- and postmenopausal women: A systematic review and meta-analysis.

INTRODUCTION: Vasomotor symptoms (VMS) are the symptoms most frequently experienced by women transitioning to menopause and are a primary indication for menopausal hormone therapy. A growing body of evidence has associated the presence of VMS with future risk for cardiovascular disease (CVD) events. This study aimed to systematically evaluate, qualitatively and quantitatively, the possible association between VMS and the risk for incident CVD. METHODS: This systematic review and meta-analysis included 11 studies evaluating peri- and postmenopausal women in a prospective design. The association between VMS (hot flashes and/or night sweats) and the incidence of major adverse cardiovascular events, including coronary heart disease (CHD) and stroke, was explored. Associations are expressed as relative risks (RR) with 95 % confidence intervals (CI). RESULTS: The risk for incident CVD events in women with and without VMS differed according to the age of participants. Women with VSM younger than 60 years at baseline had a higher risk of an incident CVD event than women without VSM of the same age (RR 1.12, 95 % CI 1.05-1.19, I2 0%). Conversely, the incidence of CVD events was not different between women with and without VMS in the age group >60 years (RR 0.96, 95 % CI 0.92-1.01, I2 55%). CONCLUSION: The association between VMS and incident CVD events differs with age. VMS increases the incidence of CVD only in women under 60 years of age at baseline. The findings of this study are limited by the high heterogeneity among studies, pertaining mainly to different population characteristics, definitions of menopausal symptoms and recall bias.

Impact of lifetime lactation on the risk and duration of frequent vasomotor symptoms: A longitudinal dose-response analysis.

OBJECTIVE: To examine the association between lifetime lactation and risk and duration of frequent vasomotor symptoms (VMS). DESIGN: Prospective cohort. SETTING: USA, 1995-2008. SAMPLE: 2356 parous midlife women in the Study of Women's Health Across the Nation. METHODS: Lifetime lactation was defined as the duration of breastfeeding across all births in months. We used generalised estimating equations to analyse risk of frequent VMS and Cox regression to analyse duration of frequent VMS in years. MAIN OUTCOME MEASURES: Frequent VMS (hot flashes and night sweats) were measured annually for 10 years, defined as occurring ≥6 days in the past 2 weeks. RESULTS: Overall, 57.1% of women reported hot flashes and 43.0% reported night sweats during follow-up. Lifetime lactation was inversely associated with hot flashes plateauing at 12 months of breastfeeding (6 months: adjusted odds ratio [AOR] 0.85, 95% confidence interval (CI) 0.75-0.96; 12 months: AOR 0.78, 95% CI 0.65-0.93) and was inversely associated with night sweats in a downward linear fashion (6 months: AOR 0.93, 95% CI 0.81-1.08; 18 months: AOR 0.82, 95% CI 0.67-1.02; 30 months: AOR 0.73, 95% CI 0.56-0.97). Lifetime lactation was associated with shorter duration of hot flashes and night sweats in a quadratic (bell-shaped) fashion. The association was strongest at 12-18 months of breastfeeding and significant for hot flashes (6 months: adjusted hazard ratio [AHR] 1.35, 95% CI 1.11-1.65; 18 months: AHR 1.54, 95% CI 1.16-2.03; 30 months: AHR 1.18, 95% CI 0.83-1.68). CONCLUSIONS: Longer lifetime lactation is associated with decreased risk and duration of frequent VMS.

Eficacia y seguridad de una alternativa a la terapia hormonal de la menopausia: extracto purificado de polen / Efficacy and safety of an alternative to menopausal hormone therapy: purified cytoplasm of pollen

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre los SVM.

Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.

Vasomotor symptoms of menopause, autonomic dysfunction, and cardiovascular disease.

Cardiovascular disease (CVD), the leading cause of death among US adults, is more prevalent in menopausal females compared with age-matched males. Vasomotor symptoms of menopause (VMS; hot flashes/flushes and night sweats) are common among females undergoing menopausal transition and have been associated with elevated blood pressure (BP) and increased CVD risk. Autonomic dysregulation of BP has been posited as a contributing factor to the elevated CVD risk in menopausal females with VMS. This review includes 1) a brief overview of the relationship between VMS and CVD, 2) mechanisms of hot flushes and their potential impact on short- and long-term BP regulation, and 3) how the disruption of autonomic function associated with VMS might provide a mechanistic pathway to CVD development. Finally, this review will highlight knowledge gaps and future directions toward better understanding of hot flush physiology and VMS contributions to CVD.

Menopausal vasomotor symptoms and adiponectin among midlife women.

OBJECTIVE: Vasomotor symptoms (VMS) are prevalent symptoms that can have a negative impact on quality of life. VMS have also been linked to cardiovascular disease risk, yet the mechanisms underlying these associations have not been elucidated. Some initial works link VMS to adverse adipokine profiles or cytokines produced by adipose tissue. However, results are not entirely consistent and are based entirely on self-report VMS, which is influenced by a range of memory and reporting biases. The aim of this work was to test whether physiologically assessed VMS are associated with lower adiponectin, the most abundant adipokine in the body, controlling for confounding factors. We also consider whether adiponectin explains previously documented relationships between VMS and carotid atherosclerosis. METHODS: A total of 300 peri- and postmenopausal nonsmoking women aged 40 to 60 years enrolled in the MsHeart study comprised the analytic sample. Women were free of hormone therapy or other medications impacting VMS, insulin-dependent diabetes, and cardiovascular disease. Participants underwent ambulatory physiologic VMS monitoring, physical measures, a carotid ultrasound, and fasting phlebotomy. RESULTS: More frequent physiologically assessed VMS were associated with lower adiponectin ( B [SE] = -0.081 [0.028], P = 0.004; or 0.081 lower µg/mL in adiponectin for each additional VMS over 24 hours), controlling for age, race/ethnicity, education, insulin resistance, and waist circumference. Associations were not explained by endogenous estradiol. Adiponectin did not explain associations between VMS and carotid atherosclerosis. CONCLUSIONS: Physiologic VMS were associated with lower adiponectin after considering potential confounders. The role of adipokines in VMS and in links between VMS and health warrants further attention.

High low-density lipoprotein cholesterol level is associated with an increased risk of incident early-onset vasomotor symptoms.

We investigated the associations between serum lipid profiles and risk of early-onset vasomotor symptoms (VMSs) in premenopausal women. This cohort study comprised 2,540 premenopausal women aged 42-52 years without VMSs at baseline (median follow-up: 4.4 years). VMSs, including hot flashes and night sweats, were assessed using the Menopause-Specific Quality of Life questionnaire (Korean version). Early-onset VMSs were defined as VMSs that occurred premenopause; moderate/severe VMSs were defined as a score of ≥ 3 points (range: 0 to 6, 6 being most bothersome). Cox proportional hazard regression models were used to estimate hazard ratios with 95% confidence intervals (CI) for the development of VMSs across the lipid levels. Higher low-density lipoprotein (LDL) cholesterol levels were positively associated with increased risk of early-onset VMSs. Compared to the < 100 mg/dL LDL group, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for incident VMSs were 1.19 (1.03-1.37) and 1.20 (1.03-1.40) in participants with LDL cholesterol levels of 100-129 mg/dL and ≥ 130 mg/dL, respectively (P for trend = 0.027). The multivariable-adjusted HR for incident moderate/severe VMSs was 1.37 (95% CI: 1.08-1.73) in participants with LDL ≥ 130 mg/dL, compared to those with LDL < 100 mg/dL. Meanwhile, triglycerides and total and high-density lipoprotein cholesterol levels were not significantly associated with early-onset VMSs risk in premenopausal women. Premenopausal women with high serum LDL cholesterol concentrations had a higher risk of incident early-onset VMSs. Further studies should confirm our findings and examine whether LDL-lowering interventions reduce the risk of early-onset VMSs among women during menopause transition.

The longitudinal relation of inflammation to incidence of vasomotor symptoms.

OBJECTIVE: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity. METHODS: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline. RESULTS: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%). CONCLUSIONS: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS.

Epidemiology and treatment patterns of UK women diagnosed with vasomotor symptoms: Findings from the Clinical Practice Research Datalink GOLD database.

OBJECTIVES: To describe the epidemiology and treatment of vasomotor symptoms (VMS) in the UK. STUDY DESIGN: Retrospective study that used electronic medical records from UK primary care centers. MAIN OUTCOME MEASURES: The prevalence and incidence of moderate-to-severe VMS, the proportion treated, persistence with initial treatment, treatment patterns, and menopausal hormone therapy (HT) experience were investigated over the study period (Jan. 2009-Dec. 2018). The study population comprised women aged 40-65 years registered at general practitioner clinics. For incident cases, the uptake of pharmacological non-hormonal or hormonal treatment was recorded, which included experience of HT. RESULTS: Over the 10-year study period, 1,481,646 women were included from the database, among whom there were 313,031 prevalent and 90,434 incident cases of VMS. Annual prevalence and incidence rates were stable over time, with a weighted average of 21.1 % and 15.3 per 1000 person-years, respectively (results varied across age groups). Among women who were incident VMS cases, 32.4 % (29,275) were initially prescribed non-hormonal treatments for a median of 3.9 months, 49.4 % (44,700) were prescribed hormonal treatments for 4.0 months, and 18.2 % (16,459) had no treatment. Approximately one-third of treated women switched between non-hormonal and hormonal treatments. The HT experience results showed that 52.7 % (47,639) of women were HT-eligible, 13.1 % (11,872) were HT-contraindicated (they may or may not have received HT), and 34.2 % (30,923) did not receive HT. CONCLUSIONS: Variations in prescribed treatment patterns suggest that education may be needed for clinicians and women regarding the potential pharmacological options for treating VMS in the UK.

Alcohol Consumption Patterns and Risk of Early-Onset Vasomotor Symptoms in Premenopausal Women.

The role of alcohol consumption in the risk of vasomotor symptoms (VMS), the most cardinal climacteric symptoms, is not well established. We examined their relationship with early-onset VMS among premenopausal women. Moderately-to-severely bothersome VMS, the primary outcome, was assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. The alcohol consumption categories included lifetime abstainer, former drinker, or current drinker, categorized as light, moderate, heavy, and very heavy. Compared with the lifetime-abstinence (reference), the multivariable-adjusted odds ratio (95% CIs) for prevalent VMS in alcohol consumption of <10, 10−19, 20−39, and ≥40 g/day were 1.42 (1.02−1.99), 1.99 (1.27−3.12), 2.06 (1.19−3.57), and 3.52 (1.72−7.20), respectively (p trend <0.01). Compared with the lifetime-abstinence, the multivariable-adjusted hazard ratios (95% CIs) for incident bothersome VMS among average alcohol consumption of <10, 10−19, 20−39, and ≥40 g/day were 1.10 (0.85−1.41), 1.03 (0.70−1.51), 1.72 (1.06−2.78), and 2.22 (1.16−4.23), respectively (p trend = 0.02). Increased alcohol consumption positively and consistently showed a relationship with increased risk of both prevalent and incident early-onset VMS. Refraining from alcohol consumption may help prevent bothersome VMS in premenopausal women.

The association of vasomotor symptoms during the menopausal transition and cognition in later life.

OBJECTIVE: The majority of women experience vasomotor symptoms (VMS) during the menopausal transition. Whether self-reported VMS are associated with cognitive test performance later in life remains unclear. The goal of this study was to determine whether a greater burden of VMS is associated with poor later-life cognition. METHODS: The Wisconsin Longitudinal Study is a prospective study of randomly selected Wisconsin high school graduates of the class of 1957. At ages 65 and 72, a random subset of participants completed six cognitive tests, including similarities, letter and category fluency, immediate and delayed word recall, and digit ordering. Nested regression models were used to examine the association between extent of VMS, assessed at age 54, and baseline cognition at 65, adjusting for early-life socioeconomic status, women's reproductive health variables, intelligence quotient, and midlife income. This series of models was also used to examine the association between VMS and change in cognition score from age 65 to 72. In sensitivity analyses, models were repeated in a sample using multiple imputation for missing covariates. RESULTS: Of the 5,326 women enrolled, 874 had data onVMS, covariates, and all cognitive tests. In an unadjusted model, higher VMS were associated with a lower similarities score (b = -0.09 95% CI -0.16 to -0.02) at age 65 but no other cognitive tests. In adjusted models, VMS were not related to cognition at age 65 or change in cognition. Results remained similar with multiple imputation. CONCLUSIONS: Our study does not support a relationship between self-reported VMS and cognition later in life.

Eukaryotic elongation factor 2 kinase inhibitor, A484954 inhibits perivascular sympathetic nerve stimulation-induced vasoconstriction in isolated renal artery.

Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) repressively regulates protein translation through phosphorylating eEF2. We previously showed that expression and activity of eEF2K are increased in isolated mesenteric arteries from spontaneously hypertensive rats (SHR) contributing to development of essential hypertension. Furthermore, we have recently shown that 7-Amino-1-cyclopropyl-3-ethyl-1,2,3,4-tetrahydro-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide (A484954), a selective eEF2K inhibitor, induces endothelium-dependent relaxation in isolated mesenteric arteries from SHR inducing an antihypertensive effect. In order to test the hypothesis that inhibition of eEF2K activity induces vasodilatation by suppressing sympathetic nerve activity, we examined the effects of A484954 on perivascular sympathetic nerve stimulation-induced contraction in isolated renal artery from normotensive and hypertensive rats. Electrodes were placed near the isolated renal arteries that were applied with transmural nerve stimulation (TNS). Then, contraction of the arteries was isometrically measured. A484954 inhibited TNS-induced contraction. The A484954-mediated inhibition of TNS-induced contraction was significantly prevented by NG-nitro-L-arginine methyl ester. In SHR isolated renal artery, TNS-induced contraction was enhanced compared with normotensive Wistar rats. Furthermore, A484954-mediated inhibition of TNS-induced contraction in SHR was enhanced compared with Wistar rats. In conclusion, this study demonstrates for the first time that A484954 inhibits perivascular sympathetic nerve stimulation-induced vasoconstriction at least in part perhaps through nitric oxide (NO) release from NO-operating nerve.