Control In Postmenopausal Women Research Articles

Endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice.

BackgroundHypercholesterolemia is a well-established risk factor for the development of kidney injury. Considering that female sex hormones may play a preventative role in both cardiovascular and renal diseases, the aim of the present study was to evaluate the effects of female sex hormones on hypercholesterolemia-induced renal dysfunction.MethodsApolipoprotein E-deficient (ApoE) and C57 control female mice underwent an ovariectomy (OVX) or sham surgery and after 2 months, creatinine clearance, uremia and proteinuria were determined. Renal oxidative stress and lipid deposition were also quantified. Values are presented as mean ± SEM. Statistical analyses were performed using Two-way ANOVA followed by Tukey’s post hoc test.ResultsCreatinine clearance (μL/min) was similar between C57 (171 ± 17) and ApoE (140 ± 26) mice underwent sham surgery. OVX resulted in a reduced glomerular filtration rate in both C57 (112 ± 8, ~ − 35%, p < 0.05) and ApoE (61 ± 10, ~ − 56%, p < 0.05) animals. Plasma levels of urea (mg/dL) were higher in both ApoE groups (Sham: 73 ± 7; OVX: 73 ± 8, p < 0.05) when compared to C57 animals (Sham: 49 ± 3; OVX: 60 ± 4), with no changes among ovariectomized groups. Proteinuria levels (mg/24 h) were similar between C57 (Sham: 25.1 ± 5.7; OVX: 33.7 ± 4.7) and ApoE sham animals (26.4 ± 3.5), however, 24-h urine protein excretion was augmented in ApoE OVX animals (49.6 ± 5.8, p < 0.05). Histological kidney analysis demonstrated that the absence of female sex hormones resulted in increased oxidative stress, which was more severe in ApoE mice (C57 Sham: 9.2 ± 0.4; C57 OVX: 22.9 ± 1.0; ApoE Sham: 13.9 ± 0.7; ApoE OVX: 34.0 ± 1.4 au x 103, p < 0.05). As expected, ApoE mice presented higher lipid deposition, which was not affected by OVX (C57 Sham: 0 ± 0; C57 OVX: 0 ± 0; ApoE Sham: 6.8 ± 1.6; ApoE OVX: 5.2 ± 0.8% x 10−2, p < 0.05). Ovariectomy resulted in a similar reduction in ER-α protein expression in the renal cortex (C57: 0.78 ± 0.04; ApoE: 0.81 ± 0.04 au, p < 0.05) when compared to sham animals (C57:1.00 ± 0.04; ApoE: 1.03 ± 0.03 au).ConclusionTaken together these data indicate that female sex hormones may delay hypercholesterolemia-induced renal dysfunction and emphasizes the importance of plasma cholesterol control in post-menopausal women.

Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus

Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT) on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone) on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95% confidence interval (CI), 0.55–0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51–0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, –1.41 mM/L; 95% CI, –2.49 to −0.33 mM/L) and HbA1c (mean difference, –0.73%; 95% CI, from −1.28 to −0.18%) compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, –0.34 mM/L; 95% CI, from −0.53 to −0.15 mM/L) and low-density lipoprotein (mean difference, –0.43 mM/L; 95% CI, from −0.71 to −0.14 mM/L) but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from −0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.

Whole-body vibration versus proprioceptive training on postural control in post-menopausal osteopenic women

BackgroundTo prevent falls in the elderly, especially those with low bone density, is it necessary to maintain muscle coordination and balance. The aim of this study was to examine the effect of classical balance training (BAL) and whole-body vibration training (VIB) on postural control in post-menopausal women with low bone density. MethodsSixty-eight subjects began the study and 57 completed the nine-month intervention program. All subjects performed resistive exercise and were randomized to either the BAL- (N=31) or VIB-group (N=26). The BAL-group performed progressive balance and coordination training and the VIB-group underwent, in total, four minutes of vibration (depending on exercise; 24–26Hz and 4–8mm range) on the Galileo Fitness. Every month, the performance of a single leg stance task on a standard unstable surface (Posturomed) was tested. At baseline and end of the study only, single leg stance, Romberg-stance, semi-tandem-stance and tandem-stance were tested on a ground reaction force platform (Leonardo). ResultsThe velocity of movement on the Posturomed improved by 28.3 (36.1%) (p<0.001) in the VIB-group and 18.5 (31.5%) (p<0.001) in the BAL-group by the end of the nine-month intervention period, but no differences were seen between the two groups (p=0.45). Balance tests performed on the Leonardo device did not show any significantly different responses between the two groups after nine months (p≥0.09). ConclusionsStrength training combined with either proprioceptive training or whole-body vibration was associated with improvements in some, but not all, measures of postural control in post-menopausal women with low bone density. The current study could not provide evidence for a significantly different impact of whole-body vibration or balance training on postural control.

Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1–31)NH2] in postmenopausal women with osteoporosis

ContextTreatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1–34) or rhPTH(1–84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance. ObjectiveThe UGL-OR1001 trial aimed to establish the efficacy and safety parameters of a novel oral tablet formulation of rhPTH(1–31)NH2 and matching placebo tablets and open-label teriparatide positive control in postmenopausal women with osteoporosis. Design24weeks of randomized, double-blind treatment with once daily doses of 5mg oral treatment or corresponding placebo, or open-label subcutaneous teriparatide. Patients or other participantsWomen diagnosed with postmenopausal osteoporosis as detected by lumbar spine DXA, with an exclusion of those with prior treatment with bone active agents. Intervention(s)Orally formulated recombinant human PTH(1–31)NH2 and placebo, or open-label subcutaneous teriparatide as a positive control. Main outcome measure(s)The primary endpoint was to characterize the percent change from baseline in bone mineral density (BMD) at L1–L4 axial lumbar spine after 24weeks in the rhPTH(1–31)NH2 arm. Secondary and exploratory endpoints included safety and tolerability of the oral formulation, measurement of biochemical markers of bone turnover, and evaluation of the PK profile at first and last dose. The study was registered at ClinicalTrials.gov with the identifier: NCT01321723. ResultsThe oral tablet formulation of rhPTH(1–31)NH2 resulted in similar PK profiles at both timepoints with mean Cmax values similar to subcutaneous administration. In the rhPTH(1–31)NH2 arm, a 2.2% increase in lumbar spine BMD was observed compared to baseline (p<0.001), while no change was observed in the placebo arm. Open-label teriparatide resulted in a 5.1% increase in LS BMD (p<0.001). In the oral PTH study arm, the bone formation marker osteocalcin was increased by 32%, 21% and 23% at Weeks 4, 12 and 24, respectively. There was no significant increase in the level of the bone resorption marker CTx-1. ConclusionsIn summary, these data demonstrate that enteric-coated oral tablet formulation technology consistently generated robust levels of exposure of rhPTH(1–31)NH2 leading to induction of bone formation without inducing bone resorption resulting in significantly increased levels of LS BMD. Few adverse events were observed, recommending this orally delivered drug candidate for further development.

Ventilatory responses to exercise and CO2 after menopause in healthy women: Effects of age and fitness

The extent to which aging affects respiratory control in postmenopausal women remains relatively unknown. In a cross-sectional study of 39 postmenopausal women (50–79 years), we examined the influence of age and fitness on the ventilatory responses to hypercapnia (HCVR; +8mmHg) and exercise (ΔV˙E/ΔV˙CO2) above and below the anaerobic threshold (AT). Data were analyzed using the full cohort, by age (younger postmenopausal: YPM, 50–64 years; and older postmenopausal: OPM, 65–79 years) and fitness as per our previous work (Active: V˙O2 max ≥90% age-predicted values; and Sedentary: V˙O2 max <90% age-predicted values).Although age did not affect the sensitivity of HCVR, Active women had significantly lower HCVR gain compared to sedentary women (Sedentary: 2.12±0.80; Active: 1.57±0.73, p=0.02). In contrast, age, but not fitness, was inversely related to ΔV˙E/ΔV˙CO2 above AT (YPM: 46.8±11.5; OPM: 34.8±6.9, p<0.01) which may be explained, at least in part, by age-related declines in lung function. HCVR and ΔV˙E/ΔV˙CO2 were not correlated.

Abstract P1-12-05: Factors Affecting Local Recurrence after Breast Conserving Surgery Following Neoadjuvant Endocrine Therapy with Letrozole

Abstract Background Few data exist on local recurrence rates after breast conserving surgery in post menopausal patients following neoadjuvant endocrine therapy with letrozole. The aim was to investigate the outcome of a large series of patients treated in the Edinburgh Breast Unit. Patients 208 patients underwent breast conserving surgery after at least a 3 month course of neoadjuvant letrozole. The median age was 77 years (range 51 to 93). Of these patients 73% (151/208) received postoperative radiotherapy. Median follow up was 2.95 years (range 0.28 to 8.43) Results At two years 97% were local recurrence free and by five years 95% were recurrence free. By the Log Rank (Mantel-Cox) non-parametric method of analysis, there was a significant difference between patients treated by postoperative whole breast radiotherapy (RT) compared with no radiotherapy (p=0.02). There were very small numbers of local recurrences (five in no RT group, two in RT group by the end of five years). At two years 93% of patients with no RT were recurrence-free, compared with 98% of those with RT, at five years this is 86% and 98% respectively There was a borderline significant difference between HER2 positive and negative breast cancers, (p=0.055). At two years 97% of HER2 negative patients were recurrence-free, compared with 91% of HER2 positive patients. At five years, it was 96% and 85% respectively. Death from other causes was very common in this elderly age group and the median survival time was 7.2 years (95% CI 5.8 to 8.5). 90% of patients survived to the end of two years (95% CI: 86% to 94%), while only 68% survived to the end of years (60% to 76%). By the Log Rank test, there was a significant difference between patients treated by radiotherapy and those who did not receive radiotherapy (p=0.004). The median survival with no RT was 4.7 years (95% CI: 3.7 to 5.8) and for patients following RT was 8.1 years (95% CI: 6.2 to 10.0). The reason for this was selection of fitter patients for radiotherapy and avoiding radiotherapy in frail patients. Conclusions Local recurrence after breast conserving therapy following neoadjuvant endocrine therapy with letrozole is uncommon in this group of patients. Following radiotherapy local recurrence is only 2% at 5 years. Rates of recurrence are over 10% at 5 years without radiotherapy. HER2 positive patients have a higher local recurrence rate than HER2 negative patients. Breast Conserving Surgery followed by whole breast radiotherapy produces excellent rates of local control in postmenopausal women following neoadjuvant endocrine therapy with letrozole. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-05.

Cardio-respiratory Fitness Affects Glucose Control And Thus Cardiovascular Disease Risk In Postmenopausal Women.

Increased glucose levels above a threshold of 4.9 mmol/L are associated with a greater risk of cardiovascular disease (CVD). The menopause has been associated with impaired glucose control, including poor glucose tolerance, increased glycosylated haemoglobin (HbA1C) and fasting insulin concentration. The positive effect of increased cardio-respiratory fitness (CRF) upon glucose control in postmenopausal women (PM-women) is unclear. PURPOSE: To determine the effects of CRF upon glucose control in PM-women. METHODS: CRF was assessed via Bruce treadmill test in 79 sedentary-to-moderately active and 10 marathon running (MR) PM-women. Sedentary-to-moderately active women were classified into low, medium or high CRF levels according to VO2 peak, MR were a separate group. Assessment of glucose control included analysis of fasting venous glucose and insulin (thus the homeostasis model assessment (HOMA)) and HbA1c concentrations The following additional CVD risk factors were assessed: body composition (skinfold analysis/waist and hip circumferences, BMI and body mass), flow mediated dilation (reactive hyperaemia) as an index of endothelial function, total cholesterol, high and low density lipoproteins, triglycerides and high sensitivity C-reactive protein (hsCRP). CRF level differences in glucose control variables were analysed via ANCOVA (all other variables as covariates), and multiple regression assessed which variables best predicted glucose control variables. RESULTS: Fasting plasma glucose concentration was the only glucose control variable to differ between CRF levels with the MR group having significantly lower concentrations (4.1mmol/L) than all other CRF levels (low CRF 5.7; medium CRF 5.5; high CRF 5.5 mmol/L). Additionally, MR women were the only group to have a glucose concentration less that 4.9 mmol/L (threshold for CVD risk). CRF was found to be the strongest predictor for glucose concentration. Conversely, body mass, waist circumference and hsCRP were the strongest predictors of insulin concentration and HOMA, whereas CRF had little predictive influence. CONCLUSION: Very high levels of CRF similar to marathon runners may be required to lower glucose concentration in PM-women to levels below the threshold for increased risk of CVD. Supported by a Heart Research UK grant 2508/06/08

Dietary Magnesium Deficiency Induces Heart Rhythm Changes, Impairs Glucose Tolerance, and Decreases Serum Cholesterol in Post Menopausal Women

Objective: To determine whether or not dietary magnesium restriction to about 33% of the Recommended Dietary Allowance (RDA) causes changes in glucose, cholesterol and electrolyte metabolism that could lead to pathologic consequences.Design: The length of the experiment was 136 days. Subjects were fed a basal Western-type diet that provided 4.16 mmol (101 mg) magnesium per 8.4 MJ (2000 kcal) for 78 days then replenished with magnesium by supplementing the diet with 200 mg magnesium as the gluconate per day for 58 days. If a subject exhibited adverse heart rhythm changes before 78 days of depletion were completed, she entered the repletion period early.Setting: The metabolic research unit of the Grand Forks Human Nutrition Research Center.Subjects: A total of 14 post menopausal women were recruited by advertisement throughout the United States. Thirteen women (ages 47 to 75 years) completed the study.Results: During magnesium depletion, heart rhythm changes appeared in 5 women and resulted in 4 prematurely entering the magnesium repletion period (42 to 64 days of depletion instead of 78). Three women exhibited atrial fibrillation and flutter that responded quickly to magnesium supplementation. Magnesium deprivation resulted in a non-positive magnesium balance that became highly positive with magnesium repletion. Magnesium deprivation decreased red blood cell membrane magnesium, serum total cholesterol and erythrocyte superoxide dismutase concentrations, increased the urinary excretion of sodium and potassium, and increased serum glucose concentration.Conclusions: Magnesium balance may be a suitable indicator of magnesium depletion under experimental conditions. Magnesium deficiency resulting from feeding a diet that would not be considered having an atypical menu induces heart arrhythmias, impairs glucose homeostasis, and alters cholesterol and oxidative metabolism in post menopausal women. A dietary intake of about 4.12 mmol (100 mg) Mg/8.4 MJ is inadequate for healthy adults and may result in compromised cardiovascular health and glycemic control in post menopausal women.

Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women

Background:Little evidence exists regarding the effects of soy consumption on the metabolic syndrome in humans.Objective:We aimed to determine the effects of soy consumption on components of the metabolic syndrome, plasma lipids, lipoproteins, insulin resistance, and glycemic control in postmenopausal women with the metabolic syndrome.Design:This randomized crossover clinical trial was undertaken in 42 postmenopausal women with the metabolic syndrome. Participants were randomly assigned to consume a control diet (Dietary Approaches to Stop Hypertension, DASH), a soy-protein diet, or a soy-nut diet, each for 8 wk. Red meat in the DASH period was replaced by soy-protein in the soy-protein period and by soy-nut in the soy-nut period.Results:The soy-nut regimen decreased the homeostasis model of assessment-insulin resistance score significantly compared with the soy-protein (difference in percentage change: −7.4 ± 0.8; P< 0.01) or control (−12.9 ± 0.9; P< 0.01) diets. Consumption of soy-nut also reduced fasting plasma glucose more significantly than did the soy-protein (−5.3 ± 0.5%; P< 0.01) or control (−5.1 ± 0.6%; P< 0.01) diet. The soy-nut regimen decreased LDL cholesterol more than did the soy-protein period (−5.0 ± 0.6%; P< 0.01) and the control (−9.5 ± 0.6%; P< 0.01) diet. Soy-nut consumption significantly reduced serum C-peptide concentrations compared with control diet (−8.0 ± 2.1; P< 0.01), but consumption of soy-protein did not.Conclusion:Short-term soy-nut consumption improved glycemic control and lipid profiles in postmenopausal women with the metabolic syndrome.

Medroxyprogesterone improves cardiac autonomic control in postmenopausal women with respiratory insufficiency

Objective: To study the effect of medroxyprogesterone acetate (MPA) on autonomic cardiac control in respiratory insufficiency in postmenopausal women. Design: A prospective, single-blind study. Subjects: Eighteen postmenopausal women with respiratory insufficiency and eight asymptomatic postmenopausal women with nocturnal hypoxaemia as controls. Methods: Oral MPA treatment was given at 30 mg twice daily for 2 weeks. All-night polysomnography including a two-channel electroencephalogram, an electro-oculogram, an electromyogram, an electrocardiogram, arterial oxyhaemoglobin saturation, maximum end-tidal CO 2 partial pressure, a ballistocardiogram and breathing movements were recorded at baseline and at the end of MPA treatment. Heart rate variability (HRV) was calculated in time and frequency domains during various sleep stages on and off MPA, and the results were correlated to respiratory variables. Results: At baseline, patients had higher heart rate and lower HRV than controls, suggesting increased cardiac sympathetic output. MPA increased HRV in patients, but not in controls. End-tidal CO 2 partial pressure decreased, and respiratory rate increased during treatment in both groups. Conclusions: HRV is compromised in women with respiratory insufficiency. Peroral MPA increases their HRV to levels comparable with those in controls. This suggests an improvement in vagal cardiac control beneficial to cardiovascular health.

Raloxifene Does Not Affect Insulin Sensitivity or Glycemic Control in Postmenopausal Women with Type 2 Diabetes Mellitus: A Randomized Clinical Trial

Raloxifene Does Not Affect Insulin Sensitivity or Glycemic Control in Postmenopausal Women with Type 2 Diabetes Mellitus: A Randomized Clinical Trial

Dietary Soy Supplementation and Phytoestrogen Levels

In Brief Objective To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. Methods Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. Results Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. Conclusion Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes. Phytoestrogen levels increase with soy supplementation in climacteric women but do not correlate with a decrease in the number of hot flushes.

Dietary soy supplementation and phytoestrogen levels

Objective: To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. Methods: Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. Results: Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. Conclusion: Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.