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Objectives: To compare menopausal symptoms of breast cancer survivors on adjuvant endocrine therapy with those of menopausal women., Study Design: In a retrospective nested case-control study menopausal symptoms were compared of breast cancer survivors in pre-, peri- or post-menopause at the time of diagnosis, on tamoxifen or an aromatase inhibitor, plus a gonadotrophin-releasing hormone analogue, if pre- or peri-menopausal, and age-matched control women either in the late peri-menopause, or in surgical or in physiological post-menopause on no hormone replacement therapy. Differences between women on tamoxifen and those on aromatase inhibitors were also evaluated. Weighted and non-weighted t-tests, chi-square tests, and linear or logistic regressions were applied as appropriate., Main Outcome Measures: Score on the Greene's Climacteric Scale and so of its subscales evaluating vasomotor, anxiety, depression, somatisation and sexuality symptoms., Results: A total of 99 breast cancer survivors (45 on tamoxifen, 54 on aromatase inhibitors) and 554 controls (173 in late perimenopause, 353 in natural and 28 in surgical menopause) were enrolled. The score on the Greene's Climacteric Scale was similar in cases and controls (means ± standard deviation) (21.3 ± 10.4 vs. 22.8 ± 11.5, p = 0.199), as were the subscale scores for vasomotor symptoms, anxiety, and somatisation. The depression score was lower (4.63 ± 3.3 vs. 5.98 ± 3.8; p = 0.001) in breast cancer survivors on adjuvant endocrine therapy, mainly due to a lower score of -2.132 (95 % confidence interval - 3.858/-0.407; p = 0.016) for users of aromatase inhibitors. The sexuality score was higher (1.76 ± 1.1 vs. 1.50 ± 1.1, p = 0.011) than in controls. Differences remained significant when corrected for age, menarche, body mass index, menopausal status (peri- or post-), type of menopause (natural, surgical), use of gonadotrophin-releasing hormone analogues, years of amenorrhea, smoking, alcohol use, and for breast radiotherapy, chemotherapy, tamoxifen or aromatase inhibitors. Among breast cancer survivors, women on aromatase inhibitors had lower scores for anxiety (5.75 ± 2.5vs.5.75 ± 2.5; p = 0.045) and depression (3.89 ± 2.5 vs. 5.13 ± 3.6; p = 0.046) than women on tamoxifen., Conclusions: In breast cancer survivors, adjuvant therapy induces symptoms similar in type and intensity to those of symptomatic menopausal women. Compared with menopausal women, breast cancer survivors, particularly those on aromatase inhibitors, appear to experience less severe depressive symptoms., Competing Interests: Declaration of competing interest M. Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Gilead; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead all outside the submitted work. Prof. Lucia L. Del Mastro reports advisory role and/or speaker honoraria for Roche, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Eisai, Gilead, Astrazeneca, Daiichi Sankyio, Gilead, Exact sciences, Agendia, Menarini Stemline, Olema, Ipsen, MSD; travel grants from Gilead, daiichi Sankyo, Astrazeneca, Roche; research funding (to the institution) from Pfizer, all outside the submitted work. The other authors declare no conflict of interest with the content of the present article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Obesity is not a choice or a result of lack of willpower, but a multifactorial, chronic, progressive, and relapsing disease. During menopause, hormonal and body composition changes lead to greater visceral adiposity, that aggravates women's health at a cardiometabolic, mechanic and mental level. Adiposity has been identified as an important modifier of reproductive hormones. During female midlife, obesity has been associated with menstrual cycle alterations (anovulatory cycles ending with abnormal bleedings), menopausal symptoms including hot flashes, poor quality of sleep, aches and joint pain, genitourinary symptoms, and reduced quality of life. However, the relationships between weight, the menopausal process, aging, and hormone levels remain poorly understood. Women with obesity have an increased risk of thromboembolic disease when using menopause hormone therapy (MHT), and it is probably the main medical condition to prescribe or not MHT. However, this risk depends on the route and type of MHT. The use of estrogen-only or combined transdermal MHT does not increase the risk of a thrombotic event in women with obesity.

Background: This 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., Methods: 57 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., Results: 44 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., Conclusions: Results 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., (© 2023. The Author(s).)

These guidelines have been developed jointly by the British Gynaecological Cancer Society and British Menopause Society to provide information for all healthcare professionals managing women treated for gynaecological cancer. Menopausal symptoms can have a significant impact on quality of life for women. Cancer therapies, including surgery, pelvic radiotherapy, chemotherapy and endocrine therapy, can all affect ovarian function. The benefits and risks of using hormone replacement therapy are considered by cancer type with guidance on the type of HRT and optimal time of commencement after cancer treatment. Vaginal estrogens can be very effective for improving urogenital symptoms and are safe for the majority of women, including those for whom systemic HRT is contraindicated with rare exceptions. Alternative options to HRT are reviewed including pharmacological and non-pharmacological approaches., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RM: Grants from GSK, NHS England, Yorkshire Cancer Research, Barts Charity, Rosetrees Trust outside the submitted work, and honoraria for advisory board membership from Astrazeneca/MSD/GSK/EGL. RM was clinical lead/topic advisor for NICE Guideline NG241 Ovarian cancer: identifying and managing familial and genetic risk.SG-M: membership of NICE HRT guidelines committee.TH: Consultancy and lecture fees from Astellas. JS: Funding for conference attendance, speaking and advisory board funding from Bayer, Astellas, Gedeon Richter and Theramex.

Objective: 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., Methods: 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., Results: 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)., Conclusion: 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., (© 2024 Wiley Periodicals LLC.)

Purpose: Vasomotor symptoms (VMS) are common among individuals with breast cancer (BC) and poorly managed symptoms are associated with reduced quality of life, treatment discontinuation, and poorer breast cancer outcomes. Direct comparisons among therapies are limited, as prior studies evaluating VMS interventions have utilized heterogeneous change measures which may not fully assess the perceived impact of change in VMS severity., Methods: We performed a prospective study where BC patients chose one of four categories of interventions to manage VMS. Change in VMS severity at 6 weeks was assessed using the validated Hot Flush Rating Scale (HFRS). A novel weighted change score integrating baseline symptom severity and directionality of change was computed to maximize the correlation between the change score and a perceived treatment effectiveness score. Variables influencing change in VMS severity were included in a regression tree to model factors influencing the weighted change score., Results: 100 baseline and follow-up questionnaires assessing VMS were completed by 88 patients. Correlations between treatment effectiveness and VMS outcomes strengthened following adjustment for baseline symptoms. Patients with low VMS severity at baseline did not perceive change in treatment effectiveness. Intervention category was predictive of change in HFRS at 6 weeks., Conclusion: Baseline symptom severity and the directionality of change (improvement or deterioration of symptoms) influenced the perception of clinically meaningful change in VMS severity. Future interventional studies utilizing the weighted change score should target moderate-high baseline severity patients., (© 2024. The Author(s).)

Background: Electronic patient-reported outcomes (ePRO) monitoring is a useful communication tool for cancer patients and healthcare providers. In this study, we examined the impact of symptom monitoring using an ePRO app on quality of life (QoL) in postmenopausal breast cancer patients receiving adjuvant endocrine therapy., Methods: The free app "Welby My Carte ONC" was used in the study. Patients with breast cancer starting adjuvant endocrine therapy were randomly assigned in a 1:1 ratio to ePRO monitoring (ONC) and control groups. The ONC group reported five symptoms extracted from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) (insomnia, joint pain, headache, anxiety, and hot flashes) weekly for 3 months through the app. Reported symptoms were shared with medical personnel. When serious symptoms were reported, these personnel ascertained the patient's health status and provided advice over the phone. The primary endpoint was QoL measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 3 months from enrollment. Differences between groups were tested using analysis of covariance., Results: The study included 125 subjects with mean age of 64 years in the ONC group (n = 61) and 63 years in the control group (n = 64). In the ONC group, the response rate to PRO-CTCAE was about 70% or higher until week 10. The item missing rate was 0. The ONC group reported more symptoms related to joint pain and insomnia. The difference in FACT-B total score between the groups was - 1.55 (95% confidence interval: - 5.91, 2.81), indicating no significant difference., Conclusions: Symptom monitoring using ePRO early after initiation of adjuvant endocrine therapy after surgery did not improve QoL of breast cancer patients., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

SPORT AND MENOPAUSE. The menopause is a physiological period in a woman's life that can be marked by a lot of symptoms impacting her quality of life. The most frequent complaints are hot flushes, mood, sleep and memory disorders. The risk of osteoporosis, loss of muscular strength, cardiovascular and metabolic risk increases more as there is a reduction in physical activity and an increase in sedentary time during this period. Recommendations for physical activity and sport help to limit the symptoms and health risks, induced by hypoestrogenism during this period of a woman's life. It is the combination of regular physical activity, at least moderate in endurance and muscular strengthening, that provides the greatest benefits, and women should be made aware of this., Competing Interests: L’auteure déclare n’avoir aucun lien d’intérêts.

Objective: This study aimed to determine how women felt cold water swimming affected their menstrual and perimenopausal symptoms., Study Design: An online survey that asked women who regularly swim in cold water about their experiences. The survey was advertised for 2 months on social media. Questions related to cold water swimming habits and menstrual and perimenopausal symptoms were analysed., Main Outcome Measures: Quantitative and qualitative data including; frequency of menstrual and menopause symptoms, the effect of cold water swimming on these symptoms., Results: 1114 women completed the survey. Women reported that cold water swimming reduced their menstrual symptoms, notably psychological symptoms such as anxiety (46.7%), mood swings (37.7%) and irritability (37.6%). Perimenopausal women reported a significant improvement in anxiety (46.9%), mood swings (34.5%), low mood (31.1%) and hot flushes (30.3%). The majority of women with symptoms swam specifically to reduce these symptoms (56.4% for period and 63.3% for perimenopause symptoms). Women said they felt it was the physical and mental effects of the cold water that helped their symptoms. For the free text question, five themes were identified: the calming and mood-boosting effect of the water, companionship and community, period improvements, an improvement in hot flushes and an overall health improvement., Conclusion: Women felt that cold water swimming had a positive overall effect on menstrual and perimenopause symptoms. Studies on other forms of exercise to relieve menstrual and perimenopause symptoms may show similar findings., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Joyce Harper gives paid talks on menopause to employers and conferences.

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

Vasomotor symptoms (VMS) are characteristic of menopause experienced by over 75% of postmenopausal women with significant health and socioeconomic implications. Although the average duration of symptoms is seven years, 10% of women experience symptoms for more than a decade. Although menopausal hormone therapy (MHT) remains an efficacious and cost-effective treatment, its use may not be suitable in all women, such as those at an increased risk of breast cancer or gynaecological malignancy. The neurokinin B (NKB) signaling pathway, together with its intricate connection to the median preoptic nucleus (MnPO), has been postulated to provide integrated reproductive and thermoregulatory responses, with a central role in mediating postmenopausal VMS. This review describes the physiological hypothalamo-pituitary-ovary (HPO) axis, and subsequently the neuroendocrine changes that occur with menopause using evidence derived from animal and human studies. Finally, data from the latest clinical trials using novel therapeutic agents that antagonise NKB signaling are reviewed., Competing Interests: Conflict of interest statement WSD and AA have conducted consultancy work for Myovant Sciences Ltd. WSD has also conducted consultancy work for KaNDy therapeutics., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The objective of this study was to assess differences in long-term sexual and menopausal side effects after uterine cancer treatment among treatment modalities., Methods and Materials: This is a cross-sectional study that examined women treated for uterine cancer from 2006-2018. Eligible women included those who underwent a hysterectomy/bilateral salpino-oophorectemy alone (HS), with brachytherapy (BT), or with external beam radiation therapy (EBRT). A noncancer cohort of women who underwent a hysterectomy/BSO for benign indications were also identified (non-CA). To compare outcomes, we utilized a shortened form of the female sexual function index (FSFI) and the menopause survey, which consists of 3 subscales: hot flashes, vaginal symptoms, and urinary symptoms. Demographic, comorbidity, and other treatment variables were collected. Survey totals were compared across cohorts using ANOVA tests and logistic regression., Results: A total of 284 women completed the Menopause Survey (Non-CA 64, HS 60, BT 69, EBRT 91); 116 women reported sexual activity in the last 4 weeks and completed the FSFI (NC 32, HS 21, BT 31, EBRT 32). The mean FSFI score for the entire cohort was 11.4 (SD 4.16), which indicates poor sexual function. There was no significant difference between any cohort in the overall FSFI score (p = 0.708) or in any of the FSFI subscales (all p > 0.05). On univariate analysis, BT was associated with fewer menopausal hot flashes and vaginal symptoms compared to the non-CA cohort (p < 0.05), which did not persist on multivariable analysis., Conclusion: There was no significant difference in sexual dysfunction or menopausal symptoms in those treated for uterine cancer with or without adjuvant radiation. Most patients reported poor sexual function., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile., Objective: To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile., Methods: A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant., Results: There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group., Discussion and Implications: Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Effective management of vasomotor symptoms (VMS) in patients undergoing treatment for breast cancer (BC) represents a critical but frequent unmet need. This review summarizes the epidemiology, pathophysiology, and clinical features of VMS in patients with BC and provides a synopsis of the complementary and alternative medicine (CAM) approaches in relieving VMS with a focus on purified cytoplasm of pollen (PCP)., Methods: The literature on VMS epidemiology, pathophysiology, clinical burden, and CAM treatment in healthy women and patients with BC was reviewed., Results: VMS are common in patients with BC undergoing hormonal treatment and negatively impact quality of life, leading to treatment discontinuation in up to 25% of patients with detrimental impact on risk of BC recurrence and overall survival. CAM approaches to treat VMS in patients with BC include vitamin E, phytoestrogens, and black cohosh, even if there is a lack of solid evidence to guide clinicians in the choice of treatment. PCP, obtained according to standards of good manufacturing practice, has a definite pharmacological mechanism of action, is devoid of estrogen activity, and has shown clinical efficacy on menopause-associated symptoms with a favorable safety profile and high compliance. As such, it appears to represent a valid management option to improve quality of life in patients with pre- and postmenopausal BC., Conclusions: Physicians should actively investigate the presence and impact of VMS in patients receiving therapy for BC. Additional and appropriately sized randomized clinical trials are needed to provide clear evidence on how to best meet the needs of patients with BC suffering from menopause-associated symptoms.

The huge impact of climate change on humankind is multidimensional, and includes direct and indirect challenges to the physical, psychological and socio-cultural wellbeing. Women may be more vulnerable to climate-sensitive diseases, but little attention has been paid to specific needs and challenges associated with the menopause transition. The increase in average and extreme temperatures may modulate the manifestation of vasomotor symptoms; in particular, environmental temperature and seasonality may affect hot flushes and night sweats. However, more research is needed to define the impact of climate-related factors among the determinants influencing the individual experience of menopause. In addition, increased exposure to environmental pollution and toxins may also have a role in the modulation of ovarian aging mechanisms, possibly influencing timing of menopause. Finally, both air pollution and menopause transition are associated with unfavorable modifications of cardio-metabolic, bone and cognitive health, and account should be taken of these in the evaluation of the individual woman's health vulnerabilities. Overall, the evidence reported in this narrative review supports the need for specific strategies aimed at reducing the burden of climate and environmental change on menopausal women. Healthcare providers should promote behavioral measures that reduce anthropogenic climate change and at the same time have a beneficial role on several domains of physical and psychological wellbeing. From this perspective, menopause represents a golden moment to implement virtuous behaviors that will benefit at the same time women's longevity and the planet., Competing Interests: Declaration of competing interest Rossella E. Nappi had past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Gedeon Richter, HRA Pharma, Procter & Gamble Co, TEVA Women's Health Inc. and Zambon SpA. At present, she has on-going relationship with Astellas, Bayer HealthCare AG, Exeltis, Fidia, Merck Sharpe & Dohme, Novo Nordisk, Palatin Technologies, Pfizer Inc., Shionogi Limited, Theramex, and Viatris. None of these are relevant to the present work. All the other authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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

Background: Hot flashes are the common and debilitating symptom among prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies indicated that pharmacological option such as venlafaxine provides partial relief, but the tolerability is poor when dose is not tapered. Hence, alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence., Methods: Five hospitals will recruit 120 acupuncture naïve patients with moderate-to-severe hot flashes after prostate cancer received ADT in China from February 2023 to December 2024. Participants will be randomly 2:1:1 allocated to the 18 sessions of verum acupuncture at true acupuncture points plus usual care, 18 sessions of non-penetrating sham acupuncture at non-acupuncture points plus usual care, or usual care alone over 6 weeks. The primary outcome measure is the change of mean weekly hot flashes symptom severity score (HFSSS) at the end of treatment compared with baseline., Expected Results and Conclusion: We will be able to measure the effectiveness of acupuncture for patients with PCa suffering from ADT-induced hot flashes and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients., Trial Registration: Clinicaltrials.gov (NCT05069467)., (© 2023. The Author(s).)

► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.

Objective: To update the evidence-based Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society., Methods: An advisory panel of clinicians and research experts in women's health were selected to review and evaluate the literature published since the Nonhormonal Management of Menopause-Associated Vasomotor Symptoms: 2015 Position Statement of The North American Menopause Society. Topics were divided into five sections for ease of review: lifestyle; mind-body techniques; prescription therapies; dietary supplements; and acupuncture, other treatments, and technologies. The panel assessed the most current and available literature to determine whether to recommend or not recommend use based on these levels of evidence: Level I, good and consistent scientific evidence; Level II, limited or inconsistent scientific evidence, and Level III, consensus and expert opinion., Results: Evidence-based review of the literature resulted in several nonhormone options for the treatment of vasomotor symptoms. Recommended: Cognitive-behavioral therapy, clinical hypnosis, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors, gabapentin, fezolinetant (Level I); oxybutynin (Levels I-II); weight loss, stellate ganglion block (Levels II-III). Not recommended: Paced respiration (Level I); supplements/herbal remedies (Levels I-II); cooling techniques, avoiding triggers, exercise, yoga, mindfulness-based intervention, relaxation, suvorexant, soy foods and soy extracts, soy metabolite equol, cannabinoids, acupuncture, calibration of neural oscillations (Level II); chiropractic interventions, clonidine; (Levels I-III); dietary modification and pregabalin (Level III)., Conclusion: Hormone therapy remains the most effective treatment for vasomotor symptoms and should be considered in menopausal women within 10 years of their final menstrual periods. For women who are not good candidates for hormone therapy because of contraindications (eg, estrogen-dependent cancers or cardiovascular disease) or personal preference, it is important for healthcare professionals to be well informed about nonhormone treatment options for reducing vasomotor symptoms that are supported by the evidence., (Copyright © 2023 by The North American Menopause Society.)

Objective: To further examine a potential link between migraine and vasomotor symptoms as well as hypertension as a cardiovascular disease risk factor, potentially explaining the association in midlife women., Patients and Methods: We conducted a cross-sectional analysis from the Data Registry on Experiences of Aging, Menopause, and Sexuality using questionnaire data from women aged 45 to 60 years seen in women's clinics at a tertiary care center from May 15, 2015, through January 31, 2022. A history of migraine was self-reported; menopause symptoms were assessed with the Menopause Rating Scale. Associations between migraine and vasomotor symptoms were evaluated utilizing multivariable logistic regression models adjusting for multiple factors., Results: Of 5708 women included in the analysis, 1354 (23.7%) reported a migraine history. The total cohort had a mean age of 52.8 years, most (5184 [90.8%]) were White, and 3348 (58.7%) were postmenopausal. In adjusted analysis, women with migraine were significantly more likely to have severe/very severe hot flashes vs no hot flashes compared with women without migraine (odds ratio, 1.34; 95% CI, 1.08 to 1.66; P=.007). Migraine was associated with a diagnosis of hypertension in adjusted analysis (odds ratio, 1.31; 95% CI, 1.11 to 1.55; P=.002)., Conclusion: This large cross-sectional study confirms an association between migraine and vasomotor symptoms. Migraine also was associated with hypertension, potentially providing a link with cardiovascular disease risk. Given the high prevalence of migraine in women, this association may help identify those at risk for more severe menopause symptoms., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aim: Individual differences and sociodemographic, gynecological, and cultural characteristics affect the severity of menopausal symptoms. This study aimed to reveal the severity of menopausal symptoms experienced by Turkish women and the risk factors that cause women to experience very severe menopausal symptoms., Methods: This cross-sectional and descriptive study was conducted with 435 women in menopause. The Personal Information Form and the Menopause Rating Scale were used to collect data. In logistic regression analysis, backward stepwise Wald binary logistic regression method was used. In the logistic regression analysis, there were 30 independent variables. The dependent variable was determined as the total MRS score., Results: The mean score of the somatic symptoms sub-dimension was 3.14 ± 2.12, the mean score of the psychological symptoms sub-dimension was 10.11 ± 5.66, and the mean score of the urogenital symptoms sub-dimension was 3.58 ± 2.90. The total mean score of the Menopause Rating Scale was 16.83 ± 9.31. Menopausal age between 44 and 50 years old (OR = 10.681), having a chronic illness (OR = 6.432), having more than 5 pregnancies (OR = 5.372), and spouse's primary school or below education level (OR = 4.02) increase the severity of menopausal symptoms., Conclusion: It is recommended that healthcare professionals evaluate the symptoms of women in the menopause period to provide them with psychological and social support and to help the spouse and family cooperate with women in menopause in compliance with the process., (© 2023 Japan Society of Obstetrics and Gynecology.)

Importance: Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM])., Observations: Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene., Conclusions and Relevance: During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.

Objective: To determine treatment priorities in women cancer patients attending a dedicated Menopausal Symptoms After Cancer service., Methods: Cancer type and stage were abstracted from medical records. Women ranked up to three symptoms as treatment priorities from the list "hot flushes/night sweats," "mood changes," "vaginal dryness or soreness," "sleep disturbances," "feeling tired or worn out (fatigue)," "sexual problems and/or pain with intercourse," "joint pain," and "something else" with free-text response. For each prioritized symptom, patients completed standardized patient-reported outcome measures to determine symptom severity and impact., Results: Of 189 patients, most had breast cancer (48.7%, n = 92), followed by hematological (25.8%, n = 49), gynecological (18.0%, n = 34), or colorectal (2.6%, n = 5). The highest (first-ranked) treatment priority was vasomotor symptoms (33.9%, n = 64), followed by fatigue (18.0%, n = 34), vaginal dryness/soreness (9.5%, n = 18), and sexual problems/pain with intercourse (9.5%, n = 18). Symptoms most often selected in the top three ("prioritized") were fatigue (57.7%, n = 109), vasomotor symptoms (57.1%, n = 108), and sleep disturbance (49.2%, n = 93). In patients who prioritized vasomotor symptoms, medians on the "problem," "distress," and "interference" dimensions of the Hot Flash Related Daily Interference Scale were, respectively, 6.0 (interquartile range [IQR], 5.0-8.0), 5.5 (IQR, 3.0-8.0), and 5.0 (IQR, 3.-7.0), indicating moderate severity. In patients who prioritized fatigue, the median Fatigue Scale score was 28 (IQR, 19-36), 37% worse than general population., Conclusions: Vasomotor symptoms, fatigue, sexual problems, and vaginal dryness/soreness were the leading priorities for treatment. Understanding symptom severity and patient priorities will inform better care for this growing population., Competing Interests: Financial disclosure/conflicts of interest: M.P. currently receives institutional funding from AE Rowden White and Edward R. White Foundation Trust “People and People Support” Grant, Cancer Council NSW Project Grant RG 21-06, and NHMRC (APP1163202). She has received past funding from Centre for Research Excellence in Women's Health in Reproductive Life (CREWHiRL) Seed Funding and Project Support Grant, Department of Obstetrics and Gynaecology Innovation Grants, Melbourne Medical School Minor Infrastructure Funding Scheme 2020, Department of Obstetrics and Gynecology MCR Fellowship, and Royal Children's Hospital Foundation. The other authors have nothing to disclose., (Copyright © 2022 by The North American Menopause Society.)

Objective: The aim of this study was to examine if there are any differences in the prevalence of daily hot flashes in 50-year-old women in a longitudinal perspective (from 1968 to 2017)., Methods: Cohort comparisons of four population-based samples of 50-year-old women born in 1918, 1930 (earlier-born cohorts), 1954, and 1966 (later-born cohorts) from the Prospective Population Study of Women in Gothenburg examined in 1968-1969, 1980-1981, 2004-2005, and 2016-2017. Questions about frequency of hot flashes have been formulated in the same way throughout all follow-up examinations. Changes between four generations of 50-year-old women were studied., Results: In the unadjusted model, we found an increased prevalence of daily hot flashes in 50-year-old women born in 1954 and 1966 compared with 50-year-old women born in 1918 and 1930 (odds ratio, 1.74; 95% confidence interval, 1.37-2.22). When considering potential predictors for daily hot flashes (smoking, perceived level of high stress, BMI, waist-to-hip ratio, hormone therapy, and hormonal contraceptives) in the adjusted model, there was a notable difference; odds ratio increases from 1.74 to 1.92 (95% confidence interval, 1.46-2.52). Smoking frequency was substantially lower in the later-born cohorts, 39% compared with 17%., Conclusions: In this prospective longitudinal study of 50-year-old women, we found nearly twice as high odds of reporting daily hot flashes in the later-born women compared with earlier-born. When controlling for potential predictors, there was still an obvious difference, which cannot be explained in our study. These findings have not earlier been described, and there is a need for further longitudinal population studies investigating the prevalence of hot flashes over time. Moreover, additional research is required exploring the underlying mechanism of hot flashes, as well as studies that take into account potential risk factors in the environment and societal development over time, that is, impacts of endocrine-disrupting chemicals changes in lifestyle, environmental, and dietary factors, as well as working conditions., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Background: People have been teaching self-acupuncture (SA) in the United Kingdom since 1977. More recently, a small body of research has been conducted on SA. However, detailed guidelines on teaching and delivery of SA have so far, to our knowledge, not been developed., Methods: Acupuncturists were invited to participate in an online survey about their experiences of teaching SA. Data from the survey were extracted, analysed using descriptive statistics and translated into SA teaching guidelines., Results: One hundred thirty-eight acupuncturists completed the survey. Nineteen percent of participants had taught SA. The most common symptoms for which acupuncturists taught SA were pain, nausea, anxiety, hot flushes, headaches/migraines and breathlessness. The six most commonly taught traditional acupuncture point locations were LI4, ST36, SP6, PC6, LR3 and TE5. No participants had received reports of adverse effects from their patients., Conclusion: Acupuncturists who teach SA find it to be an acceptable and safe option for patients. The presented data have important implications for guiding the practice of SA.

The aim of this study was to evaluate the relationship between the menopausal symptoms and sleep quality in women in the climacteric period. This cross-sectional study was conducted on 383 women aged 40-64 years at the Cancer Early Diagnosis Screening and Training Centre. The data were collected with the questionnaire form, Menopause Rating Scale (MRS) and the Pittsburgh Sleep Quality Index (PSQI). The sleep quality was poor in 77.8% of the women in the study. A significant relationship was found between PSQI scores and the somatic and psychological subscale scores of the MRS in the presence of other variables that could affect sleep according to multiple linear regression analysis ( p <  .05). We recommend training and consulting services provided by health care professionals and further experimental studies on the subject to decrease the negative effects of the somatic and psychological symptoms found to worsen sleep quality in women in the climacteric period. IMPACT STATEMENT What is already known on this subject? Sleep problems are a common health problem in women in the climacteric period. What do the results of this study add? The most common menopausal symptoms were joint and muscle problems, physical and emotional fatigue, nervousness, hot flushes, unhappiness, anxiety, and sleep problems in order of frequency. There was a weak positive significant relationship between the total PSQI score and the psychological and urogenital subscale scores of the MRS, in addition to a moderate positive significant relationship between the total PSQI scores and the total and somatic subscale scores of the MRS. What are the implications of these findings for clinical practice and/or further research? We believe effective management of the somatic and psychological symptoms during the climacteric period with health care staff providing training and consultancy services to the women aimed at decreasing the symptoms according to evidence-based procedures could help improve the sleep quality. Conducting multicenter studies with a larger subject group where the effect of menopausal symptoms on sleep quality in addition to that of multifactorial causes are evaluated in depth is recommended.

Objective: Vasomotor symptoms (VMS), the most frequently reported symptoms during the menopausal transition, have been associated with inflammation. Whether inflammation is a risk factor for or a consequence of VMS remains unclear. The objectives of these analyses were to determine if elevated proinflammatory marker levels were associated with increased incident VMS in women without VMS at baseline and whether these associations varied by menopause transition stage or race/ethnicity., Methods: We used longitudinal data on incident VMS, high-sensitivity C-reactive protein (hs-CRP; n = 1,922) and interleukin-6 (IL-6; n = 203) from 13 follow-up visits in the Study of Women's Health Across the Nation, which included five racial/ethnic groups of midlife women. We performed multivariable discrete-time survival analyses to determine adjusted hazard ratios (aHRs) for the association of these proinflammatory markers with incident VMS in women without VMS at baseline., Results: We found no significant associations of incident VMS with dichotomized hs-CRP (>3 vs ≤3 mg/L) at baseline, concurrent or prior visit (aHRs, 1.04-2.03) or IL-6 (>1.44 vs ≤1.44 pg/mL) at visit 1, concurrent or prior visit (aHRs, 0.67-1.62), or continuous hs-CRP or IL-6 values over 13 follow-up visits (with nonsignificant adjusted increased hazards ranging from 0% to 2%)., Conclusions: Our results showed no significant association of the proinflammatory biomarkers, hs-CRP or IL-6, either concurrently or with subsequent incident VMS, indicating that inflammation was unlikely to be a risk factor for VMS. Thus, clinical treatments directed at reducing inflammation would be unlikely to reduce the occurrence of VMS., Competing Interests: Financial disclosure/conflicts of interest: N.E.A. reports internal pilot funding from the Wake Forest School of Medicine. H.J. reports money paid to the institution (current) from Merck and Pfizer and from (past) NErre/KaNDy and Que Oncology, money paid to her from Bayer, consulting contracts no longer active from Jazz and Esai, and that her spouse is an employee of Arsenal Biosciences and has an equity stake in Merck Research Labs and Tango Therapeutics. J.M.P. reports money paid to her from (past) Abbvie, Biohaven, Lundbeck advisory board and American Headache Society (travel costs). R.C.T. reports money paid to her from (current) Astellis Pharma, Bayer, Happy Health, and Viva Health, and from (past) Pfizer Inc., Proctor & Gamble, and Virtue Health. The other authors have nothing to report., (Copyright © 2022 by The North American Menopause Society.)

Background: Menopause is a stage in life when a woman stops having menstruation and the ovaries produce less estrogen. Hot flashes (HFs) are the classical symptoms for menopausal transition and cessation of menses. Increased anxiety had been reported as a significant risk factor of HFs. Vitamin D deficiency and low daily dietary calcium intake may be associated with the occurrence of hot flashes (HFs) in adolescents and young females that are not related to hormonal changes of menopausal transition., Objective: The aim of this study is to validate this hypothesis., Methods: A case-control study was conducted. Thirty-eight females (38) with HFs aged 18-40 years, and 38 age-matched healthy controls with no HFs were involved. Participants answered questions about HFs symptoms. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Serum vitamin D, Follicle Stimulating Hormone, Estradiol, and Prolactin were measured., Results: Vitamin D deficiency, psychological symptoms, and Musculoskeletal pain (MSP) were more prevalent in cases versus controls. About 73.68% of females had HFs on a daily basis, 73.7% of them reported that their HFs associated with excessive sweating. Spearman correlation revealed that number of daily HFs were correlated positively and significantly with anxiety scores (r 2 = -0.278, p=0.045), and average MSP pain (r 2 =-0.536, p=<0.001). Binary logistic regression showed that, Anxiety score and vitamin D status, (OR=1.33(1.104-1.7), p=0.02, and OR=0.89(0.79-0.99, p=0.03) respectively were the predictors for HFs., Conclusion: This study showed that adolescents and young females may experience HFs that are not related to hormonal changes of menopausal transition. The predictors for HFs were vitamin D deficiency and anxiety., Competing Interests: No conflict of interest was declared by the authors., (© 2022 Amer M Sindiani, Mohammad J. Alkhatatbeh, Khalid K. Abdul-Razzak.)

Purpose: While clinical trials provide valuable data about efficacy of interventions, findings often do not translate into clinical settings. We report real world clinical outcomes of a 15-year service offering breast cancer survivors auricular acupuncture to manage hot flushes and night sweats (HFNS) associated with adjuvant hormonal treatments. This service evaluation aims to (1) assess whether usual practice alleviates symptoms in a clinically meaningful way and (2) compare these results with scientific evidence., Methods: Data were analysed from 415 referrals to a service offering women eight standardised treatments using the National Acupuncture Detoxification Association (NADA) protocol. Outcome measures administered at baseline, end of treatment (EOT), and 4 and 18 weeks after EOT included hot flush diaries, hot flush rating scale (HFRS) and women's health questionnaire (WHQ)., Results: Over 2285 treatments were given to 300 women; 275 (92.3%) completed all eight treatments. Median daily frequency of HFNS reduced from 9.6 (IQR 7.3) to 5.7 (IQR 5.8) at EOT and 6.3 (IQR 6.5) 18 weeks after EOT. HFRS problem rating showed a clinically meaningful reduction of ≥ 2 points at all measurement points. WHQ showed improvements in several symptoms associated with the menopause. Two adverse events were reported, neither were serious. Results are comparable to published research., Conclusion: This first analysis of a long-term auricular acupuncture service compares favourably with outcomes of other studies for reducing HFNS frequency and associated menopausal symptoms. In day-to-day clinical practice, NADA appears to be a safe effective intervention for breast cancer survivors., (© 2022. The Author(s).)

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

Background: Despite the frequency of vasomotor symptoms (VMS) in patients with early breast cancer (EBC), their optimal management remains unknown. A patient survey was performed to determine perspectives on this important clinical challenge., Methods: Patients with EBC experiencing VMS participated in an anonymous survey. Patients reported on the frequency and severity of VMS using the validated Hot Flush Rating Scale (HFRS) and ranked their most bothersome symptoms. Respondents were also asked to determine endpoints that defined effective treatment of VMS and report on the effectiveness of previously tried interventions., Results: Responses were received from 373 patients, median age 56 years (range 23-83), who experienced an average of 5.0 hot flashes per day (SD 6.57). Patients reported the most bothersome symptoms to be feeling hot/sweating (155/316, 49%) and sleeping difficulties (86/316, 27%). Fifty-five percent (201/365) of patients would consider a treatment to be effective if it reduced night-time awakenings. While 68% of respondents were interested in trying interventions from their healthcare team to manage VMS, only 18% actually did so. Of the 137 patients who had tried an intervention for VMS, pharmacological treatments, exercise, and relaxation strategies were more likely to be effective, while therapies such as melatonin and black cohosh were deemed less effective., Conclusion: VMS are a common and bothersome problem for EBC patients, with a minority receiving interventions to manage these symptoms. Further research is needed to identify patient-centered strategies for managing these distressing symptoms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The increasing interest in Western countries regarding phytotherapy use to treat menopause-related symptoms has led the Spanish Menopause Society (AEEM) to update its position statement performed in 2009 on the role of black cohosh ( Cimicifuga racemosa ) for the treatment of menopausal symptoms., Material and Methods: A panel of experts from both clinical and research backgrounds were assembled to investigate the best available evidence. Selected studies were obtained by an electronic search, including the Internet search engines MEDLINE-Pubmed (1997-December 2021) and the Cochrane Controlled Trials Register., Results: Most of the well-designed studies published in recent years have been conducted with the isopropanolic extract of black cohosh/ C. racemosa . The most common dose is 40 mg/day capable of achieving a significant reduction in hot flushes (particularly in women with intense hot flushes) and an improvement in mood. Used at the recommended doses, C. racemose produces no significant adverse reactions., Conclusion: Black cohosh is an effective and safe treatment option for the relieving of vasomotor symptoms. Finally, further clinical trials with sufficient patient enrollment and longer study follow-up are needed.

Background: Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting., Patients and Methods: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes., Results: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21-1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41-2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39-2.35) or died from cancer (HR, 1.71; 95% CI, 1.37-2.12)., Conclusions: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Purpose: This study aimed to measure the prevalence of menopausal symptoms in patients attending a multidisciplinary model of care clinic at their initial clinic visit and their subsequent follow-up consultation using a validated patient-reported outcome measure to assess whether menopausal symptoms after cancer had improved., Methods: A retrospective review was conducted of patients attending the clinic in a 12-month period in 2017 (n = 189). Recorded variables included patient demographics, details of index cancer, previous treatments, and menopausal symptom management strategies. Severity of menopausal symptoms was evaluated using the Greene Climacteric Scale. The extent to which patients were bothered by symptoms was combined into two categories and dichotomized (present/absent). Differences in symptom prevalence between the initial consultation and first follow-up visit were examined using McNemar's test., Results: The majority of patients attending the clinic had a history of breast cancer (72%). Fifty-five percent of patients were prescribed a non-hormonal therapy at their initial visit, most commonly gabapentin. Significantly fewer patients reported being bothered by hot flushes, fatigue, sleep difficulties, and loss of interest in sex, anxiety, or troubles concentrating at the first follow-up visit compared to their initial consultation (p < 0.01)., Conclusion: In this study, there was an improvement in self-reported menopausal symptoms in a significant proportion of cancer survivors attending a multidisciplinary menopause clinic between their initial and first subsequent follow-up consultations., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate in postmenopausal women the association between menopause symptom intensity and the quality of life and clinical, anthropometric, and lifestyle factors, focusing on food consumption by degree of processing., Study Design: A cross-sectional study of 288 postmenopausal women using interviews., Main Outcome Measures: The Kupperman-Blatt Menopausal Index and the Women's Health Questionnaire were used to evaluate the main outcomes of menopausal symptom intensity and quality of life, respectively. Data on socioeconomic, clinical, anthropometric, and lifestyle variables (smoking, alcohol intake, physical activity, and food consumption) were collected., Results: Most women had moderate to severe intensity of menopausal symptoms. The highest tertile of ultra-processed food consumption was associated with a greater intensity of vasomotor symptoms (prevalence ratio [PR] 0.73, 95% confidence intervals [CI] 0.55-0.96) and sexual behavior (PR 1.22, CI 1.01-1.49). Higher intakes of sugar-sweetened beverages and sausages were associated with somatic symptoms (PR 1.23, CI 1.01-1.49) and poorer memory/concentration (PR 1.22, CI 1.02-1.47/ PR 1.22, CI 1.01-1.48). The highest tertile of vegetable intake was associated with greater protection against depressive mood (PR 0.64, CI 0.43-0.96), vasomotor symptoms (PR 0.79, CI 0.63-0, 99), and sleep disorders (PR 0.83, CI 0.69-0.99), and better quality of life (PR 0.79, CI 0.62-0.99)., Conclusion: More intense vasomotor, sexual, somatic, and memory and concentration symptoms are associated with a higher consumption of ultra-processed foods, whereas those with a higher consumption of vegetables reported lower menopause symptom intensity and a better quality of life., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Menopausal complaints are a critical aspect of women's lives. In particular vasomotor symptoms, such as hot flashes, may seriously impact quality of life and are considered the most bothersome complaint by patients. Although Menopausal Hormone Therapy (MHT) is considered the best option, women increasingly ask for a natural and more tailored treatment approach., Areas Covered: Nutraceutical compounds represent the most widespread alternative therapy for vasomotor symptoms, and their use is somewhat increasing. In this review, the authors analyzed the mechanism of action and the related safety of non-hormonal treatments, including new approaches and future aspects., Expert Opinion: MHT represents the traditional therapy for menopausal complaints, especially for severe and moderate symptoms; however, evidence has not defined a safety profile for all patients. To address this issue, nutraceuticals could represent a compelling and useful non-hormonal approach in selected patients.

Purpose: We compared trajectories of vasomotor symptoms (VMS) and their risk factors in women with breast cancer (BrCa) to those of cancer-free controls., Methods: Data were from 15 nearly annual follow-up visits (1996-2017) of the multi-racial/ethnic cohort of midlife women enrolled in the Study of Women's Health Across the Nation (SWAN). We compared women with incident BrCa to controls for patterns of VMS, controlling for risk factors identified in bivariate analyses using multivariable longitudinal analyses., Results: Characteristics at study entry largely did not differ between cases (n = 151) and controls (n = 2161). Adjusted prevalence of any VMS increased significantly among cases from diagnosis to 2.75 years post diagnosis [per-year adjusted odds ratio (aOR) = 1.76, 95% confidence interval (CI) 1.39-2.24], peaking at 2.75 years post diagnosis, whereas prevalence was stable among controls in this interval [aOR = 1.04, 95% CI 0.99-1.11]. Beyond 2.75 years post diagnosis, prevalence declined significantly in cases [aOR = 0.72, 95% CI 0.61-0.84] and less in controls [aOR = 0.96, 95% CI 0.92-1.00]. Patterns were similar for frequent VMS. Adjustment for tamoxifen use slightly reduced the per-year OR for any prevalent VMS post diagnosis, partially explaining excess VMS in cases. Other treatments were unassociated with VMS., Conclusions: Patterns of prevalent VMS reporting differed significantly between cases and controls, particularly post diagnosis, the latter only partially explained by tamoxifen use among cases. Risk factors for VMS largely did not differ between cases and controls., (© 2021. The Author(s).)

Context: Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons)., Objective: We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood-brain barrier) and impedes their downstream effects., Design: Case/control., Setting: Academic medical center., Participants: Mice., Interventions: Administration of peripherally restricted kappa receptor agonists and frequent blood sampling to determine hormone release and body temperature., Main Outcome Measures: LH pulse parameters and body temperature., Results: First, chronic administration of a PRKA to bilaterally ovariectomized mice with experimentally induced hyperactivity of KNDy neurons reduces the animals' elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity., Conclusion: The inhibition of kisspeptin neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Methods: The subjects included 13 PI patients from the Hubei Provincial Hospital of TCM, Hubei University of TCM, and Wuhan Traditional Chinese Medicine Hospital, and the corresponding noninsomniac spouses of the patients were selected as controls. TWBXG was continuously administered for 4 weeks. The feces of PI patients and their noninsomniac spouses before and after treatment with TWBXG were collected. The intestinal flora composition of each group was detected by metagenomic sequencing, and the efficacy of TWBXG was evaluated by the PSQI scale., Results: Compared with the control group, the model group showed an increase in the abundance of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum, while those of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii were decreased. Compared with pretreatment, the PSQI score was significantly reduced ( P < 0.05), the abundance of Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii increased, and that of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, and Blautia obeum decreased after treatment. However, there was still a certain gap in the abundance of related flora in the treatment group compared with the control., Conclusion: PI is associated with disturbances in the intestinal flora and is mainly related to the disorders of Roseburia faecis, Ruminococcus, Prevotella copri, Fusicatenibacter saccharivorans, Blautia obeum, Bacteroides, fecal Bacteroidetes, and Faecalibacterium prausnitzii. TWBXG can effectively treat PI, and its effect may be achieved by regulating the disordered intestinal flora. Clinical Trials. The study was registered in the Chinese clinical trial registry and approved by the World Health Organization clinical trial registration platform (Effects of the modified Tianwang Buxin granule and modified Tianwang Buxin decoction pieces on insomnia: a randomized, controlled trial, ChiCTR-IPR-17011549)., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Xiqian Yang et al.)

The majority of women experience vasomotor symptoms (VMS), such as hot flashes and night sweats, during the menopausal transition. Recent evidence strongly suggests a connection between neurokinin 3 (NK3) receptor signaling and VMS associated with menopause. The NK3 receptor antagonist fezolinetant is currently in phase 3 development for treatment of moderate to severe VMS associated with menopause. We investigated the pharmacological effects of repeated administration of fezolinetant on levels of sex hormones and gonadotropins, neuronal activity in the hypothalamus, and skin temperature as an index of hot flash-like symptoms in ovariectomized rats as a model of menopause. Ovariectomized rats exhibited several typical menopausal symptoms: hyperphagia, increased body weight, significantly decreased plasma estradiol levels, increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and significantly increased skin temperature. Increased c-Fos expression (an indirect marker of neuronal activity) in median preoptic nucleus (MnPO) hypothalamic neurons was also observed in ovariectomized rats. Repeated oral administration of fezolinetant (1-10 mg/kg, twice daily) for 1 week dose-dependently reduced plasma LH levels without affecting estradiol or FSH levels, inhibited the activation of MnPO neurons, and attenuated hot flash-like symptoms. In addition, fezolinetant dose-dependently reduced hyperphagia and weight gain in ovariectomized rats. These preclinical findings suggest that fezolinetant attenuates hot flash-like symptoms via inhibition of neuronal activity in the MnPO of ovariectomized rats and provides further support for the ongoing clinical development of fezolinetant for the treatment of VMS associated with menopause., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Declining and variable levels of estrogens around the time of menopause are associated with a suite of metabolic, vascular, and neuroendocrine changes. The archetypal adverse effects of perimenopause are vasomotor symptoms, which include hot flashes and night sweats. Although vasomotor symptoms are routinely treated with hormone therapy, the risks associated with these treatments encourage us to seek alternative treatment avenues. Understanding the mechanisms underlying the effects of estrogens on temperature regulation is a first step toward identifying novel therapeutic targets. Here we outline findings in rodents that reveal neural and molecular targets of estrogens within brain regions that control distinct components of temperature homeostasis. These insights suggest that estrogens may alter the function of multiple specialized neural circuits to coordinate the suite of changes after menopause. Thus, defining the precise cells and neural circuits that mediate the effects of estrogens on temperature has promise to identify strategies that would selectively counteract hot flashes or other negative side effects without the health risks that accompany systemic hormone therapies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Vasomotor symptoms (VMS) such as hot flashes and night sweats are common in breast cancer patients and can affect both quality of life and treatment adherence. However, there is limited practical data to guide clinicians in the optimal selection of therapeutic strategies. A survey of health care providers was performed to better understand perspectives and prescribing practices for managing this problem., Methods: Canadian health care providers who treat patients with early stage breast cancer (EBC) participated in an anonymous electronic survey. Participants provided their perspectives on the prevalence and severity of VMS among patients with EBC, outlined their management strategies, and provided feedback on the perceived efficacy of interventions for VMS., Results: Responses were received from 65 providers including breast oncologists (36/65, 55%) and nurses with oncology expertise (29/65, 45%). Seventy-seven percent of participants reported regularly asking patients about VMS, and most indicated that bothersome VMS occurred in the majority of patients. Health care providers cited hot flash severity and sleep disruption as the most important issues for patients. The most common first- and second-line interventions recommended were lifestyle modifications (n = 32/65, 49.2%) and pharmacologic strategies (n = 27/65, 41.5%), respectively. Most respondents felt that interventions, including pharmacologic, over-the-counter, and complementary therapies, were only "somewhat effective". Overall, half of respondents (n = 35/65, 54%) reported being "confident" in managing VMS., Conclusion: Given the variability of treatment recommendations, and health care provider uncertainty around the benefits of therapies for VMS, more 'real-world' trials are needed to optimize patient care.

Introduction: Introduction: in women with breast cancer and gynecologic cancer, as well as in men with prostate carcinoma, hot flashes, asthenia, and insomnia are common and bothersome symptoms that impair quality of life. Objective: to evaluate the effectiveness of tryptophan intake as a treatment for hot flushes, asthenia, and insomnia in patients with prostate, breast, and uterine cervical cancer. Materials and methods: intervention study without a control group at the HUCA Radiation Oncology Service, from July 2018 to July 2019. A total of 60 patients with prostate, breast, or uterine cervical cancer who had received treatment with radiotherapy and hormone therapy, and who presented with hot flushes, asthenia, and insomnia were included. L-tryptophan was administered at a dose of 3 g per day. Results: a significant increase in serum tryptophan levels at the end of the study (p < 0.001) and a significant decrease in the scores of the study symptoms were reported. Although statistical significance was not found, a significant improvement in each symptom was observed, as well as an improvement in quality of life (p < 0.001). Conclusions: the study suggests that, in patients with breast, prostate, or uterine cervical cancer, and symptoms such as hot flushes, asthenia, and insomnia, the administration of tryptophan as a nutritional supplement is well tolerated, improves quality of life, and is associated with improvement in the scale scores of the symptoms of interest, although no statistically significant relationship with increased blood tryptophan levels was found.

Purpose: To determine the nature and severity of vasomotor symptoms, sexual problems, mood and sleep disturbance in community-dwelling breast cancer patients, whether and where they received treatment for these symptoms and their satisfaction with treatment received., Methods: Online cross-sectional survey distributed through Breast Cancer Network Australia (BCNA)., Results: 524/2286 women responded to the invitation to participate. Of these, 74% (385/523) reported symptoms of interest and were included in the analysis. Mean age was 55.2 years and mean time since breast cancer diagnosis was 5.7 years. Most (66%) had received chemotherapy and were taking endocrine therapy (64%). The most common symptoms were hot flushes/night sweats and sleep disturbance (both 89%), vaginal dryness (75%), mood swings (62%) and sexual problems (60%). Symptoms were mild (21-33%) or moderate (21-38%) in around one third and severe in up to one quarter (8-26%). Symptoms affected the ability to "get on with their life" for 36%, predicted by severity of hot flushes (OR 1.4), sleep disturbance (OR 1.3), mood disturbance (OR 1.3), and sexual problems (OR 1.3). Only 32% were offered treatment, mostly delivered by GPs (33%) or oncologists (26%). Only 49% found this "somewhat effective" and 34% found it ineffective. The majority (60%) wanted more support to manage their symptoms., Conclusion: Menopausal symptoms, sexual problems, mood and sleep difficulties are common after breast cancer and often not effectively managed. There is an unmet need for coordinated care providing effective treatments.

Background: To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning., Methods: Data on 3,298 women, aged 40-80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS., Results: In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen., Conclusion: Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Despite literature pointing to a relation between dietary intake and menopausal symptoms, most studies have evaluated either only supplements or only specific nutrients or foods. Therefore, this study aimed to provide a systematic review of the literature regarding the association between dietary intake and menopausal symptoms in postmenopausal women. A systematic search was conducted across PubMed/Medline, Web of Science, Scopus, and Embase to identify studies published between 2009 and 2019. We identified 3828 studies; after screening, 73 studies were reviewed and 19 of these investigated nutrient and food intake and eating patterns associated with the intensity of menopausal symptoms. Studies evaluating diet quality or dietary patterns showed an association between lower intensity of psychological symptoms, sleep disorders, and vasomotor, urogenital, and somatic symptoms and higher consumption of vegetables, whole grains, and unprocessed foods. Also, the intensity of these symptoms is associated with high-processed foods, saturated fats, and sugars. Regarding nutrient and/or specific food, the studies indicated an association between caffeine intake and type of fat intake and the intensity of menopausal symptoms. Dietary intake was found to be associated with the severity of menopausal symptoms; however, evidence for the association between dietary intake and menopausal symptoms is inconsistent and inconclusive, and is provided by a small number of studies.

Objective: To examine the association between age at menarche and risk of vasomotor menopausal symptoms (VMS) and whether midlife body mass index (BMI) modified the association., Design: A pooled analysis of six cohort studies., Setting: The International collaboration on the Life course Approach to reproductive health and Chronic disease Events (InterLACE)., Population: 18 555 women from the UK, USA and Australia., Methods: VMS frequency data (never, rarely, sometimes and often) were harmonised from two studies (n = 13 602); severity data (never, mild, moderate and severe) from the other four studies (n = 4953). Multinominal logistic regression models were used to estimate relative risk ratios (RRRs) and 95% CIs adjusted for confounders and incorporated study as random effects., Main Outcome Measures: Hot flushes and night sweats., Results: Frequency data showed that early menarche ≤11 years was associated with an increased risk of 'often' hot flushes (RRR 1.48, 95% CI 1.24-1.76) and night sweats (RRR 1.59, 95% CI 1.49-1.70) compared with menarche at ≥14 years. Severity data showed similar results, but appeared less conclusive, with RRRs of 1.16 (95% CI 0.94-1.42) and 1.27 (95% CI 1.01-1.58) for 'severe' hot flushes and night sweats, respectively. BMI significantly modified the association as the risk associated with early menarche and 'often' VMS was stronger among women who were overweight or obese than those of normal weight, while this gradient across BMI categories was not as strong with the risk of 'severe' VMS., Conclusions: Early age at menarche is a risk factor for VMS, particularly for frequent VMS, but midlife BMI may play an important role in modifying this risk., Tweetable Abstract: Overweight and obesity exacerbate the risk of vasomotor symptoms associated with early menarche., (© 2020 Royal College of Obstetricians and Gynaecologists.)