Role of caveolin-eNOS platform and mitochondrial ATP-sensitive potassium channel in abrogated cardioprotective effect of ischemic preconditioning in postmenopausal women

Abstract Caveolin, the protein of the caveolar membrane, interacts and binds with endothelial nitric oxide synthase (eNOS), forming a caveolin-eNOS complex leading to suppression of the eNOS activity. Caveolin, therefore, maintains eNOS in the inactivated state leading to reduced nitric oxide (NO) production. Ischemic preconditioning disrupts the caveolin-eNOS complex leading to activation of the eNOS and thus results in cardioprotection. During ischemic preconditioning, NO produces cardioprotection by the opening of the KATP channel, and the caveolin forms a suitable signalling platform facilitating the interaction of NO with the KATP channel. Estrogen deficiency has been reported to upregulate caveolin-1 expression. The article aims to review the various mechanisms that placed the women at the risk of coronary artery diseases after postmenopausal estrogen deficiency and their role in the cardioprotective effect of ischemic preconditioning.

Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women

ABSTRACT Objective: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. Subjects and methods: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. Results: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). Conclusion: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

The role of moderate-to-vigorous physical activity in mediating the relationship between central adiposity and immunometabolic profile in postmenopausal women

ABSTRACT Objectives To analyze the role of moderate-to-vigorous physical activity (MVPA) in mediating the relationship between central adiposity and immune and metabolic profile in postmenopausal women. Materials and methods Cross-sectional study comprising 49 postmenopausal women (aged 59.26 ± 8.32 years) without regular physical exercise practice. Body composition was measured by dual-energy X-ray absorptiometry. Fasting blood samples were collected for assessment of nonesterified fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, insulin and estimation of insulin resistance (HOMA-IR). Physical activity level was assessed with an accelerometer (Actigraph GTX3x) and reported as a percentage of time spent in sedentary behavior and MVPA. All analyses were performed using the software SPSS 17.0, with a significance level set at 5%. Results Sedentary women had a positive relationship between trunk fat and IL-6 (rho = 0.471; p = 0.020), and trunk fat and HOMA-IR (rho = 0.418; p = 0.042). Adiponectin and fat mass (%) were only positively correlated in physically active women (rho = 0.441; p = 0.027). Physically active women with normal trunk fat values presented a 14.7% lower chance of having increased HOMA-IR levels (β [95%CI] = 0.147 [0.027; 0.811]). Conclusions The practice of sufficient levels of MVPA was a protective factor against immunometabolic disorders in postmenopausal women.

Publicaciones de artículos originales de autores cubanos sobre algunas afecciones endocrinas en la mujer de edad mediana / Publication of original papers on some endocrine illnesses in middle-aged women by Cuban authors

Introducción: en la posmenopausia se incrementa la morbilidad por afecciones endocrinas, cuya frecuencia varía en las diferentes regiones del mundo y que desconocemos en nuestro medio. Objetivo: identificar la frecuencia que en artículos originales autores cubanos hacen referencia sobre afecciones endocrinas frecuentes en la edad mediana de la mujer cubana, y reportar los artículos útiles. Métodos: estudio infométrico referido a las publicaciones de autores cubanos recuperados de las bases de datos (Lilacs, Medicc Review, Esbco, PubMed, Cochrane Library, Scielo Cuba y Cumed), repositorios de tesis, eventos médicos nacionales, relacionados con la osteoporosis posmenopausia, la diabetes mellitus tipo 2, el nódulo del tiroides, el hipo e hipertiroidismo y la tiroiditis autoinmune. Se incluyeron los artículos originales reportados entre 1995-2012, accesibles, con referencia a mujeres con edades 40-59 años, y en los que se especificara la metodología utilizada para establecer los diagnósticos de referencia. Resultados: se identificaron 7 703 trabajos que incluían al menos uno de los descriptores definidos. El 2,4 por ciento de los reportes de autores cubanos fueron útiles, y en todos se identificó una alta frecuencia de las afecciones referidas. La dificultad en el acceso virtual e impreso fue la principal causa de no utilidad de los artículos. Conclusiones: se evidencia la poca frecuencia o visibilidad de la morbilidad por afecciones endocrinas en la mujer de edad mediana(AU)

Introduction: in the postmenopausal period, morbidity from endocrine illnesses increases and their frequency varies in different parts of the world, but knowledge about this topic is limited in our country. Objective: to determine the frequency of reference to common endocrine illnesses affecting Cuban middle-aged women in original papers by Cuban authors and to report on useful articles. Methods: informative study of the publication of Cuban papers retrieved in Lilacs, Medicc Review, Esbco, PubMed, Cochrane Library, Scielo Cuba and Cumed databases, thesis repositories and national medical events, which cover postmenopausal osteoporosis, type 2 diabetes mellitus, thyroid modes, hypo and hyperthyroidism and autoimmune thyroiditis. It included accessible original papers from the 1995 to 2012 period, making reference to 40-59 years-old women and specifying the used methodology to make diagnoses. Results: there were found 7 703 papers that comprised at least one of the defined subject headings. In the group, 2.4 percent of reports by Cuban authors were useful and all identified high frequency of the above-mentioned illnesses. The extent of difficulties in having access, either digital or printed, to these articles was the main cause of classifying them as useless. Conclusions: low frequency of visibility of morbidity from endocrine illnesses in the Cuban middle-aged women was demonstrated(AU)

Índice de masa corporal y características clinicopatológicas de pacientes con cáncer de mama / Body mass index and clinical and pathological characteristics of breast cancer patients

Introducción: estudios previos han sugerido la relación del índice de masa corporal elevado con una mayor incidencia y un peor pronóstico del cáncer de mama. Objetivo: identificar la relación entre el índice de masa corporal en el momento del diagnóstico, y las características clinicopatológicas de pacientes con cáncer de mama de acuerdo con la presencia o no de menopausia. Métodos: estudio transversal y descriptivo de 47 mujeres, entre 36 y 84 años, con carcinoma ductal invasivo. Se midieron el peso y la estatura. Se calculó el índice de masa corporal para la clasificación de las pacientes en tres categorías: peso normal, sobrepeso y obesa. Se determinaron las características clinicopatológicas: tamaño del tumor, presencia de ganglios linfáticos metastásicos, etapa clínica, grado histológico y estado de los receptores de estrógeno, progesterona y receptor 2 para el factor de crecimiento epidérmico. Resultados: el índice de masa corporal varió en el rango de 18,54 a 44,92 kg/m2. No se observaron diferencias estadísticamente significativas entre los valores promedio globales de esta variable en las mujeres premenopáusicas y posmenopáusicas (26,76 kg/m2 ± 5,26 vs. 28,11 ± 5,61 kg/m2; p= 0,450), ni en el análisis realizado por categorías. La obesidad y el sobrepeso fueron asociados con un alto grado histológico, tanto en mujeres premenopáusicas (p= 0,038) como posmenopáusicas (p= 0,037). Adicionalmente, una asociación significativa entre el índice de masa corporal y el subtipo positivo al receptor de estrógenos o progesterona/receptor 2 para el factor de crecimiento epidérmico, se observó solo para las mujeres posmenopáusicas (p= 0,032). Conclusiones: estos resultados muestran que las mujeres obesas y con sobrepeso desarrollan fenotipos agresivos de cáncer de mama, independientemente de la presencia o no de menopausia. Además, entre las mujeres posmenopáusicas con índice de masa corporal elevado predominó el subtipo positivo al receptor de estrógenos o progesterona/receptor 2 para el factor de crecimiento epidérmico. Estudios futuros deberán realizarse para comprender los factores relevantes del hospedero y del tumor, para la prevención y el manejo clínico de las pacientes obesas con cáncer de mama(AU)

Introduction: previous studies have suggested the relationship of the high body mass index with higher incidence and bad prognosis of the breast cancer. Objective: to determine the relationship between the body mass index at the time of diagnosis of cancer, and the clinical-pathological characteristics of menopausal or non-menopausal breast cancer patients. Methods: descriptive and cross-sectional study of 47 women aged 36 to 84 years, with invasive duct carcinoma. Their weight and height were taken. Body mass index calculation served to classify the patients into 3 categories: normoweighed, overweighed and obese. The studied clinical-pathological characteristics were size of tumor, presence of metastatic lymph nodes, clinical staging, histological grade and state of estrogen receptor, progesterone receptor and 2 receptor for the epidermal growth factor. Results: the body mass index changed from 18.54 to 44.92 kg/m2. There were no statistically significant differences among the average overall values of this variable either in premenopausal and postmenopausal women ((26.76 kg/m2 ± 5.26 vs. 28.11 ± 5.61 kg/m2; p= 0.450) or in the analysis by categories. Obesity and overweight were associated to high histological grade both in premenopausal (p= 0.035) and postmenopausal women (p= 0.037). Additionally, a significant association was found between the body mass index and the estrogen or progesterone receptor /receptor 2-positive subtype (for the epidermal growth factor) in postmenopausal women (p= 0.032). Conclusions: these results show that obese and overweighed women may develop aggressive breast cancer phenotypes regardless of menopause. Moreover, the estrogen or progesterone receptor/receptor 2-positive subtype for the epidermal growth factor prevailed in postmenopausal women with high body mass index. Further studies should be conducted to better understand the relevant factors in the host and the tumor for the prevention and the clinical management of obese patients with breast cancer(AU)

Sedentary Lifestyle and High-Carbohydrate Intake are Associated with Low-Grade Chronic Inflammation in Post-Menopause: A Cross-sectional Study / Sedentarismo e alto consumo de carboidratos associados à inflamação crônica de baixo grau na pós-menopausa: um estudo transversal

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of death in post menopausal women, and inflammation is involved in the atherosclerosis process. Purpose to assess whether dietary pattern, metabolic profile, body composition and physical activity are associated with low-grade chronic inflammation according to highsensitivity C-reactive protein (hs-CRP) levels in postmenopausal women. Methods ninety-five postmenopausal participants, with no evidence of clinical disease, underwent anthropometric, metabolic and hormonal assessments. Usual dietary intake was assessed with a validated food frequency questionnaire, habitual physical activity was measured with a digital pedometer, and body composition was estimated by bioelectrical impedance analysis. Patients with hs-CRP ≥ 10 mg/L or using hormone therapy in the last three months before the study were excluded from the analysis. Participants were stratified according to hs-CRP lower or ≥3 mg/L. Sedentary lifestyle was defined as walking fewer than 6 thousand steps a day. Two-tailed Student's t-test, Wilcoxon-Mann-Whitney U or Chi-square (x 2) test were used to compare differences between groups. A logistic regression model was used to estimate the odds ratio of variables for high hs-CRP. Results participants with hs-CRP ≥ 3 mg/L had higher body mass index (BMI), body fat percentage, waist circumference (WC), triglycerides, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.01 for all variables) than women with hs-CRP <3 mg/L. Also, women with hs-CRP ≥3 mg/L had a higher glycemic load diet and lower protein intake. Prevalence of sedentary lifestyle (p < 0.01) and metabolic syndrome (p < 0.01) was higher in women with hs-CRP ≥3 mg/L. After adjustment for age and time since menopause, the odds ratio for hs- CRP ≥3 mg/L was higher for sedentary lifestyle (4.7, 95% confidence interval [95%CI] 1.4-15.5) and carbohydrate intake (2.9, 95%CI 1.1-7.7). Conclusions sedentary lifestyle and high-carbohydrate intake were associated with low-grade chronic inflammation and cardiovascular risk in postmenopause.

Resumo Introdução A doença cardiovascular é a principal causa de morte em mulheres na pós-menpausa e inflamação está envolvida com o processo de aterosclerose. Objetivo avaliar se o padrão alimentar, o perfilmetabólico, a composição corporal e a atividade física estão associados à inflamação crônica de baixo grau, de acordo com os níveis de proteína C-reativa (PCR-us), em mulheres na pós-menopausa. Métodos noventa e cinco participantes pós-menopáusicas foram submetidas a avaliações antropométrica, metabólica e hormonal. A ingestão alimentar foi avaliada por meio de questionário de frequência alimentar, a atividade física habitual, com pedômetro digital, e a composição corporal, por bioimpedância elétrica. Pacientes com PCR-us ≥10 mg/L ou em uso de terapia hormonal nos últimos três meses antes do estudo foram excluídas. As participantes foram estratificadas de acordo PCR-us inferior ou ≥3 mg/L. Pacientes com menos de 6 mil passos/dia foram consideradas sedentárias. Para análise estatística foram utilizados teste t de Student, Wilcoxon-Mann- Whitney U ou Qui-quadrado (x 2), além de modelo de regressão logística para estimar a razão de chances para PCR-us elevada. Resultados participantes com PCR-us ≥3 mg/L apresentaram maior índice de massa corporal (IMC), percentual de gordura corporal, circunferência da cintura, triglicerídeos, glicose e índice de insulino-resistência (HOMA-IR) (p = 0,01) comparadas às mulheres com PCR-us <3 mg/L. O grupo PCR-us ≥3 mg/L apresentou uma dieta com maior carga glicêmica e menor ingestão de proteínas. A prevalência de sedentarismo e síndrome metabólica foi maior em mulheres com PCR-us ≥3 mg/L (p < 0,01). Após ajuste para idade e tempo de menopausa, a razão de chances para PCR-us ≥3mg/L foi maior nas sedentárias (4,7, intervalo de confiança de 95% [95%CI] 1,4-15,5) e com maior ingestão de carboidratos (2,9, 95%CI 1.1-7,7). Conclusões Sedentarismo e alta ingestão de carboidratos foram associados com inflamação crônica de baixo grau e risco cardiovascular em mulheres na pósmenopausa.

Prevalencia de Síndrome metabólico en mujeres indígenas mayores de 45 años / Prevalence of metabolic syndrome in indigenous women older than 45 years

Antecedentes: El síndrome metabólico es un desorden que resulta en obesidad visceral, hipertensión arterial, dislipidemia y resistencia a la insulina. Después de la menopausia, su incidencia es secundaria al hipoestrogenismo. La enfermedad cardiovascular y el síndrome metabólico, después de la menopausia, tienen un insidencia de 35% y se estima que la mitad de las enfermedades cardiovasculares podrían estar relacionadas con el síndrome. Objetivo: Determinar la prevalencia de síndrome metabólico en mujeres indígenas...

Background: The metabolic syndrome is a disorder that results from visceral obesity, hypertension, dyslipidemia, and insulin resistance. After menopause, the incidence is secondary to hypoestrogenism. Cardiovascular disease and metabolic syndrome have an incidence of 35% after menopause and it is estimated that half of cardiovascular diseases could be related to this syndrome. Objective: Determine the prevalence of the metabolic syndrome in native women...

Marcadores de recambio óseo en mujeres postmenopáusicas: utilidad clínica / Bone remodelling markers in postmenopausal women: clinical utility

Bone metabolism is a dynamic process, which includes formation and resorption. Osteoblast and osteoclast are responsible of replacing 20 percent of bone each year. Bone Markers are fragments of bone matrix; these peptides are released in the process of formation and resorption, later accumulated in body compartments (bone and blood) and finally excreted in the urine, reflecting bone dynamic. The international Federation of Osteoporosis and the International Federation of Laboratory and Clinical Chemistry recommend the use of these two markers (one representing bone formation and the other bone resorption) to evaluate bone turnover, especially in high-risk groups such as postmenopausal women. The collagen C-terminal telopeptide or carboxi-terminal collagen crosslinking (CTX) is one of the most used, among different bone markers. This is a blood biomarker that can be measured to assess bone turnover; this marker increases when the bone resorption is accelerated. On the other hand, osteocalcin (a non-collagen protein) is a bone formation marker, which has been widely studied and can be measured in venous blood during bone formation. Both markers are important for monitoring anti-resorptive therapy, and they have been validated to predict fracture risk complementing densitometry in osteoporosis diagnosis. Main disadvantages are variability of the laboratory techniques and lack of information about normal reference values in different populations. Therefore it is necessary to establish normal reference values for each population before its incorporation as a clinical tool.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Effects of strength training on blood lipoprotein concentrations in postmenopausal women / Efeitos do treinamento de força sobre as concentrações de lipoproteínas sanguíneas em mulheres pós-menopausa

Strength training is often identified as a contributing factor in prevention of diseases and as a non-pharmacological treatment for metabolic disorders and for control of body mass. Its protective effects and utility for management of disease are amplified in people at risk of diabetes mellitus and dyslipidemias, and cardiovascular diseases (CVD). Recently the benefits of strength training have been used to reduce the risk of these diseases emerging in postmenopausal women, who are at greater risk of CVD than men of the same age. Notwithstanding, little is known about the effects of strength training on metabolism of blood lipoproteins. The objective of this review was to compare the results of articles that have investigated the effects on lipoprotein concentrations of strength training in postmenopausal women. Current articles dealing with the subject, with publication dates from 1979 to 2012 and large numbers of citations by well-known researchers were identified on the Pubmed, Scopus and EBSCO databases. It was concluded that strength training possibly has an action that affects lipoprotein metabolism and concentrations in postmenopausal women.

O treinamento de força tem sido frequentemente relacionado como contribuinte para a prevenção do aparecimento de doenças e como tratamento não farmacológico para distúrbios metabólicos e controle de massa corporal. Os efeitos protetores e de manejo de doenças se ampliam para sujeitos com riscos para diabetes mellitus e dislipidemias, e doenças cardiovasculares (DCV). Recentemente, os benefícios do treinamento de força têm sido usados para reduzir o risco do aparecimento dessas doenças em mulheres pós-menopausa, as quais apresentam um risco maior para desenvolver DCV quando comparadas aos homens de mesma idade. Entretanto, pouco se sabe sobre a efetividade do treinamento de força sobre metabolismo das lipoproteínas sanguíneas. O objetivo desta revisão foi comparar os resultados de artigos que abordaram os efeitos do treinamento de força em mulheres pós-menopausa e quais os resultados sobre as concentrações de lipoproteínas. Foram pesquisadas referências atuais sobre o tema a ser abordado, sendo que os artigos foram selecionados nas bases de dados Pubmed, Scopus e EBSCO, artigos atuais datados do período de 1979 a 2012, com grande número de citações de pesquisadores renomados no assunto. Em conclusão, o treinamento de força possivelmente tenha uma ação efetiva no metabolismo e na concentração de lipoproteínas em mulheres pós-menopausa.

The association of breast arterial calcification and metabolic syndrome

OBJECTIVES: We investigated the relationship between metabolic syndrome and breast arterial calcification detected via mammography in a cohort of postmenopausal subjects. METHODS: Among 837 patients referred to our radiology department for mammographic screening, 310 postmenopausal females (105 patients with and 205 patients without breast arterial calcification) aged 40 to 73 (mean 55.9±8.4) years were included in this study. The groups were compared with respect to clinical characteristics and metabolic syndrome criteria. Univariate and multivariate analyses identified the factors related to breast arterial calcification. RESULTS: Age, postmenopausal duration and the frequencies of diabetes mellitus, hypertension and metabolic syndrome were significantly higher in the subjects with breast arterial calcification than in those without (p<0.05). Multivariate analysis indicated that age (OR = 1.3, 95% CI = 1.1-1.6, p = 0.001) and metabolic syndrome (OR = 4.0, 95% CI = 1.5−10.4, p = 0.005) were independent predictors of breast arterial calcification detected via mammography. The independent predictors among the features of metabolic syndrome were low levels of high-density lipoproteins (OR = 8.1, 95% ...

A terapia aquática como coadjuvante na variação do humor em mulheres pós-menopáusicas / Aquatic Therapy Supporting the Variation of humor in women post menopausal women

Objetivo: Observar a influência de um programa de exercícios terapêuticos em piscina, nas sintomatologias menopáusica e depressiva em um grupo de mulheres na menopausa. Material e Métodos: Estudo de intervenção do tipo longitudinal, com abordagem quantitativa e medidas pré e pós-tratamento, em população de mulheres menopáusicas. Instrumentos de coleta de dados: Índice Menopausal de Blatt e Kuppermanne Escala de Depressão Geriátrica de Black & Yesavage. Osdados foram analisados utilizando-se o software Statiscal Package for the Social Sciences (SPSS) versão 16.0 para Windows, além do teste estatístico Wilcoxon e do teste de Correlação de Spearman. Resultados: No que diz respeito àsintomatologia menopáusica, observou-se Média (SD) antes de 11,73 (9,90) e depois da intervenção de 7,60 (5,60), com uma diferença significativa (z=-3,293; p=0,001) entre as medidas pré e pós-tratamento. Quanto aos sintomas de depressão, observou-se Média (SD) antes de 13,3 (5,5) e depois de 9,0 (5,9), houve diferença significativa (z=-2,003;p=0,045) entre as medidas pré e pós-tratamento, resultados confirmados pelo teste de Correlação de Spearman.Conclusão: Verificou-se que a hidroterapia proporciona benefícios físicos e funcionais, tais como alívio nas ondas de calor e melhoria no humor e na imagem corporal,aumentando a auto-estima feminina e diminuindo asintomatologia depressiva abundantemente encontrada nas mulheres menopáusicas.

Objective: To observe the influence of an aquatic therapeuticexercise program on menopausal symptoms and depressionin a group of menopausal women. Material and Methods:This was a longitudinal intervention study, with a quantitativeapproach and pre- and post-treatment measures in apopulation of menopausal women. Instruments for datacollection: Blatt and Kuppermann Menopausal Index and Black& Yesavage Geriatric Depression Scale. Data were analyzedusing the software Statistical Package for Social Sciences(SPSS) version 16.0 for Windows, in addition to Wilcoxonstatistical test and Spearman’s correlation test. Results: The mean (SD) of menopausal symptoms before and afterintervention was found to be 11.73 (9.90) and 7.60 (5.60),respectively, with a significant difference (z=-3.293; p=0.001) between pre- and post-treatment measures. For symptoms of depression, means (SD) of 13.3 (5.5) and 9.0 (5.9) were observed before and after intervention, with a significant difference (z=-2.003; p=0.045) between pre- and post treatment measures, confirmed by the Spearman correlationtest. Conclusion: Hydrotherapy was found to provide physicaland functional benefits, such as relief of heat waves and improvement in mood and body image, increasing female self esteem and reducing depression symptoms abundantly found in menopausal women.

Níveis séricos de vitamina B12 não se relacionam com baixa densidade mineral óssea em mulheres brasileiras na pós-menopausa / Serum levels of vitamin B12 are not related to low bone mineral density in postmenopausal Brazilian women

INTRODUÇÃO: Osteoporose e deficiência de vitamina B12 são condições de prevalência crescente com o envelhecimento. A associação entre níveis séricos de vitamina B12, baixa massa óssea e risco aumentado de fraturas ósseas tem sido descrita, mas os estudos não são homogêneos e os resultados são controversos. OBJETIVO: Investigar a associação entre níveis plasmáticos de vitamina B12 e densidade mineral óssea em mulheres assintomáticas na pós-menopausa. MÉTODOS: Mulheres assintomáticas no período pós-menopausa foram consecutivamente incluídas neste estudo transversal. A densidade mineral óssea (coluna lombar e fêmur) foi avaliada pelo método DXA Lunar Prodigy Vision, e foram determinados níveis sanguíneos de vitamina B12, cálcio, fósforo, fosfatase alcalina óssea e hormônio paratireoidiano. Os critérios da Organização Mundial de Saúde foram considerados para o diagnóstico de osteoporose. RESULTADOS: Foram incluídas neste estudo 70 mulheres, com média de idade de 62,5 ± 7 anos. Do total, 18 (25,7%) apresentaram densidade mineral óssea normal, 33 (47,1%) tinham osteopenia e 19 (27,1%) tinham osteoporose. Seis (8,6%) pacientes haviam apresentado fratura de punho, duas (2,8%) reportaram diagnóstico de fratura vertebral e apenas uma (1,4%) paciente havia sofrido fratura de quadril. Os níveis de vitamina B12 (média ± DP; pg/mL) das mulheres com densidade mineral óssea normal, osteopenia e osteoporose foram 590,2 ± 364,3, 536,6 ± 452,3 e 590,2 ± 497,9, respectivamente (P = 0,881). A análise de regressão múltipla mostrou que o índice de massa corporal e a fosfatase alcalina óssea foram preditores da densidade mineral óssea na coluna lombar. CONCLUSÃO: Os resultados indicam que níveis de vitamina B12 não se relacionam à densidade mineral óssea neste grupo de mulheres brasileiras na pós-menopausa.

INTRODUCTION: Osteoporosis and vitamin B12 deficiency are conditions with an increasing prevalence over time. It has been described an association between low serum vitamin B12, osteoporosis and increased risk of bone fractures, but the studies are heterogeneous and the results are controversial. OBJECTIVE: To investigate the association between plasma levels of vitamin B12 and bone mineral density in a group of asymptomatic women after menopause. METHODS: Asymptomatic postmenopausal women were consecutively invited to participate in this cross-sectional study. Bone mineral density (lumbar spine and femur) was measured by DXA Lunar Prodigy Vision, and blood levels of vitamin B12, calcium, phosphorus, bone alkaline phosphatase (BAF), and parathyroid hormone were determined. For the diagnostic of osteoporosis the World Health Organization criteria were considered. RESULTS: Seventy women were included, mean age 62.5 ± 7 years. Eighteen (25.7%) women had normal bone mineral density, 33 (47.1%) had osteopenia and 19 (27.1%) had osteoporosis. Six (8.6%) patients had wrist fracture; two (2.8%) reported a diagnosis of vertebral fracture and only one (1.4%) patient had suffered a hip fracture. The levels of vitamin B12 (mean ± SD, pg/mL) of women with normal bone mineral density, osteopenia and osteoporosis were 590.2 ± 364.3, 536.6 ± 452.3, and 590.2 ± 497.9, respectively (P = 0.881). Multiple regression analysis showed that body mass index and BAF were the main predictors of lumbar spine bone mineral density. CONCLUSION: The results indicate that vitamin B12 serum levels are not related to bone mineral density in this group of Brazilian postmenopausal women.

The prevalence and significance of oestrogen receptor (ER) positivity in breast cancer at the University Hospital of the West Indies, Jamaica / Prevalencia y significación de la positividad del receptor de estrógeno (RE) en el cáncer de mama en el Hospital Universitario de West Indies, Jamaica

OBJECTIVE: To identify the prevalence of oestrogen receptor (ER) positivity, and determine the relationship of ER status with patient and tumour characteristics, in patients with breast cancer. SUBJECTS AND METHODS: A retrospective review was conducted regarding the prevalence and clinical significance of ER in patients with breast cancer at the University Hospital of the West Indies (UHWI). Oestrogen receptor status results of 243 patients treated at UHWI were collected for the period January 1, 2002 to December 31, 2009. One hundred and ninety-nine were available for review. RESULTS: Oestrogen receptor status was positive in 125 (63%) and negative in 74 (37%) patients. Mean age at diagnosis was 52.6 ± 13.0 years for the ER positive group and 58.5 ± 14.23 years for the ER negative group. Postmenopausal women accounted for 55.2% and 64.9% of the ER positive and negative groups, respectively. Mean BMI was 28.0 kg/m² and 29.6 kg/m² for the ER positive and negative groups, respectively. Menarche occurred mainly between ages 12 and 13 years for both groups. Mean age at 1st parity was 23.4 years for the ER positive and 21.4 years for the ER negative group with median parity of two for both groups. The most prevalent risk factors were oral contraceptive pill (OCP) use (24.3% for the ER positive group, 17.1% for the ER negative group), family history of breast cancer (12.0%; 13.4%) and previous smoking (8.4%; 6.9%). Tumour node metastasis (TNM) stage was Stage II in most cases (46%; 49%). Infiltrating ductal histology was most common (81.5%; 87.7%). Her 2/ neu status was negative for most patients (91.3%; 91.5%). Most patients were disease free (77.6%; 70.0%) after an average follow-up period of 3.5 years. More persons in the ER negative group had locoregional recurrence (8%) and metastases (22%). CONCLUSIONS: Oestrogen receptor positive cohort was more prevalent. The ER negative group was older (p = 0.003).

OBJETIVO: Identificar la prevalencia del receptor de la positividad de receptor de estrógeno (RE), y determinar la relación del estatus de RE con el paciente y las características del tumor, en las pacientes con cáncer de mama. SUJETOS Y MÉTODOS: Se realizó un estudio retrospectivo con respecto a la prevalencia e importancia clínica del RE en los pacientes con cáncer de mama en el Hospital Universitario de West Indies (UHWI). Se recogieron los resultados del estatus del receptor de estrógeno de 243 pacientes tratados en UHWI en el periodo del 1 de enero de 2002 al 31 de diciembre de 2009. Ciento noventa y nueve estuvieron disponibles para examen. RESULTADOS: El estatus del receptor de estrógeno fue positivo en 125 (63%) y negativo en 74 (37%) pacientes. La edad promedio al momento del diagnóstico fue 52.6 ± 13.0 años para el grupo de RE positivo y 58.5 ± 14.23 años para el RE grupo negativo. Las mujeres menopáusicas representaron el 55.2% y el 64.9% del RE de los grupos positivos y negativos respectivamente. El índice de masa corporal (IMC) promedio fue 28.0 kg/m2 y 29.6 kg/m2 para el RE de los grupos positivos y negativos respectivamente. La menarquia ocurrió principalmente entre las edades de 12 y 13 años para ambos grupos. La edad promedio en la primera paridad fue 23.4 años para el grupo de RE positivo y 21.4 años para el de RE negativo, siendo la paridad mediana igual a dos para ambos grupos. Los factores de riesgo de mayor preponderancia fueron el uso de anticonceptivos orales (ACO) (24. 3% para el grupo de RE positivo, 17.1% para el grupo RE negativo); historia familiar de cáncer de mama (12.0%; 13.4%); y hábito de fumar con anterioridad (8.4%; 6.9%). De acuerdo con la estadificación tumor-nódulo-metástasis (TNM), se trataba de la Etapa II en la mayor parte de los casos (46%; 49%). La histología ductal infiltrante fue la más común (81.5%; 87.7%). El estatus Her2/neu fue negativo para la mayoría de las pacientes (91.3%; 91.5%). La mayoría de las pacientes se hallaban libres de enfermedad (77.6%; 70.0%) después de un periodo promedio de seguimiento de 3.5 años. En el grupo de RE negativo había más personas con recurrencia locoregional (8%) y metástasis (22%). CONCLUSIONES: La cohorte positiva del receptor de estrógeno positiva fue más prevaleciente. El grupo negativo de RE fue de mayor edad (p = 0.003).

Tratamento da atrofia urogenital com a administração local de estrogênios: um estudo randomizado, controlado em mulheres no climatério e na pós-menopausa / Treatment of urogenital atrophy with the local administration of oestrogens: a randomized, controlled study in climateric and postmenopausal women

Objetivo: Avaliar a eficácia, segurança e aceitabilidade de cremes vaginais contendo promestriene (Colpotrofine®, Laboratórios Teva do Brasil) ou estriol (Ovestrion®, MSD, Brasil), em mulheres no climatério e na menopausa. Método: Estudo prospectivo, randomizado, aberto, de grupos paralelos e controlado. Locais: Instituto de Ginecologia da Universidade Federal do Rio de Janeiro e Faculdade de Medicina da Valença. Material: 80 mulheres na menopausa ou climatério, para quem o tratamento com creme vaginal de estrogênio foi indicado. Intervenção(s): As pacientes aplicaram 1g do creme vaginal, respectivo, a cada noite por 20 dias e depois uma aplicação semanal durante seis meses consecutivos. As pacientes foram distribuídas aleatoriamente sucessivamente numa proporção de 1:1, de acordo com a sua ordem de chegada: as pacientes ímpares foram designadas para receber promestriene e as com números pares foram designadas para receber estriol. Principal medida de desfecho(s): A variável de resposta primária foi a maturação do epitélio vaginal, avaliada pela citologia vaginal e medida pelo índice de Frost. Ambos os tratamentos melhoraram significativamente o trofismo do epitélio vaginal. Resultado(s): Uma melhoria acentuada (94,1%) foi indicado para pacientes do grupo promestriene por três meses, culminando na melhoria de 100% em 6 meses (p <0,0001). Houve clara melhoria dos sintomas da menopausa para ambos os grupos, sendo os tratamentos seguros e bem tolerados. Pacientes do grupo promestriene foram significativamente (p <0,038) mais satisfeitas (100%) com seu tratamento em comparação ao grupo estriol (73,33%). Conclusão(s): Ambos os tratamentos reverteram a atrofia vaginal, levando a um epitélio vaginal saudável, com destaque estatisticamente significativo para o promestriene, o que condicionou a uma melhoria da qualidade de vida.

Influence of eNOS gene polymorphism on cardiometabolic parameters in response to physical training in postmenopausal women

The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9 percent and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15 percent), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3 percent and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3 percent) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.

Menopausia y riesgo cardiovascular / Menopause and cardiovascular risk

En el período posmenopáusico aumentan la morbilidad y la mortalidad por enfermedad cardiovascular. Se ha demostrado que la disminución en el nivel de estrógenos actúa incrementando el riesgo de aterotrombosis, al incidir en la aparición de cambios en el metabolismo lipídico y en algunos factores de coagulación y la fibrinólisis, asi como en una tendencia al incremento del peso corporal, acentuándose la acumulación de grasa en la región abdominal. Para contrarrestar estos y otros cambios desfavorables que aparecen en la mujer posmenopáusica se emplea la terapia de reemplazo hormonal, cuyos beneficios reales sobre el sistema vascular se encuentran aún en discusión...

Composição da matriz extracelular do ligamento cardinal de mulheres na pós-menopausa com e sem prolapso uterino / Composition of extracellular matrix of the cardinal ligament in postmenopausal women with and without uterine prolapse

O prolapso uterino tem sua incidência aumentada na pós-menopausa. O objetivo deste estudo é identificar as alterações na matriz extracelular do ligamento cardinal associadas à menopausa e ao prolapso uterino. Ligamento cardinal de três diferentes grupos de mulheres, pré-menopausa, prolapso uterino e pós-menopausa, foram identificados e biopsiados durante 57 histerectomias abdominais ou vaginais. As amostras foram processadas por métodos bioquímicos para caracterização e quantificação de glicosaminoglicanos sulfatados e colágeno. As concentrações relativas de glicosaminoglicanos foram obtidas por eletroforese. Procedimentos histológicos foram feitos para identificar fibras elásticas (Weigert), distribuição de colágeno (Picro Sirius) e decorin (imunohistoquímica). Nossos resultados mostraram aumento na concentração de GAG de 72,2%, redução na concentração de colágeno de 37% e diminuição de 22% de fibras elásticas no grupo de prolapso uterino quando comparado ao grupo da pós-menopausa (p<0,05, p<0,04 e p<0,05 respectivamente). As concentrações relativas de glicosaminoglicanos sulfatados para condroitin sulfato, heparan sulfato e dermatan sulfato não mostraram diferenças entre os três grupos. A organização do colágeno foi similar entre os três grupos e a marcação do decorin pareceu estar diminuída no grupo de prolapso uterino. Nossos resultados indicam alterações no metabolismo do tecido conjuntivo. O ligamento cardinal da mulher na pós-menopausa possui uma matriz extracelular mais densa. Esta alteração não ocorre na mulher com prolapso uterino.

Uterine prolapse has increase of incidence after menopause. The aim of this study was to identify the changes in extracellular matrix of cardinal ligaments associated to menopause and uterine prolapse. Cardinal ligament of 3 different groups (pre-menopause, menopause and uterine prolapse) are identified and biopsied during 57 women's abdominal or vaginal hysterectomy. Biopsy specimens were assessed by biochemical methods to characterize and quantify sulfated glycosaminoglycans and collagen. Relative concentrations of GAG were obtained by electrophoresis. Histological procedures are made to identify elastic fibers (Weigert) collagen distribution (Picro sirius) and decorin (immunohistochemistry). Our results showed increase in GAG concentration 72.2% in uterine prolapse group compared to menopause group (p<0.05). Collagen concentration was 37% lower in uterine prolapse group compared to menopause group (p<0.04). Relative concentration of GAG: heparan sulfate, chondroitin sulfate and dermatan sulfate showed no differences among three groups. Elastic fibers showed a significant reduction of aproximately 22% uterine prolapse group compared to menopause group (p<0.05). Collagen organization was similar in three groups and the staining pattern of decorin seemed to be decreased in uterine prolapse group. Our results indicate changes in connective tissue metabolism. Cardinal ligament in postmenopausal women has a denser extracellular matrix. This change is not observed in women with uterine prolapse.

Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil / Vias Wnt canônica e não canônica: uma comparação entre o câncer endometrial tipo I e endométrio atrófico no Brasil

CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de São Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at São Paulo Hospital, Universidade Federal de São Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS: Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0 percent) than in group B (31.1 percent). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION: FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium.

CONTEXTO E OBJETIVO: A via Wnt está envolvida na tumorigênese de diversos tipos de tecidos. Por essa razão, propusemo-nos a avaliar a expressão de genes da família Wnt no câncer endometrial tipo I. TIPO DE ESTUDO E LOCAL: Estudo transversal com coleta de materiais do banco de tecidos do Departamento de Patologia da Universidade Federal de São Paulo. MÉTODOS: Amostras endometriais foram obtidas de cirurgias que ocorreram entre 1995 e 2005 no Hospital São Paulo, Universidade Federal de São Paulo. Foram separados dois grupos segundo o tipo de tecido obtido: grupo A, com endométrio atrófico (n = 15); e grupo B, com adenocarcinoma endometrial (n = 45). Comparamos a expressão imunoistoquímica de Wnt 1, Frizzled-1 (FZD1), Wnt 5a, Frizzled-5 (FZD 5) e beta-catenina entre câncer endometrial tipo I e endométrio atrófico. RESULTADOS: Na expressão do Wnt1, FZD1 e Wnt5a, não observamos associação significante entre os grupos. Na expressão do FZD5, encontramos associação significante entre os grupos (P = 0,001). A proporção de positividade do FZD5 foi significantemente maior no grupo A comparado ao grupo B (31,1 por cento). Em relação à curva de sobrevida para o FZD5 no grupo B, não tivemos associação significante entre endométrio atrófico e adenocarcinoma do endométrio. Também não observamos associação significante na expressão da beta-catenina (P = 1,000). CONCLUSÃO: FZD5 é downregulated no adenocarcinoma endometrial quando comparado ao endométrio atrófico.