Selección de Resúmenes de Menopausia

Semana del 4 al 10 de Marzo de 2009

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

 

 

 

Gynecol Endocrinol. 2009 Feb;25(2):130-5

Quality of life impairment during the female menopausal transition is related to personal and partner factors.

Chedraui P, San Miguel G, Avila C.

Collaborative Group for Research of the Climacteric in Latin America (REDLINC, Ecuador Group 1), Guayaquil, Ecuador. institutochedraui@gmail.com

OBJECTIVE: To assess the female quality of life (QoL) during the menopausal transition and determine factors (personal and partner) related to its impairment. The frequency of menopausal symptoms was also assessed. METHODS: In this cross-sectional study, healthy women aged 40-59 years were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire assessing personal and partner demographic data. RESULTS: During the study period, a total of 409 women were surveyed. Mean age was 47 +/- 5.3 years (median 46). Mean educational level was 13.2 +/- 4.1 years (median 14), with 28.1% having 12 or less years of schooling; premenopausal (42.1%), perimenopausal (24.4%) and postmenopausal (33.5%). At the time of the survey, 9.8% were receiving hormonal therapy (HT) for the menopause, 1.5% were on psychotropic drugs and 1.2% on alternative treatments for the menopausal. Regarding partner profile, 10.3% had erectile dysfunction, 11.2% had precocious ejaculation and 7.3% had abused alcohol. Mean total MRS score was 9.1 +/- 6.4 (median 9); for the somatic subscale, 4 +/- 2.7; the psychological subscale, 3 +/- 2.8 and the urogenital subscale, 2.1 +/- 2.5. Of the surveyed women, 50.6% presented a total MRS scoring of 9 or more (moderate to severe intensity). The four most frequently found symptoms of those composing the MRS were hot flushes (68.9%), sleeping problems (68.4%), depressive mood (55.2%) and irritability (51.6%). After adjusting for confounding factors, logistic regression analysis determined that female age, menopause and partner precocious ejaculation increased the risk for presenting higher total MRS scores (impaired female QoL) whereas HT use, church assistance and partner faithfulness decreased this risk. CONCLUSIONS: A high rate of middle-aged women in this series presented impaired QoL associated to female age and hormonal status and additionally to partner's health and sexual behavior.

 

 

Eur Heart J. 2009 Feb 26. [Epub ahead of print

Effect of hormone replacement therapy on vasomotor function of the coronary microcirculation in post-menopausal women with medically treated cardiovascular risk factors.

Schindler TH, Campisi R, Dorsey D, Prior JO, Olschewski M, Sayre J, Schelbert HR.

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Ave, 23-120 CHS, Box 173517, Los Angeles, CA 90095-1735, USA.

Aims The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on coronary vasomotor function in post-menopausal women (PM) with medically treated cardiovascular risk factors (RFs) in a cross-sectional and a longitudinal follow-up (FU) study. Methods and results Myocardial blood flow (MBF) response to cold pressor testing (CPT) and during pharmacologically induced hyperaemia was measured with positron emission tomography in pre-menopausal women (CON), in PM with HRT and without HRT, and repeated in PM after a mean FU of 24 +/- 14 months. When compared with CON at baseline, the endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in PM with HRT and without HRT (0.35 +/- 0.23 vs. 0.24 +/- 0.20 and 0.16 +/- 0.12 mL/g/min; P = 0.171 and P = 0.021). In PM without HRT and in those with HRT at baseline but with discontinuation of HRT during FU, the endothelium-related DeltaMBF to CPT was significantly less at FU than at baseline (0.05 +/- 0.19 vs. 0.16 +/- 0.12 and -0.03 +/- 0.14 vs. 0.25 +/- 0.18 mL/g/min; P = 0.023 and P = 0.001), whereas no significant change was observed in PM with HRT (0.19 +/- 0.22 vs. 0.23 +/- 0.22 mL/g/min; P = 0.453). Impaired hyperaemic MBFs when compared with CON were not significantly altered from those at baseline exam. Conclusion Long-term administration of oestrogen may contribute to maintain endothelium-dependent coronary function in PM with medically treated cardiovascular RFs.

 

 

Menopause. 2009 Feb 26. [Epub ahead of print

Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy.

Freedman M, Kaunitz AM, Reape KZ, Hait H, Shu H.

From the 1Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, GA; 2Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL; and 3Duramed Research, Inc., Bala Cynwyd, PA.

OBJECTIVE:: The aim of this study was to evaluate low-dose synthetic conjugated estrogens A (SCE-A) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy (VVA) in a symptomatic postmenopausal population. METHODS:: In a multicenter, double-blind, randomized, placebo-controlled study, 305 women with symptoms of VVA were treated with either 1 g SCE-A cream (n = 150) or matching placebo (n = 155) for a period of up to 12 weeks. Participants had to have a vaginal pH of greater than 5, less than or equal to 5% superficial cells on a vaginal smear, and at least one of five symptoms of VVA (dryness, soreness, irritation, pain with intercourse, and bleeding after intercourse) that was moderate or severe in intensity. Women had to select one moderate or severe symptom as the most bothersome. RESULTS:: Efficacy was assessed at 2, 3, 4, 8, and 12 weeks and included the change from baseline in the severity of the most bothersome symptom (MBS), maturation index, and pH. Most women identified vaginal dryness as the MBS (48%) followed by pain with intercourse (31.3%). A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo. CONCLUSIONS:: A low dose (1 g = 0.625 mg) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three coprimary efficacy measures of maturation index, pH, and severity of the MBS.

 

 

Maturitas. 2009 Feb 26. [Epub ahead of print

Safety of testosterone use in women.

Shufelt CL, Braunstein GD.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Female sexual desire appears to be in part androgen dependent, which has lead to the use of testosterone in women for low libido. Despite this benefit, the long-term safety of testosterone as a hormone replacement or therapy has not been well established. Side effects of testosterone therapy include mild and reversible acne and hirsuitism, as well as changes to the lipid profile with oral, but not transdermal testosterone. Short-term studies, up to 2 years, have shown that for serum plasma testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women, testosterone does not increase the risk of hepatotoxicity, endometrial hyperplasia, or behavioral hostility. No adverse cardiovascular effects including changes in blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, and polycythemia have been shown. Data is mixed with outcomes of breast cancer risk, with some experimental studies suggesting a decrease in estrogen-induced breast epithelial proliferation with low dose testosterone. Additionally, models of superphysiologic testosterone levels, such as polycystic ovarian disease, have not shown an increased risk of breast cancer. As with all hormone therapy in postmenopausal women, testosterone therapy should be individualized and requires that each woman weigh the risk and benefits. Nevertheless, only long-term safety studies will provide conclusive evidence as to testosterone safety in women.

 

 

Osteoporos Int. 2009 Mar 6. [Epub ahead of print

Comparative gastrointestinal safety of weekly oral bisphosphonates.

Cadarette SM, Katz JN, Brookhart MA, Stürmer T, Stedman MR, Levin R, Solomon DH.

Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, s.cadarette@utoronto.ca.

Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. INTRODUCTION: Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. METHODS: We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. RESULTS: A total of 10,420 new users were studied, mean age = 79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. CONCLUSIONS: We found no important difference in gastrointestinal safety between weekly oral bisphosphonates.

 

 

Menopause. 2009 Mar 4. [Epub ahead of print

Mammary gland and endometrial effects of testosterone in combination with oral estradiol and progesterone.

Wood CE, Lees CJ, Cline JM.

OBJECTIVE:: The goal of this pilot study was to evaluate the effects of testosterone (T) cotherapy on mammary gland and endometrial measures in a postmenopausal primate model. METHODS:: Twenty-five surgically postmenopausal cynomolgus monkeys were randomized by social group to receive daily treatment with (1) placebo, (2) oral micronized 17beta-estradiol (1 mg/d equivalent in women) + progesterone (200 mg/d equivalent in women) (E + P), or (3) E + P with T administered via subcutaneous pellets for 8 weeks at a high dose (15 mg) followed by 8 weeks at a low dose (1.5 mg) (E + P + T). The main outcome measures were breast and endometrial epithelial proliferation, as measured by Ki67/MIB1 immunolabeling. RESULTS:: Intralobular breast proliferation did not differ significantly among groups after 8 weeks of treatment but was marginally higher (P = 0.03) in the E + P + T group after 16 weeks of treatment. No significant increase in proliferation was seen for E + P alone. Comparable changes in mammary gland markers of estrogen-receptor activity were seen for the E + P and E + P + T groups. In the endometrium, the addition of T did not increase endometrial glandular proliferation or estrogen-receptor activity or result in any distinct histologic changes. CONCLUSIONS:: The findings of this study do not support the idea that T antagonizes the effects of combined hormone therapy on breast proliferation or markers of estrogen-receptor activity. Overall, the short-term effects of T cotherapy on the mammary gland and endometrium were minimal.

 

 

Immun Ageing. 2009 Mar 5;6(1):1. [Epub ahead of print

Alterations of T cell activation signalling and cytokine production by postmenopausal estrogen levels.

Ku LT, Gercel-Taylor C, Nakajima ST, Taylor DD.

ABSTRACT: BACKGROUND: Immunosenescence is an age-associated disorder occurring primarily in T cell compartments, including altered subset composition, functions, and activation. In women, evidence implicates diminished estrogen in the postmenopausal period as a contributing factor to diminished T cell responsiveness. Since hypoestrogenism is present in postmenopausal women, our objective focused on whether T cell activation, defined as signalling molecule expressions and activation, and function, identified as IL-2 production, were affected by low estrogen. METHODS: Using Jurkat 6.1 T cells, consequences of 4pg/ml (corresponding to postmenopausal levels) or 40pg/ml (premenopausal levels) of estradiol (E2) were analyzed on signalling proteins, CD3-zeta, JAK2, and JAK3, determined by Western immunoblotting. These consequences were correlated with corresponding gene expressions, quantified by real time-polymerase chain reaction. Tyrosine phosphorylation of CD3-zeta was defined by immunoprecipitation and western immunoblotting following activation by T cell receptor (TcR) cross-linking. CD3-zeta expression and modulation was also confirmed in T cells from pre- and postmenopausal women. To assess functional consequences, IL-2 production, induced by PMA and ionomycin, was determined using enzyme-linked immunosorbent spot assay (ELISpot). RESULTS: At 40pg/ml E2, the level of signalling protein CD3-zeta was elevated 1.57-fold, compared with cells exposed to 4pg/ml E2. The CD3-zeta proteins also exhibited altered levels of activation-induced phosphorylation in the presence of 40pg/ml E2 versus 4pg/ml: 23kD phosphorylated form increased 2.64-fold and the 21kD form was elevated 2.95-fold. Examination of kinases associated with activation signalling also demonstrated that, in the presence of 40pg/ml E2, JAK2 protein expression was increased 1.64-fold (p<0.001) and JAK3 enhanced 1.79-fold (p<0.001) compared to 4pg/ml. mRNA levels for CD3-zeta, JAK2, and JAK3 were significantly increased following exposure to 40pg/ml E2 (2.39, 2.01, and 2.21 fold, respectively) versus 4pg/ml. These findings were confirmed in vivo, since T cells from postmenopausal women exhibited 7.2-fold diminished CD3-zeta expression, compared to pre-menopausal controls and this expression was elevated 3.8-fold by addition of 40pg/ml E2. Functionally, Jurkat cells exposed to 40pg/ml E2 and activated exhibited significantly elevated numbers of IL-2 producing colonies compared to 4pg/ml (75.3+/-2.2 versus 55.7+/-2.1 colonies, p<0.0001). CONCLUSIONS: Jurkat T cells exposed to 4pg/ml E2 expressed significantly diminished activation signalling proteins, correlating with reduced IL-2 production. Lower signalling protein levels appear to result from decreased CD3-zeta, JAK2, and JAK3 gene expressions. These findings may provide a molecular basis for immunosenescence associated with the postmenopausal state.

 

 

Bone. 2009 Feb 27. [Epub ahead of print

Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX((R)).

Kanis JA, Johansson H, Oden A, McCloskey EV.

WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.

Introduction Bazedoxifene has been shown to significantly decrease the risk of vertebral fractures in postmenopausal women. No significant effect was noted on the risk of clinical fractures, but fracture risk reduction was reported in a post hoc subgroup analysis in a high risk group categorised on the basis of BMD and prior fracture. Aims The aim of this study was to re-evaluate the efficacy of bazedoxifene on fracture outcomes avoiding subgroup analysis by examining the efficacy of intervention as a function of fracture risk. Methods The phase III study was a doubleblind, randomized, placebo and raloxifenecontrolled randomised 3-year multinational study that enrolled 7492 osteoporotic women aged 55 years or more (mean age= 66 years). For the present analysis, women taking raloxifene were excluded (n=1849), and we compared the effects of two doses of bazedoxifene (20 and 40 mg daily combined) with placebo on the risk of all clinical fractures as well as the risk of morphometric vertebral fracture. The risk of a major osteoporotic fracture was assessed using region specific FRAX((R)) algorithms, and the relationship between pre hoc 10 year fracture probabilities and efficacy examined by Poisson regression. Results Overall, bazedoxifene was associated with a significant 39% decrease in incident morphometric vertebral fractures (hazard ratio HR= 0.61; 95% CI= 0.43-0.86; p= 0.005) and a non-statistically significant 16% decrease in all clinical fractures (hazard ratio HR= 0.84; 95% CI= 0.67-1.06; p= 0.14) compared to placebo. Hazard ratios for the effect of bazedoxifene on all clinical fractures decreased with increasing fracture probability. In patients with 10-year fracture probabilities at or above 16%, bazedoxifene was associated with a significant decrease in the risk of all clinical fractures. The 16% probability threshold corresponded to the 80(th) percentile of the study population. Hazard ratios for the effect of bazedoxifene on morphometric vertebral fractures also decreased with increasing fracture probability. In patients with 10-year fracture probabilities above 6.9% (corresponding to the 41(st) percentile), bazedoxifene was associated with a significant decrease in the risk of morphometric vertebral fractures. At equivalent fracture probability percentiles, the treatment effect of bazedoxifene was greater on vertebral fracture risk than on the risk of all clinical fractures. For example, at the 90(th) percentile of FRAX((R)) probability, bazedoxifene was associated with a relative risk reduction of 33% (95% CI= 7-51%) for all clinical fractures and 51% reduction (95% CI= 21-69%) for morphometric vertebral fractures. The findings were robust to several sensitivity analyses. Conclusion Bazedoxifene (20 and 40 mg doses combined) significantly decreased the risk of all clinical fractures and morphometric vertebral fractures in women at or above a FRAX( based fracture probability threshold. These results, consistent with the previous sub group analysis, suggest that bazedoxifene should be targeted prefentially to women at high fracture risk.

 

 

 

Selección de Resúmenes de Menopausia

                                                      Semana del 11 al 17 de Marzo de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

 

 

 

J Natl Cancer Inst. 2009 Mar 10. [Epub ahead of print

Prevention of Breast Cancer in Postmenopausal Women: Approaches to Estimating and Reducing Risk.

Cummings SR, Tice JA, Bauer S, Browner WS, Cuzick J, Ziv E, et al.

Background It is uncertain whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk. Methods We systematically reviewed prospective studies about models and sex hormone levels to assess breast cancer risk and used meta-analysis with random effects models to summarize the predictive accuracy of breast density. We also reviewed prospective studies of the effects of exercise, weight management, healthy diet, moderate alcohol consumption, and fruit and vegetable intake on breast cancer risk, and used random effects models for a meta-analyses of tamoxifen and raloxifene for primary prevention of breast cancer. All studies reviewed were published before June 2008, and all statistical tests were two-sided. Results Risk models that are based on demographic characteristics and medical history had modest discriminatory accuracy for estimating breast cancer risk (c-statistics range = 0.58-0.63). Breast density was strongly associated with breast cancer (relative risk [RR] = 4.03, 95% confidence interval [CI] = 3.10 to 5.26, for Breast Imaging Reporting and Data System category IV vs category I; RR = 4.20, 95% CI = 3.61 to 4.89, for >75% vs <5% of dense area), and adding breast density to models improved discriminatory accuracy (c-statistics range = 0.63-0.66). Estradiol was also associated with breast cancer (RR range = 2.0-2.9, comparing the highest vs lowest quintile of estradiol, P < .01). Most studies found that exercise, weight reduction, low-fat diet, and reduced alcohol intake were associated with a decreased risk of breast cancer. Tamoxifen and raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer and invasive breast cancer overall. Conclusions Evidence from this study supports screening for breast cancer risk in all postmenopausal women by use of risk factors and breast density and considering chemoprevention for those found to be at high risk. Several lifestyle changes with the potential to prevent breast cancer should be recommended regardless of risk.

 

 

Arch Neurol. 2009 Mar;66(3):324-8

The metabolic syndrome and development of cognitive impairment among older women.

Yaffe K, Weston AL, Blackwell T, Krueger KA.

Department of Psychiatry, University of California, San Francisco, the San Francisco Veterans' Affairs Medical Center, 94121, USA. Kristine.yaffe@ucsf.edu

BACKGROUND: Several studies support a role for cardiovascular risk factors in cognitive aging. The metabolic syndrome, a constellation of cardiovascular risk factors, is common in elderly people. A growing but conflicting body of literature suggests that the metabolic syndrome may be associated with cognitive impairment. OBJECTIVE: To investigate the association between the metabolic syndrome and its components and incident cognitive impairment in older women. DESIGN: We prospectively determined if the metabolic syndrome and its components were associated with a 4-year risk of developing cognitive impairment (dementia, mild cognitive impairment, or low global cognitive test score). SETTING: The study was conducted at 180 clinical centers in 25 countries. PARTICIPANTS: A total of 4895 older women (mean age, 66.2 years) with osteoporosis who were part of an ancillary study to determine clinically relevant cognitive impairment were included in this study. These women were free of baseline cognitive impairment and had metabolic syndrome component measures. MAIN OUTCOME MEASURES: Clinically significant cognitive impairment was defined to include women with clinically adjudicated dementia or MCI and women who had a Short Blessed test score greater than 6 (consistent with impairment), but whose cases were not clinically adjudicated. Logistic regression analysis was used to examine the association between presence of the metabolic syndrome and development of clinically significant cognitive impairment. RESULTS: A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41). The mean (SD) number of metabolic syndrome components for all women was 1.0 (1.1); 518 women (10.6%) were obese, 895 (18.3%) had hypertriglyceridemia, 1200 (24.5%) had low high-density lipoprotein cholesterol levels, 1944 (39.7%) had high blood pressure, and 381 (7.8%) had high fasting blood glucose levels. There was a 23.0% age-adjusted increase in the risk of developing cognitive impairment (odds ratio, 1.23; 95% confidence interval, 1.09-1.39) per unit increase in the number of components. Further multivariable adjustment somewhat reduced the effect. CONCLUSION: We found an association between the metabolic syndrome and the number of components and risk of developing cognitive impairment in older women. Additional studies are needed to determine if screening and close management of these at-risk elderly women would diminish the incidence of cognitive impairment.

 

 

J Gen Intern Med. 2009 Mar 11. [Epub ahead of print]

Obesity and Mammography: A Systematic Review and Meta-Analysis.

Maruthur NM, Bolen S, Brancati FL, Clark JM.

Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, USA.

BACKGROUND: Obese women experience higher postmenopausal breast cancer risk, morbidity, and mortality and may be less likely to undergo mammography. OBJECTIVES: To quantify the relationship between body weight and mammography in white and black women. DATA SOURCES AND REVIEW METHODS: We identified original articles evaluating the relationship between weight and mammography in the United States through electronic and manual searching using terms for breast cancer screening, breast cancer, and body weight. We excluded studies in special populations (e.g., HIV-positive patients) or not written in English. Citations and abstracts were reviewed independently. We abstracted data sequentially and quality information independently. RESULTS: Of 5,047 citations, we included 17 studies in our systematic review. Sixteen studies used self-reported body mass index (BMI) and excluded women <40 years of age. Using random-effects models for the six nationally representative studies using standard BMI categories, the combined odds ratios (95% CI) for mammography in the past 2 years were 1.01 (0.95 to 1.08), 0.93 (0.83 to 1.05), 0.90 (0.78 to 1.04), and 0.79 (0.68 to 0.92) for overweight (25-29.9 kg/m(2)), class I (30-34.9 kg/m(2)), class II (35-39.9 kg/m(2)), and class III (>/=40 kg/m(2)) obese women, respectively, compared to normal-weight women. Results were consistent when all available studies were included. The inverse association was found in white, but not black, women in the three studies with results stratified by race. CONCLUSIONS: Morbidly obese women are significantly less likely to report recent mammography. This relationship appears stronger in white women. Lower screening rates may partly explain the higher breast cancer mortality in morbidly obese women.

 

 

Osteoporos Int. 2009 Mar 7. [Epub ahead of print

Weight loss and distal forearm fractures in postmenopausal women : The Nord-Trřndelag health study, Norway.

Omsland TK, Schei B, Grřnskag AB, Langhammer A, Forsén L, Gjesdal CG, Meyer HE.

Section for Preventive Medicine and Epidemiology, Institute of General Practice and Community Medicine, University of Oslo, Oslo, Norway, t.k.omsland@medisin.uio.no.

Weight loss is a risk factor for hip fractures, but few studies have evaluated the effect of weight loss on distal forearm fracture risk. In this longitudinal study including 7,871 postmenopausal women, weight loss of 5% or more was associated with an increased risk of distal forearm fractures. INTRODUCTION: Weight loss is an established risk factor for hip fractures, but little is known about weight loss and distal forearm fractures risk. METHODS: The study included 7,871 women aged 65 years or more in the Nord-Trřndelag health study (HUNT) in 1994-1995 (HUNT II) who also had their height and weight measured in 1984-1986 (HUNT I). Forearm bone mineral density (BMD) by single energy x-ray absorptiometry was available for 5,688 women (HUNT II). Fractures sustained after HUNT II were registered during an average of 5.8 years. RESULTS: A total of 536 women sustained a distal forearm fracture. After adjustments for age and body mass index (BMI) at HUNT I, women who lost >/=5% of their weight between HUNT I and HUNT II had a relative risk of fractures of 1.33 (95% confidence interval: 1.09, 1.62) compared with the rest of the women. The higher risk of forearm fracture among women with weight loss was at least partially explained by their lower forearm BMD. CONCLUSION: Weight loss of 5% or more was associated with a 33% increased risk of distal forearm fractures.

 

 

Calcif Tissue Int. 2009 Mar 11. [Epub ahead of print

Addition of Aerobic Exercise to a Weight Loss Program Increases BMD, with an Associated Reduction in Inflammation in Overweight Postmenopausal Women.

Silverman NE, Nicklas BJ, Ryan AS.

University of Maryland School of Medicine and the Geriatric Research, Education and Clinical Center of the Baltimore Veterans Affairs Medical Center, GRECC (BT/18/GR), 10 North Greene Street, Baltimore, MD, 21201-1524, USA, nsilverm@grecc.umaryland.edu.

Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50-70 years of age; BMI, 25-40 kg/m(2)) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-alpha, soluble receptors of IL-6, and TNF-alpha (sTNFR1 and sTNFR2; receptors in a subset of the population), VO(2) max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO(2) max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO(2) max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.

 

 

Menopause. 2009 Mar 6. [Epub ahead of print]

Memory complaints and memory performance in the menopausal transition.

Weber M, Mapstone M.

From the Departments of 1Physical Medicine and Rehabilitation and 2Neurology, The University of Rochester Medical Center, Rochester, NY.

OBJECTIVE:: The aim of this study was to examine the relationship between perimenopausal memory complaints and performance on objective neuropsychological tests. A secondary aim was to determine if putative deficits are related to other relevant factors, such as hormone levels, mood state, or sleep quality. METHODS:: Twenty-four perimenopausal women were enrolled. Participants completed questionnaires assessing mood, anxiety, menopausal symptoms, health, and subjective memory function. They also underwent comprehensive cognitive testing, which included measures of attention, working memory, verbal memory, verbal fluency, visuospatial skill, and fine motor dexterity. We obtained serum estradiol and follicle-stimulating hormone levels on the day of testing. RESULTS:: We found no association between memory complaints and performance on tests of retentive memory. However, memory complaints were associated with poorer memory encoding and increased depressive symptoms. Regression analyses revealed that memory complaints were best predicted by depressive symptoms, whereas encoding performance was predicted by depressive symptoms and estrogen level. Women with significant memory complaints performed worse on tests of encoding, after controlling for depression and sleep disturbance. CONCLUSIONS:: These results suggest a complex relationship between mood, memory, and hormones that may underlie perimenopausal memory complaints. Furthermore, they suggest that some women may be particularly vulnerable to the subjective experience of memory problems and relative decreases in attentionally mediated cognitive function.

 

 

Menopause. 2009 Mar 6. [Epub ahead of print

Association between serum 25-hydroxyvitamin D levels and body composition in postmenopausal women: the Postmenopausal Health Study.

Moschonis G, Tanagra S, Koutsikas K, Nikolaidou A, Androutsos O, Manios Y.

From the Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.

OBJECTIVE:: The present study examined the association between body composition measurements, using dual-energy x-ray absorptiometry and anthropometry, with serum 25-hydroxyvitamin D levels in nonosteoporotic, postmenopausal women. METHODS:: Serum 25-hydroxyvitamin D, intact parathyroid hormone, insulin-like growth factor I levels, dual-energy x-ray absorptiometry measurements of fat and fat-free mass, anthropometric and handgrip strength measurements, dietary intake estimations, ultraviolet B radiation exposure, and physical activity levels were collected from 112 nonosteoporotic, postmenopausal women (age, 60.3 +/- 5.0 y; body mass index, 29.5 +/- 4.8 kg/m). RESULTS:: At a bivariate level, serum 25-hydroxyvitamin D levels were inversely associated with regional and total body fat mass (P < 0.05), whereas positive associations were observed with regional and total body fat-free mass (P < 0.05). After controlling for age, serum intact parathyroid hormone, insulin-like growth factor I levels, ultraviolet B radiation exposure, and physical activity levels, most of the associations observed at a bivariate level between serum 25-hydroxyvitamin D levels and body composition indices (as obtained by dual-energy x-ray absorptiometry) remained significant. No significant associations were observed between anthropometric indices of body mass and serum 25-hydroxyvitamin D levels. CONCLUSIONS:: An independent inverse association between serum 25-hydroxyvitamin D levels and dual-energy x-ray absorptiometry measurements of total body and regional fat mass was observed in nonosteoporotic, overweight, postmenopausal women. Further clinical trials are required to come to safe conclusions on whether it is the fat mass that affects serum 25-hydroxyvitamin D levels or vice versa and whether there is a need to also take into account body composition when providing recommendations for vitamin D intake in postmenopausal women.

 

 

Lupus. 2009;18(4):313-7

Hormone replacement therapy in women with systemic lupus erythematosus and risk of cardiovascular disease.

Hochman J, Urowitz M, Ibańez D, Gladman D.

University of Toronto Lupus Clinic, Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.

We sought to determine the impact of hormone replacement therapy (HRT) on the occurrence of coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE). Women in the University of Toronto lupus database who had taken HRT with no history of CAD were compared with all post-menopausal female patients with no history of HRT or CAD. Chi-squared and t-tests were used to compare the risk factors of CAD and Kaplan-Meier curve, log rank test and proportional hazard model with time-dependent covariates were used to compare the time from entry into the clinic to occurrence of CAD. A total of 114 HRT-user patients with no history of CAD were compared with 227 post-menopausal non-HRT user SLE controls. The groups were similar with respect to lupus anticoagulant, antiphospholipid antibody, cumulative steroid dose and classic cardiac risk factors. A similar percentage of patients developed CAD in the control (13.7%) and HRT (11.4%) groups. There was no difference in the time to development of CAD. In the multivariate analysis, HRT was not a risk factor for CAD. Only age (P = 0.0001, HR = 1.11, 95% CI = 1.05, 1.17) and SLEDAI-2K (P = 0.0001, HR = 1.10, 95% CI = 1.05, 1.16) were significantly associated with the risk of CAD. In this small group of patients with SLE, HRT alone did not appear to predispose to CAD.

 

 

Selección de Resúmenes de Menopausia

                                                      Semana del 18 al 24 de Marzo de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

 

 

 

 

Osteoporos Int. 2009 Mar 20. [Epub ahead of print

Chronic obstructive pulmonary disease is associated with osteoporosis and low levels of vitamin D.

Franco CB, Paz-Filho G, Gomes PE, Nascimento VB, Kulak CA, Boguszewski CL, Borba VZ.

Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná (SEMPR), Rua. Agostinho Leăo Junior, 285, Curitiba, Brazil, CEP: 80030-110.

We did a cross-sectional analysis of chronic pulmonary obstructive disease (COPD) patients without chronic use of systemic glucocorticoids (CUG). Osteoporosis was found in 51% and bone mineral density (BMD) was correlated with severity of disease. Low levels of vitamin D were found in 94%. All COPD patients may benefit from vitamin D supplementation and screening for low BMD. INTRODUCTION: Patients with chronic pulmonary obstructive disease have low bone mineral density, caused by chronic use of systemic glucocorticoids and hypovitaminosis D. However, patients without CUG may also have low BMD. METHODS: We performed a cross-sectional analysis in 49 patients (21 men, 28 postmenopausal women), with COPD without CUG, from Brazil (25 degrees 25' S). Several markers of bone metabolism were measured, plus BMD. Osteoporosis risk factors and history of fractures were investigated. Respiratory function was assessed by venous gasometry, spirometry, and oximetry. BMD results were compared to those of 40 healthy non-smokers controls. RESULTS: COPD patients had lower BMD at all sites (p < 0.01). Osteoporosis was observed in 51%. BMD independently correlated with stage of disease (lumbar spine, R = 0.38, p = 0.01; total femur, R = 0.36, p = 0.01; femoral neck, R = 0.40, p < 0.01). Ninety-four percent had low levels of vitamin D (<30 ng/mL) and 67% had secondary hyperparathyroidism. Vitamin D was correlated with oxygen saturation (R = 0.36, p = 0.01), with lower levels in those with saturation <88% (p = 0.01). CONCLUSION: Patients with COPD without CUG have increased risk for osteoporosis. Such patients have hypovitaminosis D, which is correlated with the severity of disease. Screening for low BMD and vitamin D supplementation may be warranted to all COPD patients.

 

 

Curr Opin Endocrinol Diabetes Obes. 2009 Apr;16(2):125-31

Bone metabolism in type 2 diabetes and role of thiazolidinediones.

Vestergaard P.

Department of Endocrinology and Metabolism C, Aarhus University Hospital, Aarhus Amtssygehus, Aarhus, Denmark. p-vest@post4.tele.dk

PURPOSE OF REVIEW: To assess bone turnover both at the biochemical and organ level in patients with type 2 diabetes (T2D) and the effects of the thiazolidinediones. RECENT FINDINGS: Studies have shown a decreased bone formation and an increased risk of fractures in patients with T2D. Changes in bone strength from glycation of collagen and negative calcium balance from calcium loss in the urine due to hyperglycaemia may also be seen. The thiazolidinediones affect bone turnover by increasing the formation of adipocytes instead of the bone-forming osteoblasts from the common mesenchymal stem cell. A decreased bone formation with decreased bone density and an increased risk of fractures has been observed among users of thiazolidinediones. Differences exist between type 1 diabetes (T1D) and T2D with a much higher increase in the risk of hip fractures in T1D than in T2D compared with the general population. The often higher body mass index in T2D than in T1D appears to explain some of the differences in risk of fractures. SUMMARY: Diabetes is a hitherto overlooked risk factor for osteoporosis and fractures. Thiazolidinediones may increase risk of fractures and should not be used by patients at risk of fractures. More research is needed.

 

 

Clin Breast Cancer. 2009 Feb;9(1):45-50.

Incidence of invasive breast cancer in postmenopausal women after discontinuation of long-term raloxifene administration.

Vogel VG, Qu Y, Wong M, Mitchell B, Mershon JL.

Department of Research, American Cancer Society.

Background: Postmenopausal women with osteoporosis had a 66% relative risk reduction for invasive breast cancer over 8 years of raloxifene therapy in the randomized, placebo-controlled 4-year MORE (Multiple Outcomes of Raloxifene Evaluation) trial and the CORE (Continuing Outcomes Relevant to Evista) trial, a 4-year follow-up to MORE. Patients and Methods: The first post hoc analysis examined the effects of raloxifene on the cumulative incidence of invasive breast cancer on a yearly basis. Another analysis compared the incidence of invasive breast cancer in 3967 patients who continued raloxifene for 8 years (RLX-C, n = 2280), discontinued raloxifene after 4 years in MORE (RLX-D, n = 401), or took placebo (n = 1286) for a mean 2.9 years' treatment duration (57,338 patient-years). Results: The unadjusted breast cancer incidence rate was 5.39 per 1000 patient-years in the placebo group compared with 2.26 in the RLX-C group (hazard ratio [HR], 0.41 [95% CI 0.21-0.81]) and 3.59 in the RLX-D group (HR, 0.69 [95% CI 0.23-2.01]). Because the choice of taking the study drug was not randomized in CORE, propensity scores were used to adjust for potential imbalances in baseline characteristics before CORE. Results after adjustment by the propensity score method were similar to the unadjusted results. Conclusion: This analysis suggests a persistent effect for breast cancer risk reduction in patients who discontinued raloxifene, although this conclusion is limited by the small sample size.

 

 

Joint Bone Spine. 2009 Mar 16. [Epub ahead of print

Prevalence and features of osteoporosis in the French general population: The Instant study.

Lespessailles E, Cotté FE, Roux C, Fardellone P, Mercier F, Gaudin AF.

Rheumatology Department, Orléans University Hospital, 45000 Orléans, France.

OBJECTIVES: To determine the prevalence of diagnosed osteoporosis, the extent of treatment use and the incidence of fracture in a representative sample of the French general population. METHODS: A cross-sectional epidemiological survey of osteoporosis in 2613 women over 45 years in the general population was conducted using a stratified random sampling method and face-to-face interviews. Information was collected on the diagnosis of osteoporosis, fracture history, treatments, clinical and sociodemographic variables. Variables potentially associated with fracture were evaluated using stepwise multivariate logistic regression analysis. RESULTS: The overall prevalence of diagnosed osteoporosis was 9.7% [8.6%; 10.9%] and prevalence increased linearly with age. Overall, 155 women (61.0%) received osteoporosis treatment and treatment rates also increased with age. The most frequently prescribed treatments were bisphosphonates, in 50.3% of treated women. The treatment duration was over 2 years for 72.9% of treated women. Overall, 115 (45.3%) reported at least one previous fracture. Vertebral fractures were reported by 101 women (39.8%) and limb fractures by 41 women (16.1%). Multivariate logistic regression analysis identified fracture before the age of 40, menopause before the age of 40, use of sleeping pills, consultation with an eye specialist and history of cardiovascular disease as variables independently associated with fracture. CONCLUSIONS: Osteoporosis in France appears to be under-diagnosed and under-treated. Awareness and management of risk factors for osteoporosis and fracture could thus be improved.

 

 

Menopause. 2009 Mar 17. [Epub ahead of print

Newer antidepressants and gabapentin for hot flashes: a discussion of trial duration.

Loprinzi CL, Diekmann B, Novotny PJ, Stearns V, Sloan JA.

From the 1Mayo Clinic, Rochester, MN; and 2Johns Hopkins School of Medicine, Baltimore MD.

OBJECTIVE:: Information regarding the ideal length of hot flash trials is scarce. In the literature, hot flash trial durations have commonly varied from 4 to 12 weeks. This article is devoted to providing scientific data to better ascertain how long it is necessary to conduct hot flash trials with newer centrally acting agents. METHODS:: Individual participant data were collected from all known published, through December 2007, randomized, placebo-controlled, double-blinded clinical trials regarding the use of newer antidepressants and gabapentin for hot flash relief. Trials that studied periods longer than 4 weeks were included for this project. Profile analysis was applied to the hot flash activity longitudinal data for each study individually, allowing a comparison of data collected for 6 to 12 treatment weeks versus data collected for only 4 treatment weeks. RESULTS:: Ten studies were identified, five of them fulfilled the eligibility criteria for this investigation, three evaluating gabapentin, and two newer antidepressants. Flatness tests from a profile analysis did not provide any evidence that hot flash activity increased or decreased between week 4 and time periods up to 12 weeks. CONCLUSIONS:: Changes in hot flash scores from newer antidepressants and gabapentin are apparent within 4 weeks of therapy. Available data indicate that hot flash treatment efficacy, compared with that of placebo, remains stable for up to 12 weeks of follow-up.

 

 

Am J Prev Med. 2009 Apr;36(4):366-75

Screening for osteoporosis in the adult U.S. population: ACPM position statement on preventive practice.

Lim LS, Hoeksema LJ, Sherin K; ACPM Prevention Practice Committee.

Department of Internal Medicine, Griffin Hospital, Derby, Connecticut, USA. msurricchio@acpm.org

CONTEXT: Osteoporosis is a common and costly disease that is associated with high morbidity and mortality. There is a lack of direct evidence supporting the benefits of bone mineral density (BMD) screening on osteoporosis outcomes. However, there is indirect evidence to support screening for osteoporosis given the availability of medications with good antifracture efficacy. This paper addresses the position of the American College of Preventive Medicine (ACPM) on osteoporosis screening. EVIDENCE ACQUISITION: The medical literature was reviewed for studies examining the benefits and harms of osteoporosis screening. An overview is also provided of available modalities for osteoporosis screening, risk-assessment tools, cost effectiveness, benefits and harms of screening, rationale for the study, and recommendations from leading health organizations and ACPM. A review was done of English language articles published prior to September 2008 that were retrieved via search on PubMed, from references from pertinent review or landmark articles, and from websites of leading health organizations. EVIDENCE SYNTHESIS: There were no randomized controlled trials (RCTs) of osteoporosis screening on fracture outcomes. However, there was one observational study that demonstrated reduced fracture incidence among recipients of BMD testing. Dual energy x-ray absorptiometry is currently one of the most widely accepted and utilized methods for assessing BMD. Other potential tests for detecting osteoporosis include quantitative ultrasound, quantitative computer tomography, and biochemical markers of bone turnover. Testing via BMD is a cost-effective method for detecting osteoporosis in both men and women. Osteoporosis risk-assessment tools such as the WHO fracture-risk algorithm are useful supplements to BMD assessments as they provide estimates of absolute fracture risks. They can also be used with or without BMD testing to assist healthcare providers and patients in making decisions regarding osteoporosis treatments. CONCLUSIONS: All adult patients aged >or=50 years should be evaluated for risk factors for osteoporosis. Screening with BMD testing for osteoporosis is recommended in women aged >or=65 years and in men aged >or=70 years. Younger postmenopausal women and men aged 50-69 years should undergo screening if they have at least one major or two minor risk factors for osteoporosis. It is also recommended that clinicians consider using an osteoporosis risk-assessment tool to evaluate absolute fracture risk to determine appropriate osteoporosis therapies.

 

 

Selección de Resúmenes de Menopausia

                                                      Semana del 25 al 31 de Marzo de 2009

                                   Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

 

 

 

 

 

Int J Cancer. 2009 Jan 22. [Epub ahead of print

A population-based cohort study on the use of hormone treatment and endometrial cancer in southern Sweden.

Epstein E, Lindqvist PG, Olsson H.

Institute of Clinical Sciences Lund, Department of Obstetrics and Gynaecology, Lund University Hospital, University of Lund, Lund, Sweden.

Our aim was to determine the risk of endometrial cancer associated with long-term use of combined hormone therapy (HT) and low-potency estrogens. In this prospective population-based cohort, 40,000 women aged 25-64 years, without prior cancer or hysterectomy, were included. The women answered 2 questionnaires at a 10-year interval regarding HT use and personal details. Women were followed up for an average of 15.5 years through the National Cancer and Causes of Death Registry, representing 236,611 women years. Among the 17,822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. Only use of combined HT was related to a decreased risk of endometrial cancer (OR 0.3, 95% CI 0.1-0.8), the protective effect was found after 2 years, and increased with extended duration of use. "Only use" of low-potency estrogens increased the risk of endometrial cancer almost to the same extent as use of high-potency estrogens (OR 2.0, 95% CI 1.1-3.6 vs. OR 2.5, 95% CI 1.3-4.8), the increased risk was confined to non-obese women in both groups. The risk was significantly increased for oral but not for local low-potency estrogen users (OR 2.1, 95% CI 1.1-3.6 vs. OR 1.5, 95% CI 0.4-6.2, respectively). In long-term estrogen users the risk was highest during the first 2 years, dropping slightly thereafter. Since low-potency estrogen use increases the risk of endometrial cancer almost as much as high-potency estrogen use, they should only be given if medically indicated.

 

 

Menopause. 2009 Mar 26. [Epub ahead of print

Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women.

Huang AJ, Sawaya GF, Vittinghoff E, Lin F, Grady D.

Departments of Medicine, University of California, San Francisco, CA. USA.

OBJECTIVE:: The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. METHODS:: We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes "some" to "all" of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. RESULTS:: The mean age of participants was 66.7 +/- 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. CONCLUSIONS:: Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes.

 

 

Menopause. 2009 Mar 26. [Epub ahead of print

Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women.

Huang AJ, Sawaya GF, Vittinghoff E, Lin F, Grady D.

From the 1Departments of Medicine, 2Obstetrics, Gynecology, and Reproductive Sciences, and 3Epidemiology and Biostatistics, University of California, San Francisco, CA; and 4General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, San Francisco, CA.

OBJECTIVE:: The aim of this study was to examine interactions between hot flushes, estrogen plus progestogen therapy (EPT), and coronary heart disease (CHD) events in postmenopausal women with CHD. METHODS:: We analyzed data from the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled trial of 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate in 2,763 postmenopausal women with CHD. Hot flushes were assessed at baseline using self-administered questionnaires; women reporting bothersome hot flushes "some" to "all" of the time were considered to have clinically significant flushing. Cox regression models were used to examine the effect of EPT on risk of CHD events among women with and without significant flushing at baseline. RESULTS:: The mean age of participants was 66.7 +/- 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35); among women without baseline flushing, treatment did not significantly affect CHD event risk in the first year (hazard ratio = 1.32; 95% CI, 0.86-2.03; P = 0.07 for interaction of hot flushes with treatment). The trend toward differential effects of EPT on risk for CHD among women with and without baseline flushing did not persist after the first year of treatment. CONCLUSIONS:: Among older postmenopausal women with CHD, EPT may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes.

 

 

Eur J Endocrinol. 2009 Mar 25. [Epub ahead of print

Hormone therapy protects from diabetes: the Kuopio Osteoporosis Risk Factor and Prevention Study.

Pentti K, Tuppurainen M, Honkanen R, Sandini L, Kroger H, Alhava E, Saarikoski S.

K Pentti, Department of Obstetrics and Gynaecology, Kuopio University Hospital, Kuopio, Finland.

Objectives: The purpose of this population-based prospective cohort study was to examine the effect of hormone therapy (HT) on incidence of diabetes (DM). Design and Methods: 8483 DM free postmenopausal women aged 52-62 from the population-based OSTPRE-study were followed for 5 years in 1994-1999. Information about use of HT and health events was obtained from three repeated questionnaires in 1989, 1994 and 1999. DM morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Kaplan-Meyer survival curves and Cox's proportional-hazards models were used to estimate the risk of incident DM in relation to the use of HT. Results: During the follow-up, 40.8 % DM free postmenopausal women had never used HT, 27.3 % women were HT past users and 31.9 % women had used HT currently during the follow-up. During the follow-up 162 incident DM cases were recorded. Compared with never users of HT, the adjusted hazard ratio (HR) of DM was 0.81 (95% confidence interval (CI) 0.57 to 1.16) for only in the past users, 0.53 (95% CI 0.24 to 1.15) in part-time (during the follow-up <2.5 years) users and 0.31 (95% CI 0.16 to 0.60) in continuous (during the follow-up 2.5-5.0 years) users of HT. Conclusions: HT use decreases the incidence of diabetes in postmenopausal women.

 

 

Clin Endocrinol (Oxf). 2009 Mar 6. [Epub ahead of print

Increased C-reactive protein levels in overweight and obese women taking exogenous hormones: the United Kingdom Women's Heart Study (UKWHS).

Kwok S, Canoy D, Ashton WD, Lowe GD, Wood D, Humphries SE, Charlton-Menys V, Durrington PN.

Cardiovascular Research Group, University of Manchester, Manchester M13 9NT, UK.

Summary Objective: Women's cardiovascular risk factors, including inflammatory markers such as C-reactive protein (CRP) which is emerging as a major association with CVD risk, can be influenced by the oral contraceptive (OC) pill in premenopausal and hormone replacement (HR) in postmenopausal women and by central adiposity which is associated with a heightened inflammatory state. The interaction between central obesity and different hormone use in both pre- and post-menopausal women has not previously been reported in a study spanning the whole age range associated with hormone use. Design: Observational, cross-sectional study. Patients: Healthy women only. Measurements: 21,310 women aged 30-64 employed by Marks & Spencer participated. They completed a health questionnaire and were screened for cardiovascular disease (CVD) risk factors including blood pressure, weight, height, waist and hip circumference, lipids and lipoproteins, C-reactive protein (CRP) and fibrinogen. Results: Compared with non-users, women who took the OC or HR had significantly higher CRP levels. This was more marked than effects on other CVD risk factors. It was further compounded by the independent effect of increased waist circumference. The CRP increase was greatest (more than twice that of non-hormone-users) in premenopausal women with the highest quartile of waist circumference who took the combined contraceptive pill. Conclusions: Women who received first the combined OC and then HR may be exposed over much of their life to high CRP levels aggravated by central obesity. The health consequences of this require further investigation.

 

 

Med Care. 2009 Mar 23. [Epub ahead of print]

Hormone Replacement Therapy and Cardiovascular Health in the United States.

Shetty KD, Vogt WB, Bhattacharya J.

Veteran's Affairs Palo Alto, Palo Alto, California. USA

BACKGROUND:: Hormone replacement therapy (HRT) was widely used among postmenopausal women until 2002 because observational studies suggested that HRT reduced cardiovascular risk. The Womens' Health Initiative randomized trial reported opposite results in 2002, which caused HRT use to drop sharply. OBJECTIVE:: We examine the relationship between HRT use and cardiovascular outcomes (deaths and nonfatal hospitalizations) in the entire US population, which has not been studied in prior clinical trials or observational studies. METHODS:: We use an instrumental variables regression design to analyze the relationship between medication use, cardiovascular risk factors, and acute stroke and myocardial infarction event rates in women aged 40 to 79 years. The natural experiment of the 2002 decline in HRT usage mitigates confounding factors. We use US death records, hospital discharge data obtained from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, and nationally representative surveys of medication usage, and behavioral risk factors. RESULTS:: Decreases in HRT use were not associated with statistically significant changes in hospitalizations or deaths due to acute stroke (0.000002, P = 0.999, 95% CI: -0.0027 to 0.0027). Decreased HRT use was associated with a decrease in the incidence of acute myocardial infarction (-0.0025 or -25 events/10,000 person-years, P = 0.021, 95% CI: -0.0047 to -0.0004). The results were similar in a sensitivity analysis using alternate data sources. CONCLUSIONS:: Decreased HRT use was not associated with reduced acute stroke rate but was associated with a decreased acute myocardial infarction rate among women. Our results suggest that observational data can provide correct inferences on clinical outcomes in the overall population if a suitable natural experiment is identified.

 

 

Obstet Gynecol. 2009 Apr;113(4):902-908

Evidence for a Role of Hot Flushes in Vascular Function in Recently Postmenopausal Women.

Tuomikoski P, Ebert P, Groop PH, Haapalahti P, Hautamäki H, Rönnback M, Ylikorkala O, Mikkola TS.

Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.

OBJECTIVE: Observational studies indicate that postmenopausal hormone therapy (HT) prevents cardiovascular disease, but randomized clinical trials have not confirmed this effect. Hot flushes were more likely to be present in women starting HT in observational studies, whereas these symptoms were mild or absent among women attending randomized clinical trials. We hypothesized that vascular function may differ in women with and without vasomotor hot flushes. METHODS: One hundred forty-three recently postmenopausal women showing a broad range of variation in hot flushes were studied with radial artery tonometry. Pulse wave analyses were assessed at baseline and after nitroglycerin and salbutamol challenges. Wilcoxon signed rank test was used for paired comparisons after challenges with nitroglycerin and salbutamol. RESULTS: Neither baseline arterial stiffness nor endothelial function differed between women without or with mild, moderate, or severe hot flushes. However, after nitroglycerin challenge, the time to the onset of the reflected wave (dependent on pulse wave velocity) was 9.5% longer (P=.014), and the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) was 13.9% longer (P=.025) in women with severe hot flushes as compared with asymptomatic women. CONCLUSION: Women with severe vasomotor hot flushes show greater vascular responsiveness to nitroglycerin than women without hot flushes. This may partially explain the conflicting data between observational and randomized HT studies.