A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers.

BACKGROUND: Most women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women. METHODS: This observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT. RESULTS: Although all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010). CONCLUSIONS: A 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG. TRIAL REGISTRATION: Clinical trials.gov registered ID: NCT01987778, trial registration date 2013-11-19.

Treatment satisfaction, unmet needs, and new treatment expectations for vasomotor symptoms due to menopause: women's and physicians' opinions.

OBJECTIVE: To assess treatment satisfaction, unmet treatment needs, and new vasomotor symptom (VMS) treatment expectations among women with moderate to severe VMS and physicians treating women with VMS. METHODS: This noninterventional, nonrandomized survey included qualitative interviews and quantitative surveys of women and physicians in the US. Participating women had moderate to severe VMS in the past year and received ≥1 hormone therapy (HT), non-HT, or over-the-counter (OTC) treatment for VMS in the past 3 months. Participating physicians were obstetrician-gynecologists (OB-GYNs) and primary care physicians (PCPs) who treated ≥15 women with VMS in the past 3 months. Two online survey questionnaires were developed using insights from literature, qualitative interviews, and clinical experts. Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) measured treatment satisfaction. Results were summarized descriptively. RESULTS: Questionnaires were completed by 401 women with VMS and 207 physicians treating VMS. Among women, mean total MS-TSQ score ranges were 62.8-67.3 for HT, 59.8-69.7 for non-HT, and 58.0-64.9 for OTC treatments. Among physicians, mean total MS-TSQ scores were considerably higher for HT than for non-HT and OTC treatments (HT: 73.4-75.6; non-HT: 55.6-62.1; OTC: 49.2-54.7). Women reported "lack of effectiveness" (41.2%), and physicians reported "long-term safety concerns" (56.5%) as main features that do not meet their current treatment expectations. The majority of women and physicians would consider trying a new non-HT treatment for VMS (75.8 and 75.9%, respectively). CONCLUSIONS: Treatment satisfaction and new treatment expectations were similar but with some differences between women and physicians; the need for additional treatments for VMS was identified.

Menopausal Vasomotor Symptoms and Subclinical Atherosclerotic Cardiovascular Disease: A Population-Based Study.

BACKGROUND: Menopausal vasomotor symptoms (VMS) are increasingly emphasized as a potentially important cardiovascular risk factor, but their role is still unclear. We assessed the association between VMS and subclinical atherosclerotic cardiovascular disease in peri- and postmenopausal women. METHODS AND RESULTS: Using a cross-sectional study design, questionnaire data were collected from a population-based sample of women aged 50 to 64. The questionnaire asked whether menopause was/is associated with bothersome VMS. A 4-point severity scale was used: (1) never, (2) mild, (3) moderate, and (4) severe. The VMS duration and time of onset were also assessed. Associations with subclinical atherosclerotic cardiovascular disease, detected via coronary computed tomography angiography, coronary artery calcium score, and carotid ultrasound were assessed using the outcome variables "any coronary atherosclerosis," "segmental involvement score >3," "coronary artery calcium score >100," and "any carotid plaque," using logistic regression. Covariate adjustments included socioeconomic, lifestyle, and clinical factors. Of 2995 women, 14.2% reported ever severe, 18.1% ever moderate, and 67.7% ever mild/never VMS. Using the latter as reference, ever severe VMS were significantly associated with coronary computed tomography angiography-detected coronary atherosclerosis (multivariable adjusted odds ratio, 1.33 [95% CI, 1.02-1.72]). Corresponding results for ever severe VMS persisting >5 years or beginning before the final menstrual period were 1.50 (95% CI, 1.07-2.11) and 1.66 (95% CI, 1.10-2.50), respectively. No significant association was observed with segmental involvement score >3, coronary artery calcium score >100, or with any carotid plaque. CONCLUSIONS: Ever occurring severe, but not moderate, VMS were significantly associated with subclinical coronary computed tomography angiography-detected atherosclerosis, independent of a broad range of cardiovascular risk factors and especially in case of long durations or early onset.

Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause.

INTRODUCTION: During menopause, the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms, offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns. AREAS COVERED: This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies. EXPERT OPINION: Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms. The most common adverse event is headache (5-10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for vasomotor symptoms, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

Treatment utilization and non-drug interventions for vasomotor symptoms in breast cancer survivors taking endocrine therapy: Real-world findings from the United States and Europe.

OBJECTIVES: Vasomotor symptoms induced by endocrine therapy are common in breast cancer survivors and a risk factor for therapy discontinuation and lower quality of life. The REALISE study evaluated the real-world treatment landscape in breast cancer survivors with vasomotor symptoms taking endocrine therapy, including pharmaceuticals, lifestyle changes, and over-the-counter products. STUDY DESIGN: Secondary analysis of the Adelphi Vasomotor Disease Specific Programme™, a large cross-sectional point-in-time survey and chart review conducted in the US and five European countries (February-October 2020). Oncologists provided demographic, clinical, and treatment data for adult breast cancer survivors with induced vasomotor symptoms taking endocrine therapy (tamoxifen or aromatase inhibitors); patients voluntarily completed self-report surveys on their symptom severity, concomitant sleep and/or mood symptoms, lifestyle changes, and use of over-the-counter products. MAIN OUTCOME MEASURES: Patient characteristics; vasomotor symptom severity; use of pharmaceuticals, lifestyle changes, and over-the-counter products (from pre-defined lists); lines of treatment. RESULTS: Overall, 77 oncologists reported data for 618 breast cancer survivors, of whom 183 (29.6 %) completed self-report forms. Physicians classified 420 (68.0 %) women as experiencing moderate-severe vasomotor symptoms, of whom 66.9 % were receiving treatment. In total, 15.2 % of all breast cancer survivors were prescribed systemic hormone therapy. Venlafaxine (24.7 %), citalopram (16.5 %), and paroxetine (13.6 %) were the most commonly prescribed nonhormonal medications. Lifestyle changes (77.8 %) and over-the-counter products (61.6 %) were common, especially in patients with concomitant sleep and/or mood symptoms. CONCLUSIONS: Despite contraindications, a relatively large proportion of treatment-seeking breast cancer survivors with vasomotor symptoms were prescribed systemic hormone therapy. This, combined with high patient-reported use of lifestyle changes and over-the-counter products, suggests a need for symptomatic relief and demand for new nonhormonal alternatives with established safety profiles in this population.

Retrospective text and qualitative analyses of patient experience and management of vasomotor symptoms due to menopause: voices from the PatientsLikeMe community.

OBJECTIVE: Vasomotor symptoms (VMS) due to menopause cause substantial burden and distress. Some women join online communities to share experiences and treatment outcomes through peer-to-peer interactions. This study describes women's experiences with VMS and symptom management on the PatientsLikeMe online support group. METHODS: Mixed-methods research included women aged 40 to 65 years in the PatientsLikeMe community who were recruited using convenience sampling. Text from online posts by members was analyzed retrospectively using natural language processing. Relevant data, including numbers and percentages of women and frequencies of mentions, were summarized descriptively. Qualitative semistructured interviews were conducted; data, notes, and recordings were transcribed and deidentified and thematic analyses were performed. RESULTS: Demographic information was available from 1,614 accounts included in retrospective text analyses. Women had a mean age of 56.7 years; most were White (87.8%) and not Hispanic/Latino (90.2%). Hot flashes and night sweats were most commonly mentioned symptoms (n = 146). Of 16 women who were interviewed, 14 met the inclusion criteria, and their responses were included in the analysis. VMS impacted life quality in terms of physical (43%) and mental well-being (36%), social activities (21%), and productivity (14%). Symptom management included temperature regulation (43%), lifestyle changes (36%), over-the-counter Estroven (29%), hormone therapy (21%), and contraceptives (21%). Half of the women were surprised by symptom intensity and duration; many felt unheard by their healthcare providers. CONCLUSIONS: VMS have a substantial negative impact on multiple aspects of women's life. Management strategies for these symptoms vary widely, and many women feel unprepared for navigating the complex challenges of menopause.

Prevalence of Coronary Vasomotor Disorders in Patients With Angina and Nonobstructive Coronary Arteries: A Sydney Experience.

BACKGROUND: Patients with angina and non-obstructive coronary arteries (ANOCA) frequently have coronary vasomotor disorders (CVaD), characterised by transient pathological vasoconstriction and/or impaired microvascular vasodilatation. Functional coronary angiography is the gold standard for diagnosing CVaD. Despite recommendations, testing is only available at a limited number of Australian and New Zealand centres. This study aimed to determine the prevalence of CVaDs in an Australian ANOCA population and identify predictive factors associated with specific endotypes. METHOD: Functional coronary angiography was performed in patients with suspected ANOCA. Vasoreactivity testing was performed using intracoronary acetylcholine provocation. A pressure-temperature sensor guidewire was used for coronary physiology assessment. Comprehensive clinical data on patient characteristics, cardiac risk factors, and symptom profiles was collected before testing. RESULTS: This prospective observational study at Royal Prince Alfred and Concord Repatriation General Hospital included 110 patients (58±13 years with 63.6% women), with 81.8% (90/110) having a CVaD. Regarding specific ANOCA endotypes, microvascular angina (MVA) occurred in 31.8% (35/110) of cases, vasospastic angina (VSA) in 25.5% (28/110) and a mixed presentation of MVA and VSA in 24.5% (27/110) of patients. Patients with CVaD were found to be older (59±11 vs 51±15, p=0.024), overweight (61.1% vs 15.0%, p<0.001) and had a worse quality of life (EuroQol 5 Dimensions-5 Levels; 0.61 vs 0.67, p=0.043). MVA was associated with being overweight (odds ratio [OR] 4.2 [95% confidence interval [CI] 1.9-9.3]; p=0.015) and ischaemia on stress testing (OR 2.4 [95% CI 1.1-4.3]; p=0.028), while VSA was associated with smoking (OR 9.1 [95% CI 2.21-39.3]; p=0.007). CONCLUSIONS: Coronary vasomotor disorders are highly prevalent among ANOCA patients. This study highlights the importance of increasing national awareness and the use of functional coronary angiography to evaluate and manage this unique cohort.

Real-world clinical evaluation of natural and induced vasomotor symptoms in the USA and Europe.

OBJECTIVE: This study aimed to examine physicians' and patients' perceptions regarding symptom burden and impact in women experiencing natural vasomotor symptoms (nVMS) or vasomotor symptoms induced by endocrine therapy for breast cancer (iVMS). METHODS: The cross-sectional survey based on real-world clinical consultations was conducted in the USA and five European countries. Obstetrician-gynecologists, primary-care physicians and oncologists provided demographic and symptom data for patients experiencing VMS; patients optionally self-reported their experiences via questionnaires, including their symptom profile and work/activity burden through the Menopause Quality of Life (MENQOL) and Work Productivity and Activity Impairment (WPAI) tools. RESULTS: Physicians completed survey forms on 2451 consulting patients; patients completed 1029 questionnaires. nVMS and iVMS severity was significantly associated with the severity of mood symptoms and sleep disturbances (p < 0.0001). However, around half of the patients with mild nVMS/iVMS also experienced moderate-severe mood changes (55.4%/43.7%) or sleep disturbances (42.4%/40.4%). Presence of mood/sleep disturbances alongside nVMS increased MENQOL vasomotor scores (p = 0.004/p < 0.001). Presence of sleep disturbances increased WPAI activity impairment (p < 0.001) but mood changes did not. Similar findings were reported for iVMS patients. CONCLUSION: Significant burden from the triad of natural or induced menopausal symptoms, sleep disturbances and mood changes affected women's daily activities, work and quality of life more than vasomotor symptoms alone.

Development and application of a weighted change score to evaluate interventions for vasomotor symptoms in patients with breast cancer using regression trees: a cohort study.

PURPOSE: Vasomotor symptoms (VMS) are common among individuals with breast cancer (BC) and poorly managed symptoms are associated with reduced quality of life, treatment discontinuation, and poorer breast cancer outcomes. Direct comparisons among therapies are limited, as prior studies evaluating VMS interventions have utilized heterogeneous change measures which may not fully assess the perceived impact of change in VMS severity. METHODS: We performed a prospective study where BC patients chose one of four categories of interventions to manage VMS. Change in VMS severity at 6 weeks was assessed using the validated Hot Flush Rating Scale (HFRS). A novel weighted change score integrating baseline symptom severity and directionality of change was computed to maximize the correlation between the change score and a perceived treatment effectiveness score. Variables influencing change in VMS severity were included in a regression tree to model factors influencing the weighted change score. RESULTS: 100 baseline and follow-up questionnaires assessing VMS were completed by 88 patients. Correlations between treatment effectiveness and VMS outcomes strengthened following adjustment for baseline symptoms. Patients with low VMS severity at baseline did not perceive change in treatment effectiveness. Intervention category was predictive of change in HFRS at 6 weeks. CONCLUSION: Baseline symptom severity and the directionality of change (improvement or deterioration of symptoms) influenced the perception of clinically meaningful change in VMS severity. Future interventional studies utilizing the weighted change score should target moderate-high baseline severity patients.

Long-term safety of fezolinetant in Chinese women with vasomotor symptoms associated with menopause: the phase 3 open-label MOONLIGHT 3 clinical trial.

OBJECTIVE: We aimed to assess long-term safety and tolerability of fezolinetant, a nonhormonal neurokinin 3 receptor antagonist, among Chinese women with vasomotor symptoms associated with menopause participating in the MOONLIGHT 3 trial. METHODS: In this phase 3 open-label study, women in menopause aged 40-65 years received fezolinetant 30 mg once daily for 52 weeks. The primary endpoint was frequency and severity of treatment-emergent adverse events (TEAEs), assessed at every visit through week 52 and one follow-up visit at week 55. RESULTS: Overall, 150 women were enrolled (mean age, 54 years) and 105 completed treatment. The frequency of TEAEs was 88.7%. Most TEAEs were mild (63.3%) or moderate (22.7%). The most common TEAE was upper respiratory tract infection (16.0%), followed by dizziness, headache, and protein urine present (10.7% each). There was no clinically relevant change (mean ± standard deviation) in endometrial thickness (baseline, 2.95 ± 1.11 mm; week 52, 2.94 ± 1.18 mm). Alanine aminotransferase and/or aspartate aminotransferase levels >3 times the upper limit of normal were reported in 1.4% of women; no Hy's Law cases occurred. CONCLUSIONS: Fezolinetant 30 mg once daily was generally safe and well tolerated over a 52-week period among women in China with vasomotor symptoms associated with menopause.ClinicalTrials.gov Identifier: NCT04451226.

Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.

A descending pathway from the lateral/ventrolateral PAG to the rostroventral medulla mediating the vasomotor response evoked by social defeat stress in rats.

The stress-induced cardiovascular response is based on the defensive reaction in mammals. It has been shown that the sympathetic vasomotor pathway of acute psychological stress is indirectly mediated via neurons in the rostroventral medulla (RVM) from the hypothalamic stress center. In this study, direct projections to the RVM and distribution of neuroexcitatory marker c-Fos-expressed neurons were investigated during social defeat stress (SDS) in conscious rats. The experimental rat that was injected with a neural tracer, FluoroGold (FG) into the unilateral RVM, was exposed to the SDS. Double-positive neurons of both c-Fos and FG were locally distributed in the lateral/ventrolateral periaqueductal gray matter (l/vl PAG) in the midbrain. These results suggest that the neurons in the l/vl PAG contribute to the defensive reaction evoked by acute psychological stress, such as the SDS. During the SDS period, arterial pressure (AP) and heart rate (HR) showed sustained increases in the rat. Therefore, we performed chemical stimulation by excitatory amino acid microinjection within the l/vl PAG and measured cardiovascular response and sympathetic nerve activity in some anesthetized rats. The chemical stimulation of neurons in the l/vl PAG caused significant increases in arterial pressure and renal sympathetic nerve activity. Taken together, our results suggest that neurons in the l/vl PAG are a possible candidate for the cardiovascular descending pathway that modulates sympathetic vascular resistance evoked by acute psychological stress, like the SDS.NEW & NOTEWORTHY The sympathetic vasomotor pathway of an acute psychological stress-induced cardiovascular response is mediated via neurons in the RVM indirectly from the hypothalamus. In this study, we showed the relaying area of the efferent sympathetic vasomotor pathway from the hypothalamus to the RVM. The results suggested that the pressor response during psychological stress is mediated via neurons in the lateral/ventrolateral PAG to the RVM.

The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. METHODS: Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. RESULTS: Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84 vs. 0.68, p-value: .008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. CONCLUSIONS: High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Does everyday discrimination account for the increased risk of vasomotor symptoms in Black women?: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVES: Vasomotor symptoms (VMS), including hot flashes and night sweats, are hallmark symptoms of the menopause transition. Previous research has documented greater frequency, duration, and severity of VMS in Black women compared with women from other racial/ethnic groups, even after accounting for other factors. This analysis examined the association between discrimination and VMS and the extent to which discrimination accounts for the disproportionate burden of VMS in Black women. METHODS: Using available discrimination and VMS data from the SWAN cohort study (n = 2,377, 48% White, 32% Black, 6% Japanese, 4% Chinese, and 9% Hispanic women) followed approximately yearly in midlife from premenopause (42-52 y) through postmenopause (~20 y), we assessed concurrent associations between discrimination and VMS frequency in the past 2 weeks using weighted generalized mixed models. We also assessed associations between chronic discrimination across first four visits and VMS trajectories from premenopause to postmenopause using weighted multinomial logistic regression. Models were adjusted for known risk factors for VMS. RESULTS: Higher levels of discrimination were associated with concurrent reporting of any (odds ratio [OR], 1.57 [1.31-1.89]) and frequent (≥6 d) VMS (OR, 1.55 [1.21-1.99]). After adjustment, associations remained significant for any (OR, 1.30 [1.09-1.54]) but not frequent VMS. For any VMS trajectories, chronic discrimination was associated with "continuously high" (OR, 1.69 [1.03-2.77]) and "high pre-FMP-decline post-FMP" (OR, 1.70 [1.01-2.88]) versus "FMP-onset low" trajectories. After adjusting for discrimination, odds of reporting any, frequent, and of being in the "continuously high" any VMS trajectory remained elevated for Black versus White women. CONCLUSIONS: Discrimination is associated with greater concurrent risk of any (but not frequent) VMS, and chronic discrimination is associated with a continuously high reporting of any VMS over time, independent of known risk factors. Adjusting for discrimination attenuates but does not eliminate the increased risk of VMS for Black women.

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.