Physiologically assessed hot flashes and endothelial function among midlife women.
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ABSTRACT:
SUBMITTER: Thurston RC
PROVIDER: S-EPMC5524590 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Physiologically assessed hot flashes and endothelial function among midlife women.
Thurston Rebecca C RC Chang Yuefang Y Barinas-Mitchell Emma E Jennings J Richard JR von Känel Roland R Landsittel Doug P DP Matthews Karen A KA
Menopause (New York, N.Y.) 20170801 8
<h4>Objective</h4>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.<h4>Methods</h4>Two hundred seventy-two nonsmoking women reportin ...[more]
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Project description:Emerging evidence suggests associations between menopausal hot flashes and cardiovascular risk. However, whether hot flashes are associated with intima media thickness (IMT) or IMT changes over time is unknown. We hypothesized that reported hot flashes would be associated with greater IMT cross-sectionally and with greater IMT progression over 2 years.Participants were 432 women aged 45 to 58 years at baseline participating in the Study of Women's Health Across the Nation (SWAN) Heart, an ancillary study to the SWAN. Measures at the SWAN Heart baseline and follow-up visit 2 years later included a carotid artery ultrasound, reported hot flashes (past 2 weeks: none, 1-5 d, ?6 d), and a blood sample for measurement of estradiol.Women reporting hot flashes for 6 days or more in the prior 2 weeks had significantly higher IMT than did women without hot flashes at the baseline (mean [SE] difference, 0.02 [0.01] mm; P=0.03) and follow-up (mean [SE] difference, 0.02 [0.01] mm; P=0.04) visits, controlling for demographic factors and cardiovascular risk factors. Reporting hot flashes at both study visits was associated with higher follow-up IMT relative to reporting hot flashes at neither visit (mean [SE] difference, 0.03 [0.01] mm; P=0.03). Associations between hot flashes and IMT largely remained after adjusting for estradiol. An interaction between hot flashes and obesity status was observed (P=0.05) such that relations between hot flashes and IMT were observed principally among overweight/obese women. Hot flashes were not associated with IMT progression.These findings provide some indication that women reporting hot flashes for 6 days or more in the prior 2 weeks may have higher IMT than do women without hot flashes, particularly for women who are overweight or obese. Further work should determine whether hot flashes mark adverse underlying vascular changes.
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Project description:ContextPhthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes.ObjectiveTo investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women.DesignA cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006-2015), a convenience sample from an urban setting.Participants728 multi-racial/ethnic pre- and perimenopausal women aged 45-54 years.Outcome measuresWomen completed questionnaires about hot flash experience and provided 1-4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; DEHP: ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA). Covariate-adjusted logistic regression models were used to assess associations of continuous natural log-transformed phthalate metabolite concentrations with hot flash outcomes. Analyses were conducted to explore whether associations differed by menopause status, body mass index (BMI), race/ethnicity, and depressive symptoms.ResultsOverall, 45% of women reported a history of hot flashes. Compared to women who never experienced hot flashes, every two-fold increase in ƩPlastic was associated with 18% (OR: 1.18; 95%CI: 0.98, 1.43) and 38% (OR: 1.38; 95%CI: 1.11, 1.70) higher odds of experiencing hot flashes in the past 30 days and experiencing daily/weekly hot flashes, respectively. Some associations of phthalates with certain hot flash outcomes differed by menopause status, BMI, race/ethnicity, and depressive symptoms.ConclusionsThis study suggests that phthalates are associated with hot flash experience and may impact hot flash risk in women who are susceptible to experiencing hot flashes.
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Project description:ObjectiveSleep disturbance and hot flashes are common during menopause, but their association is not well understood. We sought to understand the associations among sleep disturbance and the frequency, bothersomeness, and interference of hot flashes in mid-life women.Study designSTRIDE is a study of women ages 40-65 years at varied menopausal stages. We examined the cross-sectional associations of sleep disturbance with the frequency and bothersomeness of hot flashes, and interference of hot flashes with work, social, and leisure activities during the 2nd year of STRIDE.Main outcome measureSelf-reported sleep disturbance.ResultsOf the 623 women with complete data, 370 (59%) reported having hot flashes. Bivariate analyses showed that reporting hot flashes with bother, but not hot flashes alone, was associated with sleep disturbance (odds ratio [OR] [95% confidence interval (CI)]: 2.8 [2.0-4.0] and 1.3 [0.7-2.5], respectively). In multivariable models, women reporting bothersome hot flashes were more likely to report sleep disturbance (OR [95% CI]: 2.1 [1.4-3.2]) compared to women who reported no hot flashes. When the perceived interference of hot flashes with work, social activities, and leisure activities were included in the model, the relationships between bothersome hot flashes and sleep disturbance disappeared.ConclusionsHot flashes are not associated with sleep disturbance, unless they are bothersome. Mid-life patients should routinely be queried about the bothersomeness of their hot flashes.
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Project description:OBJECTIVE:The aim of the study was to examine whether anxiety and depressive symptoms are associated with an adverse cardiac autonomic profile among midlife women with hot flashes. METHODS:Anxiety and depressive symptoms were evaluated by validated self-administered questionnaires among peri- and postmenopausal women in a randomized trial of slow-paced respiration for hot flashes. Pre-ejection period (PEP), a marker of sympathetic activation, and respiratory sinus arrhythmia (RSA), a marker of parasympathetic activation, were measured at baseline and 12 weeks using impedance cardiography and electocardiography. Multivariable repeated measures linear regression models examined associations between anxiety and depression symptoms and autonomic markers, corrected for multiple comparisons with Benjamini-Hochberg procedure, and adjusted for age and body mass index. RESULTS:Among the 121 participants, greater state anxiety was associated with shorter PEP, reflecting higher sympathetic activity (??=?-0.24, P?=?0.02). Greater trait anxiety and cognitive anxiety were associated with lower RSA, reflecting decreased parasympathetic activity (??=?-0.03, P?<?0.01 for Spielberger Trait Anxiety; ??=?-0.06, P?=?0.02 for Hospital Anxiety and Depression Scale [HADS] Anxiety Subscale). Greater depressive symptoms were associated with lower RSA (??=?-0.06, P?=?0.03 for HADS Depression Subscale; ??=?-0.03, P?=?0.04 for Beck Depression Inventory). CONCLUSIONS:Among peri- and postmenopausal women with hot flashes, greater self-reported anxiety and depressive symptoms were associated with lower levels of resting cardiac parasympathetic activity, and greater state anxiety was associated with higher levels of cardiac sympathetic activity. Findings suggest that midlife women with increased anxiety and depressive symptoms may have an unfavorable cardiac autonomic profile with potential implications for their overall cardiovascular risk.
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Project description:ObjectiveTo quantify the impact of objectively recorded hot flashes on objective sleep in perimenopausal women.DesignCross-sectional study. Participants underwent 1-5 laboratory-based polysomnographic recordings for a total of 63 nights, including sternal skin-conductance measures, from which 222 hot flashes were identified according to established criteria. Data were analyzed with hierarchical mixed-effect models and Spearman's rank correlations.SettingSleep laboratory.Patient(s)Thirty-four perimenopausal women (age ± SD: 50.4 ± 2.7 years).Intervention(s)None.Main outcome measure(s)Perceived and polysomnographic sleep measures (sleep quality, amount of time spent awake after sleep onset, and number of awakenings). Subjective (frequency and level of bother) and objective (frequency and amount of hot flash-associated awake time) hot-flash measures.Result(s)Women had an average of 3.5 (95% confidence interval: 2.8-4.2, range = 1-9) objective hot flashes per night. A total of 69.4% of hot flashes were associated with an awakening. Hot flash-associated time awake per night was, on average, 16.6 minutes (95% confidence interval: 10.8-22.4 minutes), which accounted for 27.2% (SD 27.1) of total awake time per night. Hot flash-associated time awake, but not hot flash frequency, was negatively associated with sleep efficiency and positively associated with waking after sleep onset. In addition, self-reported wakefulness correlated with hot flash-associated waking, suggesting that women's estimates of wakefulness are influenced by the amount of time spent awake in association with hot flashes during the night. Having more perceived and bothersome hot flashes was correlated with more perceived wakefulness and awakenings and more objective hot flash-associated time awake and hot-flash frequency.Conclusion(s)The presence of physiological hot flashes accounts for a significant proportion of total objective time awake during the night in perimenopausal women.
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Project description:Based on a common mechanism of action with gabapentin, we investigated the effects of L-methionine on hot flashes in postmenopausal women.After a 1-week baseline period, 51 postmenopausal women experiencing at least five moderate-severe hot flashes per day were randomized to one of three groups in a 13:13:25 ratio: placebo/placebo, placebo/L-methionine, or L-methionine/L-methionine, respectively (phase 1/phase 2). Phase 1 was 12 weeks long, and phase 2 was 8 weeks long. Participants took 1 g PO BID in phase 1 and 2 g PO BID in phase 2 of either L-methionine or placebo. All participants also took folate 1 mg and methylcobalamin 0.5 mg a day to help minimize the L-methionine-induced elevation in serum homocysteine. The primary outcome variable was the percent change in hot flash composite score from baseline to week 12 obtained from participants' daily hot flash diaries.In phases 1 and 2, there were no significant differences between the L-methionine and placebo groups for any of the hot flash outcome measures. At week 12, there was a mean of 37.4% decrease in hot flash composite score compared with baseline in the L-methionine group and a mean of 33.4% decrease in the placebo group (P = 0.60). There were expected significant increases in fasting serum homocysteine (1.7 and 5.8 micromol/L) and fasting serum methionine (13.9 and 22.3 micromol/L) at weeks 12 and 20, respectively, associated with the two doses of L-methionine therapy relative to placebo therapy.L-methionine therapy seems to be ineffective in the treatment of hot flashes in postmenopausal women.
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Project description:IntroductionHot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women.Participants and designIn this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins.SettingsThe study was performed in a hospital medical center.ResultsThe hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels.ConclusionsThis study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.
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Project description:ContextWomen are at increased risk for mood disturbance during the menopause transition. Hot flashes (HFs), sleep disruption, and fluctuating estradiol levels correlate with menopause-associated depression but co-occur, making cause and effect relationships difficult to disentangle.ObjectiveUsing a GnRH agonist (GnRHa) experimental model, we investigated whether depressive symptoms are associated with HFs and/or are explained by concomitant sleep fragmentation in the absence of estradiol fluctuation.Design and interventionDepressive symptoms, objective polysomnographic sleep parameters, subjective sleep quality, serum estradiol, and HFs were assessed before and 4 weeks after open-label depot GnRHa (leuprolide 3.75-mg) administration.SettingAcademic medical center.ParticipantsTwenty-nine healthy nondepressed premenopausal volunteers (mean age, 27.3 years).ResultsSerum estradiol was rapidly and uniformly suppressed. HFs developed in 69% of the subjects. On univariate analysis, worsening of mood was predicted by increases in time in light sleep (stage N1), number of transitions to wake, non-REM arousals, subjective sleep quality, and reductions in perceived sleep efficiency (all P < .045), as well as the number of nighttime (P = .006), but not daytime (P = .28), HFs reported. In adjusted models, the number of nighttime HFs reported, increases in non-REM arousals, time in stage N1, transitions to wake, and reduced sleep quality remained significant predictors of mood deterioration (P ≤ .05).ConclusionsDepressive symptoms emerged after estradiol withdrawal in association with objectively and subjectively measured sleep disturbance and the number of nighttime, but not daytime, HFs reported. Results suggest that sleep disruption and perceived nighttime HFs both contribute to vulnerability to menopause-associated depressive symptoms in hypoestrogenic women.
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Project description:IntroductionHot 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 designIn 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.SettingsThe study was performed in a hospital medical center.ResultsThe 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-? (P-trend = 0.008), and MIP1? (P-trend = 0.04). Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with IL-8 (P-trend < 0.001) and TNF? (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 TNF? (51.27%; 6.64,114.57; P < 0.05).ConclusionThe present study provides evidence that hot flashes are associated with circulating IL-8 and TNF-? in healthy postmenopausal women. It suggests that hot flashes might be related to low-grade systemic inflammation.
| S-EPMC5573141 | biostudies-literature
Project description: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.
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