Selección de Resúmenes de Menopausia

Enero de 2008

Semana del 23 al 29 de Enero de 2008

 

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Stroke. 2008 Jan;39(1):30-5. Epub 2007 Dec 6.

Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study.

Boden-Albala B, Sacco RL, Lee HS, Grahame-Clarke C, Rundek T, Elkind MV, Wright C, Giardina EG, DiTullio MR, Homma S, Paik MC.

Department of Neurology, Columbia University College of Physicians and Surgeons, Mailman School of Public Health, New York, NY, USA. bb87@columbia.edu

BACKGROUND AND PURPOSE: More than 47 million individuals in the United States meet the criteria for the metabolic syndrome. The relation between the metabolic syndrome and stroke risk in multiethnic populations has not been well characterized. METHODS: As part of the Northern Manhattan Study, 3298 stroke-free community residents were prospectively followed up for a mean of 6.4 years. The metabolic syndrome was defined according to guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs for ischemic stroke and vascular events (ischemic stroke, myocardial infarction, or vascular death). The etiologic fraction estimates the proportion of events attributable to the metabolic syndrome. RESULTS: More than 44% of the cohort had the metabolic syndrome (48% of women vs 38% of men, P<0.0001), which was more prevalent among Hispanics (50%) than whites (39%) or blacks (37%). The metabolic syndrome was associated with increased risk of stroke (HR=1.5; 95% CI, 1.1 to 2.2) and vascular events (HR=1.6; 95% CI, 1.3 to 2.0) after adjustment for sociodemographic and risk factors. The effect of the metabolic syndrome on stroke risk was greater among women (HR=2.0; 95% CI, 1.3 to 3.1) than men (HR=1.1; 95% CI, 0.6 to 1.9) and among Hispanics (HR=2.0; 95% CI, 1.2 to 3.4) compared with blacks and whites. The etiologic fraction estimates suggest that elimination of the metabolic syndrome would result in a 19% reduction in overall stroke, a 30% reduction of stroke in women; and a 35% reduction of stroke among Hispanics. CONCLUSIONS: The metabolic syndrome is an important risk factor for ischemic stroke, with differential effects by sex and race/ethnicity.

 

Del Med J. 2007 Nov;79(11):441-4.

Black cohosh-induced hepatitis.

Nisbet BC, O'Connor RE.

Department of Emergency Medicine at Christiana Care Health System, Newark, Del, USA.

Herbal products are widely used by American consumers. Herbal remedies are not regulated by the Food and Drug Administration, but they are not immune from serious medication side-effects. We report the case of a 50-year-old woman who presented with fatigue and right upper quadrant pain. The patient had begun the popular postmenopausal herbal remedy black cohosh two weeks prior to presentation. Laboratory results revealed acute hepatitis. After other causes of liver failure were ruled out, the patient was diagnosed with black cohosh-induced hepatitis. She recovered uneventfully following withdrawal of the herb. There are five prior reports of hepatitis or hepatic failure likely caused by the herbal remedy black cohosh in the English literature. This case illustrates the importance of a broad differential diagnosis for abdominal pain and highlights the importance of a complete medication list, including herbs.

 

Am J Epidemiol. 2008 Jan 23 [Epub ahead of print]

Incidence of Dementia in Long-term Hormone Users.

Petitti DB, Crooks VC, Chiu V, Buckwalter JG, Chui HC.

Department of Clinical Analysis, Kaiser Permanente Southern California, Pasadena, CA.

Results from epidemiologic studies of postmenopausal hormone use and dementia have been conflicting. Investigators from the Women's Health Initiative Memory Study reported that the incidence of dementia in women aged >/=65 years assigned to hormone use was increased. Here the authors report results from a prospective cohort study of 2,906 dementia-free women (1,519 hormone users and 1,387 hormone nonusers) aged >/=75 years who were recruited from a Southern California health plan in 1999 and followed through 2003. Cognitive status was assessed annually using the Telephone Interview of Cognitive Status-modified, supplemented by the Telephone Dementia Questionnaire and medical record review. The mean self-reported age at initiation of hormone use was 48.3 years for users of estrogen alone (n = 1,072) and 54.9 years for users of estrogen plus progestin (n = 447); self-reported mean durations of hormone use were 30.5 years and 23.2 years, respectively. There were 283 incident dementia cases identified during follow-up. After adjustment for age, education, and medical history, hazard ratios for incident dementia were 1.34 (95% confidence interval: 0.95, 1.89) in estrogen/progestin users and 1.23 (95% confidence interval: 0.94, 1.59) in estrogen users. These findings do not provide support for an effect of estrogen or estrogen/progestin use in preventing dementia.

 

J Clin Invest. 2008 Jan 24 [Epub ahead of print

Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice.

Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, Jones DC, Vallet S, et al.

Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston.

Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.

 

Endocr J. 2008 Jan 24 [Epub ahead of print

Increased Bone Turnover in Patients with Hypercholesterolemia.

Majima T, Komatsu Y, Shimatsu A, Satoh N, Fukao A, Ninomiya K, Matsumura T, Nakao K.

Department of Endocrinology and Metabolism, Clinical Research Institute for Endocrine Metabolic Diseases, National Hospital Organization, Kyoto Medical Center.

Osteoporosis has been linked with arteriosclerotic vascular diseases, suggesting that hypercholesterolemia or dyslipidemia may be a common pathogenetic factor underlying these diseases. However, little is known about the relationship between osteoporosis and hypercholesterolemia. The purpose of this study was, therefore, to investigate the effects of hypercholesterolemia upon bone metabolism, by measuring bone turnover markers in hypercholesterolemic patients. This study included 281 Japanese patients with hypercholesterolemia, and 267 control subjects. Serum bone-specific alkaline phosphatase (BAP) of the patients was significantly higher than that of the controls in women. Serum N-terminal telopeptide of type I collagen (NTx) of the patients was significantly higher than that of the controls in both men and women. In addition, both BAP and NTx in men showed a significantly negative correlation with high density lipoprotein cholesterol (HDL-C). On the other hand, in women, both BAP and NTx showed a significantly positive correlation with total cholesterol and low density lipoprotein cholesterol (LDL-C). These results indicate increased bone turnover in hypercholesterolemic or dyslipidemic patients regardless of gender, and suggest the importance of treating hypercholesterolemia or dyslipidemia in order to prevent not only arteriosclerotic complications but also osteoporotic bone loss and subsequent fractures.

 

Breast Cancer Res Treat. 2008 Jan 23 [Epub ahead of print

Effect of a low-fat, high-carbohydrate dietary intervention on change in mammographic density over menopause.

Martin LJ, Greenberg CV, Kriukov V, Minkin S, Jenkins DJ, Yaffe M, Hislop G, Boyd NF.

Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, ON, Canada.

We have previously shown that a low-fat dietary intervention for 2 years in women with extensive mammographic density decreased mammographic density to a greater extent than in the control group. Post-hoc analysis indicated that this effect was strongest in women who became postmenopausal during the follow-up period. The purpose of the present study was to determine if this potentially important finding could be confirmed in a new and larger group of subjects with a longer follow-up time. Participants in a low-fat dietary intervention trial who were premenopausal at entry and became postmenopausal during follow-up were examined. Total breast, dense, and non-dense area and percent density were measured in baseline and postmenopause mammograms using a computer-assisted method. Total breast and non dense area increased more in the control group compared to the intervention group (for breast area 2.6 and 0.2 cm(2), respectively; P = 0.05, and for non-dense area 10.9 and 8.1 cm(2), respectively; P = 0.06). Dense area decreased to a similar degree in both groups (-8.2 and -8.0 cm(2), respectively; P = 0.84). Percent density decreased to a slightly greater degree in the control compared to intervention group (-9.4 and -7.8%, respectively, P = 0.11). There were no significant differences between study groups after adjustment for weight change. Menopause reduced density to a similar extent in the low-fat diet and control groups. If a low-fat diet reduces breast cancer risk, the effect is unlikely to be through changes in mammographic density at menopause.

 

Digestion. 2008 Jan 21;77(1):4-9 [Epub ahead of print

Hormone Replacement Therapy and Symptomatic Gallstones - A Prospective Population Study in the EPIC-Norfolk Cohort.

Hart AR, Luben R, Welch A, Bingham S, Khaw KT.

School of Medicine, Health Policy & Practice, University of East Anglia, Norwich, UK.

Background/Aims: Hormone replacement therapy (HRT) may increase the risk of symptomatic gallstones, but this association has not been investigated in a prospective study in a European population. The aim of the study was to investigate the relationship between HRT and the development of symptomatic gallstones in a free-living population. Methods: Use of HRT was ascertained by questionnaire in 13,433 women aged 45-74 years living in Norfolk, UK, who participated in the EPIC-Norfolk Study (European Prospective Investigation Into Cancer). The use of HRT was that at the time of recruitment rather than at the point of diagnosis. Participants were followed up for the development of symptomatic gallstones. The analysis used a nested case-control method in a prospective study. Results: A total of 117 women developed symptomatic gallstones. Women who reported either ever using HRT, currently using HRT or who had been past users all had a greater risk of gallbladder disease than age-matched control women who had never used HRT, after adjusting for known risk factors for gallstones. Women who had ever used HRT had a risk of 1.94 (95% CI = 1.17-3.22) compared with women who had never used HRT. For past users of HRT, the risk of symptomatic gallstones was greater, the longer the duration of use (OR = 4.05, 95% CI = 1.12-14.76 for use >1 year, compared to OR = 2.04, 95% CI = 0.79-5.30 for </=1 year). Conclusions: Use of HRT was positively associated with an increased risk of symptomatic gallstones in this population. This confirms trial data and additionally shows effects of duration of use and increased risk associated with past use.

 

Lancet. 2008 Jan 16 [Epub ahead of print]

Maternal and child undernutrition: consequences for adult health and human capital.

Victora CG, Adair L, Fall C, Hallal PC, Martorell R, Richter L, Sachdev HS; for the Maternal and Child Undernutrition Study Group.

Universidade Federal de Pelotas, Pelotas, Brazil.

In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and-for women-lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain-especially after infancy-is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.

 

J Aging Phys Act. 2008 Jan;16(1):53-60.

Enhanced rate of resting energy expenditure in women using hormone-replacement therapy: preliminary results.

Aubertin-Leheudre M, Goulet ED, Dionne IJ.

Research Centre on Aging, Faculty of Physical Education and Sports, University of Sherbrooke, Sherbrooke, QC, Canada.

Hormone-replacement therapy (HRT) attenuates the menopause-associated alterations in body composition. It is not known, however, whether this effect is a result of a concomitant increase in energy expenditure. The authors examined whether women submitted to a long-term HRT treatment presented greater energy expenditure than women who had never used HRT. We compared 13 postmenopausal women using HRT (>1 yr) with 13 age- (+/-2 yr) and body-mass-index-matched (BMI; +/-1.5kg/m2) postmenopausal women not using HRT. Resting energy expenditure (REE; indirect calorimetry), body composition, and daily (DEE) and physical activity (PAEE) energy expenditure (accelerometry) were obtained. Although BMI, fat mass, fat-free mass, DEE, and PAEE were similar between groups, the HRT group displayed a significantly greater REE than the no-HRT group (D +222 kcal/day). In conclusion, the authors observed that a long-term treatment with HRT is associated with a greater REE in postmenopausal women. These results need to be confirmed.

 

Menopause. 2008 Jan 18 [Epub ahead of print

Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN).

Wildman RP, Colvin AB, Powell LH, Matthews KA, Everson-Rose SA, Hollenberg S, Johnston JM, Sutton-Tyrrell K.

of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.

OBJECTIVE:: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. DESIGN:: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation. RESULTS:: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenhorrhea), and 27% were postmenopausal (>/=12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P = 0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P = 0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P = 0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P = 0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. CONCLUSIONS:: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

 

 

Semana del 16 al 22 de Enero de 2008

 

Climacteric. 2008 Feb;11(1):84-8.

Black cohosh: a cause of abnormal postmenopausal liver function tests.

Joy D, Joy J, Duane P.

Locum Consultant Gastroenterologist, Prince Phillip Hospital, Llanelli, Carmarthenshire.

The health scares restricting the use of hormone replacement therapy have made women tend to opt for 'natural' remedies that are generally perceived as safe. Unfortunately, there is lack of definite opinion on the safety of herbal remedies. Black cohosh is commonly used for postmenopausal symptoms. We present two cases of liver toxicity related to this and recommend close monitoring of women on this herbal preparation.

 

Climacteric. 2008 Feb;11(1):74-83

Lipid levels and cardiovascular risk in elderly women: a general population study of the effects of hormonal treatment and lipid-lowering agents.

Dupuy AM, Carrière I, Scali J, Cristol JP, Ritchie K, Dartigues JF, Gambert P, Ancelin ML.

Inserm U888, Montpellier.

Objective To evaluate plasma lipid levels in elderly women in the general population as a function of use of lipid-lowering agents (LLA) and hormone therapy (HT). Methods A total of 4271 women aged over 65 years were recruited from three French cities. Analyses were performed after stratification by LLA treatment and HT and adjusting for a large range of sociodemographic and clinical factors. Results Fifteen percent of women currently used HT (78% transdermal estradiol), and 30% were taking LLA. In this population, 4.6% of women were taking both HT and LLA (fibrate for 2.4% and statin for 2.2%). In non-LLA-treated women, current HT was associated with lower total cholesterol, low density lipoprotein cholesterol (LDL-C), and non-high density lipoprotein cholesterol (non-HDL-C) compared to never users. Women treated with LLA also had lower total cholesterol, LDL-C, and non-HDL-C compared to non-LLA users, whereas triglyceride levels were the highest in statin users and lowest in fibrate users. Fibrate use was associated with a more favorable lipid pattern than statin treatment independently of HT use. In women without coronary heart disease or diabetes, HT, statin or fibrate use were associated with lower LDL-C level risk based on National Cholesterol Education Program guidelines (adjusted odds ratio (OR) = 0.67 (95% confidence interval (CI) = 0.53-0.85), 0.38 (95% CI = 0.29-0.47), and 0.32 (95% CI = 0.25-0.42), respectively) with a possible interaction between fibrate and HT (0.18 (95% CI = 0.10-0.30)). Conclusions Estradiol-based HT may lower atherogenic lipoproteins in postmenopausal women. In primary prevention of coronary heart disease, combining HT and a fibrate may provide additional benefits compared to fibrate use.

 

Climacteric. 2008 Feb;11(1):63-73

Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women.

Sturdee DW, Archer DF, Rakov V, Lang E, Investigators OB.

Department of Obstetrics and Gynecology, Solihull Hospital, Solihull, West Midlands, UK.

Objective To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding. Methods A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval and informed consent were obtained prior to initiation and enrolment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound at baseline and on completion. An endometrial biopsy was obtained when indicated clinically. Results In months 1-6, the amenorrhea rates with E2/NETA 0.1 were 89%, 89%, 86%, 85%, 89% and 89%, respectively and the no-bleeding rates were correspondingly high: 95%, 94%, 93%, 90%, 95% and 95%. The amenorrhea and spotting-only rates were similar with both ultra-low-dose combinations. The withdrawal rates due to bleeding were very low and the same in all three treatment arms (n = 1; 1%). There was a slight increase in the mean endometrial thickness in all three groups, which remained less than 5 mm. Conclusions The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment or placebo.

 

Climacteric. 2008 Feb;11(1):55-62

The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study.

Szoeke CE, Cicuttini FM, Guthrie JR, Dennerstein L.

Office for Gender and Health, Department of Psychiatry, University of Melbourne, Victoria.

Objectives Part I: To determine factors associated with reported joint symptoms across the menopausal transition. Part II: To investigate the relationship between symptom reporting and radiological arthritis in postmenopausal women. Design Part I: The Melbourne Women's Mid-life Health Project, commenced in 1991, is a population-based prospective study of 438 Australian-born women, aged 45-55 years and menstruating at baseline; they were interviewed annually over 8 years. The retention rate was 88% (n = 387). Part II: After 12 years of follow-up, 257 (57%) women returned for assessment and 224 agreed to undergo X-rays of their hands and knees. Methods Part I: Annual fasting blood collection, physical measurements, and interviews including questions about bothersome aches or stiff joints in the previous 2 weeks. A score for this symptom was calculated from the product of the severity and frequency data. These data were analyzed using random-effects time-series regression models. Part II: X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. Results Part I: 'Aches and stiff joints' were the most commonly reported symptom and reporting increased over time in the longitudinal study. Variables significantly associated with reporting bothersome aches and stiff joints were high body mass index (BMI) (p < 0.001), high negative mood (p < 0.01), not being employed (p < 0.001), and experiencing the menopausal transition (p < 0.05). A higher severity and frequency of this symptom were associated with BMI (p < 0.01), not being employed (p < 0.05) and high negative mood (p < 0.005). Part II: The relationship between radiological osteoarthritis and symptom reports approached statistical significance (p = 0.06). Knee osteoarthritis was significantly associated with symptom reports (p = 0.008) but not hand osteoarthritis (p = 0.2). Conclusion Menopausal status, BMI, employment status and depressed mood were all associated with the experience of bothersome aches and stiff joints. Aches and stiff joints, common in postmenopausal women, are not necessarily indicative of radiological osteoarthritis.

 

Acta Med Port. 2007 Jul-Aug;20(4):299-306. Epub 2007 Nov 15.

Nutritional intake and bone mineral density in female adolescents

Leite M, Padrão P, Moreira P.

Centro de Investigação em Actividade Física, Saúde e Lazer da Universidade do Porto, Faculdade de e Ciências da Nutrição e Alimentação da Universidade do Porto, Porto.

INTRODUCTION: Adolescence is a critical time in skeletal development, during which the amount of bone gained along with the subsequent rate of bone loss have a crucial impact on an individual's total bone mass in adulthood and old age. Factors believed to influence bone accretion and peak bone mass include adequate nutritional intake, namely for calcium. However, the findings of several studies have raised questions about the benefit of the total dietary calcium consumption for young adult bone health. The objective of this study was to evaluate the association between nutritional intake, namely calcium, and bone mineral density in female teenagers. METHODS: The study design was a cross-sectional analysis and data derived from a school-based survey of adolescents from high schools. In all, the study sample included 254 female adolescents with ages between 15 and 17 years. The questionnaire was anonymous and confidential, and provided information on the following variables: bone mineral density (BMD), evaluated in the calcaneus by ultrasound through the Sahara Clinical Bone Sonometer from Hologic; weight and height, measured according to international standards; nutritional intake assessed by a food-frequency questionnaire developed by the Epidemiology Department, Faculty of Medicine, University of Porto; sociodemographic characteristics; age of first menstruation; regularity of menstrual cycles; use of contraceptives and drugs; history of bone fractures; smoking habits; and physical activity. In order to study the association between nutritional intake and BMD, uni and multivariate regression analysis (with adjustment for confounders, namely irregular menses, energy and protein intake) was used. RESULTS: The following main results were reached: positive and significant effects were found for calcium intake in BMD, even after adjustment for confounders (ss = 0.003, 95% CI = 0.000 - 0.006, p = 0.031); 15.1% of adolescents showed t-scores that suggested osteopenia; mean calcium intake (1229 +/- 778 mg/day) was lower than recommended for optimal bone acquisition in achieving maximal peak bone mass. CONCLUSION: Calcium intake was positively associated with BMD, but mean calcium intake was lower tan recommended. It should be therefore important to assure good dietary habits and adequate calcium intake in female adolescents for the development of peak bone mass, and reducing the risk of osteoporosis later in life.

 

Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):51-66

Full-term Pregnancy Induces a Specific Genomic Signature in the Human Breast.

Russo J, Balogh GA, Russo IH; and the Fox Chase Cancer Center Hospital Network Participants.

Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111.

Breast cancer risk has traditionally been linked to nulliparity or late first full-term pregnancy, whereas young age at first childbirth, multiparity, and breast-feeding are associated with a reduced risk. Early pregnancy confers protection by inducing breast differentiation, which imprints a specific and permanent genomic signature in experimental rodent models. For testing whether the same phenomenon was detectable in the atrophic breast of postmenopausal parous women, we designed a case-control study for the analysis of the gene expression profile of RNA extracted from epithelial cells microdissected from normal breast tissues obtained from 18 parous and 7 nulliparous women free of breast pathology (controls), and 41 parous and 8 nulliparous women with history of breast cancer (cases). RNA was hybridized to cDNA glass microarrays containing 40,000 genes; arrays were scanned and the images were analyzed using ImaGene software version 4.2. Normalization and statistical analysis were carried out using Linear Models for Microarrays and GeneSight software for hierarchical clustering. The parous control group contained 2,541 gene sequences representing 18 biological processes that were differentially expressed in comparison with the other three groups. Hierarchical clustering of these genes revealed that the combined parity/absence of breast cancer data generated a distinct genomic profile that differed from those of the breast cancer groups, irrespective of parity history, and from the nulliparous cancer-free group, which has been traditionally identified as a high-risk group. The signature that identifies those women in whom parity has been protective will serve as a molecular biomarker of differentiation for evaluating the potential use of preventive agents.

 

Climacteric. 2008 Feb;11(1):32-43

Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States.

Williams RE, Kalilani L, Dibenedetti DB, Zhou X, Granger AL, Fehnel SE, Levine KB, Jordan J, Clark RV.

Worldwide Epidemiology, Research Triangle Park, NC.

Objective To describe characteristics of vasomotor symptoms, specifically daily frequency and severity, among women 40-65 years old in the United States (US). Design A survey was completed by a nationally representative sample of 4402 US women aged 40-65 years old. A questionnaire focusing on menopausal symptoms was administered online in April 2005. Results The prevalence of vasomotor symptoms was 79% in peri- and 65% in postmenopausal women. Women with daily vasomotor symptoms had an average of 2.5 very mild/mild, 2.6 moderate, 2.5 severe, and 1.4 very severe daytime hot flushes in a typical day. Women with night sweats every night had an average of 2.4 moderate, 3.2 severe, and 2.7 very severe night sweats in a typical night. Overall, 9% of peri- and 7% of postmenopausal women reported 7+ moderate to very severe vasomotor symptoms in a typical day. Although some women reported that symptoms were worse in the evening and in the summer, many women reported they were consistent, both throughout the day and throughout the seasons of the year. Conclusions The Menopause Epidemiology Study builds upon existing literature by providing data on daily frequency and severity of vasomotor symptoms. There are many women with frequent and severe vasomotor symptoms who may benefit from treatment.

 

Climacteric. 2008 Feb;11(1):17-25

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women.

Penteado SR, Fonseca AM, Bagnoli VR, Abdo CH, Júnior JM, Baracat EC.

Department of Psychiatry, São Paulo University Medical School, São Paulo.

Objective To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. Methods Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n = 29) received one tablet of equine estrogens (CEE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg and one capsule of placebo; EP + A (n = 31) received one tablet of CEE 0.625 mg plus MPA 2.5 mg and one capsule of methyltestosterone 2.0 mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. Results There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p = 0.021). No significant effect on orgasmic capacity was noted after the treatment period. Conclusion Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.

 

BMJ. 2008 Jan 15 [Epub ahead of print

Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial.

Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, Gamble GD, Grey A, Reid IR.

Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.

OBJECTIVE: To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women. DESIGN: Randomised, placebo controlled trial. SETTING: Academic medical centre in an urban setting in New Zealand. PARTICIPANTS: 1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo. MAIN OUTCOME MEASURES: Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death. RESULTS: Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49). CONCLUSION: Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.

                         

 

Semana del 9 al 15 de Enero de 2008

 

ALERTA DE LA FDA  (7 Enero de 2008)

 La FDA está destacando la posibilidad de dolor de hueso, articulaciones y/o músculos (músculo esquelético) severo y algunas veces incapacitante en pacientes tomando bisfosfonatos. A pesar de que el dolor músculo esquelético severo está incluido en la información para prescribir  de todos los bisfosfonatos, la asociación entre bisfosfonatos y dolor músculo esquelético severo puede ser pasada por alto por los profesionales de la salud, retardando el diagnóstico, prolongando el dolor y/o el deterioro, y haciendo necesario el uso de analgésicos. El dolor músculo esquelético severo puede ocurrir dentro de los primeros días, meses o años después de iniciar un bisfosfonatos. Algunos pacientes han reportado  alivio complete de los síntomas después de descontinuarlos bisfosfonatos, mientras que otros han reportado resolución lenta o incompleta.  Se desconocen los factores de riesgo y la incidencia del dolor músculo esquelético severo asociado con bisfosfonatos. Este dolor músculo esquelético severo es en contraste con la respuesta de fase aguda caracterizada por fiebre, escalofríos, dolor óseo, mialgias, y artralgias que algunas veces acompaña a la administración inicial de bisfosfonatos intravenosos y puede ocurrir con la exposición inicial  a bisfosfonatos orales una vez por semana o una vez por mes. Los síntomas relacionados con la respuesta de fase aguda tienden a resolverse dentro de los primeros días con el uso continuado del medicamento. Los profesionales de la salud deben considerar si el uso de bisfosfonatos puede ser responsable de dolor músculo esquelético severo en pacientes que presenten estos síntomas y considerar la suspensión temporal o permanente del medicamento. Esta información refleja el análisis de los datos disponibles por la FDA concernientes a estos fármacos. La FDA intenta actualizar éstos, cuando hay información o análisis disponibles.

 

Am J Epidemiol. 2008 Jan 11 [Epub ahead of print]

The Association between In Utero Cigarette Smoke Exposure and Age at Menopause.

Strohsnitter WC, Hatch EE, Hyer M, Troisi R, Kaufman RH, Robboy SJ, Palmer JR, Titus-Ernstoff L, Anderson D, Hoover RN, Noller KL.

Department of Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA.

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero. Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke. Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31). In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.

 

Menopause. 2008 Jan 9 [Epub ahead of print]

Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women.

Levine KB, Williams RE, Hartmann KE.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

OBJECTIVE: The relationship between vulvovaginal atrophy and female sexual dysfunction is unclear. We investigated this association among sexually active postmenopausal women. DESIGN: The Menopause Epidemiology Study is a cross-sectional, population-based study of women 40 to 65 years old in the United States chosen from a source population selected by random digit dialing and probability sampling. We focused on sexually active postmenopausal women (N = 1,480) for our analyses. Vulvovaginal atrophy was defined as one or more of the following: vaginal dryness, itching, irritation; pain on urination; or pain or bleeding on intercourse. The Arizona Sexual Experience Survey was used to define female sexual dysfunction. Sexual dysfunction subtypes for desire, arousal, and orgasm difficulties were individually scored. We evaluated demographic, behavioral, reproductive history, and medication covariates for effect modification and confounding. Multivariate logistic regression was used to assess the relationship between vulvovaginal atrophy and female sexual dysfunction. RESULTS: The prevalence of vulvovaginal atrophy (57%) and female sexual dysfunction (55%) was high. Women with female sexual dysfunction were 3.84 times more likely to have vulvovaginal atrophy than women without female sexual dysfunction (95% CI: 2.99-4.94). Hot flashes modified the association between vulvovaginal atrophy and desire difficulty. Educational level modified the association between vulvovaginal atrophy and arousal difficulty. Parity modified the association between vulvovaginal atrophy and orgasm difficulty. CONCLUSIONS:: This large population-based study provides evidence of an association between vulvovaginal atrophy and overall female sexual dysfunction and its subtypes. Therapies aiming to reduce symptoms of one condition may also relieve symptoms of the other.

 

Osteoporos Int. 2008 Jan 11 [Epub ahead of print]

Positive effects of exercise on falls and fracture risk in osteopenic women.

Hourigan SR, Nitz JC, Brauer SG, O'Neill S, Wong J, Richardson CA.

Division of Physiotherapy, The University of Queensland, St. Lucia, Qld. 4072, Brisbane, Australia.

Exercise may affect osteopenic women at risk of falls and fractures. A workstation approach to exercise was evaluated in a randomised study of 98 women. The intervention group improved in measures of balance, strength and bone density. This study supports a preventative exercise approach that aims to reduce risk factors for fractures and falls, in women already at risk, through balance training and weight-bearing activity. INTRODUCTION: The objective of this study was to determine the effects of a workstation balance training and weight-bearing exercise program on balance, strength and bone mineral density (BMD) in osteopenic women. A single-blinded randomised controlled trial (RCT) was undertaken for 20 weeks with measurements at baseline and completion. MATERIALS AND METHODS: Ninety-eight (98) community-dwelling osteopenic women aged 41-78 years were recruited through the North Brisbane electoral roll. Subjects were randomised via computer-generated random numbers lists into either a control (receiving no intervention), or exercise group (two one-hour exercise sessions per week for 20 weeks with a trained physiotherapist). Assessments at baseline and post-intervention included balance testing (five measures), strength testing (quadriceps, hip adductors / abductors / external rotators and trunk extensors), and DXA scans (proximal femur and lumbar spine). Baseline assessment showed no significant differences between groups for all demographics and measures except for subjects taking osteoporosis medication. The percentage differences between pre- and post-intervention measurements were examined for group effect by ANOVA using an intention-to-treat protocol. RESULTS: Ninety-eight women (mean age 62.01 years, SD 8.9 years) enrolled in the study. The mean number of classes attended for the 42 participants in the exercise group who completed the program was 28.2 of a possible 40 classes (71%). At the completion of the trial the intervention group showed markedly significant better performances in balance (unilateral and bilateral stance sway measures, lateral reach, timed up and go and step test) (p < 0.05) with strong positive training effects reflecting improvements of between 10% to 71%. Similarly there were gains in strength of the hip muscles (abductors, adductors, and external rotators), quadriceps and trunk extensors with training effects between 9% and 23%. CONCLUSIONS: Specific workstation exercises can significantly improve balance and strength in osteopenic women. This type of training may also positively influence bone density although further study is required with intervention over a longer period. A preventative exercise program may reduce the risk of falls and fractures in osteopenic women already at risk.

 

Results Probl Cell Differ. 2008 Jan 12 [Epub ahead of print]

Structure and Function of Ghrelin.

Kojima M, Kangawa K.

Molecular Genetics, Institute of Life Science, Kurume University, Hyakunenkouen, Fukuoka, Japan.

The endogenous ligand for growth-hormone secretagogue receptor (GHS-R) was purified from the stomach and we named it "ghrelin", after a word root ("ghre") in Proto-Indo-European languages meaning "grow", since ghrelin has potent growth hormone (GH) releasing activity. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the blood stream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining growth hormone release and energy homeostasis in vertebrates. The diverse functions of ghrelin raise the possibility of its clinical application for GH deficiency, eating disorder, gastrointestinal disease, cardiovascular disease, osteoporosis and aging, etc.

 

Int J Obes (Lond). 2008 Jan 8 [Epub ahead of print]

Adipocytokine and ghrelin levels in relation to cardiovascular disease risk factors in women at midlife: longitudinal associations.

Wildman RP, Mancuso P, Wang C, Kim M, Scherer PE, Sowers MR.

1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Background:There are limited data concerning the relationships between changes in adipocytokines and cardiovascular disease (CVD) risk factors.Objective:To examine the longitudinal associations between leptin, adiponectin, resistin and ghrelin levels and CVD risk factor levels in women at midlife.Design:Prospective, observational study.Subjects and measurements:Leptin, adiponectin, resistin, ghrelin levels and CVD risk factors were measured in specimens collected from 40 women at 3 points in time corresponding to the pre-, peri- and postmenopause stages of their natural menopause transition.Results:In longitudinal analyses adjusted for CVD risk factors and leptin at the previous menopausal stage, aging, education, smoking and physical activity, greater increases in leptin over the menopause transition were associated with greater decreases in high-density lipoprotein cholesterol (HDL-c) and greater increases in diastolic blood pressure, glucose, insulin and insulin resistance (all P<0.05). Larger decreases in adiponectin over the menopause transition were associated with greater increases in systolic blood pressure, insulin and insulin resistance and with greater decreases in HDL-c. Greater increases in ghrelin levels over the menopausal transition were associated with greater low-density lipoprotein cholesterol increases (P=0.014). Resistin was not associated with CVD risk factor changes.Conclusion:There were significant adverse associations of adipocytokines and ghrelin with multiple CVD risk factor changes in women across midlife. Given that this time period is dynamic for CVD risk, these data underscore the need for additional prospective studies.

 

J Clin Endocrinol Metab. 2008 Jan 8 [Epub ahead of print]

Post-Menopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) Sponsored Women's Ischemia Syndrome Evaluation (WISE).

Shaw LJ, Merz CN, Azziz R, Stanczyk FZ, Sopko G, Braunstein GD, Kelsey SF, Kip KE, Cooper-Dehoff RM, Johnson BD, Vaccarino V, Reis SE, Bittner V, Hodgson TK, Rogers W, Pepine CJ.

Division of Cardiology, Department of Medicine,  Cedars-Sinai Medical Center, Los Angeles, California.

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described. Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the NIH-NHLBI sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (>/=701 pg/ml), testosterone (T; >/=30.9 ng/dl), or free T (>/=4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (MI) (n = 55). Results: Women with clinical features of PCOS were more often diabetic (p<0.0001), obese (p=0.005), had the metabolic syndrome (p<0.0001), and more angiographic coronary artery disease (CAD, p=0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n=104) versus 88.7% for women without clinical features of PCOS (n = 286) (p=0.006). PCOS remained a significant predictor (p<0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates. Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic coronary artery disease and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

 

J Clin Oncol. 2008 Jan 10;26(2):279-82.

Is there an association between meningioma and hormone replacement therapy?

Blitshteyn S, Crook JE, Jaeckle KA.

Department of Neurology and Biostatistics Unit, Mayo Clinic, Jacksonville, FL 32224, USA.

PURPOSE: Molecular and clinical observations suggest a role of sex steroid hormones in the occurrence of meningioma. However, there is limited and often conflicting data on the use of hormone replacement therapy (HRT) as a possible risk factor for meningioma. The goal of this study was to investigate whether there is an association between a diagnosis of meningioma and either current or past HRT use in women. METHODS: We retrospectively reviewed records in the Mayo Clinic Jacksonville electronic patient database between 1993 and 2003 to identify women with a diagnosis of either symptomatic or incidentally discovered, clinically silent meningioma. Records were also searched to identify women with a documented history of either current or past HRT use. RESULTS: Of the 355,318 women, ages 26 to 86, evaluated for any medical issue, 18,037 (5%) were documented as current or past HRT users. A total of 1,390 women with a history of symptomatic or incidentally discovered meningiomas were identified, 156 (11%) of whom were either current or past HRT users. A logistic regression analysis, adjusted for age, demonstrated a positive association between a diagnosis of meningioma and HRT use, with an odds ratio of 2.2 (95% CI, 1.9 to 2.6; P < .0001). The frequency of meningioma in women with either current or past HRT use was 865 in 100,000, whereas the frequency of meningioma in women without the history of HRT use was 366 in 100,000. CONCLUSION: The study provides evidence of a positive association between HRT use and diagnosis of meningioma, and therefore, HRT use may be a risk factor for meningioma.

 

Osteoporos Int. 2008 Jan 8 [Epub ahead of print]

Progression of vascular calcifications is associated with greater bone loss and increased bone fractures.

Naves M, Rodríguez-García M, Díaz-López JB, Gómez-Alonso C, Cannata-Andía JB.

Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, Hospital Universitario Central de Asturias, Universidad de Oviedo, Oviedo, Spain.

In this prospective study, we found a positive relationship between the prevalence of aortic calcifications and age. Aortic calcifications at baseline were positively associated with osteoporotic fractures. In addition, progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine. INTRODUCTION: The aim of this study was to analyze the relationship between the progression of abdominal aortic calcification and osteoporosis in a Spanish cohort of men and women older than 50. METHODS: Men and women (n = 624) aged 50 and over underwent two lateral X-rays of thoracic and lumbar spine and a dual X-ray absorptiometry (DXA) study at lumbar spine and hip, and were followed during 4 years. Abdominal aortic calcifications were classified as absent, mild-moderate and severe. RESULTS: There was a positive relationship between the prevalence of aortic calcifications and age. In both sexes, prevalent severe aortic calcifications were positively associated with prevalent osteoporotic fractures [odds ratio (OR) = 1.93 (1.02-3.65)]. The association was stronger when only vertebral fracture was considered [OR = 2.45 (1.23-4.87)]. In addition, progression of aortic calcifications showed a positive association with the rate of decline in bone mineral density (BMD) at lumbar spine. CONCLUSIONS: Aortic calcifications at baseline were positively associated with osteoporotic fractures. The progression of aortic calcifications was also positively associated with the rate of decline in BMD at lumbar spine.

 

 

Semana del 3 al 8 de Enero de 2008

 

Gynecol Obstet Fertil. 2008 Jan 3 [Epub ahead of print]

Postmenopausal malignant transformation of extragenital endometriosis. A case report.

Chung Fat B, Terzibachian JJ, Govyadovskiy A, Grisey A.

Service de gynécologie–obstétrique, centre hospitalier de Belfort–Montbéliard, 14, rue de Mulhouse, 90016 Belfort cedex, France.

Malignant transformation of endometriosis is a rare event. The ovaries are the most common sites reported in the literature. Postmenopausal cancer arising in extragenital endometriosis is still more exceptional. Hormone replacement therapy and perhaps, to a lesser extent, Tamoxifen could be risk factors for the malignant transformation of endometriosis. We herein report the case of a patient who has developed, after 11years of hormone replacement therapy, an extragenital endometrioid carcinoma in the vesico-uterine pouch.

 

Am J Gastroenterol. 2008 Jan 2 [Epub ahead of print]

Hormonal Replacement Therapy After Menopause Is Protective of Disease Activity in Women With Inflammatory Bowel Disease.

Kane SV, Reddy D.

Mayo Clinic, Rochester, Minnesota and University of Chicago, Chicago, Illinois, USA.

BACKGROUND AND AIMS: The nature of inflammatory bowel disease (IBD) following menopause has not been previously studied. The aim of this study was to characterize the effect of menopause on disease activity and identify possible modifiers of disease activity. METHODS: This was a retrospective study of women followed at the University of Chicago IBD Clinic. Disease activity was assessed using clinical scoring systems during the pre- and postmenstrual periods of subjects. Variables of interest included: history of smoking, use of oral contraceptives (OCP) prior to onset of menopause, and use of hormone replacement therapy (HRT). RESULTS: Sixty-five women were included, 20 with ulcerative colitis and 45 with Crohn's disease. The median age of menopause was similar to historical controls. Twenty-three patients (35%) experienced active symptoms in the premenopausal time period and 25 patients (38%) had disease indices consistent with a flare within the first 2 yr after menopause (P > 0.05). There was no relation between those who had a pre- versus postmenstrual flare as a group (P > 0.05). However, there was a significant protective effect on disease activity with postmenopausal HRT use (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.04-0.72). There was also a dose-response effect noted with an HR with longer duration of use (0.20, 0.07-0.65). CONCLUSIONS: The likelihood of having a flare postmenopause is not different from having it premenopause. HRT, however, may provide a protective effect for disease activity in the postmenopausal period. The anti-inflammatory effects of estrogen may be the mechanism for this observation.

 

Am J Clin Nutr. 2008 Jan;87(1):175-80.

Chocolate consumption and bone density in older women.

Hodgson JM, Devine A, Burke V, Dick IM, Prince RL.

Royal Perth Hospital Unit, the University of Western Australia School of Medicine and Pharmacology, Perth, Australia; Western Australian Institute for Medical Research, Perth, Australia.

BACKGROUND: Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated. OBJECTIVE: We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength. DESIGN: Randomly selected women aged 70-85 y (n = 1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories: <1 time/wk, 1-6 times/wk, >/=1 time/d. RESULTS: Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P < 0.05). Daily (>/=1 times/d) consumption of chocolate, in comparison to <1 time/wk, was associated with a 3.1% lower whole-body bone density; with similarly lower bone density of the total hip, femoral neck, tibia, and heel; and with lower bone strength in the tibia and the heel (P < 0.05, for all). Adjustment for covariates did not influence interpretation of the results. CONCLUSIONS: Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.

 

Maturitas. 2008 Jan 3 [Epub ahead of print]

The medical management of menopause: A four-country comparison care in urban areas.

Sievert LL, Saliba M, Reher D, Sahel A, Hoyer D, Deeb M, Obermeyer CM.

Department of Anthropology, Machmer Hall, 240 Hicks Way, UMass Amherst, Amherst, MA 01003-9278, USA.

OBJECTIVE: To compare the medical management of menopause across urban areas in four countries which differ by level of income and degree of medicalization. METHODS: Surveys of health providers who advise women on the menopausal transition were carried out in Beirut, Lebanon (n=100), Madrid, Spain (n=60), Worcester, MA, U.S. (n=59), and Rabat, Morocco (n=50) between 2002 and 2004. Physician characteristics, hormone therapy (HT) prescribing practices, and concerns about the management of menopause were compared across countries using chi(2) and logistic regression analyses. RESULTS: Across sites, physicians were generally well informed about HT and thought that symptom alleviation and disease prevention were equally important. They had concerns about risks associated with HT, particularly breast cancer, and in 3 sites where the survey was conducted after the WHI (Beirut, Rabat, and Madrid) physicians changed their practices to prescribe HT less frequently, for shorter durations, or shifted to other medications. There were significant differences across sites in the recommended duration of HT, time spent talking with patients, perceived benefits of HT, tests recommended before prescribing HT, and concern about the risks associated with HT. Physicians in Madrid and Massachusetts were more likely to report that decisions about the management of menopause were difficult, but in all sites the main reason for difficulties was concerns about risks. The results also suggest discrepancies between physicians' perceptions and women's reports about the reasons why women consult at menopause. CONCLUSIONS: Prescription patterns and perceived benefits of HT appear to reflect local medical culture rather than simply physician characteristics. The impact of the WHI study was seen in prescribing patterns and concerns about HT. Physicians in all four countries were generally well informed.

 

Cell Metab. 2008 Jan;7(1):7-10.

Bone remodeling, energy metabolism, and the molecular clock.

Rosen CJ.

Maine Medical Center Research Institute, Scarborough, USA; The Jackson Laboratory, Bar Harbor, ME, USA.

The adult skeleton is constantly renewed through bone remodeling. Four recent papers (Baldock et al., 2007; Lee et al., 2007; Lundberg et al., 2007; Sato et al., 2007) provide new insights into central and peripheral control of this remodeling sequence. Two of the studies add to our knowledge of the complex hypothalamic modulation of bone turnover mediated by NMU and NPY via the sympathetic nervous system, while the other two focus on the peripheral neural target, the osteoblast, and its regulation by neuropeptides and osteocalcin. These findings support a new paradigm concerning the regulation of bone remodeling and provide a foundation for novel approaches to preventing osteoporosis.

 

 

Calcif Tissue Int. 2008 Jan 4 [Epub ahead of print]

Dietary Intake of Folate, but not Vitamin B(2) or B (12), Is Associated with Increased Bone Mineral Density 5 Years after the Menopause: Results from a 10-Year Follow-Up Study in Early Postmenopausal Women.

Rejnmark L, Vestergaard P, Hermann AP, Brot C, Eiken P, Mosekilde L.

The Osteoporosis Clinic, Department of Endocrinology and Metabolism C, Aarhus Sygehus, Aarhus University Hospital, Aarhus Sygehus, Tage-Hansens Gade 2, DK-8000, Aarhus C, Denmark, rejnmark@post6.tele.dk.

Folate, vitamin B(2) (riboflavin), and vitamin B(12 )may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on whether dietary intakes affect bone. Our aim was to investigate whether intake of folate, vitamin B(2,) and vitamin B(12), as assessed by food records affects BMD and fracture risk. In a population-based cohort including 1,869 perimenopausal women from the Danish Osteoporosis Prevention Study, associations between intakes and BMD were assessed at baseline and after 5 years of follow-up. Moreover, associations between intakes and 5- and 10-year changes in BMD as well as risk of fracture were studied. Intakes of folate, vitamin B(2), and vitamin B(12) were 417 (range 290-494) mug/day, 2.70 (range 1.70-3.16) mg/day, and 4.98 (range 3.83-6.62) mug/day, respectively, i.e., slightly above the intakes recommended by the United Nations Food and Agriculture Organization. At year 5, but not at baseline, cross-sectional analyses showed positive correlations between daily intake from diet and from diet plus supplements of folate and BMD at the femoral neck (P < 0.01). However, no associations were found between intakes and changes in BMD. During 10 years of follow-up, 360 subjects sustained a fracture. Compared with 1,440 controls, logistic regression analyses revealed no difference in intakes between cases and controls. A high dietary intake of folate, but not vitamin B(2) or B(12), exerts positive effects on BMD; but further studies are needed to confirm this association.

 

J Vasc Surg. 2008 Jan;47(1):55-62.

The relationship between serum levels of vascular calcification inhibitors and carotid plaque vulnerability.

Kadoglou NP, Gerasimidis T, Golemati S, Kapelouzou A, Karayannacos PE, Liapis CD.

Department of Vascular Surgery, Medical School, University of Athens, Athens, Greece; First Department of Internal Medicine, "Hippokratio" General Hospital, Thessaloniki, Greece.

OBJECTIVE: Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events. METHODS: A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis. RESULTS: Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006). CONCLUSIONS: The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.