Obesity and menopause.

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.

How do women feel cold water swimming affects their menstrual and perimenopausal symptoms?

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.

New advances in menopause symptom management.

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.

Comparing long-term sexual dysfunction across different uterine cancer treatment modalities.

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.

Vasomotor symptoms and cardiovascular health: findings from the SWAN and the MsHeart/MsBrain studies.

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

Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis.

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.

Acupuncture versus sham acupuncture and usual care for Antiandrogen-Induced hot fLashes in prostate cancer (AVAIL): study protocol for a randomized clinical trial.

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).

Global view of vasomotor symptoms and sleep disturbance in menopause: a systematic review.

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

Impact of climate and environmental change on the menopause.

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.

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

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

Association of Migraine and Vasomotor Symptoms.

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.

The 2023 nonhormone therapy position statement of The North American Menopause Society.

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.

Modeling the risk factors of women with very severe menopausal symptoms.

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.

Management of Menopausal Symptoms: A Review.

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.

Priorities for alleviating menopausal symptoms after cancer.

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.

Vasomotor symptoms and management of women undergoing treatment for breast cancer: literature review with focus on the therapeutic potential of cytoplasmic pollen extract.

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.

Hot Flashes in Adolescence and Young Adult Females: a Link to Vitamin D and Calcium.

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 (r2= -0.278, p=0.045), and average MSP pain (r2=-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.

Perception of higher frequency of daily hot flashes in 50-year-old women today: a study of trends over time during 48 years in the Population Study of Women in Gothenburg, Sweden.

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.