Hormone therapy in perimenopause and postmenopause (HT): Interdisciplinary S3 Guideline, Association of the Scientific Medical Societies in Germany AWMF 015/062-short version

This short version of the interdisciplinary S3 guideline on hormone therapy in peri- and postmenopause (HT) is intended as a decision-making instrument for physicians and women considering HT. It is designed to assist daily practice. This short version summarises the long version that contains detailed information about the development of the guideline, particularly about establishing the evidence levels. The statements and recommendations, quoted completely, are marked with the relevant levels of evidence (LoE) and grades of recommendation. The classification system from the Centre for Evidence-based Medicine in Oxford was used in this guideline (see “Attachment”)

Is postmenopausal hormone replacement therapy suitable after a cardio- or cerebrovascular event?

PURPOSE Vascular disease is the leading cause of death in women. One-third of acute events affect women below age 60, when the prevalence of menopausal symptoms is high. This raises the question if hormone replacement therapy (HRT) may be an appropriate treatment for individual women although vascular disease is generally considered a contraindication. METHODS Selective literature search was used for this study. RESULTS In healthy women, HRT increases risks for venous thromboembolism and ischemic stroke, but for cardiovascular disease apparently only beyond 10 years after menopause or 60 years of age. Limited data in women with cardio or cerebrovascular disease have not demonstrated an increased risk for a vascular recurrent event, but for the first year after initiation. In HRT users affected by a cardiovascular event continuation of HRT has not been found to be associated with adverse outcome. Low dose estradiol--preferentially as transdermal patches, if necessary combined with metabolically neutral progestins--appears to convey lower risk. CONCLUSIONS Safety data on HRT in survivors of cardiovascular events or ischemic stroke are limited, but exceptionally increased risk appears to be excluded. If off-label use of HRT is considered to be initiated or continued in women with cardio- or cerebrovascular disease, extensive counseling on the pros and cons of HRT is mandatory

Association of plasma phytosterol concentrations with incident coronary heart disease Data from the CORA study, a case-control study of coronary artery disease in women

Aims: Phytosterols have been proposed to be atherogenic. This research investigates whether plasma concentrations of phytosterols correlate with the manifestation of coronary heart disease. Methods and results: The CORA study compares clinical, biochemical, and lifestyle factors in consecutive pre- and postmenopausal women with incident coronary heart disease to those in age-matched population-based controls. Controls (n = 231) had significantly higher plasma concentrations of the major phytosterol species than cases (it = 186) (4.649 mg/l vs. 4.092 mg/l; p <0.001). Cases had a higher dietary intake of phytosterols, but the ratio of lathosterol over sitosterol did not significantly differ. Phytosterols correlated with cholesterol concentrations of LDL and HDL, the phytosterol-carrying lipoproteins. The age-adjusted odds ratio for the association of total phytosterols and risk of coronary heart disease was 0.69 per 5 mg/dl (95% CI 0.46-0.99). After adjustment for LDL- and HDL-cholesterol the odds ratio approached 1 (0.89; 95% CI 0.61-1.30), which was reached after additional adjustment for major risk factors, particularly those reflecting the metabolic syndrome (1.05; 95% CI 0.64-1.97). Conclusions: Healthy controls had higher unadjusted concentrations of plasma phytosterols, but the adjusted odds ratio for coronary heart disease did not point to an impact of plasma phytosterols on coronary heart disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved

Differential Association of Anthropometric Parameters with Coronary Risk in Women - Data of the CORA Study

Objective: The predictive value of weight gain, BMI, waist circumference (WC) and waist-to-hip ratio (WHR) as to cardiovascular risk factors and coronary heart disease (CHD) is still controversial. Methods: 200 consecutive pre- and postmenopausal women with incident CHD (cases) were compared with 255 randomized age-matched population-based controls recruited from corresponding neighborhoods of Hamburg between 1997 and 2001. Results: At the time of recruitment cases and controls did not differ in BMI, but at any BMI in WC and WHR. Both parameters of central obesity were related to coronary risk. However, after adjustment for conventional risk factors, the odds ratio of WC for CHD lost its significance while the odds ratio of WHR was still 2.20 per 0.1 unit (95% confidence interval 1.48-3.27; p = 0.0001). The pattern of weight gain differed considerably in women with WHR >= 0.85 o

The association of genetic markers for type 2 diabetes with prediabetic status - cross-sectional data of a diabetes prevention trial.

OBJECTIVE: To investigate the association of risk alleles for type 2 diabetes with prediabetes accounting for age, anthropometry, inflammatory markers and lifestyle habits. DESIGN: Cross-sectional study of 129 men and 157 women of medium-sized companies in northern Germany in the Delay of Impaired Glucose Tolerance by a Healthy Lifestyle Trial (DELIGHT). METHODS: Besides established risk factors, 41 single nucleotide polymorphisms (SNPs) that have previously been found to be associated with type 2 diabetes were analyzed. As a nonparametric test a random forest approach was used that allows processing of a large number of predictors. Variables with the highest impact were entered into a multivariate logistic regression model to estimate their association with prediabetes. RESULTS: Individuals with prediabetes were characterized by a slightly, but significantly higher number of type 2 diabetes risk alleles (42.5±4.1 vs. 41.3±4.1, p = 0.013). After adjustment for age and waist circumference 6 SNPs with the highest impact in the random forest analysis were associated with risk for prediabetes in a logistic regression model. At least 5 of these SNPs were positively related to prediabetic status (odds ratio for prediabetes 1.57 per allele (Cl 1.21-2.10, p = 0.001)). CONCLUSIONS: This explorative analysis of data of DELIGHT demonstrates that at least 6 out of 41 genetic variants characteristic of individuals with type 2 diabetes may also be associated with prediabetes. Accumulation of these risk alleles may markedly increase the risk for prediabetes. However, prospective studies are required to corroborate these findings and to demonstrate the predictive value of these genetic variants for the risk to develop prediabetes

Peri- and postmenopause—diagnosis and interventions interdisciplinary S3 guideline of the association of the scientific medical societies in Germany (AWMF 015/062): short version

This short version of the interdisciplinary S3 guideline 'Peri- and Postmenopause-Diagnosis and Interventions' is intended as a decision-making instrument for physicians who counsel peri- and postmenopausal women. It is designed to assist daily practice. The present short version summarizes the full version of the guideline which contains detailed information on guideline methodology, particularly regarding the critical appraisal of the evidence and the assignment of evidence levels. The statements and recommendations of the full version of the guideline are quoted completely in the present short version including levels of evidence (LoE) and grades of recommendation. The classification system developed by the Centre for Evidence-based Medicine in Oxford was used in this guideline

Addendum to: Peri- and postmenopause—diagnosis and interventions interdisciplinary S3 guideline of the association of the scientific medical societies in Germany (AWMF 015/062): short version

Purpose!#!Enzymes with epigenetic functions play an essential part in development of cancer. However, the significance of epigenetic changes in cervical carcinoma as a prognostic factor has not been fully investigated. Nuclear receptor corepressor (NCoR) presents itself as a potentially important element for epigenetic modification and as a potential prognostic aspect in cervical cancer.!##!Methods!#!By immunohistochemical staining of 250 tumor samples, the expression strength of NCoR was measured and evaluated by immunoreactive score (IRS) in the nucleus and cytoplasm.!##!Results!#!A low expression of NCoR in our patients was a disadvantage in overall survival. Expression of NCoR was negatively correlated with viral oncoprotein E6, acetylated histone H3 acetyl K9 and FIGO status, and positively correlated to p53.!##!Conclusions!#!Our study has identified epigenetic modification of tumor cells thus seems to be of relevance in cervical cancer as well for diagnosis, as a marker or as a potential therapeutic target in patients with advanced cervical carcinoma