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Is Cardiac Diastolic Dysfunction a Part of Post-Menopausal Syndrome?
Maslov, PZ, Kim, JK, Argulian, E, Ahmadi, A, Narula, N, Singh, M, Bax, J, Narula, J
JACC. Heart failure. 2019;(3):192-203
Abstract
Post-menopausal women exhibit an exponential increase in the incidence of heart failure with preserved ejection fraction compared with men of the same age, which indicates a potential role of hormonal changes in subclinical and clinical diastolic dysfunction. This paper reviews the preclinical evidence that demonstrates the involvement of estrogen in many regulatory molecular pathways of cardiac diastolic function and the clinical data that investigates the effect of estrogen on diastolic function in post-menopausal women. Published reports show that estrogen deficiency influences both early diastolic relaxation via calcium homeostasis and the late diastolic compliance associated with cardiac hypertrophy and fibrosis. Because of the high risk of diastolic dysfunction and heart failure with preserved ejection fraction in post-menopausal women and the positive effects of estrogen on preserving cardiac function, further clinical studies are needed to clarify the role of endogenous estrogen or hormone replacement in mitigating the onset and progression of heart failure with preserved ejection fraction in women.
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Lipid profile differences during menopause: a review with meta-analysis.
Ambikairajah, A, Walsh, E, Cherbuin, N
Menopause (New York, N.Y.). 2019;(11):1327-1333
Abstract
OBJECTIVES The aim of the study was to determine lipid profile differences between premenopausal and postmenopausal women. METHODS The present review used a meta-analytic approach. Sixty-six studies were included, which provided a total sample of 114,655 women consisting of 68,394 that were premenopausal and 46,261 that were postmenopausal. RESULTS The main findings were that (1) lipoproteins were significantly higher in postmenopausal women compared to premenopausal women including triglycerides (0.27 mmol/L, 95% confidence interval, 0.22-0.31), total cholesterol (0.58, 0.50-0.65), low-density lipoprotein (0.45, 0.38-0.53), and total cholesterol to high-density lipoprotein levels (0.39, 0.16-0.62); (2) there was no difference in high-density lipoprotein levels between premenopausal and postmenopausal women (0.02, -0.00-0.04); and (3) the differences in lipid levels was partly attributable to the mean age difference between premenopausal and postmenopausal women. CONCLUSIONS These findings are important as they provide precise estimates of lipid differences in women around menopause. Furthermore the results suggest that the unfavorable lipid profile that develops in postmenopausal women puts them at higher risk of cardiovascular disease such as heart disease and stroke if appropriate lifestyle/pharmacological interventions are not implemented.
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Impact of meal fatty acid composition on postprandial lipaemia, vascular function and blood pressure in postmenopausal women.
Rathnayake, KM, Weech, M, Jackson, KG, Lovegrove, JA
Nutrition research reviews. 2018;(2):193-203
Abstract
CVD are the leading cause of death in women globally, with ageing associated with progressive endothelial dysfunction and increased CVD risk. Natural menopause is characterised by raised non-fasting TAG concentrations and impairment of vascular function compared with premenopausal women. However, the mechanisms underlying the increased CVD risk after women have transitioned through the menopause are unclear. Dietary fat is an important modifiable risk factor relating to both postprandial lipaemia and vascular reactivity. Meals rich in SFA and MUFA are often associated with greater postprandial TAG responses compared with those containing n-6 PUFA, but studies comparing their effects on vascular function during the postprandial phase are limited, particularly in postmenopausal women. The present review aimed to evaluate the acute effects of test meals rich in SFA, MUFA and n-6 PUFA on postprandial lipaemia, vascular reactivity and other CVD risk factors in postmenopausal women. The systematic search of the literature identified 778 publications. The impact of fat-rich meals on postprandial lipaemia was reported in seven relevant studies, of which meal fat composition was compared in one study described in three papers. An additional study determined the impact of a high-fat meal on vascular reactivity. Although moderately consistent evidence suggests detrimental effects of high-fat meals on postprandial lipaemia in postmenopausal (than premenopausal) women, there is insufficient evidence to establish the impact of meals of differing fat composition. Furthermore, there is no robust evidence to conclude the effect of meal fatty acids on vascular function or blood pressure. In conclusion, there is an urgent requirement for suitably powered robust randomised controlled trials to investigate the impact of meal fat composition on postprandial novel and established CVD risk markers in postmenopausal women, an understudied population at increased cardiometabolic risk.
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Isoflavones and bone health in perimenopausal and postmenopausal women.
Lambert, MNT, Jeppesen, PB
Current opinion in clinical nutrition and metabolic care. 2018;(6):475-480
Abstract
PURPOSE OF REVIEW Isoflavones exert estrogenic activity distinct from estrogen, they have the potential to treat diseases and symptoms related to estrogen deficiency with minimal side effects and risks. Isoflavone supplementation, in general, is shown to exert beneficial effects against estrogen-deficient bone loss in women, however, some clinical trials still produce conflicting findings. The purpose of this review is to highlight and summarize the most recent and up-to-date research in the field and to bring attention to factors that play a major role in the outcomes of clinical trials that investigate phytoestrogens. Here, we also discuss the latest and most relevant data regarding the clinical safety of these substances. RECENT FINDINGS Isoflavones are naturally occurring secondary metabolites found in the Fabacaea plant family. Clinical data from isoflavone interventions support that aglycones (abundant in fermented products) exert enhanced beneficial effects against estrogen-deficient bone loss in women compared with isoflavone glycosides. Studies that employ methods to determine isoflavone content and form of treatments are more likely detect beneficial effects on bone. EFSA have confirmed the safety of isoflavones for women in the most comprehensive report to date. SUMMARY Isoflavone aglycones exert greater effects against bone loss than glycosides. Isoflavones show promise as a first-line prophylactic/treatment for bone loss in women.
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Effect of programmed exercise on insulin sensitivity in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
Bueno-Notivol, J, Calvo-Latorre, J, Alonso-Ventura, V, Pasupuleti, V, Hernandez, AV, Pérez-López, FR, ,
Menopause (New York, N.Y.). 2017;(12):1404-1413
Abstract
OBJECTIVE We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of programmed exercise for at least 12 weeks, in postmenopausal women on insulin sensitivity-related outcomes (ISROs), including fasting insulin, C-peptide, insulin growth factor (IGF-1) and IGF-binding protein (IGFBP-3), Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), and anthropometric variables. METHODS Searches were conducted in PubMed-Medline, Embase, Scopus, Web of Science, and Cochrane Library from inception through May 3, 2016, for studies published in all languages. Extracted data included characteristics of the study design, study participants, intervention, and outcome measures. Types of exercise were classified into "mid-term exercise intervention" (MTEI, 3-4 months exercise duration) and a "long-term exercise intervention" (LTEI, 6-12 months exercise duration). Risk of bias in RCTs was evaluated with the Cochrane tool. We used random-effects models for meta-analyses. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Seven RCTS (n = 580) evaluating the effects of programmed exercise on ISROs were included. In three RCTs, MTEI significantly lowered insulin levels (mean difference [MD] -6.50 pmol/L, 95% confidence interval [CI] -11.19, -1.82, P = 0.006) and HOMA-IR values (MD -0.18, 95% CI -0.34, -0.03, P = 0.02) when compared with controls. LTEI had no significant effect on insulin levels (P = 0.19) or HOMA-IR values (P = 0.68) in four and three RCTs, respectively. There were no significant differences between exercise intervention versus controls in circulating IGF-1, glucose, triglycerides with both MTEI and LTEI, and in IGFBP-3 with LTEI. There were significant reductions in body mass index (BMI, kg/m) (MD -1.48, 95% CI -2.48, -0.48, P = 0.004) and in body fat percentage (MD -2.99, 95% CI -4.85, -1.14, P = 0.01) after MTEI; and in waist circumference after both MTEI (MD -1.87, 95% CI -3.02, -0.72, P = 0.001) and LTEI (MD -3.74, 95% CI -6.68, -0.79). Heterogeneity of effects among studies was moderate to low. CONCLUSION Exercising for 3 to 4 months significantly lowered insulin levels and HOMA-IR values, BMI waist circumference, and percentage body fat mass; exercising for 6 to 12 months lowered waist circumference in postmenopausal women.
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6.
The potential contribution of dietary factors to breast cancer prevention.
Shapira, N
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP). 2017;(5):385-395
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Abstract
Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early/timely prevention, optimally merging with other dietary/health goals, for lifelong BC prevention.
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Effect of soybean protein on blood pressure in postmenopausal women: a meta-analysis of randomized controlled trials.
Kou, T, Wang, Q, Cai, J, Song, J, Du, B, Zhao, K, Ma, Y, Geng, B, Zhang, Y, Han, X, et al
Food & function. 2017;(8):2663-2671
Abstract
The effect of soybean protein on blood pressure (BP) in postmenopausal women is controversial, so we aimed to conduct a systematic review and a meta-analysis of published randomized controlled trials (RCTs) to investigate whether supplementation with soy protein improves their blood pressure. PubMed and Embase were searched up to February 2016. Weighted mean differences were calculated for net changes in BP by using fixed-effect or random-effect models. Subgroup and meta-regression analyses were performed to clarify heterogeneity among the trials. A total of twelve trials (1551 postmenopausal women participants) were included in the present meta-analysis. The overall pooled estimates of the effect of soy protein indicated a significant effect on systolic blood pressure (SBP) (mean difference: -3.03 mmHg; 95% CI: -5.03, -1.02; P = 0.003) and diastolic blood pressure (DBP) (mean difference: -0.71 mmHg; 95% CI: -1.26, -0.16; P = 0.012). Subgroup analyses further demonstrated that soy protein intake ≥25 g d-1 significantly reduced BP, and the mean difference in SBP and DBP was -4.62 mmHg (95% CI: -8.42, -0.81; P = 0.04) and -1.63 mmHg (95% CI: -2.85, -0.41; P = 0.009), respectively. Soy isoflavone intake ≥100 mg d-1 had a better reduction effect both in SBP (-5.47 mmHg; 95% CI: -8.42, -2.51; P = 0.00) and DBP (-2.03 mmHg; 95% CI: -3.35, -0.72; P = 0.002). However, soy protein intake <25 g d-1 or soy isoflavone intake <100 mg d-1 had no such effects (P > 0.05). This meta-analysis suggests that ingestion of ≥25 g soy protein per day has BP-lowering effects, and the improvements in BP may be due to the isoflavones component of soy protein. More high-quality RCTs need to be carried out to confirm the present findings.
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Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.
Anagnostis, P, Karras, S, Lambrinoudaki, I, Stevenson, JC, Goulis, DG
International journal of clinical practice. 2016;(12):967-977
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Abstract
INTRODUCTION Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). RESULTS Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. CONCLUSIONS Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.
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Dietary exposure to cadmium and risk of breast cancer in postmenopausal women: A systematic review and meta-analysis.
Van Maele-Fabry, G, Lombaert, N, Lison, D
Environment international. 2016;:1-13
Abstract
BACKGROUND With tobacco smoking, diet is the main source of cadmium (Cd) exposure in the general population. The carcinogenic and estrogenic activities of Cd make it a contaminant of potential concern for hormone-dependent cancers including breast cancer. Postmenopausal women represent the most appropriate population to investigate the possible impact of exogenous factors with potential estrogenic activity on breast cancer as, after menopause, their estrogenic influence is predominant. OBJECTIVES We systematically reviewed available studies on the association between dietary exposure to Cd and breast cancer focusing on postmenopausal women. A meta-analysis combining the risk estimators was performed and potential sources of between studies heterogeneity were traced. METHODS Studies were searched from MEDLINE through 31 January 2015 and from the reference lists of relevant publications. Six eligible studies published between 2012 and 2014 were identified and relative risk estimates were extracted. Meta-rate ratio estimates (mRR) were calculated according to fixed and random-effect models. Meta-analyses were performed on the whole set of data and separate analyses were conducted after stratification for study design, geographic location, use of hormone replacement therapy (HRT), tumor estrogen receptor status (ER+ or ER-), progesterone receptor status (PGR+ or PGR-), body mass index (BMI), smoker status, zinc or iron intake. RESULTS No statistically significant increased risk of breast cancer was observed when all studies were combined (mRR=1.03; 95% confidence interval [CI]: 0.89-1.19). Several sources of heterogeneity and inconsistency were identified, including smoker status, HRT use, BMI, zinc and iron intake. Inconsistency was also strongly reduced when only considering ER-, PGR-, tumors subgroups from USA and from Japan. The risks were, however, not substantially modified after stratifications. No evidence of publication bias was found. CONCLUSION The present study does not provide support for the hypothesis that dietary exposure to Cd increases the risk of breast cancer in postmenopausal women. Misclassification in dietary Cd assessment in primary studies could have biased the results towards a finding of no association.
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Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta-analysis of randomized controlled trials.
Fang, K, Dong, H, Wang, D, Gong, J, Huang, W, Lu, F
Molecular nutrition & food research. 2016;(7):1602-14
Abstract
SCOPE The aim of this meta-analysis was to investigate whether soy isoflavones, a type of phytoestrogen, would affect glucose homeostasis in menopausal women. METHODS AND RESULTS Studies concerning about the relationship between soy isoflavone treatment and glucose metabolism were searched on MEDLINE and WEB OF SCIENCE (updated through April 2015) and EMBASE (1990-April 2015). Seventeen randomized controlled trials (RCTs) with a total number of 1529 menopausal women were identified for meta-analysis. Soy isoflavones were found to show great significance for the improvement of glucose metabolism, though marked heterogeneity was found between studies. The overall results showed that the average difference in fasting blood glucose values between women assigned to soy isoflavones and women in placebo groups was -0.22 mmol/L (95% CI: -0.38 to -0.07 mmol/L) under a random-effects model. In addition, the effect of soy isoflavones on insulin was also significant: -0.43 μIU/mL (95% CI: -0.71 to -0.14 μIU/mL), as was the effect on homeostasis model assessment insulin resistance (HOMA-IR): -0.52 (95% CI: -0.76 to -0.28). CONCLUSION Although the results displayed a significant tendency in favor of soy isoflavones, it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity.