Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

The relation between age at menopause and age at first childbirth.

Analysis of data from the representative "GGP - Contemporary Czech Family Survey" (2020-2022) on the population of women aged 40-69 years showed that the age of onset of menopause is associated with a low age at the birth of the first child. Women who had their first child before their 20th birthday, a pattern of reproductive behaviour common among generations of women before 1989, have an earlier onset of menopause than older first-time mothers. Conversely, the effect of higher age at first birth (35 years or more) on the delay of menopause has not been proved. However, this issue requires further investigation, as the sample analysed suggests certain tendencies. A larger sample size would be needed to make a conclusive finding.

Questions and questionnaires about acute climacteric syndrome.

The acute climacteric syndrome has a large scale of symptoms. Main symptoms are hot flashes and night sweats. Each symptom could be presented alone or commonly in combination with other symptoms. The acute climacteric syndrome is induced by decrease and fluctuations of estrogen and neurosteroids levels. Therapy could be focused on hormone replacement. Changes of quality of life and especially effects of the therapy could be measured by standardized questionaries.

Female Reproductive Factors and Risk of Mild Cognitive Impairment and Dementia: The HUNT Study.

BACKGROUND: More women are living with dementia than men worldwide and there is a need to investigate causes for this female preponderance. While reproductive factors have been investigated as risk factors, the results are conflicting. We aim to clarify this using a large cohort with a long observation time, adjusting for multiple health and lifestyle variables and encompassing a wider range of cognitive impairment. OBJECTIVE: To study the association between menopause age, menarche age and risk of and risk of mild cognitive impairment (MCI) and dementia. SETTING: The Trøndelag Health study (HUNT), a longitudinal population health study in Norway (1984-2019). PARTICIPANTS: Women who were ≥70 years in 2017-2019 were assessed for cognitive impairment. MEASUREMENTS: Data on menopause age and menarche age were obtained from questionnaires. Diagnosis of MCI or dementia was set using a standardised procedure by a diagnostic group of nine physicians. Multinomial logistic regression was used to study the association between menopause age, menarche age and risk of MCI and dementia with adjustment for birth year, education, smoking, ApoE4, number of children, diabetes, body mass index, alcohol use and physical inactivity. RESULTS: We evaluated 5314 women where 900 (16.9%) had dementia, and 1747 (32.8%) had MCI. Multiple adjusted relative risk ratio (RRR) and 95% confidence intervals (CI) for dementia were: 0.96(95%CI 0.95-0.98) (p<0.001) for menopause age, 0.97(95%CI 0.94-0.99) (p=0.007) for natural menopause age (excluding hysterectomy and/or oophorectomyp<55 years) and 0.97(95%CI 0.95-0.99) (pp<0.001) for reproductive span (menopause age minus menarche age). Menopause age p<45years was associated with a 56% higher risk compared to mean menopause age 50 years. We found no significant associations between menarche age and dementia and no associations with MCI. CONCLUSIONS: Older menopause age and longer reproductive span corresponding to longer oestrogen exposure were associated with a lower dementia risk. Future studies should explore therapeutical options to offset this risk in women.

Menopause and metabolic syndrome: anthropometric, lipid, and dietary profiles.

OBJECTIVE: The aim of this study was to characterize the anthropometric, lipid, and dietary profiles of postmenopausal women with metabolic syndrome attending a public health service and compare them with a group of women without metabolic syndrome. METHODS: A cross-sectional study was conducted with 60 postmenopausal women who were divided into two groups: control group and metabolic syndrome group, attending the Climacteric Outpatient Clinic at Santa Casa de São Paulo Hospital, Brazil, between February 2019 and December 2021. Participants were evaluated using a validated semi-quantitative food frequency questionnaire, body mass index, waist circumference, and serum laboratory tests. RESULTS: Significant differences were observed between the groups regarding body mass index and all parameters of metabolic syndrome. The nutritional profile revealed an imbalance in the number of food portions consumed, particularly in the intake of carbohydrates in the form of flour and sweets, which was higher in the metabolic syndrome group. CONCLUSION: The analysis of the three profiles of postmenopausal women revealed significant imbalances, particularly in the metabolic syndrome group, highlighting the importance of regular adjustments and evaluations during this phase of a woman's life.

The effect of mandala coloring on anxiety and quality of life of women in the climacteric period: a randomized controlled study.

OBJECTIVE: This study was conducted to determine the effect of mandala coloring on anxiety and quality of life of women in the climacteric period. METHODS: This research was conducted as an experimental study based on a randomized controlled pre-test and post-test model (single-blind). The study was conducted with women in the climacteric period who presented to a training and research hospital in a western city of Turkey between November 1, 2022, and April 28, 2023. Participants were divided into mandala coloring (n=38) and control groups (n=38). RESULTS: According to the women's socio-demographic and descriptive characteristics, mean age, body mass index, and frequency of menopausal symptoms were similar in both groups. The mean post-test scores of the women in the mandala coloring group on the state-trait anxiety inventory and menopause-specific quality of life questionnaire vasomotor, psychosocial, physical, and sexual subscales (29.71±5.22, 0.86±0.97, 0.53±0.61, 0.79±0.84, and 0.92±1.24, respectively) were lower than the mean post-test scores of the women in the control group on the same scales (41.02±1.20, 1.79±1.76, 1.49±1.39, 1.72±1.38, and 1.95±1.82, respectively) (p=0.000). CONCLUSION: Mandala coloring reduces menopause-related anxiety levels and improves quality of life effectively.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Menopause status- and sex-related differences in age associations with spatial context memory and white matter microstructure at midlife.

Decline in spatial context memory emerges in midlife, the time when most females transition from pre- to post-menopause. Recent evidence suggests that, among post-menopausal females, advanced age is associated with functional brain alterations and lower spatial context memory. However, it is unknown whether similar effects are evident for white matter (WM) and, moreover, whether such effects contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using a face-location memory paradigm, while WM microstructure was assessed using diffusion tensor imaging. Behaviorally, advanced age was associated with lower spatial context memory in post-menopausal females but not pre-menopausal females or males. Additionally, advanced age was associated with microstructural variability in predominantly frontal WM (e.g., anterior corona radiata, genu of corpus callosum), which was related to lower spatial context memory among post-menopausal females. Our findings suggest that post-menopausal status enhances vulnerability to age effects on the brain's WM and episodic memory.

Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause.

INTRODUCTION: During menopause, the majority of women experience vasomotor symptoms which may lead to several untoward effects and negatively impact quality of life. Fezolinetant, a novel agent directly targeting the underlying pathophysiology of menopause-associated vasomotor symptoms, offers an alternative to hormonal therapies for which many patients have a contraindication or unwillingness to take due to safety concerns. AREAS COVERED: This review summarizes key pharmacologic, pharmacokinetic, and pharmacodynamic parameters of fezolinetant along with efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications evaluating the efficacy and safety of fezolinetant was conducted using PubMed and EMBASE databases. A review of registered trials in clinicaltrials.gov was evaluated to identify ongoing studies. EXPERT OPINION: Placebo-controlled studies demonstrated that fezolinetant led to a statistically significant reduction in vasomotor symptom frequency and severity among patients with moderate-to-severe vasomotor symptoms. The most common adverse event is headache (5-10%) and no serious safety signals have been noted. Direct head-to-head comparison with hormonal therapies and nonhormonal therapies for vasomotor symptoms, assessment of sleep outcomes, and evaluation of efficacy and safety beyond 1 year are key areas where additional data are still needed.

Differences in menopausal quality of life, body appreciation, and body dissatisfaction between women at high and low risk of an eating disorder.

OBJECTIVE: Experiences of menopause and quality of life during menopause can vary extensively among women. While menopause has been associated with negative impacts on eating and body image, it is unclear to what extent quality of life differs by eating disorder risk status. The aim of this study was to explore how menopause symptoms and quality of life differ between those women at high- or low-risk of an eating disorder and the potential protective role of body appreciation. METHOD: This cross-sectional survey study explored differences in menopausal quality of life, body appreciation, and body dissatisfaction among women classified as high- or low-risk of an eating disorder as part of a wider survey on aging, health, and psychological complaints during midlife. Participants were 255 females aged between 40 and 60 years. Participants were classified as high-risk and low-risk of an eating disorder based on Eating Attitudes Test-26 (EAT-26) scores. Differences between groups on the Menopause-Specific Quality of Life Questionnaire (MENQOL), Body Shape Questionnaire (BSQ-16), and Body Appreciation Scale-2 were analyzed. The predictive relationship between menopausal quality of life and body appreciation was also explored. RESULTS: Participants in the high-risk group (n = 111) reported significantly poorer menopausal quality of life compared to the low-risk group (n = 144), scoring significantly higher on the sexual, physical, and psychosocial subscales of the MENQOL. The high-risk group also had significantly greater body dissatisfaction and less body appreciation than the low-risk group. Overall, menopausal quality of life was a significant predictor of body appreciation. DISCUSSION: Women with greater eating disorder risk may be faring less well with menopause. Treating and preventing menopause-related eating disorders will benefit from interventions aimed at not only reducing body dissatisfaction, but actively bolstering body appreciation and supporting the sexual, physical, and psychosocial aspects of the menopausal transition.

The impact of physical activity and exercise interventions on symptoms for women experiencing menopause: overview of reviews.

BACKGROUND: Women experiencing problematic menopausal symptoms report lower health-related quality of life and greater healthcare use than women without symptoms. Not all women want to or are able to take hormone replacement therapy. Strengthening the evidence for menopause symptom-management options, including physical activity, improves agency for women. AIM: This overview assesses effectiveness of physical activity and exercise interventions targeting women experiencing menopause symptoms. METHODS: Medline, Embase, CINAHL, Scopus, The Cochrane Database of Systematic Reviews and Social Science Citation Index were searched (June 2023) for systematic reviews of physical activity and exercise interventions targeting women experiencing menopause. Reviews were assessed using AMSTAR-2 and a best-evidence approach to synthesis without meta-analysis (SWIM) was adopted. The protocol was registered on PROSPERO (CRD42022298908). RESULTS: Seventeen reviews included 80 unique relevant primary studies with 8983 participants. There is evidence showing improvement of physical, urogenital, and total symptoms following yoga interventions. Evidence for vasomotor and psychological symptoms was inconclusive. Findings for aerobic exercise were inconclusive although there were some examples of beneficial effects on total and vasomotor symptoms. Evidence was very limited for other types of physical activity and impact on physical, sexual and urogenital symptoms. CONCLUSION: There is some evidence that yoga, and to lesser extent, aerobic exercise may be beneficial for some menopause symptoms, but there is insufficient evidence to recommend a particular form of exercise. Current reviews categorise women on menopause status; broadening this to include ethnicity, income status, employment and other factors will allow better understanding of context for successful interventions.

Symptom network and quality of life of breast cancer patients receiving multimodal cancer treatment: Cross-sectional study.

PURPOSE: Breast cancer patients experience symptoms and side effects from multimodal treatments, which often include menopausal symptoms resulting from cytotoxic chemotherapy or estrogen suppression therapy. This study aimed to explore the symptom network and clusters and its relationship to quality of life (QoL) in breast cancer patients who receive multimodal cancer treatment and experience treatment-related menopausal symptoms. METHODS: A correlational study was conducted. Breast cancer patients receiving multimodal cancer treatment and experiencing treatment-related menopausal symptoms were included while they were receiving radiation therapy (N = 250). Symptoms, functions and QoL were assessed using the EORTC QLQ-C30 and BR45. Network analysis, principal component analysis, exploratory factor analysis, and multiple linear regression analysis were conducted. RESULTS: Fatigue was the most central symptom in the symptom-only network as well as in the network consisting of symptoms and QoL. Fatigue, systemic therapy side effects, appetite loss, and cognitive symptoms demonstrated significant associations with QoL. The cancer and treatment related symptom cluster consisted of fatigue, cognitive symptoms, emotional symptoms and systemic therapy side effects. Breast cancer therapy-specific symptoms, such as arm symptoms, skin mucosis symptoms, and breast symptoms, formed a cluster with pain. CONCLUSION: Fatigue was the most central symptom in breast cancer patients receiving multimodal cancer treatment and experiencing menopausal symptoms. Evaluation of fatigue and providing interventions to manage fatigue would contribute to improvement of QoL of breast cancer patients receiving multimodal cancer treatments. Future network analysis and symptom cluster studies should specify the population of interest and the treatment phase using comprehensive symptom evaluation tools.

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes.

We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36-0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32-0.74), and (HR 0.51, 95% Cl 0.35-0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.

The effect of oral capsules containing Ocimum basilicum leaf extract on menopausal symptoms in women: a triple-blind randomized clinical trial.

BACKGROUND: Menopause, characterized by various physical and mental changes, is primarily caused by hormonal fluctuations, resulting in numerous complications. Recently, herbal treatments have gained significant attention for their minimal side effects compared to chemical drugs. This study aimed to investigate the effects of oral capsules containing Ocimum basilicum leaf extract (OBLE) on menopausal symptoms. METHODS: This placebo-controlled clinical trial study was conducted in 2020. The research focused on 60 menopausal women referred to Mashhad health centers. Eligible participants were administered either an OBLE 500 mg capsule or a placebo daily for 1 month. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS) before, two weeks, and one month after the intervention. Data were analyzed using SPSS21, independent t, Mann-Whitney, and Friedman tests. A significance level of p < 0.05 was considered significant. RESULTS: The independent t-test indicated that the mean (SD) scores of menopausal symptoms in both the OBLE and placebo groups were initially similar before the intervention (P = 0.141). Two weeks after the intervention, the menopausal symptom scores were 9.5 ± 3.5 and 11.2 ± 5.6 in the OBLE and placebo groups, respectively (P = 0.163, df = 58, t = 1.4). After one month, the menopausal symptom scores were 6.9 ± 0.3 in the OBLE group and 11.26 ± 0.6 in the placebo group (P = 0.001, df = 58, t = 3.4). This indicates a significant difference between the two groups one month after the intervention, compared to before and two weeks after the intervention. Additionally, there was a significant difference in the scores of the physical and somato-vegetative dimension between the intervention and placebo groups two weeks and one month after the intervention (P < 0.05). CONCLUSION: The study results suggested that taking OBLE capsules led to a decrease in the scores of menopausal symptoms. This indicates that OBLE can be considered as a safe and cost-effective medicinal plant for alleviating menopausal symptoms among women.

Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.

BACKGROUND: Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-ß1), and other indicators in the presence and absence of ovaries in AKI female rats. METHODS: The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. RESULTS: After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-ß1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-ß1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-ß1, SIRT1, urea, creatinine, and albumin. CONCLUSION: The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-ß1 in ovary-intact animals.

Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model.

As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states. The perimenopausal gland showed moderate regression in ductal structure with no responsiveness to external hormones, while the menopausal gland showed severe regression with hypersensitivity to hormones. Leveraging the findings on the VCD model, effects of a major endocrine disruptor (polybrominated diphenyl ethers, PBDEs) on the mammary gland were examined during and after menopausal transition, with the two exposure modes; low-dose, chronic (environmental) and high-dose, subacute (experimental). All conditions of PBDE exposure did not augment or compromise the macroscopic ductal reorganization resulting from menopausal transition and/or hormonal treatments. Single-cell RNA sequencing revealed that the experimental PBDE exposure during the post-menopausal period caused specific transcriptomic changes in the non-epithelial compartment such as Errfi1 upregulation in fibroblasts. The environmental PBDE exposure resulted in similar transcriptomic changes to a lesser extent. In summary, the VCD mouse model provides both perimenopausal and menopausal windows of susceptibility for the breast cancer research community. PBDEs, including all tested models, may affect the post-menopausal gland including impacts on the non-epithelial compartments.

[Sport and menopause]. / Sport et ménopause.

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.

SPORT ET MÉNOPAUSE. La ménopause est une période physiologique de la vie de la femme qui peut être marquée par de nombreux symptômes impactant sa qualité de vie. Les plaintes les plus fréquentes sont les bouffées de chaleur, les troubles de l'humeur, du sommeil et de la mémoire. Le risque d'ostéoporose, de perte de force musculaire, les risques cardiovasculaire et métabolique augmentent d'autant plus qu'il y a une diminution de la pratique d'activité physique et une majoration du temps de sédentarité, fréquentes à cette période. Les recommandations d'activité physique et sportive contribuent à limiter les symptômes et les risques sur la santé induits par l'hypo-estrogénie. La pratique régulière d'activité physique au moins modérée en endurance et en renforcement musculaire apporte le plus de bénéfices, ce dont les femmes doivent être informées.

Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.