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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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Natural menopause is associated with somatic, vasomotor, psychological, and sexual complaints that may affect women's quality of life (QOL). Aims: To determine the prevalence and severity of menopausal symptoms and their impact on QoL among Palestinian women visiting primary care centers. Methods: A cross-sectional study was conducted from November 2018 through March 2019. Convenience sampling was used to interview 380 women aged 45–60 years attending primary care centers in the West Bank city of Nablus. The Menopause Rating Scale (MRS) assessed the prevalence and severity of menopausal symptoms and QoL. Mean scores of menopausal categories were compared for different symptoms. Descriptive and analytical analyses were performed. The level of significance was set at P<0.05. Results: The age of menopausal onset (12-month absence) was 49.37 ±3 years (N = 200). The most prevalent symptoms were physical and mental exhaustion (86%), anxiety (85.5%), and irritability (85.3%). Only the prevalence of sleep problems was statistically different between the pre-, peri, and post-menopausal groups (P <0.001). The average MRS score was 18.64 ± 9.19, indicating severe symptoms and a low QoL. Conclusion: The physical and psychosocial problems experienced by Palestinian post-menopausal women negatively impacted their QoL. Therefore, all women approaching menopause should have access to supportive networks and preventive programs for a healthy transition. [ABSTRACT FROM AUTHOR]

The Thai Menopause Society is an academic organization consisting of healthcare professionals engaged in menopause medicine. The position statement was first issued in 1994 and updated in 2003 and 2023. Herein, we reviewed the important updates of the 2023 position statement on menopausal hormone therapy (MHT) as an international reference for healthcare professionals in Thailand. An advisory panel of clinicians and research experts in the field of menopause reviewed the recommendation of published International Consensus Statements and updated the evidence using the MEDLINE database through PubMed. The evidence-based information and relevant publications were assessed, and a consensus on recommendations was subsequently achieved using the level of evidence to determine the recommendation strength and evidence quality. MHT remains the most effective treatment for vasomotor symptoms and genitourinary syndromes of menopause even after 20 years. Additionally, it is effective in preventing bone loss and fractures in postmenopausal women. The cardiovascular risk of MHT increased in women who initiated MHT after 60 years of age. Hormone therapy should be individualized following the hormone type, dose, administration route, use duration, and progestogen inclusion. The necessary pretreatment evaluation and appropriate follow-up recommendations were added for improved MHT standard care. The updated 2023 Clinical Practice Guideline on MHT is useful for gynecologists, general physicians, endocrinologists, and other healthcare professionals in treating menopausal women receiving hormone therapy in Thailand. [ABSTRACT FROM AUTHOR]

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.

ObjectiveThe menopausal transition is characterized by progressive changes in ovarian function and increasing circulating levels of gonadotropins, with some women having irregular menstrual cycles well before their final menstrual period. These observations indicate a progressive breakdown of the hypothalamic-pituitary-ovarian axis often associated with an increase in menopausal symptoms. Relationships between vasomotor symptoms (VMS) and depressed mood and sleep as well as a bidirectional association between VMS and depressed mood in mid-life women have been reported, but the endocrine foundations and hormone profiles associated with these symptoms have not been well described. Our objective was to determine the relationship between daily urinary hormone profiles and daily logs of affect and VMS during the early perimenopausal transition.Study designSWAN, the Study of Women's Health Across the Nation, is a large, mutli-ethnic, multisite cohort study of 3302 women aged 42-52 at baseline, designed to examine predictors of health and disease in women as they traversed the menopause. Inclusion criteria were: an intact uterus and at least one ovary present, at least one menstrual period in the previous three months, no use of sex steroid hormones in the previous three months, and not pregnant or lactating. A subset (n = 849) of women aged 43-53 years from all study sites in the first Daily Hormone Study collection were evaluated for this substudy.Outcome measuresWe measured daily VMS, and urinary hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), pregnanediol glucuronide (PdG) and estradiol (estrone conjugate, E1C).ResultsA variable pattern of LH and negative LH feedback were the hormone patterns most strongly associated with increased VMS. In contrast, no hormone pattern was significantly related to negative mood.ConclusionFluctuations of LH associated with low progesterone production were associated with VMS but not negative mood, suggesting different endocrine patterns may be related to increased negative mood than to the occurrence of VMS.

Objective: To analyze vaginal health based on three dimensions: symptoms, information, and treatment in menopausal Peruvian women attended in first level health care facilities. Material and Methods: This is a descriptive, prospective, cross-sectional research, with the participation of women attended in first level health care facilities during the year 2021. A non-probability sample of 855 women was used. A vaginal health survey composed of 26 indicators was used through 3 dimensions: symptoms, information, and treatment, with a reliability coefficient of 0.79. Results: The mean age was 54.8±6.4 years, 67.8% had no knowledge of hormone therapy for menopause, while 80.9% said they did not use it. In the symptoms dimension: 22.6% experienced hot flashes frequently and 15.2% had vaginal symptoms (dryness, burning, and soreness), 54.9% considered them as a mild discomfort and described the symptoms as part of aging. In the information dimension: 60.4% stated that there is not enough information; 44.6% of women have access to information through their gynecologists, and 46.9% feel comfortable asking about treatment options. In the treatment dimension: 39.2% consider hormonal vaginal suppositories as an effective treatment; 23.5% did not use any treatment; and 73.8% would consider using hormone therapy during menopause. Conclusion: There was a high prevalence of vasomotor and vaginal symptoms affecting quality of life. The information given to patients was insufficient despite being provided by the gynecologist. There is acceptance for the use of local estrogen therapy. [ABSTRACT FROM AUTHOR]

Context: Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. Objective: We aimed to assess efficacy/safety of fezolinetant for treatment of moderate to severe VMS associated with menopause. Methods: In this double-blind, placebo-controlled, 12-week phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to week 4 (W4) and W12 in VMS frequency and severity. Safety was also assessed. Results: Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, –1.82 (0.46; P<.001); 45 mg, –2.55 (0.46; P<.001); W12: 30 mg, –1.86 (0.55; P<.001); 45 mg, −2.53 (0.55; P<.001). For VMS severity, W4: 30 mg, −0.15 (0.06; P<.05); 45 mg, −0.29 (0.06; P<.001); W12: 30 mg, −0.16 (0.08; P<.05); 45 mg, −0.29 (0.08; P<.001). Improvement in VMS frequency and severity was observed by W1 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. Conclusion: Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of of adding oophorectomy on patients who underwent abdominal hysterectomy in the perimenopausal period on menopause, sexual function and mental status. Materials and Methods: The study was designed prospectively. Women who underwent total abdominal hysterectomy and bilateral salpingectomy (TAH+BS) and total abdominal hysterectomy and bilateral salpingo-ophorectomy (TAH+BSO) in the perimenopausal period for benign indications were included in the study. Three months after surgery, menopausal symptoms (such as vasomotor symptoms, vaginal dryness and/or dyspareunia, memory and sleep problems) were investigated. Beck Anxiety Inventory (BAI) scores were investigated one day before the operation and three months after the operation. Results: 51 patients with TAH+BS and 55 patients with TAH+BSO included in study. Vasomotor symptoms and postoperative BAI scores were significantly higher in the oophorectomy group (p<0.001 and p=0.009, respectively). Vaginal dryness and/or dyspareunia, which adversely affect sexual function, were significantly higher in the oophorectomy group (p=0.005). Memory and sleep problems were higher in the oophorectomy group (p=0.009 and p<0.001, respectively). Postoperative BAI scores were found to be correlated with postmenopausal symptoms (vasomotor symptoms, vaginal dryness and/or dyspareunia, memory problems, sleeping disorders) in the TAH+BSO group. Conclusion: Vasomotor symptoms, vaginal dryness and/or dyspareunia, memory and sleeping problems, and anxiety levels were significantly higher in patients who underwent bilateral salpingo-ophorectomy with hysterectomy compared to patients who underwent only hysterectomy and bilateral salpingectomy. It seems useful to inform the patients who are planned for the operation regarding these effects before the decision of oophorectomy. [ABSTRACT FROM AUTHOR]

The importance of sharing experimental data in neuroscience grows with the amount and complexity of data acquired and various techniques used to obtain and process these data. However, the majority of experimental data, especially from individual studies of regular-sized laboratories never reach wider research community. A graphical user interface (GUI) engine called Neurovascular Network Explorer 2.0 (NNE 2.0) has been created as a tool for simple and low-cost sharing and exploring of vascular imaging data. NNE 2.0 interacts with a database containing optogenetically-evoked dilation/constriction time-courses of individual vessels measured in mice somatosensory cortex in vivo by 2-photon microscopy. NNE 2.0 enables selection and display of the time-courses based on different criteria (subject, branching order, cortical depth, vessel diameter, arteriolar tree) as well as simple mathematical manipulation (e.g. averaging, peak-normalization) and data export. It supports visualization of the vascular network in 3D and enables localization of the individual functional vessel diameter measurements within vascular trees. NNE 2.0, its source code, and the corresponding database are freely downloadable from UCSD Neurovascular Imaging Laboratory website1. The source code can be utilized by the users to explore the associated database or as a template for databasing and sharing their own experimental results provided the appropriate format.

Essentials Vasomotor symptoms have been proposed as markers of changing cardiovascular risk. In this cohort study, we evaluated these symptoms as markers of venous thrombosis (VT) risk. We found no evidence that vasomotor symptom presence or severity were associated with VT risk. Among these postmenopausal women, vasomotor symptoms are not a useful marker of VT risk. SUMMARY:Background Vasomotor symptoms may be markers of changes in cardiovascular risk, but it is unknown whether these symptoms are associated with the risk of venous thrombosis (VT). Objective To evaluate the association of vasomotor symptom presence and severity with incident VT risk among postmenopausal women, independent of potential explanatory variables. Methods This cohort study included participants of the Women's Health Initiative (WHI) Hormone Therapy Trials (n = 24 508) and Observational Study (n = 87 783), analyzed separately. At baseline, women reported whether hot flashes or night sweats were present and, if so, their severity. Using Cox proportional hazards models, we estimated the VT risk associated with vasomotor symptom presence and severity, adjusted for potential explanatory variables: age, body mass index, smoking status, race/ethnicity, and time-varying current hormone therapy use. Results At baseline, WHI Hormone Therapy Trial participants were aged 64 years and WHI Observational Study participants were aged 63 years, on average. In the WHI Hormone Therapy Trials over a median of 8.2 years of follow-up, 522 women experienced a VT event. In the WHI Observational Study, over 7.9 years of follow-up, 1103 women experienced a VT event. In adjusted analyses, we found no evidence of an association between vasomotor symptom presence (hazard ratio [HR]adj  0.91, 95% confidence interval [CI] 0.75-1.1 in the WHI Hormone Therapy Trials; HRadj  1.1, 95% CI 0.99-1.3 in the WHI Observational Study) or severity (HRadj for severe versus mild 0.99, 95% CI 0.53-1.9 in the WHI Hormone Therapy Trials; HRadj  1.3, 95% CI 0.89-2.0) in the WHI Observational Study) and the risk of incident VT. Conclusions Although vasomotor symptoms have been associated with the risk of other cardiovascular events in published studies, our findings do not suggest that vasomotor symptoms constitute a marker of VT risk.

Global warming has caused an increase in the frequency, duration, and intensity of summer heatwaves (HWs). Prolonged exposure to hot environments and orthostasis may cause conflicting demands of thermoregulation and blood pressure regulation on the vasomotor system, potentially contributing to cardiovascular complications and occupational heat strain. This study assessed cardiovascular and skin blood flow (SkBF) responses to orthostasis before, during and after a 3-day simulated HW. Seven male participants maintained a standard work/rest schedule for nine consecutive days split into three 3-day parts; thermoneutral pre-HW (25.4 °C), simulated HW (35.4 °C), thermoneutral post-HW. Gastrointestinal (Tgi) and skin (Tsk) temperatures, cardiovascular responses, and SkBF were monitored during 10-min supine and 10-min 60° head-up tilt (HUT). SkBF, indexed using proximal–distal skin temperature gradient (∆TskP-D), was validated using Laser-Doppler Flowmetry (LDF). The HW significantly increased heart rate, cardiac output and SkBF of the leg in supine; HUT increased SkBF of the arm and leg, and significantly affected all cardiovascular variables besides cardiac output. Significant regional differences in SkBF presented between the arm and leg in all conditions; the arm displaying vasodilation throughout, while the leg vasoconstricted in non-HW before shifting to vasodilation in the HW. Additionally, ∆TskP-D strongly correlated with LDF (r = −.78, p < 0.001). Prolonged HW exposure and orthostasis, individually, elicited significant changes in cardiovascular and SkBF variables. Additionally, varying regional blood flow responses were observed, suggesting the upper and lower vasculature receives differing vasomotor control. Combined cardiovascular alterations and shifts towards vasodilation indicate an increased challenge to industrial workers during HWs. [ABSTRACT FROM AUTHOR]

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Context: Nocturnal vasomotor symptoms (nVMS), depressive symptoms (DepSx), and female reproductive hormone changes contribute to perimenopause-associated disruption in sleep continuity. Hormonal changes underlie both nVMS and DepSx. However, their association with sleep continuity parameters resulting in perimenopause-associated sleep disruption remains unclear. Objective: We aimed to determine the association between female reproductive hormones and perimenopausal sleep discontinuity independent of nVMS and DepSx. Methods: Daily sleep and VMS diaries, and weekly serum assays of female reproductive hormones were obtained for 8 consecutive weeks in 45 perimenopausal women with mild DepSx but no primary sleep disorder. Generalized estimating equations were used to examine associations of estradiol, progesterone, and follicle stimulating hormone (FSH) with mean number of nightly awakenings, wakefulness after sleep onset (WASO) and sleep-onset latency (SOL) adjusting for nVMS and DepSx. Results: Sleep disruption was common (median 1.5 awakenings/night, WASO 24.3 and SOL 20.0 minutes). More awakenings were associated with estradiol levels in the postmenopausal range (β = 0.14; 95% CI, 0.04 to 0.24; P = 0.007), and higher FSH levels (β [1-unit increase] = 0.12; 95% CI, 0.02 to 0.22; P = 0.02), but not with progesterone (β [1-unit increase] = -0.02; 95% CI, -0.06 to 0.01; P = 0.20) in adjusted models. Female reproductive hormones were not associated with WASO or SOL. Conclusion: Associations of more awakenings with lower estradiol and higher FSH levels provide support for a perimenopause-associated sleep discontinuity condition that is linked with female reproductive hormone changes, independent of nVMS and DepSx. [ABSTRACT FROM AUTHOR]

Purpose: Menopause is associated with complications that may affect quality of life, such as hot flashes, night sweats, and mood swings. This study aimed to compare the effects of phone versus face-to-face counseling based on cognitive-behavioral therapy (CBT) for vasomotor symptoms in postmenopausal women. Methods: In this study, 40 eligible postmenopausal women were randomly assigned to face-to-face (n = 20) and phone counseling methods (n = 20). Six counseling sessions were held weekly for each person, and the women were requested to record their hot flashes (HF) and night sweats (NS) in a diary. HF and NS were measured at baseline, and 6 and 8 weeks after the completion of intervention. Data were analyzed using X2, repeated measures ANCOVA, and independent t-test. Results: Means of weekly hot flashes and night sweats decreased after intervention in both groups (face-to-face group: HF frequency from 31.92 ± 7.98 to 18.83 ± 7.35, HF severity from 2.24 ± 0.28 to 1.21 ± 0.23, HF duration from 4.22 ± 1.17 min to 2.79 ± 0.91 min, NS frequency from 2.34 ± 0.31 to 1.21 ± 0.24 and NS severity from 1.70 ± 0.34 to 1.03 ± 0.29; and also in the phone counseling group: HF frequency from 33.32 ± 7.77 to 19.53 ± 7.7, HF severity from 2.23 ± 0.24 to 1.20 ± 0.18, HF duration from 4.29 ± 1.23 min to 2.68 ± 0.95 min, NS frequency from 2.33 ± 0.31 to 1.14 ± 0.16 and NS severity from 1.59 ± 0.34 to 1.01 ± 0.30). Although the differences within each group were significant (p < 0.001), there was no significant difference between the groups after the intervention in terms of HF frequency, severity, and duration, as well as NS frequency and severity (p > 0.05). Conclusions: Face-to-face and phone counseling methods based on CBT had a similar effect on reducing hot flashes and night sweats. Both methods can be used for women with postmenopausal complications such as hot flashes and night sweats. [ABSTRACT FROM AUTHOR]

Introduction: Menopause is the last physiological menstrual period and is a complex process involving the following: endocrine, genitourinary, cardiovascular, and locomotor system, and it leads to vasomotor symptoms and psychological complaints. This study aims to investigate the influence of smoking and body mass index (BMI) as risk factors on the age of onset of menopause in women in Bosnia and Herzegovina. Material and methods: This study included 460 women in natural menopause. The study was conducted in 2 phases: interview and measurement of BMI. Each patient underwent an interview based on the questionnaire, following the verbal consent of the patient, who had previously been explained the nature of the research. Results: The age at which menopause occurs increases with the BMI increase, and it can be described by the regression equation: age = 0.096 x BMI + 45.7, which has statistical significance. The mean age of menopause occurrence in current smokers was lower (47.5 ±0.4 years) than in non-smokers (48.8 ±0.2 years) (p = 0.010). Conclusions: Our study confirmed the statistically significant correlation between smoking, BMI, and age of onset of menopause. [ABSTRACT FROM AUTHOR]

ObjectiveThe objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years.MethodsA total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling.ResultsModerate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P

Parkinson's disease (PD), and other parkinsonian syndromes are known to cause striatonigral dopaminergic system dysfunction and autonomic disturbances, including the vasomotor and sudomotor nervous systems. The detection of 123I-FP-CIT SPECT (DaT scan) imaging and autonomic dysfunction helps differentiate PD from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The sympathetic skin response (SSR) is a simple, non-invasive electrophysiological test that assesses the sympathetic sudomotor nervous system. It is reported that the SSR is impaired in patients with PD, MSA, and PSP. To study the relationship between SSR, 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and DaT scan imaging parameters in patients with PD, MSA, and PSP. The study included 62, 25, and 19 patients with PD, MSA, and PSP, respectively. The SSR, MIBG cardiac scintigraphy, and DaT scan imaging were examined. The amplitude and latency of the SSR were measured in all limbs and were compared with the results of MIBG cardiac scintigraphy and DAT scan imaging. The SSR amplitudes were lower than reported normal subjects' reference values in PD, MSA, and PSP. The SSR amplitude only correlated with MIBG cardiac scintigraphy and DaT scan imaging parameters in PD. Multiple regression analyses also showed a significant relationship between the amplitudes of SSR and DaT scan imaging in PD. Unlike MSA, and PSP, the sudomotor nervous system is parallelly involved with cardiac sympathetic and central dopaminergic dysfunction from the early stage of PD. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BackgroundVasomotor symptoms such as hot flashes and night sweats are a common concern of perimenopausal and postmenopausal women and are associated with a decreased quality of life. These symptoms can be effectively managed with hormone therapy, but safety concerns limit its use. Thus, understanding the effectiveness of nonpharmacologic therapies such as acupuncture or yoga is critical to managing these common symptoms in older women. Our review seeks to address the following question: In women with menopause-associated vasomotor symptoms, what are the effects on health-related quality of life, vasomotor symptoms, and adverse events of the following nonpharmacologic, nonherbal interventions as compared with any inactive control or active comparator: (a) acupuncture, (b) yoga, tai chi, and qigong, (c) structured exercise, and (d) meditation, mindfulness-based practices, and relaxation?MethodsWe describe a protocol for an umbrella review approach, supplemented by evaluating randomized controlled trials (RCTs) published after the most recent good-quality systematic review for each of the eligible interventions. Specific interventions were chosen based on current literature and with input from a technical expert panel and organizational stakeholders. We will conduct a thorough literature search and perform a quality assessment of potentially included systematic reviews and RCTs.DiscussionOur umbrella review, supplemented by an additional search for eligible RCTs, aims to synthesize existing evidence on the use of nonpharmacologic, nonherbal interventions to manage bothersome vasomotor symptoms in perimenopausal and postmenopausal women.Systematic review registrationPROSPERO CRD42016029335.

Tamoxifen provides a 50% reduction in the incidence of breast cancer (BC) among high-risk women, yet many do not adhere to the five-year course of therapy. Using the prospective double-blind National Surgical Adjuvant Breast and Bowel Project P-1 study, we evaluated whether participant-reported outcomes were associated with drug adherence and whether baseline behavioral risk factors modified those associations. P-1 participants were randomly assigned to placebo vs tamoxifen (20mg/day). Mixed effects logistic regression was used to evaluate whether baseline or three-month SF-36 quality of life (QOL) mental and physical component summaries (MCS, PCS), and participant-reported symptoms (gynecologic, vasomotor, sexual, and other) predicted 12-month drug adherence (76-100% of assigned medication). The evaluation accounted for age, treatment, estimated breast cancer risk, education, baseline smoking, alcohol consumption, and obesity. All statistical tests were two-sided. Participants enrolled at least three years before trial unblinding and without medically indicated discontinuation before 12 months were eligible for the present analyses (n = 10 576). At 12 months, 84.3% were adherent. Statistically significant predictors of adherence were: three-month MCS (odds ratio [OR] = 1.15 per 10 points, 95% confidence interval [CI] = 1.06 to 1.25); three-month gynecologic symptoms among moderate alcohol drinkers (OR = .79, 95% CI = 0.72 to 0.88); baseline vasomotor symptoms among participants assigned tamoxifen (OR = .88, 95% CI = 0.80 to 0.97); and three-month sexual symptoms among younger participants (OR = .89 at age 41 years, 95% CI = 0.80 to 0.99). The strongest association was with three-month other symptoms (OR = .77, 95% CI = 0.63 to 0.93). PCS was not associated with adherence. Symptom and QOL associations were not modified by smoking or obesity. Promoting QOL and managing symptoms early in therapy may be important strategies to improve adherence.

ObjectiveResearch has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function.MethodsWomen (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks.ResultsBaseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up.InterpretationHeart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms.

Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer's disease (AD) in elderly population.Objective: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population.Methods: We recruited 490 middle-aged community-based participants (30-60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter.Results: In 369 participants (median age 52 years [IQR 47-56], 48.8% men) with robust acoustic windows, the factors related to poorer MoCA scores were older age, less education extent, and the habitats of cigarette smoking or alcohol consumption. Multivariate analyses did not show a significant association between any intracranial hemodynamic parameters in both MCAs and MoCA scores in the total study population. Left MCA BHI was found to be significantly and independently correlated with the MoCA scores only in people aged 55-60 years (n = 111, B = 0.70, 95% confidence interval, 0.13-1.26, p = 0.017), however, not in people younger than 55 years.Conclusion: Our results emphasize the role of neurovascular abnormalities in the early pathophysiology of cognitive impairment and suggest cerebral vasoreactivity as the earliest detectable cognition-associated hemodynamic parameter. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Carotid artery stenosis increases cerebral ischemic event risk through changing different cerebral hemodynamic parameters. Objective: To investigate how cerebral hemodynamics in the M1 segment of middle cerebral artery change in patients with carotid artery stenosis, after motor tasks using transcranial Doppler sonography (TCD). Methods: Thirty-two healthy subjects and 30 patients with unilateral symptomatic carotid artery stenosis were recruited. The patient population was divided into three groups according to the degree of stenosis (group 1: ≥50 to 69%, group 2: 70 to 89% and group 3: ≥90 to 99%). TCD was used to measure the pulsatility index (PI) and cerebral vasomotor reactivity (CVR). Results: In the patient group, significant differences for symptomatic side PI values (p=0.01) and mean CVR increases (p=0.05) were observed, compared with the healthy controls. However, the difference was not statistically significant for asymptomatic side PI values and mean CVR increases. The results from the intergroup comparison showed significantly higher percentages of symptomatic and asymptomatic side CVR increases in group 1, compared with groups 2 and 3 (p=0.001 and p=0.002, respectively). Conclusions: Our study showed that cerebral autoregulation and hemodynamic mechanisms are impaired in patients with carotid artery stenosis. Furthermore, the impairment of PI and CVR tends to get worse with increasing degrees of stenosis. In addition, this study demonstrated that assessment of these two hemodynamic parameters in clinical practice might be helpful for monitoring the progress of carotid artery stenosis.

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.

ObjectiveTo describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials.MethodsAn analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time.ResultsThe 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements.ConclusionThese analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), and NCT01418209 (MsFLASH 03).

ContextVasomotor symptoms (VMS) are common. Whether VMS are associated with fracture incidence or bone mineral density (BMD) levels is unknown.ObjectiveThis study aimed to examine associations of baseline VMS with fracture incidence and BMD.DesignThis was a prospective observational study with mean (SD) followup of 8.2 (1.7) years (1993-2005).SettingForty United States clinical centers.ParticipantsWe examined data from Women's Health Initiative Clinical Trial participants (n = 23 573) age 50-79 years not using menopausal hormone therapy, and 4,867 participants of the BMD sub-study.InterventionsNone.Main outcome measuresWe measured baseline VMS, incident adjudicated fractures, and BMD (baseline, annual visits 1, 3, 6, and 9).ResultsAfter adjustment for baseline age, body mass index, race/ethnicity, smoking, and education, the hazard ratio for hip fracture among women with baseline moderate/severe VMS (vs no VMS) was 1.78 (95% confidence interval [CI], 1.20-2.64; P = .01). There was no association between VMS and vertebral fracture. VMS severity was inversely associated with BMD during followup (P = .004 for femoral neck, P = .045 for lumbar spine). In repeated measures models, compared with women who reported no VMS, women with moderate/severe VMS had 0.015 g/cm(2) lower femoral neck BMD (95% CI, -0.025--0.005) and 0.016 g/cm(2) lower lumbar spine BMD (95% CI, -0.032--0.004).ConclusionsWomen with moderate/severe VMS have lower BMD and increased hip fracture rates. Elucidation of the biological mechanisms underlying these associations may inform the design of preventive strategies for at-risk women prior to occurrence of fracture.

Objective: To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17β-estradiol/progesterone (17β-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus. Data Sources: Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva. Study Selection and Data Extraction: All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included. Data Synthesis: In 1 phase 3 clinical study, 17β-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population. Relevance to Patient Care and Practice: Concerns over content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration–regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17β-E/P is approved for the treatment of VMS associated with menopause. Conclusions: 17β-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms. [ABSTRACT FROM AUTHOR]

Bayer has announced positive results from two phase 3 clinical trials for elinzanetant, a novel treatment for menopausal vasomotor symptoms (VMS). The trials showed statistically significant reductions in the frequency and severity of VMS, as well as improvements in sleep disturbance and quality of life. Elinzanetant is the first dual antagonist targeting both NK-1 and NK-3 receptors and is administered orally once daily. The results are promising for women experiencing moderate to severe hot flashes, providing a potential nonhormonal solution for their symptoms. [Extracted from the article]

BackgroundSignificant alterations in autonomic nervous system (ANS) function, vasomotor reactivity, and cerebral blood flow may develop from damage to brain ANS regulatory areas in heart failure (HF). This preferentially right-sided injury occurs largely in autonomic structures perfused by the middle cerebral artery. Indications of altered, asymmetrical perfusion raise the potential for further neural damage.ObjectiveTo determine whether the extent of middle cerebral artery blood flow velocity and vasomotor reactivity is altered on one side of the brain over the other in HF versus control subjects, three ANS challenges were administered-each challenge recruited ANS regulatory areas potentially injured in HF.MethodsTranscranial Doppler ultrasonography was used to measure cerebral blood flow velocity and vasomotor reactivity in 40 HF (mean age = 52.7 years, SD = 7.5; 27 men; left ventricular ejection fraction = 26.8, SD = 8.3) and 42 control subjects (mean age = 48.3 years, SD = 6.0; 22 men) during 5% CO2 and hyperventilation, Valsalva, and orthostatic (upper body tilt) challenges.ResultsLower cerebral blood flow velocity and abnormal vasomotor reactivity (p < .01) were noted in HF middle cerebral arteries during all challenges. More right-sided flow velocity reductions appeared in HF, with laterality differences noted during CO2 and orthostatic (p < .05), but not Valsalva challenges.DiscussionDiminished cerebral blood flow velocity and altered vasomotor reactivity were associated with HF, changes being preferentially on the right side; the asymmetry was more pronounced during CO2 and orthostatic challenges. The impaired blood flow regulation may contribute to the lateralized brain pathology in ANS areas, undermining autonomic control in HF.

Purpose: We evaluated the impact of menopause-associated vasomotor symptoms (VMS) on sleep. We also sought to establish the content validity of Patient-Reported Outcomes Measurement Information System (PROMIS) short form Sleep-Related Impairment and Sleep Disturbance measures in postmenopausal women with moderate to severe VMS. Methods: Cross-sectional, in-person, qualitative interviews were conducted in the United States (Texas, Illinois) and European Union (UK, France) with women aged 40–64 years experiencing moderate to severe VMS (≥35/wk). Main outcomes were impact of VMS on sleep based on concept elicitation and content validity of PROMIS Sleep-Related Impairment and Sleep Disturbance short forms via cognitive debriefing. Results: Thirty-two women (US: n = 16; EU: n = 16) participated. A majority (US: 93.8%; EU: 93.8%) said VMS affected sleep; specifically, they had sleep interrupted by sweating or overheating and had difficulty returning to sleep. Sleep disturbance was the most bothersome aspect of VMS (US: 75%; EU: 50%). VMS-associated sleep disturbance affected next-day work productivity, mood, relationships, daily activities, concentration, social activities, and physical health. Participants found both PROMIS sleep measures relevant and easy to answer; the Sleep Disturbance measure was considered the most relevant. Participants had no difficulty remembering their experiences over the 7-day recall period and found the response options to be distinct. Conclusion: VMS associated with menopause significantly interferes with sleep and next-day functioning (e.g., work productivity), supporting assessment of sleep outcomes in studies evaluating treatment of VMS. Women with moderate to severe VMS found that the PROMIS Sleep-Related Impairment and Sleep Disturbance short forms assessed constructs important to understanding sleep in the context of menopause-associated VMS. [ABSTRACT FROM AUTHOR]

The association between vasomotor tone of the peripheral arteries and cerebral hemisphere function has not been established. This study analyzed the peripheral vasoreactivity of patients with acute ischemic stroke and hemiplegia using a modified Raynaud scan, which is a new technology for blood flow measurement. In this retrospective case–control study, we examined patients with unilateral weakness consistent with ischemic lesions who underwent brain magnetic resonance imaging and modified Raynaud scanning within five days from the onset of symptoms. The modified Raynaud scan was used to quantify the radioactivity of the bilateral fingertips during rest and cooling-heating thermal stress conditions and estimate vasoreactivity based on the change in the blood amount per time under rest-thermal stress. The subjects were classified into the preserved and impaired groups based on their degrees of vasomotor reaction. Based on the modified Raynaud scanning, 37 (mean age = 69.1 ± 10.6) and 32 (mean age = 62.6 ± 11.8) subjects were allocated to the preserved and impaired groups, respectively. Binary logistic regression showed that the affected limb edema (odds ratio (OR) 6.15; confidence interval (CI) 1.40–26.97; p = 0.016) and anterior circulation (OR 3.68; CI 1.01–13.48; p = 0.049) were associated with impaired vasoreactivity. The modified Raynaud scans confirmed that central lesions in the anterior circulation with hemiparesis may influence the vasoreactivity of edematous peripheral arteries. These results may inform treatment and rehabilitation for stroke patients with hemiparesis. [ABSTRACT FROM AUTHOR]

Moderate-intensity endurance exercise training improves vascular endothelial vasomotor function; however, the impact of high-intensity exercise training has been equivocal. Thus, the effect of the physiological stress of the exercise remains poorly understood. Furthermore, enhanced vascular repair mediated by circulating progenitor cells may also be improved. To address whether the physiological stress of exercise training is an important factor contributing to these adaptations, 20 healthy participants trained for 6 weeks. Training involved either moderate (MSIT; n = 9) or heavy metabolic stress (HSIT; n = 11) interval exercise training programmes matched for total work and duration of exercise. Before and after training, flow-mediated dilatation, low-flow-mediated constriction and total vessel reactivity were measured at the brachial artery using Doppler ultrasound. Circulating progenitor cells (CD34(+), CD133(+) and CD309/KDR(+)) were measured by flow cytometry (means ± SD). Relative (MSIT pre- 5.5 ± 3.4 versus post-training 6.6 ± 2.5%; HSIT pre- 6.6 ± 4.1 versus post-training 7.0 ± 3.4%, P = 0.33) and normalized (P = 0.16) flow-mediated dilatation did not increase with either training programme. However, low-flow-mediated constriction was greater after training in both groups (MSIT pre- -0.5 ± 3.2 versus post-training -1.9 ± 3.1%; HSIT pre- -1.0 ± 1.7 versus post-training -2.9 ± 3.0%, P = 0.04) and contributed to greater total vessel reactivity (MSIT pre- 7.4 ± 3.3 versus post-training 10.1 ± 3.7%; HSIT pre- 10.9 ± 5.9 versus post-training 12.7 ± 6.2%, P = 0.01). Peak reactive hyperaemia and the area under the shear rate curve were not different between groups, either before or after training. Although circulating progenitor cell numbers increased following heavy-intensity interval exercise training, variability was great amongst participants [MSIT pre- 16 ± 18 versus post-training 14 ± 12 cells (ml whole blood)(-1); HSIT pre- 8 ± 6 versus post-training 19 ± 23 cells (ml whole blood)(-1), P = 0.50]. Overall, vasoconstrictor function may be augmented by moderate- and heavy-intensity interval exercise training in young adults. However, circulating progenitor cell numbers were not increased, suggesting that these cells are not likely to be upregulated as a result of training.

The article is devoted to the problem of studying blood microcirculation in healthy individuals at different stages of ontogenesis. The aim of the study was to investigate the peculiarities of the skin blood flow in students aged 17-21. Materials and ways of the research. In order to study the functional state of blood microcirculation the method of laser Doppler flowmetry (LDF) was used. Results. Determination of the age dynamics of the tissue blood flow in subjects aged 17-21 years showed that the parameter of microcirculation in the subjects increased from minimal values at 17 years to maximal values at 21 years. In the female subjects, the value of the microcirculation parameter was higher at 17 years than in the male subjects, while the maximum perfusion value for girls was at 19 years and at 20 years in the male subjects. Assessment of the regulatory devices showed that the amplitude value of low-frequency oscillations in females fell at the age of 19 years and in males at 20 years. The maximal amplitude index of vasomotor oscillations was registered at the age of 19 years both for boys and girls. The amplitude of vasomotor oscillations in the high-frequency range varied in both girls and boys. Three types of LDF-grams were identified among the young adolescents: aperiodic LDF-grams, which correspond to normoemic type of microcirculation, monotonous low amplitude LDF-grams, which correspond to hypooemic type of microcirculation, sinusoidal LDF-grams, which correspond to hyperemic type of microcirculation. Conclusions. As many studies have shown, the heterochronicity of values of blood microcirculation indices is preserved in male and female subjects: in one age section the indices are higher in females, in the other one -- in adolescents. This fact reflects the general biological regularity of different maturation of male and female organisms [ABSTRACT FROM AUTHOR]

For patients with apical compartment pelvic organ prolapse (POP), abdominal sacrocolpopexy has been considered superior to the vaginal approach in terms of less dyspareunia and decreased risk of recurrence. Robot-assisted sacrocolpopexy (RSC) can help overcome difficulties in laparoscopic sacrocolpopexy (LSC) by facilitating deep dissection and suturing. Moreover, RSC is a safe and efficacious option for patients with POP. It has several benefits, such as its high anatomical cure rate, improvement of sexual function, reduction of perioperative complications, and low recurrence rate. In addition, it can be a safe option for elderly patients. RSC has a steep learning curve and numerous other reported advantages compared with LSC; however, insufficient data conclude that the former is universally superior, especially in cost effectiveness. Thus, further studies are needed to support the widespread adoption of robot-assisted surgery for pelvic floor reconstruction. [ABSTRACT FROM AUTHOR]

Vasomotor symptoms (VMS), such as hot flashes and night sweating, are classic menopausal symptoms experienced by a majority of perimenopausal and postmenopausal women. VMS have received a great deal of attention due to their relationship with cardiometabolic risk. Further, accumulating evidence indicates that VMS are associated with an increased risk of several chronic diseases, including metabolic syndrome, type 2 diabetes mellitus, nonalcoholic fatty liver diseases, and osteoporosis in perimenopausal and postmenopausal women. These findings suggest VMS as biomarkers of impaired cardiometabolic conditions rather than just temporary symptoms in menopausal women, warranting further studies to confirm the casual relationship of VMS with these diseases and the exact underlying mechanism in this context. [ABSTRACT FROM AUTHOR]

The complex ergot alkaloids, ergovaline and ergotamine, cause dysregulation of physiological functions, characterised by vasoconstriction as well as thermoregulatory and cardiovascular effects in grazing livestock. To assess the effect of the mycotoxins, blood pressure and heart rate of male mice were measured, and metabolite profiling undertaken to determine relative abundances of both ergotamine and its metabolic products in body and brain tissue. Ergotamine showed similar cardiovascular effects to ergovaline, causing elevations in blood pressure and reduced heart rate. Bradycardia was preserved at low-levels of ergovaline despite no changes in blood pressure. Ergotamine was identified in kidney, liver and brainstem but not in other regions of the brain, which indicates region-specific effects of the toxin. The structural configuration of two biotransformation products of ergotamine were determined and identified in the liver and kidney, but not the brain. Thus, the dysregulation in respiratory, thermoregulatory, cardiac and vasomotor function, evoked by ergot alkaloids in animals observed in various studies, could be partially explained by dysfunction in the autonomic nervous system, located in the brainstem. [ABSTRACT FROM AUTHOR]

Introduction: The cutaneous form of decompression sickness (DCS) known as cutis marmorata is a frequent clinical presentation. Beyond a general acceptance that bubbles formed from dissolved inert gas are the primary vector of injury, there has been debate about pathophysiology. Hypotheses include: 1) local formation of bubbles in the skin or its blood vessels; 2) arterialisation of venous bubbles across a right to left shunt (RLS) with local amplification in bubble size after reaching supersaturated skin via the arterial circulation; and 3) passage of arterialised venous bubbles to the cerebral circulation with stimulation of a sympathetically mediated vasomotor response. Methods: Four divers exhibiting cutis marmorata had the underlying tissue examined with ultrasound 4–5.5 hours after appearance of the rash. All subsequently underwent transthoracic echocardiography with bubble contrast to check for a RLS. Results: In all cases numerous small bubbles were seen moving within the skin microvasculature. No bubbles were seen in adjacent areas of normal skin. All four divers had a large RLS. Conclusion: This is the first report of bubbles in skin affected by cutis marmorata after diving. The finding is most compatible with pathophysiological hypotheses one and two above. The use of ultrasound will facilitate further study of this form of DCS. [ABSTRACT FROM AUTHOR]

End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. Other two sets of data were obtained during vasomotor increase by phenylephrine (PHE) infusion in BL and BW. We estimated the change of stroke volume (∆SVEEOT) and aortic flow (∆AoFEEOT) during the EEOT. PPV and SVV were obtained by the variation of beat-to-beat PP and SV, respectively. Baseline PPV, SVV, ∆SVEEOT, and ∆AoFEEOT increased significantly after BW, with a decrease of aortic flow (P < 0.05). PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase. [ABSTRACT FROM AUTHOR]

Introduction. Transcranial Doppler is the only non-invasive neuroimaging modality in the diagnosis and monitoring of various neurovascular diseases. Apart from assessing cerebral hemodynamics of blood flow in the basal brain arteries, transcranial Doppler provides physiological data and anatomical images. Quantification analysis of vasomotor reactivity. Various transcranial Doppler methods evaluate cerebral vasomotor reactivity, providing important information on the properties of arterioles under induced hemodynamic conditions. Exogenous and endogenous vasoactive stimuli of different potency (apnea, acetazolamide, carbon dioxide, L-arginine) are most commonly used, making transcranial Doppler a prognostic indicator of future ischemic events. This article reviews principles of various transcranial Doppler methods in the evaluation of vasomotor reactivity, emphasizing their advantages and disadvantages. Transcranial Doppler in the field of reduced vasomotor reactivity. Evaluation of vasomotor reactivity has a role in the prediction of future ischemic events, evaluation of revascularization effect after carotid endarterectomy, but also in the increasingly significant choice of the right time to perform it. In recent years, transcranial Doppler methods have found application in other areas of dysfunctional cerebral hemodynamics: dementia, hypertension, migraines, and sepsis. Conclusion. Due to an excellent temporal resolution, non-invasive approach, good cost-benefit ratio, bedside monitoring, relative simplicity in terms of interpretation and performance, and portability, transcranial Doppler in vasomotor reactivity may be the ideal tool in the evaluation of cerebral hemodynamics, arterial perfusion integrity and collateral capacity. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to obtain information about reactivity differences in ophthalmic artery (OA) and middle cerebral artery (MCA) presented as a change in blood flow velocity (BFV) induced by the breath holding in healthy individuals. Methods: Cerebral vasomotor reactivity (VMR) is interpreted indirectly with the increase in the BFV detected in the basal arteries, secondary to a vasodilatory stimulus as breath holding. Bilateral MCA and OA were evaluated by using transcranial Doppler ultrasonography in 15 volunteers. Results: The basal velocities obtained from MCAs and from bilateral OA were symmetrical and did not change according to the side (p>0.05). The ratio of MCA to OA flow velocities had no significant difference between the sides (p>0.05). The OA flow velocities were significantly lower than the ipsilateral MCA flow velocities. Breath-holding index (BHI) was used to evaluate the VMR. Although the BHI values were not symmetrical and statistically different between the sides (p>0.05), the difference between the ipsilateral MCA BHI and OA BHI was significant (p<0.05). We determined the ratio of MCA VMR to OA artery VMR as 1.47±0.15. Conclusion: We found out that the VMR measurement with the BHI method could be used in the OA and VMR in the OA was decreased compared to the MCA on the same side. Future studies on OA VMR in patients with different degrees of carotid stenosis and determination of changes in the OA VMR as a result of angioplasty or stenting will provide valuable information. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT).DesignThis was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared.ResultsThe five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point.ConclusionBlack cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.

ObjectiveTo evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT).DesignThis was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared.ResultsThe five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P < 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P < 0.001). Among postmenopausal women, HT significantly decreased follicle-stimulating hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point.ConclusionBlack cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.

According to a press release from Bayer, the phase III study OASIS 3 has shown that elinzanetant, a novel oral medication, significantly reduces the frequency of moderate-to-severe vasomotor symptoms (VMS) in menopausal women compared to a placebo. The long-term safety profile of elinzanetant was consistent with previous studies, and the results support its potential as a non-hormonal solution for menopause-related symptoms. Elinzanetant modulates estrogen-sensitive neurons and may also help with sleep disturbance. Bayer plans to present the results from all three studies at upcoming medical conferences and seek marketing authorization. [Extracted from the article]