Acupuncture for hot flashes in hormone receptor-positive breast cancer: A pooled analysis of individual patient data from parallel randomized trials.

BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.

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.

Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers.

BACKGROUND: Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors. OBJECTIVE: This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers. STUDY DESIGN: Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid ß 42-to-amyloid ß 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep. RESULTS: A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid ß 42/amyloid ß 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid ß pathology. The findings remained significant after additional adjustments for estradiol and sleep. CONCLUSION: Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.

Trajectories of Blood Pressure in Midlife Women: Does Menopause Matter?

BACKGROUND: Whether changes in blood pressure (BP) over women's midlife are more driven by chronological aging or the menopause transition has been debated. We sought to determine whether women can be classified into distinct trajectory groups based on pattern and level of systolic BP (SBP), diastolic BP, pulse pressure (PP), and mean arterial pressure (MAP) over the menopause transition, and to assess whether menopause-related factors predict the group and level of BP measures. METHODS: Participants were from the SWAN (Study of Women's Health Across the Nation). Group-based trajectory modeling was used to identify women who shared distinct BP trajectories over time relative to menopause onset and to assess associations of menopause-related factors with trajectory group and level of BP measures. An accelerated rise relative to menopause onset suggests a menopause contribution. RESULTS: The study included 3302 multiracial and multiethnic women with BP measures over 17 follow-up visits (baseline age [SD]: 46.3 [2.7]). Women were classified into either low, medium, or high trajectory group in each BP measure. The low SBP, PP, and MAP trajectories (in 35%, 53%, and 28% of the cohort, respectively) were rising slowly before menopause but showed a significant accelerated rise 1 year after menopause, indicating a menopause contribution. The remaining BP trajectories were rising up until menopause and either continued with the same rise or declined after menopause. A younger menopause age predicted the low SBP, PP, and MAP trajectories. A greater follicle-stimulating hormone level predicted lower SBP and PP levels, while vasomotor symptoms occurrence predicted higher SBP, PP, and MAP levels over time. Estradiol did not predict trajectory or level of any BP measure. CONCLUSIONS: Distinct BP trajectories over the menopause transition exist that revealed a group of women whose SBP, PP, and MAP trajectories are consistent with a menopause contribution. Our findings support frequent monitoring of BP during the menopause transition.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

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.

FDA approved fezolinetant (Veozah): a critical evaluation of its efficacy and safety for menopausal vasomotor symptoms, calling for prospective research.

Women going through menopause frequently experience vasomotor symptoms such as hot flashes, night sweats, and sleep disturbances, significantly influencing their quality of life. Hormonal therapy has been demonstrated to be beneficial in treating VMS. However, due to specific restrictions, it is not recommended for every woman. Fezolinetant, a neurokinin 3 antagonist and non-hormonal treatment for severe to moderate VMS, functions by inhibiting neuronal impulses originating from the hypothalamic thermoregulatory center. Current Skylight 2 and 4 trials statistically demonstrate the safety and acceptability of fezolinetant, with relatively few adverse effects reported. Fezolinetant has been shown great potential for treating menopausal-related VMS, supporting its further advancement. However, further investigation is required to thoroughly evaluate its safety, effectiveness, and its impact on sleep patterns.

A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

Pomegranate effects on the health aspects of women during peri- and postmenopause: A systematic review and meta-analysis.

Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women's health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention's effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women.

Treating Hot Flashes with Hypnosis: Does Hypnotizability Modulate Reductions?

Hypnosis is an effective treatment option for a variety of concerns. Past research has suggested that those who score in the high range of hypnotizability initially show greater improvement than those in the low range. A post hoc analysis was conducted to examine the extent to which hypnotizability modulates the reduction of hot flash frequency. Average number of hot flashes reported during hypnosis treatment and a 12-week follow-up were grouped according to participants' level of hypnotizability. Using baseline data, the reduction percentage of hot flash frequency was plotted and visually examined to determine when a clinically significant reduction (50%) in hot flashes was reached. Our results suggested that, regardless of hypnotizability, participants ultimately obtained a 50% reduction in hot flash frequency. Interestingly, participants who were rated as either moderately or highly hypnotizable achieved a 50% reduction by Week 3 while those of low hypnotizability did not cross the 50% reduction threshold until the 12-week follow-up. Implications from these findings include the importance of assessing hypnotizability in clinical settings to better tailor treatment dose and expectations.

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.

Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study.

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45-54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.

Associations of fat mass index with hot flashes and lean mass index with insomnia in middle-aged women.

OBJECTIVE: This cross-sectional study examined the relationship between body composition and physical and mental symptom severity in middle-aged women. METHODS: The first-visit records of 554 women aged 40-64 years were examined. The fat mass index (FMI) and lean mass index (LMI) were defined as fat mass and lean mass divided by the height squared, respectively. The participants were divided into two groups according to their median values. RESULTS: The only menopausal symptom with significantly different severity between the high and low FMI groups was hot flashes (HF) on the Menopausal Health-Related Quality of Life Questionnaire. The factors associated with severe HF were investigated using multiple logistic regression analysis. After adjusting, the FMI (kg/m2) was independently positively associated with severe HF (odds ratio, 1.08; 95% confidence interval, 1.02-1.15). Insomnia was the only menopausal symptom with significantly different severity between the LMI groups (defined as Athens Insomnia Scale score ≥10 points). The factors associated with moderate-to-severe insomnia were investigated using multiple logistic regression analysis. After adjusting, the LMI (kg/m2) was independently negatively associated with moderate-to-severe insomnia (odds ratio, 0.72; 95% confidence interval, 0.55-0.94). CONCLUSIONS: The FMI was positively associated with severe HF, whereas the LMI was negatively associated with moderate-to-severe insomnia in middle-aged women.

Psychometric properties of the French Hot Flash Related Daily Interference Scale (HFRDIS).

OBJECTIVE: Hot flashes are one of the major symptoms of climacteric syndrome. Despite the high prevalence of these symptoms, few questionnaires assessing the impact of hot flashes on quality of life have been validated. The aim of this study was to validate a French version of the Hot Flash Related Daily Interference Scale (HFRDIS) in a sample of French women. METHODS: In this prospective study, data were obtained from two groups of women aged between 40 and 60 years from both women without breast cancer and women under hormone therapy for breast cancer between March 2021 and February 2022. Translation was made by an official English-French translator using the forward-backward method. RESULTS: One hundred and sixty-seven women completed the HFRDIS questionnaire. The scree plots confirmed unidimensional structure. Cronbach's α coefficient was 0.92 [0.90-0.94] similar to the original version. The intra-class correlation coefficients of each item ranged between 0.58 and 0.71 Concordance of the scores of each item with those obtained during the validation of the original version of the HFRDIS was confirmed. CONCLUSION: The validation results show that the French version of the HFRDIS questionnaire is a valid tool to evaluate the impact of hot flashes on the daily life activities of patients.

The 2023 Practitioner's Toolkit for Managing Menopause.

OBJECTIVE: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature. METHODS: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps. RESULTS: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health. CONCLUSIONS: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

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.

Optimizing sleep across the menopausal transition.

Women frequently experience sleep disturbances, particularly night-time awakenings, as they transition menopause and enter postmenopause. Sleep is essential for optimal functioning and health. Persistent and distressing sleep disturbances across menopause can negatively impact daytime functioning and productivity, and increase risk for mental and physical health conditions. While multiple factors can disturb sleep, two unique factors in the context of menopause are vasomotor symptoms and the changing reproductive hormone environment. Vasomotor symptoms are associated with sleep disturbances and contribute significantly to awakenings and amount of time spent awake during the night. Even after accounting for vasomotor and depressive symptoms, lower estradiol and higher follicle stimulating hormone levels, indicative of menopause, are associated with sleep disturbance, particularly awakenings, suggesting that the hormone environment may directly affect sleep. Management strategies for clinically significant menopausal sleep disturbances include cognitive behavioral therapy for insomnia, which is effective and durable in treating menopausal insomnia. Hormone therapy alleviates sleep disturbances, particularly in the presence of disruptive vasomotor symptoms. Sleep disturbances have a significant impact on women's functioning and health, and there is a need for further research of the underlying mechanisms to advance effective preventative and treatment strategies that ensure optimal health and well-being of midlife women.

Transient Receptor Potential Melastatin 2 Thermosensitive Neurons in the Preoptic Area Involved in Menopausal Hot Flashes in Ovariectomized Mice.

INTRODUCTION: Menopausal hot flashes are related to hypothalamic preoptic area (POA) dysfunction. Thermosensitive transient receptor potential channels (ThermoTRPs) are involved in temperature sensing and regulation of thermosensitive neurons (TSNs) in the POA. Whether ThermoTRP-TSNs in the POA, particularly the non-noxious thermoreceptor, transient receptor potential melastatin 2 (TRPM2), are involved in the occurrence of hot flashes is still unclear. METHODS: Twenty wild-type and 50 Trpm2-Cre adult female mice were randomly divided into sham (SHAM) and ovariectomy (OVX) groups. In the POA, ERα, ERß, GPR30, TRPA1, TRPM8, TRPM2, and TRPV1 expression was detected by Western blot or/and quantitative real-time polymerase chain reaction and the number of TSNs expressing TRPM2 (TRPM2-TSNs) by immunofluorescence. Before and after TRPM2-TSN activation/inhibition, back (BST) and tail skin temperature (TST) and the proportion of glutamatergic and GABAergic neurons among TRPM2-TSNs were recorded. RESULTS: Compared with SHAM, the expression of ERα, ERß, TRPM2, and TRPM8 in the POA of the OVX group decreased, with a significantly larger change range for TRPM2 than TRPM8. In addition, the number of TRPM2-TSNs showing TRPA1, TRPM8, and TRPV1 expression in the OVX group decreased, and the proportion of glutamatergic and GABAergic neurons in TRPM2-TSNs decreased and increased, respectively. Meanwhile, BST and TST increased. After activating or inhibiting TRPM2-TSNs, the proportions of glutamatergic and GABAergic neurons in TRPM2-TSNs changed, along with the BST and TST. CONCLUSION: In menopause, the abnormal quantity and function of TRPM2-TSNs in the POA is key for the development of hot flashes, characterized by an imbalance in heat dissipation and production due to the corresponding imbalance in glutamatergic and GABAergic neurons.

Vasomotor symptoms in early breast cancer-a "real world" exploration of the patient experience.

BACKGROUND: Despite the frequency of vasomotor symptoms (VMS) in patients with early breast cancer (EBC), their optimal management remains unknown. A patient survey was performed to determine perspectives on this important clinical challenge. METHODS: Patients with EBC experiencing VMS participated in an anonymous survey. Patients reported on the frequency and severity of VMS using the validated Hot Flush Rating Scale (HFRS) and ranked their most bothersome symptoms. Respondents were also asked to determine endpoints that defined effective treatment of VMS and report on the effectiveness of previously tried interventions. RESULTS: Responses were received from 373 patients, median age 56 years (range 23-83), who experienced an average of 5.0 hot flashes per day (SD 6.57). Patients reported the most bothersome symptoms to be feeling hot/sweating (155/316, 49%) and sleeping difficulties (86/316, 27%). Fifty-five percent (201/365) of patients would consider a treatment to be effective if it reduced night-time awakenings. While 68% of respondents were interested in trying interventions from their healthcare team to manage VMS, only 18% actually did so. Of the 137 patients who had tried an intervention for VMS, pharmacological treatments, exercise, and relaxation strategies were more likely to be effective, while therapies such as melatonin and black cohosh were deemed less effective. CONCLUSION: VMS are a common and bothersome problem for EBC patients, with a minority receiving interventions to manage these symptoms. Further research is needed to identify patient-centered strategies for managing these distressing symptoms.

Using machine learning to predict individual patient toxicities from cancer treatments.

PURPOSE: Machine learning (ML) is a powerful tool for interrogating datasets and learning relationships between multiple variables. We utilized a ML model to identify those early breast cancer (EBC) patients at highest risk of developing severe vasomotor symptoms (VMS). METHODS: A gradient boosted decision model utilizing cross-sectional survey data from 360 EBC patients was created. Seventeen patient- and treatment-specific variables were considered in the model. The outcome variable was based on the Hot Flush Night Sweats (HFNS) Problem Rating Score, and individual scores were dichotomized around the median to indicate individuals with high and low problem scores. Model accuracy was assessed using the area under the receiver operating curve, and conditional partial dependence plots were constructed to illustrate relationships between variables and the outcome of interest. RESULTS: The model area under the ROC curve was 0.731 (SD 0.074). The most important variables in the model were as follows: the number of hot flashes per week, age, the prescription, or use of drug interventions to manage VMS, whether patients were asked about VMS in routine follow-up visits, and the presence or absence of changes to breast cancer treatments due to VMS. A threshold of 17 hot flashes per week was identified as being more predictive of severe VMS. Patients between the ages of 49 and 63 were more likely to report severe symptoms. CONCLUSION: Machine learning is a unique tool for predicting severe VMS. The use of ML to assess other treatment-related toxicities and their management requires further study.