Effects of long-term estrogen replacement therapy in postmenopausal women with coronary risk factors

Objective: Hormone replacement therapy (HRT) with estrogen alone or in concert with progesterone may exert beneficial effects on coronary endothelium-dependent vasomotion in postmenopausal women without traditional coronary risk factors. We aimed to evaluate the effect of HRT on coronary vasomotor function in postmenopausal women with traditional coronary risk factors such as hypertension, hypercholesterolemia and smoking as compared to those without HRT. Methods: Combining N-13 ammonia with PET, myocardial blood flow (MBF) was measured in ml/g/min at rest, during cold pressor test (CPT, reflecting predominantly endothelium-dependent vasomotion)and during pharmacologic vasodilation (representing predominantly endothelium-independent vasomotion) in 48 postmenopausal women with various coronary risk factors during a mean follow up (FU) of 20_9 months. postmenopausal women wer grouped according to HRT: group 1 with HRT (n_18), group 2 without HRT (n_18) and group 3 with HRT at baseline but not at FU (n_12). Results: during FU, HRT did not significantly affect lipid profile and plasma glucose levels. At baseline resting MBF was similar between groups (Table).After the FU, in group 2 and 3 the endothelium-related increase in MBF from rest to CPT (_ MBF) was significantly less than at baseline (*p_0.05) (Table). Conversely, in group 1 _MBF to CPT at FU was not significantly different from the baseline study. The group comparison of CPT-induced _MBF in group 2 and group 3 after the FU period was significantly different from group 1 (p_0.006 by ANOVA). Finally, in all three groups, hyperemic MBFs during pharmacologic vasodilation did not differ significantly between baseline and FU (Table). Conclusion: In postmenopausal women with coronary risk factors, HRT may counterbalance the adverse effects of traditional coronary risk factors on endothelium-dependent coronary vasomotion. Consequently, in addition to standard management of coronary risk factors, HRT may exert beneficial effects on the coronary endothelium that may delay the progression of coronary artery disease in postmenopausal women.

Fracture ostéoporotique chez les femmes ménopausées: l'alendronate réduit le risque. [Osteoporotic fracture in menopausal women: alendronate reduces the risk]

Cette rubrique présente les résultats d'une revue systématique publiée par la Collaboration Cochrane dans la Cochrane Library au premier trimestre 2008 (www.cochrane.org/). Volontairement limité à un champ de recherche circonscrit, cet article reflète l'état actuel des connaissances de ce domaine. Il ne s'agit donc pas de recommandations pour guider la prise en charge d'une problématique clinique considérée dans sa globalité (guidelines).

Hommes et femmes: la même organisation cérébrale ? [Men and women: the same cerebral organisation ?]

Des différences entre les hommes et les femmes en ce qui concerne la taille du cerveau, les compétences dans des domaines particuliers et la récupération suite aux lésions cérébrales ont soulevé la question des dissimilitudes d'organisation cérébrale entre les deux sexes. Interprétée tout d'abord comme touchant à la latéralisation des fonctions cognitives, cette différence se révèle aujourd'hui davantage liée au fonctionnement des réseaux neuronaux.

Effects of Exemestane and Tamoxifen Treatment on Bone Texture Analysis Assessed by TBS in Comparison With Bone Mineral Density Assessed by DXA in Women With Breast Cancer.

We performed an analysis of a substudy of the randomized Tamoxifen Exemestane Adjuvant Multinational trial to determine the effects of exemestane (EXE) and tamoxifen (TAM) adjuvant treatment on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry compared with the trabecular bone score, a novel grey-level texture measurement that correlates with 3-dimensional parameters of bone texture in postmenopausal women with hormone receptor-positive breast cancer for the first time. In total, 36 women were randomized to receive TAM (n = 17) or EXE (n = 19). Patients receiving TAM showed a mean increase of BMD in lumbar spine from baseline of 1.0%, 1.5%, and 1.9% and in trabecular bone score of 2.2%, 3.5%, and 3.3% at 6-, 12-, and 24-mo treatment, respectively. Conversely, patients receiving EXE showed a mean decrease from baseline in lumbar spine BMD of -2.3%, -3.6%, and -5.3% and in trabecular bone score of -0.9%, -1.7%, and -2.3% at 6-, 12-, and 24-mo treatment, respectively. Changes in trabecular bone score from baseline at spine were also significantly different between EXE and TAM: p = 0.05, 0.007, and 0.006 at 6, 12, and 24mo, respectively. TAM induced an increase in BMD and bone texture analysis, whereas EXE resulted in decreases. The results were independent from each other.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5 %. TBS decline rate increases after 65 years by 50 %. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5 %, but this rate increased after 65 years by 50 %. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.

Hospitalized women experiencing an episode of excessive oral anticoagulation had a higher bleeding risk than men.

OBJECTIVE: Overanticoagulated medical inpatients may be particularly prone to bleeding complications. Among medical inpatients with excessive oral anticoagulation (AC), we sought to identify patient and treatment factors associated with bleeding. METHODS: We prospectively identified consecutive patients receiving oral AC admitted to the medical ward of a university hospital (February-July 2006) who had at least one international normalized ratio (INR) value >3.0 during the hospital stay. We recorded patient characteristics, AC-related factors, and concomitant treatments (e.g., platelet inhibitors) that increase the bleeding risk. The outcome was overall bleeding, defined as the occurrence of major or minor bleeding during the hospital stay. We used logistic regression to explore patient and treatment factors associated with bleeding. RESULTS: Overall, 145 inpatients with excessive oral AC comprised our study sample. Atrial fibrillation (59%) and venous thromboembolism (28%) were the most common indications for AC. Twelve patients (8.3%) experienced a bleeding event. Of these, 8 had major bleeding. Women had a somewhat higher risk of major bleeding than men (12.5% vs 4.1%, p = 0.08). Multivariable analysis demonstrated that female gender was independently associated with bleeding (odds ratio [OR] 4.3, 95% confidence interval [95% C1] 1.1-17.8). Age, history of major bleeding, value of the index INR, and concomitant treatment with platelet inhibitors were not independent predictors of bleeding. CONCLUSIONS: We found that hospitalized women experiencing an episode of excessive oral AC have a 4-fold increased risk of bleeding compared with men. Whether overanticoagulated women require more aggressive measures of AC reversal must be examined in further studies.

High prevalence of osteoporosis in Swiss women aged 60 and older: a 2-year pilot screening campaign.

Background: Osteoporosis (OP) is frequent in postmenopausal women, but remains underdiagnosed and undertreated. In Switzerland, DXA is not reimbursed by the insurances for screening, even if it is recommended to test women's Bone Mineral Density (BMD) at the age of 65. Methods: To assess the feasibility of a screening program for OP, the Bone diseases center of Lausanne has been mandated to perform a 2-year information and screening campaign (3 days per months) for women age 60 and older through the state of Vaud using a mobile unit for bone assessment. This project is still ongoing. Women are informed by media for dates and screening locations. Appointments are taken by phone. Women known for osteoporosis or already treated are excluded. During the evaluation every women is assessed by a questionnaire for risk factors, by a DXA measurement (Discovery C, Hololgic), and by Vertebral Fracture Assessment (VFA) for Genant's grades 2 and 3 prevalent vertebral fractures (VF). Women are considered at high risk of fracture if they have a hip fracture, a VF, another fragility fracture with a BMD T-score ≤-2 or a BMD T-score ≤-2.5. Results: After 17 months (50 days of screening), 752 women were assessed, mean age 66±6 yrs, mean BMI 26±5 kg/m2, mean lowest T-score -1.6±1.0 SD. 215 women (29%) were considered at high risk, 92 of them (12%) having established OP and 50 (7%) having one or more fragility VF. VF were unknown for 83% of the women and discovered by VFA. The number needed to screen (NNS) were 3.5 for high risk women, 8.2 for established OP and 15 for VF. Conclusions: After near ¾ of the project, prevalence of women at high risk of fracture was high, with a NNS below 4. Knowing the global cost of OP and that current treatment have a high efficacy for fracture risk reduction, such a screening program could have a positive economic impact. VFA allowed discovering many women with unknown VF, who were at very high risk of further fractures. A systematic screening for VF should be added to BMD measurements after the age of 60.

Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.