Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women
ABSTRACT To quantify the effects of hormone-replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women.
Comprehensive searches of electronic databases were performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non-diabetic women.
Pooled results of 107 trials showed that HRT reduced abdominal fat [-6.8% (CI, -11.8 to -1.9%)], HOMA-IR [-12.9% (CI, -17.1 to -8.6%)] and new-onset diabetes [relative risk 0.7 (CI, 0.6-0.9)] in women without diabetes. In women with diabetes, HRT reduced fasting glucose [-11.5% (CI, -18.0 to -5.1%)] and HOMA-IR [-35.8% (CI, -51.7 to -19.8%)]. HRT also reduced low-density lipoprotein/high-density lipoprotein cholesterol ratio [-15.7% (CI, -18.0 to -13.5%)], lipoprotein(a) [Lp(a)] [-25.0% [CI, -32.9 to -17.1%)], mean blood pressure [-1.7% (CI, -2.9 to -0.5%)], E-selectin [-17.3% (CI, -22.4 to -12.1%)], fibrinogen [-5.5% (CI, -7.8 to -3.2%)] and plasminogen activator inhibitor-1 [-25.1% (CI, -33.6 to -15.5%)]. Oral agents produced larger beneficial effects than transdermal agents, but increased C-reactive protein (CRP) [37.6% (CI, 17.4-61.3%)] and decreased protein S [-8.6% CI, -13.1 to -4.1%)], while transdermal agents had no effect.
HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.
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ABSTRACT: There is strong evidence that breast cancer risk is influenced by environmental factors. Blood lipid and lipoprotein levels are also influenced by environmental factors and are associated with some breast cancer risk factors. We examined whether serial measures of serum lipids and lipoproteins were associated with breast cancer risk. We carried out a nested case-control study within a randomized long-term dietary intervention trial with 4690 women with extensive mammographic density followed for an average of 10 years for breast cancer incidence. We measured lipids in an average of 4.2 blood samples for 279 invasive breast cancer case subjects and 558 matched control subjects. We calculated subaverages of lipids for each subject based on menopausal status and use of hormone replacement therapy (HRT) at blood collection and analyzed their association with breast cancer using generalized estimating equations. All statistical tests were two-sided. High-density lipoprotein-cholesterol (HDL-C) (P = .05) and apoA1 (P = .02) levels were positively associated with breast cancer risk (75(th) vs 25(th) percentile: HDL-C, 23% higher; apoA1, 28% higher) and non-HDL-C (P = .03) and apoB (P = .01) levels were negatively associated (75(th) vs 25(th) percentile: non-HDL-C, 19% lower; apoB, 22% lower). These associations were observed only when lipids were measured when HRT was not used. Total cholesterol and triglyceride levels were not statistically significantly associated with breast cancer risk. These results demonstrate that serum lipids are associated with breast cancer risk in women with extensive mammographic density. The possibility that interventions for heart disease prevention, which aim to reduce non-HDL-C or raise HDL-C, may have effects on breast cancer risk merits examination. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.CancerSpectrum Knowledge Environment 05/2015; 107(5). DOI:10.1093/jnci/djv032 · 15.16 Impact Factor
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ABSTRACT: There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.Mediators of Inflammation 01/2014; 2014:615917. DOI:10.1155/2014/615917 · 2.42 Impact Factor
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ABSTRACT: Context: Hormone therapy (HT), the most efficient treatment for menopausal symptoms, might have deleterious cardiovascular (CV) effects. Objective: To evaluate the effects of low-dose estrogen HT on CV risk factors vs. conventional dose HT and placebo in postmenopausal women with no established CV disease. Data sources: MEDLINE, Cochrane Central, EMBASE were searched for trials published in 1990-2013; hand search of reference lists of selected articles; and ClinicalTrials.gov for unpublished trials. Study selection: Randomized controlled trials of healthy postmenopausal women, comparing low-dose HT to placebo or conventional dose HT. Initially, 11,418 studies were identified. Data extraction: Data were independently extracted by two investigators. Disagreements were resolved by a third author. Data synthesis: Twenty-eight trials (3,360 patients) were included. Low-dose HT vs. placebo or conventional dose HT did not impact weight, BMI, blood pressure, C-reactive protein, and HDL-cholesterol. Low-dose HT was associated with lower levels of total cholesterol (-12.16 mg/dL, 95%CI -17.41,-6.92) and LDL-C (-12.16 mg/dL, 95%CI -16.55,-7.77) vs. placebo. Compared to conventional dose HT, low-dose HT was associated with higher total cholesterol (5.05 mg/dL 95%CI 0.88,9.21) and LDL-cholesterol (4.49 mg/dL, 95%CI 0.59,8.39). Low-dose HT was not associated with differences in triglycerides vs. placebo. Oral low-dose HT was associated with lower triglycerides vs. conventional dose HT (-14.09 mg/dL, 95%CI -24.2,-3.93). Conclusion: In this population of apparently healthy postmenopausal women, the effect of low-dose HT did not differ from that of placebo or conventional dose HT regarding weight, BMI, blood pressure, CRP, and HDL-c. In contrast, low-dose HT was associated with better lipid profile vs. placebo, and induced higher total and LDL cholesterol and lower triglycerides vs. conventional dose HT.Journal of Clinical Endocrinology & Metabolism 12/2014; 100(3):jc20143301. DOI:10.1210/jc.2014-3301 · 6.31 Impact Factor