Informing women about hormone replacement therapy: the consensus conference statement

Background: The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/ benefits. Methods: We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: A literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results: Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone therapy" should be the preferred definition. Conclusion: This CC led to the identification of specific information drawbacks. Women are exposed to messages that are often partial, non evidence-based nor transparently developed. The structured and participative methodology of this CC allowed a multidisciplinary perspective and a substantial lay people input

Generalization and fine mapping of red blood cell trait genetic associations to multiâ ethnic populations: The PAGE study

Red blood cell (RBC) traits provide insight into a wide range of physiological states and exhibit moderate to high heritability, making them excellent candidates for genetic studies to inform underlying biologic mechanisms. Previous RBC trait genomeâ wide association studies were performed primarily in Europeanâ or Asianâ ancestry populations, missing opportunities to inform understanding of RBC genetic architecture in diverse populations and reduce intervals surrounding putative functional SNPs through fineâ mapping. Here, we report the first fineâ mapping of 6 correlated (Pearson’s r range: |0.04â 0.92|) RBC traits in up to 19â 036 African Americans and 19â 562 Hispanic/Latino participants of the Population Architecture using Genomics and Epidemiology consortium. Transâ ethnic metaâ analysis of race/ethnicâ and studyâ specific estimates for approximately 11â 000 SNPs flanking 13 previously identified association signals as well as 150â 000 additional arrayâ wide SNPs was performed using inverseâ variance metaâ analysis after adjusting for study and clinical covariates. Approximately half of previously reported index SNPâ RBC trait associations generalized to the transâ ethnic study population (pâ <â 1.7 Ã 10â 4); previously unreported independent association signals within the ABO region reinforce the potential for multiple functional variants affecting the same locus. Transâ ethnic fineâ mapping did not reveal additional signals at the HFE locus independent of the known functional variants. Finally, we identified a potential novel association in the Hispanic/Latino study population at the HECTD4/RPL6 locus for RBC count (pâ =â 1.9 Ã 10â 7). The identification of a previously unknown association, generalization of a large proportion of known association signals, and refinement of known association signals all exemplify the benefits of genetic studies in diverse populations.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145575/1/ajh25161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145575/2/ajh25161.pd

Modulating an oxidative-inflammatory cascade: potential new treatment strategy for improving glucose metabolism, insulin resistance, and vascular function

Type 2 diabetes is a result of derangement of homeostatic systems of metabolic control and immune defense. Increases in visceral fat and organ adipose, environmental factors and genetic predisposition create imbalances of these homeostatic mechanisms, ultimately leading to a condition in which the oxidative environment cannot be held in check. A significant imbalance between the production of reactive oxygen species and antioxidant defenses, a condition called to oxidative stress, ensues, leading to alterations in stress-signalling pathways and potentially end-organ damage. Oxidative stress and metabolic inflammation upregulate the expression pro-inflammatory cytokines, including tissue necrosis factor alpha, monocyte chemoattractant protein-1 and interleukin-6, as well as activating stress-sensitive kinases, such as c-Jun N-terminal kinase (JNK), phosphokinase C isoforms, mitogen-activated protein kinase and inhibitor of kappa B kinase. The JNK pathway (specifically JNK-1) appears to be a regulator that triggers the oxidative-inflammation cascade that, if left unchecked, can become chronic and cause abnormal glucose metabolism. This can lead to insulin resistance and dysfunction of the vasculature and pancreatic β-cell. The series of events set in motion by the interaction between metabolic inflammation and oxidative stress constitutes an ‘oxidative-inflammatory cascade’, a delicate balance driven by mediators of the immune and metabolic systems, maintained through a positive feedback loop. Modulating an oxidative-inflammation cascade may improve glucose metabolism, insulin resistance and vascular function, thereby slowing the development and progression to cardiovascular diseases and type 2 diabetes

Chocolate-candy consumption and 3-year weight gain among postmenopausal U.S. women

OBJECTIVE: To test the hypothesis that greater chocolate-candy intake is associated with more weight gain in postmenopausal women. METHODS: A prospective cohort study involved 107,243 postmenopausal American women aged 50-79 years (mean = 60.7) at enrollment in the Women\u27s Health Initiative, with 3-year follow-up. Chocolate-candy consumption was assessed by food frequency questionnaire, and body weight was measured. Linear mixed models, adjusted for demographic, socio economic, anthropomorphic, and behavioral variables, were used to test our main hypotheses. RESULTS: Compared with women who ate a 1 oz ( approximately 28 g) serving of chocolate candy \u3c 1 per month, those who ate this amount 1 per month to \u3c 1 per week, 1 per week to \u3c 3 per week and \u3e =3 per week showed greater 3-year prospective weight gains (kg) of 0.76 (95% CI: 0.66, 0.85), 0.95 (0.84, 1.06), and 1.40 (1.27, 1.53), respectively, (P for linear trend \u3c 0.0001). Each additional 1 oz/day was associated with a greater 3-year weight gain (kg) of 0.92 (0.80, 1.05). The weight gain in each chocolate-candy intake level increased as BMI increased above the normal range (18.5-25 kg/m(2) ), and was inversely associated with age. CONCLUSIONS: Greater chocolate-candy intake was associated with greater prospective weight gain in this cohort of postmenopausal women

Heart Rate Variability, Ambient Particulate Matter Air Pollution, and Glucose Homeostasis: The Environmental Epidemiology of Arrhythmogenesis in the Women's Health Initiative

Metabolic neuropathophysiology underlying the prediabetic state may confer susceptibility to the adverse health effects of ambient particulate matter <10 μm in diameter (PM10). The authors therefore examined whether impaired glucose homeostasis modifies the effect of PM10 on heart rate variability in a stratified, random sample of 4,295 Women's Health Initiative clinical trial participants, among whom electrocardiograms and fasting blood draws were repeated at 3-year intervals from 1993 to 2004. In multilevel, mixed models weighted for sampling design and adjusted for clinical and environmental covariables, PM10 exposure was inversely associated with heart rate variability. Inverse PM10–heart rate variability associations were strongest for the root mean square of successive differences in normal-to-normal RR intervals (RMSSD). Among participants with impaired fasting glucose, there were −8.3% (95% confidence interval: −13.9, −2.4) versus −0.6% (95% confidence interval: −2.4, 1.3), −8.4% (95% confidence interval: −13.8, −2.7) versus −0.3% (95% confidence interval: −2.1, 1.6), and −4.3% (95% confidence interval: −9.4, 1.0) versus −0.8% (95% confidence interval: −2.7, 1.0) decreases in the RMSSD per 10-μg/m3 increase in PM10 at high versus low levels of insulin (P < 0.01), insulin resistance (P < 0.01), and glucose (P = 0.16), respectively. These associations were stronger among participants with diabetes and weaker among those without diabetes or impaired fasting glucose. The findings suggest that insulin and insulin resistance exacerbate the adverse effect of PM10 on cardiac autonomic control and thus risk of coronary heart disease among nondiabetic, postmenopausal women with impaired fasting glucose