Intervention In Postmenopausal Women Research Articles

Abstract B2: Effects of individual and combined diet and exercise intervention in postmenopausal women on adiponectin and leptin

Abstract Introduction: Obesity and sedentary lifestyles are modifiable risk factors for several chronic diseases. Adiponectin and leptin play central roles in energy balance, insulin homeostasis and lipid/glucose metabolism. We examined the individual and combined effects of dietary weight loss and/or exercise on serum adiponectin and leptin concentrations. Methods: We conducted a 12-month randomized controlled trial in 439 overweight/obese postmenopausal women to examine biomarkers of breast cancer risk. Participants were randomly assigned to dietary weight loss (D) (N=118), moderate-to-vigorous intensity aerobic exercise (E), 225 minutes/week (N=117), combined diet + exercise (D+E) (N=117), or control (N=87). Blood samples were taken at baseline and 12 months follow-up. Changes in adiponectin and leptin were measured via radioimmunoassay. Results: Adiponectin increased significantly over the intervention period in the D+E (+6.6%; p=.0001) and D group (+9.5%; p<.0001), compared to controls (−0.4%). No statistically significant adiponectin changes were observed in the E intervention. In all intervention groups leptin decreased significantly compared to controls (D+E −40.1% p<.0001; D −27.1% p<.0001; E −12.1% p=0.005). When stratified by baseline BMI, we observed slightly stronger increases in adiponectin among those with BMI ≥ 30kg/m2 in the D+E intervention. Changes in leptin with the intervention were equally strong independent of baseline BMI. With increasing weight loss, adiponectin increased independent of the intervention group (D, D+E or E). Conclusion: Our study showed that a dietary weight-loss intervention had strong effects on adiponectin levels, independent of exercise. We also observed that lifestyle interventions associated with weight loss, are successful in reducing serum leptin concentrations. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B2.

Lifestyle intervention in postmenopausal women

Departments of Medicine and Obstetrics and Gynecology, Divisions of Endocrinology, Diabetes and Metabolism, and Reproductive Endocrinology and Infertility, University of Alabama, Birmingham, Alabama Financial disclosure/conflicts of interest: None reported.

Evaluation of Intervention Research in Weight Reduction in Post Menopausal Women

To describe the evidence that has accrued for interventions targeting weight loss in postmenopausal women, and to assess the strengths and limitations of weight loss interventions in postmenopausal women using the framework of evaluation theory, including definition of the problem and the use of theoretical framework and mediators. Electronic databases were used, including CINAHL, EBSCO Host, Google scholar, Medline, and the Science Citation Index, Expanded, in the Web of Science from 1995 to December 2009. Keyword searches included the terms obesity, obese, overweight, menopause, and weight management interventions. Searches were combined to find reports addressing 1 or more keywords. Experimental design studies that examined physical activity or dietary intervention effects on weight loss or body composition changes in postmenopausal women were selected for review. Reports of 15 intervention studies met inclusion criteria from the list of 120 generated through the database searches. Each article was evaluated for 1) effects produced as a result of the intervention, 2) the characteristics of the problem of postmenopausal obesity, 3) specification of theoretical constructs and critical inputs that guide the design of an intervention, and 4) link of the theoretical predictors and the outcome measures selected. Four types of interventions were tested in the 15 research reports. Only 5 of the 15 used theories or models to guide the interventions. All of the interventions resulted in some positive weight management outcome, such as lowered body mass index, fat mass, waist circumference, systolic blood pressure, glucose, and cholesterol. Overall, the reviewed research showed efficacy of varying intensities of exercise when combined with hypocaloric diet or meal replacement therapy in producing low body weight, low fat, improved insulin sensitivity, glycemic control, and cardio-respiratory fitness. The external validity of the 15 studies was limited in reporting of a clear delineation of the problem, theoretical frameworks, and application of the findings.

Maintaining Functionality in Later Years: A Review of Nutrition and Physical Activity Interventions in Postmenopausal Women

Independence and quality of life of postmenopausal women are influenced by functional status. Nutrition and physical activity impact functional changes through changes in body composition. The article presents a narrative review of the literature to identify interventions that improve the functionality of community-dwelling postmenopausal women. The authors used the Evidence Analysis Approach developed by the American Dietetic Association to appraise current research. Strong evidence does exist that interventions that incorporate both physical activity and nutrition can improve physical function of older women. However, research focusing on functional status and quality of life, in addition to nutrition and exercise, is extremely limited.

Good maintenance of physical benefits in a 12-month exercise and nutritional intervention by voluntary, home-based exercise: a 6-month follow-up of a randomized controlled trial

We assessed the maintenance of physical benefits in a 12-month exercise and nutritional intervention in postmenopausal women (55-75 years of age) after 6-month postintervention follow-up by voluntary, home-based exercise, and examined whether physical factors responded differently to high or low exercise frequency during the 6-month postintervention period. Forty-five women completed the 12-month intervention program, followed by 6-month cessation of intervention, and were compared with 19 matched controls. Twenty-one of the former exercisers reported that they continued exercise training at least 30 min at least 3 days/week (high-frequency exerciser, HFE), while the remaining 24 former exercisers reported that they had done exercise training at least 30 min twice per week or less during the postintervention follow-up (low-frequency exerciser, LFE). The following items were measured at baseline, 12, and 18 months: bone strength, CS-30 test, 10-m obstacle walk, whole-body reaction time, one-leg stance, and grip strength. After 6-month postintervention follow-up, the beneficial effect on bone was not fully maintained. These benefits in physical performance obtained in the 12-month intervention program, except one-leg stance, were fully maintained for 6 months by voluntary, home-based exercise. The gained benefit in one-leg stance was not fully maintained; LFE showed a significant decrease over the 6-month postintervention follow-up period, suggesting that continued exercise training of at least 30 min at least 3 days/week is required to maintain the balance benefit. These findings suggest that a continued exercise program of voluntary, home-based exercise may be effective to maintain the physical benefits of exercise intervention that may lower fracture risk in later life.

Rapid Estrogen Receptor-α Activation Improves Ischemic Tolerance in Aged Female Rats through a Novel Protein Kinase Cε-Dependent Mechanism

The effects of estrogen deficiency on the loss of cardioprotection with advancing age are complex and poorly understood. A major focus of the current study was to uncover a cardioprotective role for rapid, nongenomic estrogen receptor (ER) signaling in the aged female myocardium. We hypothesized that selective ERalpha activation in aged females would reduce infarct size in part, through reversal of age-associated reductions in mitochondrial protein kinase Cepsilon (PKCepsilon). Hearts isolated from adult (6 month old) and aged (23-24 months old) female F344 rats with ovaries removed (n = 20 per group) were subjected to ischemia/reperfusion (47 min global ischemia). Rats were injected sc with the ERalpha agonist propylpyrazole triol (PPT) or vehicle 45 min before heart isolation (5 microg/kg). Infarct size was greatest in aged vs. adult ovariectomized rats, significantly reduced by PPT, and the protection reversed by prior administration of the ER inhibitor ICI 182,780 (3 mg/kg). Increased ERalpha particulate targeting occurred after PPT in conjunction with reversal of age-related reductions in nuclear PKCepsilon, mitochondrial PKCepsilon and pAkt (P < 0.05). PPT also increased mRNA levels for the PKCepsilon anchoring protein, receptor for activated C kinase2 (RACK2; P < 0.05). Our data suggest, for the first time, that selective ERalpha activation reduces ischemic injury in the aged, estrogen-deficient heart through a mechanism involving nongenomic redistribution of ERalpha and PKCepsilon activation. A novel feed-forward transcriptional mechanism to potentially enhance PKCepsilon-RACK2 interactions was also observed. Collectively, our findings may provide key insight into developing targeted therapeutic interventions in postmenopausal women to reduce ischemia/reperfusion injury, including selective ERalpha mimetics.

Evaluation of 41Calcium as a New Approach to Assess Changes in Bone Metabolism: Effect of a Bisphosphonate Intervention in Postmenopausal Women With Low Bone Mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

Changes in diet quality score, macro‐ and micronutrients intake following a nutrition education intervention in postmenopausal women

The aim of the current study was to assess the effectiveness of a nutrition education programme on post-menopausal women using self-reported nutrient intake data as well as a qualitative data obtained by the Healthy Eating Index (HEI). Seventy-five women (55-65 years old) were randomized to a dietary intervention group (IG: n=39), attending regular nutrition education sessions for 5 months and to a control group (CG: n=36). The intervention scheme was based on a combined application of the Health Belief Model and the Social Cognitive Theory, aiming to increase nutritional knowledge and self-efficacy of the subjects to adopt and maintain healthy dietary choices. Changes in self-reported macro- and micronutrients' intake as well as in the HEI total score and in its ten components were obtained. The IG subjects reported increasing their milk (P<0.001) and total fat (P=0.01) HEI scores, decreasing total fat intake (P=0.050) and increasing calcium and vitamin D intakes (P<0.001 respectively) to a higher extent compared with the changes reported by the CG. The current nutrition education programme appears to have induced favourable changes for the IG in micronutrients' intake primarily related to bone health and in total fat intake. These changes were reflected in the individual HEI indices but not in total HEI score.

Soy isoflavones modulate immune function in healthy postmenopausal women

The immune system may be compromised after menopause because of the effects of aging and diminishing concentrations of estrogen, an immune-modulating hormone. Isoflavones, plant-derived compounds with estrogenic and antioxidant properties, may offer immunologic benefits to women during this stage of life. The objective of this study was to evaluate the effects of soy isoflavones, both in soymilk and in supplement form, on markers of immunity and oxidative stress in postmenopausal women. Postmenopausal women aged 50-65 y (n = 52) enrolled in this 16-wk double-blind, placebo-controlled trial were randomly assigned to 1 of 3 experimental groups: 1) control, 706 mL cow milk/d plus a placebo supplement; 2) soymilk, 71.6 mg isoflavones derived from 706 mL soymilk/d plus a placebo supplement; and 3) supplement, 70 mg isoflavones in a supplement plus 706 mL cow milk/d. Plasma and 24-h urine samples were obtained at baseline and at 16 wk. Immune variables included lymphocyte subsets, cytokine production, and markers of inflammation and oxidative damage. Isoflavone intervention in postmenopausal women resulted in higher (P < 0.05) B cell populations and lower (P < 0.05) plasma concentrations of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage. Isoflavone treatment did not significantly influence concentrations of interferon gamma, interleukin 2, tumor necrosis factor alpha, or C-reactive protein in plasma or of 8-isoprostane in urine. Soymilk and supplemental isoflavones modulate B cell populations and appear to be protective against DNA damage in postmenopausal women.

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

WOMEN'S HEALTH INITIATIVE UPDATE: Health-Related Quality of Life

The Women's Health Initiative (WHI) is an NIH-sponsored, multicenter effort to evaluate therapeutic interventions in postmenopausal women. The arm of the trial that randomly assigned 16,608 women to receive either placebo or conjugated estrogens (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) was halted in 2002 because hormone recipients showed increased risks for breast cancer, stroke, and heart disease (Journal Watch Women's Health Aug 7 2002). Many publications now are in press reporting outcomes of this arm of the study. JWWH will …

Automated Current Health Time-Trade-Off Assessments in Women's Health

Objective To motivate the role for preference assessment in women's health and to report pilot data addressing the performance of automated time-trade-off (TTO) valuations of current health, which were developed to estimate quality-adjusted life years (QALYs) in the women's health setting. Methods Values for current health relative to perfect health and death were assessed using an annual time trade-off (1-year horizon and sleep as the trading metaphor), a lifetime time trade-off, and a visual analog scale (VAS). All instruments were administered twice within a 12- to 14-day window among a convenience sample of 27 women. Results Valuation of health was similar for both time trade-offs (mean of 0.95 for both), but was significantly lower for the VAS (mean of 0.84, Wilcoxon signed-rank p-value < 0.001). Reliability using the intraclass correlation coefficient was 0.67 ± 0.09 and 0.75 ± 0.07 for the annual and lifetime time trade-offs, respectively, and 0.89 ± 0.03 for the VAS. Construct validity was supported by consistent trends in time-trade-off utilities across tertiles of the Short Form 36 (SF-36) general health subscale (trend test p-value < 0.001). Conclusion Automated time trade-offs for current health provide a promising approach for use in women's health studies where impact on QALYs must be measured. Natural areas of application include the economic evaluation of preventive interventions in postmenopausal women.

News and Notes

By using the meta-analytic approach, the purpose of this study was to examine the effects of exercise on regional bone mineral density in postmenopausal women. A total of 11 randomized trials yielding 40 outcome measures and a total of 719 subjects (370 exercise, 349 nonexercise) met the criteria for inclusion: (1) randomized trials; (2) exercise as a primary intervention in postmenopausal women; (3) changes in regional bone mineral density reported; (4) comparative nonexercise group included; (5) studies published in English-language journals between January 1975 and December 1995. Across all designs and categories, treatment effect changes in bone density, weighted by sample size, ranged from -17.10 to 17.30% (mean, 0.27%; 95% confidence interval, 0.16-0.37%). When analyzed separately, sample weighted decreases of approximately -0.51 and -0.86% were found for exercise and nonexercise groups, respectively. Larger effects were observed when groups that did not measure bone density specific to the site loaded and groups that received some type of supplementation (calcium or hormone replacement therapy) were deleted from the model (mean change, 0.76%; 95% confidence interval, 0.6-0.93). Both aerobic and strength training enhanced regional bone mineral density (mean change: aerobic, 1.62% and 95% confidence interval, 1.12-2.12; strength, 0.65% and 95% confidence interval, 0.48-0.83). In conclusion, meta-analytic review of included studies suggests that exercise may slow the rate of bone loss in postmenopausal women. However, it is premature to form strong conclusions regarding the effects of exercise on regional bone mineral density in postmenopausal women. A need exists for additional, well designed studies on this topic before a recommendation can be made regarding the efficacy of exercise as a nonpharmacologic therapy for maintaining and/or increasing regional bone mineral density in postmenopausal women.

Postmenopausal Hormone Replacement Therapy and Cardiovascular Disease

Cardiovascular disease is the leading cause of mortality in postmenopausal women in developed countries. A possible cardioprotective role of hormone replacement therapy (HRT) is suggested by epidemiologic studies of HRT and reduced risk of coronary heart disease, as well as by randomized trials of HRT and lipid subfractions. Estrogen has beneficial effects on the lipid profile, raising high-density lipoprotein cholesterol levels and reducing low-density lipoprotein cholesterol levels each by approximately 10%. Other possible biologic mechanisms include beneficial effects on vascular function, oxidative status, endothelial-dependent vasodilation, intimal hyperplasia and insulin sensitivity. Estrogen's net effects on coagulation and fibrinolysis are less clear. Estrogen replacement therapy is associated with decreased atherosclerosis in several animal models. However, most of the available data on HRT derive from observational studies or small randomized trials assessing biologic intermediates rather than clinical events. Further research, including large-scale randomized clinical trials, are required to evaluate definitively the role of estrogen replacement therapy, especially given uncertainties about the effects of combined estrogen-progestin therapy and the balance of benefits and risk of this common intervention in postmenopausal women.

Therapy of Osteoporosis: Calcium, Vitamin D, and Exercise

<h2>ABSTRACT:</h2> Calcium supplementation has long been regarded as a fundamental part of the prevention and treatment of postmenopausal osteoporosis, but it is only in recent years that clear evidence has emerged demonstrating its impact on bone mass. Calcium supplementation does not completely arrest postmenopausal bone loss but slows the rate of decline by 30 to 50%. The effect of calcium supplementation on fracture incidence in post-menopausal women has not been established. Vitamin D deficiency is common in the frail elderly, particularly in countries where fortification or food with this vitamin is not practiced. Treatment of vitamin D deficiency has been associated with significant reductions in the number of hip fractures. The role of the potent vitamin D metabolites, calcitriol and alphacalcidol, in the management of postmenopausal osteoporosis is not clear. Although some studies show substantial benefits in bone density or fracture rate from the use of these compounds, the published data are inconsistent. In general, hormone replacement therapy and the potent bisphosphonates produce greater effects on bone density and there is a greater consistency among the results of the published studies of these other interventions. Controlled trials of exercise interventions in postmenopausal women show that exercise can positively influence bone density by a few percent. Exercise interventions in the elderly have been reported to decrease fall frequency by 10%. This latter effect may have a greater impact on fracture frequency than the modest benefits of exercise on bone density.

Therapy of osteoporosis: calcium, vitamin D, and exercise.

Calcium supplementation has long been regarded as a fundamental part of the prevention and treatment of postmenopausal osteoporosis, but it is only in recent years that clear evidence has emerged demonstrating its impact on bone mass. Calcium supplementation does not completely arrest postmenopausal bone loss but slows the rate of decline by 30 to 50%. The effect of calcium supplementation on fracture incidence in postmenopausal women has not been established. Vitamin D deficiency is common in the frail elderly, particularly in countries where fortification or food with this vitamin is not practiced. Treatment of vitamin D deficiency has been associated with significant reductions in the number of hip fractures. The role of the potent vitamin D metabolites, calcitriol and alphacalcidol, in the management of postmenopausal osteoporosis is not clear. Although some studies show substantial benefits in bone density or fracture rate from the use of these compounds, the published data are inconsistent. In general, hormone replacement therapy and the potent bisphosphonates produce greater effects on bone density and there is a greater consistency among the results of the published studies of these other interventions. Controlled trials of exercise interventions in postmenopausal women show that exercise can positively influence bone density by a few percent. Exercise interventions in the elderly have been reported to decrease fall frequency by 10%. This latter effect may have a greater impact on fracture frequency than the modest benefits of exercise on bone-density.