Sochiclim

Selección de Resúmenes de Menopausia

Abril de 2008

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

Semana del 23 al 29 de Abril de 2008

Curr Osteoporos Rep. 2008 Mar;6(1):39-46

Treatment of premenopausal women with low bone mineral density.

Columbia University, College of Physicians and Surgeons, Department of Medicine, New York, NY 10032, USA.

Interpretation of bone mineral density (BMD) results in premenopausal women is particularly challenging, because the relationship between BMD and fracture risk is not the same as for postmenopausal women. Z scores rather than T scores should be used to define "low BMD" in premenopausal women. The finding of low BMD in a premenopausal woman should prompt an evaluation for secondary causes of bone loss. If a secondary cause is found, management should focus on treatment of this condition. In some cases in which the secondary cause cannot be addressed, such as glucocorticoid therapy or cancer chemotherapy, treatment with a bone-active agent to prevent bone loss should be considered. In women with no fractures and no known secondary cause, low BMD may not signify compromised bone strength. BMD is likely to remain stable in these women, and pharmacologic therapy is rarely justified. Assessment of markers of bone turnover and follow-up bone density measurements can help to identify those with an ongoing process of bone loss that may indicate a higher risk for fracture, and possible need for pharmacologic intervention.

Curr Osteoporos Rep. 2008 Mar;6(1):24-30.

Combination anabolic and antiresorptive therapy for osteoporosis: opening the anabolic window.

Bilezikian JP.

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently increased our options. By stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities in addition to increasing bone mass. The only anabolic agent currently approved for osteoporosis by the US Food and Drug Administration, teriparatide (recombinant human parathyroid hormone ), has emerged as a major approach to selected patients with osteoporosis. Recombinant human parathyroid hormone (1-84) is also available in Europe. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. A current concept in the mechanism of teriparatide action is related to its effect to stimulate processes associated with bone formation before it stimulates processes associated with bone resorption. This sequence of events has led to the concept of the anabolic window, the period of time when teriparatide is maximally anabolic. Newer approaches to the use of teriparatide alone and in combination with antiresorptive agents have led to ways in which the anabolic window can be expanded.

Curr Osteoporos Rep. 2008 Mar;6(1):5-11.

Vitamin D therapy.

Geller JL, Adams JS.

Orthopaedic Hospital Research Center, UCLA, CA, USA.

The fat-soluble vitamin D prohormones, ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), are essential for the efficient intestinal absorption of calcium and phosphate and the subsequent mineralization of bone. Inadequate vitamin D leads to chronic secondary hyperparathyroidism and osteoporosis. The increasing prevalence of osteoporosis has paralleled a pandemic of vitamin D insufficiency. Based on observational and prospective trials with clinical end points, the standards for vitamin D sufficiency have been recently revised. All patients with osteopenia or osteoporosis should be monitored with a reliable assay to maintain serum 25-hydroxyvitamin D levels more than 32 ng/dL. Patients who are taking bisphosphonates and those with coexisting primary hyperparathyroidism are not exempt from taking supplemental vitamin D.

Curr Osteoporos Rep. 2007 Dec;5(4):153-9

The role of hormone therapy and calcium plus vitamin D for reduction of bone loss and risk for fractures: lessons learned from the Women's Health Initiative.

Jackson RD, Shidham S.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, OH 43210, USA.

Osteoporosis, a major public health problem, is characterized by increased risk for fracture. To reduce the morbidity and excess loss of life associated with this common disease, we need to understand the efficacy of treatment strategies for fracture reduction. The Women's Health Initiative Clinical Trials have extended our understanding of the effect of hormone therapy and calcium plus vitamin D supplements on risk for hip and total fractures. Although estrogen, with or without progestin, significantly decreases fracture risk at all skeletal sites-almost irrespective of underlying risk for osteoporosis-its risks outweigh its benefits, negating its general use for fracture reduction. For calcium-replete women, calcium plus vitamin D supplementation has a non-significant effect, hence the case for universal supplementation loses merit. But, that argument gains credibility for women over age 60-as a 21% reduction in hip fractures attests-showing that calcium plus vitamin D has a positive effect on bone health in older postmenopausal women.

Pol Arch Med Wewn. 2007 Nov-Dec;117(11-12):504-11.

Efficacy of non-pharmacological methods used for treating tobacco dependence: meta-analysis.

Bala MM, Lesniak W.

Department of Internal Medicine, Jagiellonian University School of Medicine, Krakow, Poland.

OBJECTIVES: The present paper discusses available data concerning the efficacy of non-pharmacological methods used in smoking cessation and describes the results of newly performed meta-analyses testing the 12-month efficacy of these methods. This study is part of a more comprehensive program analyzing the efficacy and cost-effectiveness of different methods used in smoking cessation. PATIENTS AND METHODS: During the first stage of the study a systematic review of available data was made in order to identify methods used in smoking cessation and assess their efficacy on the basis of already existing reliable systematic reviews or meta-analyses. In the second stage of the study the efficacious and available in Poland methods (identified during the first stage by available data search and interviews with healthcare providers) were tested using new meta-analyses with the aim to define their efficacy in achieving at least the 12-month continuous or prolonged abstinence. RESULTS: The findings of the first stage of the study revealed that the reviews performed according to the Cochrane Collaboration methodology contained the most complete and up-to-date data. Meta-analyses of randomised controlled trials performed during the second part of the study showed that non-pharmacological smoking cessation methods available in Poland, namely the physician's simple advice and individual and group counseling, increased the probability of smoking cessation and smoking abstinence for > or =12 months by 1.5 to 2 times and the number of patients who need to be treated to have one patient who stops smoking was about 30 for more intensive methods and 60 for the physician's simple advice. CONCLUSIONS: The study confirmed that non-pharmacological smoking cessation methods available in Poland, i.e. the physician's advice and individual and group counseling, increase the probability of smoking abstinence, and determined the 12-month effects of these interventions.

Thromb Haemost. 2008 Feb;99(2):338-42

Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis.

Adomaityte J, Farooq M, Qayyum R.

Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21187, USA.

Raloxifene, a selective estrogen receptor modulator, is indicated for the prevention of osteoporosis in postmenopausal women. However, its effect on the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is unclear. Therefore, we conducted a meta-analysis to evaluate the effect of raloxifene on these outcomes. To identify randomized controlled trials of raloxifene, a systematic search of PubMed, EMBASE, and Cochrane Collaboration databases was performed from the date of inception of these databases to October 2007. Search was limited to trials that were published in peer-reviewed English-language medical journals. Articles were included in the meta-analysis if they had reported on DVT, PE, or thromboembolic events. Nine trials, including 24,523 postmenopausal women, (median age 59.4 years, range 55 to 67 years; median follow-up 24 months, range 3 to 67 months) met inclusion criteria. Therapy with raloxifene was associated with a 62% increase in odds of either DVT or PE (odds ratio = 1.62; 95% confidence interval = 1.25 to 2.09; p-value < 0.001). Similarly, raloxifene therapy was associated with 54% increase in odds of DVT (odds ratio = 1.54; 95% confidence interval = 1.13 to 2.11; p-value = 0.006) and 91% increase in odds of PE alone (odds ratio = 1.91;95% confidence interval = 1.05 to 3.47; p-value = 0.03). Raloxifene increases the risk of DVT and PE in postmenopausal women.

Aust N Z J Obstet Gynaecol. 2008 Apr;48(2):207-13

Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women.

Viola AS, Gouveia D, Andrade L, Aldrighi JM, Viola CF, Bahamondes L.

Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Background: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. Aims: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. Methods: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m(2)). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. Results: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36-3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30-8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65-11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. Discussion: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.

JAMA. 2008 Apr 9;299(14):1678-89.

Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial.

Howard BV, Roman MJ, Devereux RB, Fleg JL, Galloway JM, Henderson JA, Howard WJ, et al.

MedStar Research Institute, 6495 New Hampshire Ave, Suite 201, Hyattsville, MD 20783, USA.

CONTEXT: Individuals with diabetes are at increased risk for cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested. OBJECTIVE: To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower vs standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, blinded-to-end point, 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events. INTERVENTIONS: Participants were randomized to aggressive (n=252) vs standard (n=247) treatment groups with stepped treatment algorithms defined for both. MAIN OUTCOME MEASURES: Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness (IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events. RESULTS: Mean target LDL-C and SBP levels for both groups were reached and maintained. Mean (95% confidence interval) levels for LDL-C in the last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (-0.012 mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also regressed (-0.02 mm(2) vs 1.05 mm(2); P < .001); and there was greater decrease in left ventricular mass index (-2.4 g/m(2.7) vs -1.2 g/m(2.7); P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87) did not differ significantly between groups. CONCLUSIONS: Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.

Semana del 16 al 22 de Abril de 2008

Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005131.

Oestrogens for preventing recurrent urinary tract infection in postmenopausal women.

Perrotta C, Aznar M, Mejia R, Albert X, Ng C.

BACKGROUND: Recurrent urinary tract infection (RUTI) is defined as three episodes of urinary tract infection (UTI) in the previous 12 months or two episodes in the last six months. The main factors associated with RUTI in postmenopausal women are vesical prolapse, cystocoele, post-voidal residue and urinary incontinence, all associated with a decrease in oestrogen. The use of oestrogens to prevent RUTI has been proposed. OBJECTIVES: To estimate the efficacy and safety of oral or vaginal oestrogens for preventing RUTI in postmenopausal women. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1950), EMBASE (from 1980), reference lists of articles without language restriction.Date of last search: February 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which postmenopausal women (more than 12 months since last menstrual period) diagnosed with RUTI received any type of oestrogen (oral , vaginal) versus placebo or any other intervention were included. DATA COLLECTION AND ANALYSIS: Authors extracted data and assessed quality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Nine studies (3345 women) were included. Oral oestrogens did not reduce UTI compared to placebo (4 studies, 2798 women: RR 1.08, 95% CI 0.88 to 1.33). Vaginal oestrogens versus placebo reduced the number of women with UTIs in two small studies using different application methods. The RR for one was 0.25 (95% CI 0.13 to 0.50) and 0.64 (95% CI 0.47 to 0.86) in the second. Two studies compared oral antibiotics versus vaginal oestrogens (cream (1), pessaries (1)). There was very significant heterogeneity and the results could not be pooled. Vaginal cream reduced the proportion of UTIs compared to antibiotics in one study and in the second study antibiotics were superior to vaginal pessaries. Adverse events for vaginal oestrogens were breast tenderness, vaginal bleeding or spotting, nonphysiologic discharge, vaginal irritation, burning and itching. AUTHORS' CONCLUSIONS: Based on only two studies comparing vaginal oestrogens to placebo, vaginal oestrogens reduced the number of UTIs in postmenopausal women with RUTI, however this varied according to the type of oestrogen used and the treatment duration.

Sao Paulo Med J. 2008 Jan;126(1):23-28.

Accuracy study on "Osteorisk": a new osteoporosis screening clinical tool for women over 50 years old.

Steiner ML, Fernandes CE, Strufaldi R, Azevedo LH, Stephan C, Pompei LM, Peixoto S.

Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, São Bernardo do Campo, São Paulo, Brazil.

CONTEXT AND OBJECTIVE: Osteoporosis is the greatest cause of quality-of-life reductions, morbidity and mortality among postmenopausal women, with growing incidence as populations age. Clinical tools like Osteorisk provide an easy-access and low-cost alternative method that helps physicians to reduce the need for dual-energy X-ray absorptiometry (DXA), the expensive gold standard examination for diagnosing osteoporosis. The aim here was to study the accuracy of Osteorisk using heel ultrasonography for bone mineral density (BMD). DESIGN AND SETTING: Cross-sectional study, at Faculdade de Medicina do ABC. METHODS: A structured questionnaire was applied to 615 postmenopausal women, with anthropometric measurements, Osteorisk calculations and quantitative ultrasound on the heel using Sonost 2000 equipment. RESULTS: 461 women were included, with mean age 60 ± 9 years, weight 67.6 ± 12.9 kg and body mass index (BMI) 28.8 ± 5.0 kg/m(2). Their Osteorisk classifications were: 61.0% low-risk, 28.4% medium-risk and 10.6% high-risk. Quantitative ultrasound showed 81.3% low-risk, 10.0% medium-risk and 8.7% high-risk regarding osteoporosis. Statistically significant results were observed (p < 0.001) when Osteorisk was correlated with age, years since menopause and BMI. Correlating these same variables with quantitative ultrasound, statistically significant results were observed for age (p < 0.001), years since menopause (p < 0.001) and BMI (p < 0.006). The sensitivity, specificity, negative predictive value and positive predictive value for Osteorisk were 64%, 6.7%, 89% and 30.6%, respectively. CONCLUSION: Osteorisk is a valid tool for screening for women at low risk of osteoporosis, making it possible for these women not to have to undergo densitometry.

Endocrinology. 2008 Apr 17 [Epub ahead of print]

Comparative analysis of the uterine and mammary gland effects of drospirenone and medroxyprogesterone acetate.

Otto C, Fuchs I, Altmann H, Klewer M, Walter A, Prelle K, Vonk R, Fritzemeier KH.

TRG Women's Healthcare (C.O., I.F., H.A., M.K., A.W., K.P., K.-H.F.), and Nonclinical Statistics (R.V.), Bayer Schering Pharma AG, Berlin, Germany.

The role of progestins in combined hormone therapy is the inhibition of uterine epithelial cell proliferation. The Women's Health Initiative (WHI) study provided evidence for an increased risk of breast cancer in women treated with conjugated equine estrogens (CEE) plus the synthetic progestin medroxyprogesterone acetate (MPA), compared to CEE-only treatment. These findings continue to be discussed and it remains to be clarified whether the results obtained for MPA in the WHI study are directly applicable to other progestins employed in hormone therapy. In this study we compared in a mouse model the effects of the synthetic progestins, MPA and drospirenone, in two major target organs: the uterus and the mammary gland. As quantitative measures of progestin activity, we analyzed maintenance of pregnancy, ductal sidebranching in the mammary gland, proliferation of mammary and uterine epithelial cells, as well as target gene induction in both organs. The outcome of this study is that not all synthetic progestins exhibit the same effects. MPA demonstrated uterine activity and mitogenic activity in the mammary gland at the same doses. In contrast, drospirenone behaved similarly to the natural hormone, progesterone, and exhibited uterine activity at doses lower than those leading to considerable proliferative effects in the mammary gland. We hypothesize that the safety of combined hormone therapy in postmenopausal women may be associated with a dissociation between the uterine and mammary gland activities of the progestin component.

Public Health Nutr. 2008 Apr 15;:1-4 [Epub ahead of print]

Low dietary calcium in European postmenopausal osteoporotic women.

Bruyere O, De Cock C, Mottet C, Neuprez A, Malaise O, Reginster JY.

1WHO Collaborating Center for Public Health Aspects of Osteoarticular Disorders and Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium.

OBJECTIVE: The WHO recommends a daily Ca intake for postmenopausal women of 1300 mg. The objective of the present study was to assess the dietary Ca intake in European postmenopausal osteoporotic women.Design, setting and subjectsAssessment of dietary Ca intake (food and supplements) was performed with a validated self-questionnaire in 8524 osteoporotic women from nine European countries (Belgium, Denmark, France, Germany, Hungary, Italy, Poland, Spain and the UK). RESULTS: Mean age of the patients was 74.2 (sd 7.1) years, mean BMI was 25.7 (sd 4.2) kg/m2. Of the study population, 37.2 % of the women took Ca supplements. The mean dietary intake of Ca was 930.7 (sd 422.9) mg/d. The lowest Ca intake was found in Hungary (586.7 (sd 319.1) mg/d) and the highest in Denmark (1145.6 (sd 463.0) mg/d). In the whole study population, only 19.1 % of the women had a dietary Ca intake >1300 mg/d. Only 17.1 % of women aged over 75 years achieved 1300 mg/d compared with 20.5 % of women aged less than 75 years (P = 0.0001 for the difference between the two groups).ConclusionDietary intake of Ca is very low in European postmenopausal women. A greater awareness is needed to resolve this public health problem.

J Sex Med. 2008 Apr 10 [Epub ahead of print]

Genital Responsiveness in Healthy Women With and Without Sexual Arousal Disorder.

Laan E, van Driel EM, van Lunsen RH.

Department of Sexology and Psychosomatic Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, The Netherlands.

Introduction. Most pharmacological treatments that are currently being developed for women with sexual arousal disorder are aimed at remedying a vasculogenic deficit. Aim. This study investigated whether pre- and postmenopausal women with sexual arousal disorder are less genitally responsive to visual sexual stimuli than pre- and postmenopausal women without sexual problems. Method. Twenty-nine medically healthy women with sexual arousal disorder (15 premenopausal and 14 postmenopausal), diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, and 30 age-matched women without sexual problems (16 premenopausal and 14 postmenopausal) were shown sexual stimuli depicting cunnilingus and intercourse. Main Outcome Measure. Genital arousal was assessed as vaginal pulse amplitude (VPA) using vaginal photoplethysmography. Results. Results showed no significant differences between the two groups in mean and maximum VPA, nor in latency of VPA response. Conclusion. Women with sexual arousal disorder diagnosed according to DSM-IV criteria were not less genitally responsive to visual sexual stimuli than women without such problems. These findings are in line with previous studies. The sexual problems these women report are clearly not related to their potential to become genitally aroused. We argue that the DSM-IV criteria for sexual arousal disorder are in need of revision. In medically healthy women, impaired genital responsiveness is not a valid diagnostic criterion.

J Sex Med. 2008 Apr 11 [Epub ahead of print]

Risk Factors for Female Sexual Dysfunction in the General Population: Exploring Factors Associated with Low Sexual Function and Sexual Distress.

Hayes RD, Dennerstein L, Bennett CM, Sidat M, Gurrin LC, Fairley CK.

School of Population Health, The University of Melbourne, Australia.

Introduction. No previous population-based studies have used validated instruments to measure female sexual dysfunction (FSD) in Australian women across a broad age range. Aim. To estimate prevalence and explore factors associated with the components of FSD. Main Outcome Measures. Sexual Function Questionnaire measured low sexual function. Female Sexual Distress Scale measured sexual distress. Methods. Multivariate analysis of postal survey data from a random sample of 356 women aged 20-70 years. Results. Low desire was more likely to occur in women in relationships for 20-29 years (odds ratio 3.7, 95% confidence intervals 1.1-12.8) and less likely in women reporting greater satisfaction with their partner as a lover (0.3, 0.1-0.9) or who placed greater importance on sex (0.1, 0.03-0.3). Low genital arousal was more likely among women who were perimenopausal (4.4, 1.2-15.7), postmenopausal (5.3, 1.6-17.7), or depressed (2.5, 1.1-5.3), and was less likely in women taking hormone therapy (0.2, 0.04-0.7), more educated (0.5, 0.3-0.96), in their 30s (0.2, 0.1-0.7) or 40s (0.2, 0.1-0.7), or placed greater importance on sex (0.2, 0.05-0.5). Low orgasmic function was less likely in women who were in their 30s (0.3, 0.1-0.8) or who placed greater importance on sex (0.3, 0.1-0.7). Sexual distress was positively associated with depression (3.1, 1.2-7.8) and was inversely associated with better communication of sexual needs (0.2, 0.05-0.5). Results were adjusted for other covariates including age, psychological, socioeconomic, physiological, and relationship factors. Conclusions. Relationship factors were more important to low desire than age or menopause, whereas physiological and psychological factors were more important to low genital arousal and low orgasmic function than relationship factors. Sexual distress was associated with both psychological and relationship factors.

JAMA. 2008;299(15):1764.

Testosterone and Depression

Joan Stephenson, PhD

Older men with lower levels of free testosterone may be morelikely to experience depression than are men with higher levelsof the sex hormone, according to a study by Australian scientists(Almeida O et al. Arch Gen Psychiatry. 2008;65[3]:283-289).The study involved nearly 4000 men aged 71 to 89 years, 203of whom met criteria for depression. After controlling for suchfactors as education level and cognitive scores, the researchersfound that the odds of depression in men with a free testosteroneconcentration in the lowest quintile (<6 ng/dL) was nearly3 times higher than that of men with a free testosterone concentrationof at least 10 ng/dL.A randomized controlled trial is needed to determine whetherthe link between testosterone and depression is causal, andif it is, "older men with depression may benefit from systematicscreening of free testosterone concentration and testosteronesupplementation"

Semana del 9 al 15 de Abril de 2008

IUBMB Life. 2008 Apr 11 [Epub ahead of print]

Estrogen is a modulator of vascular inflammation.

Chakrabarti S, Lekontseva O, Davidge ST.

Department of Obstetrics and Gynecology, Perinatal Research Centre and Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada.

Vascular inflammation underlies the pathogenesis of atherosclerosis. Atherosclerotic changes in the vasculature lead to conditions such as coronary artery disease and stroke, which are the major causes of morbidity and mortality worldwide. Epidemiological studies in premenopausal women suggest a beneficial role for estrogen in preventing vascular inflammation and consequent atherosclerosis. However, the benefits of estrogen areabsent or even reversed in older postmenopausal subjects. The modulation of inflammation by estrogen under different conditions might explain this discrepancy. Estrogen exerts its antiinflammatory effects on the vasculature through different mechanisms such as direct antioxidant effect, generation of nitric oxide, prevention of apoptosis in vascular cells and suppression of cytokines and the renin-angiotensin system. On the other hand, estrogen also elicits proinflammatory changes under certain conditions, which are less completely understood. Some of the mechanisms underlying a possible proinflammatory role for estrogen include increased expression of the proinflammatory receptor for advanced glycation end products, increased tyrosine nitration of cellular proteins, and generation of reactive oxygen species through an uncoupled eNOS. In this review, we have presented evidence for both antiinflammatory and proinflammatory pathways modulated by estrogen and how interactions among such pathways might determine the effects of estrogen on the vascular system.

Bone. 2008 Mar 7 [Epub ahead of print]

Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: A key mechanism in osteoporosis.

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

Department of Internal Medicine, University of Torino, Italy.

Compelling evidences suggest that increased production of osteoclastogenic cytokines by activated T cells plays a relevant role in the bone loss induced by estrogen deficiency in the mouse. However, little information is available on the role of T cells in post-menopausal bone loss in humans. To investigate this issue we have assessed the production of cytokines involved in osteoclastogenesis (RANKL, TNFalpha and OPG), in vitro osteoclast (OC) formation in pre and post-menopausal women, the latter with or without osteoporosis. We evaluated also OC precursors in peripheral blood and the ability of peripheral blood mononuclear cells to produce TNFalpha in both basal and stimulated condition by flow cytometry in these subjects. Our data demonstrate that estrogen deficiency enhances the production of the pro-osteoclastogenetic cytokines TNFalpha and RANKL and increases the number of circulating OC precursors. Furthermore, we show that T cells and monocytes from women with osteoporosis exhibit a higher production of TNFalpha than those from the other two groups. Our findings suggest that estrogen deficiency stimulates OC formation both by increasing the production of TNFalpha and RANKL and increasing the number of OC precursors. Women with post-menopausal osteoporosis have a higher T cell activity than healthy post-menopausal subjects; T cells thus contribute to the bone loss induced by estrogen deficiency in humans as they do in the mouse.

Gynecol Oncol. 2008 Apr 11 [Epub ahead of print]

Bilateral oophorectomy before 50 years of age is significantly associated with the metabolic syndrome and Framingham risk score: A controlled, population-based study (HUNT-2).

Dørum A, Tonstad S, Liavaag AH, Michelsen TM, Hildrum B, Dahl AA.

Department of Gynecologic Oncology, The Norwegian Radium Hospital, Rikshospitalet HF, University of Oslo, N-0310 Oslo, Norway.

OBJECTIVE: Bilateral oophorectomy (BOE) is often recommended in order to prevent cancer at hysterectomy for non-malignant diseases and when familial risk of ovarian and breast cancer has been identified. Surgical menopause increases the risk of cardiovascular mortality, however, the intervening mechanisms are not clear. We compared the prevalence of the metabolic syndrome (MetS) and Framingham cardiovascular risk scores in women with BOE before 50 years of age to age-matched controls in a population-based study. METHODS: 20,765 women aged 40-69 years were invited to a health study (HUNT-2 Norway 1995-97) and 17,650 (85%) attended. We compared 263 women with BOE before 50 years of age [63 with intact uterus (BO1 group), and 200 with hysterectomy also (BO2 group)] with 3 age-matched controls per case (n=789). Data on demographic, somatic, mental, and lifestyle variables, physical measurements and blood tests were obtained. RESULTS: The BO1 and BO2 groups did not differ significantly regarding risk variables, and 4% had natural menopause. The combined BOE group had increased prevalence of MetS compared to controls according to the International Diabetes Federation's definition (47% versus 36%; p=.001) and the revised NCEP ATP III definition (35% versus 25%; p=.002), which remained after adjustments (for reproductive, global health, and lifestyle variables). The prevalence of Framingham risk score >/=10% was higher in cases (22%) versus controls (15%) p=.005. CONCLUSION: The higher prevalence of MetS and increased Framingham risk scores in women with bilateral oophorectomy before 50 years of age suggests that these women may be at higher risk of type 2 diabetes and cardiovascular disease compared to their counterparts in the general population.

Trends Endocrinol Metab. 1998 Jan-Feb;9(1):32-8.

Hormone replacement therapy in women with previous breast cancer.

Marsden J, Baum M, Sacks NP.

St Heliers Hospital, Carshalton, Surrey UK SM5 1AA.

As breast cancer is known to be a tumour sensitive to the effects of endogenous oestrogens, clinicians are reluctant to prescribe hormone replacement therapy (HRT) to women with a history of previous breast cancer for fear of stimulating disease recurrence, and it is currently contraindicated in this group of women. However, an increasing proportion of breast cancer patients are requesting the use of HRT to relieve the symptoms of oestrogen deficiency, which are also a common side-effect of adjuvant therapy for breast cancer. Observational data on the use of HRT in breast cancer survivors has not demonstrated an increase in disease recurrence, but uncertainty will continue in the absence of data from prospective, randomized trials. This review aims to demonstrate why it is ethical and scientifically important to undertake such studies.

Clin Ther. 2008 Mar;30(3):443-52.

Significance of a decline in bone mineral density while receiving oral bisphosphonate treatment.

Sebba AI.

Department of Rheumatology, University of South Florida, Tampa, Florida.

Background: Oral bisphosphonates are routinely prescribed for the treatment of postmenopausal osteoporosis. In clinical trials, oral bisphosphonates have been found to increase bone mineral density (BMD) and decrease fracture risk in the majority of the treated population. However, in both clinical trials and clinical practice, not all patients experience significant increases in BMD. In clinical trials, nonresponse is often defined as a BMD change of </=0%. In clinical practice, a decrease in BMD greater than the calculated least significant change (LSC) is considered nonresponse to therapy. It is important to discern whether patients with a decline in BMD may still benefit from oral bisphosphonate therapy, that is, have a reduced risk for fracture, despite having a suboptimal BMD response. Objectives: The objectives of this review were to determine whether meaningful BMD nonresponder rates exist with all oral bisphosphonates and to examine the relationship between BMD nonresponder status and fracture risk. Finally, we discuss the potential implications of BMD nonresponse for patients in clinical practice. Methods: Publications on BMD response and bone loss during treatment with bisphosphonates were identified by searches of MEDLINE (1990-October 2007) and ISI Web of Science (1997-October 2007). Search terms included nonresponse, responder, osteoporosis, bone mineral density, bisphosphonate, alendronate, risedronate, ibandronate, bone loss, and fracture. Results: In clinical trials of alendronate, risedronate, and ibandronate, the percentages of patients with a change in BMD </=0% at the lumbar spine after 2 years of treatment ranged from 8% to 25%. Results from post hoc analyses of clinical trial data from studies of alendronate and risedronate that have examined fracture risk among BMD responders, BMD nonresponders, and patients receiving placebo suggest that patients who experienced an increase in BMD have reduced vertebral fracture risk relative to those with a decline in BMD (range, 38%-50%). Additional analyses suggest that patients who experience a decline in BMD while receiving oral bisphosphonate therapy still appear to receive some benefit (fracture risk reduction, 38%-60%) from treatment compared with patients receiving placebo. Conclusions: Results from post hoc analyses of clinical trial data suggest that patients receiving oral bisphosphonate therapy who experience a decline in BMD have a higher risk for fracture compared with patients whose BMD increases, but may have a reduced fracture risk compared with patients receiving placebo. Further investigation is needed to determine how these results impact patients in clinical practice whose BMD loss exceeds the LSC.

J BUON. 2008 Jan-Mar;13(1):55-9.

Impact of body mass index on cancer development.

Yumuk PF, Dane F, Yumuk VD, Yazici D, Ege B, Bekiroglu N, Toprak A, Iyikesici S, Basaran G, Turhal NS.

Dept. Internal Medicine, Division of Medical Oncology, Marmara University Medical School, Istanbul, Turkey.

Purpose: To determine the impact of body mass index (BMI) on cancer in a hospital-based Turkish population. Patients and methods: The study group consisted of 2015 (1172 females: 423 pre- and 749 postmenopausal; and 843 males) patients with histologically proven cancer who applied to Marmara University Medical School, Medical Oncology Clinic. The control group included 305 healthy caregivers (192 females: 110 pre- and 82 postmenopausal; and 113 males). Results: Mean BMI of the patients with breast, ovarian and cervical carcinoma was significantly higher than that of the healthy female controls (p<0.001, 0.003, <0.001, respectively). Postmenopausal breast cancer patients had significantly higher BMI than postmenopausal female controls (odds ratio [OR] 1.3; 95% confidence interval [CI], 1.06-1.6; p=0.012), while this was not seen in premenopausal patients. When compared with controls obese postmenopausal female patients had 3.26-fold (95% CI 1.54-6.90) increased risk for breast cancer (p=0.002). Mean BMI of lung, stomach, esophagus, pancreas and head and neck carcinoma patients was significantly lower than that of the healthy controls. Female patients with lung and colorectal carcinoma had higher BMI than female controls. Conclusion: Elevated BMI might be a risk factor for breast cancer in postmenopausal women. Case-control studies may not show the actual association between BMI and cancers that present with pre-diagnosis weight loss and advanced stage.

Maturitas. 2008 Apr 11 [Epub ahead of print]

Metabolic syndrome after menopause and the role of hormones.

Lobo RA.

Department of Obstetrics & Gynecology, Columbia University College of Physicians & Surgeons, New York, NY

OBJECTIVES: The purpose of this review is to focus on the importance of metabolic syndrome (MBS) and its increased prevalence in postmenopausal (PM) women. Also the role of hormonal therapy in PM women with MBS will be discussed. METHODS: Review of the relevant literature and results from recent clinical trials. RESULTS: MBS may occur in 40% of PM women and is largely determined by overweight status and obesity. Weight gain, particularly an increase in central fat mass increases in PM women, beginning a few years prior to menopause. Hormonal Therapy (HT) in normal PM women, generally decreases abdominal fat, but the effect of transdermal estrogen is preferable to oral therapy in this regard. In women with MBS, oral therapy was found to increase leptin and the leptin/adiponectin ratio, while transdermal therapy showed no changes. HT has been found to improve insulin resistance in PM women, although the data are mixed. In women with MBS, oral therapy was found to worsen parameters of insulin resistance, while transdermal therapy had minimal effects overall. Women with MBS have elevations in several inflammation and coagulation factors. Both oral and transdermal HT reduce inflammation markers except for levels of CRP and MMP-9, which increase with oral therapy, but are unaffected by the transdermal route. Oral estrogen has a small pro-coagulant effect, not observed with transdermal therapy, in both normal PM women and those with MBS. The beneficial effects of HT on lipids occur in PM women with and without MBS, although the changes in the latter are minimal. Blood pressure was not affected by HT in women with MBS. CONCLUSIONS: Weight gain and obesity largely drives the increased prevalence of MBS in PM women. Use of HT is beneficial overall for reducing many of the parameters of MBS. Our own data would suggest that in MBS, transdermal therapy may be preferable to oral therapy, at least in standard doses.

Breast Cancer Res Treat. 2008 Apr 11 [Epub ahead of print]

Transcriptional profiles of progestogen effects in the postmenopausal breast.

Wood CE, Register TC, Cline JM.

Department of Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1040, USA, chwood@wfubmc.edu.

Estrogen plus progestin hormone therapy has been associated with increased breast proliferation, breast density, and breast cancer risk in postmenopausal women, beyond that seen with estrogen alone. The goal of this study was to evaluate progestogen effects on gene expression profiles in the breast contributing to this promotional effect. Twenty-five ovariectomized adult female cynomolgus monkeys were given the following treatments (expressed as equivalent doses for women) in a randomized crossover design: (1) placebo; (2) oral estradiol (E2, 1 mg/day); (3) E2 + micronized progesterone (P4, 200 mg/day); and (4) E2 + medroxyprogesterone acetate (MPA, 2.5 mg/day). Treatments were given for two months, and breast biopsies were taken after each treatment period. On microarray analysis E2 + MPA treatment resulted in a greater number of significantly regulated genes compared to E2 + P4 and E2 alone (P < 0.0001). Treatment with E2 alone induced modest effects on select genes related to epidermal growth factor receptor (EGFR) activity which were augmented by the addition of MPA but not P4, consistent with patterns of epithelial cell proliferation. Genes induced by E2 + MPA included the EGFR ligands EGF, TGFA, and AREG, and downstream targets such as STAT5A, STAT5B, SRC, EIF4EBP1, and MYC. Progestogens showed mixed antagonistic effects on E2-induced genes which tended to be greater for P4 than MPA. These findings suggest that a standard dose of oral E2 + MPA has a more pronounced effect on gene expression in the breast compared to E2 alone or E2 + P4 and that promotional effects of E2 + MPA may be mediated in part by increased EGFR activity.

Neuro Endocrinol Lett. 2008 Apr 11;29(2) [Epub ahead of print]

Effects of bisphosphonates on lipid metabolism.

Guney E, Kisakol G, Ozgen AG, Yilmaz C, Kabalak T.

Department of Endocrinology, Medical Faculty of Adnan Menderes University, Aydin, Turkey. enginguney@hotmail.com.

OBJECTIVES: Bisphosphonates are widely used for the treatment of metabolic bone disorders and their effects on lipid metabolism have also been investigated. Some studies reported that bisphosphonates have beneficial effects on serum cholesterol levels. In this study we aimed to assess the effects of bisphosphonates on lipid levels in hyperlipidemic patients who received bisphosphonates because of osteoporosis. METHODS: 49 female patients (age: 54.2 +/- 7.2 years) with diagnosis of osteoporosis and hyperlipidemia were enrolled. Patients received alendronate 10 mg/day and they were followed up for 6 months. Pretreatment total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 and apolipoprotein B levels were measured and compared with post-treatment levels. RESULTS: Pretreatment and post-treatment levels of total cholesterol were 255.2 +/- 34.3; 233.02 +/- 37.0 mg/dL, triglyceride levels were 153.0 +/- 57.3; 129.1 +/- 54.4 mg/dL, and LDL levels were 170.7 +/- 30.5; 160.0 +/- 34.2 mg/dL, respectively. Reductions in total cholesterol, triglyceride and LDL-cholesterol levels were statistically significant; whereas differences in HDL-cholesterol, apolipoprotein-A1 and apolipoprotein-B levels were not significant. CONCLUSIONS: Data from our study suggest that alendronate therapy may have beneficial effects on lipid metabolism. Thus, when hyperlipidemia is detected in patients receiving bisphosphonates, it is considered reasonable to follow the patient for a while before initiating antihyperlipidemic agent to prevent unnecessary use of drugs.

Am J Clin Nutr. 2008 Apr;87(4):1080S-6S.

Vitamin D deficiency: a worldwide problem with health consequences.

Holick MF, Chen TC.

Department of Medicine, Boston University School of Medicine, 715 Albany Street, M-1013, Boston, USA.

Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.

J Natl Cancer Inst. 2008 Apr 8 [Epub ahead of print]

Conjugated Equine Estrogen and Risk of Benign Proliferative Breast Disease: A Randomized Controlled Trial.

Rohan TE, Negassa A, Chlebowski RT, Habel L, McTiernan A, Ginsberg M, Wassertheil-Smoller S, Page DL.

Affiliations of authors: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. USA

Background Estrogens stimulate proliferation of breast epithelium and may therefore increase the risk of benign proliferative breast disease, a condition that is associated with increased risk of breast cancer. We tested the effect of conjugated equine estrogen (CEE) on risk of benign proliferative breast disease in the Women's Health Initiative (WHI) randomized controlled trial. Methods In the WHI CEE trial, 10739 postmenopausal women were randomly assigned to 0.625 mg/d of CEE or to placebo. Baseline and annual breast examinations and mammograms were required. We identified women in the trial who reported breast biopsies that were free of cancer, obtained the associated histological sections, and subjected them to standardized central review. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results A total of 232 incident cases of benign proliferative breast disease were ascertained during follow-up (average duration, 6.9 years), with 155 in the CEE group and 77 in the placebo group. Use of CEE was associated with a more than two-fold increase in the risk of benign proliferative breast disease (HR = 2.11, 95% CI = 1.58 to 2.81). For benign proliferative breast disease without atypia, the HR was 2.34 (95% CI = 1.71 to 3.20), whereas for atypical hyperplasia, it was 1.12 (95% CI = 0.53 to 2.40). Risk varied little by levels of baseline characteristics. Conclusion Use of 0.625 mg/d of CEE was associated with a statistically significant increased risk of benign proliferative breast disease.

J Thromb Haemost. 2008 Apr 3 [Epub ahead of print]

Differential impact of conventional dose and low dose postmenopausal hormone therapy, tibolone and raloxifene on C-reactive protein and other inflammatory markers.

Eilertsen AL, Sandvik L, Steinsvik B, Sandset PM.

Department of Haematology, Ullevål University Hospital Trust, Oslo, Norway.

Background: Postmenopausal hormone therapy (HT) is associated with an increased risk for arterial and venous thrombosis. Objectives: To compare the impact of HT, tibolone, and raloxifene on C-reactive protein (CRP) and other inflammatory markers, and to investigate possible underlying mechanisms for changes in CRP and D-dimer. Methods: 202 healthy women were randomly assigned to treatment for 12 weeks with either low-dose HT containing 1 mg 17 beta-estradiol + 0.5 mg norethisterone acetate (NETA)(n=50), conventional-dose HT containing 2 mg 17 beta-estradiol and 1 mg NETA (n=50), 2.5 mg tibolone (n=51), or 60 mg raloxifene (n=51). Results: CRP increased in the conventional and low-dose HT-group. These changes were significantly more pronounced in the conventional-dose group (RMANOVA p=0.02). Also tibolone was associated with an increase in CRP, in contrast to raloxifene which reduced CRP. Reduction in levels of Lp(a), ICAM, P-selectin, E-selectin, MCP-1 and IL-6 were observed in all treatment groups. The changes were most pronounced for the conventional dose HT group, least pronounced for the raloxifene, whereas the changes in those allocated to tibolone and low-dose HT were intermediary. Increased levels of TNF-alpha and VWF were seen in the raloxifene group. We observed positive associations between changes in IL-6, VWF, MCP-1 and CRP. Conclusions: The regimens had markedly different impact on markers of inflammation. The average increase in CRP was not accompanied by an increase in average IL-6 or TNF-alpha or other markers, but women with large reductions in IL-6 had reduced increase in CRP.

Curr Vasc Pharmacol. 2008 Apr;6(2):112-23.

Hormone replacement therapy and stroke.

Billeci AM, Paciaroni M, Caso V, Agnelli G.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Ospedale S.M. della Misericordia, Sant'Andrea delle Fratte, 06129 Perugia, Italy. antobilly@yahoo.it.

Stroke is the third most common cause of death in women and a major cause of disability. Stroke occurs in older age in women compared with men. High premenopausal estrogen concentrations in women are thought to be protective against stroke and cardiovascular disease. Estrogens are essential for normal reproductive function and they exert complex and diverse non reproductive actions on multiple tissues such as neuroprotective effects, vasodilatation, improved vascular reactivity, antithrombotic effects and lipid lowering effects. After menopause estrogen concentrations are depleted and in the past estrogen replacement therapy was considered as a potential protective agent against both cardiovascular disease and stroke. Although the use of hormone therapy was originally associated with a reduction in the risk of heart disease by about 50% in observational studies, the results regarding stroke have been less clear. In order to investigate the effect of hormone therapy on stroke risk, randomized controlled trials of cardio-and/or cerebrovascular-disease prevention in women with established heart disease have been designed. The Heart Estrogen-Progestin Replacement Study included stroke as secondary outcome. This study did not show any differences in myocardial infarction (MI) or coronary death (HR 0.99; 95%CI 0.80-1.22) and in stroke rate. In another study, the Women Estrogen Stroke Trial, 17 beta estradiol 1 mg/placebo was administered to women with previous ischemic stroke or transient ischaemic attack (TIA) having a mean age 71. No differences in stroke rate (RR 1.1; 95% CI 0.8-1.4) and in mortality rate (RR 1.2; 95% CI 0.8-1.8) were found, while a trend showing an increased rate of fatal strokes (RR 2.9; 95% CI 0.9-9.0) and for more severe non-fatal strokes (% patients with final National Institutes of Health Stroke Scale (NIHSS) 0-1: 19 % vs. 33%; p = 0.12) was observed. The Women's Health Initiative, a primary prevention study, where conjugated equine estrogen (CEE) plus medroxyprogesterone acetate/placebo was utilized, was stopped because of an excess in breast cancer and increased stroke rates (RR 1.4; 95% CI 1.1-1.8). Recently, a meta-analysis including 39,769 women participating in 28 trials has been published. Twelve studies were of secondary prevention and the overall stroke rate was 2%. In the hormone replacement therapy (HRT) arm there was a 29% increased rate of ischemic stroke (Number Needed to Harm, NNH:147). Furthermore, a 56% increased rate of death or dependency after stroke and a tendency of more fatal stroke were observed. Additionally, a higher stroke risk was reported in the first year of treatment. Conclusions: There seems to be no indication for hormone replacement therapy in the prevention of stroke in women. Further studies are needed to discover why estrogens have different effects on the heart and brain. Conventional risk-factors which could increase the risk of estrogen therapy need to be identified and as well as more restrictive inclusion and exclusion criteria such as coagulation parameters and intimal thickness should be adopted before new randomized trials are started.

Eur J Endocrinol. 2008 Apr 7 [Epub ahead of print]

Centrally-Located Body Fat is Related to Appetitive Hormones in Healthy Postmenopausal Women.

Ritland L, Alekel D, Matvienko O, Hanson K, Stewart J, Hanson L, Reddy M, Van Loan M, Genschel U.

L Ritland, Food Science and Human Nutrition, Iowa State University, Ames, United States.

Objective: Body composition and energy homeostasis are thought to affect the appetitive hormones: adiponectin, leptin, insulin, and ghrelin. This study examined whether centrally-located fat and/or overall adiposity were related to these appetitive hormones in healthy postmenopausal women. Design: Overall and regional body composition was assessed by dual-energy X-ray absorptiometry in relation to plasma adiponectin, serum leptin, serum insulin, and plasma ghrelin in 242 postmenopausal women. Results: Regression analyses revealed that the androidal-to-gynoidal fat mass ratio (18.0%), age (3.2%), and white blood cell count (1.8%) accounted for 28% of the variability in adiponectin (F=22.2; P</=0.0001); androidal (waist + hip) fat mass (66.0%), androidal fat mass2 (6.2%), whole body lean mass (2.2%), and age (0.8%) accounted for 69% of the variability in leptin (F=102.5; P</=0.0001). Regression analyses revealed that sagittal abdominal diameter (8.4%), glucose (5.4%), white blood cell count (2.6%), and dietary omega-3 fatty acids (2.0%) accounted for 32% of the variability in insulin (F=20.8; P</=0.0001); waist circumference (12.7%), hip lean mass (2.0%), and white blood cell count (1.9%) accounted for 26% of the variability in ghrelin (F=20.7; P</=0.0001). Our results indicated that centralized fat mass was the primary contributor to these appetitive hormones in healthy postmenopausal women. Conclusion: Since central adiposity in postmenopausal women was related to appetitive hormones, minimizing weight gain during the menopausal transition may optimize appetitive hormones, thereby facilitating appetite control and weight maintenance.

Semana del 2 al 8 de Abril de 2008

J Nutr Sci Vitaminol (Tokyo). 2008 Feb;54(1):25-9

Development of a simple food frequency questionnaire to estimate intakes of calcium and other nutrients for the prevention and management of osteoporosis.

Uenishi K, Ishida H, Nakamura K.

Laboratory of Physiological Nutrition, Kagawa Nutrition University.

There have been no simple methods to estimate dietary nutrient intakes for the prevention and management of osteoporosis. The aim of this study was to develop and validate a new, simple food frequency questionnaire (FFQ) for dietary intake of calcium and other nutrients relevant to the bone health of adult Japanese women. We developed a 28-item FFQ. To validate this, 208 and 72 adult women aged between 18 and 69 y were recruited for testing reliability and reproducibility, respectively. In the 208 women, moderate-to-high Spearman's correlation coefficients between our FFQ and the conventional diet record method were found in intakes of calcium (r=0.668), sodium chloride (NaCl) (r=0.475), vitamin A (r=0.501), vitamin D (r=0.413), vitamin K (r=0.649), and energy (r=0.471). In the 72 women, coefficients of variance of the four repeated measurements of intakes throughout a year were 14.1% for calcium, 7.3% for NaCl, 21.2% for vitamin A, 13.6% for vitamin D, 36.8% for vitamin K, and 9.6% for energy. In conclusion, the FFQ we developed is a useful tool to evaluate the intake of dietary calcium of adult Japanese women. Although it can also measure intakes of dietary vitamin A, vitamin D, vitamin K, NaCl, and energy, further improvement is needed to measure intakes of these nutrients and energy.

Curr Med Res Opin. 2008 Apr 2 [Epub ahead of print]

New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion.

Bischoff-Ferrari HA, Papapoulos SE, de Papp AE, West JA.

BACKGROUND: Adequate vitamin D and calcium nutrition play a critical role in the maintenance of musculoskeletal health and are considered the first step in osteoporosis treatment.ROUNDTABLE DISCUSSION: In February 2008 Merck Sharp & Dohme sponsored a 2-day, evidence-based expert panel on the benefits of vitamin D for the patient with osteoporosis and the role of vitamin D in combination with antiresorptive therapy for the management of osteoporosis. One of the primary objectives of the meeting was to review new data on the optimal serum 25-hydroxyvitamin D [25(OH)D] levels. The symposium was attended by 29 researchers and clinicians from Europe and the Middle East. The discussion focused on optimizing vitamin D and calcium nutrition and reducing falls and fractures in osteoporotic patients.CONCLUSIONS: Current evidence and expert opinion suggests that optimal serum 25(OH)D concentrations should be at least 50 nmol/L (20 ng/mL) in all individuals. This implies a population mean close to 75 nmol/L (30 ng/mL). In order to achieve this level, vitamin D intake of at least 20 microg daily is required. There is a wider therapeutic window for vitamin D than previously believed, and doses of 800 IU per day, regardless of sun exposure, season or additional multivitamin use, appear to present little risk of toxicity. Apart from fracture and fall prevention, optimization of vitamin D status may also have additional general health benefits. Based on newly emerging data regarding calcium supplementation, and recommendations for increased vitamin D intake, the current recommendations for calcium intake in postmenopausal women may be unnecessarily high. In addition to vitamin D and calcium, treatment of patients with osteoporosis at high risk of fractures should also include pharmacologic agents with proven vertebral and non-vertebral fracture efficacy.

Am J Epidemiol. 2008 Apr 2 [Epub ahead of print

Age-specific Trends in Mammographic Density: The Minnesota Breast Cancer Family Study.

Kelemen LE, Pankratz VS, Sellers TA, Brandt KR, Wang A, Janney C, Fredericksen ZS, Cerhan JR, Vachon CM.

Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.

Mammographic density is a strong risk factor for breast cancer, yet few studies have evaluated density trends, and associated factors, over time. The authors retrieved and digitized mammograms (>/=1 per woman) imaged in 1990-2003 to evaluate percent density (PD) in the Minnesota Breast Cancer Family cohort. Multivariable-adjusted, mixed-effects, repeated-measures models incorporating a natural cubic spline provided estimates of nonlinear trends in PD with age and were used to examine association with covariates. Overall, 5,698 mammograms from 1,689 women with covariate information were digitized. In descriptive analyses, the highest median PD was 33.1% (interquartile range, 21.8%; n = 230) among premenopausal women, 31.0% (interquartile range, 23.2%; n = 175) among women who transitioned from pre- to postmenopause, and 18.7% (interquartile range, 22.2%; n = 1,284) among postmenopausal women. On average, premenopausal compared with postmenopausal women had 1.9% (p = 0.001) higher PD. In repeated-measures analyses, greater declines in PD occurred with menopause and among women with higher baseline PD; current postmenopausal hormone use and higher body mass index modified these declines (p interaction < 0.001). No significant modification of the density change with age was seen with parity/age at first birth, age at menarche, oral contraceptive use, family history of breast or ovarian cancer in a first- or second-degree relative, educational level, smoking status, or alcohol intake were observed. These data suggest that menopause, baseline PD, postmenopausal hormone use, and body mass index predict changes in mammographic density trends during adult life.

J Clin Endocrinol Metab. 2008 Apr 1 [Epub ahead of print

Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women.

Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J.

Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; The Bethesda Health Research Center (M.A.B.), Bethesda, MD 20817-1106; University of Manitoba (C.K.Y.), Winnipeg, Manitoba, Canada R3T 2N2; University of British Columbia (D.L.K.), Vancouver, BC, Canada V6T 1Z4; Amgen Inc. (H.W., Y.L., J.S.M.), Thousand Oaks, CA 91320-1799.

Context: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor kappa B ligand (RANKL), a mediator of osteoclastogenesis and osteoclast survival. Objective: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. Design and Setting: This 2-year randomized, double-blind, placebo-controlled study was conducted in North America. Participants: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. Interventions: Subjects were randomly assigned to receive denosumab subcutaneously, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (</= 5 years or > 5 years). Main Outcome Measures: The primary endpoint was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry (DXA) at 24 months. Additional endpoints were percent change in volumetric BMD (vBMD) of the distal radius by quantitative computed tomography (QCT); percent change in BMD by DXA for the total hip, 1/3 radius, and total body; hip structural analysis (HSA); percent change in BTMs; and safety. Results: Denosumab significantly increased lumbar spine BMD compared with placebo at 24 months (6.5% vs -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, 1/3 radius, and total body (P<0.0001 vs placebo); increased distal radius vBMD (P<0.01); improved HSA parameters; and significantly suppressed serum CTX, TRAP-5b, and P1NP. The overall incidence of adverse events was similar between both study groups. Conclusions: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.

Br J Nutr. 2008 Apr 1;:1-5 [Epub ahead of print

Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.

Schulz M, Hoffmann K, Weikert C, Nöthlings U, Schulze MB, Boeing H.

Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, Nuthetal 14558, Germany.

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet-cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15 351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6.0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2.00; 95 % CI 1.30, 3.09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

Altern Med Rev. 2008 Mar;13(1):21-33

Vitamin D and fracture reduction: an evaluation of the existing research.

Brown SE.

Director of Osteoporosis Education Project and the Nutrition Education and Consulting Service, Syracuse, NY; medical anthropologist, certified nutrition specialist (CNS); Email: drsbrown@earthlink.net.

This article re-evaluates the literature on vitamin D and fracture reduction, highlighting the relevance of new understandings for fracture prevention. A new set of science-based research guidelines for clinical trials on vitamin D and fracture is proposed. The existing clinical trials on vitamin D and fracture are analyzed, focusing on studies that most closely meet the proposed guidelines. An estimation of the true fracture-reduction potential of therapeutic-level vitamin D supplementation is offered. The analysis outlined in this article leads to a series of striking conclusions. First, most of the available clinical trials and meta-analyses of vitamin D and fracture underestimate the true fracture reduction potential of vitamin D. Second, achievement of vitamin D serum sufficiency levels (now set in the United States, Europe, and many other places at a minimum of 32 ng per mL) could provide for a 50 - to 60 - percent fracture reduction. And third, providing for vitamin D sufficiency is the simplest, most life-supporting, and most cost effective means of significantly reducing the incidence of osteoporotic fractures worldwide. Given the urgent need, the Osteoporosis Education Project (OEP) has initiated a call for universal vitamin D repletion as the primary basis for osteoporotic fracture prevention worldwide.