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Objective: This study aims to investigate the association between systemic inflammation, measured by the systemic immune-inflammatory index (SII), and menopausal symptoms in postmenopausal women., Methods: A cross-sectional study was conducted with 702 postmenopausal women recruited from a tertiary hospital. Participants completed the Menopause Rating Scale (MRS) to assess somatic, psychological, and urogenital symptoms. Blood samples were collected to calculate SII. Statistical analyses included correlation, univariate regression, and multivariate regression to determine the association between SII and menopausal symptoms., Results: The most commonly reported symptoms were muscle and joint problems (75.9%), hot flashes and sweating (72.5%), sleeping problems (71.2%), and depressive mood (69.9%). Women with higher total and somatic subscale scores had significantly elevated SII levels compared with those with lower scores. SII was the most associated variable for high total MRS (odds ratio, 4.77; 95% CI, 3.36-6.78; P < 0.001) and somatic subscale scores (odds ratio, 6.32; 95% CI, 4.45-8.99; P < 0.001). Exercise and gravidity were negatively associated with high total MRS and somatic subscale scores. Conversely, no significant associations were observed between SII and the urogenital or psychological subscale scores., Conclusion: Elevated SII levels were found associated with higher somatic subscale and total MRS scores, suggesting that inflammation may contribute to worsened somatic menopausal symptoms in this group. These findings suggest that exploring inflammatory pathways could be beneficial in managing menopausal symptoms and enhancing quality of life for postmenopausal women., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2024 by The Menopause Society.)

Objective: To investigate the relationship of dyslipidemia and menopausal symptoms in Chinese menopausal women., Material and Methods: A total of 989 eligible participants with menopausal syndrome were recruited from outpatient clinics in several cities in China. Menopausal symptoms were assessed using the Chinese Menopause Rating Scale (CMRS), the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS). Serum lipid profile was measured using enzyme colorimetry. The relationship between lipid profile and menopausal symptoms was assessed using Student's t test/nonparametric Mann-Whitney U test, Spearman's correlation test, and binary logistic regression analysis., Results: Among the 989 patients, 527 had dyslipidemia while 462 did not. Patients with dyslipidemia had significantly higher Self-rating Anxiety Scale (SAS) scores than those without (p < 0.001), while there was no significant difference in Self-rating Depression Scale (SDS) scores. Patients without dyslipidemia had higher scores on the Chinese Menopause Rating Scale (CMRS) vascular dimension compared to those with dyslipidemia (p = 0.003). The correlation test revealed that variables associated with dyslipidemia included age (p = 0.031), CMRS hot flashes dimension score (P = 0.003), and SAS score (p < 0.001). Regression analysis demonstrated that BMI (OR: 1.08, 95% CI: 1.01-1.16, p = 0.027), SAS scores (OR = 1.10, 95% CI = 1.07-1.13), vasomotor dimension (OR = 0.89, 95% CI = 0.83-0.95), physical dimension (OR = 0.96, 95% CI = 0.93-1.00), and social dimension (OR = 0.84, 95% CI = 0.74-0.95) were independently associated with an increased risk of dyslipidemia., Conclusions: This study showed that anxiety was associated with an unfavorable lipid profile, and menopausal depression seemed to have no relationship with lipid profile, while vasomotor symptoms appeared to be a favorable factor for dyslipidemia in Chinese menopausal women., Competing Interests: Declarations. Ethics approval: This study was approved by the ethics committee of Guangdong Provincial hospital of Chinese Medicine (B2013-074-01) on April 26, 2013. All participants provided written informed consent before participating in the study. Consent to participate: In the original survey, verbal and written informed consent was obtained from all respondents who were able to accept or decline their participation in the study. Consent for publication: Manuscript has been approved by all authors for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The severity of menopausal symptoms, despite being triggered by hormonal imbalance, does not directly correspond to hormone levels in the blood; thus, the level of unpleasantness is assessed using subjective questionnaires in clinical practice. To provide better treatments, alternative objective assessments have been anticipated to support medical interviews and subjective assessments. This study aimed to develop a new objective measurement for assessing unpleasantness., Methods: Fourteen participants with menopausal symptoms and two age-matched participants who visited our outpatient section were enrolled. Resting-state brain activity was measured using magnetoencephalography. The level of unpleasantness of menopausal symptoms was measured using the Kupperman Kohnenki Shogai Index. The blood level of follicle-stimulating hormone and luteinizing hormone were also measured. Correlation analyses were performed between the oscillatory power of brain activity, index score, and hormone levels., Results: The level of unpleasantness of menopausal symptoms was positively correlated with high-frequency oscillatory powers in the parietal and bordering cortices (alpha; P = 0.016, beta; P = 0.015, low gamma; P = 0.010). The follicle-stimulating hormone blood level was correlated with high-frequency oscillatory powers in the dorsal part of the cortex (beta; P = 0.008, beta; P = 0.005, low gamma; P = 0.017), whereas luteinizing hormone blood level was not correlated., Conclusion: Resting-state brain activity can serve as an objective measurement of unpleasantness associated with menopausal symptoms, which aids the selection of appropriate treatment and monitors its outcome., Competing Interests: Financial disclosure/conflicts of interest: Dr. Yoshihito Shigihara is leading a joint research project with RICOH Co., Ltd. (manufacturer of the magnetoencephalography equipment) and receives ongoing institutional funding from ITO EN, Ltd. Mr. Hideyuki Hoshi is employed by RICOH Co., Ltd. Dr. Kohei Nakamura, Ms. Momoko Kobayashi, Mr. Keisuke Fukasawa, and Ms. Sayuri Ichikawa declare no potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The Menopause Society.)

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.)

Purpose: This study aimed to find the associations between vasomotor symptoms (VMS) and metabolic syndrome (MetS) in Chinese middle-aged women in a cross-sectional study., Methods: A total of 675 participants were recruited from an urban Chinese community. MetS was defined by the 2009 criteria of the Joint Interim Statement. VMS including hot flashes and sweats, blood pressure, weight, height, waist circumference (WC), serum glucose, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), estradiol, and follicle-stimulating hormone (FSH) were collected., Results: The presence of hot flashes was independently associated with the risk of MetS after adjusting for age, menopausal status, FSH log , estradiol log , and physical activity (odds ratio: 1.98, 95% confidence interval: 1.21-3.24, p  = 0.006). Both hot flashes and sweats were also independently associated with WC (for hot flashes, p  = 0.016; and for sweats, p  = 0.007) and triglycerides (for hot flashes, p  = 0.041; and for sweats, p  = 0.014) significantly. However, VMS were not significantly associated with blood pressure, glucose, HDL, and LDL., Conclusion: Women with hot flashes had a higher risk of MetS. Both hot flashes and sweats were related to a higher amount of central fat indicated by WC and higher triglycerides, but were not related to blood pressure, glucose, and HDL in Chinese women.

Objectives: This study investigated the links between the severity of vasomotor symptoms (VMS) and the dietary consumption of a variety of nutrients. Method: A cross-sectional analysis of the first-visit records of 262 women aged 40-65 years was conducted. The severity of their hot flushes (HF) and night sweats (NS) and their dietary consumption of nutrients were evaluated using the Menopausal Health-Related Quality of Life Questionnaire and the brief-type self-administered Diet History Questionnaire, respectively. The relationships between severity of HF/NS and dietary intake were analyzed separately for 43 major nutrients. We then evaluated different food items as sources of the nutrients. Results: After adjustment for age, body mass index, menopausal status, and background factors significantly related to VMS, only vitamin B 6 (VB 6 ) was significantly related to severity of HF (adjusted odds ratio per 10 μg/MJ in VB 6 intake, 0.92; 95% confidence interval, 0.86-0.97). Moreover, a significant inverse relationship was found between the consumption of oily fish as a source of VB 6 and the severity of HF. Conclusions: VB 6 and oily fish intake is inversely associated with the severity of HF in middle-aged women. Therefore, increased intake of VB 6 could help attenuate HF.

Objective: To assess the association between hot flashes (HFs) severity and oxidative stress (OS) in Mexican postmenopausal women., Methods: A cross-sectional study was carried out with perimenopausal women aged 40-59 years community-dwelling from Mexico City, Mexico. They participated in Menopause and Oxidative Stress Project. The baseline sample consisted of 476 women recruited to participate; 161 women were excluded due to different reasons. Hence, 315 women were selected to establish two groups, a) 145 premenopausal women (yet with menstrual bleeding), and b) 170 postmenopausal women (without menses). All women were free of cardiovascular, kidney, hepatic or cancer disease, and without antioxidant supplement intake for at least six months prior to the beginning of the study; none had previously received hormone therapy. As OS markers, we measured plasma malondialdehyde using the TBARS assay, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), uric acid, and total antioxidant status; also, we calculated SOD/GPx ratio, antioxidant gap and an oxidative stress score ranging from 0 to 7. The HFs were evaluated using the Menopause Rating Scale. The women completed Spanish version of the Athens Insomnia Scale, Zung Self-Rating Anxiety Scale and Zung Self-Rating Depression Scale and a questionnaire of pro-oxidant factors., Results: Stress score increased with HFs severity (mild 2.7±0.17, moderate 2.9±0.20 and severe 3.7±0.20, p = 0.001) in postmenopausal women. We observed a positive correlation between HFs severity and stress score, r = 0.247 (p = 0.001) in postmenopausal women; other test scores were not correlated. Severe HFs were a risk factor for OS (OR = 5.12, 95%CI: 1.99-13.17, p<0.05) in an adjusted multivariate analysis by different postmenopausal symptoms and pro-oxidant factors; we did not see any association in premenopausal women., Conclusion: Our findings suggest an association between HFs severity and OS in Mexican postmenopausal women., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine whether vitamin D levels correlate with menopausal symptoms and female sexual functions., Study Design: A cross-sectional study., Place and Duration of Study: Izmir Katip Celebi University Hospital, Izmir, Turkey, between February and October 2017., Methodology: Menopausal and sexual active ladies aged 40-70 years were inducted. Those with psychiatric disorders, endocive abnormalities, related therapy, and malignancy were excluded. Menopause Rating Scale (MRS), and the Female Sexual Function Index (FSFI) were used to collect data. Also blood samples were collected from the patients. The study's data were examined with logistic and linear regression models., Results: Total MRS scale scores of the 303 subjects with one of the following conditions had a higher menopause symptom score; chronic disease, vaginal discharge, chronic pain, unsatisfied with sex, sleep problems, and low vitamin D level (p=0.023, p=0.007, p<0.001, p<0.001, p=0.017, and p<0.001; respectively). It was found that those who have middle income level were more likely to have better sexual function (OR: 0.209, 95% CI: 0.065; 0.671) compared to those who have low income level. It was found that those with higher MRS somatic complaint (OR: 1.274; 95% CI: 1.087; 1.494) and urogenital complaint (OR: 1.670; 95% CI: 1.326; 2.102) and ones with lower vitamin D levels (OR: 0.963; %95 CI: 0.941; 0.987) were more likely to report complaints for sexual function disorders., Conclusion: Vitamin D of all women in menopause should be evaluated. High vitamin D levels should reduce menopausal symptoms and positively affect sexual function.

Background: Hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurones regulate LH pulsatility. It is widely accepted that the menopausal hot flush (HF) consistently synchronizes with the LH pulse, implicating the hypothalamic KNDy neurones in generating LH pulsatility and HF. Using a modern immunoassay and mathematical modeling, we investigated if the HF and LH pulse were consistently synchronized in menopausal women., Methods: Eleven menopausal women (51 to 62 years of age and experiencing ≥7 HF in 24 hours) participated in an 8-hour study. Subjects self-reported HF and underwent peripheral blood sampling every 10 minutes. LH pulsatility was determined using two mathematical models: blinded deconvolution analysis and Bayesian spectrum analysis. The probability that the LH pulse and HF event intervals matched was estimated using the interval distributions observed in our data., Results: Ninety-six HFs were self-reported, and 82 LH pulses were identified by blinded deconvolution analysis. Using both models, the probability that the two event intervals matched was low in the majority of participants (mean P = 0.24; P = 1 reflects perfect association)., Interpretation: Our data challenge the widely accepted dogma that HFs consistently synchronize with an LH pulse and therefore have clinically important therapeutic and mechanistic implications., (Copyright © 2019 Endocrine Society.)

The most common symptoms during menopausal transition and menopause are vasomotor symptoms. We aimed to investigate the relationship between menopausal symptoms and metabolic syndrome (MetS) in postmenopausal women. Two hundred and fifty-four and 317 postmenopausal women were in the MetS and non-MetS groups, respectively. The total menopause rating scale and psychological subscale scores were higher in the MetS group than the non-MetS group, and the differences were significant (p < .05). A positive correlation was found between the abdominal circumferences, systolic-diastolic blood pressures, triglycerides and total MRS scores. However, a significant positive correlation was found between the abdominal circumference and total urogenital scores (p = .008). Impact statement What is already known on this subject? MetS and its dominant component (abdominal obesity) significantly increase the prevalence and severity of menopausal symptoms. Data regarding the relationship between metabolic syndrome (MetS) and vasomotor symptoms remain limited. What do the results of this study add? We showed that sleeping problems, depressive symptoms and bladder problems were more frequently encountered in the MetS group than in the non-MetS group (p<0.05). What are the implications of these findings for clinical practice and/or further research? There is a need for more randomised controlled studies to demonstrate the relationship between MetS and the severity of menopausal symptoms.

Purpose: Calcitonin gene-related peptide (CGRP) is a neuropeptide widely distributed in the central and peripheral nervous systems, which is known as a potent vasodilator. Postmenopausal women who experience hot flushes have high levels of plasma CGRP, suggesting its involvement in menopausal vasomotor symptoms., Methods: In this review, we describe the biochemical aspects of CGRP and its effects associated with deficiencies of sexual hormones on skin temperature, vasodilatation, and sweating as well as the possible peripheral and central mechanisms involved in these events., Results: Several studies have shown that the effects of CGRP on increasing skin temperature and inducing vasodilatation are potentiated by a deficiency of sex hormones, a common condition of postmenopausal women. Additionally, the medial preoptic area of the hypothalamus, involved in thermoregulation, contains over 25-fold more CGRP-immunoreactive cells in female rodents compared with male rodents, reinforcing the role of female sex hormones on the action of CGRP. Some studies suggest that ovarian hormone deficiency decreases circulating endogenous CGRP, inducing an upregulation of CGRP receptors. Consequently, the high CGRP receptor density, especially in blood vessels, amplifies the stimulatory effects of this neuropeptide to raise skin temperature in postmenopausal women during hot flushes., Conclusions: The duration of the perception of each hot flush in a woman is brief, while local reddening after intradermal administration of α-CGRP persists for 1 to 6 h. This contrast remains unclear.

Objectives: In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women., Methods: A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements., Results: Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported., Conclusion: After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Hot flashes are believed to be related to hormonal changes. However, the relationship between hormonal fluctuations and hot flashes has not been studied. The objective of this study is to determine hormone measurement summaries that best explain the incidence of hot flashes in midlife women., Study Design: In a cohort study of 798 midlife women over 1-7 years, women provided 4 weekly blood samples annually and completed a survey detailing life history, ongoing behaviors, and menopausal symptoms. Estradiol, progesterone, and testosterone were measured in all serum samples. Annual summary variables of each hormone were median, mean, maximum, minimum, variance, and range. The association of these values with hot flashes was assessed using multivariable logistic regression and Bayesian network analysis, controlling for smoking history and menopausal status., Main Outcome Measures: Hot flash incidence, severity, and frequency., Results: For most outcomes, the best-fit model included progesterone variability; increased progesterone variance or range was correlated with decreased hot flash frequency (OR = 0.82, 95% CI = 0.74-0.91) and severity (OR = 0.82, 95% CI = 0.77-0.88). In the Bayesian network model, the maximum estradiol value was negatively correlated with many outcomes (OR for hot flashes = 0.68). Relationships between progesterone variability, maximum estradiol level, maximum progesterone level, and hot flashes indicate that the effects of progesterone variance on hot flash outcomes are likely mediated through progesterone's relationship with maximum estradiol level., Conclusions: Variability of progesterone, as opposed to mean values, should be used as an indicator of risk of hot flashes in midlife women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations., Methods: Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol., Results: In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P < 0.05) indicated that among the younger tertile of women in the sample (age 40-53 years), the presence of hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol., Conclusions: Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Purpose: Tamoxifen is frequently prescribed to prevent breast cancer recurrence. Tamoxifen is a prodrug and requires bioactivation by CYP2D6. Tamoxifen use is often limited by adverse effects including severe hot flashes. There is paucity of prospectively collected data in terms of CYP2D6 genotype and measured tamoxifen, 4-hydroxytamoxifen and endoxifen concentrations in relation to hot flash severity during tamoxifen therapy., Methods: We conducted a longitudinal prospective study of breast cancer patients on tamoxifen (n = 410). At each visit, blood samples were collected, and patients completed a standardized hot flash survey (n = 1144) that reflected hot flash severity during the 7 days prior to the visit. Plasma concentrations of tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using liquid chromatography-tandem mass spectrometry and genotyping was carried out for CYP2D6. A linear mixed-effects regression analysis assessed the association of covariates in relation to the hot flash severity score (HFSS)., Results: Median age at first assessment was 50 years with 61.9% of patients considered peri-menopausal. Most patients (92.2%) experienced hot flash symptoms with 51.0% having low HFSS (0-4) and 7.32% experiencing HFSS > 25. Age was significantly associated with hot flash severity, with patients aged 45-59 more likely to have higher HFSS. Neither duration of tamoxifen therapy nor observed tamoxifen, endoxifen and 4-hydroxy tamoxifen plasma concentration predicted hot flash severity. Genetic variation in CYP2D6 or CYP3A4 was not predictive of hot flash severity., Conclusions: Hot flash severity during tamoxifen therapy can not be accounted for by CYP2D6 genotype or observed plasma concentration of tamoxifen, 4-hydroxytamoxifen, or endoxifen.

Objective: The mechanism underlying hot flashes is not well-understood, primarily because of complex relationships between and among hot flashes and their risk factors., Methods: We explored those relationships using a Bayesian network approach based on a 2006 to 2015 cohort study of hot flashes among 776 female residents, 45 to 54 years old, in the Baltimore area. Bayesian networks were fit for each outcome (current hot flashes, hot flashes before the end of the study, hot flash severity, hot flash frequency, and age at first hot flashes) separately and together with a list of risk factors (estrogen, progesterone, testosterone, body mass index and obesity, race, income level, education level, smoking history, drinking history, and activity level). Each fitting was conducted separately on all women and only perimenopausal women, at enrollment and 4 years after enrollment., Results: Hormone levels, almost always interrelated, were the most common variable linked to hot flashes; hormone levels were sometimes related to body mass index, but were not directly related to any other risk factors. Smoking was also frequently associated with increased likelihood of severe symptoms, but not through an antiestrogenic pathway. The age at first hot flashes was related only to race. All other factors were either not related to outcomes or were mediated entirely by race, hormone levels, or smoking., Conclusions: These models can serve as a guide for design of studies into the causal network underlying hot flashes.

Introduction: Many postmenopausal women experience hot flashes, night sweats, non-specific emotional and psychological distresses. Our aim was to investigate the relation among steroid hormone levels, lipid profile and menopausal symptom severity using the menopause rating scale (MRS)., Methods: A cross-sectional study was performed at our outpatient clinic with natural postmenopausal women. A total of 444 women were included in this study. The basic characteristics of the study population, such as age, gravidity, parity, time to menopause onset and body mass index (BMI) were recorded. Venous blood samples were collected from subjects after overnight fasting. The levels of high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglyceride (TG), fasting plasma glucose, C-reactive protein, thyroid-stimulating hormone (TSH), cortisol, estradiol (E2), progesterone, testosterone and dehydroepiandrostenedione sulfate (DHEA-S) were analyzed. The MRS questionnaire validated for the Turkish population was used to assess the menopausal symptoms., Results: There was a statistically significant difference between mild and severe total symptom scores for TG, and elevated TG levels were observed in the severe group (p = 0.04). Elevated testosterone levels were observed with severe psychological symptom and total symptom scores. There were significant differences in progesterone level in psychological, urogenital, and total scores and lower levels were seen in severe symptom groups. There was a significant negative correlation between urogenital symptom scores and progesterone levels (p < 0.001)., Discussion: Elevated levels of testosterone were related to severe psychological symptom and total menopausal symptom scores. A decrease in progesterone levels was related to high psychological, urogenital and total menopausal symptom scores. Elevated TG levels were also related to the total severe symptom scores.

Introduction: Hot flashes have been postulated to be linked to systemic inflammation. This study aimed to investigate the relationship between hot flashes, pro-inflammatory factors, and leukocytes in healthy, non-obese postmenopausal women., Participants and Design: In this cross-sectional study, a total of 202 women aged 45-60 years were stratified into one of four groups according to their hot-flash status: never experienced hot flashes (Group N), mild hot flashes (Group m), moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, leukocytes, and fasting plasma levels of nine circulating cytokines/chemokines measured by using multiplex assays. Multiple linear regression analysis was used to evaluate the associations of hot flashes with these pro-inflammatory factors., Settings: The study was performed in a hospital medical center., Results: The mean values of leukocyte number were not different between these four groups. The hot flash status had a positive tendency toward increased levels of circulating IL-6 (P-trend = 0.049), IL-8 (P-trend < 0.001), TNF-α (P-trend = 0.008), and MIP1β (P-trend = 0.04). Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with IL-8 (P-trend < 0.001) and TNFα (P-trend = 0.007) among these nine cytokines/chemokines after adjustment for age, menopausal duration, BMI and FSH. Multivariate analysis further revealed that severe hot flashes were strongly associated with a higher IL-8 (% difference, 37.19%; 95% confidence interval, 14.98,63.69; P < 0.001) and TNFα (51.27%; 6.64,114.57; P < 0.05)., Conclusion: The present study provides evidence that hot flashes are associated with circulating IL-8 and TNF-α in healthy postmenopausal women. It suggests that hot flashes might be related to low-grade systemic inflammation.

Introduction: Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women., Participants and Design: In this cross-sectional study, a total of 151 women aged 45-60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance., Settings: The study was performed in a hospital medical center., Results: The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00-90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin., Conclusion: The present study provides evidence that hot flashes are associated with insulin resistance in postmenopausal women. It further suggests that hot flash association with insulin resistance is dependent on the combination of leptin and adiponectin variables.

Objective: Vasomotor symptoms (VMS) may be a marker of cardiovascular risk. We aimed to evaluate the cross-sectional association of VMS presence and severity with hemostatic parameter levels measured at baseline among Women's Health Initiative (WHI) Hormone Therapy trial postmenopausal participants., Methods: This cross-sectional analysis included 2,148 postmenopausal women with measures of VMS presence and severity reported in the 4 weeks before WHI baseline, who were not using warfarin or hormone therapy and for whom the following baseline hemostatic parameters were measured within the WHI Cardiovascular Disease Biomarker Case-Control Study: antithrombin, plasminogen activator inhibitor-1, protein C antigen, total and free protein S antigen, total and free tissue factor pathway inhibitor, D-dimer, normalized activated protein C sensitivity ratio, and thrombin generation. Using multiple linear regression, we estimated the adjusted average difference in each hemostatic parameter associated with VMS presence and severity. A multiple comparisons-corrected P value was computed using the P-min procedure to determine statistical significance of our smallest observed P value., Results: Women were 67 years of age on average and 33% reported VMS presence at baseline. There was some suggestion that VMS presence may be associated with a -0.34 adjusted difference in normalized activated protein C sensitivity ratio compared with no VMS (95% CI, -0.60 to -0.087; P = 0.009), but this association was not significant after correction for multiple comparisons (P = 0.073). VMS presence or severity was not significantly associated with the other hemostatic parameters., Conclusions: We found no convincing evidence that VMS presence or severity was associated with levels of hemostatic parameters among postmenopausal women.

Objective: To compare the effect and differences sex the influence of hormone levels of perimenopau-sal syndrome patients between manual acupuncture and electroacupuncture (EA)., Methods: A total of 50 cases with perimenopausal syndrome were randomly assigned into an manual acupuncture group (27 cases) and an EA group (23 cases), and 1 case dropped in the EA group. The acupoints in the two groups were Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), and Sanyinjiao (SP 6). Acupuncture with 3-time small and even manipulation of lifting, thrusting and twirling was used in the acupuncture group, once 10 min. EA with sparse-dense wave and 10 Hz/50 Hz was applied in the EA group for 30 min. The treatments in the two groups were for continuous 8 weeks (24 times in total), once the other day, 3 times a week. The scores of 24-hour hot flashes even, menopausal rating scale (MRS) and menopause-specific quality of life questionnaire (MENQOL) were recorded before treatment and after 4-week and 8-week treatment, as well as 12 and 24 weeks after treatment. Serum sex hormone levels were tested before and after 8-week treatment as well as 12 weeks after treatment, including serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estracliol (E 2 )., Results: Compared with those before treatment, the 24-hour hot flashes even score, MRS and MENQOL scores were significantly lower after 4-week and 8-week treatments, 12 and 24 weeks after treatment (all P <0.05). All the above scores after 8-week treatment were lower than those after 4-week treatment (all P <0.05); and the scores 12 and 24 weeks after treatment were lower than those after 4-week and 8-week treatments (all P <0.05); all the scores after treatment were not significantly different at any time between the two groups (all P >0.05). Compared with those before treatment, serum FSH and E 2 apparently improved in the two groups after 8-week treatment and 12 weeks after treatment (all P <0.05). LH levels did not significantly change in the two groups (all P >0.05). All the serum sex hormone levels showed no significant difference between the two groups (all P >0.05)., Conclusions: Both acupuncture and EA can improve perimenopausal symptoms and serum sex hormone. The effects are similar.

During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.

Objective: This study aims to evaluate the effectiveness and safety of Gua sha therapy on perimenopausal symptoms, quality of life, and serum female hormones in participants with perimenopausal syndrome., Methods: A prospective, randomized, controlled clinical trial was conducted at the First Affiliated Hospital of Nanjing University of Chinese Medicine in China. Eighty women with perimenopausal syndrome were recruited and randomized into an intervention group or a control group. Participants in the intervention group received 15-minute Gua sha treatment sessions once a week plus conventional treatment for 8 weeks, whereas participants in the control group received conventional treatment alone. The primary outcome was the change in perimenopausal symptoms and quality of life as obtained through the modified Kupperman Index (KI) and the Menopause-Specific Quality of Life. The secondary outcome was the change of serum female hormones including estrogen, follicle-stimulating hormone, and luteinizing hormone., Results: Seventy-five out of 80 participants (93.8%) completed the study-38 in the intervention group and 37 in the control group. The baseline levels of demographic and outcome measurements were comparable between the two groups. After eight sessions of intervention, the reduction in the total modified KI score was, however, 16.32 ± 4.38 in the intervention group and 11.46 ± 5.96 in the control group, with a difference of 4.86 ± 6.15 (P < 0.01) between the two groups. Also the reductions of hot flash/sweating, paresthesia, insomnia, nervousness, melancholia, fatigue, and headache were greater in the intervention group than in the control group (P < 0.05). The reduction in the total Menopause-Specific Quality of Life score was 17.87 ± 3.84 in the intervention group and 13.62 ± 7.40 in the control group, with a difference of 4.46 ± 7.52 (P < 0.01) between the two groups. And the scores for vasomotor, psychosocial, and physical domains in the intervention group were significantly lower than those in the control group (P < 0.05). There were no significant differences in serum estrogen, follicle-stimulating hormone, and luteinizing hormone between the two groups., Conclusions: The results of this study suggest that Gua sha therapy was effective and safe in relieving perimenopausal symptoms and improving the quality of life in participants with perimenopausal syndrome. The therapy may serve as a promising, effective, nondrug treatment for perimenopausal syndrome in clinical work. Additional research is needed to better understand its effectiveness and examine its mechanism for treating perimenopausal syndrome.

The aim of this case report is to show that hemochromatosis can present, unusually, with night sweats. At presentation, hemochromatosis often tends to have non-specific symptoms, making it easy to misdiagnose, especially if it presents with rare symptoms. Misdiagnosis of hemochromatosis can lead to lethal outcomes, given it can cause multiple organ dysfunctions if left untreated and hence the need to identify it early on. The case we present is a 41-year-old woman with previously undiagnosed hemochromatosis complaining of night sweats. She thought she was menopausal. The diagnosis of hemochromatosis was made solely on investigations given that she did not have any other symptoms other than night sweats. Her serum iron concentrations were within the normal range due to menstruation. It is uncommon for women to present with symptoms of hemochromatosis during their reproductive life since their iron concentration is kept within normal range through monthly menstrual bleeding.

Introduction: Evidence suggests that hot flushes are associated with fluctuating levels of oestradiol (E2) during menopause, as well as changes in the levels of follicle-stimulating hormone (FSH) and inhibin B. The relationship between hot flushes and anti-Müllerian hormone (AMH) is unknown., Aim: To examine specific hormone levels and ethnic differences in relation to hot flushes., Methods: Data were drawn from 108 women aged 40-59 years. There were three groups of participants: European women in London, UK; Bangladeshi women in Sylhet, Bangladesh; and Bangladeshi women who had migrated to London as adults. Symptom information was collected via questionnaires. Serum blood samples were collected to detect inhibin B, AMH, FSH, and E2., Results: AMH and FSH were significantly associated with the experience of hot flushes in the past 2 weeks. Inhibin B and E2 were not associated with hot flushes. Body mass index (BMI), ethnicity, and education level were associated with both the occurrence and the frequency hot flushes. Menopausal status was also associated with the frequency of hot flushes., Conclusion: Relationships between AMH, FSH and symptoms are indicative of women's progress through the menopausal transition. The influence of BMI and education suggest that lifestyle changes may contribute to the management of symptoms. This merits further research., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Despite the high prevalence of depressive symptoms in women, the precise role of sex hormones in mood changes during the menopausal transition is unclear. Previous studies have been inconsistent with regard to identifying the association of androgens, namely total testosterone, with depressive symptoms., Objective: The objectives of this study were to evaluate changes in serum total testosterone levels and depressive symptoms during the entire menopausal transition, and examine the impact of covariates on the association between concurrent serum total testosterone levels and depressive symptoms during this time period., Methods: A longitudinal cohort study (428 women at baseline with 3634 repeated measures) using data from the Penn Ovarian Aging Study, a population-based cohort of late reproductive-aged women, followed through the menopausal transition. Serum hormone parameters and depression scores using the Center for Epidemiological Studies of Depression scale (CES-D) were measured at each annual visit over a 14-year period. General linear (for testosterone) and a generalized negative-binomial model (for depressive symptoms) for repeated measures were used for analysis., Results: Serum total testosterone levels increased progressively over the study period and were significantly associated with older age and with current smoking (p<0.001, respectively). In the post menopause total testosterone levels were significantly higher in African Americans compared to Caucasians (p=0.012). The proportion of women with CES-D ≥16 significantly decreased with increasing age and in the post-menopausal period, and were higher in women with a history of depression and hot flashes (p<0.001). The association between concurrent testosterone levels and high depressive symptoms (CES-D ≥16) differed by race (p=0.008). In Caucasians, but not African Americans, higher serum testosterone levels were associated with increased depressive symptoms after controlling for several variables including age, obesity status, hot flashes and menopausal status (RR 1.09, 95% CI 1.00-1.17, p=0.042)., Conclusion: In our cohort, testosterone levels were low but progressively increased from premenopause through post menopause. In addition to age and history of depression, we identified race to have a significant interaction between the association of testosterone levels and depressive symptoms. This study further supports the associations between sex hormones and increased risk of having depressive symptoms, although the precise underlying mechanisms for this association remain unclear., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to examine the associations of demographic characteristics, health behaviors, and hormone concentrations with the experience of any, current, more severe, and more frequent midlife hot flashes., Methods: Baseline data from 732 women aged 45 to 54 years who were enrolled in the Midlife Women's Health Study were analyzed. A clinic visit was conducted to collect blood samples for hormone assays and to measure ovarian volume using transvaginal ultrasound. A self-administered questionnaire ascertained information on demographic factors, health habits, and hot flash history. Multivariable logistic regression was conducted to examine associations between potential risk factors and hot flash outcomes., Results: Approximately 45% of participants reported experiencing midlife hot flashes. In covariate-adjusted models, older age, perimenopause status, current and past cigarette smoking, and depressive symptoms were significantly associated with increased odds of all of the hot flash outcomes. In addition, history of oral contraceptive use was associated with increased odds of any hot flashes. In contrast, higher current alcohol intake was significantly associated with decreased odds of any, current, and more severe hot flashes. Higher estradiol and progesterone concentrations were significantly associated with decreased odds of all hot flash outcomes., Conclusions: Although the temporality of such associations is not known because of the cross-sectional nature of the data, these observed relationships can help to identify women at risk for hot flashes.

Objective: At present, there is growing demand for alternative, or additional, treatments to hormone replacement therapy for menopause-related hot flashes (HF). Antioxidant supplements have been recently proposed as possible candidates for this purpose, regardless of the absence of clear evidence in support of a link between these vasomotor symptoms and oxidative stress (OxS). The aim of our study was to evaluate the association between HF and OxS serum markers in a large sample of middle-aged women., Materials and Methods: We conducted a cross-sectional study on 245 perimenopausal and early postmenopausal women (age 45-60 years). The variables examined were presence of self-reported HF and levels of 8-iso-prostaglandin F2α, 8-OH-deoxy-2'-guanosine, advanced oxidation protein products, total antioxidant power, uric acid, thiols, and paroxonase-1., Results: Seventy-six women (31%) reported to suffer from HF (either medium or high intensity). None of the peripheral markers of OxS examined was found to be significantly associated with the presence of HF., Conclusion: Taken together, our data suggest that systemic OxS might not be implicated with the onset of the climacteric vasomotor symptoms that most commonly affect women experiencing perimenopause and early postmenopause., (Copyright © 2015. Published by Elsevier B.V.)

Objective: This study determined the impact of breastfeeding on hypoestrogenic symptoms among women in the postpartum period and correlated these findings with the Estrogen Threshold Hypothesis, which postulates that the hypoestrogenic symptoms experienced are related to circulating estrogen levels., Study Design: Using a survey instrument that combined previously validated assessments of postpartum mood changes and menopausal symptoms, women were evaluated in the immediate postpartum period, prior to hospital discharge, and at 3 and 6 weeks postpartum. Each time period was analyzed independently, in a cross-sectional design, where women were categorized as "breastfeeding" or "bottle feeding.", Results: Of 236 women recruited, 171 (72.5%) intended to breastfeed, and 62 (26.3%) intended to bottle feed. At both the 3- and 6-week postpartum evaluations, a similar percentage of women in the breastfeeding and bottle-feeding groups reported hot flashes. However, breastfeeding women were more likely to report vaginal dryness than those who did not breastfeed: 20/150 (13.3%) versus 3/80 (3.8%) at 3 weeks, p<0.05; 25/143 (17.5%) versus 2/87 (2.3%) at 6 weeks, p<0.001., Conclusions: The Estrogen Threshold Hypothesis accurately predicts the findings of increased reported vaginal dryness but not hot flashes during lactation.

Aim: The aim of this study was to assess the effect of body iodine status on hot flashes and cardiovascular disease risk in postmenopausal women., Methods: Two hundred and ten consecutive postmenopausal women without known any risk factor for cardiovascular disease risk or systemic disorder were recruited for the study. All participants underwent serum screening consisted of lipid profile including lipoprotein-a (Lp(a)) and urinary iodine excretion. Participants were also asked for the frequency and the duration of hot flashes. All parameters were assessed for the association between urine iodine excretion and other parameters., Results: Urine spot iodine level was significantly correlated with Lp(a) (r = -0.287, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = -0.187, p = 0.006), cholesterol level (r = -0.573, p < 0.001), TG level (r = -0.211, p = 0.02), frequency of hot flashes per a day (r = -0.467, p < 0.001), durations of hot flashes (r = -0.424, p < 0.001), fasting glucose level (r = 0.331, p < 0.001), and fT3 level (r = 0.475, p < 0.001). In multivariate analysis, Lp(a) levels were significantly associated with the urine iodine level (beta coefficient = -0.342, p < 0.001) after adjustment for LDL-C (beta coefficient = 0.225, p < 0.001), glucose (beta coefficient = 0.303, p < 0.001), and age (beta coefficient = 0.146, p < 0.017)., Conclusion: Body iodine status during postmenopausal period is associated with the menopausal symptoms and lipid profile including Lp(a).

Objective: Sleep disturbance is an important change in menopause because it affects quality of life and can lead to other conditions such as depression. This study measured sleep alterations and explored associated physical, emotional, hormonal, and lifestyle factors during perimenopause and postmenopause., Methods: This cross-sectional study enrolled 160 women who were classified as perimenopausal (n = 85) or postmenopausal (n = 75). Using diaries, we collected data on duration of sleep, time awake in bed, and sleep efficiency. Follicle-stimulating hormone, 17β-estradiol, and cortisol levels were quantified by radioimmunoassay, and serum anti-Müllerian hormone levels were measured using enzyme-linked immunosorbent assay. Correlations between sleep measurements and symptoms were assessed using a generalized linear model., Results: The reported duration of sleep was similar for both groups of women (close to 6.9 h), and sleep efficiency was 88%. We did not find any factor that was associated with duration of sleep. Sleep efficiency was negatively associated with age, perimenopause/postmenopause status, loss of sexual interest, hot flashes, and depressed mood. Time awake in bed was positively associated with depressed mood (P < 0.000001), cigarette smoking (P < 0.000041), menopause status (P < 0.00009), and age (P < 0.0009). These associations remained after controlling for exercise, alcohol consumption, and caffeine consumption as confounding variables. Finally, morning salivary cortisol was reduced in postmenopausal women., Conclusions: Time awake in bed shows the most significant associations. Depressed mood, age, and menopause status are the main factors associated with sleep disturbances.

Objective: There is a renewed interest in the delivery of estradiol (E2) for the reduction of menopausal symptoms in young symptomatic menopausal women. This paper compares experimentally and theoretically obtained E2 plasma values by oral and transdermal delivery and compares them with relevant menopausal symptoms., Study Design: Two independent previously published studies were compared, which each contained 42 young symptomatic menopausal women. Experimentally obtained plasma values at days 1, 7 and 21 were compared with a theoretical model, taken from the literature, for describing plasma values for an oral immediate release formulation, consecutively for 21 days. Menopausal symptoms were determined in the steady state for oral and transdermal delivery with the Kuppermann index, previously not reported. In the case of oral delivery, estradiol was compared with estradiol valerate., Results: Previously published results for transdermal delivery of E2 showed that the matrix system establishes a steady state condition with the application of the first patch. Excellent agreement between theoretically predicted and experimentally obtained E2 plasma values for oral delivery in menopausal women was obtained. Circadian E2 plasma levels were observed continuously for transdermal delivery, were seen in oral delivery during first application and disappeared when steady state was achieved. Application of the prodrug E2-valerate delayed the maximum plasma peak from 1 pm to 4 pm, similar to the transdermal matrix patch. Investigating menopausal symptoms determined with the Kuppermann index did not reveal differences between oral or transdermal "E2 kinetic (hot flushes) relationship". This relationship was similar to symptomatic women suffering from hot flushes in untreated menopausal women or premenopausal women. Different menopausal symptoms required different E2 plasma levels: the average E2 levels higher than 23 pg/mL in plasma did abolish insomnia in 50% of postmenopausal women, with 28 pg/mL is needed to suppress 50% of dysthymia; however, rather high levels of 41 pg/mL are needed to suppress 50% of hot flushes, suggesting a rather complex mechanism beyond an E2 receptor mediated process., Conclusion: There is a difference in the steady state between oral and transdermal E2 delivery. Steady state condition is achieved in the first application of a matrix patch, whereas with the application of a tablet the steady state is achieved in transdermal delivery within 12-14 days. Our reported calculated missed intake of a E2 tablet shows that E2 plasma levels drop for 4 days consecutively. Our conducted study has several limitations: firstly, no cross-over was conducted, but a rather cumbersome mathematical modeling; secondly, healthy women with no accompanying severe diseases were included in this study. The higher the oral dose, the higher the E2 steady state levels, but the time to achieve steady state levels is independent from the E2 dose.

Objective: To test relationships between adipokines, adiposity, and vasomotor symptoms (VMS), including how these associations vary by menopause stage., Design: A subcohort of the longitudinal cohort Study of Women's Health Across the Nation completed questionnaires, physical measures, and a fasting blood draw annually for 8 years. Associations between a poorer adipokine profile (lower adiponectin, lower high-molecular-weight [HMW] adiponectin, higher leptin, lower soluble leptin receptor, higher monocyte chemoattractant protein 1 [MCP-1]) and VMS were tested with the use of generalized estimating equations adjusting for potential confounders. Interactions by menopause stage (pre-/early perimenopause, late peri-/postmenopause) were tested., Setting: Community., Patient(s): A total of 536 women ages 42-52 at baseline., Intervention(s): None., Main Outcome Measure(s) Vms Result(s): Associations between adipokines and hot flashes varied by menopause stage, with a poorer adipokine profile associated with higher odds of hot flashes early in the transition (adiponectin(log): odds ratio [OR] 0.68, 95% confidence interval [CI] 0.51-0.90; HMW adiponectin(log): OR 0.70, 95% CI 0.58-0.85; leptin(log): OR 1.23, 95% CI 0.99-1.54; multivariable models including body mass index [BMI]), but not later in the transition. The direction of associations between BMI and VMS also varied by menopausal stage. Higher MCP-1 was associated with more night sweats (OR 1.37, 95% CI 1.06-1.76) across menopausal stages., Conclusion(s): An adverse adipokine profile was associated with more VMS, particularly early in the menopause transition., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: We sought to study the effect of tubal ligation on lipid profile, ovarian reserve and hot flashes during perimenopausal years., Methods: A total of 210 perimenopausal women complaining of abnormal vaginal bleeding were enrolled for the study. Subjects' menstrual, reproductive and medical histories were recorded. Serum FSH, LH and estradiol levels were screened in all women to determine menopausal status. In order to rule out any gynecologic pathology, all subjects underwent transvaginal sonography. Women were divided into two groups according to presence (study group, n = 68) or absence (control group, n = 142) of tubal ligation history. Lipid profiles and ovarian reserve tests were compared between groups., Results: Mean age, parity, serum hemoglobin (Hb), high density lipoprotein (HDL-C), triglyceride, estradiol levels, endometrial thickness and frequency of hot flashes were significantly different between groups (p < 0.05). Mean age was 42.8 ± 1.9 years in women with tubal ligation and 45.9 ± 3.5 years in control group. Mean serum estradiol level was lower in group with tubal ligation (41.4 versus 92.5 pg/ml). Mean endometrial thickness was higher in control group (10.2 versus 7.5 mm). Age-adjusted serum Hb, HDL-C, triglyceride, estradiol, FSH level, endometrial thickness and frequency of hot flashes remained significantly different between groups (p < 0.05)., Conclusion: Tubal ligation is associated with unfavorable lipid profile and higher frequency of hot flashes during perimenopausal years.

Objective: 7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors., Methods: A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 postmenopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity., Results: Pharmacokinetic studies demonstrated 7-HMR C max = 757.08 ng/ml at 1 hour and ENL C max = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study., Conclusion: The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population.

Objective: Recent data have indicated that menopausal hot flashes may be a determinant for cardiovascular health. Therefore, we studied the impact of hot flashes on insulin resistance, one of the most powerful markers of cardiovascular health, in recently postmenopausal women., Methods: We studied 143 recently postmenopausal (amenorrhea 6-36 mo) healthy and normal-weight women without previous hormone therapy use. The women prospectively recorded the number and severity of hot flashes for 2 weeks, and a validated total symptom score, the hot flash weekly weighted score, was calculated for each woman. Insulin resistance was assessed from fasting blood levels of glucose and insulin with the homeostasis model assessment., Results: In 12 women, the assessment of insulin (n = 11) or glucose (n = 1) failed, and they were excluded from further analysis. Thus, hot flashes were absent in 19, mild in 32, moderate in 27, and severe in 53 women. The levels of glucose or insulin, or HOMA showed no differences between these groups, nor was insulin resistance related to the number or severity of hot flashes or to the levels of C-reactive protein or sex hormone-binding globulin. Overall, insulin resistance showed a positive association with body mass index (mean difference, 0.058; 95% CI, 0.015-0.102; P = 0.009) and a negative association with level of estradiol (mean difference, -0.002; 95% CI, -0.003 to -0.001; P = 0.009)., Conclusions: Insulin resistance may not be involved in hot flash-related changes in cardiovascular health. However, because of the small sample size, these findings need to be interpreted with caution.

Context: Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis., Objective: The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women., Design, Setting, and Participants: This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women (controls)., Main Outcomes: Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured., Results: P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive protein levels did not differ (P = 0.4) between the groups. Hot flush severity was the most important independent predictor of P-selectin levels (P = 0.011) in early menopausal women. Women with moderate/severe/very severe hot flushes had increased P-selectin compared with women with no/mild hot flushes or controls (P < 0.05 for both). The sCD40L levels were also higher in menopausal women with moderate/severe/very severe hot flushes compared with controls (P = 0.03) but did not differ significantly compared with women with no/mild hot flushes (P = 0.2)., Conclusions: Increased indices of vascular inflammation in early menopausal compared with age-matched premenopausal women may indicate a higher atherosclerotic risk. Increased severity of hot flushes was associated with adverse changes in vascular inflammation, further supporting the emerging role of hot flushes in cardiovascular prognosis in these women.

Aim: To study a possible association between the potent vasodilatory nitric oxide and postmenopausal hot flushes., Methods: We compared the release of nitric oxide in 150 recently menopausal women reporting no (n = 23), mild (n = 34), moderate (n = 30), or severe (n = 63) hot flushes. Plasma samples, collected after a 48-h arginine-poor diet, were assessed for the metabolites of nitric oxide (NOx), using the Griess reaction., Results: Levels of NOx showed no association with the severity of hot flushes. Furthermore, no relationships with individual hot flushes and serum levels of estradiol or high-sensitivity C-reactive protein were detected., Conclusions: These preliminary data indicate that nitric oxide appears not to be a factor in hot flushes and might not be related to their etiology. Since a fasting plasma NOx measurement may not reflect what happens at the time of the hot flush episode, in future studies there should be an attempt to assess nitric oxide release during a concomitant hot flush.

Objective: To examine associations between vasomotor symptoms and lipids over 8 years, controlling for other cardiovascular risk factors, estradiol, and follicle-stimulating hormone., Methods: Study of Women's Health Across the Nation participants (N=3,201), aged 42-52 years at entry, completed interviews on frequency of hot flushes and night sweats (none, 1-5 days, 6 days or more, in the past 2 weeks) physical measures (blood pressure, height, weight), and blood draws (low-density lipoprotein [LDL], high-density lipoprotein [HDL], apolipoprotein A-1, apolipoprotein B, lipoprotein[a], triglycerides, serum estradiol, follicle-stimulating hormone) yearly for 8 years. Relations between symptoms and lipids were examined in linear mixed models adjusting for cardiovascular risk factors, medications, and hormones., Results: Compared with no flushes, experiencing hot flushes was associated with significantly higher LDL (1-5 days: β [standard error]=1.48 [0.47], P<.01; 6 days or more: β [standard error]=2.13 [0.62], P<.001), HDL (1-5 days: β [standard error]=0.30 [0.18]; 6 days or more: β [standard error]=0.77 [0.24], P<.01), apolipoprotein A-1 (1-5 days: β [standard error]=0.92 [0.47], P<.10; 6 days or more: β [standard error]=1.97 [0.62], P<.01), apolipoprotein B (1-5 days: β [standard error]=1.41 [0.41], P<.001; 6 days or more: β [standard error]=2.51 [0.54], P<.001), and triglycerides (1-5 days: percent change [95% confidence interval]=2.91 [1.41-4.43], P<.001; 6 days or more: percent change [95% confidence interval[=5.90 [3.86-7.97], P<.001) in multivariable models. Findings largely persisted adjusting for hormones. Estimated mean differences in lipid levels between hot flushes 6 days or more compared with no days ranged from less than 1 (for HDL) to 10 mg/dL (for triglycerides). Night sweats were similar. Associations were strongest for lean women., Conclusion: Vasomotor symptoms were associated with higher LDL, HDL, apolipoprotein A-1, apolipoprotein B, and triglycerides. Lipids should be considered in links between hot flushes and cardiovascular risk., Level of Evidence: II.

Objectives: Conflicting evidence indicates an increased risk for cardiovascular disease in postmenopausal women suffering from hot flushes. In this study, we tested whether, beyond hot flushes, menopausal symptoms are associated with biochemical and biophysical risk factors for cardiovascular disease., Methods: Retrospective cross-sectional analysis on 951 women in surgical or physiological postmenopause, recruited at the menopause outpatient service of our university hospital between April 2002 and December 2009. The Greene Climacteric Scale and its subscales for anxiety, depression, somatic symptoms, vasomotor symptoms and sexuality were used to evaluate menopausal complaints. Blood pressure, fasting glucose and lipids levels were evaluated as risk factors for cardiovascular disease. Anthropometric parameters and those derived by remote and reproductive medical history were used as possible confounders. All data were anonymously retrieved from an electronic database., Results: By multiple regression analysis, high density lipoprotein (HDL) cholesterol was inversely related to body mass index, the Greene Climacteric Scale score and years since menopause (R = 0.390; p = 0.0001). The total cholesterol/HDL cholesterol ratio was positively related to waist circumference and the Greene Climacteric Scale score (R = 0.356; p = 0.0001). Triglycerides (R = 0.353; p = 0.0001) and triglyceride/HDL cholesterol (R = 0.425; p = 0.0001) were positively related to waist circumference, the Greene Climacteric Scale score and the Greene vasomotor subscore. Glucose was positively related to waist circumference, years since menopause and the Greene Climacteric Scale score (R = 0.390; p = 0.0001). Blood pressure was not related to menopausal symptoms. The 10-year risk for cardiovascular disease calculated by the Framingham formula was related independently and directly to body mass index and the Greene Climacteric Scale score (R = 0.183; p = 0.0001)., Conclusions: Menopausal symptoms evaluated by a validated climacteric scale are associated with a worsening of biochemical risk factors for atherosclerosis and cardiovascular disease.

Purpose: Menopausal symptoms are major concerns of postmenopausal women. Metabolic syndrome (MetS) is a risk factor for cardiovascular disease, and menopause is associated with an increased prevalence of MetS. The purpose of this study was to determine the association between menopausal symptoms and MetS in postmenopausal women., Methods: We selected 183 women who attended St. Vincent Hospital of the Catholic University of Korea in 2008 and 2009 and divided them into two groups (with and without MetS). Menopausal status was assessed with the Menopause Rating Scale (MRS) questionnaire. The body mass index and waist-to-hip ratio were determined, and the serum fasting glucose, lipid profile, and blood pressure were measured in all participants., Results: Of 183 postmenopausal women, 64 (35.0%) had MetS. A significant increase was observed in the total MRS score and the total somatic symptom subscale score in the MetS group (p = 0.021, p = 0.043, respectively). Vasomotor symptoms such as hot flashes and sweating occurred with higher frequency in the MetS group than in those without MetS (p = 0.034). High triglyceride levels and an increase of the number of components of MetS were associated with a higher total subscale score of somatic symptoms (p = 0.044, p = 0.039, respectively)., Conclusions: These results showed that a higher total subscale score and a higher frequency of somatic symptoms such as hot flashes and sweating were present in the MetS group. Larger scale studies are needed to clarify the association between other menopausal symptoms and MetS in postmenopausal women.

Objective: Emerging research suggests links between menopausal hot flashes and cardiovascular risk. The mechanisms underlying these associations are unclear due, in part, to the incomplete understanding of the physiology of hot flashes. We aimed to examine the longitudinal associations between hot flashes/night sweats and both inflammatory and hemostatic markers, controlling for cardiovascular risk factors and estradiol concentrations., Methods: Participants in the Study of Women's Health Across the Nation (n = 3,199), a longitudinal cohort study, were aged 42 to 52 years at cohort entry. Women completed interviews (hot flashes, night sweats: none, 1-5, and ≥6 d in the past 2 weeks), physical measures (blood pressure, height, weight), and a blood draw (high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, factor VIIc, tissue plasminogen activator antigen [tPA-ag], fibrinogen, glucose, serum estradiol) yearly for 8 years. Hot flashes/night sweats were examined in relation to each inflammatory/hemostatic marker in linear mixed models adjusting for demographic factors, cardiovascular risk factors, and medication use, as well as serum estradiol., Results: Compared with experiencing no flashes, reporting hot flashes was associated with higher tPA-aglog (hot flashes 1-5 d: percent change, or % change [95% CI], 3.88 [2.22-5.58]; P < 0.0001; ≥6 d: % change [95% CI], 4.11 [1.95-6.32]; P < 0.001) and higher factor VIIclog (hot flashes ≥6 d: % change [95% CI], 2.13 [0.80-3.47]; P < 0.01) in multivariable models. Findings persisted after adjusting for estradiol. Findings for night sweats were similar but attenuated with adjustment., Conclusions: Frequent hot flashes were associated with higher factor VIIc and tPA-ag. Hemostatic pathways may be relevant to understanding hot flash physiology and links between hot flashes and cardiovascular risk.

Objective: To evaluate the influence of CYP17 polymorphism on menopausal symptoms after estrogen treatment., Methods: A total of 130 women were recruited, but only 100 of these were selected according to inclusion and exclusion criteria; they were treated with 0.3 mg/day conjugated equine estrogens. One year later, the study was completed by 71 women. The analysis of the Kupperman menopausal index symptoms was made with information provided by the patients on daily diary cards. Blood samples were analyzed and the women were divided into two groups based on the CYP17, 5'-untranslated region: group A (wild-type homozygote and heterozygote) and group B (mutated homozygote)., Results: The values for the Kupperman menopausal index were similar in both groups at baseline. The symptoms in both groups decreased after 1 year of treatment when compared to those at baseline. The improvement rate was approximately 27.09% and 32.18%, in groups A and B, respectively. The levels of estrogen after treatment were higher in both groups in comparison with the baseline values. The testosterone level rose in group B with the 1-year treatment (0.48 + 0.16 ng/ml), reaching a higher level than the level in group A after treatment. The sex hormone binding globulin (SHBG) level showed a significant increase after the 1-year treatment in group B, surpassing both the baseline and the after-treatment values in group A (p < 0.01)., Conclusion: Our data suggest that the CYP17 polymorphism did not influence the action of estrogen on menopause symptoms during the 1-year treatment. The extra production of estrogen and androgen may have been countered by the elevation of SHBG levels.

Background: It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders., Method: Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Women's Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually., Results: Women were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study., Conclusions: The risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.

Statins have pleiotropic vascular protective effects that are independent of their cholesterol-lowering effects. The aim of the present study was to determine if statins have anti-flushing actions in an animal model of forced exercise-induced temperature dysregulation in menopausal hot flushes, and to clarify the critical role of statins in regulating vascular reactivity in the tail arteries of ovariectomized rats. Administration of fluvastatin or pravastatin (3mg/kg/day for 7days, p.o.) significantly ameliorated the flushing of tail skin in ovariectomized mice, and the effect of each statin was comparable with that of estrogen replacement (1mg/kg/week for 3weeks, i.m.). In phenylephrine-pre-contracted rat-tail arteries, ovariectomy inhibited acetylcholine-induced relaxation, but augmented sodium nitroprusside-induced relaxation. These ovariectomy-altered vasodilator responses were restored by fluvastatin treatment as well as by estrogen replacement. Nitrite/nitrate levels in the plasma of ovariectomized animals showed significantly lower values than those in sham-operated animals; this ovariectomy-reduced production of nitric oxide was improved by fluvastatin treatment. These data provide the first experimental evidence that statins such as fluvastatin and pravastatin exert anti-flushing effects by improving vasomotor dysfunction through nitric oxide-mediated mechanisms in ovariectomized animals. Thus, therapeutic methods that target improvement of vasomotor dysfunction could be novel strategies for reducing menopausal hot flushes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Introduction: Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy (HT). We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes., Methods: Healthy, non-smoking freshly postmenopausal women (n = 150) with no previous HT use were studied. Seventy-two women reported intolerable hot flushes (> or =7 moderate/severe episodes/day) and 78 women tolerable hot flushes (< or =3 mild episodes/day). The participants were treated in randomized order with either transdermal estradiol gel (1 mg), oral estradiol valerate (2 mg) with or without medroxyprogesterone acetate (5 mg), or placebo for 6 months. Treatment-induced changes in lipids, lipoproteins, apolipoproteins, sex hormone binding globulin (SHBG) and high-sensitivity C-reactive protein were compared. The trial is registered in the US National Institutes of Health Clinical Research Registry (no. NCT00668603)., Results: Pretreatment hot flush status was not related to the responses of these markers to different forms of HT. However, when all active regimens were evaluated together as a post-hoc analysis, 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes. Furthermore, in women with intolerable hot flushes and with HT use, the increases in SHBG (Spearman's rho = - 0.570, p < 0.001) were related to the reductions in hot flushes during the use of HT., Conclusions: Hot flushes appear to be no significant determinant for the responses of vascular markers to HT use.

Background: Interest in menopausal symptoms in general and hot flushes (HFs) in particular has grown in recent years. This is mostly due to increased awareness and the vast impact these symptoms have on women's lives. Despite the high prevalence of women who experience HFs, a definitive etiology for HFs is yet to be found. Our objective was to review the current literature dealing with associated factors for experiencing HFs and to provide a synthesized overview on this common and often debilitating condition., Methods: We systematically searched the English-language literature in the PubMed database using relevant key words and included only those articles that contained information on associated factors for HFs in generally healthy midlife women., Results: Both conflicting scientific results between studies documenting factors that influence HFs and the lack of validated measuring tools make it difficult to truly pinpoint associated factors for HFs. Nonetheless, we identified the following clusters of associated factors: the menopausal stages, sex steroid hormones, other endocrine agents, genetic polymorphisms, race/ethnicity, body mass index (BMI) and obesity, mood disorders, smoking, soy isoflavones and phytoestrogens, alcohol consumption, and physical activity., Conclusions: No single associated factor was consistently identified as having a major role in experiencing HFs. More resources should be directed to develop a unified study system along with multivariable analyses to get a better understanding of this condition, which often imposes a tremendous social and personal toll on the women who experience it.