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The Diverse Efficacy of Food-Derived Proanthocyanidins for Middle-Aged and Elderly Women.
Izumi, T, Terauchi, M
Nutrients. 2020;(12)
Abstract
Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy.
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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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3.
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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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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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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The role of ovarian sex steroids in metabolic homeostasis, obesity, and postmenopausal breast cancer: molecular mechanisms and therapeutic implications.
Boonyaratanakornkit, V, Pateetin, P
BioMed research international. 2015;:140196
Abstract
Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.
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The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials.
Lewis, JR, Radavelli-Bagatini, S, Rejnmark, L, Chen, JS, Simpson, JM, Lappe, JM, Mosekilde, L, Prentice, RL, Prince, RL
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2015;(1):165-75
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Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta-analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta-analyses. We, therefore, undertook a meta-analysis of randomized controlled trials with placebo or no-treatment control groups to determine if these supplements increase all-cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random-effects meta-analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96-1.09; p = 0.51). Seventeen trials contributed all-cause mortality data with pooled RR of 0.96 (95% CI, 0.91-1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I(2) = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92-1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95-1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73-1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all-cause mortality risk in elderly women.
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Phytoestrogens in postmenopause: the state of the art from a chemical, pharmacological and regulatory perspective.
Poluzzi, E, Piccinni, C, Raschi, E, Rampa, A, Recanatini, M, De Ponti, F
Current medicinal chemistry. 2014;(4):417-36
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Abstract
Phytoestrogens represent a diverse group of non-steroidal natural products, which seem to have some oestrogenic effects and are often marketed as food supplements. Population exposed to phytoestrogens is potentially increasing, in part because an unfavourable risk-benefit profile of Hormone Replacement Therapy (HRT) for prolonged treatments (e.g., osteoporosis prevention) highlighted by the publication of the Women Health Initiative (WHI) trial in 2002, but also because many post-menopausal women often perceived phytoestrogens in food supplements as a safer alternative than HRT. Despite of increasing preclinical and clinical studies in the past decade, appealing evidence is still lacking to support the overall positive risk-benefit profile of phytoestrogens. Their status as food supplements seems to discourage studies to obtain new evidence, and the chance to buy them by user's initiative make it difficult to survey their prevalence and pattern of use. The aim of the present review is to: (a) outline the clinical scenario underlying the increased interest on phytoestrogens, by overviewing the evolution of the evidence on HRT and its main therapeutic goals (e.g., menopausal symptoms relief, chemoprevention, osteoporosis prevention); (b) address the chemical and pharmacological features (e.g. chemical structure, botanical sources, mechanism of action) of the main compounds (e.g., isoflavones, lignans, coumestans); (c) describe the clinical evidence on potential therapeutic applications; (d) put available evidence on their riskbenefit profile in a regulatory perspective, in light of the recent regulation on health claims of food supplements.
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Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.
Bauer, SR, Hankinson, SE, Bertone-Johnson, ER, Ding, EL
Medicine. 2013;(3):123-131
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Previous evidence suggests that higher circulating 25-hydroxyvitamin D (25[OH]D) levels are variably associated with lower breast cancer risk; however, prospective studies and clinical trials have been inconsistent, particularly between older and younger women of differing menopausal status. We conducted a quantitative nonlinear dose-response meta-analysis of prospective studies evaluating the association between circulating 25(OH)D and breast cancer risk, stratified by menopause. A systematic search of MEDLINE and EMBASE included studies published through May 2011. We reviewed references from retrieved articles and contacted relevant investigators for additional data from prospective studies on circulating 25(OH)D levels and incident breast cancers. Prospective studies of circulating vitamin D and breast cancer risk were reviewed, and no language restrictions were imposed. Information on study population, menopausal status, 25(OH)D levels, and relative risk (RR) estimates were extracted using a standardized protocol.A total of 9 prospective studies were included, comprising 5206 cases and 6450 controls. Data were pooled using dose-response random-effects meta-regression models. Identifying nonlinear effects, spline models were optimized for thresholds. The relationship between circulating 25(OH)D and breast cancer risk differed by menopausal status (p = 0.05 for effect modification). While no association was found in premenopausal women, dose-response modeling revealed a nonlinear inverse association among postmenopausal women. Notably, a flat association was observed in the lowest range of 25(OH)D levels <27 ng/mL (RR = 1.01 per 5 ng/mL; 95% confidence interval [CI], 0.98-1.04). In contrast, postmenopausal breast cancer risk decreased with 25(OH)D levels 27-<35 ng/mL (p = 0.02 for nonlinear risk change), where a 5 ng/mL increase in 25(OH)D was associated with a 12% lower risk of breast cancer (RR = 0.88 per 5 ng/mL; 95% CI, 0.79-0.97), with suggestive flattening at higher doses >35 ng/mL. The significant inverse association did not appear to vary across strata of invasive/in-situ cases, body mass index adjustment, region, postmenopausal hormone use, or assay method.In summary, this dose-response meta-analysis of prospective studies of plasma 25(OH)D suggested a breast cancer risk differential by menopause, whereby a step-wise inverse association was observed beyond a threshold of 27 ng/mL, but with flattening of effects above 35 ng/mL, in postmenopausal women. These findings help resolve prior inconsistent findings and may carry important clinical and public health implications.
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The role of vitamin D in blood pressure, endothelial and renal function in postmenopausal women.
Liu, ZM, Woo, J, Wu, SH, Ho, SC
Nutrients. 2013;(7):2590-610
Abstract
BACKGROUND Vitamin D is a pro-hormone that plays an essential role in the vasculature and in kidney function. AIMS To review the extra-skeletal effects of vitamin D on blood pressure, endothelial and renal function with emphasis on recent findings in postmenopausal women. METHODS Included in this review was a PubMed database search for English language articles through March 2013. This review discussed the physiology and definition of vitamin D deficiency, the recent evidence for the role vitamin D in blood pressure, vascular and renal function. RESULTS Experimental and epidemiological data suggest that vitamin D plays an important role in the vasculature and in kidney function. Low vitamin D concentrations appear to significantly associate with hypertension, endothelial and renal dysfunction. However, the results of clinical trials have generally been mixed. Studies specifically conducted among postmenopausal women are limited and findings are still inconsistent. CONCLUSIONS Definitive studies are warranted to elucidate the effects of vitamin D supplementation on vascular and renal function and a more detailed work is needed to outline the route, duration and optimal dose of supplementation. It is premature to recommend vitamin D as a therapeutic option in the improvement of vascular and renal function at the current stage.