Intervention In Postmenopausal Women Research Articles

Improving Diet Quality Is Associated with Decreased Inflammation: Findings from a Pilot Intervention in Postmenopausal Women with Obesity

BackgroundChronic inflammation is associated with obesity, morbidity, and mortality in postmenopausal women. ObjectiveThe objective of this pilot study was to determine preliminary feasibility and efficacy of a dietary intervention to improve diet quality and lower inflammation. DesignThe study had a single-arm, pre- and posttest design. Participants/settingFourteen postmenopausal women (body mass index >30 [calculated as kg/m2]) from the greater Columbus, OH, area participated between August 2015 and April 2016. InterventionThis was a 12-week individualized dietary intervention targeting lower consumption of added sugars and increased fiber and fatty fish. Main outcome measuresPrimary outcomes of this analysis were serum tumor necrosis factor α receptor-2 (TNFαR-2), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP); other outcomes included intake of targeted food components and Healthy Eating Index-2010 (HEI-2010) scores calculated from food frequency questionnaires at baseline, end of intervention (week 12 [WK12]), and 24-week (WK24) follow-up. Statistical analyses performedRepeated measures analysis of variance and partial Pearson correlations, respectively, were used to assess changes in outcomes and associations between dietary variables and inflammatory markers, controlling for percent weight change. ResultsMean levels of TNFαR-2 decreased pre- to postintervention (P<0.01) and remained reduced at WK24 (P<0.001). Mean intake of added sugars and n-3-rich fish improved from baseline to WK12 and remained better at WK24 (all P<0.001); mean fiber intake did not change significantly (P=0.66; baseline to WK24). Mean HEI-2010 score increased (P<0.001; baseline to WK12). Change in HEI-2010 score inversely correlated with change in TNFαR-2 (P<0.05; baseline to WK24). Change in added sugars directly correlated with change in TNFαR-2 (P<0.05; baseline to WK24), but inversely correlated with change in hsCRP (P<0.05; baseline to WK12, and WK12 to WK24). All participants lost weight by WK12 (P<0.001). ConclusionsThese pilot intervention findings suggest that improving diet quality is associated with decreases in TNFαR-2.

Effect of Dietary Nitrate on Blood Pressure and Vascular Control in Post‐Menopausal Hypertensive Women

Individuals with hypertension exhibit abnormal pressor responses during rest‐to‐exercise transitions, significantly increasing the likelihood of sudden cardiac events. Dietary nitrate supplementation can lower resting blood pressure in patients with hypertension and improve bulk muscle blood flow in older healthy adults. However, investigations using dietary nitrate as a non‐pharmacological intervention in post‐menopausal women diagnosed with hypertension are lacking. Therefore, the purpose of the current investigation was to determine if acute dietary nitrate supplementation would improve the pressor response to exercise and increase forearm blood flow during steady‐state hand‐grip exercise in post‐menopausal hypertensive women. It was hypothesized that the pressor response to exercise would be attenuated and muscle blood flow would be improved in the nitrate‐rich (NR) versus nitrate‐poor (NP) treatment.METHODSTen hypertensive post‐menopausal women [age 56 ± 3 years (mean±SD); height 165 ± 2 cm; mass 84 ± 13 kg; body mass index 31 ± 5 kg/m2] agreed to participate in the current study. Patients underwent a randomized double‐blind placebo‐controlled trial with a NR or NP beet root juice supplement. Blood samples were taken at the beginning of each testing session (~2 h post ingestion) to determine plasma nitrite levels. Forearm blood flow (FBF) was measured via ultrasonography at the brachial artery of the exercising limb. Beat‐by‐beat blood pressure and heart rate were recorded throughout the trial on the non‐exercising limb. After resting measurements were completed, patients performed hand‐grip exercise at 20% maximal voluntary contraction (MVC) for five minutes to obtain steady‐state blood flow and blood pressure response to exercise.RESULTSPlasma nitrite levels were significantly higher during the NR (809 ± 146 nM) than the NP (79 ± 19 nM) condition. No differences were found between conditions for resting blood flow (NR: 64±2; NP: 62 ± 4 ml min−1; P &gt; 0.05), systolic (NR: 144 ± 2; NP: 145 ± 2 mmHg−1; P &gt; 0.05) or diastolic blood pressure (NR: 78 ± 1; NP: 80 ± 1 mmHg−1; P &gt; 0.05). In addition, there were no significant differences across 10‐second bins (e.g., 0–10, 11–20 seconds) during the first minute pressor response to hand‐grip exercise in either condition (systolic: P &gt; 0.05; diastolic: P &gt; 0.05). As such, the rate pressure product was not significantly different during steady‐state between conditions (NR: 11,562 ± 437; NP: 11,728 ± 437 bpm · mmHg−1; P &gt; 0.05). During steady‐state exercise, FBF (NR: 189 ± 8; NP: 218 ± 8 ml min−1; P = 0.03) and forearm vascular conductance (FVC) (NR: 157 ± 4; NP: 183 ± 4 ml min−1; P = 0.04) were significantly lower during the steady‐state NR condition.CONCLUSIONAcute dietary nitrate supplementation did not improve the pressor response to hand‐grip exercise in hypertensive post‐menopausal women. However, it is important to note that steady‐state FBF (~30 ml min−1) and FVC (~27 ml min mmHg−1) were significantly reduced during the nitrate‐rich condition, which suggests a reduced O2 cost for a given workload because blood flow typically matches metabolic rate.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Low-Fat Dietary Pattern and Diabetes: A Secondary Analysis From the Women’s Health Initiative Dietary Modification Trial

We performed a secondary analysis to evaluate the effect of the Women's Health Initiative dietary intervention on incident diabetes and diabetes treatment in postmenopausal women. A total of 48,835 women were randomized to a comparison group or an intervention group that underwent a behavioral/nutritional modification program to decrease fat and increase vegetable, fruit, and grain intake for an average of 8.1 years. Ninety-three percent of participants completed the intervention, and 71% participated in active follow-up through 30 September 2015 (median 17.3 years). We measured time to development of treated diabetes and progression from oral antihyperglycemic agents to insulin. Serum glucose and insulin were measured in a subsample of women (N = 2,324) at baseline and years 1, 3, and 6. During the trial, intervention group women had lower rates of initiation of insulin therapy (hazard ratio [HR] 0.74 [95% CI 0.59, 0.94]; P = 0.01). Moreover, women with baseline waist circumference ≥88 cm (P interaction = 0.01) and worse metabolic syndrome scores (P interaction = 0.02) had the greatest reduction in risk of initiating insulin therapy. The decreased risk from the intervention was present during the cumulative follow-up (HR 0.88 [95% CI 0.78, 0.99]; P = 0.04). In participants with measured biomarkers (5.8% subsample) who had baseline glucose <100 mg/dL, the intervention reduced the risk of developing glucose ≥100 mg/dL by 25% (odds ratio 0.75 [95% CI 0.61, 0.93]; P = 0.008). Adjustment for weight change did not alter the results. In this secondary analysis, a dietary intervention in postmenopausal women aimed at reducing fat and increasing intake of vegetables, fruits, and grains did not increase risk of diabetes and may have slowed progression.

Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: A systematic review and meta-analysis.

Introduction:Bazedoxifene may be promising to treat osteoporosis of postmenopausal women. We conducted a systematic review and meta-analysis to explore the efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis.Methods:PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of bazedoxifene on osteoporosis of postmenopausal women were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were vertebral fracture and spine BMD at 3 and 7 years.Results:Four RCTs are included in the meta-analysis. Overall, compared with placebo intervention in postmenopausal women with osteoporosis, bazedoxifene intervention can significantly reduce the risk of vertebral fracture [risk risks (RRs) = 0.69; 95% confidence interval (95% CI) = 0.52–0.93; P = .01], and increase spine BMD at 3 years (Std. mean difference = 1.71; 95% CI = 1.55–1.87; P < .005) and 7 years (Std. mean difference = 8.31; 95% CI = 8.07–8.55; P < .005). Bazedoxifene intervention results in no increase in adverse events (RR = 1.00; 95% CI = 0.99–1.00; P = .34), serious adverse events (RR = 1.04; 95% CI = 0.97–1.12; P = .31), myocardial infarction (RR = 0.88; 95% CI = 0.51–1.52; P = .64), stroke (RR = 0.97; 95% CI = 0.64–1.46; P = .87), venous thromboembolic event (RR = 1.56; 95% CI = 0.92–2.64; P = .10), and breast carcinoma (RR = 1.03; 95% CI = 0.59–1.79; P = .92).Conclusions:Compared with placebo intervention for the osteoporosis of postmenopausal women, bazedoxifene intervention is found to significantly reduce the incidence of vertebral fracture and increase spine BMD at 3 and 7 years, and results in no increase in adverse events, serious adverse events, myocardial infarction, stroke, venous thromboembolic event, and breast carcinoma.

Psychosocial Outcomes 12 Months Following a Dose–Response Aerobic Exercise Intervention in Postmenopausal Women

We previously reported no postintervention differences in quality of life and other psychosocial outcomes when comparing 12-month high versus moderate volume of aerobic exercise in postmenopausal women. Here, we report the 24-month follow-up for these outcomes. At 24-month follow-up, 333 out of 400 postmenopausal women were randomized to a year-long intervention of 150 (moderate) or 300 (high) minutes per week of aerobic exercise returned a battery of self-reported measures assessing quality of life, psychosocial outcomes, and sleep quality, also assessed at baseline and postintervention. Intention-to-treat analyses using linear models were conducted to determine the changes between baseline and 24-month follow-up. No significant effects between moderate- and high-volume aerobic exercise groups were observed among any outcomes. There was some evidence of effect moderation by baseline body mass index in relation to quality of life, psychosocial outcomes, and sleep quality, where obese women benefitted from the moderate-volume exercise and nonobese women benefitted from the high-volume exercise prescription. Although high-volume aerobic exercise did not improve psychosocial outcomes when compared with moderate volume at the 24-month follow-up, we did observe potential effect of moderation between obese and nonobese women. Confirmation of these interactions is warranted in this population.

The effects of green kiwifruit combined with isoflavones on equol production, bone turnover and gut microflora in healthy postmenopausal women.

Isoflavone (daidzein and genistein) interventions in postmenopausal women have produced inconsistent skeletal benefits, partly due to population heterogeneity in daidzein metabolism to equol by enteric bacteria. This study assessed changes in microflora and bone turnover in response to isoflavone and ki-wifruit supplementation in New Zealand postmenopausal women. Healthy women 1-10 years post-menopause were randomly allocated to group A (n=16) or B (n=17) for a 16-week crossover trial. Two consecutive 6-week treatment periods had a 2-week lead-in period at intervention commencement and a 2-week washout period between treatments. Treatments prescribed either (1) daily isoflavone supplementation (50 mg/day aglycone daidzein and genistein) alone, or (2) with two green kiwifruit. At treatment baseline and end-point (four time points) the serum bone markers C Telopeptide of Type I collagen (CTx), undercarboxylated os-teocalcin (unOC), and serum and urinary daidzein and equol, were measured. Changes in gut microflora were monitored in a subgroup of the women. Equol producers made up 30% of this study population (equol producers n=10; non-equol producers n=23) with serum equol rising significantly in equol producers. Serum ucOC decreased by 15.5% (p<0.05) after the kiwifruit and isoflavone treatment. There were no changes in serum CTx or in the diversity of the gut microflora. 50 mg/day isoflavones did not reduce bone resorption but kiwifruit and isoflavone consumption decreased serum ucOC levels, possibly due to vitamin K1 and/or other bioactive components of green kiwifruit.

Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity.

Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed. Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters. Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001). A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

Acyl-CoA synthetase long-chain 5 genotype is associated with body composition changes in response to lifestyle interventions in postmenopausal women with overweight and obesity: a genetic association study on cohorts Montréal-Ottawa New Emerging Team, and Complications Associated with Obesity.

BackgroundGenetic studies on Acyl-CoA Synthetase Long-Chain 5 (ACSL5) demonstrate an association between rs2419621 genotype and rate of weight loss in women with obesity in response to caloric restriction. Our objectives were to (1) confirm results in two different populations of women with overweight and obesity (2) study rs2419621’s influence on body composition parameters of women with overweight and obesity following lifestyle interventions.Methodsrs2419621 genotype was determined in women with overweight and obesity who participated in the Montréal-Ottawa New Emerging Team (MONET n = 137) and Complications Associated with Obesity (CAO n = 37) studies. Genotyping was done using TaqMan MGB probe-based assay. Multiple linear regression analyses were used to test for associations.ResultsWhen studying women with overweight and obesity, rs2419621 [T] allele carriers had a significantly greater decrease in visceral fat, absolute and percent fat mass and a greater increase in percent lean mass in response to lifestyle intervention in comparison to non-carriers. Studying only individuals with obesity showed similar results with rs2419621 [T] allele carriers also displaying a significantly greater decrease in body mass index following the lifestyle intervention in comparison to non-carriers.ConclusionWomen with overweight and obesity carrying the ACSL5 rs2419621 [T] allele are more responsive to lifestyle interventions in comparison to non-carriers. Conducting such genetic association studies can aid in individualized treatments/interventions catered towards an individual’s genotype.

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

Quantitative insight into species differences in risk assessment is expected to reduce uncertainty and variability related to extrapolation from animals to humans. This paper explores quantification and comparison of gene expression data between tissues and species from intervention studies with isoflavones.Gene expression data from peripheral blood mononuclear cells (PBMCs) and white adipose tissue (WAT) after 8wk isoflavone interventions in postmenopausal women and ovariectomized F344 rats were used. A multivariate model was applied to quantify gene expression effects, which showed 3–5-fold larger effect sizes in rats compared to humans. For estrogen responsive genes, a 5-fold greater effect size was found in rats than in humans. For these genes, intertissue correlations (r = 0.23 in humans, r = 0.22 in rats) and interspecies correlation in WAT (r = 0.31) were statistically significant. Effect sizes, intertissue and interspecies correlations for some groups of genes within energy metabolism, inflammation and cell cycle processes were significant, but weak.Quantification of gene expression data reveals differences between rats and women in effect magnitude after isoflavone supplementation. For risk assessment, quantification of gene expression data and subsequent calculation of intertissue and interspecies correlations within biological pathways will further strengthen knowledge on comparability between tissues and species.

The Effect of Spiritual Intervention on Postmenopausal Depression in Women Referred to Urban Healthcare Centers in Isfahan: A Double-Blind Clinical Trial.

Background:Depression is not only common after menopause, but also affects postmenopausal women more than other women. Some studies show the positive effects of spiritual intervention on postmenopausal women and depressed patients. However, there is inadequate experimental data for supporting the effectiveness of such interventions.Objectives:This study investigated the effect of a spiritual intervention on postmenopausal depression in women referred to urban healthcare centers in Isfahan, Iran.Patients and Methods:A randomized controlled clinical trial was conducted on postmenopausal women referred to the healthcare centers of Isfahan. Sixty-four women with postmenopausal depression were assigned randomly into an experimental group (n = 32) and a control group (n = 32). The experimental group received eight sessions of spiritual intervention while the control group received two sessions of training on healthy diet for postmenopausal women. All subjects in the experimental group and the control group responded to the Beck’s depression inventory at the start of the study, at the end of the fourth week, and a month after the last educational session. In addition to descriptive statistics, the chi-square test, independent samples t-test and repeated measures analysis of variance were used to analyze the data.Results:Before the intervention, the study groups did not differ significantly in terms of mean depression scores (20.76 ± 4.61 vs. 19.58 ± 5.27, P = 0.33). However, immediately after intervention and after one month, the mean depression scores of 11.01 ± 7.85 and 11.21 ± 9.23 in the experimental group were significantly lower than the control group (19.22 ± 4.94 and 19.34 ± 4.92, respectively) (P = 0.001). In repeated measures analysis of variance, Mauchly’s test of sphericity was not significant (P = 0.672), and in the test of within-subjects effects, a significant interaction was found between the spiritual intervention and time.Conclusions:Spiritual intervention effectively could reduce the severity of postmenopausal depression. Considering the high prevalence of depression in postmenopausal women and the effectiveness, simplicity, and affordability of spiritual intervention, using such interventions in postmenopausal women is recommended.

No effect of caloric restriction or exercise on radiation repair capacity.

Maintenance of normal weight and higher levels of physical activity are associated with a reduced risk of several types of cancer. Because genomic instability is regarded as a hallmark of cancer development, one proposed mechanism is improvement of DNA repair function. We investigated links between dietary weight loss, exercise, and strand break rejoining in an ancillary study to a randomized-controlled trial. Overweight/obese postmenopausal women (n = 439) were randomized to the following: a) reduced calorie weight loss diet ("diet," n = 118), b) moderate- to vigorous-intensity aerobic exercise ("exercise," n = 117), c) a combination ("diet + exercise," n = 117), or d) control (n = 87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 min of moderate to vigorous aerobic activity 5 d·wk for 12 months. DNA repair capacity was measured in a subset of 226 women at baseline and 12 months from cryopreserved peripheral mononuclear cells using the comet assay. Anthropometric and body composition measures were performed at baseline and 12 months. DNA repair capacity did not change significantly with any of the 12-month interventions compared with control; there were also no significant changes when stratified by changes in body composition or aerobic fitness (V˙O2max). At baseline, DNA repair capacity was positively associated with weight, body mass index, and fat mass (r = 0.20, P = 0.003; r = 0.19, P = 0.004; r = 0.13, P = 0.04, respectively) and inversely with lean body mass (r = -0.14, P = 0.04). In conclusion, DNA repair capacity in cryopreserved PBMCs (Comet Assay) did not change with dietary weight loss or exercise interventions in postmenopausal women within a period of 12 months. Other assays that capture different facets of DNA repair function may be needed.

Effects of tai chi in postmenopausal women with osteoporosis: a systematic review

Tai chi has been increasingly applied in osteoporosis patients. However, systematic reviews of the efficacy of this practice have been few and of limited scope. This study reviews previous experimental research work using tai chi as an intervention in postmenopausal women with osteoporosis and to appraise the reported research designs used, tai chi methods used, and outcomes. A systematic review method was used to search 14 databases for articles published between January 1980 and July 2013. Searched keywords included: "tai chi," "osteoporosis," and "postmenopausal women". The 2,458 articles initially identified were reduced to 4 valid articles based on considerations of criteria and repeatability. The 4 valid articles used either a randomized clinical trial (RCT) or a controlled clinical trial (CCT). They were further analyzed and synthesized in terms of common variables such as balance, muscle strength, and quality of life. Three of the 4 studies identified significant pretest / posttest differences in physiological aspects of quality of life in participants but did not obtain consistent results in terms of the psychological aspects. While reports identified a significant and positive tai chi effect on balance, they all used different measurements to do so. Only one of the four studies identified significant improvement in muscle strength. Therefore, this review could not identify clear support for the effectiveness of tai chi on balance or muscle strength. This review did not definitively support the positive effects of tai chi on balance, muscle strength, and quality of life in postmenopausal women with osteoporosis. The designs used in the tai chi interventions may be referenced for future studies. We suggest that future studies use data triangulation rather than a single-item tool to validate the research in order to cross-verify the same information. This may strengthen the research and increase the credibility and the validity of related findings.

Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed.

Effect of Dietetic Intervention in Brazilian Postmenopausal Women with Metabolic Syndrome

The study aim was to investigate the effects of individualized dietary intervention in postmenopausal women with metabolic syndrome. In this randomized and controlled clinical trial, a total of 55 women 40-65 years old presenting metabolic syndrome diagnosis were randomly assigned into intervention and control groups (50.9%). The intervention group received individualized diets prescribed by nutritionists. Participants were assessed at baseline moment (M0) and after a 16 weeks period (M1) for anthropometric, clinical, biochemical, and dietary parameters. The Student’s t-test was applied for independent and dependent numerical variables. It was hypothesized that postmenopausal women with metabolic syndrome obtaining dietary intervention would show improvement in the assessed parameters. At M0 there was no significant difference in all parameters between groups, demonstrating homogeneity samples. Yet, at M1, the intervention group showed statistical significant differences: decline in body weight (−3.5 kg), body mass index (−0.3 kg/m2), waist circumference (−4.1 cm), and systolic (−7.6 mmHg) and diastolic blood pressure (−1.6 mmHg); reductions in plasma levels of total cholesterol, triglycerides, and LDLcholesterol; as well as increase of HDL-cholesterol and decrease in habitual consumption of energy and dietary lipids. Regarding diet quality, we observed increase of fish, low-fat dairy, fruits, and vegetables consumption; and decrease of butter, margarine, sweets, soft drinks, and fast food consumption. In contrast, the control group showed no improvement in any of these parameters; quite the contrary, they even showed significant weight gain (+0.6 kg). The intervention group had 18.5% reversal rate in metabolic syndrome diagnosis, showing that individualized nutrition care was effective in controlling the metabolic syndrome.

Bifidogenic effect of whole-grain wheat during a 12-week energy-restricted dietary intervention in postmenopausal women

Consumption of whole-grain products is known to have beneficial effects on human health. The effects of whole-grain products on the intestinal microbiota and intestinal integrity have, however, only been studied limitedly. We investigate changes of the human gut microbiota composition after consumption of whole-grain (WW) or refined wheat (RW) and further study effects on gut wall integrity. Quantitative PCR was used to determine changes in the gut bacterial composition in postmenopausal women following a 12-week energy-restricted dietary intervention with WW (N=38) or RW (N=34). Intestinal integrity was determined by measuring trans-epithelial resistance (TER) across a Caco-2 cell monolayer, following exposure to faecal water. No significant differences in microbiota composition were observed between the two dietary groups; however, the whole-grain intervention increased the relative abundance of Bifidobacterium compared to baseline, supporting a prebiotic effect of whole-grain wheat. Faecal water increased TER independent of dietary intervention, indicating that commensal bacteria produce metabolites that generally provide a positive effect on intestinal integrity. Combining microbiota composition data from the run-in period with its effect on TER revealed a tendency for a negative correlation between the relative abundance of Bifidobacterium and TER (P=0.09). This contradicts previous findings but supports observations of increased Salmonella infection in animal models following treatment with bifidogenic prebiotics. The present study shows that whole-grain wheat consumption increases the abundance of bifidobacteria compared to baseline and may have indirect effects on the integrity of the intestinal wall.

A larger weight reduction is necessary to elicit an increase in adiponectin and a decrease in leptin levels

We read the article ‘Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels’ by Abbenhardt et al. 1 with interest. The authors concluded that diet-induced weight loss with or without exercise increased the serum adiponectin concentration and resulted in a reduction in leptin levels 1. The role of adipose tissue for storage of fuel has recently been extended by Ryan and co-workers to include a contribution to whole-body metabolism due to the proteins secreted by this tissue including leptin, tumour necrosis factor-alpha and adiponectin 2. Adiponectin levels are decreased in obesity 3, and cross-sectional studies have shown an inverse relationship between adiponectin and body mass index 3. In addition, adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content 4. Adiponectin has been shown to have a range of anti-inflammatory, antioxidant and anti-atherosclerotic actions 5. Furthermore, plasma adiponectin levels are blunted in conditions that suggest a high cardiovascular disease risk, such as coronary artery disease, type 2 diabetes and obesity, as well as by cigarette smoking 6. Leptin production is mainly regulated by insulin-induced changes in adipocyte metabolism 4, and the primary biological role of leptin appears to be adaptation to low energy intake rather than as a brake on overconsumption and obesity 4. It is expected that weight loss (>20% of body weight) will result in increased adiponectin expression and decreased leptin levels within 6–12 months 3. Indeed, diet-induced weight loss (approximately 20 kg in 24 months) in obese subjects resulted in a significant increase in adiponectin levels 3. In the study by Ryan et al., a 6-month behavioural dietary weight loss (6 kg) programme did not significantly change plasma adiponectin levels 2. Thus, we believe that a large weight loss is necessary to elicit an increase in adiponectin and a decrease in leptin levels. Also, behavioural dietary weight loss programmes should be maintained for a minimum of 12 months. The authors have no conflict of interest to declare.

A Statistical Perspective on Prevention Trials: A View from the Women’s Health Initiative

Chronic disease prevention trials test strategies to reduce the risk of a specific health event in generally healthy people. These strategies are often thought to affect other health conditions and their use in the population requires a very favorable safety profile. A prevention trial assessing such a strategy is most valuable when designed to capture the overall public health impact and hence provide more comprehensive, reliable information for policy and practice. This broad agenda, and particularly the assessment of multiple outcomes, creates statistical challenges in the design, monitoring, and reporting of such a trial. In this article these issues are described in the context of the Women’s Health Initiative, a large randomized prevention trial testing three interventions in post-menopausal women: hormone therapy, a low-fat diet and calcium and vitamin D supplementation. Each intervention was hypothesized to influence multiple chronic disease rates including cardiovascular disease, stroke, cancers, and fractures. Here the design, monitoring, and reporting of the WHI trials is reviewed in the context of multiple outcomes and the approach to a global assessment of these interventions is described.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Overweight/obese postmenopausal women (n=439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N=118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N=117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117), and (iv) control (N=87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45min of moderate-to-vigorous aerobic activity 5days per week. Adiponectin and leptin levels were measured at baseline and after 12months of intervention using a radioimmunoassay. Adiponectin increased by 9.5% in the diet group and 6.6% in the diet+exercise group (both P≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, -40.1%, P<0.0001; diet, -27.1%, P<0.0001; exercise, -12.7%, P=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend=0.0002; diet+exercise, P-trend=0.0005) and directly associated with leptin (diet, P-trend<0.0001; diet+exercise, P-trend<0.0001). Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.

Abstract A01: Independent and combined effects of dietary weight loss and aerobic exercise on leukocyte telomere length in overweight and obese postmenopausal women

Abstract The purpose of this study was to investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in overweight and obese postmenopausal women. Four hundred and thirty nine women (50-75 y) were randomized to one of four groups: i) dietary weight loss (N=118); ii) moderate-to-vigorous aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based reduced-calorie program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous intensity aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Telomere length was calculated as the ratio of telomeric DNA divided by a single-copy control gene. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. At baseline, leukocyte telomere length was not significantly correlated with body mass index (r=0.02, p=0.68) or % body fat (r=-0.003, p=0.95), but was inversely associated with age (r=-0.12 p&amp;lt;0.01) and positively associated with VO2max (r=0.11, p=0.03). Mean telomere length (SD) was not significantly different between overweight and obese women [1.045 (0.184) vs. 1.057 (0.201); p=0.63]. After 12 months, mean weight changes were -2.4% (p=0.03) in the exercise group, -8.5% (p&amp;lt;0.001) in the diet group, and -10.8% (p&amp;lt;0.001) in the diet + exercise group, compared to -0.8% among controls. No significant changes in leukocyte telomere length were detected in any of the intervention groups compared to controls, nor was the magnitude of weight loss associated with telomere length changes after 12 months. Over 12-months there was a net increase (mean T/S ratio: 0.124, range: 0.002-0.736) in telomere length among 48% (n=190) of women. The proportion of women who experienced a net 12-month increase was not significantly different between groups (χ2 p=0.90). Although telomere shortening represents a compelling link between genetics, accumulated lifestyle exposures and cancer, leukocyte telomere length is not significantly changed by 12 months of dietary weight loss and/or aerobic exercise intervention in postmenopausal women. Citation Format: Caitlin Mason, Rosa-Ana Risques, Liren Xiao, Catherine R. Duggan, Ikuyo Imayama, Kristin L. Campbell, Angela Kong, Karen E. Foster-Schubert, Ching-Yun Wang, Catherine M. Alfano, George L. Blackburn, Peter S. Rabinovitch, Anne McTiernan. Independent and combined effects of dietary weight loss and aerobic exercise on leukocyte telomere length in overweight and obese postmenopausal women. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A01.

Impact of a pharmacist-directed intervention in postmenopausal women after fracture

The impact of decentralized clinical pharmacy services on the implementation of appropriate care in postmenopausal women with a recent history of a fracture was assessed. Women 67 years of age or older with a documented fracture between January 1 and December 31, 2007, were identified in two geographic regions. At the intervention site, a decentralized clinical-pharmacy-based osteoporosis management service (CPOMS) intervened on postmenopausal women following fracture, while the comparison group utilized a centralized registered nurse to manage this population. In both groups, interventions included initiation of either osteoporosis medication or bone mineral density (BMD) screening. Of the 827 women in the CPOMS group, 65% (523) initiated a medication for osteoporosis or completed BMD screening within 6 months of the fracture, compared with 46% (139) of the 302 women in the comparison group (p < 0.001; cumulative incidence ratio [CIR], 1.75; 95% confidence interval [CI], 1.44-2.12). CPOMS patients were nearly twice as likely as comparison group patients to purchase osteoporotic medications (42% [347 of 827] versus 24% [73 of 302]; CIR, 1.89; 95% CI, 1.50-2.40) and equally likely to undergo BMD testing (35% [289 of 827] versus 31% [94 of 302]; CIR, 1.13; 95% CI, 0.91-1.39). Both interventions achieved results substantially higher than national averages. Of patients receiving a medication and continuous membership for 12 months, adherence was also significantly higher in the CPOMS group (46% [39 of 291] versus 28% [20 of 71], respectively; p = 0.007). An integrated pharmacist-run osteoporosis management service demonstrated a substantial increase in the rate of osteoporosis drug initiation among post-menopausal women who experienced a fracture compared with a centrally located nurse-run service. BMD screening rates did not significantly differ between groups.