Frequency Of Hot Flashes Research Articles

Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause.

Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self-reported or biometrically measured HFs. Women aged 45-55 years (n = 270) participated in face-to-face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self-reported health. Linear regressions were used to examine the frequency of self-reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders. Menopausal status, childhood exposure to cold, waist-to-hip ratio (WHR), and self-reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26-6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report (β = 0.163, p = 0.010). To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs.

Effects of early midlife ovarian removal on sleep: Polysomnography-measured cortical arousal, homeostatic drive, and spindle characteristics

Bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) prior to age 48 is associated with elevated risk for both Alzheimer's disease (AD) and sleep disorders such as insomnia and sleep apnea. In early midlife, individuals with BSO show reduced hippocampal volume, function, and hippocampal-dependent verbal episodic memory performance associated with changes in sleep. It is unknown whether BSO affects fine-grained sleep measurements (sleep microarchitecture) and how these changes might relate to hippocampal-dependent memory. We recruited thirty-six early midlife participants with BSO. Seventeen of these participants were taking 17β-estradiol therapy (BSO+ET) and 19 had never taken ET (BSO). Twenty age-matched control participants with intact ovaries (AMC) were also included. Overnight at-home polysomnography recordings were collected, along with subjective sleep quality and hot flash frequency. Multivariate Partial Least Squares (PLS) analysis was used to assess how sleep varied between groups. Compared to AMC, BSO without ET was associated with significantly decreased time spent in non-rapid eye movement (NREM) stage 2 sleep as well as increased NREM stage 2 and 3 beta power, NREM stage 2 delta power, and spindle power and maximum amplitude. Increased spindle maximum amplitude was negatively correlated with verbal episodic memory performance. Decreased sleep latency, increased sleep efficiency, and increased time spent in rapid eye movement sleep were observed for BSO+ET. Findings suggest there is an association between ovarian hormone loss and sleep microarchitecture, which may contribute to poorer cognitive outcomes and be ameliorated by ET.

Clinical evaluation of the efficiency of combined phytotherapy in the postoperative period in patients with uterus cancer

As it is well known, that operative procedures which influence on ovary functions and relieve the patient of some suffering and danger from diseases, are realized by pronounced changes in hormonal self-regulation, homeostasis disturbance, deep psycho-emotional disorders, which leads to a change in the quality of life, an increased risk of long-term complications development (cardiac vascular pathology, osteoporosis, etc.).Some authors explain the changes in neurovegetative and endocrine homeostasis after hysterectomy not only by the insufficient development of collateral blood flow, but also by the removal of one of the links of the self-regulatory system – APUD – the uterine system, which causes the disorders in hypothalamic-pituitary-ovarian relationships. Menopausal symptoms with the appearance of neurovegetative, psychoemotional disorders, urological disorders, sexual dysfunction, as well as metabolic manifestations do not always provide an opportunity to assess the parameters of a woman’s health, which are combined into the concept of quality of life.The article presents the results of a study on the use of Cimicifuga racemosa for the treatment and prevention of post-hysterectomy syndrome in patients with uterine cancer in the postoperative period.The objective: to study the clinical effectiveness of the drug, which contains the estrogen receptor modulator Cimicifuga racemosa, in patients after surgical treatment for hormone-dependent uterine tumors.Materials and methods. The study included 50 uterine cancer patients after hysterectomy. 30 patients (main group) of them had rehabilitation therapy in the postoperative period (postoperative antibacterial prophylaxis, analgesic therapy, vaginal sanation) and, starting from the second month, they additionally received a herbal preparation with an extract of Cimicifuga racemosa, 1 tablet 1 time a day for 4 months.The control group included 20 women who received only rehabilitation therapy after surgery.Quality of life was assessed after 6 months of therapy based on a comprehensive assessment using the modified MENQOL scale and the study of such important indicators as energy, sleep, emotional reactions, social isolation, physical activity, and pain.All types of statistical processing were performed using the standard package «Statistica for Windows – 10».Results. The use of selective combined herbal therapy of the post-hysterectomy syndrome in patients with hormone-dependent tumors after 6 months of treatment leads to a decrease in the frequency of hot flashes by 63.3%, profuse sweating by 63.4%, sleep disturbances by 43.3%, increased fatigue by 40.0%, depressive disorders – by 36.7% and irritability – by 33.3%.Additional use of the herbal preparation with Cimicifuga racemosa extract reliably (p<0.05) reduces the manifestations of post-hysterectomy syndrome, improves the quality of life, is well tolerated and has no side effects.Conclusions. The use of selective combined herbal therapy in the postoperative period in patients with cancer of the uterine body allows to reliably improve the quality of life of patients and reduce the clinical manifestations of post-hysterectomy syndrome, which is especially relevant in patients with cancer of the uterine body, for whom replacement hormone therapy is contraindicated. Selective herbal therapy is well tolerated by patients and can be used for a long time.

Hot flashes and sleep disruption in a randomized trial in menopausal women

BackgroundHot flashes, common during menopause, affect up to 80% of Western menopausal women and are reported to contribute to sleep disturbances in midlife. Few prospective data are available to confirm the specific role of hot flashes in disrupting sleep in midlife women, however, or confirm whether changes in hot flashes in response to clinical therapies result in improvement in sleep. ObjectiveTo examine the effects of continuous nitroglycerin therapy on sleep quality in peri- and postmenopausal women with frequent hot flashes (pre-specified secondary trial endpoint), and to examine prospective associations between hot flashes and sleep disruption in this population. Study DesignSleep data were analyzed from a randomized, double-blinded, placebo-controlled trial of continuous transdermal nitroglycerin (NTG) therapy to suppress nitric oxide-mediated vasodilation in peri- or postmenopausal women with hot flashes. Participants were randomized to uninterrupted use of transdermal NTG (0.2-0.6 mg/hour) or placebo for 12 weeks. Nocturnal hot flashes awakening participants from sleep were evaluated using 7-day symptom diaries at baseline, 5 weeks, and 12 weeks. Sleep disruption (wake time after sleep onset, WASO) was assessed using validated sleep diaries, and global sleep quality was assessed by the validated Pittsburgh Sleep Quality Index (PSQI: range 0 [best] 21 [worst]) questionnaire. Mixed linear models examined changes in sleep quality and disruption, as well as the strength of associations between nocturnal hot flash frequency and sleep outcomes, over 5 and 12 weeks, adjusting for baseline values, age, race, and ethnicity. ResultsAmong the 141 participants (70 to NTG and 71 to placebo, mean age 54.6 [±3.9] years), the mean baseline hot flash frequency was 10.8 (±3.5) per day, including 2.6 (±1.7) nocturnal hot flashes awakening participants. At baseline, hot flashes were the most commonly reported reason for nocturnal awakening, with 62.6% of participants reporting waking due to hot flashes at least twice nightly. Over 5 and 12 weeks, mean frequency of nocturnal hot flashes causing awakenings decreased in both groups (NTG: -0.9 episodes/night, placebo: -1.0 episodes/night). Sleep disruption as measured by average nightly WASO also decreased (NTG: -10.1 minutes, placebo: -7.3 minutes), and mean PSQI score improved (NTG: -1.3 points, placebo: -1.2 points). No significant between-group differences in change in sleep outcomes were detected from baseline to 5 and 12 weeks, including PSQI sleep quality score as a pre-specified secondary trial endpoint (P ≥ .05 for all). Greater improvement in nocturnal hot flash frequency over 5 and 12 weeks was associated with greater improvement in PSQI sleep quality score (β= -0.30, P=.01) and sleep disruption reflected by WASO (β= -1.88, P=.02) in the combined sample. ConclusionAmong menopausal women in a randomized trial of continuous NTG therapy for hot flashes, hot flashes were the most frequently reported cause of nocturnal awakenings. Compared to placebo, continuous NTG therapy did not result in greater improvements in sleep quality from baseline to 5 and 12 weeks. Based on night-by-night symptom diaries and questionnaires, however, greater improvement in nocturnal hot flash frequency in both groups was associated with greater improvement in sleep quality and disruption.

Alliance A222001: A randomized, double-blind, placebo controlled phase II study of oxybutynin versus placebo for the treatment of hot flashes in men receiving androgen deprivation therapy.

LBA12004 Background: Hot flashes are among the most common adverse events impacting quality of life reported by patients receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. Oxybutynin is an effective therapy for reducing frequency and severity of hot flashes in women. Pilot information supports that this drug may also benefit men with hot flashes related to ADT. Methods: Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomized to receive either oral oxybutynin 2.5 mg twice a day, oxybutynin 5 mg twice a day, or matching placebo doses for 6 weeks. The primary endpoint was the change in patient-reported hot flash scores (determined by multiplying the number of hot flashes by the mean hot flash severity [grade 0: none, 1: mild, 2: moderate, 3: severe, and 4: very severe]) from baseline to 6 weeks, as measured by a daily hot flash diary. A total of 87 patients provided 76% power to reject the null hypothesis of no between-arm mean difference in hot flash score reduction from baseline to 6 weeks, when comparing each oxybutynin arm to the combined placebo arms. This was based on a two-sided contrast estimated from a generalized linear mixed model, α= 0.10, intraclass correlation of 0.50, population standardized mean difference of 0.50, and 10% missing data rate. Results: 88 patients were accrued between 10/28/21 and 12/02/23. Six patients cancelled before starting treatment and one was ineligible, leaving 81 analyzed patients with a median age of 68. Baseline characteristics were balanced between arms with patients reporting an average of 10.15 (SD = 5.55) hot flashes per day and an average daily hot flash score of 18.23 (SD = 13.48) at enrollment. On average, patients on the placebo arm, low dose oxybutynin arm, and high dose oxybutynin arm had reductions of 2.15, 4.77, and 6.89 hot flashes/day, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in hot flashes/day (p < 0.001), as did low dose oxybutynin arm patients (p = 0.02). Daily hot flash scores for the same three protocol arms reduced by an average of 4.85, 9.94, and 13.95 points, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in daily hot flash scores (p = 0.002), as did low dose oxybutynin arm patients (p = 0.07). No treatment-related grade 3+ adverse events occurred. The most commonly reported oxybutynin-related grade 2 adverse event was dry mouth. Conclusions: Oxybutynin is superior to a placebo for the management of hot flashes in men associated with androgen deprivation therapy and appears to be well tolerated. Support: UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT04600336 .

Menopausal Hot Flashes Are Not Associated with Pressor Responses to Cold Stress

Menopausal females who experience frequent hot flashes (episodes of increased body temperature and sweating) have a greater risk of hypertension and cardiovascular disease than females without hot flashes. Individuals with exaggerated blood pressure (BP) responses to cold stress have a higher risk of hypertension than those with lower responses. It is unknown if females who experience hot flashes have exaggerated pressor responses to cold stress, indicating their greater risk of hypertension. The aim of this study was to determine the pressor responses to cold stress in females who experience hot flashes and those who do not. An additional goal was to understand the relation between daily hot flash frequency and pressor responses. We hypothesized that females with hot flashes would have exaggerated pressor responses to cold stress compared to females without hot flashes. We also hypothesized that pressor responses would be positively correlated to daily hot flash frequency. We recruited 17 females, ages 45-60 years, without hypertension or cardiovascular disease, who did and did not have hot flashes. They reported hot flash frequency in a 3-day written diary. On the study day, continuous BP (finger photoplethysmography, calibrated to brachial cuff BP) and heart rate (HR; 3-lead ECG) were recorded while the participant rested during a 2-minute baseline period, then subsequently had an ice-water pack placed on their forehead for 3 minutes. The changes in mean BP (MBP) and HR are calculated as the change in MBP or HR during the cold pressor test minus the average MBP or HR during baseline. Data were analyzed using the Student’s t-test and Pearson correlation. Twelve females reported hot flashes (age: 51±4 years; average number of hot flashes: 3 per day) and five did not (age: 49±5 years). These groups did not differ in age, body mass index, resting MBP, or resting HR (p>0.05 for all). The change in MBP from baseline to the cold pressor test did not differ between females with and without hot flashes (Δ17±10 vs. Δ19±14 mmHg, respectively; p=0.860). The change in HR with the cold pressor test also did not differ between females who did and did not report hot flashes (Δ10±6 vs. Δ12±8 mmHg, respectively; p=0.647). In females with hot flashes, the number of hot flashes reported per day (range: 1-12 per day) was not correlated with the change in MBP (p=0.824) or HR (p=0.460) during the cold pressor test. These current data show that menopausal females who experience hot flashes do not exhibit exaggerated BP or HR responses to cold stress in comparison to females who do not experience hot flashes. In addition, BP and HR responses are not correlated with daily hot flash frequency. There are likely other vascular mechanisms that place menopausal females with hot flashes at an increased risk for hypertension. In addition, incorporating information on the age at which hot flashes began, as well as hot flash severity, might help us to further understand cardiovascular risk in this population. AHA 898649, NIH T32 DK07352, K01 HL148144, NCATS UL1 TR002377. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Physical Activity Influences the Relationship between Objectively Measured Hot Flashes and Endothelial Function in Perimenopausal Women

Hot flashes (HF) are disruptive symptoms experienced by approximately 80% of women undergoing menopause. The transition to menopause is associated with increases in CVD risk factors. The frequency and severity of HF have been associated with poorer cardiovascular health but most of these studies have quantified HF by self-report and have not considered physical activity (PA), known for its cardiovascular benefits. The association between HFs and CVD risk may be through their effect on endothelial health. The objective of this study was to evaluate the relationship between objectively measured HF and endothelial function and determine the effect of physical activity on the relationship in healthy perimenopausal women. We hypothesized that more HF would be associated with lower endothelial function and PA would influence this relationship. Healthy perimenopausal women (n=52, age 43-54) were included in this analysis. Perimenopause was defined as ≥7d difference in the length of consecutive cycles to <12 months of amenorrhea. Hot flashes were measured objectively using sternal skin conductance for 24 hours. The number of HF experienced and HF rate (normalized to actual wear time) were quantified. Endothelial function was assessed with measures of brachial artery flow mediated dilation (FMD, %) on the non-dominant arm. Moderate to vigorous physical activity (MVPA) was assessed with 7-days of actigraphy monitoring on the non-dominant wrist. The R package GGIR and Hildebrand (2016) cut points were used to quantify PA intensity and reported as sum of the average minutes of moderate and vigorous physical activity per day. Pearson correlations and multiple regression analyses were used to evaluate relationships between variables. Data met all assumptions for statistical tests. Modeling was performed to evaluate whether HFs were predictors of the main outcome of FMD (R version 4.2.3 and RStudio version 2023.06.2+561). Age and BMI were included in all models. Lower FMD was significantly correlated with a higher objective HF rate ( r (52) =-0.27, p=0.05). Objective HF rate predicted FMD (β=-3.91, p=0.04) when controlling for age and BMI (adj R2=0.100, F(3,48) =2.892, p=.05). When MVPA was added to the model, MVPA alone was not a significant predictor but the interaction between MVPA and HF was (β=0.12, p=0.04; adj R2=0.147, F(5,46) =2.761, p<0.03). This interaction was such that higher levels of MVPA were related to a less strongly negative relationship between objective HF rate and FMD. A simple slopes analysis found that the HF rate effect at one SD below the mean MVPA was significantly negative, (β=-8.64, p=0.004), whereas the HF rate effect at one SD above the mean MVPA was not significant, (β=0.18, p=0.95). These data provide strong evidence that support the hypothesis that a greater number of objectively-assessed hot flashes is associated with lower endothelial function in perimenopausal women and that higher amount of physical activity serves as a buffer against the negative relation between hot flashes and FMD. NIH NHLBI R15 Grant 1R15HL145650-01A1 (Witkowski); Smith College McKinley s Honors Fellowship (Tha Ra Wun); Smith College STRIDE (Buszkiewicz). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The influence of habitual physical activity and sedentary behavior on objective and subjective hot flashes at midlife.

The purpose of this study was to evaluate relationships between physical activity, sedentary time, and hot flashes during both waking and sleeping periods using concurrent objective and subjective measures of hot flashes in midlife women. Women aged 45 to 55 years (n = 196) provided self-reported data on physical activity and underwent 24 hours of hot flash monitoring using sternal skin conductance. Participants used event marking and logs to indicate when hot flashes were perceived. Wake and sleep periods were defined by actigraphy. Mean ambient temperature and humidity were recorded during the study period. Generalized linear regression modeling was used to evaluate the effect of physical activity types and sedentary time on hot flash outcomes. Isotemporal substitution modeling was used to study the effect of replacing sedentary time with activity variables on hot flash frequency. Modeled results indicated that increasing sitting by 1 hour was associated with a 7% increase in the rate of objectively measured but not subjectively reported hot flashes during sleep. Replacing 1 hour of sitting with 1 hour of vigorous activity was associated with a 100% increase in subjectively reported but not objectively measured waking hot flashes. There was little evidence for an effect of temperature or humidity on any hot flash outcome. These data provide support for relations between sedentary time, physical activity, and hot flashes and highlight the importance of using objective and subjective assessments to better understand the 24-hour hot flash experience.

Supplementation with cassis polyphenol has no effect on menopausal symptoms in healthy middle-aged women: A randomized, double-blind, parallel-group, placebo-controlled trial

Hormonal changes during the menopause transition may lead to vasomotor symptoms, including hot flashes (HFs) and neuropsychiatric symptoms such as anxiety and irritability. We hypothesized that the effects of cassis polyphenol (CaP) to improve microcirculation and vasorelaxation may alleviate menopausal symptoms. We performed a randomized, double-blind, parallel-group, placebo-controlled trial involving 59 healthy women (mean [standard deviation] age, 51.3 [4.3] years; body mass index, 20.8 [2.6] kg/m2). Participants experiencing subjective menopausal symptoms consumed CaP tablets (400 mg/d, CaP group) or placebo tablets (placebo group) for 4 weeks. Participants were evaluated using questionnaires at baseline, during the 4-week intervention period, and during a 2-week postinterventional observation period. The primary objective was to evaluate the effects of supplementation with CaP on HFs in healthy Japanese women with menopausal symptoms. Additional assessments included the modified Kupperman menopausal index, World Health Organization-5 Well-Being Index, World Health Organization quality-of-life 26-item index, State-Trait Anxiety Inventory (anxiety and trait components), and Oguri–Shirakawa–Azumi sleep inventory (middle-aged and elderly versions). During the 4-week intervention period, no significant between-group differences were detected in the HF frequency, HF score, sweating frequency, menopausal symptoms, quality of life, anxiety, or sleep. During the 2-week postintervention observational period, the HF score and sweating frequency were significantly decreased in the CaP group compared with the placebo group. These findings suggest that twice daily intake of CaP for 4 weeks does not alleviate menopause symptoms, but the improvement observed in the CaP intake group during the postintervention period warrants confirmation through further large-scale studies.

Characteristics of Users of a Digital Hypnotherapy Intervention for Hot Flashes: Retrospective Study.

Hot flashes are associated with a lower quality of life and sleep disturbances. Given the many consequences of hot flashes, it is important to find treatments to reduce them. Hypnotherapy, the use of hypnosis for a medical disorder or concern, has been shown in clinical trials to be effective in reducing hot flashes, but it is not routinely used in clinical practice. One solution to close this implementation gap is to administer hypnotherapy for hot flashes via a smartphone app. Evia is a smartphone app that delivers hypnotherapy for hot flashes. Evia has made hypnotherapy more widely accessible for women who are experiencing hot flashes; however, the app has yet to undergo empirical testing. Additionally, research on user characteristics is lacking. This study aims to (1) determine the average age, stage of menopause, and length of menopause symptoms for users of the Evia app; (2) determine the characteristics of hot flashes and night sweats for users of the Evia app; (3) determine the self-reported sleep quality of users of the Evia app; (4) determine the self-reported mental health of users of the Evia app; and (5) determine the relationship between hot flash frequency and anxiety and depression for users of the Evia app. This study analyzed data collected from participants who have downloaded the Evia app. Data were collected at 1 time point from a self-report questionnaire that assessed the demographic and clinical characteristics of users. The questionnaire was given to users when they downloaded the Evia app. Users of the Evia app fill out a questionnaire upon enrolling in the program and prior to beginning the intervention. This included 9764 users. Results showed that the mean age of users was 49.31 years. A total of 41.6% (1942/4665) of users reported experiencing 5 or more hot flashes per day, while 51.2% (1473/2877) of users reported having difficulty falling asleep each night and 47.7% (1253/2626) of users reported their sleep quality to be terrible. In addition, 38.4% (1104/2877) of users reported that they often feel anxious or depressed. There was a small, significant, and negative correlation between hot flash frequency and self-report frequency of anxiety and depression (r=-0.09). This study showed that the average age of app users is in line with the median age of natural menopause. A large percentage of users reported experiencing 5 or more hot flashes per day, reported difficulties with sleep, and reported experiencing depression and anxiety. These findings are in line with previous studies that assessed hot flash frequency and the consequences of hot flashes. This was the first study to report on the characteristics of users of the Evia app. Results will be used to optimize the hypnotherapy program delivered via the Evia app.

Effects of Viola odorata syrup on hot flashes and night sweats in menopausal women: A randomized, triple-blind, controlled trial

BackgroundHot flashes and night sweats are among the most common and disruptive symptoms in menopausal women. The present study aimed to assess the effects of Viola odorata syrup on hot flashes and night sweats in menopausal women. V. odorata contain flavonoids, saponins, mucilage, alkaloid, vitamin C, magnesium and melatonin. MethodsThis triple-blind, Randomized Controlled Trial was conducted on 84 menopausal women aged 40–65 years referring to the healthcare centers in Mashhad, Iran. Eligible menopausal women received the V. odorata syrup (5 ml) or placebo twice daily for one month. Data were collected before, during, and after the intervention using valid and reliable daily hot flash checklists. Data analysis was performed in SPSS using independent t-test, Mann-Whitney U test, Friedman test, and Chi-square at the significance level of 0.05. ResultsIn the first week (before the intervention), the intervention group (V. odorata syrup) and placebo group (control) were homogenous in terms of the frequency and intensity of hot flashes and night sweats. The Mann-Whitney U test indicated a significant difference in the duration of hot flashes between the two groups. In addition, significant differences were observed between the V. odorata syrup and placebo groups between the mean duration of hot flashes in the second (P = 0.044), third (P = 0.031), fourth (P < 0.001), and fifth weeks (P<0.001), mean frequency of hot flashes in the third, fourth, and fifth weeks (P < 0.001), and mean intensity of hot flashes in the third (P = 0.003), fourth, and fifth weeks (P < 0.001), as well as night sweats in the second week, the mean values of which were significantly lower in the V. odorata group compared to the control group. ConclusionV. odorata syrup could reduce the frequency, intensity, and duration of hot flashes since the second week of the treatment. Therefore, the use of this plant is recommended for the reduction of hot flashes and night sweats in 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.

Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence.

Feasibility of a novel wearable thermal device for management of bothersome hot flashes in patients with prostate cancer

BackgroundThis single-arm prospective study evaluated the feasibility of a novel wrist-worn thermal device that applies cooling to the inside of the wrist for management of bothersome hot flashes in prostate cancer survivors.Methods57 individuals were enrolled and instructed to use the thermal device as needed for management of hot flashes for 4 weeks. The primary outcome was thermal device usage (hours and sessions per day). Additional outcomes included the change in Hot Flash Related Daily Interference Scale (HFRDIS, range 0–10) and Patient Reported Outcomes Measurement Information System Sleep Disturbance 4a (PROMIS SD T-score, range 0–100) and Sleep-Related Impairment 8a (PROMIS SRI T-score, range 0–100). Study procedures were conducted remotely from May to Dec 2021 in the US.Results44 participants completed the study and 39 had retrievable usage data. The mean ± SD age was 67 ± 6 years and 5 ± 5 years since cancer diagnosis. The baseline mean ± SD HFRDIS score of 4.3 ± 2.0 indicated moderate hot flash interference in this population. During the study, participants used the thermal device (mean ± SD) 3.2 ± 2.5 hours/day and 7.6 ± 3.6 sessions/day. Most (67%) participants reported using the device 7 days and 7 nights each week. Statistically significant improvements from baseline at Week 4 were observed for HFRDIS (mean ± SE change: −1.1 ± 0.3), PROMIS SD (−6.0 ± 1.0), and PROMIS SRI (−5.5 ± 1.2) scores (all p < 0.001). The majority (69%) of participants reported that the thermal device was effective at helping them manage hot flashes. No adverse events were reported.ConclusionsResults support the feasibility of using the thermal device for management of bothersome hot flashes in prostate cancer survivors. Future randomized controlled studies are warranted to evaluate the impact of the thermal device on frequency and severity of hot flashes, sleep quality, fatigue, and overall quality of life.

A dietary intervention for postmenopausal hot flashes: A potential role of gut microbiome. An exploratory analysis

ObjectiveThis study examined the role of gut microbiome changes in mediating the effects of a dietary intervention on the frequency and severity of postmenopausal vasomotor symptoms MethodsPostmenopausal women (n = 84) reporting ≥2 moderate-to-severe hot flashes daily were randomly assigned, in 2 successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to stay on their usual diet. Over a 12-week period, frequency and severity of hot flashes were recorded with a mobile application. In a subset of 11 women, gut microbiome was analyzed at baseline and after 12 weeks of the dietary intervention (low-fat vegan diet with soybeans), using deep shotgun metagenomic sequencing. Differences in the microbiome between baseline and 12 weeks were assessed by comparing alpha diversity with Wilcoxon signed rank tests, beta diversity with permanovaFL, and taxon abundance with Wilcoxon signed rank tests. Pearson correlations were used to assess the association between changes in hot flashes and gut bacteria. ResultsIn the subset for which microbiome testing was done, total hot flashes decreased by 95 % during the dietary intervention (p = 0.007); severe hot flashes disappeared (from 0.6 to 0.0/day; p = 0.06); and moderate-to-severe hot flashes decreased by 96 % (p = 0.01). Daytime and nighttime hot flashes were reduced by 96 % (p = 0.01) and 94 % (p = 0.004), respectively. Alpha and beta diversity did not significantly differ in the intervention group between baseline and 12 weeks. Two families (Enterobacteriaceae and Veillonellaceae), 5 genera (Erysipelatoclostridium, Fusicatenibacter, Holdemanella, Intestinimonas, and Porphyromonas), and 6 species (Clostridium asparagiforme, Clostridium innocuum, Bacteroides thetaiotaomicron, Fusicatenibacter saccharivorans, Intestinimonas butyriciproducens, Prevotella corporis, and Streptococcus sp.) were differentially abundant, but after correction for multiple comparisons, these differences were no longer significant. Changes in the relative abundance of Porphyromonas and Prevotella corporis were associated with the reduction in severe day hot flashes both unadjusted (r = 0.61; p = 0.047; and r = 0.69; p = 0.02), respectively), and after adjustment for changes in body mass index (r = 0.63; p = 0.049; and r = 0.73; p = 0.02), respectively). Changes in relative abundance of Clostridium asparagiforme were associated with the reduction in total severe hot flashes (r = 0.69; p = 0.019) and severe night hot flashes (r = 0.82; p = 0.002) and the latter association remained significant after adjustment for changes in body mass index (r = 0.75; p = 0.01). ConclusionsThis exploratory analysis revealed potential associations between changes in vasomotor symptoms in response to a diet change and changes in the gut microbiome. Larger randomized clinical trials are needed to investigate these findings.

3 The Menopause Transition in Women with Traumatic Brain Injury

Objective:All premenopausal women who survive traumatic brain injury (TBI) will eventually experience menopause. Challenges experienced by women with TBI are superimposed on challenges associated with hormonal changes in midlife. Some women with stressful life contexts such as TBI are more vulnerable to the added burdens of the menopause transition, potentiating its effects. Although it may be argued that TBI research correctly overrepresents the male experience given disparities in injury rates (4:1), there are important differences in how females and males age, their specific health needs, and the psychosocial context of midlife. Development of evidence-based interventions begins with understanding the experience of menopause after TBI, including where and when key problems may emerge.Participants and Methods:All participants were women 40-60 years old, not taking hormones (i.e., replacement therapy or other systematic hormones), with intact ovaries. Women with TBI were &gt; 2 years post injury, whose menstrual period returned after injury, and were living in the community. Severity of injury ranged from complicated-mild to severe TBI. Pre/peri and postmenopausal status was determined by presence/absence of menstrual period in previous 6 months, respectively. Eighteen common menopause symptoms (vasomotor, somatic, psychological, and cognitive) were assessed for presence and frequency (rarely-always), along with Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance and Traumatic Brain Injury Quality of Life (TBIQOL) Anxiety, Depression, and Fatigue scales.Results:Overall, women with TBI (n = 68) showed greater presence and frequency of symptoms than women without TBI (n = 153), with fewer within-group differences by menopausal status. Among pre/peri-menopausal women, TBI and non-TBI groups did not significantly differ and showed small effect sizes on symptoms associated with changes in estrogen during menopause, including hot flashes, night sweats, bowel and bladder sequelae, and breast tenderness. However, pre/peri-menopausal women with TBI also endorsed body aches and headaches, as well as troubles with memory, focus, fatigue, cognitive concerns, sleep, and anxiety significantly more than their pre/peri-menopausal counterparts (all medium effect sizes). Among postmenopausal women, those with TBI had significantly greater frequency of hot flashes, crying spells, poor memory, worry, moodiness, panic attacks, sleep disturbance, and anxiety than women without TBI. Within TBI, only hot flashes and breast tenderness were greater in postmenopausal versus pre/peri-menopausal women. Within non-TBI, postmenopausal status was associated with significantly greater hot flashes, night sweats, restlessness, poor memory, irritability, sleep disturbance, and anxiety, with greater fatigue but not significantly.Conclusions:The findings support a model of TBI and menopause in which symptoms most closely associated with estrogen decline in pre/peri-menopause are generally similar between women with and without TBI, and symptoms that overlap with common TBI sequelae were generally more often present and frequently experienced among women with TBI versus non-TBI. We did not observe a synergistic or potentiating effect of TBI on menopause symptoms in post-menopause. These findings offer insight that contextualizes the experience of menopause symptoms among women with TBI. Such insights are essential for the development of treatment approaches that maximize health and wellbeing during the menopause transition for women with TBI.

Efficacy of keishibukuryogan for hot flashes in prostate cancer patients receiving androgen deprivation therapy: a sub-analysis focusing on hormonal and cytokine levels.

The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study. Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted. Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration. Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.

The Effect of Salvia Officinalis on Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis.

The experience of hot flashes during menopause has a negative effect on quality of life and can cause disturbance in the workplace and disrupt daily activities. Phytoestrogens in Salvia officinalis reduce menopause symptoms due to their anti-dopaminergic effects. This study was conducted to systematically review and summarize the results of clinical trials on the effect of Salvia officinalis on hot flashes in postmenopausal women. In this systematic review, databases including Pubmed, Web of Science, Cochrane library, Scopus, SID, and Magiran were searched using keywords such as menopause, hot flashes, Salvia officinalis, and herbal medicines; all possible combinations of these words were used with the Boolean operators of "OR" and "AND". To evaluate the quality of articles, we used Cochrane's Risk of bias tools. After eliminating the duplicates, a total of 148 articles were found. Following the exclusion of irrelevant articles, 4 studies with number of 310 people were examined. Among them, 3 out of 4 studies examined the effect of Salvia officinalis on the frequency of hot flashes, 3 out of 4 studies examined the severity of hot flashes, and only 1 out of 4 studies examined the effect of Salvia officinalis on the duration of hot flashes. All 4 reviewed studies indicated that the use of Salvia officinalis reduced the frequency and severity of hot flashes in postmenopausal women. Meta-analysis results showed that the effect of Salvia Officinalis on the frequency [ES=-1.12 (%95 CI:-2.37; 0.14), I2=71%] of hot flashes in postmenopausal women was significant compared to placebo, but severity [ES=-2.05 (%95 CI:-6.53; 2.43), I2=70%] was not significant. Salvia officinalis can be used to reduce the frequency of menopausal hot flashes. Expansive use of this plant can be suggested in case it is confirmed in further investigations.

Neurokinin 1/3 receptor antagonists for menopausal women: A current systematic review and insights into the investigational non-hormonal therapy.

Over 75% of menopausal women experience vasomotor symptoms (VMS), such as night sweats and hot flashes. Despite the prevalence of these symptoms, there is limited data on non-hormonal therapies to alleviate them. PubMed, Cochrane, Scopus, Ovid, Web of Science, and ClinicalTrials.Gov were searched for relevant studies. The search was performed using the following keywords, which were customized to suit the specific databases/registers: menopause, women, neurokinin 3, and/or Fezolinetant. The search was conducted until December 20, 2022. This systematic review was conducted in compliance with the PRISMA Statement 2020 guidelines. A total of 326 records were found, with 10 studies (enrolling 1993 women) selected for inclusion. The women received 40-mg doses of NK1/3 receptor antagonists twice daily, with follow-ups at 1 to 3 weeks. Moderately strong evidence was found suggesting that NK1/3 receptor antagonists can help limit the frequency and severity of hot flashes in menopausal women. While the results should be interpreted with caution until further clinical trials validate the efficacy and safety of NK1/3 receptor antagonists among menopausal women, these findings suggest that they are promising targets for future pharmacological and clinical studies in addressing vasomotor symptoms.

Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women

Due to the potential risks of long-term systemic estrogen therapy, many menopausal women are interested in nonhormonal treatments for vasomotor symptoms. Physiologic studies indicate that nitric oxide plays a key role in mediating hot flash-related vasodilation, suggesting that nonhormonal medications that induce nitrate tolerance in the vasculature may offer therapeutic benefit for vasomotor symptoms. To determine whether uninterrupted administration of transdermal nitroglycerin (NTG) to induce nitrate cross-tolerance decreased the frequency or severity of menopause-related hot flashes. This randomized, double-blinded, placebo-controlled clinical trial included perimenopausal or postmenopausal women reporting 7 or more hot flashes per day who were recruited from northern California by study personnel at a single academic center. Patients were randomized between July 2017 and December 2021, and the trial ended in April 2022 when the last randomized participant completed follow-up. Uninterrupted daily use of transdermal NTG (participant-directed dose titration from 0.2-0.6 mg/h) or identical placebo patches. Validated symptom diaries assessing changes in any hot flash frequency (primary outcome) and moderate-to-severe hot flash frequency over 5 and 12 weeks. Among the 141 randomized participants (70 NTG [49.6%], 71 placebo [50.4%]; 12 [85.8%] Asian, 16 [11.3%] Black or African American, 15 [10.6%] Hispanic or Latina, 3 [2.1%] multiracial, 1 [0.7%] Native Hawaiian or Pacific Islander, and 100 [70.9%] White or Caucasian individuals), a mean (SD) of 10.8 (3.5) hot flashes and 8.4 (3.6) moderate-to-severe hot flashes daily was reported at baseline. Sixty-five participants assigned to NTG (92.9%) and 69 assigned to placebo (97.2%) completed 12-week follow-up (P = .27). Over 5 weeks, the estimated change in any hot flash frequency associated with NTG vs placebo was -0.9 (95% CI, -2.1 to 0.3) episodes per day (P = .10), and change in moderate-to-severe hot flash frequency with NTG vs placebo was -1.1 (95% CI, -2.2 to 0) episodes per day (P = .05). At 12 weeks, treatment with NTG did not significantly decrease the frequency of any hot flashes (-0.1 episodes per day; 95% CI, -1.2 to 0.4) or moderate-to-severe hot flashes (-0.5 episodes per day; 95% CI, -1.6 to 0.7) relative to placebo. In analyses combining 5-week and 12-week data, no significant differences in change in the frequency of any hot flashes (-0.5 episodes per day; 95% CI, -1.6 to 0.6; P = .25) or moderate-to-severe hot flashes (-0.8 episodes per day; 95% CI, -1.9 to 0.2; P = .12) were detected with NTG vs placebo. At 1 week, 47 NTG (67.1%) and 4 placebo participants (5.6%) reported headache (P < .001), but only 1 participant in each group reported headache at 12 weeks. This randomized clinical trial found that continuous use of NTG did not result in sustained improvements in hot flash frequency or severity relative to placebo and was associated with more early but not persistent headache. Clinicaltrials.gov Identifier: NCT02714205.