Selección de Resúmenes de Menopausia

                                               Semana del 28 de Octubre al 3 de Noviembre de 2009

                        Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Circulation. 2009 Oct 26. [Epub ahead of print]

Anthropometry, Body Fat, and Venous Thromboembolism. A Danish Follow-Up Study.

Severinsen MT, Kristensen SR, Johnsen SP, Dethlefsen C, Tjřnneland A, Overvad K.

Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; and Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.

BACKGROUND: -Obesity, measured as body mass index, is associated with venous thromboembolism (VTE). Body mass index is a marker of excess weight and correlates well with body fat content in adults; however, it fails to consider the distribution of body fat. We assessed the association between anthropometric variables and VTE. Methods and Results-From 1993 to 1997, 27 178 men and 29 876 women 50 to 64 years of age were recruited into a Danish prospective study (Diet, Cancer, and Health). During 10 years of follow-up, the outcome of VTE events was identified in the Danish National Patient Registry and verified by review of medical records. Body weight, body mass index, waist circumference, hip circumference, and total body fat were measured at baseline. We used Cox proportional hazard models to assess the association between anthropometry and VTE. Age was used as a time axis, with further adjustment for smoking, physical activity, height, hypertension, diabetes mellitus, cholesterol, and, among women, use of hormone replacement therapy. We verified 641 incident VTE events and found monotonic dose-response relationships between VTE and all anthropometric measurements in both sexes. In mutually adjusted analyses of waist and hip circumference, we found that hip circumference was positively associated with VTE in women but not in men, whereas waist circumference was positively associated with VTE in men but not in women. Conclusions-All measurements of obesity are predictors of the risk for VTE. Positive associations were found between VTE and body weight, body mass index, waist circumference, hip circumference, and total body fat mass.

 

 

Pharmacotherapy. 2009 Nov;29(11):1357-74.

Use of antidepressants for management of hot flashes.

Carroll DG, Kelley KW.

Department of Pharmacy Practice, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA. dgc0001@auburn.edu

A growing body of evidence suggests that antidepressant therapies, particularly selective serotonin reuptake inhibitors and venlafaxine, are effective in the management of hot flash symptoms. Several of these agents have the support of the American College of Obstetricians and Gynecologists and the North American Menopause Society. To review the literature on antidepressants for the treatment of hot flashes in women, we searched the PubMed, International Pharmaceutical Abstracts, and MEDLINE databases from inception through May 2009. All publication types that included human participants and that were published in English were eligible for review. These articles, relevant abstracts, and additional references were used to collect pertinent data. Although initial small pilot trials were conducted solely in breast cancer survivors, additional studies have been conducted both in breast cancer survivors and in relatively healthy menopausal women. Data on the benefits with many of these agents are conflicting. Venlafaxine and paroxetine have been studied more extensively than any of the other antidepressants and are more consistent in effectively reducing the frequency and severity of hot flashes, based on these study results. Desvenlafaxine, sertraline, fluoxetine, and citalopram should be considered second- or third-line options if patients fail therapy with or cannot tolerate venlafaxine or paroxetine, based on the current published data. Duloxetine, escitalopram, fluvoxamine, and mirtazapine should be reserved as last-line therapy until more rigorous studies are conducted assessing their use in the management of hot flashes.

 

 

Am J Med. 2009 Nov;122(11):1016-1022.e1.

Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women.

Salpeter SR, Cheng J, Thabane L, Buckley NS, Salpeter EE.

Santa Clara Valley Medical Center, 751 S. Bascom Ave, San Jose, CA 95128, USA. salpeter@stanford.edu

BACKGROUND: There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue. METHODS: A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 month's duration that evaluated hormone therapy in women with mean age <60 years and reported at least one death, and prospective observational cohort studies that evaluated the relative risk of mortality associated with hormone therapy after adjustment for confounding variables. RESULTS: The results were synthesized using a hierarchical random-effects Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8 observational studies were added to the analysis, the resultant relative risk was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone therapy reduces total mortality in younger women is almost 1. CONCLUSIONS: The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy.

 

 

Osteoporos Int. 2009 Oct 30. [Epub ahead of print]

Immune changes in post-menopausal osteoporosis: the Immunos study.

Breuil V, Ticchioni M, Testa J, Roux CH, Ferrari P, Breittmayer JP, Albert-Sabonnadičre C, Durant J, De Perreti F, Bernard A, Euller-Ziegler L, Carle GF.

Service de Rhumatologie, CHU de Nice, Hôpital l'Archet, Route Saint Antoine de Ginestičre,Nice, France.

The phenotypic and functional characteristics of immune cells of osteoporotic women compared to healthy controls similar for age and estrogen level showed for the first time significant changes in several B lymphocytes populations in postmenopausal osteoporosis, related to bone mineral density (BMD) and fractures, and a significant lower basal secretion of interferon-gamma (IFN-gamma) by CD4(+). INTRODUCTION: To investigate the interactions between bone and immune system, we studied the phenotypic and functional characteristics of immune cells of 26 postmenopausal women with osteoporotic (OP) fractures compared to 24 healthy controls. METHODS: We analyzed surface markers of peripheral B, CD4(+) and CD8(+) lymphocytes and cytokine secretion in supernatants of these cells cultured with or without stimulation. Body composition was assessed by dual energy X-ray absorptiometry. RESULTS: The two groups were similar for age and estrogen level. OP women had a significantly lower body mass index, fat mass, and lean mass. The number of CD19(+), CD19(+)/CD27(+), CD19(+)/CD27(+)/CD5(-)/CD38(+) and CD19(+)/CD27(+)/RANK(+), CD4(+)/CD27(+)/CD45RA(-)/RANK(+), and CD4(+)/CD27(+)/CD45RA(-)/CD28(+) was lower in OP women and positively correlated to BMD. In OP women, under basal conditions, CD4(+) secreted less IFN-gamma and B lymphocytes more granulocyte macrophage colony-stimulating factor (GM-CSF). GM-CSF was positively correlated to fracture rate and negatively to BMD. CONCLUSIONS: Our results suggest that, regardless of age and estrogen status, postmenopausal OP is associated with immune changes, highlighting a possible role of IFN-gamma in the pathophysiology of OP and reporting, for the first time, changes in several B lymphocyte populations. These alterations may reflect the frailty observed after fracture, providing new insight into the mechanisms of morbidity and mortality associated with OP fractures.

 

 

Womens Health (Lond Engl). 2009 Nov;5(6):637-47.

Long-term prevention with hormone-replacement therapy after the menopause: which women should be targeted?

Alexandersen P, Karsdal MA, Christiansen C.

Center for Clinical & Basic Research a/s, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. peter.alexandersen@ccbr.com

For decades, hormone-replacement therapy (HRT) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency. Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherogenesis and coronary heart disease (CHD) in women after the menopause. However, the fact that these promising results were not translated into lower incidences of CHD events in hormone-treated women compared with placebo in subsequent, large, randomized studies of healthy subjects as well as women with known CHD raised a very intense debate concerning the safety of HRT in terms of cardiovascular risk. A critical mass of data points toward a protective influence of HRT on cardiovascular disease end points in early postmenopausal women, but increased harm in elderly women, especially those with abdominal adiposity or metabolic syndrome. Once the quasi-hysterical reaction to the largest of the randomized studies (the Women's Health Initiative) has abated, a future strategy should be to concentrate on identifying those relatively few individuals who are not suitable for HRT, as HRT still remains the most thoroughly investigated pharmacological prevention strategy of osteoporosis.

 

 

J Clin Endocrinol Metab. 2009 Oct 26. [Epub ahead of print]

Effect of Transdermal Teriparatide Administration on Bone Mineral Density in Postmenopausal Women.

Cosman F, Lane NE, Bolognese MA, Zanchetta JR, Garcia-Hernandez PA, Sees K, Matriano JA, Gaumer K, Daddona PE.

Regional Bone Center (F.C.), Helen Hayes Hospital, West Haverstraw, New York, New York 10993.

Context: Treatment of osteoporosis with an anabolic agent, teriparatide [human PTH 1-34 (TPTD)], is effective in reducing incident fractures, but patient resistance to daily sc injections has limited its use. A novel transdermal patch, providing a rapid, pulse delivery of TPTD, may provide a desirable alternative. Objective: The aim of the study was to determine the safety and efficacy of a novel transdermal TPTD patch compared to placebo patch and sc TPTD 20-mug injection in postmenopausal women with osteoporosis. Design: Our study consisted of 6-month, randomized, placebo-controlled, positive control, multidose daily administration. Patients: We enrolled 165 postmenopausal women (mean age, 64 yr) with osteoporosis. Interventions: A TPTD patch with a 20-, 30-, or 40-mug dose or a placebo patch was self-administered daily for 30-min wear time, or 20 mug of TPTD was injected daily. Outcomes: The primary efficacy measure was mean percentage change in lumbar spine bone mineral density (BMD) from baseline at 6 months. Results: TPTD delivered by transdermal patch significantly increased lumbar spine BMD vs. placebo patch in a dose-dependent manner at 6 months (P < 0.001). TPTD 40-mug patch increased total hip BMD compared to both placebo patch and TPTD injection (P < 0.05). Bone turnover markers (procollagen type I N-terminal propeptide and C-terminal cross-linked telopeptide of type I collagen) increased from baseline in a dose-dependent manner in all treatment groups and were all significantly different from placebo patch (P < 0.001). All treatments were well tolerated, and no prolonged hypercalcemia was observed. Conclusion: Transdermal patch delivery of TPTD in postmenopausal women with osteoporosis for 6 months is safe and effective in increasing lumbar spine and total hip BMD.

 

 

Osteoporos Int. 2009 Oct 27. [Epub ahead of print]

Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism.

Vestergaard P, Schwartz K, Pinholt EM, Rejnmark L, Mosekilde L.

Department of Endocrinology and Metabolism C, Aarhus University Hospital, Tage Hansens Gade 2, 8000, Arhus C, Denmark, p-vest@post4.tele.dk.

Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism and pulmonary embolism. In a cohort study, we observed an increased risk also with the bisphosphonates. However, the increase was present already before the start of bisphosphonates pointing at an effect of the underlying condition. INTRODUCTION: We seek to study the association between use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT) and pulmonary embolism (PE). METHODS: Nationwide register-based cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and gender-matched controls from the general population (n = 310,683). RESULTS: Before start of a drug against osteoporosis, an increased risk of DVT/PE was present in the crude analysis for alendronate, etidronate, and risedronate. However, upon adjustment, this increase in risk disappeared. Before start of raloxifene, a decreased risk of DVT/PE was present (odds ratio (OR) = 0.53, 95% confidence interval (CI), 0.39-0.71). After start of a drug, alendronate (HR = 1.20, 95% CI, 1.00-1.43), clodronate (HR = 4.06, 95% CI, 1.47-11.2), and etidronate (HR = 1-37, 95% CI, 1.23-1.51) were all associated with an increased risk of DVT/PE, while raloxifene was only borderline, significantly associated with risk of DVT/PE (HR = 1.64, 95% CI, 0.97-2.77). No dose-reponse relationship was present except for alendronate, where the risk was inversely associated with dose, i.e., the risk of DVT/PE decreased with increasing average daily dose. The HR for DVT/PE was higher with clodronate and etidronate than with alendronate. Alendronate and raloxifene carried the same risk for DVT/PE. CONCLUSION: Bisphosphonates seem associated with an increased risk of DVT/PE. However, the association does not seem to be causal.

 

Semana del 21 al 27 de Octubre de 2009

 

Clin Interv Aging. 2009;4:357-65. Epub 2009 Oct 12.

Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment.

Derman R, Kohles JD, Babbitt A.

Department of Obstetrics and Gynecology, Christiana Hospital, Newark, DE, USA.

Data from two open-label trials (PRIOR and CURRENT) of women with postmenopausal osteoporosis or osteopenia were evaluated to assess whether monthly oral and quarterly intravenous (IV) ibandronate dosing improved self-reported gastrointestinal (GI) tolerability for patients who had previously experienced GI irritation with bisphosphonate (BP) use. In PRIOR, women who had discontinued daily or weekly BP treatment due to GI intolerance received monthly oral or quarterly IV ibandronate for 12 months. The CURRENT subanalysis included women receiving weekly BP treatment who switched to monthly oral ibandronate for six months. GI symptom severity and frequency were assessed using the Osteoporosis Patient Satisfaction Questionnaire. In PRIOR, mean GI tolerability scores increased significantly at month 1 from screening for both treatment groups (oral: 79.3 versus 54.1; IV: 84.4 versus 51.0; p < 0.001 for both). Most patients reported improvement in GI symptom severity and frequency from baseline at all post-screening assessments (>90% at Month 10). In the CURRENT subanalysis >60% of patients reported improvements in heartburn or acid reflux and >70% indicated improvement in other stomach upset at month 6. Postmenopausal women with GI irritability with daily or weekly BPs experienced improvement in symptoms with extended dosing monthly or quarterly ibandronate compared with baseline.

 

 

J Clin Endocrinol Metab. 2009 Oct 22. [Epub ahead of print]

Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women with Prior Hysterectomy.

Resnick SM, Espeland MA, An Y, Maki PM, Coker LH, Jackson R, Stefanick ML, Wallace R, Rapp SR.

Context: Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women. Objective: The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy. Design: This was a randomized, double blind, placebo-controlled clinical trial. Setting: The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers. Participants: Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr. Intervention: Intervention was 0.625 mg of CEE daily or placebo. Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured. Results: Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect. Conclusions: CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women.

 

 

J Clin Endocrinol Metab. 2009 Oct 22. [Epub ahead of print]

The Effect of Transdermal Testosterone on Mammographic Density in Postmenopausal Women Not Receiving Systemic Estrogen Therapy.

Davis SR, Hirschberg AL, Wagner LK, Lodhi I, von Schoultz B.

Procter & Gamble Pharmaceuticals (L.K.W., I.L.), Mason, Ohio 45040.

Context: Greater mammographic density is associated with increased breast cancer risk and reduced diagnostic mammographic sensitivity and may be seen with estrogen/progestin therapy (EPT). The effects of testosterone therapy on mammographic density in postmenopausal women not on EPT are not known. Objective: Our objective was to compare effects of two doses of the testosterone transdermal patch (TTP) with placebo in postmenopausal women without concomitant EPT on mammographic density over 52 wk. Design: We conducted a randomized, double-blind, placebo-controlled, parallel-group, multinational trial. Patients: Patients included 279 postmenopausal women participating in a testosterone and sexual function study with paired mammograms for baseline and 52 wk/exit. Interventions: Patients were randomized to placebo, TTP 150 mug/d, or TTP 300 mug/d, stratified by menopause type (natural or surgical). Main Outcome Measures: Change from baseline to wk 52 in the percentage of dense tissue (PD) on digital mammograms. Results: A total of 250 women with paired mammograms for study baseline and wk 52 were included in the primary analysis. Mean age was 54.6 yr, baseline body mass index was 27.5 kg/m(2), and 78% were naturally menopausal. There were no baseline differences between groups. Mean changes from baseline (+/-SEM) in PD for placebo, TTP 150 mug/d and TTP 300 mug/d were small (0.05 +/- 0.16, 0.06 +/- 0.19, and 0.21 +/- 0.17%) and not significantly different. There were no statistically significant differences from placebo for total dense or nondense area and no significant relationships between hormone levels and PD after adjustment for body mass index. Conclusion: TTP therapy over 52 wk appears to have no significant effect on digitally quantified absolute or percent dense mammographic area in postmenopausal women not using EPT.

 

 

Gend Med. 2009 Sep;6(3):433-43.

Relationship between serum progesterone concentrations and cardiovascular disease, diabetes, and mortality in elderly Swedish men and women: An 8-Year prospective study.

Nilsson SE, Fransson E, Brismar K.

Institute of Gerontology, School of Health Sciences, Jönköping University, Jönköping, Sweden.

Background: The use of synthetic progesterone-like substances in hormone replacement therapy and birth control pills has been associated with increases in cardiovascular morbidity and the prevalence of diabetes. Objectives: The primary aims of this study were to investigate whether physiologic concentrations of progesterone might also be associated with cardiovascular disease and diabetes, and to explore potential gender differences in these associations in elderly Swedish men and women. Methods: This prospective, longitudinal study was performed in a Swedish population-based sample of opposite-sex twins aged between 71 and 80 years who were not receiving sex hormone therapy. Serum concentrations of progesterone, estradiol, C-reactive protein (CRP), and urea were measured at baseline (1996) and at 8-year follow-up (2004), and serum concentrations of cystatin and insulin were measured only at follow-up. The outcomes of interest were cardiovascular morbidity (myocardial infarction, angina pectoris, peripheral arterial disease, stroke, congestive heart failure [CHF], cardiac arrhythmia, hypertension, and thromboembolism), diabetes, and mortality throughout the observation period. Results: At baseline, the study sample included 230 men and 195 women (mean [SD] age, 74.6 [2.6] years). At follow-up, 132 men and 145 women (mean age, 82.4 [2.5] years) met the inclusion criteria, of whom 128 men and 112 women did so at both baseline and follow-up. Serum progesterone concentrations, which did not differ significantly from reported concentrations for the age group, were significantly associated with mortality across the observation period (P < 0.001). At follow-up, higher serum progesterone was significantly associated with the occurrence of CHF (P < 0.01); this association remained robust after adjustment for CRP, cystatin, and insulin levels. Conclusion: In these elderly Swedish men and women, increased physiologic concentrations of progesterone were found to be associated with an increased prevalence of CHF, independent of inflammatory factors, markers of renal function, and insulin metabolism.

 

 

Climacteric. 2009 Oct 22. [Epub ahead of print]

Comparative effects of continuous combined hormone therapy and tibolone on body composition in postmenopausal women.

Ziaei S, Moaya M, Faghihzadeh S.

Departments of Obstetrics & Gynecology.

ObjectiveTo compare the effects of tibolone with those of continuous combined hormone replacement therapy (HT) on body composition in postmenopausal women. MethodsOne hundred and fifty postmenopausal women were enrolled in a randomized, controlled trial to compare the effects of tibolone with continuous combined HT on body composition. Patients were randomly allocated into three groups and followed for 9 months. Of the subjects included, 50 women received 2.5 mg tibolone plus one Cal+D tablet (500 mg calcium and 200 IU vitamin D) daily, 50 women received 0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate (CEE/MPA) plus one Cal+D tablet daily, and the rest (50 women) received only one Cal+D tablet and served as a control group. Body composition was evaluated with measurements of body mass index (BMI), weight, waist-to-hip ratio (WHR), fat mass and fat-free mass (FFM) before and after the intervention. Measurements of body fat mass percentage, fat mass, body fat-free mass percentage and fat-free mass (FFM) were assessed by measurement of skin-fold thickness. Results Tibolone significantly increased weight, BMI and FFM and decreased WHR after the treatment in comparison with baseline (p < 0.05). However, only weight and BMI increased significantly in the CEE/MPA group after the treatment (p < 0.05). There were significant increases in weight, BMI and fat mass in the control group after 9 months. In the comparison of the parameters after the treatment between the three groups, tibolone significantly increased FFM compared with the control and CEE/MPA groups (p < 0.01). Conclusions The effect of tibolone on body composition is favorable and therefore tibolone may be regarded as an alternative to continuous combined hormone therapy in postmenopausal women.

 

 

J Clin Endocrinol Metab. 2009 Oct 21. [Epub ahead of print]

Higher Serum Testosterone Concentration in Older Women is Associated with Insulin Resistance, Metabolic Syndrome, and Cardiovascular Disease.

Patel SM, Ratcliffe SJ, Reilly MP, Weinstein R, Bhasin S, Blackman MR, Cauley JA, et al.

Mailman School of Public Health, Columbia University, New York, New York 10032.

Context: Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular risk factors, but whether this translates into increased cardiovascular disease later in life is unknown. Objective: The objective of the study was to determine whether higher T levels are associated with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) in elderly women. Design: Total T and free T by equilibrium dialysis were measured using ultrasensitive assays in 344 women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to examine the associations between total and free T and IR, MetSyn, and CHD. Results: There was a stepwise increase in the homeostasis model assessment of insulin resistance with increasing total (P = 0.0.003) and free T (P = 0.02) level and a corresponding decrease in Quantitative Insulin Sensitivity Check Index (P < 0.001 and P = 0.002, respectively). In adjusted models, higher levels of both total and free T were strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, women in the top quartile of total T levels had a 3-fold greater odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than those in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95, 95% confidence interval 1.2-7.3) than those in second quartile, whereas free T was not significantly associated with MetSyn or CHD. Conclusions: Higher levels of T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a marker or mediator of cardiovascular disease in this population merits further investigation.

 

 

J Vasc Surg. 2009 Oct 16. [Epub ahead of print]

Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization.

Kadoglou NP, Sailer N, Moumtzouoglou A, Kapelouzou A, Gerasimidis T, Liapis CD.

Department of Vascular Surgery, University of Athens, Thessaloniki, Greece and Athens, Greece.

OBJECTIVE: Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis. METHODS: One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05). RESULTS: There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021). CONCLUSIONS: Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner.

 

 

Cancer Causes Control. 2009 Oct 21. [Epub ahead of print]

Screening mammography intervals among postmenopausal hormone therapy users and nonusers.

Onega T, Mackenzie T, Weiss J, Goodrich M, Titus-Ernstoff L.

Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH, USA.

BACKGROUND: The recent decline in US breast cancer incidence rates has been attributed to the marked reduction in use of postmenopausal hormone therapy (HT). An alternative explanation is that women who are not routinely seeking medical care to renew HT prescriptions may be less adherent to recommendations for mammographic screening. To investigate the latter possibility, we compared mammographic intervals according to HT use. METHODS: Using data (1995-2007) from the New Hampshire Mammography Network (NHMN), a state-based mammography registry, we assessed mammographic intervals corresponding to HT use or nonuse among postmenopausal women. We used linear mixed effects models to assess whether the length of screening mammogram intervals differed according to HT use. RESULTS: A total of 310,185 mammograms, representing 76,192 postmenopausal women and 319,353 person-years of screening, were included in the analysis. The median screening interval corresponding to HT use overall was 13.0 months (interquartile range: 12.4-15.1) and for nonuse was 13.1 (interquartile range: 12.4-15.8). Virtually, all screening mammograms occurred within a 2-year interval regardless of HT use or nonuse (98.5 and 98.1%, respectively). CONCLUSIONS: Our findings indicate that screening mammography intervals are similar whether or not women are using HT. Thus, reduced utilization of screening mammography is unlikely to account for the decrease in breast cancer incidence seen soon after the WHI report.

 

 

Cancer Epidemiol Biomarkers Prev. 2009 Oct 20. [Epub ahead of print]

Colorectal Cancer Incidence and Postmenopausal Hormone Use by Type, Recency, and Duration in Cancer Prevention Study II.

Hildebrand JS, Jacobs EJ, Campbell PT, McCullough ML, Teras LR, Thun MJ, Gapstur SM.

Department of Epidemiology, American Cancer Society, Atlanta, Georgia.

The Women's Health Initiative randomized trials showed a reduction in colorectal cancer risk with the use of estrogen plus progesterone (E + P), but not with estrogen alone (E-only), after intervention periods <7 years. Using data from the Cancer Prevention Study II Nutrition Cohort, we examined associations of colorectal cancer risk with E-only and E + P, including analyses by recency and duration of hormone use. During 13.2 years of follow-up, 776 cases of invasive colorectal cancer occurred among 67,412 postmenopausal women participants. Cox proportional hazards models were used to estimate multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI) of colorectal cancer for current and former hormone users according to hormone type and duration of use. Relative to women who never used postmenopausal hormones, current, but not former, use of E-only was associated with a reduced risk of colorectal cancer (RR 0.76; 95% CI, 0.59-0.97). Among current E-only users, duration of use was inversely and linearly associated with risk (P(trend) = 0.01). Use of E-only for <5 years was not associated with reduced risk, whereas use for >/=20 years was associated with a 45% reduction in risk (RR, 0.55; 95% CI, 0.36-0.86). There were no statistically significant associations between E + P and colorectal cancer risk. Our results suggest a strong inverse association of long-term use of E-only with colorectal cancer risk, underscoring the importance of collecting data on duration of hormone use in epidemiologic studies of postmenopausal hormones and risk of disease.

 

 

 Semana del 14 al 20 de Octubre de 2009

                                  

 

Arterioscler Thromb Vasc Biol. 2009 Oct 15. [Epub ahead of print]

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism. Results From the E3N Cohort Study.

Canonico M, Fournier A, Carcaillon L, Olié V, Plu-Bureau G, Oger E, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F, Scarabin PY.

Inserm Unit 780, Cardiovascular Epidemiology Section, Cedex, France; University Paris-South 11, Cedex, France; Inserm ERI20/University Paris-South 11, Villejuif, France; University Paris Descartes, Paris, France; and Centre Régional de PharmacoVigilance, Service de Pharmacologie, CHU de Rennes, France.

OBJECTIVE: Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. METHODS AND RESULTS: We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1 to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity: P=0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: P<0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0 and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7). CONCLUSIONS: In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

 

 

Eur J Nutr. 2009 Oct 13. [Epub ahead of print]

Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women's Health Initiative Observational Study.

Rajpathak SN, Freiberg MS, Wang C, Wylie-Rosett J, Wildman RP, Rohan TE, Robinson JG, Liu S, Wassertheil-Smoller S.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA, swapnil.rajpathak@einstein.yu.edu.

BACKGROUND: Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes. METHODS: We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women's Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders. RESULTS: During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (</=0.5, 0.5-2 and >/=2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed. CONCLUSIONS: Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.

 

 

Am J Epidemiol. 2009 Oct 14. [Epub ahead of print]

Postmenopausal Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort Study.

Cottet V, Touvier M, Fournier A, Touillaud MS, Lafay L, Clavel-Chapelon F, Boutron-Ruault MC.

Drs. Vanessa Cottet and Mathilde Touvier contributed equally to this article, and their names are given in alphabetical order.

Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993-2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: "alcohol/Western" (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and "healthy/Mediterranean" (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The "healthy/Mediterranean" pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.

 

 

Arch Intern Med. 2009 Oct 12;169(18):1684-91

New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk.

Crandall CJ, Aragaki AK, Chlebowski RT, McTiernan A, Anderson G, Hendrix SL, Cochrane BB, Kuller LH, Cauley JA.

Department of Medicine, David Geffen School of Medicine at University of California, UCLA Medicine/GIM, Los Angeles, CA 90024, USA. ccrandall@mednet.ucla.edu

BACKGROUND: Estrogen plus progestin therapy increases breast cancer incidence and breast tenderness. Whether breast tenderness during estrogen plus progestin therapy is associated with breast cancer risk is uncertain. METHODS: We analyzed data from the Women's Health Initiative Estrogen + Progestin Trial, which randomized postmenopausal women with an intact uterus to receive daily conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg (n = 8506), or placebo (n = 8102). At baseline and annually, participants underwent mammography and clinical breast examination. Self-reported breast tenderness was assessed at baseline and at 12 months. The incidence of invasive breast cancer was confirmed by medical record review (mean follow-up of 5.6 years). RESULTS: Of women without baseline breast tenderness (n = 14,538), significantly more assigned to receive conjugated equine estrogens plus medroxyprogesterone vs placebo experienced new-onset breast tenderness after 12 months (36.1% vs 11.8%, P < .001). Of women in the conjugated equine estrogens plus medroxyprogesterone group, breast cancer risk was significantly higher in those with new-onset breast tenderness compared with those without (hazard ratio, 1.48; 95% confidence interval, 1.08-2.03; P = .02). In the placebo group, breast cancer risk was not significantly associated with new-onset breast tenderness (P = .97). CONCLUSIONS: New-onset breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy was associated with increased breast cancer risk. The sensitivity and specificity of the association between breast tenderness and breast cancer were similar in magnitude to those of the Gail model.

 

 

J Bone Miner Res. 2009 Oct 12. [Epub ahead of print]

Obesity and Fractures in Postmenopausal Women.

Premaor MO, Pilbrow L, Tonkin C, Parker R, Compston J.

Abstract Low BMI is a recognized risk factor for fragility fracture whilst obesity is widely believed to be protective. As part of a clinical audit of guidance from the National Institute of Health and Clinical Excellence (NICE) we have documented the prevalence of obesity and morbid obesity in postmenopausal women aged < 75 years presenting to our Fracture Liaison Service (FLS). Between January 2006 and December 2007 1005 postmenopausal women aged < 75 years with a low trauma fracture were seen in the FLS. 805 of these women (80%) underwent assessment of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and values for body mass index (BMI were available in 799. The prevalence of obesity (BMI 30-34.9 kg/m(2)) and morbid obesity (BMI >/= 35 kg/m(2)) in this cohort was 19.3% and 8.4% respectively. 59.1% of obese and 73.1% of morbidly obese women had normal BMD, and only 11.7% and 4.5% respectively had osteoporosis (p<0.0001). Multiple regression analysis revealed significant negative associations between hip T-score and age (p<0.0001), and significant positive associations with BMI (p<0.0001) and previous fracture (p=0.001). Our results demonstrate a surprisingly high prevalence of obesity in postmenopausal women presenting to a FLS with low trauma fracture. The majority of these women had normal BMD as measured by DXA. Our findings have important public health implications in view of the rapidly rising increase in obesity in many populations and emphasise the need for further studies to establish the pathogenesis of fractures in obese individuals and to determine appropriate preventive strategies.

 

 

Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001405.

Oestrogen therapy for urinary incontinence in post-menopausal women.

Cody JD, Richardson K, Moehrer B, Hextall A, Glazener CM.

Cochrane Incontinence Review Group, University of Aberdeen, 1st Floor, Health Sciences Building, Foresterhill, Aberdeen, UK, AB25 2ZD.

BACKGROUND: It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women. OBJECTIVES: To assess the effects of local and systemic oestrogens used for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register of trials (2 April 2009) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that included oestrogens in at least one arm, in women with symptomatic or urodynamic diagnoses of stress, urgency or mixed urinary incontinence or other urinary symptoms post-menopause. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the review authors. Data were extracted by at least two authors and cross checked. Subgroup analyses were performed grouping participants under local or systemic administration. Where appropriate, meta-analysis was undertaken. MAIN RESULTS: Thirty- three trials were identified which included 19,313 (1,262 involved in trials of local administration) incontinent women of whom 9417 received oestrogen therapy. Sample sizes ranged from 16 to 16,117. The trials used varying combinations of type of oestrogen, dose, duration of treatment and length of follow up. Outcome data were not reported consistently and were available for only a minority of outcomes.Systemic administration (of oral oestrogens) resulted in worse incontinence than on placebo (RR 1.32, 95% CI 1.17 to 1.48). This result is heavily weighted by a subgroup of women from the Hendrix trial, which had large numbers of participants and a longer follow up of one year; all the women had had a hysterectomy and the treatment used was conjugated equine oestrogen. The result for women with an intact uterus where oestrogen and progestogen combined were used also showed a statistically significant worsening of incontinence (RR 1.11, 95% CI 1.04 to 1.18).There was some evidence that oestrogens used locally (for example vaginal creams or tablets) may improve incontinence (RR 0.74, 95% CI 0.64 to 0.86). Overall, there were around one to two fewer voids in 24 hours and nocturnal voids amongst women treated with local oestrogen, and there was less frequency and urgency. No serious adverse events were reported although some women experienced vaginal spotting, breast tenderness or nausea.Women who were continent and received systemic oestrogen replacement, with or without progestogens, for reasons other than urinary incontinence were more likely to report the development of new urinary incontinence in one large study.The data were too few to address questions about oestrogens compared with or in combination with other treatments, different types of oestrogen or different modes of delivery. AUTHORS' CONCLUSIONS: Local oestrogen treatment for incontinence may improve or cure it, but there was little evidence from the trials on the period after oestrogen treatment had finished and none about long-term effects. However, systemic hormone replacement therapy, using conjugated equine oestrogen, may make incontinence worse. There were too few data to reliably address other aspects of oestrogen therapy, such as oestrogen type and dose, and no direct evidence on route of administration. The risk of endometrial and breast cancer after long-term use suggests that oestrogen treatment should be for limited periods, especially in those women with an intact uterus.

 

   Semana del 7 al 13 de Octubre de 2009

 

Maturitas. 2009 Oct 6. [Epub ahead of print]

Effects of sleep disturbance on the quality of life of Turkish menopausal women: A population-based study.

Timur S, Sahin NH.

Inonu University School of Health, Malatya, Turkey.

OBJECTIVES: The purpose of this study was to investigate sleep disturbances among menopausal women: their prevalence, risk factors for them and the quality of life of women who have them. DESIGN: A population-based sample of 887 Turkish women aged 45-59 years and living in Malatya was recruited in this cross-sectional descriptive study. The women were administered the Interview Form, which covers sociodemographic, health and lifestyle variables, as well as the Women's Health Initiative Insomnia Rating Scale, the Menopause Specific Quality of Life Questionnaire and the Beck Depression Inventory. RESULTS: The prevalence of sleep disturbance in this sample of menopausal women was 54%. Logistic regression models revealed that the risk of sleep disturbance was 2.4 times higher in the perimenopausal than in the premenopausal period, 1.7 times higher among those who received hormone therapy than among those who did not, 1.5 times higher among those with a physical disease than among those without, and 3.9 times higher among those with depression than among those without; an increase of one year in age was associated with a 5% increase in the prevalence of sleep disturbance. Average scores on the vasomotor, psychosocial, physical and sexual sub-scales of the Menopause Specific Quality of Life Questionnaire were significantly higher for women with sleep disturbance than for those without (P<0.001). CONCLUSIONS: The prevalence of sleep disturbance was found to be high among menopausal women. Initiatives aimed at reducing sleep disturbance should be added to menopausal care programmes in order to improve the quality of life of menopausal women.

 

 

Vascul Pharmacol. 2009 Oct 5. [Epub ahead of print]

Alendronate affects calcium dynamics in cardiomyocytes in vitro.

Kemeny-Suss N, Kasneci A, Rivas D, Afilalo J, Komarova SV, Chalifour LE, Duque G.

Faculty of Dentistry, McGill University, Montreal, Quebec, Canada, H3A 2B2.

Therapy with bisphosphonates, including alendronate (ALN), is considered a safe and effective treatment for osteoporosis. However, recent studies have reported an unexpected increase in serious atrial fibrillation (AF) in patients treated with bisphosphonates. The mechanism that explains this side effect remains unknown. Since AF is associated with an altered sarcoendoplasmic reticulum calcium load, we studied how ALN affects cardiomyocyte calcium homeostasis and protein isoprenylation in vitro. Acute and long-term (48h) treatment of atrial and ventricular cardiomyocytes with ALN (10(-8)-10(-6)M) was performed. Changes in calcium dynamics were determined by both fluorescence measurement of cytosolic free Ca(2+) concentration and western blot analysis of calcium-regulating proteins. Finally, effect of ALN on protein farnesylation was also identified. In both atrial and ventricular cardiomyocytes, ALN treatment delayed and diminished calcium responses to caffeine. Only in atrial cells, long-term exposure to ALN induced transitory calcium oscillations acutely, and led to development of oscillatory component in calcium responses to caffeine. Changes in calcium dynamics were accompanied by changes in expression of proteins controlling sarcoendoplasmic reticulum calcium. In contrast, ALN minimally affected protein isoprenylation in these cells. In summary, treatment of atrial cardiomyocytes with ALN induced abnormalities in calcium dynamics consistent with induction of a self-stimulatory, pacemaker-like behavior, which may contribute to development of cardiac side effects associated with these drugs.

 

 

N Engl J Med. 2009 Oct 8;361(15):1459-65.

Osteoporosis associated with neutralizing autoantibodies against osteoprotegerin.

Riches PL, McRorie E, Fraser WD, Determann C, van't Hof R, Ralston SH.

Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.

Autoantibodies against osteoprotegerin, which block the inhibitory effect of osteoprotegerin on signaling by the receptor activator of nuclear factor (NF)-kappaB (RANK), were identified in a man with celiac disease who presented with severe osteoporosis and high bone turnover. The osteoporosis did not respond to the treatment of his celiac disease but was completely reversed by bisphosphonate therapy. Autoantibodies against osteoprotegerin were detected in three additional patients with celiac disease. Such autoantibodies may be associated with the development of high-turnover osteoporosis, but whether autoantibodies against osteoprotegerin commonly contribute to the pathogenesis of osteoporosis in patients with celiac disease remains to be determined.

 

 

Am J Physiol Regul Integr Comp Physiol. 2009 Oct 7. [Epub ahead of print]

Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats.

Leblanc AJ, Reyes R, Kang LS, Dailey RA, Stallone JN, Moningka NC, Muller-Delp JM.

West Virginia University School of Medicine.

The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared to men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular estrogen. The purpose of this study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mos), middle-aged (14 mos), and old (24 mos) intact, ovariectomized (OVX) and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (Young: 50 +/- 4 vs. Old: 34 +/- 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen-replacement improved flow-induced dilation by ~ 160%. The contribution of NO to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with L-NAME, declined with age. L-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, L-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flow-induced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen and estrogen supplementation can improve flow-induced dilation, even at an advanced age.

 

 

J Clin Endocrinol Metab. 2009 Oct 6. [Epub ahead of print]

Influence of Age and Obesity on Serum Estradiol, Estrone, and Sex Hormone Binding Globulin Concentrations following Oral Estrogen Administration in Postmenopausal Women.

Karim R, Mack WJ, Hodis HN, Roy S, Stanczyk FZ.

Department of Pediatrics (R.K.), Department of Preventive Medicine (R.K., W.J.M., H.N.H), Atherosclerosis Research Unit (R.K., W.J.M., H.N.H), Department of Medicine (H.N.H.), and Department of Obstetrics and Gynecology (S.R., F.Z.S.), University of Southern California, Los Angeles, California 90033.

Objective: Hormone therapy (HT) increases the risk of venous thrombosis and stroke. Risk of venous thrombosis and stroke is higher in older, overweight, and obese women using HT. However, the impact of age and obesity on estrogen concentrations among HT users is not well defined. Method: We measured serum levels of estrone, total and free estradiol, and SHBG in 180 postmenopausal women participating in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT), 91 receiving estradiol therapy (ET) and 89 taking placebo, every 6 months over 2 yr. Mean on-trial levels of estrogens and SHBG were compared across age, body mass index (BMI), and waist to hip ratio categories among ET users and placebo separately. Results: Among the ET users, total (P = 0.01) and free estradiol (P = 0.002) were significantly directly associated with BMI adjusted for age. SHBG was inversely related to waist to hip ratio adjusted for age (P = 0.005). Age was not associated with any of the estrogen or SHBG concentrations in ET or placebo groups. BMI was positively associated with estrone concentrations among older but not younger ET users (P for interaction = 0.03). Conclusion: Overweight and obese women using ET attain greater concentrations of estrogen compared to women with normal BMI, whereas ET users with abdominal obesity attain lower SHBG levels. Obese older women using ET have the highest concentration of estrone. It may be useful to consider age and obesity when prescribing HT to minimize the risk of venous thrombosis or stroke in postmenopausal women. Further research regarding relationships among circulating hormone levels and risk for these conditions is required to substantiate this conclusion.

 

 

Climacteric 2009; 12: 445 - 453

Risk of cardiovascular outcomes in users of estradiol/dydrogesterone or other HRT preparations

C. Schneider;  S. S. Jick; C. R. Meier  

Background. Use of postmenopausal hormone replacement therapy (HRT) used to be promoted to reduce the risk of ischemic cardiovascular diseases, a concept which has been challenged by results of the large Women's Health Initiative trial in users of estrogen and progestin. It is postulated that the type of progestin used in HRT affects the cardiovascular risk. Methods We used the UK-based General Practice Research Database to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing myocardial infarction, thrombotic stroke or venous thromboembolism in estradiol/dydrogesterone users, users of other HRT, or non-users of HRT. Results The incidence rates of myocardial infarction, thrombotic stroke and venous thromboembolism in estradiol/dydrogesterone users were 0.40 (95% confidence interval (CI) 0.18-0.76), 0.27 (95% CI 0.10-0.58) and 0.31 (95% CI 0.13-0.64) per 1000 person-years, respectively. As compared to non-users of HRT, the adjusted relative risk estimates (odds ratios) in the nested case-control analysis for estradiol/dydrogesterone users or users of other HRT were 1.06 (95% CI 0.48-2.36) and 1.12 (95% CI 0.84-1.51) for myocardial infarction, 0.50 (95% CI 0.21-1.22) and 1.18 (95% CI 0.94-1.48) for thrombotic stroke, and 0.84 (95% CI 0.37-1.92) and 1.42 (95% CI 1.10-1.82) for venous thromboembolism, respectively. Conclusion The study provides evidence that estradiol/dydrogesterone use of several months to a few years is not associated with a higher risk of cardiovascular events than use of other HRT.

 

 

J Sex Med. 2009 Oct;6(10):2690-2697.

The Relationship between Self-Reported Sexual Satisfaction and General Well-Being in Women.

Davison SL, Bell RJ, Lachina M, Holden SL, Davis SR.

Women's Health Program, Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Prahran, Vic., Australia;

Introduction. The extent to which low sexual function or sexual dissatisfaction in women impacts on well-being remains uncertain, yet this is a critical issue in the controversy as to the benefits of pharmacotherapy for women seeking treatment for female sexual dysfunction. Aim. To explore the relationship between well-being and self-perceived satisfaction with sexual function in women and to determine if there is an independent effect of menopausal status or age. Design. A community-based cross-sectional study. Patients. A total of 421 women, aged 18 to 65 years were recruited from the community. Women were required to self-identify at study outset as being either satisfied or dissatisfied with their sexual life and be premenopausal or postmenopausal. Main Outcome Measures. Scores from the Psychological General Well-Being Index (PGWB), the Beck Depression Index (BDI) and a daily diary of sexual function. Results. A group of 349 women were included in the analysis. Total PGWB and domain scores of positive well-being and vitality were lower in dissatisfied women compared to satisfied women. PGWB total and domain scores of depressed mood, positive well-being and vitality were higher in older women. Menopause did not have an independent effect on well-being. Conclusions. Women who self-identify as having sexual dissatisfaction have lower psychological general well-being. These findings reinforce the importance of addressing sexual health and well-being in women as an essential component of their health care.

 

                                                   Semana del 30 de Septiembre al 6 de Octubre de 2009

                                    

 

Obesity (Silver Spring). 2009 Oct 1. [Epub ahead of print]

Metabolic Syndrome and Changes in Body Fat From a Low-fat Diet and/or Exercise Randomized Controlled Trial.

Camhi SM, Stefanick ML, Katzmarzyk PT, Young DR.

Population Science, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight-stable randomized controlled trial of low-fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (DeltaMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (DeltaBF) as a covariate. In men, DeltaMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, DeltaMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for DeltaBF, all differences between groups were attenuated and no longer significant. DeltaMetS were associated with DeltaBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for DeltaBF, low-fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low-fat diet and/or increased physical activity appears to be body fat loss.

 

 

J Bone Joint Surg Am. 2009 Oct;91(10):2376-80.

Patients with wrist fractures are less likely to be evaluated and managed for osteoporosis.

Gong HS, Oh WS, Chung MS, Oh JH, Lee YH, Baek GH.

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, South Korea.

BACKGROUND: Although osteoporosis is being evaluated and treated increasingly in elderly patients with fragility fractures, some studies have suggested that physicians may be missing important opportunities, especially in patients with nonvertebral fractures. The purpose of the present study was to determine whether specialists responsible for treating fractures at various locations have different propensities for evaluating and treating osteoporosis after a fracture in female patients over the age of fifty years. METHODS: A retrospective nationwide cohort study was performed with use of data collected during 2007 by the Korean Health Insurance Review Agency, which covers 97% of the population. The incidences of fractures around the hip, spine, and wrist in female patients more than fifty years of age and the frequencies of bone density scans for osteoporosis and the use of medications for its treatment were analyzed and compared. RESULTS: The database identified 31,540 hip fractures, 58,291 spine fractures, and 61,234 wrist fractures in female patients who were more than fifty years of age in Korea during 2007. Of these patients, 7095 (22.5%) with a hip fracture, 16,779 (28.8%) with a spine fracture, and 5348 (8.7%) with a wrist fracture underwent diagnostic bone density scans. Furthermore, 7060 patients (22.4%) with a hip fracture, 17,551 (30.1%) with a spine fracture, and 4594 (7.5%) with a wrist fracture were managed with at least one medication approved for the treatment of osteoporosis. CONCLUSIONS: Despite a recent increase in the recognition of osteoporosis in patients with fragility fractures, our review of this national cohort indicates that patients with a wrist fracture are less likely to be evaluated and managed for osteoporosis than those with a hip or spine fracture by physicians who are responsible for treating symptomatic fractures. Additional studies and intervention programs are necessary to improve this care gap, beginning with physicians who are responsible for fracture treatment.

 

 

BMC Cancer. 2009 Oct 1;9(1):349. [Epub ahead of print]

Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP Diet and Health Study.

Peters TM, Moore SC, Gierach GL, Wareham NJ, Ekelund U, Hollenbeck AR, Schatzkin A, Leitzmann MF.

ABSTRACT: BACKGROUND: Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. METHODS: In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. RESULTS: In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous intensity activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. CONCLUSIONS: A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.

 

 

Calcif Tissue Int. 2009 Oct 1. [Epub ahead of print]

Minimum Required Vitamin D Level for Optimal Increase in Bone Mineral Density with Alendronate Treatment in Osteoporotic Women.

Ishijima M, Sakamoto Y, Yamanaka M, Tokita A, Kitahara K, Kaneko H, Kurosawa H.

Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo.

Vitamin D insufficiency and deficiency are common in the elderly. Most previous studies using alendronate have used vitamin D supplementation regardless of individual vitamin D status. However, the minimum required vitamin D levels for the efficacy of alendronate treatment of osteoporosis remain unclear. Fifty-two postmenopausal women, diagnosed with osteoporosis, were enrolled in this prospective study, in which they took 5 mg of alendronate daily for 6 months without any supplements. Associations between baseline factors and their changes during the treatment and the change in the lumbar spine bone mineral density (LS-BMD) were examined. The most appropriate cut-off level of 25-hydroxyvitamin D (25[OH]D) for the optimal increase in LS-BMD with alendronate was determined using the Akaike information criterion statistical criterion. Overall, alendronate treatment significantly increased LS-BMD by 4.7%. The basal serum 25(OH)D and change in urinary NTX were significantly associated with the increase in LS-BMD. The increase in LS-BMD between the two groups was not different when comparing those with baseline 25(OH)D above vs. below 30 ng/ml. However, 25(OH)D of 25 ng/ml was determined to be the minimum required vitamin D level for an adequate effect of alendronate. Vitamin D status may affect the increase in LS-BMD with alendronate treatment in individuals being treated for osteoporosis, and a 25(OH)D level >25 ng/ml appears to be required for an optimal LS-BMD response.

 

 

Hum Reprod Update. 2009 Sep 30. [Epub ahead of print]

Should the ovaries be removed or retained at the time of hysterectomy for benign disease?

Hickey M, Ambekar M, Hammond I.

School of Women's and Infants' Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, WA 6008, Australia.

BACKGROUND Bilateral oophorectomy is commonly performed at the time of hysterectomy for benign disease. Indications for oophorectomy vary, but in most cases relatively little high-quality information is available to inform the surgeon or patient regarding the relative risks and benefits of ovarian conservation or removal. This review will address the common clinical situations when oophorectomy may be performed and will evaluate the evidence for risk and benefit in each of these circumstances. The aim of this review is to bring together the evidence regarding oophorectomy in pre- and post-menopausal women and to highlight the areas needing further study. METHODS We searched the published literature for studies related to outcomes following surgical menopause, risk-reducing surgery for ovarian cancer, surgical treatment for endometriosis, bilateral oophorectomy for benign disease and treatment for premenstrual syndrome/premenstrual dysphoric disorder. RESULTS Rates of oophorectomy at the time of hysterectomy for benign disease appear to be increasing. There is good evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing surgery for women at high risk of ovarian cancer, but relatively little evidence to support oophorectomy or BSO in other circumstances. There is growing evidence from observational studies that surgical menopause may impact negatively on future cardiovascular, psychosexual, cognitive and mental health. CONCLUSION Clinicians and patients should fully consider the relative risks and benefits of oophorectomy on an individual basis prior to surgery.

 

 

Hypertension. 2009 Sep 28. [Epub ahead of print]

Effect of Cardiorespiratory Fitness on Vascular Regulation and Oxidative Stress in Postmenopausal Women.

Pialoux V, Brown AD, Leigh R, Friedenreich CM, Poulin MJ.

Departments of Physiology and Pharmacology, Medicine, and Clinical Neurosciences, Hotchkiss Brain Institute, and Libin Cardiovascular Institute of Alberta, Faculty of Medicine, and Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada; Alberta Health Services, Calgary, Alberta, Canada.

Increasing evidence exists suggesting an important role for oxidative stress in the pathogenesis and progression of hypertension in women via a decrease of NO production after menopause. Regular physical training has been shown to upregulate antioxidant enzymatic systems, which may slow down the usual increase of oxidative stress in postmenopausal women. The aims of this study were to determine the impact of fitness status on enzymatic antioxidant efficiency, oxidative stress, and NO production and to determine the associations among oxidative stress, enzymatic antioxidant and NO production, mean arterial blood pressure (MABP), and cerebrovascular conductance (CVC) in postmenopausal women (n=40; 50 to 90 years old). Physical fitness, physical activity, resting MABP, and CVC were measured. End product of NO, lipid peroxidation (malondialdehyde and 8-iso-prostaglandin F2alpha), DNA oxidation (8-hydroxy-2'-deoxyguanosine), protein nitration (nitrotyrosine), antioxidant glutathione peroxidase, and catalase activities were measured in plasma. We identified significant negative associations between oxidative stress and indices of physical fitness (malondialdehyde: r=-0.33, P<0.05; 8-iso-prostaglandin F2alpha: r=-0.39, P<0.05; 8-hydroxy-2'-deoxyguanosine: r=-0.35, P<0.05) and physical activity (malondialdehyde: r=-0.30, P<0.05; 8-iso-prostaglandin F2alpha: r=-0.41, P<0.01; 8-hydroxy-2'-deoxyguanosine: r=-0.39, P<0.05). Conversely, glutathione peroxidase was positively correlated with fitness level (r=0.55; P<0.01). Finally, MABP and CVC were significantly associated with 8-hydroxy-2'-deoxyguanosine (MABP: r=0.36, P<0.05; CVC: r=-0.36, P<0.05), nitrotyrosine (MABP: r=0.39, P<0.05; CVC: r=-0.32, P<0.05), and the end product of NO (MABP: r=-0.57, P<0.01; CVC: r=0.44, P<0.01). These findings demonstrate that, after menopause, fitness level and regular physical activity mediate against oxidative stress by maintaining antioxidant enzyme efficiency. Furthermore, these results suggest that oxidative stress and NO production modulate MABP and CVC.

 

 

J Psychiatr Res. 2009 Sep 24. [Epub ahead of print]

Suicide attempts among women during low estradiol/low progesterone states.

Baca-Garcia E, Diaz-Sastre C, Ceverino A, Perez-Rodriguez MM, Navarro-Jimenez R, et al.

Department of Psychiatry at the New York State Psychiatric Institute and Columbia University, NY, USA; Department of Psychiatry, Fundacion Jimenez Diaz Hospital, Autonoma University of Madrid, Spain; Centro de Investigación Biomédica en Red en el área de Salud Mental (CIBERSAM), Madrid, Spain.

The relationship between the menstrual cycle and risk for suicidal behaviors is not clear. The aim of this study is to determine whether perimenstrual phases in fertile women are associated with acute risk for suicide attempt and explore whether risk is elevated during low estradiol/low progesterone states. Women (N=431) recruited within 24h of a suicide attempt were assessed for psychopathology, suicidal behavior and LH, FSH, estradiol and progesterone blood levels. Among fertile women (N=281/431), suicide attempts were more likely to occur during menses (26%, 72/281 observed vs. 15%, 43/281 expected attempts; p<0.001). Compared to women whose attempts occurred during other phases, women who attempted suicide during low estradiol/low progesterone states (menstrual phase, amenorrhea and menopause) reported severe suicide intent, a measure that may be predictive of eventual suicide death. Suicide attempts among women are more likely when estrogen and progesterone levels are low and attempts made under these conditions are associated with greater severity. Low gonadal hormone levels may constitute a key factor in the neurobiological basis of suicidal behavior among women, suggesting a novel, testable hypothesis regarding the underpinnings of suicidal acts.

 

 

Maturitas. 2009 Sep 23. [Epub ahead of print]

When, why and for whom there is a relationship between physical activity and menopause symptoms.

McAndrew LM, Napolitano MA, Albrecht A, Farrell NC, Marcus BH, Whiteley JA.

Dept. of Veterans Affairs NJ Healthcare System, War Related Illness and Injury Center, NJ, USA.

OBJECTIVES: The relationship between enhanced physical activity and decreased menopause symptoms is equivocal. In this study we sought to better understand this relationship by examining the association of physical activity to different symptom domains and by examining mediating and moderating variables. STUDY DESIGN: Women participating in a randomized control trial on physical activity were given a menopause symptom measure (MENQOL) at follow-up. Of the 280 women participating, 113 (mean age=52) reported having symptoms they attributed to menopause. Regression analyses were run to examine if change in physical activity predicted fewer symptoms. Exercise self-efficacy was examined as a mediator and depressive symptoms as a moderator. RESULTS: An increase in physical activity from baseline was found to be related to reporting fewer total menopause symptoms (beta=-0.22, p=.02). When the total menopause symptoms score was examined by domain, increased physical activity was found to be related to reporting fewer general symptoms attributed to menopause (psychosocial (beta=-0.18, p=.05) and physical (beta=-0.23, p=.01)), but had no effect on specific symptoms of menopause (vasomotor and sexual). Exercise self-efficacy was found to mediate the relationship between increased physical activity and total, physical and psychosocial menopause symptoms. Finally, for individuals with high depressive symptoms, those who increased physical activity the most reported fewer sexual symptoms of menopause. CONCLUSION: This study suggests that physical activity participation is associated with lower general symptom reporting as opposed to specifically impacting menopause symptoms. Further, exercise self-efficacy mediates the relationship between physical activity and general menopause symptoms, suggesting a psychological pathway.

 

 

Hear Res. 2009 Sep 22. [Epub ahead of print]

The menopause triggers hearing decline in healthy women.

Hederstierna C, Hultcrantz M, Collins A, Rosenhall U.

Division of Otorhinolaryngology and Hearing, Karolinska Institute, Stockholm, Sweden.

BACKGROUND: Epidemiological studies have shown that women have better high-frequency thresholds than men in virtually all age groups, and that age-related hearing decline starts after 30 in men but not until after the age of 50 in women. This coincides with the menopausal transition in most women, thus leading us to hypothesize that the menopause triggers auditory deterioration, possibly due to reduced levels of endogenous estrogens, which are known to have protective effects on the auditory system. Methods: 104 women with a mean age 51.2 at baseline, were tested with pure tone audiometry twice with an average interval of 7.5 years. The age at the final menstrual period (FMP) was reported by all women. Hearing decline at individual frequencies was calculated. Results: Women with a FMP 0-4 years ago, had a rate of high frequency hearing decline of 0.9-1.5 dB/year in the left ear, those with 5-7 years since the FMP had a corresponding rate of 1.1-1.5 dB/year in the right ear, and 8-13 years after the FMP the decline was more subtle, 0.7-1.1 dB/year in both ears. Conclusion: The menopause appears to act as a trigger of a relatively rapid age-related hearing decline in healthy women, starting in the left ear.