Prospects of and limitations to the clinical applications of genistein.

Genistein is an isoflavone derived from soy-rich products, which is known to exhibit several beneficial biological effects, such as anti-tumor activity, improvement of glucose metabolism, and reduction of the frequency of peri-menopausal hot flashes, and thus has potential for clinical application. Certain limitations and side effects, such as low bioavailability, biological estrogenic activity, and detrimental effects on thyroid function, have restricted its clinical applications to some extent. Recently, it has been reported that fermentation, use of micromicelles, and modification of its chemical structure can enhance the bioavailability of genistein. Moreover, the modification of its molecular structure may also eliminate its biological estrogenic activity and adverse effects on thyroid function. In this review, we summarize the clinical application prospects and limitations of genistein, as well as the plausible solutions to overcome its low bioavailability, phytoestrogenic activity, and adverse effects on thyroid function.

Severity of hot flushes is inversely associated with dietary intake of vitamin B6 and oily fish.

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 B6 (VB6) was significantly related to severity of HF (adjusted odds ratio per 10 µg/MJ in VB6 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 VB6 and the severity of HF. Conclusions: VB6 and oily fish intake is inversely associated with the severity of HF in middle-aged women. Therefore, increased intake of VB6 could help attenuate HF.

Self-awareness and the evaluation of hot flash severity: observations from the Seattle Midlife Women's Health Study.

OBJECTIVE: The purpose of this study was to test the association of two dimensions of self-awareness with hot flash (HF) severity. METHODS: A subset of women from the Seattle Midlife Women's Health Study (N = 232) provided data for these analyses. Structural equation modeling was used to evaluate two dimensions of self-awareness (Internal States Awareness [ISA] and Self-Reflectiveness [SR]), and secondary factors of perceived stress, anxiety, and attitudes toward menopause as continuous with earlier life, health perceptions, and menopausal stage with respect to HF severity. The measurement and structural models were tested with a maximum likelihood missing values estimator and displayed good model fit. RESULTS: Women with greater ISA reported greater HF severity (ß = 0.17, P < 0.05). In addition, women in later menopausal transition stages reported greater HF severity and those with attitudes of continuity toward menopause reported less severe HFs (ß = 0.20, P < 0.01, ß = -0.30, P < 0.001, respectively). SR was not related to HF severity. Women with higher levels of SR reported greater perceived stress levels (ß = .51, P < 0.001), and those with greater perceived stress reported greater anxiety levels (ß = 0.63, P < 0.001) and attitudes of continuity toward menopause as less continuous with earlier life (ß = -0.30, P < 0.001). CONCLUSIONS: ISA (balanced self-awareness) was associated with greater HF severity, suggesting that enhanced balanced self-awareness may promote women's ability to evaluate their symptom experience. A multidimensional construct of self-awareness, perceived stress, anxiety, and attitude toward menopause are all plausible targets for future intervention studies of symptom management.

Acupuncture for the relief of hot flashes in breast cancer patients: A systematic review and meta-analysis of randomized controlled trials and observational studies.

OBJECTIVE: To critically assess the effectiveness and safety of acupuncture for treating hot flashes (HFs) among breast cancer (BC) patients, and to get much more highly compelling evidence then to guide clinical practice. METHODS: Comprehensive systematic literature searches were carried out for identifying randomized controlled trials and observational studies (OSs) published before January 2015. The meta-analysis (MA) was performed by Review Manager 5 software if data could be merged routinely, if not descriptions would be given. RESULTS: A total of 18 studies were eligible ultimately. With respect to HFs frequency, the MA during treatment showed a significant difference (MD = -1.78, 95% confidence intervals [95% CIs]: -3.42--0.14), but no statistical differences were observed when posttreatment or follow-up period. While electroacupuncture versus applied relaxation, they both helped to promote HFs markedly but did not reveal statistically significance between them. Referring to Kupperman's index, all the treatment brought out great assistance when compared with baseline conditions, and there was significant difference between real acupuncture sham acupuncture (posttreatment: MD = -4.40, 95% CI: -6.77--2.03; follow-up: MD = -4.30, 95% CI: -6.52--2.08). In terms of OS, 7 prospective single arm studies focused on exploring the efficacy of traditional acupuncture, and all revealed moderate or great benefit for BC patients suffering from HFs. CONCLUSIONS: Acupuncture still appeared to be an efficacious therapeutic strategy, especially for the less/no side effects. Because of its widespread acceptance and encouraging effectiveness for improving HFs, much more high-quality studies are in need urgently.

CYP2D6 genotype and endoxifen plasma concentration do not predict hot flash severity during tamoxifen therapy.

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.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice.

BACKGROUND: Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7-O-xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. METHODS: We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. RESULTS: The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-ß, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. CONCLUSION: Thus, these results imply that PCE17 has protective effects against hot flushes.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes.

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.

Clinical effects of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women.

OBJECTIVE: Estetrol (E4) is a natural fetal estrogen. The safety of increasing doses of E4 and its preliminary effects on the vagina, endometrium and menopausal vasomotor symptoms were investigated. STUDY DESIGN: This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Subjects with an intact uterus were randomized to receive either 2mg E4 or 2mg estradiol-valerate (E2V) for 28days. Subsequent dose-escalation groups (non-randomized) were: 10mg E4 (intact uterus and ≥35 hot flushes/week); and 20mg and 40mg E4 (hysterectomized subjects). MAIN OUTCOME MEASURE: Adverse events (AEs) and vaginal cytology were evaluated in all treatment groups; hot flushes/sweating and endometrial proliferation were analyzed with 2 and 10mg E4 and 2mg E2V. RESULTS: Estetrol appeared to be safe, without serious drug-related AEs. In all the groups there was a clear shift from parabasal to superficial vaginal cells, indicating an estrogenic effect and a potential for the treatment of vulvovaginal atrophy. The endometrial thickness remained stable in the 2mg E4 group and increased with E2V and 10mg E4. A decrease in the mean number of hot flushes and sweating was seen with 2 and 10mg E4 and 2mg E2V. CONCLUSIONS: Estetrol in a dose range of 2-40mg per day improved vaginal cytology and vasomotor symptoms in postmenopausal women. Endometrial proliferation occurred with the 10mg dose. Estetrol seems a safe and suitable candidate to develop further for hormone therapy.

Menopausal hot flashes and white matter hyperintensities.

OBJECTIVE: Hot flashes are classic symptoms of menopause. Emerging data link hot flashes to cardiovascular disease (CVD) risk, yet whether hot flashes are related to brain health is poorly understood. We examined the relationship between hot flashes (measured via physiologic monitor and self-report) and white matter hyperintensities (WMH) among midlife women. METHODS: Twenty midlife women (aged 40-60 y) without clinical CVD, with an intact uterus and ovaries, and not taking hormone therapy were recruited. Women underwent 24 hours of ambulatory physiologic and diary hot flash monitoring to quantify hot flashes; magnetic resonance imaging to assess WMH burden; 72 hours of actigraphy to quantify sleep; and a blood draw, questionnaires, and physical measures to quantify demographics and CVD risk factors. Tests of a priori hypotheses regarding relationships between physiologically monitored and self-reported wake and sleep hot flashes and WMH were conducted in linear regression models. RESULTS: More physiologically monitored hot flashes during sleep were associated with greater WMH, controlling for age, race, and body mass index (ß [SE] = 0.0002 [0.0001], P = 0.03]. Findings persisted after controlling for sleep characteristics and additional CVD risk factors. No relationships were observed for self-reported hot flashes. CONCLUSIONS: More physiologically monitored hot flashes during sleep are associated with greater WMH burden among midlife women without clinical CVD. Results suggest that the relationship between hot flashes and CVD risk observed in the periphery may extend to the brain. Future work should consider the unique role of sleep hot flashes in brain health.

Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats.

Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose-dependent manner. Inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation was significantly more potent than that of cetirizine hydrochloride, other antiallergic agent with H1R antagonistic activity, at doses in which both agents exhibit comparable H1R antagonistic activity in rats. These results suggest that H1R antagonistic activity-independent mechanism contribute to the inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation. Olopatadine also significantly inhibited increases in vascular permeability and nerve growth factor production in the skin induced by topical tacrolimus treatment. Thus, the onset of hot flashes in rats is quantitatively determined by measuring the skin temperature and olopatadine attenuates hot flashes induced by topical tacrolimus ointment in rats, suggesting that the combination application with olopatadine and tacrolimus ointment is useful for improving medication adherence with tacrolimus ointment treatment in patients with atopic dermatitis.

Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women.

OBJECTIVE: Uncontrolled intervention studies, including studies involving breast cancer survivors, have demonstrated improvements in vasomotor symptoms (VMS) after stellate ganglion blockade (SGB) with a local anesthetic. This study presents the first randomized sham-controlled trial of SGB for the treatment of VMS. METHODS: Participants included 40 postmenopausal women, aged 30 to 70 years, with moderate to severe VMS. The study was a randomized sham-controlled trial comparing the effects of SGB versus sham injection on the frequencies of total and moderate to severe VMS, as measured by daily diaries. Image-guided SGB was performed with 5 mL of 0.5% bupivacaine. Sham injection of saline was performed in subcutaneous tissues in the neck. VMS were recorded at baseline and for 6 months thereafter. Objective VMS were recorded using ambulatory sternal skin conductance monitoring during a 24-hour period at baseline and on 3-month follow-up. RESULTS: There were no significant group differences in overall VMS frequency, but the frequency of moderate to very severe VMS was reduced more in the active group compared with the sham treatment group (event rate ratio, 0.50; 95% CI, 0.35-0.71; P < 0.001). The frequency of objective VMS was also reduced to a greater degree in the SGB group than in the sham group (event rate ratio, 0.71; 95% CI, 0.64-0.99; P < 0.05). There were no study-related serious adverse events. CONCLUSIONS: SGB may provide effective treatment of VMS in women who seek nonhormonal treatments because of safety concerns and personal preference. The finding that SGB significantly reduces objectively measured VMS provides further evidence of efficacy. A larger trial is warranted to confirm these findings.

Diary of hot flashes reported upon occurrence: results of a randomized double-blind study of raloxifene, placebo, and paroxetine.

OBJECTIVE: This trial examined diaries of hot flash events reported upon occurrence to assess the test/retest reliability of the diaries and their ability to measure treatment effects on hot flash frequency and severity. METHODS: Forty-two postmenopausal women (aged ≥40 y; 5-50 hot flashes/wk) were randomized (3:3:1) to placebo, raloxifene 60 mg, or paroxetine 20 mg daily for 12 weeks. Diaries of hot flash frequency and severity were evaluated at 1-week intervals (twice before study treatment and thrice during study treatment). RESULTS: Forty-one women were evaluated. Baseline characteristics were similar between groups (eg, mean, 29.8 hot flashes/wk). Concordance correlation coefficients between screening (week -2) and baseline (week -1) measures of hot flash frequency and severity were 0.73 and 0.71, respectively. After 12 weeks, the mean (95% CI) percent changes from baseline in weekly hot flash frequency were as follows: placebo, -37.4% (-60.9 to -14.0); raloxifene, -14.2% (-37.7 to 9.3); paroxetine, -49.8% (-88.6 to -11.0); the mean (95% CI) percent changes in hot flash severity were as follows: placebo, -39.9% (-69.1 to -10.8); raloxifene, -9.6% (-38.8 to 19.6); paroxetine, -36.6% (-84.7 to 11.5). There were no significant differences in hot flash diary results between treatment groups. CONCLUSIONS: Measures of hot flash frequency and severity show acceptable test/retest reliability between screening and baseline. Reductions in vasomotor symptoms by raloxifene are numerically less than those seen with placebo, but no statistically significant treatment differences have been documented in this small study. The large effect of placebo and the significant reduction in vasomotor symptoms by paroxetine are consistent with other studies. The diary seems to be suitable for use in hot flash clinical trials.

Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort.

OBJECTIVE: This study aims to estimate the risk of hot flashes relative to natural menopause and to evaluate the associations of hormone levels, behavioral variables, and demographic variables with the risk of hot flashes after menopause. METHODS: We performed annual assessment of 255 women who were premenopausal at baseline and reached natural menopause within 16 years of follow-up. RESULTS: The prevalence of moderate/severe hot flashes increased in each premenopausal year, reaching a peak of 46% in the first 2 years after the final menstrual period (FMP). Hot flashes decreased slowly after menopause and did not return to premenopausal levels until 9 years after the FMP. The mean (SD) duration of moderate/severe hot flashes after the FMP was 4.6 (2.9) years (for any hot flashes, 4.9 [3.1] y). One third of women at 10 years or more after menopause continued to experience moderate/severe hot flashes. African-American women (obese and nonobese) and obese white women had significantly greater risks of hot flashes compared with nonobese white women (interaction, P = 0.01). In multivariable analysis, increasing follicle-stimulating hormone levels before the FMP (P < 0.001), decreasing estradiol (odds ratio, 0.87; 95% CI, 0.78-0.96; P = 0.008), and increasing anxiety (odds ratio, 1.05; 95% CI, 1.03-1.06; P < 0.001) were significant risk factors for hot flashes, whereas higher education levels were protective (odds ratio, 0.66; 95% CI, 0.47-0.91; P = 0.011). CONCLUSIONS: Moderate/severe hot flashes continue, on average, for nearly 5 years after menopause; more than one third of women observed for 10 years or more after menopause have moderate/severe hot flashes. Continuation of hot flashes for more than 5 years after menopause underscores the importance of determining individual risks/benefits when selecting hormone or nonhormone therapy for menopausal symptoms.

Pilot study of integral yoga for menopausal hot flashes.

OBJECTIVE: This study aims to obtain preliminary data on the efficacy of yoga for reducing self-reported menopausal hot flashes in a randomized study including an attention control group. METHODS: We randomized 54 late perimenopausal women (2-12 mo of amenorrhea) and postmenopausal women (>12 mo of amenorrhea)--aged 45 to 58 years and who experienced at least four hot flashes per day, on average, for at least 4 weeks--to one of three groups: yoga, health and wellness education (HW), and wait list (WL). Yoga and HW classes consisted of weekly 90-minute classes for 10 weeks. All women completed daily hot flash diaries throughout the trial (10 wk) to track the frequency and severity of hot flashes. The mean hot flash index score is based on the number of mild, moderate, severe, and very severe hot flashes. RESULTS: Hot flash frequency declined significantly across time for all three groups, with the strongest decline occurring during the first week. There was no overall significant difference in hot flash frequency decrease over time by treatment groups, but the yoga and HW groups followed similar patterns and showed greater decreases than the WL group. On week 10, women in the yoga group reported an approximately 66% decrease in hot flash frequency, women in the HW group reported a 63% decrease, and women in the WL group reported a 36% decrease. The hot flash index showed a similar pattern. CONCLUSIONS: Results suggest that yoga can serve as a behavioral option for reducing hot flashes but may not offer any advantage over other types of interventions.

ACOG Practice Bulletin No. 141: management of menopausal symptoms.

Vasomotor and vaginal symptoms are cardinal symptoms of menopause. Vasomotor symptoms can be particularly troubling to women and are the most commonly reported menopausal symptoms, with a reported prevalence of 50-82% among U.S. women who experience natural menopause (1, 2). The occurrence of vasomotor symptoms increases during the transition to menopause and peaks approximately 1 year after the final menstrual period (3-5). The purpose of this document is to provide evidence-based guidelines for the treatment of vasomotor and vaginal symptoms related to natural and surgical menopause. (Treatment of menopausal symptoms in cancer survivors is discussed in the American College of Obstetricians and Gynecologists' Practice Bulletin Number 126, Management of Gynecologic Issues in Women With Breast Cancer.).

Early severe vasomotor menopausal symptoms are associated with diabetes.

OBJECTIVE: The purpose of this study was to investigate associations between profiles of vasomotor menopausal symptoms (VMS) during the menopausal transition with the prevalence of diabetes. METHODS: VMS and diabetes were measured at baseline and 3-year intervals for 15 years in 4,895 women in the Australian Longitudinal Study on Women's Health who were aged 45 to 50 years at baseline in 1996. Latent class analysis and generalized estimating equation models for binary repeated measures were performed. The VMS profiles were labeled as mild, moderate, early severe, and late severe. RESULTS: The prevalence of diabetes in the total group was 9.0%. Compared with mild VMS, the odds of diabetes were higher in those with a late severe profile (though not statistically significant; adjusted odds ratio, 1.28; 95% CI, 0.97-1.68) and in those with an early severe profile (adjusted odds ratio, 1.67; 95% CI, 1.20-2.32). Adjustment for body mass index attenuated this association, but the odds of diabetes were still significantly higher in women with an early severe profile than in women with mild VMS (odds ratio, 1.55; 95% CI, 1.11-2.17). The moderate profile was not associated with diabetes. CONCLUSIONS: Women with an early severe VMS profile are more likely to have diabetes across a period of 15 years. This association is not explained by body mass index or other potential confounders. Our findings imply that the predictive value of VMS for diabetes may vary with the timing of VMS relative to menopause.

Temporal sequencing of brain activations during naturally occurring thermoregulatory events.

Thermoregulatory events are associated with activity in the constituents of the spinothalamic tract. Whereas studies have assessed activity within constituents of this pathway, in vivo functional magnetic resonance imaging (fMRI) studies have not determined if neuronal activity in the constituents of the tract is temporally ordered. Ordered activity would be expected in naturally occurring thermal events, such as menopausal hot flashes (HFs), which occur in physiological sequence. The origins of HFs may lie in brainstem structures where neuronal activity may occur earlier than in interoceptive centers, such as the insula and the prefrontal cortex. To study such time ordering, we conducted blood oxygen level-dependent-based fMRI in a group of postmenopausal women to measure neuronal activity in the brainstem, insula, and prefrontal cortex around the onset of an HF (detected using synchronously acquired skin conductance responses). Rise in brainstem activity occurred before the detectable onset of an HF. Activity in the insular and prefrontal trailed that in the brainstem, appearing following the onset of the HF. Additional activations associated with HF's were observed in the anterior cingulate cortex and the basal ganglia. Pre-HF brainstem responses may reflect the functional origins of internal thermoregulatory events. By comparison insular, prefrontal and striatal activity may be associated with the phenomenological correlates of HFs.

Menopausal symptoms among breast cancer patients: a potential indicator of favorable prognosis.

Menopausal symptoms have been suggested to be an indicator of better prognosis among patients treated for breast cancer, because women who experience these symptoms usually have a lower level of estrogen. We tested this hypothesis in a population-based, prospective cohort study involving 4,842 women with stage 0 to III primary breast cancer who were enrolled in the Shanghai Breast Cancer Survival Study between March 2002 and April 2006, were aged 20 to 75 years, and were recruited 6 months post-diagnosis. They were followed-up by in-person surveys and record linkages with the vital statistics registry. Cox regression analysis was used to evaluate the association of menopausal symptoms at baseline with breast cancer recurrence. Approximately 56% of patients experienced at least one menopausal symptom, including hot flashes, night sweats, and/or vaginal dryness at baseline. During a median follow-up period of 5.3 years, 720 women had a recurrence. Experiencing hot flashes or having ≥2 menopausal symptoms was associated with lower risk of recurrence among premenopausal women (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.62-0.96 for hot flashes; 0.73, 0.56-0.96 for ≥2 menopausal symptoms). Lower recurrence risk in relation to hot flashes was also observed among women who were not overweight/obese (HR=0.78, 95% CI: 0.64-0.99), those with relatively low waist-to-hip ratio (WHR) (HR=0.77, 95% CI: 0.61-0.97), and those who used tamoxifen (HR=0.75, 95% CI: 0.58-0.98). Consistently experiencing multiple menopausal symptoms was associated with lower recurrence risk among women with low WHR or who used tamoxifen. This large, population-based cohort study of women with breast cancer confirms that experiencing menopausal symptoms is an indicator of favorable breast cancer prognosis.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women.

OBJECTIVES: To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. METHODS: One hundred and ten postmenopausal women aged 45-55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima-media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. RESULTS: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.