Selección de Resúmenes de Menopausia

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

Semana del 21 al 27 de Noviembre de 2007

Women Health. 2007;45(3):31-51.

Age-Related Differences in Health Complaints:The Hilo Women's Health Study.

Sievert LL, Morrison LA, Reza AM, Brown DE, Kalua E, Tefft HA.

Machmer Hall, 240 Hicks Way, Amherst, MA, 01003, leidy@anthro.umass.edu.

The purpose of this study was to determine the age distribution of health-related complaints and symptom groupings from a random postal survey carried out in the multi-ethnic city of Hilo, Hawaii. Symptom frequencies and factor analyses were compared across three age categories: < 40 (32%), 40-60 (48%), and > 60 years (19%), (n = 1,796). Younger women were most likely to report headaches, menstrual complaints, irritability, and mood swings.Women at midlife were most likely to report fluid retention, trouble sleeping, loss of sexual desire, vasomotor symptoms, and nervous tension. Older women reported the least number of symptoms overall. Using multiple linear regression, menopause status, ethnicity, and alcohol intake were significantly associated with the factor scores for symptoms of menopause, after controlling for age, education, BMI, exercise, smoking habits, and financial comfort.

Curr Med Res Opin. 2007 Nov 20; [Epub ahead of print]

Non-vertebral fracture risk reduction with oral bisphosphonates: challenges with interpreting clinical trial data.

Miller PD.

BACKGROUND: To license a therapy for the treatment of postmenopausal osteoporosis pharmacological agents must show ability to reduce the incidence of morphometric vertebral fractures versus placebo over a 3-year study period. In Europe, recent registration guidelines require evidence of reduction of vertebral and non-vertebral fracture incidence over a minimum of 2 years compared with placebo. There is much interest in the prevention of non-vertebral fractures. While morphometric vertebral fractures are assessed and statistically powered as the registration primary endpoint in clinical trials, non-vertebral fractures are often measured as secondary endpoints or captured as adverse events, which have selection biases in data capturing. AIM: To describe factors that influence fracture risk and the rate of osteoporotic non-vertebral fractures observed in randomized controlled studies of the oral nitrogen-containing bisphosphonates licensed for the treatment of postmenopausal osteoporosis (alendronate, risedronate and ibandronate). METHODS: A literature search was conducted using PubMed and ISI Web of Knowledge and using keywords representing drug names and trial types. Results were screened using selection criteria based on trial type and vertebral fracture endpoint of trials published from 1990 to 2007. Findings and conclusion: Without comparative head to head antifracture studies, current evidence does not support a clear differentiation in fracture reduction among the different bisphosphonates. The rate of fracture in a clinical study is dependent on different factors (e.g., skeletal fragility), which may vary from study to study. Even in trials assessing non-vertebral fractures as a primary endpoint, differences in study design, randomized population and varying definitions of what constitutes a non-vertebral fracture can influence outcomes. In addition, falls and fall-related risk factors have never been controlled for in or between individual studies. Although etidronate, administered with an extended between dose interval, has demonstrated a significant reduction in fracture risk, this was in a subgroup population, with the addition of phosphate or when only data from weeks 61-150 of the study were included in the analysis. None of the remaining currently registered non-daily oral bisphosphonates have prospective fracture data, and have, therefore, been registered on the basis of non-inferiority (surrogate marker bone mineral density and bone turnover marker) endpoints. However, a lack of evidence, if the appropriately designed studies have not been completed, does not necessarily indicate a lack of efficacy. Such a conclusion can only be drawn if a suitable study has been completed that definitively shows a lack of effect on non-vertebral fractures.

Menopause. 2007 Nov 19; [Epub ahead of print

Impact of menopause on quality of life in community-based women in China.

Chen Y, Lin SQ, Wei Y, Gao HL, Wang SH, Wu ZL.

From the 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, P. R. China; 2Century Forum Hospital, Beijing, P. R. China; and 3Department of Epidemiology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, P. R. China.

OBJECTIVE:: To assess the impact of menopause, age, and other factors on quality of life (QOL). DESIGN:: Generally healthy women aged 35 to 64 years were recruited from a general community in Beijing, People's Republic of China. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. RESULTS:: A gradual decline of QOL was seen from pre- to peri- and postmenopausal women in the same age group. Statistically impaired QOL was associated with the peri- and postmenopausal women in vasomotor and physical domains but only with the postmenopausal women in psychosocial and sexual domains. Early postmenopausal women presented the worse QOL in vasomotor, psychosocial and physical domains. The gradually declining sexual QOL was related to the advance of menopause. Age had a negative impact on QOL in vasomotor and sexual domains. Women who assessed their own health as common (fair) or weak (poor) reported worse QOL than those who decribed themselves as healthy. Women with a higher body mass index reported more vasomotor symptoms. CONCLUSIONS:: Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longitudinal studies. The association of QOL with age and other factors also should be considered.

J Allergy Clin Immunol. 2007 Oct 26; [Epub ahead of print

Lung function, respiratory symptoms, and the menopausal transition.

Real FG, Svanes C, Omenaas ER, Antò JM, Plana E, Jarvis D, Janson C, Neukirch F, Zemp E, Dratva J, Wjst M, Svanes K, Leynaert B, Sunyer J.

From the Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen; Centre de Recerca en Epidemiologia Ambiental (CREAL)–Institut Municipal d'Investigació Mèdica (IMIM-IMAS), Barcelona; Respiratory Research Group, Institute of Medicine, University of Bergen.

BACKGROUND: There is limited information on potential changes in respiratory health when women enter the menopausal transition. OBJECTIVE: We sought to investigate whether the menopausal transition is related to lung function and asthma and whether body mass index (BMI) modifies associations. METHODS: Four thousand two hundred fifty-nine women from 21 centers (ECRHS II, 2002) responded to a questionnaire concerning women's health. Women aged 45 to 56 years not using exogenous sex hormones (n = 1274) were included in the present analysis. Lung function measurements (n = 1120) and serum markers of hormonal status (follicle-stimulating hormone, luteinizing hormone, and estradiol; n = 710) were available. Logistic and linear regression analyses were adjusted for BMI, age, years of education, smoking status, center, and height. RESULTS: Women not menstruating for the last 6 months (n = 432, 34%) had significantly lower FEV(1) values (-120 mL [95% CI, -177 to -63]), lower forced vital capacity values (-115 mL [95% CI, -181 to -50]), and more respiratory symptoms (odds ratio [OR], 1.82 [95% CI, 1.27-2.61]) than those menstruating regularly. Results were similar when restricting analyses to those who never smoked. Associations were significantly stronger in women with BMIs of less than 23 kg/m(2) (respiratory symptoms: OR, 4.07 [95% CI, 1.88-8.80]; FEV(1) adjusted difference: -166 [95% CI, -263 to -70]) than in women with BMIs of 23 to 28 kg/m(2) (respiratory symptoms: OR, 1.10 [95% CI, 0.61-1.97], P(interaction): .04; FEV(1) adjusted difference, -54 [95% CI, -151 to 43], P(interaction) = .06). CONCLUSIONS: Menopause is associated with lower lung function and more respiratory symptoms, especially among lean women. CLINICAL IMPLICATIONS: Clinicians should be aware of increased asthma risk and lower lung function in women reaching menopause. These problems appeared to be less pronounced among women with a BMI of approximately 25 kg/m(2)

Osteoporos Int. 2007 Nov 16; [Epub ahead of print

Greater first year effectiveness drives favorable cost-effectiveness of brand risedronate versus generic or brand alendronate: modeled Canadian analysis.

Grima DT, Papaioannou A, Thompson MF, Pasquale MK, Adachi JD.

Cornerstone Research Group Inc., 6–4380 South Service Road, Burlington, ON, L7L 5Y6, Canada, dgrima@cornerstone-research.com.

The RisedronatE and ALendronate (REAL) study provided a unique opportunity to conduct cost-effectiveness analyses based on effectiveness data from real-world clinical practice. Using a published osteoporosis model, the researchers found risedronate to be cost-effective compared to generic or brand alendronate for the treatment of Canadian postmenopausal osteoporosis in patients aged 65 years or older. INTRODUCTION: The REAL study provides robust data on the real-world performance of risedronate and alendronate. The study used these data to assess the cost-effectiveness of brand risedronate versus generic or brand alendronate for treatment of Canadian postmenopausal osteoporosis patients aged 65 years or older. METHODS: A previously published osteoporosis model was populated with Canadian cost and epidemiological data, and the estimated fracture risk was validated. Effectiveness data were derived from REAL and utility data from published sources. The incremental cost per quality-adjusted life-year (QALY) gained was estimated from a Canadian public payer perspective, and comprehensive sensitivity analyses were conducted. RESULTS: The base case analysis found fewer fractures and more QALYs in the risedronate cohort, providing an incremental cost per QALY gained of $3,877 for risedronate compared to generic alendronate. The results were most sensitive to treatment duration and effectiveness. CONCLUSIONS: The REAL study provided a unique opportunity to conduct cost-effectiveness analyses based on effectiveness data taken from real-world clinical practice. The analysis supports the cost-effectiveness of risedronate compared to generic or brand alendronate and the use of risedronate for the treatment of osteoporotic Canadian women aged 65 years or older with a BMD T-score </=-2.5.

Clin Endocrinol (Oxf). 2007 Nov 22; [Epub ahead of print

The evaluation of metabolic parameters and insulin sensitivity for a more robust diagnosis of the polycystic ovary syndrome.

Amato MC, Galluzzo A, Finocchiaro S, Criscimanna A, Giordano C.

Department: Section of Endocrinology, DOSAC, Università degli Studi di Palermo, Palermo, Italy.

Background: Polycistic Ovary Syndrome (PCOS) is considered a predominantly hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin sensitivity is not mandatory. Context: PCOS diagnostic criteria [National Institutes of Health (NIH), Rotterdam consensus (ROT), Androgen Excess Society (AES)] are unanimous recognized. We aimed to assess in women with suspected PCOS whether the application of the three diagnostic criteria differently characterizes the metabolic profile and insulin sensitivity. Design: Retrospective study in a cohort of women admitted to our Out-patient Clinic for suspected PCOS. Patients: 204 women with suspected PCOS in comparison to a group of normal, age-matched Sicilian women (N = 34) without signs of metabolic syndrome. Measurements: We evaluated hyperandrogenemia and clinical hyperandrogenism, ovarian morphology, hypothalamo-hypophyseal axis and metabolic syndrome parameters. An oral glucose tolerance test (OGTT; 75 g glucose) measured areas under the curve (AUC) for insulin, C peptide and homeostasis model assessment of insulin-resistance (HOMA-IR) were performed. Results: The prevalence of PCOS was 51% according to NIH, 83% to ROT and 70,6% to AES and only 100 patients qualified simultaneously to the three criteria. The prevalence of the metabolic syndrome in PCOS women was 26.92% (NIH), 21,77% (ROT) and 23,61% (AES), respectively. In comparison to healthy women, PCOS women showed increased fasting insulinemia (PCOS/ROT: p = 0.028; PCOS/NIH: p = 0.007; PCOS/EAS: p = 0.023), 120' insulin after OGTT insulinemia (for the 3 criteria: p < 0.001), AUC2h insulin (for the 3 criteria: p < 0.001) and AUC2h C peptide (for the 3 criteria: p < 0.001). Conclusions: Our study highlights the fact that regardless of the diagnostic criteria used, evaluation of the metabolic parameters and insulin sensitivity is important for a correct diagnosis of PCOS and a therapeutic approach.

J Am Geriatr Soc. 2007 Nov 20; [Epub ahead of print]

Weight, Mortality, Years of Healthy Life, and Active Life Expectancy in Older Adults.

Diehr P, O'Meara ES, Fitzpatrick A, Newman AB, Kuller L, Burke G.

Department of Biostatistics, University of Washington, Seattle, Washington, USA.

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults. DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults. SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline. MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated. RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes. CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a "healthy" weight may be much higher than currently believed.

MMWR Morb Mortal Wkly Rep. 2007 Nov 23;56(46):1209-12

Prevalence of regular physical activity among adults--United States, 2001 and 2005.

Centers for Disease Control and Prevention (CDC).

Regular physical activity is associated with decreased risk for obesity, heart disease, hypertension, diabetes, certain cancers, and premature mortality. CDC and the American College of Sports Medicine recommend that adults engage in at least 30 minutes of moderate physical activity on most days and preferably on all days. Healthy People 2010 objectives include increasing the proportion of adults who engage regularly in moderate or vigorous activity to at least 50% (objective 22-2). In addition, reducing racial and ethnic health disparities, including disparities in physical activity, is an overarching national goal. To examine changes in the prevalence of regular, leisure-time, physical activity from 2001 to 2005, CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the results of that analysis, which indicated that, from 2001 to 2005, the prevalence of regular physical activity increased 8.6% among women overall (from 43.0% to 46.7%) and 3.5% among men (from 48.0% to 49.7%). In addition, the prevalence of regular physical activity increased 15.0% (from 31.4% to 36.1%) among non-Hispanic black women and 12.4% (from 40.3% to 45.3%) among non-Hispanic black men, slightly narrowing previous racial disparities when compared with increases of 7.8% (from 46.0% to 49.6%) for white women and 3.4% (from 50.6% to 52.3%) for white men, respectively. CDC, state and local public health agencies, and other public health partners should continue to implement evidence-based, culturally appropriate initiatives to further increase physical-activity levels among all adults, with special focus on eliminating racial/ethnic disparities.

Semana del 14 al 20 de Noviembre de 2007

Menopause. 2007 Nov 12; [Epub ahead of print]

Effects of alcohol and cigarette smoking on change in serum estrone levels in postmenopausal women randomly assigned to fixed doses of conjugated equine estrogens with or without a progestin.

McDivit AM, Greendale GA, Stanczyk FZ, Huang MH.

From the 1Cleveland Clinic, General Internal Medicine, Cleveland, OH; 2Division of Geriatrics, David Geffen School of Medicine, University of California, Los Angeles; 3Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA.

OBJECTIVE:: To determine the effects of alcohol and smoking on serum estrone levels among women assigned to hormone therapy. DESIGN:: We analyzed the data from 676 participants in the Postmenopausal Estrogen/Progestin Interventions study. RESULTS:: Those who consumed more than 5.5 g of alcohol daily demonstrated greater rises in serum estrone than those who drank less (>0 to </=5.5 g/d) (P = 0.07) and those who were abstinent (P = 0.09). Current smokers had lesser gains in serum estrone compared with former smokers (P < 0.0001) and never smokers (P < 0.0001). CONCLUSIONS:: Alcohol consumption augmented and smoking diminished serum estrone levels achieved while women were taking hormone therapy.

Histol Histopathol. 2008 Feb;23(2):219-26.

Human postmenopausal ovary - hormonally inactive fibrous connective tissue or more?

Laszczynska M, Brodowska A, Starczewski A, Masiuk M, Brodowski J.

Laboratory of Embryology, Pomeranian Medical University, Szczecin, Poland. laszcz@sci.pam.szczein.pl.

The ovary undergoes several changes after the menopause. In this period, the main structural changes in both the cortex and medulla were observed. In the cortex, they included: 1) reduction of its thickness; 2) epithelial inclusions forming cysts; 3) blurring the line between medulla and cortex; 4) reduction of follicles number; 5) tendency to fragmentation of corpora albicantia; 6) surface epithelium invaginations. Whereas the changes in the medulla included: 1) fibrosis and scars in stroma; 2) architectonical changes in blood vessels with hyalinization of walls and constriction of lumen. The loss of follicles and several changes in the ovary are due to apoptotic processes. Despite age related atrophic changes, the postmenopausal ovary is not devoid of hormonal activity. Our results are coherent with the reports of other researchers, and reveal that postmenopausal ovary produces trace quantities of steroid hormones, mainly androgens, and confirm the presence of steroid receptors and activity of main enzymes involved in steroidogenesis process.

Maturitas. 2007 Nov 8; [Epub ahead of print]

Differences in health related quality of life in a sample of Spanish menopausal women with and without obesity.

Llaneza P, Iñarrea J, Gonzalez C, Alonso A, Arnott I, Ferrer-Barriendos J.

Central University Hospital of Asturias, C/ Celestino Villamil s/n, 33006 Oviedo, Spain.

OBJECTIVE: To investigate whether body mass index, abdominal obesity or fat distribution in postmenopausal women influence their quality of Life. METHODS: A cross-sectional study was carried out on 250 postmenopausal women (age: 50-64 years), with intact uterus and ovaries, sexually active, and non-hormone therapy users. Various anthropometric measurements were considered and a specific health-related quality of life (HR-QoL) instrument, the Cervantes scale, was performed. RESULTS: Thirty-three women were not included as they refused to participate in the study, had chronic disease such as hypertension, diabetes type 2, depression or did not answer all the scale items, so 217 patients were evaluated. According with BMI values, 34% of women were obese, 46.1% were in overweight, 19.8% were in normal weight and there were not underweight women. Any consistent relation was found between BMI and global values of HR-QoL, but obese women were diagnosed with "high level of problems" in the "psychical domain" and in the "sexuality domain". This difference in "sexuality domain" was also appreciated in women with abdominal obesity. Fat or lean mass was not correlated with HR-QoL. CONCLUSION: In our study, obesity did not affect the global HR-QoL in Spanish postmenopausal women, but could have an influence on the psychical and sexual domains. Others anthropometric measurements are not associated with changes in HR-QoL. Additional research with HR-QoL specific and validated instruments and with a longitudinal design seems necessary to confirm our results.

Fertil Steril. 2007 Nov 12; [Epub ahead of print]

Effect of oral estrogen on substrate utilization in postmenopausal women.

Lwin R, Darnell B, Oster R, Lawrence J, Foster J, Azziz R, Gower BA.

Department of Nutrition Sciences.

We tested the hypothesis that a 2-month intervention with unopposed oral conjugated equine estrogens (0.625 mg/d) would decrease lipid oxidation, as assessed by 24-hour, whole-room, indirect calorimetry in 14 postmenopausal women. Estrogen (E) treatment was associated with declines in both 24-hour and postprandial lipid oxidation and an increase in fat mass (mean [+/-SD] 2-month difference 1.1 +/- 1.0 kg; mean 6-month difference 1.8 +/- 2.2 kg), suggesting that, on an acute basis, oral E may increase adiposity by limiting lipid oxidation.

Nutr Cancer. 2007;59(2):269-277.

Black Cohosh Does Not Exert an Estrogenic Effect on the Breast.

Ruhlen RL, Haubner J, Tracy JK, Zhu W, Ehya H, Lamberson WR, Rottinghaus GE, Sauter ER.

Department of Surgery, University of Missouri-Columbia, Columbia, MO.

Women's Health Initiative findings indicate that hormone replacement therapy may increase breast cancer and cardiovascular disease risk. Black cohosh extract (BCE) is a popular alternative that reduced menopausal symptoms in several clinical trials. Preclinical studies have addressed the estrogenic properties of BCE, with conflicting results. The estrogenic influence of BCE on the breast has not been investigated. Black cohosh is standardized to triterpenes, but the activity and mechanism of action of these compounds are unknown. The study goals were to determine 1) triterpene content of 2 commercially available BCE preparations and 2) the effect of BCE on circulating and breast-specific estrogenic markers. Two black cohosh preparations were analyzed for triterpene content. Postmenopausal women took BCE for 12 wk followed by a 12-wk washout. One BCE preparation contained trace amounts and another contained 2.5% triterpenes. Women taking BCE with 2.5% triterpenes experienced relief of menopausal symptoms, with reversion toward baseline after washout. BCE had no effect on estrogenic markers in serum and no effect on pS2 or cellular morphology in nipple aspirate fluid. Triterpene content in commercially available black cohosh preparations varies. BCE standardized to 2.5% triterpenes relieved menopausal symptoms without systemic or breast-specific estrogenic effects.

J Natl Cancer Inst. 2007 Nov 15; [Epub ahead of print]

Predicting Risk of Breast Cancer in Postmenopausal Women by Hormone Receptor Status.

Chlebowski RT, Anderson GL, Lane DS, Aragaki AK, Rohan T, Yasmeen S, Sarto G, Rosenberg CA, Hubbell FA; For the Women's Health Initiative Investigators.

Affiliations of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA.

Background Strategies for estrogen receptor (ER)-positive breast cancer risk reduction in postmenopausal women require screening of large populations to identify those with potential benefit. We evaluated and attempted to improve the performance of the Breast Cancer Risk Assessment Tool (i.e., the Gail model) for estimating invasive breast cancer risk by receptor status in postmenopausal women. Methods In The Women's Health Initiative cohort, breast cancer risk estimates from the Gail model and models incorporating additional or fewer risk factors and 5-year incidence of ER-positive and ER-negative invasive breast cancers were determined and compared by use of receiver operating characteristics and area under the curve (AUC) statistics. All statistical tests were two-sided. Results Among 147 916 eligible women, 3236 were diagnosed with invasive breast cancer. The overall AUC for the Gail model was 0.58 (95% confidence interval [CI]=0.56 to 0.60). The Gail model underestimated 5-year invasive breast cancer incidence by approximately 20% (P<.001), mostly among those with a low estimated risk. Discriminatory performance was better for the risk of ER-positive cancer (AUC = 0.60, 95% CI = 0.58 to 0.62) than for the risk of ER-negative cancer (AUC = 0.50, 95% CI = 0.45 to 0.54). Age and age at menopause were statistically significantly associated with ER-positive but not ER-negative cancers (P=.05 and P=.04 for heterogeneity, respectively). For ER-positive cancers, no additional risk factors substantially improved the Gail model prediction. However, a simpler model that included only age, breast cancer in first-degree relatives, and previous breast biopsy examination performed similarly for ER-positive breast cancer prediction (AUC=0.58, 95% CI= 0.56 to 0.60); postmenopausal women who were 55 years or older with either a previous breast biopsy examination or a family history of breast cancer had a 5-year breast cancer risk of 1.8% or higher. Conclusions In postmenopausal women, the Gail model identified populations at increased risk for ER-positive but not ER-negative breast cancers. A model with fewer variables appears to provide a simpler approach for screening for breast cancer risk.

Osteoporos Int. 2007 Nov 13; [Epub ahead of print]

Calcium and vitamin D intake influence bone mass, but not short-term fracture risk, in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study.

Nieves JW, Barrett-Connor E, Siris ES, Zion M, Barlas S, Chen YT.

Clinical Research Center, Helen Hayes Hospital, Route 9W, West Haverstraw, NY, 10993, USA.

The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. INTRODUCTION: Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. METHODS: The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. RESULTS: Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score </=-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. CONCLUSIONS: Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.

J Bone Miner Res. 2007 Nov 12; [Epub ahead of print]

Strontium Ranelate Reduces the Risk of Vertebral Fractures in Patients with Osteopenia.

Seeman E, Devogelaer J, Lorenc R, Spector T, Brixen K, Balogh A, Stucki G, Reginster J.

Microabstract Many fractures occur in women with moderate fracture risk due to osteopenia. Strontium ranelate was studied in 1431 postmenopausal women with osteopenia. Vertebral fracture risk reduction of 41% to 59% was shown depending on the site and fracture status at baseline. This is the first report of anti-vertebral fracture efficacy in women with vertebral osteopenia.

Maturitas. 2007 Nov 8; [Epub ahead of print]

A study of 17beta-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy.

Cotreau MM, Chennathukuzhi VM, Harris HA, Han L, Dorner AJ, Apseloff G, Varadarajan U, Hatstat E, Zakaria M, Strahs AL, Crabtree JS, Winneker RC, Jelinsky SA.

Discovery Translational Medicine, Wyeth Research, Cambridge, MA, United States.

BACKGROUND: Vaginal atrophy (VA) is a prevalent disorder in postmenopausal women that is characterized by decreased epithelial thickness, reduced vaginal maturation index (VMI) and increased vaginal pH. Current medical therapy consists of local or systemic replacement of estrogens. OBJECTIVE: The goal of this study was to understand, at a molecular level, the effect of estradiol (E2) on the vaginal epithelium. METHODS: Nineteen women were treated with E2 delivered through a skin patch at a dose of 0.05mg/day for 12 weeks. The diagnosis of VA was confirmed by a VMI with </=5% superficial cells and vaginal pH>5.0. Vaginal biopsy samples were collected at baseline and after treatment. Differentially expressed mRNA transcripts in these biopsies were determined by microarray analysis. RESULTS: All 19 subjects had increased VMI (>5%) and/or reduced pH (</=5) following treatment. Most subjects also had increased serum E2 levels and reduced serum FSH levels. Transcriptional profiling of vaginal biopsies identified over 3000 E2-regulated genes, including those involved in several key pathways known to regulate cell growth and proliferation, barrier function and pathogen defense. CONCLUSIONS: E2 controls a plethora of cellular pathways that are concordant with its profound effect on vaginal physiology. The data presented here are a useful step toward understanding the role of E2 in vaginal tissue and the development of novel therapeutics for the treatment of VA.

Clin Biochem. 2007 Oct 26; [Epub ahead of print]

Effects of bone disease and calcium supplementation on antioxidant enzymes in postmenopausal women.

Hahn M, Conterato GM, Frizzo CP, Augusti PR, da Silva JC, Unfer TC, Emanuelli T.

Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.

OBJECTIVES:: The study was aimed at investigating the effects of osteopenia and calcium supplementation on antioxidant enzyme activity (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) in postmenopausal women. DESIGN AND METHODS:: Postmenopausal women (n=75) were divided into two groups, control (no bone disease) and osteopenia, according to their bone mineral density. Each group was still divided into calcium-supplemented and nonsupplemented sub-groups. Antioxidant enzyme activities were determined in whole blood using spectrophotometric methods. RESULTS:: CAT and SOD activities were not different among the studied groups. However, GPx activity was significantly higher in osteopenia groups as compared to control groups. Calcium supplementation had no effect on the parameters evaluated. Bone mineral density was negatively correlated with GPx activity (p<0.05). CONCLUSIONS:: Increased GPx activity could be interpreted as a defense response to counteract the overproduction of reactive oxygen species in women with osteopenia, and this effect was not prevented by calcium supplementation.

BJOG. 2007 Dec;114(12):1522-9.

Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.

Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA; TOTAL Study Investigators Group.

Division of Obstetrics and Gynecology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.

Objectives The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E(2)/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. Design A randomised, double-blind, double-dummy, group comparative intervention trial. Setting Multicentre study executed in 32 centres in 7 European countries. Sample Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years. Methods Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E(2)/NETA) daily for 48 weeks. Main outcome measures Prevalence of vaginal bleeding, hot flushes and adverse events. Results The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E(2)/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E(2)/NETA (3.2 versus 9.8%; P < 0.001). Conclusion Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.

Semana del 7 al 13 de Noviembre de 2007

Am J Clin Nutr. 2007 Nov;86(5):1572S-6S.

Keeping the young-elderly healthy: is it too late to improve our health through nutrition?

Rivlin RS.

Anne Fisher Nutrition Center, Strang Cancer Research Laboratory, and Department of Medicine, Weill Medical College of Cornell University, New York, NY.

Healthy older individuals can take several measures to preserve and improve their health. Even if past nutritional and lifestyle practices were not optimal, much can be done to reduce the risk of chronic disease and disability in future years. The first challenge is to recognize and address the profound changes in body composition that occur with aging. Older persons tend to accumulate relatively more body fat and less lean body mass, ie, muscle and bone. With a gain in body weight, which usually occurs, these changes are exaggerated. Because muscle tissue has a much higher metabolic rate than does fat tissue, older individuals generally develop lower metabolic rates. To avoid excess weight gain, older individuals must make major restrictions in caloric intake and increases in energy expenditure. Women experience changes in body composition similar to those in men, with changes becoming more prominent at menopause. Exercise improves body composition among healthy elderly, both by reducing fat mass and by increasing bone and muscle mass, thereby helping to restore higher metabolic rates. In men and women aged >/=65 y and taking calcium and vitamin D supplements for 3 y, the rate of bone loss slowed and the incidence of nonvertebral fractures was reduced. Several population studies of older persons show that following nutritional and lifestyle guidelines for cancer prevention reduces risk by one-third. Improving serum lipid concentrations in adults over 65 y of age with coronary artery disease decreases the risk of future cardiac events by as much as 45%. Furthermore, the greatest benefit from control of hypertension is in older individuals.

Am J Clin Nutr. 2007 Nov;86(5):1445-55.

Associations between healthy eating patterns and immune function or inflammation in overweight or obese postmenopausal women.

Boynton A, Neuhouser ML, Wener MH, Wood B, Sorensen B, Chen-Levy Z, Kirk EA, Yasui Y, Lacroix K, McTiernan A, Ulrich CM.

Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, WA, University of Washington, Seattle, WA.

BACKGROUND: The link between poor nutritional status and impaired immune function is well established; however, most studies have focused on individual nutrients instead of overall dietary patterns. OBJECTIVE: Our objective was to investigate associations between 3 indexes of overall diet quality [the Diet Quality Index (DQI), the DQI including supplementary calcium (DQI-Ca), and the Healthy Eating Index (HEI)] and biomarkers of inflammation and immunity. DESIGN: This cross-sectional study included 110 overweight or obese postmenopausal women. Dietary intake measured by food-frequency questionnaire was used to calculate diet quality scores. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by latex-enhanced nephelometry. Flow cytometry was used to measure natural killer (NK) cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T lymphocyte proliferation was assessed by (3)H-thymidine incorporation as well as by the carboxyfluorescein-succinimidyl ester method of cell division tracking. Multivariable-adjusted linear regression analysis was used to investigate associations between diet quality scores and markers of inflammation and immune function. RESULTS: Higher diet quality was associated with increased proportions of cytotoxic and decreased proportions of helper T lymphocytes. CRP and SAA concentrations were higher among women with a lower-quality diet; these associations became nonsignificant after adjustment for body mass index or percentage body fat. We observed limited evidence for an association between healthy eating patterns and greater lymphocyte proliferation and no evidence for an association with NK cell cytotoxicity. CONCLUSION: Our results provide limited evidence that healthy eating patterns contribute to enhanced immune function and reduced inflammation in overweight and obese postmenopausal women.

Am J Clin Nutr. 2007 Nov;86(5):1420-1425.

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women.

Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, Aviv A.

From Twin Research and Genetic Epidemiology, St Thomas’ Hospital, King's College, London School of Medicine, London, United Kingdom.

BACKGROUND: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation. OBJECTIVE: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL. DESIGN: Serum vitamin D concentrations were measured in 2160 women aged 18-79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method. RESULTS: Age was negatively correlated with LTL (r = -0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation. CONCLUSION: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.

Harefuah. 2007 Oct;146(10):781-4, 813.

Extended cycle oral contraceptives

Geist R, Beyth Y.

Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem. rgeist@isdn.net.il

Oral contraceptive pills are conventionally prescribed in a manner that causes monthly withdrawal uterine bleeding (lunar month). The reasons for this are historical without an inherent medical need. According to our literature search, there are patients' demands for less frequent menstrual cycles. We have learned from patients who were given the pill continuously for long periods due to medical or social indications that continuous administration of the contraceptive pill is feasible and safe. In the current review, the authors have searched the literature regarding extended cycle oral contraception for periods of time up to one year. This way of administration of the pill is not compromising the efficacy of pregnancy prevention, nor is it detrimental in terms of cardiovascular and hemostatic complications or endometrial malignancy. It is known that there is a slightly increased risk of breast cancer in users of oral contraceptives up to 10 years, regardless of the mode of administration. From a few studies of hormone replacement therapy in postmenopausal women, there is concern that continuous treatment may be deleterious, while sequential is not. Extended cycle contraceptive treatment has a few side effects, mainly increased breakthrough bleeding but decreased withdrawal bleeding. Other side effects were less prevalent than in conventional administration.

Br J Cancer. 2007 Nov 6; [Epub ahead of print]

Hormone replacement therapy, body mass, and the risk of colorectal cancer among postmenopausal women from Germany.

Hoffmeister M, Raum E, Winter J, Chang-Claude J, Brenner H.

1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.

Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case-control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25-0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to <30 kg m(-2) (2.76, 1.07-7.12) and obese women (3.30, 1.25-8.72), when compared with women with BMI <23 kg m(-2) (P for trend <0.01). BMI was not associated with risk of CRC among HRT users (P for interaction <0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study.

BMJ. 2007 Nov 6; [Epub ahead of print]

Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study.

Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D.

Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF.

OBJECTIVE: To examine the relation between body mass index (kg/m(2)) and cancer incidence and mortality. DESIGN: Prospective cohort study. PARTICIPANTS: 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. MAIN OUTCOME MEASURES: Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. RESULTS: 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. CONCLUSIONS: Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.

Fertil Steril. 2007 Nov 1; [Epub ahead of print]Links

Educational and organizational interventions used to improve the knowledge of metabolic syndrome among postmenopausal women.

Barriga J, Castelo-Branco C, Chedraui P, Hidalgo L, Veas P.

Institute of Biomedicine of the Medical Faculty of the Universidad Católica of Guayaquil, Ecuador.

A total of 105 postmenopausal women previously diagnosed with metabolic syndrome consented to take part in this educational program. After receiving the training, women significantly improved their knowledge regarding menopause and related issues, and, since the program increased their awareness of menopause and related risks, we propose that these cost-effective measures could eventually reduce cardiovascular morbidity and mortality among high-risk populations.

J Clin Endocrinol Metab. 2007 Nov 6; [Epub ahead of print]

Insulin Secretion and Clearance After Subacute Estradiol Administration in Postmenopausal Women.

Van Pelt RE, Schwartz RS, Kohrt WM.

Department of Medicine, Division of Geriatric Medicine, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80262.

Context: Data from large clinical trials of postmenopausal women suggest incidence of diabetes is reduced in women randomized to estrogen-based hormone therapy when compared with placebo. Whether this is due to an effect of estrogen on insulin or glucose metabolism remains unclear. Objective: To test the hypothesis that estradiol (E2) increases insulin secretion and clearance. Design: Serum insulin and C-peptide responses to hyperglycemia (250 mg/dL) plus intravenous L-arginine were measured on 2 separate days, with (EST) and without (CON) subacute (24 h) transdermal E2 administration. Study Participants: Eleven postmenopausal women (mean+/-SD; 55+/-4 y). Main Outcomes: Insulin secretion and clearance were estimated from the C-peptide AUC and the molar ratio of C-peptide-to-insulin AUC, respectively. Mean glucose disposal rate (GDR) was estimated from the rate of glucose infusion during the final 30 min of the hyperglycemic clamp. Results: There were no differences in insulin secretion or clearance between the EST day and CON day. Fasting glucose was lower on the EST day compared with the CON day (93+/-6 vs. 98+/-8 mg/dL), but mean GDR was not different. However, when one outlier was excluded from analysis GDR was increased after EST compared with CON. Further, a strong inverse association was observed between years since menopause and E2-mediated changes in GDR (r=-0.794, p=0.004). Conclusions: Contrary to our hypothesis, 24 hours of transdermal E2 administration did not alter insulin secretion or clearance in postmenopausal women. However, a longer time since menopause was associated with a reduced effect of E2 to increase glucose uptake.

Eur J Epidemiol. 2007 Nov 6; [Epub ahead of print]

Inflammation a possible link between economical stress and coronary heart disease.

Gémes K, Ahnve S, Janszky I.

Preventive Medicine, Department of Public Health Sciences, Karolinska Institutet, Karolinska Hospital, Norrbacka 6th floor, 17176, Stockholm, Sweden, staffan.ahnve@ki.se.

Objective: To assess the relationship between economical stress, as an indictor of SES, and inflammation in women patients with coronary heart disease (CHD). Design: a cross-sectional study. Setting and participants: Two hundred and thirteen women patients recruited from two hospitals in Stockholm, Sweden; mean age 63 +/- 8, range 35-75 years, hospitalised for acute myocardial infarction, coronary angioplasty or bypass surgery between 1996 and 2000, examined in a stable phase, 1 year and 5 months (+/-2.5 months) after the index event. Main outcome measures: Economical stress, and other SES indicators were assessed by questionnaires. Levels of high-sensitivity C-reactive protein (CRP) were measured by nephelometry and the concentrations of interleukin-6 (Il-6) and interleukin-1 receptor antagonist (Il-1ra) were determined by enzyme-linked immunoassay. Results: After controlling for the potential confounders, i.e. treatment, menstruational, marital and education status in addition to age, patients having economical stress showed higher levels of hsCRP (2.79 vs. 1.83 mg/l, p = 0.04), Il-6 (3.12 vs. 2.38 mg/l, p = 0.015) and Il-1ra (599 vs. 456 mg/l, p = 0.02). The association persisted after controlling for other measures of economical status, like personal and household income. According to our mediational analyses, lifestyle variables, especially BMI, could partly explain the observed association. Conclusion: High economical stress was associated with higher Il-6, CRP and Il-1ra levels in women with stable CHD. The direction of causality cannot be inferred from such a cross-sectional study however, our results raise the possibility that increased inflammatory activity is a mediator for the effect of economical stress on adverse outcomes after a coronary event.

Semana del 31 de Octubre al 6 de Noviembre de 2007

Menopause. 2007 Oct 19; [Epub ahead of print]

NIH and WHI-time for a mea culpa and steps beyond*

Utian WH.

From The North American Menopause Society.

The termination of the estrogen-progestin arm of the Women's Health Initiative (WHI) 5 years ago was abrupt and poorly planned. It has also become manifestly clear that the reporting at that time of the balance of risk and benefit for perimenopausal and early postmenopausal women was grossly exaggerated. Subsequent WHI publications including subanalyses of original data suggest a persistent pattern of over-reading of results toward a negative bias. The initial 2002 conclusion of the WHI investigators that harm was greater than benefit appears to be the result of several factors. One was the failure to recognize that initiation of therapy by decade of age or time since menopause was highly relevant; the WHI committee aggregated all outcome data into one group, even though in their demographic description they had the ability to investigate by age. An overhanging question is, therefore, what did they know, and when did they know it? Another factor was the utilization of a nonvalidated index termed the "global health index" that inexplicably assumed for comparison sake that all diseases were equivalent, for example, that a stroke was equivalent to a hip fracture in morbidity, mortality, and impact on quality of life. Although not a study about menopause, the data were extrapolated to all peri- and postmenopausal women. Despite the overall positive outcome of their results for women aged 50 to 60 years, most particularly those receiving estrogen-only therapy, the WHI investigators have irrationally maintained a defense of their misinterpretations of 2002. It is time for the National Institutes of Health and the WHI investigators to issue a final overall report that is clear and based on their actual results and not their personal interpretations. There is too much relevant and important information within the WHI to allow the overall study to continue to be perceived as biased to the detriment of both the National Institutes of Health and the study itself.

J Fam Pract. 2007 Nov;56(11):907-910.

Double-dose vitamin D lowers cancer risk in women over 55.

Schumann SA, Ewigman B.

Department of Family Medicine, The University of Chicago, Chicago, IL USA.

Wouldn't it be nice if we could recommend something as simple and safe as a daily vitamin to reduce the risk of cancer? Until now, we have had no definitive evidence to support such a recommendation. The Lappe et al trial, however, concluded that improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. Will this single, relatively small study pass the test of time and be confirmed by future clinical trials? We think so. The estimated relative risk reduction was dramatic (0.232) and the 95% confidence interval was 0.09 to 0.60, meaning that the true relative risk reduction has a 95% probability of being in the range of 40% to 91%. The P value of <.005 suggests that the probability of this finding occurring by chance alone is less than 1 in 200. Our critical appraisal found no significant flaws in this randomized controlled trial. Vitamin D is known to have cancer protective effects at the cellular level. Prior population based studies support the association between vitamin D and cancer prevention. For these reasons--and the fact that 1000 IU vitamin D is very safe for most patients--we find this single RCT convincing as a practice changer. For us, the potential benefit outweighs the potential harm. The criteria and findings leading to the selection of this study as a Priority Update from the Research Literature can be accessed at www.jfponline.com/purls.

J Cell Biochem. 2007 Nov 1; [Epub ahead of print]

Understanding the pathology and mechanisms of type I diabetic bone loss.

McCabe LR.

Department of Physiology, Michigan State University, Michigan 48824.

Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1-diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1-diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra-membranous, and axial and appendicular bones are susceptible to T1-diabetic bone loss. Exact mechanisms accounting for T1-diabetic bone loss are not known. Existing data indicate that the bone defect in T1-diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1-diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1-diabetic- and age-associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1-diabetic patients to live longer with strong healthy bones.

Carcinogenesis. 2007 Oct 31; [Epub ahead of print]

Serum 25-hydroxyvitamin D and risk of postmenopausal breast cancer - results of a large case-control study.

Abbas S, Linseisen J, Slanger T, Kropp S, Mutschelknauss E, Flesch-Janys D, Chang-Claude J.

Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.

Various studies suggest that vitamin D may reduce breast cancer risk. Most studies assessed the effects of dietary intake only, although endogenous production is an important source of vitamin D. Therefore, the measurement of serum 25-hydroxyvitamin D [25(OH)D] better indicates overall vitamin D status. To assess the association of 25(OH)D serum concentrations with postmenopausal breast cancer risk, we used a population-based case-control study in Germany, which recruited incident breast cancer patients aged 50-74 between 2002 and 2005. Information on sociodemographic and breast cancer risk factors was collected by personal interview. For this analysis, we included 1394 cases and 1365 controls, matched on year of birth and time of blood collection. Conditional logistic regression was used to calculate odds ratios for breast cancer adjusted for potential confounders. Serum 25(OH)D concentration was significantly inversely associated with postmenopausal breast cancer risk. Compared with the lowest category (< 30 nM), odds ratios and 95% confidence intervals [OR (95% CI)] for the higher categories of 25(OH)D (30-45, 45-60, 60-75, >/= 75 nM) were 0.57 (0.45-0.73), 0.49 (0.38-0.64), 0.43 (0.32-0.57) and 0.31 (0.24-0.42), respectively (p(trend) <0.0001). Analysis using fractional polynomials indicated a non-linear association. The association was stronger in women never using menopausal hormone therapy compared to past and current users (p(interaction) <0.0001). Our findings strongly suggest a protective effect for postmenopausal breast cancer through a better vitamin D supply as characterized by serum 25(OH)D measurement, with a stronger inverse association in women with low serum 25(OH)D concentrations (< 50 nM).

Clin Endocrinol (Oxf). 2007 Oct 31; [Epub ahead of print

Effect of progestins with different glucocorticoid activity on bone metabolism.

Ishida Y, Mine T, Taguchi T.

Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Japan.

Objective Progestins are commonly prescribed for hormone replacement therapy (HRT) and contraception. However, the effects of progestins on bone metabolism remain unclear and are often controversial. Design and patients This study was conducted to test the hypothesis that progestins with no significant glucocorticoid activity may be a better choice for HRT to achieve increased beneficial effects on bone metabolism than progestins with strong glucocorticoid activity. A total of 104 postmenopausal women aged 50-75 years with osteoporosis were allocated randomly to three groups: (1) conjugated oestrogen plus medroxyprogesterone acetate (HRT-MPA, with significant glucocorticoid activity); (2) conjugated oestrogen plus norethisterone (HRT-NET, with no significant glucocorticoid activity); and (3) control (no treatment). Measurements Vertebral X-rays and bone mineral density (BMD) at distal 1/3 radius were assessed at baseline and every 6 months during the 2-year study period, along with markers of bone turnover. The occurrence of new nonvertebral fractures was identified by X-ray. Results After the 2-year treatment, mean BMD changes relative to baseline in the HRT-MPA, HRT-NET and control groups were 1.6%, 2.3% and -1.9%, respectively. In addition, the rate of increase in HRT-NET was significantly greater than that in HRT-MPA (P = 0.019). The incidence of new fractures during the 2-year treatment in the control group was 26% (9/34). HRT-NET treatment significantly inhibited the occurrence of new fractures (RR 0.14, 95% CI 0.02-0.93, P = 0.04), while HRT-MPA treatment failed to show a statistically significant reduction (RR 0.41, 95% CI 0.14-1.24, P = 0.11). Both HRT-MPA and HRT-NET treatments significantly decreased serum osteocalcin levels by 29.4% and 23.5%, respectively, after 6 months of treatment, with the decrease in HRT-MPA being significantly greater than that in HRT-NET (P = 0.042). Conclusions These findings suggest that progestins with no significant glucocorticoid activity may be a better choice for HRT, resulting in increased beneficial effects on bone metabolism compared with progestins with strong glucocorticoid activity.

J Clin Endocrinol Metab. 2007 Oct 30; [Epub ahead of print

Reduced Bone Mineral Density Is Associated With Breast Arterial Calcification.

Reddy J, Bilezikian JP, Smith SJ, Mosca L.

Brigham and Women's Hospital, Boston, Columbia University College of Physicians and Surgeons, NY.

Background: Arterial calcification, a marker of atherosclerosis, results from a complex process of biomineralization resembling bone formation. Breast arterial calcification (BAC) has been associated with angiographic and clinical cardiovascular disease (CVD). The purpose of this study was to determine the association between reduced bone mineral density (BMD) and BAC, which may share a common pathophysiology. Methods: We conducted a retrospective study of 228 women (55% Hispanic, mean age 64 +/-10 yrs) who had both mammography and BMD evaluation at Columbia University Medical Center between 2001-2003. Each mammogram was reviewed for the presence of BAC using standardized methods. BMD was measured using dual-energy x-ray absorptiometry (DXA) and categorized as normal, low bone density (osteopenia) or osteoporosis as defined by the World Health Organization. Univariate and multivariate logistic regression analyses were performed to evaluate the association between reduced BMD and BAC. Results: The prevalence of BAC, low bone density (osteopenia), and osteoporosis was 39%, 42%, and 29% respectively. Women with BAC were significantly more likely to be older, Hispanic, postmenopausal, and have osteoporosis as compared to women without BAC. In age-adjusted analyses, women with BAC were more likely to have reduced BMD (OR 3.0, P < 0.01) as compared to women without BAC. Furthermore, osteoporosis was strongly associated with the presence of BAC (OR 3.5, P < 0.01). Conclusion: These data suggest that osteoporosis and arterial calcification are strongly and independently correlated. Reduced BMD may identify women at risk of vascular disease.

J Bone Miner Res. 2007 Oct 29; [Epub ahead of print

Risedronate Reduces Osteoclast Precursors and Cytokine Production in Postmenopausal Osteoporotic Women.

D'Amelio P, Grimaldi A, Di Bella S, Tamone C, Brianza SZ, Ravazzoli MG, Bernabei P, Cristofaro MA, Pescarmona GP, Isaia G.

Microabstract This paper studies the effect of oral risedronate on osteoclast precursors, osteoclast formation and cytokine production in 25 osteoporotic women. Risedronate is effective in reducing the number of osteoclast precursors, their formation, vitality and activity and the level of RANKL and TNF alpha in cultures.

Int J Cancer. 2007 Oct 26; [Epub ahead of print

Interactions between intakes of alcohol and postmenopausal hormones on risk of breast cancer.

Nielsen NR, Grønbæk M.

National Institute of Public Health, Copenhagen, Denmark.

Alcohol and postmenopausal hormone use are well-established modifiable risk factors for breast cancer. Alcohol may decrease the metabolic clearance of estradiol, whereby the risk of breast cancer associated with hormone use may depend on blood alcohol levels. The objective is to determine whether alcohol interacts with hormone use on risk of breast cancer. The 5,035 postmenopausal women who participated in the Copenhagen City Heart Study were asked about their alcohol intake and hormone use at baseline in 1981-1983 and were followed until 2002 in the Danish cancer registry, with <0.1% loss to follow-up. Proportional hazard models were used to analyze data. During follow-up, 267 women developed breast cancer. Alcohol consumption was associated with a small increased risk of breast cancer (hazard ratio = 1.11 per drink/day, 95% CI: 0.99-1.25). Women who used hormones also had a higher risk of breast cancer (HR = 2.00, 95% CI: 1.52-2.61) compared to nonhormone users. We found an interaction between these 2 factors; those who had an intake of more than 2 drinks per day and took hormones had a risk of 4.74 (95% CI: 2.61-8.59) for breast cancer compared to abstainers who did not use hormones. Alcohol was not associated with breast cancer among women who did not use hormones (HR = 0.98 per drink/day, 95% CI: 0.82-1.78). In conclusion, the interaction between alcohol and hormone use should, if confirmed in other studies, have an impact both on the prescription of hormones and on sensible drinking limits for postmenopausal women.

Osteoporos Int. 2007 Oct 27; [Epub ahead of print

Relationships between fat and bone.

Reid IR.

Faculty of Medical and Health Sciences, University of Auckland, New Zealand, i.reid@auckland.ac.nz.

Body weight impacts both bone turnover and bone density, making it, therefore, an important risk factor for vertebral and hip fractures and ranking it alongside age in importance. The effect of body weight is probably contributed to by both fat mass and lean mass, though in postmenopausal women, fat mass has been more consistently demonstrated to be important. A number of mechanisms for the fat-bone relationship exist and include the effect of soft tissue mass on skeletal loading, the association of fat mass with the secretion of bone active hormones from the pancreatic beta cell (including insulin, amylin, and preptin), and the secretion of bone active hormones (e.g., estrogens and leptin) from the adipocyte. These factors alone probably do not fully explain the observed clinical associations, and study of the actions on bone of novel hormones related to nutrition is an important area of further research. An understanding of this aspect of bone biology may open the way for new treatments of osteoporosis. More immediately, the role of weight maintenance in the prevention of osteoporosis is an important public health message that needs to be more widely appreciated.

Ann Rheum Dis. 2007 Oct 26; [Epub ahead of print

Effects of strontium ranelate on spinal osteoarthritis progression.

Bruyere O, Delferriere D, Roux C, Wark JD, Spector T, Devogelaer JP, Brixen K, Adami S, Fechtenbaum J, Kolta S, Reginster JY.

University of Liege, Belgium.

OBJECTIVE: The aim of the present study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). METHODS: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment Of Peripheral OSteoporosis (TROPOS) trials performed on 1105 osteoporotic women with concomitant radiological spinal OA at baseline and for whom lumbar x-rays were available at baseline and over the 3-year treatment period. The presence and severity of osteophytes, disc space narrowing, and sclerosis in the lumbar intervertebral spaces was graded according to the method of Lane et al, and an overall OA score was calculated for each intervertebral space. Back pain (measured on a 5-point Likert scale only in SOTI) and health-related quality of life (SF-36 questionnaire) were assessed at baseline and after 3 years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. RESULTS: Strontium ranelate, compared with placebo, reduced by 42% the proportion of patients with worsening overall spinal OA score (RR, 0.58; 95% CI, 0.42-0.79; P=0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (P=0.03), while no significant difference was observed in terms of health-related quality of life between these patients groups. CONCLUSION: The results of this post-hoc analysis suggest that strontium ranelate could reduce radiographic spinal OA progression and back pain in osteoporotic women with prevalent spinal OA.

Horm Behav. 2007 Oct 25; [Epub ahead of print

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis.

Dumas J, Hancur-Bucci C, Naylor M, Sites C, Newhouse P.

Clinical Neuroscience Research Unit, University of Vermont College of Medicine, VT 05401, USA.

Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50-62) and older (ages 70-81) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA), or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding Task) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.