Effects of Estradiol Dose and Serum Estradiol Levels on Metabolic Measures in Early and Late Postmenopausal Women in the REPLENISH Trial.
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SUBMITTER: Sriprasert I
PROVIDER: S-EPMC7759286 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: This study evaluated associations of estradiol (E2) dose and serum E2 levels with coagulation/anti-coagulation measures in early (<6 years) compared with late (≥10 years) postmenopausal women.Methods: Postmenopausal women from the REPLENISH trial tested four formulations of oral combined E2 and progesterone compared with placebo. Mixed-effects linear models tested the association of E2 dose and serum E2 levels with the prothrombin time (PT), the activated partial thromboplastin time (APTT), antithrombin (ATHRM), fibrinogen (FIBRINO), protein C (PROTC), and protein S (PROTS), assessed five times over 12 months.Results: Among 1215 early and 297 late postmenopausal women, the E2 dose was statistically significantly inversely associated with the APTT in early postmenopause, PROTC in late postmenopause, and with the PT, ATHRM, and PROTS in both groups. Serum E2 levels were statistically significantly inversely associated with the APTT, PROTS, and FIBRINO in early postmenopause, the PT in late postmenopause, and ATHRM and PROTC in both groups. With longer time since menopause, the inverse E2 dose effect and serum E2 effects became stronger.Conclusion: Increasing E2 dose and serum E2 levels were associated with changes in coagulation/anti-coagulation measures. The associations were stronger among women ≥10 years since menopause when initiating E2. The timing of E2 therapy, E2 dose, and serum E2 levels relative to time since menopause may modify the venous thromboembolism risk.
| S-EPMC7853766 | biostudies-literature
Project description:ObjectiveTo identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT).MethodsThis is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function.ResultsThe analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women.ConclusionFactors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention.Clinical trial registrationClinicalTrials.gov, NCT00114517.
| S-EPMC7529896 | biostudies-literature
Project description:ObjectiveTo examine the impact of a single-capsule 17?-estradiol (E2)/progesterone (P4) on weight and blood pressure (BP) when treating moderate to severe vasomotor symptoms in postmenopausal women with a uterus.MethodsHealthy postmenopausal women with a uterus (aged 40-65, body mass index ?34?kg/m2, BP ?140/90 mm Hg) were randomized to daily E2/P4?(mg/mg; 1/100, 0.5/100, 0.5/50, 0.25/50) or placebo in the phase 3 REPLENISH trial (NCT01942668). Changes in weight and BP from baseline to month 12 were evaluated. Potentially clinically important changes were defined as increases or decreases from baseline in weight by ?15% and ?11.3?kg, systolic BP by ?20 mm Hg (absolute value ?160 or ?90 mm Hg), and diastolic BP by ?15 mm Hg (absolute value ?90 or ?60 mm Hg).ResultsOverall mean changes in weight and BP from baseline to month 12 with E2/P4 were modest and generally not statistically or clinically significant versus placebo. Incidence of potentially clinically important changes was low for weight (E2/P4 vs placebo: 1.1-2.6% vs 2.2%), systolic BP (0.3-1.1% vs 1.1%), and diastolic BP (1.4-4.2% vs 3.2%). A small number of women had treatment-related, treatment-emergent adverse events of weight gain (1.4-2.6% vs 1.3%) or hypertension (0.2-1.2% vs 0%). Few women who discontinued E2/P4 had weight gain (1.6%) or hypertension (0.6%) as a primary reason. Efficacy profile on VMS was consistent with previous findings and not modified by body mass index.ConclusionsTwelve-month use of E2/P4 had no clinically meaningful impact on weight or BP in postmenopausal women of the REPLENISH study.
| S-EPMC7769186 | biostudies-literature
Project description:Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.
| S-EPMC7159036 | biostudies-literature
Project description:Postmenopausal changes in the hormonal milieu in women with or without hormone therapy are hypothesized to be the pathway for a number of menopause-associated modifications in physiology and disease risk. Physical activity may modify these changes in women's hormone profiles. The crucial yet complex relationship between physical activity and physiologic and pharmacologic sex hormone levels in postmenopausal women has not been investigated sufficiently.Using structured recall, physical activity was assessed longitudinally during a period of 2 years in 194 postmenopausal women (90 randomized to 1 mg 17?-estradiol treatment daily and 104 randomized to placebo) in the Estrogen in the Prevention of Atherosclerosis Trial. The levels of physical activity were correlated with the serum sex hormone and the serum hormone-binding globulin levels in each treatment group.Among the placebo-treated women, total energy expenditure was positively associated with sex hormone-binding globulin (SHBG; P < 0.001) and inversely associated with testosterones (total, bioavailable, or free) and androstenedione (P < 0.001 for all), as well as with estradiol (P = 0.02). In estradiol-treated women, estradiol levels were inversely associated with total energy expenditure (P = 0.002) and weekly hours spent in moderate or more vigorous physical activity (P = 0.001).Physical activity is associated with lower serum levels of estradiol in both hormone therapy-treated and untreated women. In placebo-treated women only, physical activity is associated with reduced androgen levels and elevated SHBG levels.
| S-EPMC3183237 | biostudies-literature
Project description:ImportanceHalf of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention.ObjectiveTo compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal.Design, setting, and participantsThis is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022.InterventionsParticipants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks.Main outcomes and measuresIn this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics.ResultsA total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.Trial registrationClinicalTrials.gov Identifier: NCT02516202.
| S-EPMC9664265 | biostudies-literature
Project description:Objective:Estradiol (E2) regulates adipose tissue resulting in increased fat mass (FM) with declining E2. However, increased visceral fat and hyperestrogenemia are features of obese individuals. It is possible that adipocytes in obese individuals are less sensitive to E2 resulting in higher FM. Our objective is to identify the range of serum E2 for which postmenopausal women have the lowest FM and best body composition. Methods:Cross-sectional data from 252 community-dwelling postmenopausal women, 42-90?years old. Subjects were stratified into categories of E2 (pg/ml): (1) ?10.5; (2) 10.6-13.9; (3) 14.0-17.4; and (4) ?17.5. Body composition by dual-energy X-ray absorptiometry. Serum E2 by radioimmunoassay. Between-group comparisons by analysis of covariance. Results:E2 linearly increased with increasing body weight and body mass index (r?=?0.15 and p?=?0.01 for both), but not with total FM (kg) or %?FM (r?=?0.07, p?=?0.34 and r?=?-0.04, p?=?0.56, respectively). However, total FM (kg) followed a U-shaped distribution and was significantly lower in group 3 (27.6?±?10.6), compared with groups 1: (34.6?±?12.5), 2: (34.0?±?12.4), and 4: (37.0?±?10.6), p?=?0.005. %?FM was also lowest in group 3. While fat-free mass (FFM, kg) increased with increasing E2 (p?<?0.001), % FFM was highest in group 3. Conclusion:In our population of postmenopausal women, FM followed a U-shaped distribution according to E2 levels. E2 between 14.0 and 17.4?pg/ml is associated with the best body composition, i.e., lowest total and %?FM and highest % FFM. Given the role of E2 in regulating body fat, high FM at the high end of the E2 spectrum may suggest reduced E2 sensitivity in adipocytes among obese postmenopausal women. Clinical Trials:ClinicalTrials.gov identifier: NCT00146107.
| S-EPMC6036116 | biostudies-literature
Project description:(1) Metabolic syndrome is a set of factors that considerably increase the risk of developing atherosclerosis, type 2 diabetes, and their cardiovascular complications. Studies show that menopause and the levels of elements may be significantly associated with increased risk of MetS. The present study evaluated the relationship between element levels (Ca, P, Na, K, Fe, Mg, Cu, Zn, Sr) and the incidence of MetS and concomitant metabolic disorders in peri-menopausal women. (2) The study involved 170 perimenopausal women. The methods used were: survey, anthropometric measurement (WC, height, BMI, WHtR), blood pressure measurement, and biochemical analysis of venous blood (lipid profile, glucose, insulin, HbA1C). (3) The study demonstrated statistically significantly higher WC, WHtR, SBP, and DBP values in women with pre-Mets than in those with Mets and the control group. Significantly higher FPG, TG, LDL, HbA1C, insulin, TG/HDL ratio, and TC/HDL ratio were recorded in the MetS group compared to the rest of respondents. In addition, post hoc analysis revealed statistically significant differences in mean K concentrations between pre-MetS and MetS women. (4) Low blood K levels in perimenopausal women are associated with an increased risk of MetS. Significantly higher Cu levels were observed in overweight women. The concentration of Cu negatively correlates with the values of TC, LDL, and SBP.
| S-EPMC9572475 | biostudies-literature
Project description:As an ancillary report to a large National Institutes of Health (NIH)-funded trial, we examined the effects of 6 months of exercise training at 50%, 100%, and 150% of the NIH Consensus Recommendations for physical activity (i.e., 4, 8, and 12 kcal/kg of energy expenditure/wk [KKW]) versus a nonexercise control group on the metabolic syndrome (MS) in sedentary, overweight, moderately hypertensive, postmenopausal women. We examined the clinically defined National Cholesterol Education Program MS, individual components scores, and summed z-scores, expressed as a continuous variable (zMS), using chi-square and general linear models to assess the clinical and progressive nature of MS, respectively. Our results showed significant improvements in zMS for all exercise groups and MS for the 8- and 12 KKW groups only (all, p for trend = 0.02). Post hoc analyses showed that 12 KKW for zMS and 8 and 12 KKW for MS was significant versus the control group (all, p <0.05). When examining the composite scores, we observed significant trends for improvement in waist circumference (p for trend = 0.001), fasting glucose (p for trend = 0.01), and systolic blood pressure (p for trend = 0.02), which appeared to be dose dependent, given the additive nature for incorporating the within-group improvements in waist circumference (4, 8, and 12 KKW), fasting glucose (8 and 12 KKW), and systolic blood pressure (12 KKW). Our results suggest that low-to-moderate intensity cardiorespiratory exercise appears to improve components of the MS in postmenopausal women at levels at or greater than NIH recommendations and that zMS improves at half the NIH recommendations. Greater levels of energy expenditure appear to enhance this effect by incorporating a greater number of requisite MS composite scores.
| S-EPMC3755613 | biostudies-literature
Project description:BackgroundData suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.MethodsA total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen.ResultsAfter a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum.ConclusionsOral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).
| S-EPMC4921205 | biostudies-literature