The cross-sectional association between vasomotor symptoms and hemostatic parameter levels in postmenopausal women.
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ABSTRACT: 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.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.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.We found no convincing evidence that VMS presence or severity was associated with levels of hemostatic parameters among postmenopausal women.
<h4>Objective</h4>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.<h4>Methods</h4>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 warf ...[more]
Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.
Project description:Uric acid is one of natural antioxidants in human body. There have been several studies on the correlation between uric acid with oxidative stress and osteoporosis. However, the data are insufficient and results are controversial. In this regard, we determined the association between uric acid levels and bone mineral density (BMD) during the postmenopausal period. We analyzed data from 328 postmenopausal women (mean age, 57.3 ± 6.5 years; mean serum uric acid level, 4.6 ± 1.0 mg/dL). The participants were divided into three groups based on tertiles of the serum uric acid level. The participants receiving hormone replacement therapy (HRT), bisphosphonates, or lipid-lowering agents were included. Blood urea nitrogen, serum creatinine, and serum triglyceride levels were significantly higher in the upper tertiles of uric acid levels. No significant difference was found in the mean uric acid levels between medication users and non-users. Each HRT regimen had a different mean serum uric acid level. A cross-sectional analysis showed no significant correlation between the serum uric acid levels and BMD in the spine and femoral neck (spine BMD: 1.050 ± 0.131, 1.060 ± 0.160, 1.084 ± 0.140, p = 0.22; femoral neck BMD: 0.837 ± 0.110, 0.849 ± 0.096, 0.863 ± 0.115, p = 0.28 for each tertile of uric acid). Longitudinal analysis of data from 186 women with follow-up examinations at a mean interval of 14.6 months also revealed no difference in reduction in both spine and femoral neck BMD between tertile groups of serum uric acid (the median BMD reduction for spine: -0.02, 0.01, -0.04, p = 0.95; the median BMD reduction for femoral neck: 0.008, 0.005, -0.003, p = 0.34). Serum uric acid level is not associated with BMD in postmenopausal women.
Project description:ObjectiveTo determine prevalence and health-related quality of life (HRQOL) of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women in Europe, the US, and Japan, and among subgroups of women not taking hormone therapy (HT).MethodsScreening surveys were sent to a random sample of women aged 40 to 65 years; full questionnaires followed to those who completed them and met inclusion criteria. Women with successfully treated VMS, breast cancer, or on HT for medical conditions were excluded. The Menopause-Specific QOL (MENQOL) and Work Productivity and Activity Impairment (WPAI) questionnaires were included in the questionnaire.ResultsOf 25,161 women completing the screening survey, 11,771 were postmenopausal and 3,460 met inclusion criteria and completed the full questionnaire. Prevalence of moderate-to-severe VMS was 40%, 34%, and 16% in Europe, the US, and Japan, respectively. A large proportion were HT averse, albeit eligible (Europe 56%, US 54%, Japan 79%). In total, 12%, 9%, and 8% in Europe, the US, and Japan, respectively, were HT-contraindicated. A high proportion were HT-cautious (Europe 70%, US 69%, Japan 52%). Most common menopausal symptoms reported in the MENQOL were feeling tired or worn out (Europe/US 74%, Japan 75%), aching in muscles and joints (Europe 69%, US 68%, Japan 61%), difficulty sleeping (Europe 69%, US 66%, Japan 60%), and hot flashes (Europe 67%, US 68%, Japan 62%). Overall, the most bothersome symptom was weight gain. As measured by the WPAI, hot flashes and night sweats had a greater impact on daily activities than on working activities.ConclusionsA high proportion of women experienced moderate-to-severe VMS, with associated symptoms impacting QOL.
Project description:ObjectiveThe aim of the study was to describe the effects of TX-001HR (17β-estradiol [E2] and natural progesterone [P4] in a single oral capsule) on menopause-specific quality of life in women with moderate to severe vasomotor symptoms (VMS).MethodsThe REPLENISH study (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial which evaluated four E2/P4 doses in postmenopausal women with VMS and a uterus. Women with moderate to severe hot flushes (≥7/d or ≥50/wk) were included in a VMS substudy. Participants self-administered the Menopause-Specific Quality of Life (MENQOL) questionnaire. Baseline changes in MENQOL overall and domains were determined as well as correlations between changes in MENQOL scores and VMS frequency or severity.ResultsIn the VMS substudy, women treated with E2/P4 had significantly greater improvements from baseline in their MENQOL overall score at week 12, and months 6 and 12, compared with placebo (all, P < 0.05, except the lowest E2/P4 dose at months 6 and 12). Improvements from baseline for the MENQOL vasomotor domain score were significantly greater with TX-001HR doses versus placebo at all time points (all, P < 0.01). Changes in MENQOL vasomotor scores moderately correlated with changes in VMS frequency (r = 0.56, P < 0.0001) and severity (r = 0.55, P < 0.0001).ConclusionIn the REPLENISH trial, women with moderate to severe VMS treated with most E2/P4 doses reported significant improvements in quality of life from baseline to 12 weeks compared with placebo, which were maintained up to 12 months. TX-001HR, if approved, may provide the first oral hormone therapy formulation in a single capsule containing E2 and P4 for the treatment of VMS in postmenopausal women with a uterus.
Project description:Middle-aged women experience various menopausal symptoms during the menopause. These symptoms can affect their quality of life and health. Several epidemiological studies reported that obesity associates with menopausal symptoms. The aim of this cross-sectional study was to examine the associations between obesity and multiple menopausal symptoms at different stages of menopause in middle-aged Korean women.The study population included women aged 44-56 years who visited a tertiary referral hospital for medical check-ups between November 2012 and March 2013 and were free from serious illness, could comprehend a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Overweight and obesity were defined as body mass index (BMI) of 23-24.9 and ?25 kg/m2, respectively.Of the 2204 middle-aged women, 929 met the eligibility criteria. Of these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause, respectively. In perimenopause, obese women were significantly more likely to have moderate/severe physical symptoms (MENQOL domain score???5) than normal or overweight women. In postmenopause, obese women were significantly more likely to have moderate/severe vasomotor symptoms. Multiple linear regression with adjustment for confounders showed that relative to normal weight, obesity in perimenopause and postmenopause associated independently with physical symptoms (beta coefficient?=?0.35; P?=?0.023) and vasomotor symptoms (beta coefficient?=?0.68; P?=?0.003), respectively. Overweight did not associate with menopausal symptoms. BMI did not associate significantly with psychosocial or sexual symptoms at either stage of menopause.Obese women had more frequent menopausal symptoms than normal or overweight women but the associated menopausal symptom differed depending on the menopausal stage. Further studies are required to confirm this result and identify the underlying mechanisms.
Project description: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.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.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.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.
Project description:Research has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function.Women (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks.Baseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up.Heart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms.
Project description:Abstract Difficulty sleeping is a common complaint of postmenopausal women. In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL), was shown to reduce moderate to severe hot flush frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. In this analysis, the effect of the E2/P4 capsules on “difficulty sleeping” in postmenopausal women experiencing hot flushes, was assessed by the menopause-specific quality of life (MENQOL) questionnaire and also analyzed by age. The phase 3 REPLENISH trial (NCT01942668), evaluated 4 daily doses of E2/P4 capsules in postmenopausal women (40-65 years, intact uterus) with vasomotor symptoms (VMS). Women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy); women with fewer/less severe VMS were randomized to active E2/P4 doses only for endometrial safety. MENQOL was administered at baseline, week 12, and months 6 and 12. The “difficulty sleeping” item was rated using a 7-item Likert scale ranging from “Not at all bothered” (analysis score of 2) to “Extremely bothered” (analysis score of 8) if difficulty sleeping was experienced, if not experienced, the score for the analysis was set to 1. Changes from baseline to week 12, and months 6 and 12 in all women (MITT population) were analyzed by ANCOVA between each E2/P4 groups vs placebo and stratified by age (pre-specified FDA subgroup; <55 and 55+). Treatment groups in the MITT population (n=1833) were E2/P4 1/100 (n=416), 0.5/100 (n=422), 0.5/50 (n=421), 0.25/50 (n=423) or placebo (n=151). The MITT population had a mean age of 55 years; in the <55-year group (n=927) mean age was 51.2 years and in the ≥55-year group (n=906) mean age was 58.1 years. Mean baseline scores for the “difficulty sleeping” item ranged from 5.1 to 5.8 points. In the MITT population, difficulty sleeping significantly improved from baseline with the three highest E2/P4 doses (1/100, 0.5/100, 0.5/50) compared with placebo at all timepoints (all, P<0.05), except for 0.5/50 at month 6. In women <55 years, the sleep difficulty item significantly improved from baseline at all timepoints with two E2/P4 doses (1/100 and 0.5/50) vs placebo. In women 55+ years, significant improvements from baseline were observed at week 12 with three E2/P4 doses (1/100, 0.5/100, 0.5/50) vs placebo. In REPLENISH, women treated with E2/P4 capsules containing 1 or 0.5 mg E2 demonstrated significant and sustained improvements in the MENQOL difficulty sleeping assessment, especially those <55 years. These data warrant further evaluation.
Project description:The purpose of this study was to determine the relationship between hormone replacement therapy (HRT) and tinnitus in South Korea using data from the Korea National Health and Nutrition Examination Surveys (KNHANES) (2010-2012).Cross-sectional analysis of a nationwide health survey.KNHANES is a nationally representative cross-sectional survey of South Korea population. Only postmenopausal women aged 19-65 years were included in the study (n=2736). Auditory function was evaluated using pure-tone audiometric testing according to established KNHANES protocols. Subjects were questioned about their experience with tinnitus. Exogenous hormone-related factors included the starting age and duration of HRT.The overall prevalence of tinnitus was 22.2% among postmenopausal women. (1) Tinnitus severity was significantly higher in women using HRT (p=0.0024) and (2) significantly lower in women who breast fed their children (p=0.0386). (3) According to logistic regression models, the longer duration of HRT was significantly associated with increasing tinnitus (OR=1.323, 95% CI 1.007 to 1.737, p=0.0441).A longer duration of HRT was associated with developing tinnitus in Korean postmenopausal women. Further experimental and epidemiological researches are needed to elucidate the causal relationship between HRT and tinnitus.
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.
