Hormone replacement therapy (HRT) has been studied as a protective factor for cognitive decline and dementia. However, study findings have been inconsistent. Variation in study findings may be due to differences in study designs, small sample size, exposure ascertainment, diagnostic procedures, and inclusion of relevant risk and confounding factors. Moreover, there may be significant differences between the characteristics of women choosing to use HRT and those opting not to use the therapy. Using a large-scale, population-based, cohort study, we examined the relationship between HRT and cognition while paying particular attention to moderating and confounding factors. The main outcomes of interest were to assess differences in risk for cognitive impairments and dementia between HRT user and never user groups; examine HRTs impact on age of onset of dementia; and explore the relationship between duration of HRT and cognitive decline. Logistic regression and Cox Proportional Hazards models were used to test HRT as a predictor for cognitive impairments, Alzheimers disease and vascular dementia, as well as to assess the effect of duration. Linear regression was used to consider the putative relationship between age at onset of dementia and HRT status. HRT use was found to be a statistically significant predictor for Alzheimers disease and vascular dementia. Overall, HRT use did not significantly predict for milder cognitive impairments, although significant interaction effects indicate that HRT may be protective at least for specific sub-groups of women. No durational effect was found for any of the outcomes. Neither did HRT appear to predict for age at onset of dementia. Notably, a large proportion of women in the current study reported using estrogen-only hormone supplements, and therefore generalizations regarding the findings are likely limited to estrogen-only preparations, not combination estrogen-progestin therapies. These findings must be considered within the context of the other known and potential risks and benefits that HRT may afford.

Introduction: About 80% of those affected by osteoporosis are postmenopausal women. Therefore, identifying beneficial or harmful dietary factors for postmenopausal osteoporosis may have a significant public health impact. Objectives: The overall objective of this thesis was to examine the relations between various dietary factors and bone health in postmenopausal women aged ≥ 45 years using different analytical approaches. Methods: First, the associations between fruit and vegetables (F&V) intake and indicators of bone health were assessed using a systematic review approach. Electronic databases were searched and peer-reviewed observational and interventional studies published in English with F&V intake as a main dietary exposure were included. Data selection, extraction and evaluation of risk of bias were performed independently by two reviewers. Second, the associations between an overall diet quality index (HEI-2005) and its components with bone turnover markers (BTMs) were examined. Third, the relationships between alpha-tocopherol intake, serum alpha- and gamma-tocopherol, two concentration biomarkers of vitamin E intake, and their ratio and BTMs were assessed. For the second and third studies, cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were used. Weighted multiple regression models with adjustments for relevant confounders were used to examine the relationship between exposures and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-Telopeptides/Creatinine (uNTx/Cr), a biomarker of bone resorption. Results: There was significant between-study heterogeneity in design, definition and amount of F&V intake, outcomes, analyses and reporting of results in the eight included studies. Overall, cross-sectional and case-control analyses reported protective associations between F&V intake and bone health, whereas interventional and prospective cohort analyses did not. There were no associations between total HEI-2005 scores and BTMs. However, the Milk Group component of HEI-2005 had a significant inverse relationship with uNTx/Cr. Higher serum gamma-tocopherol and lower ratio of serum alpha- to gamma-tocopherol were associated with higher BAP concentrations but had no associations with NTx/Cr concentrations. Conclusions: The results confirm the existing knowledge that a diet with adequate intake of dairy may reduce bone loss. Further research is needed to examine the potential anabolic effects of gamma-tocopherol on bone in postmenopausal women.

Bakgrund: Bröstcancer är den vanligaste cancerformen hos kvinnor i Sverige. Under 2008 fick ca 7300 kvinnor diagnosen bröstcancer och av dessa var 72 procent 55 år och äldre. Tidigare forskning har visat att postmenopausala kvinnor som är 55 år och äldre upplever att de inte får tillräckligt stöd från vårdpersonal och närstående. Syfte: Syftet med studien är att beskriva hur postmenopausala kvinnor med bröstcancer upplever olika former av stöd och hur dessa påverkar deras hälsa. Metod: Vi använde oss av en litteraturöversikt, med 16 kvalitativa och kvantitativa vetenskapliga artiklar som undersöktes och analyserades enligt Friberg (2006). Resultat: Dataanalysen av artiklarna resulterade i fem teman och dessa är: emotionellt stöd, vårdpersonalens stöd, närståendes stöd, religiöst stöd och informationsstöd. Vi fann att dessa stöd är viktiga för postmenopausala kvinnors hälsa och livskvalitet. Slutsats: Olika typer av stöd från närstående och vårdpersonal upplevs som viktiga för postmenopausala kvinnor med bröstcancer. Mer forskning behövs för att få en bättre förståelse för vilka stöd som är viktiga för postmenopausala kvinnor med bröstcancer och hur dessa påverkar deras hälsa. / Background: Breast cancer is the most common cancer among women in Sweden.  In 2008 there were about 7300 women diagnosed with breast cancer and of these 72 per cent were 55 years or older. Earlier research showed that postmenopausal women with breast cancer aged 55 years and older felt that they were not getting enough support from health professionals and relatives. Aim: The aim of this study is to describe how postmenopausal women with breast cancer experience different types of support and how these affect their health. Method: A literature review was used in which 16 qualitative and quantitative studies were examined and analyzed according to Friberg (2006). Results: The data analysis of the articles revealed five themes and these are: emotional support, health professionals` support, relatives´ support, religious support and information support. We found that these supports are important for postmenopausal women´s health and quality of life. Conclusions: Different types of support from relatives and health professionals are perceived as important for postmenopausal women with breast cancer. More research is needed to get a better understanding of which supports that are important for postmenopausal women with breast cancer and how it affects their health.

The purpose of this study was to determine the role of body composition and fat distribution on C-reactive protein (CRP) and interleukin-6 (IL-6); determine the differences in CRP and IL-6 among HT users and non-users; determine the effect of 12-months of resistance training and resulting body composition changes on IL-6 and CRP; determine the relationship between BMD and IL-6, CRP and creatine kinase (CK). Sedentary women (N=208, age 44-66, 3-10 years postmenopausal) taking HT (N=106) or not taking HT (N=102) were randomly assigned to resistance training: HTexercise (N=55), HT-no exercise (N=45), no HT-exercise (N=53), and no HT-no exercise (N=49). The program included three weekly 60-75 minute sessions of 8 exercises performed in 2 sets of 6-8 repetitions at 70-80% of 1RM. Total fat mass (TFM), lean soft tissue mass (LSTM) and BMD were assessed by dual-energy X-ray absorptiometry (DXA). Abdominal fat mass (AFM) was assessed using DXA region of interest. For each subject, baseline and 1- year IL-6, CRP and CK were measured. High TFM, high IL-6 and HT use were independently associated with high CRP levels. A stronger relationship between IL-6 and AFM compared to TFM was found in HT users. High TFM and LSTM were significantly related to higher IL-6 levels. A stronger relationship between CRP and AFM compared to TFM was found in HT non-users. CRP was higher in HT users (5.47±5.40 mg/L) compared to non-users (2.70±3.05 mg/L) and was higher in oral (5.76±5.29 mg/L opposed; 6.14±5.97 mg/L unopposed) compared to transdermal HT users (2.65±4.44 mg/L). CRP increased slightly (p=0.077) in exercisers (0.54 ± 0.34 mg/L) not taking HT compared to controls (-0.39 ± 0.35 mg/L). Reductions in TFM were associated with reductions in IL-6 and CRP in HT users. CK was positively associated to all BMD sites at baseline. IL-6 change was positively associated with change in femur neck BMD. CRP change was inversely correlated with change in lumbar spine BMD. CK change was directly related to change in total body and femur trochanter BMD. In conclusion, reductions in TFM were accompanied by reductions in IL-6 and CRP; AFM was more strongly correlated with inflammation than TFM; 12-months of resistance training did not decrease IL-6 or CRP; IL-6 and CK were positively related to BMD, and CRP was inversely associated with BMD.

Inflammation is a major contributor to postmenopausal bone loss. Various long chain polyunsaturated fatty acids (LCPUFAs), particularly those of the n-3 family, are known to have anti-inflammatory activity and may have a role in minimising postmenopausal bone loss. The objectives of this thesis were to determine whether some LCPUFAs have greater bone-protective effects than others; to identify some of the mechanisms of action of LCPUFAs in bone and to explore the possibility that combined treatment with LCPUFAs and phytoestrogens offers greater bone-protective effects than either treatment alone. Using the ovariectomised rat model for postmenopausal bone loss, the relative effectiveness of eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3) and gamma-linolenic acid (GLA, 18:3n-6) in minimising bone loss post-ovariectomy was investigated. GLA exacerbated bone loss post ovariectomy in rats. In vitro, treatment of MC3T3-E1/4 osteoblast-like cells with GLA resulted in greater membrane-bound RANKL expression suggesting a possible stimulatory effect of GLA on osteoclastogenesis and osteoclast activity. EPA had no effect on overall bone mass in vivo. DHA significantly ameliorated ovariectomy-induced bone loss possibly by increasing plasma IGF-1 concentration, modulating vitamin D metabolism and, as observed in a second study, by increasing the concentration of gamma-carboxylated osteocalcin. In vitro both EPA and DHA reduced the prostaglandin E2 (PGE2)-induced increase in membrane-bound RANKL expression in MC3T3-E1/4 osteoblast-like cells. However as RANKL-independent pathways are believed to be largely responsible for the ovariectomy-induced increase in osteoclastogenesis in vivo, inhibition of RANKL expression may not significantly contribute to the prevention of ovariectomy-induced bone loss. In a second study in ovariectomised rats, combined treatment with DHA and 17β-oestradiol was associated with significantly higher femur bone mineral content than either treatment alone. However, no beneficial effects of combined treatment with DHA and either of the phytoestrogens genistein or daidzein, on bone mass were apparent. In vitro, co-treatment of TNF-α - exposed MC3T3-E1/4 cells with DHA and 17β-oestradiol was associated with a higher cell number compared to either treatment alone indicating a protective effect of combined treatment against the cytotoxic and/or anti-proliferative effects of TNF-α. In contrast, combined treatment of MC3T3-E1/4 cells with DHA and genistein, but not daidzein, was associated with significantly lower cell number than either treatment alone. As genistein, but not daidzein, is a tyrosine kinase inhibitor, this may indicate that DHA requires tyrosine kinase activity for its protective effect on cell number in TNF-α - exposed osteoblasts. Whether DHA itself is bioactive in bone cells or whether lipid mediators formed from DHA are responsible for the observed bone-protective effects is unknown. Using lipid mediator lipidomic analysis, the presence of DHA-derived lipid mediators in bone marrow in quantities known to be physiologically significant in other tissues was confirmed. Further research into the effects of these lipid mediators in bone and confirmation of the mechanisms of action of DHA in bone cells is required. This thesis demonstrates that consumption of DHA provides some protection against ovariectomy-induced bone loss in vivo and mitigates the effects of inflammation on RANKL signalling and osteoblast cell number in vitro. The bone-protective effects of DHA are complemented by co-treatment with 17β-oestradiol but may be inhibited by co-treatment with the phytoestrogens daidzein or genistein.

A relação entre risco cardiovascular e terapia hormonal na pós-menopausa é controversa. Ainda que o estrogênio endógeno possa estar associado ao menor risco cardiovascular observado em mulheres na pré-menopausa em relação às pós-menopáusicas, grandes ensaios clínicos, como o WHI, falharam em demonstrar efeito benéfico da terapia hormonal. Estes resultados podem ter sido influenciados por uma série de fatores, sendo os mais importantes: idade média das pacientes e tempo de menopausa superiores às candidatas usuais de terapia hormonal, tipo e dose dos hormônios utilizados. Desenvolvemos ensaio clínico randomizado, cross-over, com objetivo de avaliar os efeitos de dois tipos de tratamento hormonal na menopausa: tratamento oral baixa dose, associação de estradiol 17 β nasal 300 μcg e drospirenona 2 mg, diário e tratamento nâo oral, estradiol 17 β nasal diário e progesterona micronizada vaginal, 200 mg, 14 dias por mês , sobre variáveis relacionadas com inflamação e função endotelial, perfil antropométrico, metabólico e hormonal em mulheres na pós-menopausa recente e sem doença clínica evidente. Quarenta mulheres na pós-menopausa foram alocadas aleatoriamente para iniciar o tratamento hormonal por um dos dois grupos de tratamento: via oral baixa dose (n=20): ou via não oral (n=20). Ao final dos primeiros 2 meses do estudo, o grupo inicialmente tratado com terapia oral passou a receber tratamento não oral por mais 2 meses, e o grupo inicialmente tratado com terapia não oral passou a receber terapia oral também por mais 2 meses. A avaliação laboratorial foi realizada antes e ao final de 2 e 4 meses de tratamento hormonal. A amostra do estudo foi composta por mulheres com média etária de 51,2 ± 2,7 anos e tempo de amenorréia de 23,1 ± 10 meses. Após os primeiros 2 meses de tratamento, não houve diferença significativa entre os tratamentos sobre circunferência da cintura, relação cintura/quadril, índice de massa corporal e níveis de pressão arterial. Colesterol total diminuiu em ambos os tratamentos de forma semelhante. O tratamento oral teve um efeito maior em reduzir os níveis de LDL-C. HDL-C, triglicerídeos, glicemia e insulinemia de jejum, glicemia e insulinemia 2 horas após sobrecarga oral de glicose não se modificaram. PCR e FVWdiminuíram significativamente, e fibrinogênio permaneceu inalterado. Após o período de 4 meses de tratamento hormonal, não houve diferença significativa entre os tratamentos sobre circunferência da cintura, relação cintura/quadril, índice de massa corporal e níveis de pressão arterial. Durante o tratamento oral observou-se redução da circunferência da cintura e da relação cintura/ quadril em relação ao basal. Colesterol total diminuiu em ambos os grupos de tratamento, e HDL-C diminuiu discreta, mas significativamente após o tratamento oral, enquanto triglicerídeos diminuíram durante tratamento não oral. A glicemia 2 horas após sobrecarga oral de glicose apresentou valores mais elevados em relação ao basal após tratamento oral. Em contraste, glicemia e insulinemia em jejum e insulinemia 2 horas após sobrecarga oral de glicose não se modificaram. Níveis de FVW encontraram-se significativamente reduzidos após 4 meses de tratamento hormonal. Em conclusão, os resultados obtidos em nosso estudo sugerem que os tratamentos não induziram efeitos deletérios sobre variáveis relacionadas com risco cardiovascular, a curto prazo, em uma população de mulheres na pós-menopausa recente e aparentemente saudáveis. O tratamento hormonal baixa dose por via oral manteve os efeitos benéficos conhecidos do tratamento hormonal por via oral, a redução do colesterol total e do LDL-C, e evitou os efeitos nocivos tradicionalmente atribuídos à via oral: o aumento de marcadores próinflamatórios, relacionados à disfunção endotelial. O tratamento hormonal por via não oral mostrou-se também uma alternativa segura, não relacionado à modificações no perfil metabólico e nos marcadores de função endotelial. / The relationship between cardiovascular risk and hormone therapy (HT) for menopause is a contemporary and complex issue. While evidences suggest an association between endogenous estrogen and cardiovascular protection among premenopausal women, recent clinical trials have failed in demonstrate a benefic impact of HT on prevention of cardiovascular events. These results seem to be related by several factors, including selection biases like higher mean age of and time since menopause of participants, fixed type and dosages of hormones administered. A cross-over, randomized clinical trial was designed in order to evaluate the effects of two types of HT: low dose oral treatment, estradiol 17 β oral 1 mg and drospirenona 2 mg, by day and non-oral treatment, estradiol 17 β nasal 300 μcg by day and vaginal micronized progesterone, 200 mg/d, 14 days by month on variables associated with endothelial function, anthropometric, metabolic and hormonal variables on early and healthy postmenopausal women.Forty postmenopausal women were randomly allocated to start with one of the treatments: low dose oral treatment or non-oral treatment. At the end of two months, the group that started with low dose oral treatment passed to receive the non oral treatment for additional two months and vice-versa. Laboratory evaluations were performed before, at 1, 2 and 4 months of HT. The sample of the study included postmenopausal women presenting mean age of 51.2 ± 2.7 years and mean time since menopause of 23.1 ± 10 months. After 2 months, no significant differences were observed between treatments on waist circumference, waist to hip ratio, BMI and arterial pressure. Total cholesterol levels were reduced on both treatments. Low oral dose treatment had greater effect in reducing LDL cholesterol. HDL cholesterol, triglycerides, fast and 2 hours glucose and insulin levels did not change with either treatment. PCR and vW factor levels were reduced in both treatment groups and fibrinogen did not change. After 4 months of low oral dose treatment, a reduction on waist circumference and waist/circumference ratio was found. Total cholesterol was lower than basal levels on bothtreatment groups and while HDL cholesterol presented a slight but significant reduction on low oral dose treatment, triglycerides decreased significantly on non oral treatment. Two hours glucose was higher than basal levels but fast glucose and fast or 2 h insulin levels did not change after low oral dose therapy. After 4 months, vW factor decreased only on non oral treatment and PCR and fibrinogens were unchanged on both treatment groups. In conclusion, the present results suggest that the studied treatments did not induce deleterious effects on variables related to cardiovascular risk, at least at short period of time, in early postmenopausal and apparently healthy women. Low dose oral HT has maintained the well known beneficial effects on lipid profile (lower total and LDL cholesterol) and did not induced an increase on pro-inflammatory or endothelial function markers. On the other hand, non oral HT has shown to be a safe alternative, and was not related to changes on metabolic profile or markers of endothelial function.

Made available in DSpace on 2015-07-22T20:50:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-25. Added 1 bitstream(s) on 2015-08-11T03:25:59Z : No. of bitstreams: 1 Publico-11912.pdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Introdução: A endocrinoterapia é uma das principais responsáveis pela redução de mortalidade do câncer de mama. Biomarcadores preditivos de resposta celular precoce vêm sendo estudados com intuito de prever precocemente a hormonioresistência. Freqüentes deleções e mutações têm sido descritas no gene p16 em diversos tipos de tumores, mas pouco se sabe sobre seu papel no câncer de mama e seu comportamento após endocrinoterapia neoadjuvante com tamoxifeno e anastrozol. Objetivos: Estudar a expressão do p16 e dos receptores de estrogênio e progesterona (RE e RP) em pacientes na pós - menopausa com carcinoma de mama RE e/ ou RP (+) após curto período (26 dias) de tratamento com tamoxifeno, anastrozol e placebo. Métodos: Estudo prospectivo randomizado duplo-cego realizado com 58 pacientes dos Hospitais Pérola Byington e São Paulo da UNIFESP (São Paulo - Brasil) com carcinoma ductal infiltrativo de mama, nos estádios II e III, que no período pré-operatório foram subdivididas em três grupos: P (placebo, N=25), T (tamoxifeno 20mg/dia, N=15) e A (anastrozol 1mg/dia, N=18). A biópsia foi realizada no momento do diagnóstico e após a cirurgia definitiva (26º dia) e os tumores foram isolados por micro-arranjos teciduais. O estudo imunoistoquímico foi realizado com anticorpos para p16 (Dako- OA315), RE (Neomarkers-M7047), RP (Dako- M3569). Realizou-se o estudo semiquantitativo utilizando-se os critérios de Allred e o estudo estatístico pelo teste paramétrico de Anova. Resultados: A positividade do p16 variou de 22 para 17%, respectivamente pré e pós tratamento com anastrozol; de 8 para 4% no grupo placebo e não houve variação, com 7% de positividade, no grupo que recebeu tamoxifeno. A comparação entre grupos e tempos não apresentou relação significativa para o p16 (p=0,17). Não foi encontrada correlação entre a positividade do p16 e o status hormonal (RE e RP). Conclusão: Não houve diferença estatística significante entre os três grupos estudados. Futuros estudos com métodos moleculares poderão esclarecer dúvidas suscitadas a respeito do tempo de exposição à droga necessária para interferir nos biomarcadores e proteínas. / Background: Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase 4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer and there is a lack in the literature about its expression behavior in neoadjuvant endocrinetherapy with tamoxifen or anastrozole. Objective: Analysis of p16INK4a expression in patients with invasive ductal carcinomas (IDC) prior to tamoxifen and anastrozole neoadjuvant treatment and possible correlation between predictive and prognostical factors – estrogen receptor (ER), progesterone receptor (PgR). Methods: We examined p16INK4a mRNA expression and its relationship with short period (26 days) neoadjuvant endocrine therapy with tamoxifen and anastrozole in 58 primary breast cancers with palpable ER-positive IDC. They were double-blind randomized in three neoadjuvant treatment groups for 21 days: Anastrozole 1mg/day (n= 17), Placebo (n=25) and Tamoxifen 20mg/day (n=15). Biomarkers status (ER, PgR and p16) were obtained by comparing single immunohistochemical evaluation of pre and post-surgery samples using Allred’s method. Statistical analyses were performed using the SPSS software for Windows. Results: Variation in p16 was 22% to 17% in anastrozole group, 8% to 4% in placebo group and there was no variation in tamoxifen group, standing in 7%. There was no significant statistical diference in p16INK4a expression among the three groups (p=0.17). Variation in p16 was 12% to 9% (p<0.05) when considering the three groups together. There was a significant decrease of p16 expression in pre and post surgery results. There was no significant statistical correlation between p16 expression and hormonal status (RE and RP). Conclusions: There was no significant statistical diference in p16INK4a expression among the three groups. There was a significant statistical decrease in p16INK4a expression when compared pre and post surgery values. These findings could indicate that expression of p16 and variation in pre and post surgery samples are associated with hormone responsiveness and mechanisms of resistance. There were no significant statistical correlation between p16 expression and hormonal status (RE and RP). Further studies are necessary to understand their functional interrelationships and whether high p16INK4a expression may be associated with a lack of hormone responsiveness in breast cancer. / TEDE / BV UNIFESP: Teses e dissertações

Menopause transition is usually associated with changes in body composition and a decrease in physical activity energy expenditure. Adipose tissue, especially visceral fat, is an important source of inflammatory markers, which contributes to the development of a pro-inflammatory state. Conversely, high levels of physical activity and exercise have an anti-inflammatory effect. One-hundred and two healthy premenopausal women participated in a 5-year longitudinal observational study (MONET: Montreal Ottawa New Emerging Team). The present secondary analyses were performed on 58 participants between the ages of 47 and 54 years with a full set of data.The aim of study was to investigate the impact of menopause transition and physical activity on inflammatory makers. The major finding of the first of 3 studies was that menopausal transition is accompanied by an increase in inflammatory markers, namely ferritin, IL-8, and sTNFR 1 and 2. The increase in IL-8 and sTNFR2 with menopause could be explained, in part, by changes in fat mass and peripheral fat, respectively. During and after menopause, significant bone loss occurs in women due to reduced estrogen production. Estrogen reduction favors bone resorption by regulating the production and activity of inflammatory markers. Therefore we further investigated the association between inflammatory markers and bone mineral density in premenopausal women transitioning to menopause (paper 2). Our results showed no significant association between change in inflammatory markers and change in bone mineral density in women transitioning to menopause. However, in premenopausal women hs-CRP was negatively associated with total, lumbar spine and femoral neck bone mineral density and along with weight and cardiorespiratory fitness may play a role in bone mineral density variation. Baseline level of hs-CRP, Hp, IL-6 and femoral neck bone mineral density along with percent change in physical activity energy expenditure and menopausal status partly explained the individual variation of bone mineral density losses in women transitioning to menopause. Finally, we investigated time spent in the postmenopausal years and the influence of the duration of the postmenopause status on body composition and cardiometabolic risk factors. We indicated that postmenopausal years and years since menopause is associated with decrease in blood glucose and increase in waist circumference, percent fat mass, total cholesterol, and high density lipoprotein. Inflammatory markers including ApoB, ferritin, adiponectin, sCD14 were higher during years after final menstrual period while sTNFR1 and sTNFR2 were higher during the menopause transition and early postmenopausal years.

A relação entre risco cardiovascular e terapia hormonal na pós-menopausa é controversa. Ainda que o estrogênio endógeno possa estar associado ao menor risco cardiovascular observado em mulheres na pré-menopausa em relação às pós-menopáusicas, grandes ensaios clínicos, como o WHI, falharam em demonstrar efeito benéfico da terapia hormonal. Estes resultados podem ter sido influenciados por uma série de fatores, sendo os mais importantes: idade média das pacientes e tempo de menopausa superiores às candidatas usuais de terapia hormonal, tipo e dose dos hormônios utilizados. Desenvolvemos ensaio clínico randomizado, cross-over, com objetivo de avaliar os efeitos de dois tipos de tratamento hormonal na menopausa: tratamento oral baixa dose, associação de estradiol 17 β nasal 300 μcg e drospirenona 2 mg, diário e tratamento nâo oral, estradiol 17 β nasal diário e progesterona micronizada vaginal, 200 mg, 14 dias por mês , sobre variáveis relacionadas com inflamação e função endotelial, perfil antropométrico, metabólico e hormonal em mulheres na pós-menopausa recente e sem doença clínica evidente. Quarenta mulheres na pós-menopausa foram alocadas aleatoriamente para iniciar o tratamento hormonal por um dos dois grupos de tratamento: via oral baixa dose (n=20): ou via não oral (n=20). Ao final dos primeiros 2 meses do estudo, o grupo inicialmente tratado com terapia oral passou a receber tratamento não oral por mais 2 meses, e o grupo inicialmente tratado com terapia não oral passou a receber terapia oral também por mais 2 meses. A avaliação laboratorial foi realizada antes e ao final de 2 e 4 meses de tratamento hormonal. A amostra do estudo foi composta por mulheres com média etária de 51,2 ± 2,7 anos e tempo de amenorréia de 23,1 ± 10 meses. Após os primeiros 2 meses de tratamento, não houve diferença significativa entre os tratamentos sobre circunferência da cintura, relação cintura/quadril, índice de massa corporal e níveis de pressão arterial. Colesterol total diminuiu em ambos os tratamentos de forma semelhante. O tratamento oral teve um efeito maior em reduzir os níveis de LDL-C. HDL-C, triglicerídeos, glicemia e insulinemia de jejum, glicemia e insulinemia 2 horas após sobrecarga oral de glicose não se modificaram. PCR e FVWdiminuíram significativamente, e fibrinogênio permaneceu inalterado. Após o período de 4 meses de tratamento hormonal, não houve diferença significativa entre os tratamentos sobre circunferência da cintura, relação cintura/quadril, índice de massa corporal e níveis de pressão arterial. Durante o tratamento oral observou-se redução da circunferência da cintura e da relação cintura/ quadril em relação ao basal. Colesterol total diminuiu em ambos os grupos de tratamento, e HDL-C diminuiu discreta, mas significativamente após o tratamento oral, enquanto triglicerídeos diminuíram durante tratamento não oral. A glicemia 2 horas após sobrecarga oral de glicose apresentou valores mais elevados em relação ao basal após tratamento oral. Em contraste, glicemia e insulinemia em jejum e insulinemia 2 horas após sobrecarga oral de glicose não se modificaram. Níveis de FVW encontraram-se significativamente reduzidos após 4 meses de tratamento hormonal. Em conclusão, os resultados obtidos em nosso estudo sugerem que os tratamentos não induziram efeitos deletérios sobre variáveis relacionadas com risco cardiovascular, a curto prazo, em uma população de mulheres na pós-menopausa recente e aparentemente saudáveis. O tratamento hormonal baixa dose por via oral manteve os efeitos benéficos conhecidos do tratamento hormonal por via oral, a redução do colesterol total e do LDL-C, e evitou os efeitos nocivos tradicionalmente atribuídos à via oral: o aumento de marcadores próinflamatórios, relacionados à disfunção endotelial. O tratamento hormonal por via não oral mostrou-se também uma alternativa segura, não relacionado à modificações no perfil metabólico e nos marcadores de função endotelial. / The relationship between cardiovascular risk and hormone therapy (HT) for menopause is a contemporary and complex issue. While evidences suggest an association between endogenous estrogen and cardiovascular protection among premenopausal women, recent clinical trials have failed in demonstrate a benefic impact of HT on prevention of cardiovascular events. These results seem to be related by several factors, including selection biases like higher mean age of and time since menopause of participants, fixed type and dosages of hormones administered. A cross-over, randomized clinical trial was designed in order to evaluate the effects of two types of HT: low dose oral treatment, estradiol 17 β oral 1 mg and drospirenona 2 mg, by day and non-oral treatment, estradiol 17 β nasal 300 μcg by day and vaginal micronized progesterone, 200 mg/d, 14 days by month on variables associated with endothelial function, anthropometric, metabolic and hormonal variables on early and healthy postmenopausal women.Forty postmenopausal women were randomly allocated to start with one of the treatments: low dose oral treatment or non-oral treatment. At the end of two months, the group that started with low dose oral treatment passed to receive the non oral treatment for additional two months and vice-versa. Laboratory evaluations were performed before, at 1, 2 and 4 months of HT. The sample of the study included postmenopausal women presenting mean age of 51.2 ± 2.7 years and mean time since menopause of 23.1 ± 10 months. After 2 months, no significant differences were observed between treatments on waist circumference, waist to hip ratio, BMI and arterial pressure. Total cholesterol levels were reduced on both treatments. Low oral dose treatment had greater effect in reducing LDL cholesterol. HDL cholesterol, triglycerides, fast and 2 hours glucose and insulin levels did not change with either treatment. PCR and vW factor levels were reduced in both treatment groups and fibrinogen did not change. After 4 months of low oral dose treatment, a reduction on waist circumference and waist/circumference ratio was found. Total cholesterol was lower than basal levels on bothtreatment groups and while HDL cholesterol presented a slight but significant reduction on low oral dose treatment, triglycerides decreased significantly on non oral treatment. Two hours glucose was higher than basal levels but fast glucose and fast or 2 h insulin levels did not change after low oral dose therapy. After 4 months, vW factor decreased only on non oral treatment and PCR and fibrinogens were unchanged on both treatment groups. In conclusion, the present results suggest that the studied treatments did not induce deleterious effects on variables related to cardiovascular risk, at least at short period of time, in early postmenopausal and apparently healthy women. Low dose oral HT has maintained the well known beneficial effects on lipid profile (lower total and LDL cholesterol) and did not induced an increase on pro-inflammatory or endothelial function markers. On the other hand, non oral HT has shown to be a safe alternative, and was not related to changes on metabolic profile or markers of endothelial function.

Body mass index (IMC) is a major determinant of bone mineral density (BMD) and obesity is widely believed to protect against fracture. Nevertheless, the higher BMD associated with obesity may just reflect the adaptation related to the increased mechanical demands on the skeleton in these subjects. The protection that it confers against fracture may not be greater than the protection that lower BMD confers in leaner individuals, particularly in view of the greater prevalence of trauma related to falls in the obese population. Therefore, the aim of this work was to evaluate the association between obesity and bone fractures in postmenopausal women in the city of Santa Maria/RS. This was a cross-sectional study carried out in the city of Santa Maria, parallel 29°, Southern Brazil, from 1st March to 31 August 2013. Were included to this survey post-menopausal women age, 55 years or over, who attend a General Practice Surgery (UBS) of its territory. Women with cognitive impairment, communication disabilities and in the menacme were excluded. Data were collected using a standardized questionnaire that covered domains about patients characteristics, fracture history, risk factors for fractures and medication use. Overall, one thousand and fifty seven women were eligible for analysis. BMI was assessed in 973 women, in which 39.6% had a BMI of 30 kg/m2 or more. A history of prevalent fracture was present in 17.4% obese women and 16.2% of non-obese women (P = 0.622). There was no difference between the BMI of the postmenopausal women with fractures and postmenopausal women without prevalent fractures. In addition, obesity has not shown to be a protective factor of bone fractures, given its odds ratio was 1.09 (95% CI 0.74 to 1.54). No association between the sites of fracture and BMI were detected. Age and mobility impairment were associated with bone fractures in obese women. On the other hand, hospital stay (at least one day overnight in the last year), disability in activities of daily living, ischemic heart disease, rheumatoid arthritis, and family history of fracture, and age were associated with prevalent fractures in nonobese women. In conclusion, our study has not identified a protective impact of obesity to the occurrence of bone fractures in postmenopausal women, although different factors associated with fractures were observed between obese and nonobese women. / O índice de massa corporal (IMC) é um importante determinante da densidade mineral óssea (DMO) e acreditava-se que a obesidade fosse fator protetor contra fraturas. Entretanto, a alta DMO associada à obesidade pode somente refletir o aumento das demandas mecânicas no esqueleto e pode não conferir uma maior proteção contra fraturas do que em indivíduos não obesos, particularmente em vista de maior prevalência de trauma associado a quedas na população obesa. Desta forma, o objetivo deste estudo foi estabelecer a associação entre obesidade e fraturas ósseas nas mulheres pós-menopausa do município de Santa Maria/RS. Este foi um estudo transversal realizado na cidade de Santa Maria, paralelo 29°, Sul do Brasil, no período de 01 março a 31 de agosto de 2013. Ao todo, foram incluídas 1057 mulheres com idade igual ou maior a 55 anos, na pós-menopausa e que frequentassem a unidade básica de saúde (UBS) de seu território. Mulheres com déficit cognitivo, com dificuldade de comunicação e que ainda menstruassem foram excluídas. Os dados foram obtidos através de questionários contendo informações que incluíam características das pacientes, história de fraturas, fatores de risco para fraturas e uso de medicações. O IMC foi avaliado em 973 mulheres, das quais 39,6% possuíam um IMC de 30 kg/m2 ou mais. Das mulheres obesas, 17,4% apresentaram história de fratura prevalente, comparativamente a 16,2% das não obesas (P = 0,622). Não houve diferença entre o IMC aferido entre os grupos de mulheres pós-menopausa com fraturas e sem fraturas prévias. Da mesma forma, a obesidade não demonstrou ser fator protetor para fraturas ósseas, pois a razão de chances foi 1,09 (IC 95% 0,74-1,54). Não houve significância estatística entre os sítios de fratura e o IMC. Idade e alguma dificuldade para locomoção foram fatores associados a fraturas ósseas em mulheres obesas. Já em mulheres não obesas os fatores associados idade, internação hospitalar (permanecer pelo menos uma noite no hospital no último ano), necessidade de auxílio de outra pessoa para o auto cuidado, cardiopatia isquêmica, artrite reumatoide e história familiar. Em resumo, nosso estudo não identificou um impacto protetor da obesidade para fraturas ósseas em mulheres pós-menopausa, embora os fatores associados a fraturas tenham sido diferentes entre mulheres obesas e não obesas.