Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Influência da suplementação de vitamina D na homeostase glicêmica, em mulheres diabéticas, na pós-menopausa / Influence of vitamin D supplementation on glycemic homeostasis in postmenopausal diabetic women

Introdução: Diabetes mellitus tipo 2 (DM2) e a menopausa estão associados com os níveis de 25-hidroxivitamina D3 25(OH)D3. O efeito da suplementação de colecalciferol sobre a glicemia ou incidência de DM2 possui resultados discordantes nos principais estudos. Objetivo: Relacionar a suplementação de colecalciferol em mulheres diabéticas, na pós-menopausa, com a homeostase glicêmica, num período de 2 anos. Método: Quarenta mulheres, entre 63,84 ± 7,56 anos, receberam colecalciferol 1000 UI/dia por 12 meses e 2000 UI/dia por outros 12 meses. Os desfechos primários foram 25(OH)D3, glicemia de jejum (GJ), hemoglobina glicada (HbA1c), insulina de jejum (I), mensuração da resistência à ação da insulina (HOMA-IR), capacidade secretória da célula  (HOMA-), colesterol total (CT), HDL colesterol (HDL-c), triglicerídeos (TG), proteína-C reativa (PCR). Os desfechos secundários foram: pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), circunferência de cintura (CC), relação cintura-quadril (RCQ), área de gordura visceral (AGV), índice de massa corporal (IMC). Resultados: As variáveis que mostraram significância nas comparações das medidas repetidas foram: a 25(OH)D3  P0 (27,99±9,23) vs P12 (38,35±9,67), p = 0,0001; P0 (27,99±9,23) vs P24 (42,78±9,17), p = 0,0001; HDL-c  P0 (46,61±8,97) vs P24 (58,97±10,98), p = 0,001; P12 (49,94±10,82) vs P24 (58,97±10,98), p = 0,02 e PAD P0 (83,24 ± 14,51) vs. P6 (77,94 ± 10,38) vs. P12 (77,42 ± 9,99) vs. P18 (78,39 ± 6,38) vs. P24 (75,81 ± 6,72) valor de p = 0,044. Nas comparações múltiplas: 25(OH)D3  P0 (27,99 ± 9,23) vs. P12 (38,35±9,67) e P0 (27,99± 9,23) vs. P24 (47,78 ± 9,17) valor de p = 0,0001; HDL-c P0 (46,61 ± 8,97) vs. P24 (58,97±97) valor de p = 0,001 e entre as medidas P12 (49,94 ± 10,82) vs. P24 (58,97±10,98) valor de p = 0,02 e PAD P0 (83,24±14,51) vs. P24 (75,81±6,72) valor de p = 0,037. Conclusão: Apesar da identificação de receptores de vitamina D em diversos órgãos e sistemas participantes na fisiopatologia do DM2, não podemos afirmar que a suplementação de colecalciferol possa vir a contribuir para o a homeostase glicêmica desta doença multifatorial.

Introduction: Type 2 diabetes mellitus (DM2) and menopause are associated with the status of 25 hydroxyvitamin D [25(OH)D3]. The effect of cholecalciferol supplementation on glycemia or incidence of DM2 has been reported in the primary trials with discordant results. Objective: This study mainly aimed to correlate the use of cholecalciferol in postmenopausal diabetic women with glycemic homeostasis within two years. Method: Forty postmenopausal diabetic women aged 63.84±7.56 years received cholecalciferol 1,000 IU/day for 12 months and 2,000 IU/day for another 12 months. The primary outcomes evaluated the levels of 25(OH)D3, fasting glycemia (FG), glycated hemoglobin (HbA1c), fasting insulin (I), insulin resistance measurement (HOMA-IR), insulin secretory capacity (HOMA-ß), total cholesterol (TC), HDL cholesterol (HDL-c), triglycerides (TG), and C-reactive protein (CRP). Secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), waist-hip ratio (WHR), visceral fat area (VFA) and body mass index (BMI). Results: Among the primary outcomes, in the comparisons of repeated measures, the variables that showed significant results were 25(OH)D3  P0 (27,99±9,23) vs P12 (38,35±9,67), p = 0,0001; P0 (27,99±9,23) vs P24 (42,78±9,17), p = 0,0001; HDL-c  P0 (46,61±8,97) vs P24 (58,97±10,98), p = 0,001; P12 (49,94±10,82) vs P24 (58,97±10,98), p = 0,02 and DBP P0 (83,24 ± 14,51) vs. P6 (77,94 ± 10,38) vs. P12 (77,42 ± 9,99) vs. P18 (78,39 ± 6,38) vs. P24 (75,81 ± 6,72) value of p = 0,044. In the multiple comparisons, there was significance between the measures: 25(OH)D3  P0 (27,99 ± 9,23) vs. P12 (38,35±9,67) e P0 (27,99± 9,23) vs. P24 (47,78 ± 9,17) with p = 0,0001; HDL-c P0 (46,61 ± 8,97) vs. P24 (58,97±97) value of p = 0,001 and P12 (49,94 ± 10,82) vs. P24 (58,97±10,98) with p = 0,02 and PAD P0 (83,24±14,51) vs. P24 (75,81±6,72) value of p = 0,037. Conclusion: Despite the identification of vitamin D receptors in several organs and systems participating in the pathophysiology of DM2, we cannot say that the supplementation of cholecalciferol may contribute to the glycemic homeostasis of this multifactorial disease.

Dilatação fluxo-mediana da artéria braquail: aspectos técnicos, aplicabilidade e reprodutividade em ginecologia e obstetrícia / Flow-mediated dilatation of brachial artery: technical aspects, applicability and reproducibility in gynecology and obstetrics

A avaliação da dilatação fluxo-mediada da artéria braquial (DILA) tem-se incorporada na prática clínica como método capaz de contribuir no estudo das doenças arterioescleróticas. Estudos demonstraram que os valores de DILA são reduzidos em pacientes com pré-eclâmpsia, e que a redução desses valores está diretamente ligada à morbidade da doença. Outros estudos correlacionam diabetes gestacional e disfunção endotelial com redução do DILA nestas pacientes. Ainda, a terapia de reposição hormonal tem sido demonstrada como fator de melhora nos valores do DILA em pacientes na pós-menopausa. O objetivo deste estudo foi realizar uma revisão bibliográfica sobre a utilização do DILA em Ginecologia e Obstetrícia. Foi realizado um levantamento bibliográfico nas bases da Bireme, Scielo e PubMed, de trabalhos publicados entre 2013 e 2017. Podemos concluir que métodos não invasivos e de fácil execução, como o DILA, podem ter impactos relevantes ao identificar grupos de riscos e, assim, viabilizar medidas protetivas.(AU)

The evaluation of the flow-mediated dilation of the brachial artery (FMD) has been incorporated into clinical practice as a method capable of contributing to the study of arteriosclerotic diseases. Studies have shown that FMD values are reduced in patients with preeclampsia, and that the reduction in these values is directly associated with disease morbidity. Other studies correlate gestational diabetes and endothelial dysfunction with reduction of FMD in these patients. Furthermore, hormone replacement therapy has been demonstrated as an improvement fator in FMD values in postmenopausal patients. The objective of this study was to perform a bibliographic review on the use of FMD in Gynecology and Obstetrics. A bibliographical survey was carried out on the Bireme, Scielo and PubMed databases, of works published between 2013 and 2017. We can conclude that non-invasive and easy-to-execute methods, such as FMD, can have relevant impacts when identifying gropups of risk and thus make feasible measures protective.(AU)

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

Statins and bonehealth: a mini review / Estatinas y salud ósea: una minirevisión

Statins are a widely prescribed class of medications that inhibit similar pathways as the anti-resorptive bisphosphonate drugs. Statins target the mevalonate pathway by blocking HMG-CoA reductase. Several recent meta-analyses concluded statins are osteoprotective in the general population. Here we present current literature exploring the mechanisms underlying the putative osteoprotective effects of statins. We also review recent clinical studies, ranging from observational cohort studies to randomized clinical trials, testing the effect of statins on bone health in various populations. (AU)

Las estatinas son un grupo de drogas prescriptas en forma habitual, con la capacidad de bloquear vías de señalización similares a las inhibidas por los amino-bisfosfonatos. Las estatinas inhiben la vía del mevalonato, a través del bloqueo de diferentes enzimas. Varios metaanálisis recientes llevaron a la conclusión de que las estatinas tienen capacidad osteoprotectora en la población general. En esta revisión presentamos la literatura actual describiendo los mecanismos que subyacen en el potencial efecto osteoprotector de las estatinas, como así también estudios observacionales y clínicos aleatorizados sobre el efecto de estatinas en la salud ósea en diversas poblaciones. (AU)

Protective effect of yerba mate intake on the cardiovascular system: a post hoc analysis study in postmenopausal women

The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P<0.049, P<0.048, and P<0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P<0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women.

Calidad de vida en posmenopáusicas tratadas con tibolona / Quality of life in postmenopausal women treated with tibolone

Comparar la calidad de vida (CV) en mujeres posmenopáusicas antes y después del tratamiento con Tibolona atendidas en la consulta ginecológica de la Maternidad "Dr. Armando Castillo Plaza", Maracaibo, Venezuela. Métodos: Investigación comparativa y aplicada, con diseño no experimental, y prospectivo, que incluyo una muestra de 100 pacientes posmenopáusicas, evaluadas antes y después de 6 y 12 meses de recibir la terapia de reemplazo hormonal con Tibolona oral (2,5mg/día) por medio del cuestionario Menopause Rating Scale (MRS).Resultados: 94 mujeres completaron el protocolo de estudio, determinándose que antes de comenzar el tratamiento la mayoría presentaba síntomas somáticos, psicológicos y genitourinarios severos, mientras que al cabo de 12 meses de tratamiento hubo una mejoría significativa en todos los síntomas estudiados (P= 0.000). Asimismo, se evidenció una mejora significativa en la CV luego del tratamiento con Tibolona, expresada por una regresión de las mediasen las puntuaciones alcanzadas con el MRS entre la medición inicial, a los 6 y a los 12 meses; con un porcentaje de cambio en la CV de las pacientes participantes de -38,33% y -82.20% después de 6 y 12 meses de la intervención farmacológica, los cuales resultaron de relevancia clínica y significancia estadística (P= 0.000). Conclusión: La terapia hormonal sustitutiva con Tibolona mejora la CV de las pacientes posmenopáusicas en todas sus dimensiones, sobre todo en cuanto a la disminución de los síntomas somáticos.Palabras clave: calidad de vida, menopausia, terapia de reemplazo hormonal, tibolona(AU)

To compare the quality of life (QOL) in postmenopausal women before and after treatment with Tibolone attending at the gynaecological consultation in the "Maternidad Dr. Armando Castillo Plaza", Maracaibo, Venezuela. Methods: Comparative and applied research with quasi experimental and prospective design, which included a sample of 100 postmenopausal women, evaluated before and after 6 and 12 months receiving hormone replacement therapy with oral Tibolone (2,5mg/day) through the questionnaire Menopause Rating Scale (MRS). Results: 94 women completed the study protocol, it was found that before treatment the majority had most somatic, psychological and severe genitourinary, while after 12 months of treatment there was a significant improvement in all symptoms studied (P = 0.000 .) We also demonstrated a significant improvement in QOL after treatment with Tibolone, expressed by a regression of the means of the scores obtained with the MRS between the initial measurement, at 6 and 12 months, with a percentage change in the CV of the patients participating -38.33% -82.20% and after 6 and 12 months of pharmacological intervention, which were of clinical relevance and statistical significance (P = 0.000). Conclusion: Hormone replacement therapy with Tibolone improves QOL of the postmenopausal patients in all its dimensions, especially in terms of reduction in somatic symptoms(AU)

Efeito do tamoxifeno sobre o endométrio em pacientes com câncer de mama na pós-menopausa / Effect of tamoxifen on the endometrium in post-menopausal patients with breast cancer

O trabalho tem como objetivo discutir, através de uma revisão da literatura, as influências do tamoxifeno sobre as alterações do padrão endometrial em pacientes com câncer de mama na pós-menopausa. Além de caracterizar os principais padrões endometriais e relacioná-los ao câncer de endométrio, são descritas também as recomendações da literatura vigente para a monitorização e seguimento destas pacientes. A literatura especializada demonstra claramente a relevância do acompanhamento clínico rigoroso destas mulheres pelo risco aumentado de câncer endometrial; no entanto, ainda não há consenso sobre qual o melhor exame de rastreio ou a periodicidade de realização do mesmo. Conclui-se que a prioridade é o exame clínico anual e orientação das pacientes quanto à sintomatologia, principalmente quanto à presença de sangramento vaginal. A partir destes sintomas, dá-se prosseguimento com investigação mais detalhada.(AU)

The present work aims to discuss, through a literature review, the influence of tamoxifen use in endometrial pattern changes in postmenopausal patients with breast cancer. In addition, to characterize the main endometrial patterns and relate them to endometrial cancer was a secondary objective. This review describes the recommendations of the current literature for endometrial monitoring of these patients. The literature clearly demonstrated to be relevant the clinical monitoring of these patients, because the increased risk of endometrial cancer. However, there is no consensus about which is the best tracking exam or the timing of completion of it. It was concluded that the priority is an annual clinical checkup for symptoms, especially the presence of vaginal bleeding; further, detailed investigation will depend on which symptoms are presented.(AU)

Estudo exploratório do uso de plantas medicinais para o controle de fatores de risco cardiometabólico em mulheres pós-menopausa / Exploratory study of the medicinal plants used to control cardiometabolic risk, in postmenopausal women

Este estudo buscou identificar o uso de plantas medicinais para o controle de fatores de risco cardiometabólico, em mulheres pós-menopausa. Trata-se de um estudo transversal, analítico e exploratório e subprojeto de uma pesquisa institucional "Estudo multidimensional de mulheres pós-menopausa do município de Catuípe/RS". As informações relativas ao uso de plantas foram obtidas em entrevista estruturada e os dados relativos ao índice de massa corporal, circunferência abdominal, pressão arterial, perfil lipídico e glicêmico do banco de dados da referida pesquisa. Foram selecionadas 51 mulheres, 37,2% relataram usar plantas para problemas cardiometabólicos e apresentavam elevado risco cardiovascular. Foram citadas 18 espécies de plantas, três usadas para diabetes mellitus, sendo a Sphagneticola trilobata a mais citada, uma para hipertrigliceridemia, cinco para hipercolesterolemia, entre as quais a Myristica fragrans foi a mais mencionada, uma para hipertensão e três para redução de peso, destacandose a Camellia sinensis. Para seis das espécies estudadas foi atribuída ação diurética e uma delas tem indicação para problemas cardíacos. Dentre as citadas, seis encontramse na RDC 10/2010 e três no Formulário de Fitoterápicos da Farmacopéia Brasileira, contudo, apenas a indicação de uma planta confere com o relato das entrevistadas, por outro lado foram encontrados estudos que relacionaram estas plantas com efeitos cardioprotetores. Considerando a importância do manejo adequado destas doenças, tornase necessário averiguar se as plantas estão sendo utilizadas para a indicação correta. Sugere-se também a implantação de ações educativas visando qualificar o uso de plantas para diminuir o risco cardiometabólico, utilizando as Políticas do SUS como instrumento de trabalho.

This study objective to identify the use of medicinal plants to control cardiometabolic risk factors in postmenopausal women. This study is cross-sectional, analytical and exploratory and subproject of an institutional research "Multidimensional study of postmenopausal women in the city of Catuípe/RS". The information about the use of plants were obtained from structured interviews and the data on body mass index, waist circumference, blood pressure, lipid and glycemic profile of said search database. The sample is 51 women, 37.2% reported using plants to cardiometabolic problems and had high cardiovascular risk. There were 18 plant species mentioned, three was used for diabetes mellitus, sphagneticola trilobata being the most cited, one for hypertriglyceridemia, and five to hypercholesterolemia, among which Myristica fragrans was the most mentioned, one medicinal plant was cited for hypertension and three to reduce weight, like Camellia sinensis. For six of the species studied was attributed diuretic action and one of them is indicated for heart problems. Among the aforementioned six are in the DRC 10/2010 and three in Brazilian Herbal Pharmacopoeia, however, only the indication of a plant gives to the account of the interviewees, however studies have found that these plants with related effects cardioprotective. Considering the importance of proper management of these diseases, it is necessary to determine whether the plants are being used for the correct indication. It also suggests the implementation of educational actions to qualify the use of plants to reduce cardiometabolic risk, using Public Health Rules as a working tool.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. .

Nonalcoholic fatty liver disease in menopausal women / Doenca hepatica gordurosa nao alcoolica em mulheres menopausadas

Context Nonalcoholic Fatty Liver Disease (NAFLD) is common in postmenopausal women. It is associated with metabolic syndrome. However, the influence of hormone replacement therapy in NAFLD development in these women needs to be investigated. This study aimed to describe the clinical characteristics of NAFLD in postmenopausal women, and the relationship between hormone replacement therapy and this disease. Methods From April 2009 to April 2011, 292 postmenopausal women from National Health System from Northeast of Brazil were selected, and 251 were included in this study. Menopause was defined as the absence of menstruation for 12 consecutive months in otherwise healthy women. Criteria to NAFLD included: presence of steatosis on abdominal ultrasound; history of alcohol consumption less than 20 g/day and exclusion of other liver diseases. All women underwent a clinical evaluation. Standard univariate and multivariate analyses were performed to evaluate the results. Results The mean age was 56.5 ± 6.7 years. Hormone replacement therapy was referred by 21.1% (53) women and 78.9% (198) was not. Prevalence of NAFLD was 37.1% (93/251) in postmenopausal women, 26,4% (14/53) in the group with hormone replacement therapy and 39,9% (79/198) without hormone replacement therapy. Gamma-glutamyl transpeptidase (P = 0.001), alanine transaminase (P<0.01), ferritin (P<0.001) and insulin resistance (homeostatic model assessment of insulin resistance ≥3) (P<0.001) were higher in the group of women with NAFLD diagnosis who did not referred the use of hormone replacement therapy. Metabolic syndrome was also more frequent in women with NAFLD, who did not refer hormone replacement therapy. Conclusion In conclusion this data suggests elevated prevalence of NAFLD in postmenopausal women; negative association of hormone replacement therapy and NAFLD. .

Contexto A doença hepática gordurosa não alcoólica (DHGNA) é comum em mulheres na pós-menopausa. Esta condição está associada à síndrome metabólica. No entanto, a influência da terapia de reposição hormonal no desenvolvimento da DHGNA nessas mulheres necessita ser investigada. Este estudo teve como objetivo descrever as características clínicas da DHGNA em mulheres na pós-menopausa e, a relação entre terapia de reposição hormonal e esta doença. Métodos De abril de 2009 a abril de 2011, 292 mulheres pós-menopausadas do Sistema Único de Saúde foram selecionados, e 251 foram incluídas neste estudo. A menopausa foi definida como a ausência de menstruação durante 12 meses consecutivos em mulheres saudáveis. Os critérios para diagnostico da DHGNA foram: presença de esteatose na ultra-som abdominal, história de consumo de álcool menor que 20 g/dia e exclusão de outras doenças hepáticas. Todas as mulheres foram submetidas a uma avaliação clínica. Para a obtenção dos resultados foram realizadas as análises uni e multivariada. Resultados A média de idade foi de 56,5 ± 6,7 anos. O uso de terapia de reposição hormonal foi referido por 21,1% (53) das mulheres e 78,9% (198) negaram seu uso. A prevalência de DHGNA foi de 37,1% (93/251) nas mulheres pós-menopausadas, sendo de 26,4% (14/53) no grupo em uso de terapia de reposição hormonal e 39,9% (79/198) no grupo sem uso desta terapia. A gama-glutamil transpeptidase (P = 0,001), alanina transaminase (P<0,01), ferritina (P<0,001) e resistência à insulina (obtida pelo modelo de avaliação homeostática de resistência à insulina ≥ 3) (P<0,001) foram ...

Tratamento pós-menopausa reduz a atividade da catalase e atenua o risco cardiovascular / Postmenopausal therapy reduces catalase activity and attenuates cardiovascular risk

FUNDAMENTO: A menopausa pode levar a alterações na saúde feminina, com mudanças no estado oxidativo de mulheres pós-menopausadas, para as quais são limitadas as informações relativas à influência da hormonioterapia (HT) sobre as atividades das enzimas antioxidantes. OBJETIVO: Avaliar a influência da HT sobre a atividade da catalase, concentrações de lipídeos e lipoproteínas, proteína de transferência de colesteril éster, substâncias reativas ao ácido tiobarbitúrico, nitratos, proteína C-reativa ultrassensível e espessura da carótida em mulheres pós-menopausadas. MÉTODOS: Foram alocadas 94 mulheres para um de quatro grupos com ou sem HT. O último grupo foi subdividido em mulheres sendo tratadas com estrógeno e outras com estrógeno mais progestágeno. Foram realizadas medidas de parâmetros bioquímicos plasmáticos e da espessura da íntima-média da carótida. RESULTADOS: A HT antagonizou a redução na atividade da catalase após a menopausa, mas não teve efeito sobre os níveis da proteína de transferência de colesteril éster, substâncias reativas ao ácido tiobarbitúrico, peróxido lipídico, nitrato e proteína C reativa ultrassensível, nem sobre a espessura da íntima-média da carótida. A análise multivariada mostrou que a HT baseada em estrógeno atenuou a relação entre os fatores de risco cardiovasculares e a espessura da íntima-média da carótida comum. CONCLUSÃO: Este estudo mostra que a HT em mulheres pós-menopausadas produz efeitos antioxidantes e antiateroscleróticos benéficos por melhorar as concentrações séricas de lipídios e lipoproteínas, aumentar a atividade da catalase sérica e atenuar a associação entre os fatores de risco cardiovasculares e a aterosclerose precoce.

BACKGROUND: Menopause can lead to alterations in women's health, with changes in the oxidative status of postmenopausal women in whom information regarding the influence of hormone therapy (HT) on antioxidant enzyme activities is limited. OBJECTIVE: To evaluate the influence of HT on catalase activity; concentrations of lipids and lipoprotein, cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, nitrates, high-sensitivity C-reactive protein and carotid thickness in postmenopausal women. METHODS: Ninety-four consecutive women were allocated to one of four groups, without HT and with HT. The latter group was subdivided into women using estrogen and those using estrogen plus progestogen therapy. Plasma biochemical parameters and common carotid intima-media thickness measurements were performed. RESULTS: HT antagonized the decrease in catalase activity after menopause, but had no effect on the levels of cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, lipid peroxide, nitrate, high-sensitivity C-reactive protein, or on the common carotid intima-media thickness. Multivariate analysis showed that estrogen-based HT attenuated the relationship between cardiovascular risk factors and the intima-media thickness of the common carotid. CONCLUSION: This study indicates that HT in postmenopausal women produces beneficial antioxidant and anti-atherosclerotic effects by ameliorating the plasma lipid and lipoprotein profiles, increasing plasma catalase activity and attenuating the association between cardiovascular risk factors and early atherosclerosis.

Breast density in women with premature ovarian failure or postmenopausal women using hormone therapy: analytical cross-sectional study / Densidade mamária em mulheres com falência ovariana prematura ou na pós-menopausa e em uso de terapia hormonal: estudo transversal analítico

CONTEXT AND OBJECTIVE: Studies on postmenopausal women have reported increased risk of breast cancer relating to the type and duration of hormone therapy (HT) used. Women with premature ovarian failure (POF) represent a challenge, since they require prolonged HT. Little is known about the impact of prolonged HT use on these women's breasts. This study aimed to evaluate the effects of one type of HT on the breast density of women with POF, compared with postmenopausal women. DESIGN AND SETTING: Cross-sectional study at the Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (Unicamp). METHODS: 31 women with POF and 31 postmenopausal women, all using HT consisting of conjugated equine estrogen combined with medroxyprogesterone acetate, and matched according to HT duration, were studied. Mammography was performed on all subjects and was analyzed by means of digitization or Wolfe's classification, stratified into two categories: non-dense (N1 and P1 patterns) and dense (P2 and Dy). RESULTS: No significant difference in breast density was found between the two groups through digitization or Wolfe's classification. From digitization, the mean breast density was 24.1 percent ± 14.6 and 18.1 percent ± 17.2 in the POF and postmenopausal groups, respectively (P = 0.15). Wolfe's classification identified dense breasts in 51.6 percent and 29.0 percent, respectively (P = 0.171). CONCLUSION: There was no difference in breast density between the women with POF and postmenopausal women, who had used HT for the same length of time. These results may help towards compliance with HT use among women with POF.

CONTEXTO E OBJETIVO: Estudos com mulheres na pós-menopausa relatam aumento no risco de câncer de mama relacionado ao tipo e duração da terapia hormonal (TH) utilizada. Mulheres com falência ovariana prematura (FOP) representam desafio por necessitarem de TH prolongada. Pouco se conhece sobre ação da TH nas mamas dessas mulheres. Este estudo objetivou avaliar os efeitos de um tipo de TH sobre a densidade mamária de mulheres com FOP comparativamente à de mulheres pós-menopausa. TIPO DE ESTUDO E LOCAL: Estudo de corte transversal no Departamento de Tocoginecologia, Universidade Estadual de Campinas (Unicamp). MÉTODOS: Estudaram-se 31 mulheres com FOP e 31 mulheres na pós-menopausa, todas usando TH com estrogênio conjugado equino mais acetato de medroxiprogesterona, pareadas pelo tempo de utilização da TH. Todas realizaram mamografia, analisada por digitalização e por classificação de Wolfe, estratificada em duas categorias: não densa (padrão N1 e P1) e densa (P2 e Dy). RESULTADOS: Não houve diferença significativa entre a densidade mamária dos grupos analisadas por digitalização ou classificação de Wolfe. Pela digitalização, calculou-se densidade mamária média em 24.1 por cento ± 14.6 e 18.1 por cento ± 17.2 nas com FOP e pós-menopausa, respectivamente (P = 0,15); pela classificação de Wolfe identificou-se mamas densas em 51,6 por cento e 29,0 por cento, respectivamente (P = 0,171). CONCLUSÃO: Não se observou diferença na densidade mamária de mulheres com FOP comparativamente à de mulheres na pós-menopausa utilizando TH pelo mesmo período de tempo. Estes resultados podem auxiliar na aderência à TH de pacientes com FOP.

Assessment of DNA nucleo base oxidation and antioxidant defense in postmenopausal women under hormone replacement therapy.

Background and Objective: The aim of the present study was to evaluate oxidative stress byinvesting oxidatively damaged DNA AS Formamidopyrimidine DNA glycosylase (Fpg) -sensitive sites, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities reduced glutathione (GSH) level and nitrite level as satble end product of in women receiving hormone replacement therapy (HRT). Materials and Methods: 127 healthy postmenopausal women receiving HRT and 25 healthy control postmenopausal women were included in this study. Women receiving HRT, comprised surgical menopausal women who underwent surgery for benign conditionsand received conjugated equine estrogen, 0.625 mg/day for 1year (group 1), 5 years (group 2) and more than 10 years (group 3), spontaneous postmenopausal women received conjugated equine estrogen, 0.625 (Premarin) mg/day and medroxyprogesterone acetate, 2.5 mg/day (Premelle) for 1 year (group 4), 5 years (group 5) and more than 5 years (group 6).We investigated in the present study the effects of HRT on nitrite level and GSH level, activities of SOD and GPx and oxidative damage to DNA by comet assays by measuring levels of Fpg-sensitive sites. Results: Although no significant differences were found in the SOD activities, in total group receiving HRT, increased DNA oxidation (P<0.001) together with an increased GPx activity (P<0.001) and nitrite level (P<0.001) as well as a decreased GSH level (P < 0.05) as compared with controls were observed. Conclusion: Estrogen alone or oestrogen in combination with progesterone and duration of use did not significantly alter the results. We evaluated that caused oxidative stress by investigating oxidative DNA damage as Fp-sensitive sites and GSH.NO levels in women receiving HRT.

Conjugated Linoleic Acid and lipid profile of postmenopausal women

Most animal studies have shown that trans-10 and cis-12 isomers of Conjugated linoleic Acid, [CLA] tend to increase insulin resistance. But the effect of equal isomers of CLA [50:50 ratios of cis-9, trans-11: trans-10, cis-12 isomers] on lipid profiles, glucose, and insulin resistance and sensitivity in postmenopausal women is not clear. In the present study, we performed a randomized, double blind, placebo-controlled trial to examine the changes in lipid profiles, glucose, and insulin concentration following 4 CLAG80 capsules containing 3.2g CLA [50:50 ratios of cis-9,trans-ll: trans-10, cis-12 isomers] or 4 placebo capsules supplementation for 12 weeks in postmenopausal women. Seventy six healthy postmenopausal women were randomized to receive placebo or 3.2 g CLA for 12 weeks. Anthropometric measurements were done. Blood samples were collected after 12-14 hours fasting before and after intervention. Insulin resistance and insulin sensitivity were estimated based on the homeostasis [HOMA] and QUIKI models. In weeks 0, 6 and 12 during the trial, subjects completed 3d dietary records. These dietary records were coded by the same dietitian, and analyzed with the Food Processor program. There were no significant effect on serum lipids, insulin, glucose, insulin resistance and insulin sensitivity over 12 weeks in postmenopausal women. Mixed isomer CLA supplementation had no effect on serum insulin, lipids profile, glucose and insulin resistance/sensitivity during 12 weeks of intervention in postmenopausal women

Efeitos do Trifolium pratense nos sintomas climatéricos e sexuais na pós-menopausa / Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause

OBJETIVO: Avaliar os efeitos do tratamento com Trifolium pratense nos sintomas climatéricos e na satisfação sexual de mulheres na pós-menopausa. MÉTODOS: Este estudo foi prospectivo, randomizado, duplo-cego e controlado com placebo. Foram selecionadas 120 mulheres na faixa etária de 45 anos a 65 anos com sintomas climatéricos, amenorreia superior a um ano e sem tratamento nos últimos seis meses. Após a seleção, foram divididas em dois grupos: GT -receberam Trifolium pratense na dose de 40 mg, 1 capsula/dia; GP -receberam placebo (controle), contendo lactose, 1 cápsula/dia. A duração do tratamento foi de 12 meses. As pacientes foram avaliadas clinica e laboratorialmente antes do tratamento e com quatro, oito e 12 meses de tratamento. Foi empregado também o Índice Menopausal de Kupperman (IMK) e o Inventário de Satisfação Sexual Golombok Rust. No final do estudo, cada grupo tinha 50 pacientes. RESULTADOS: Houve melhora significante dos sintomas menopausais após quatro meses de tratamento pelo IMK, principalmente em relação aos fogachos, comparando os dados antes do tratamento nos dois grupos, porém, não houve diferença significante entre os grupos. Não houve melhora na sexualidade antes e após o tratamento. CONCLUSÃO: O tratamento por 12 meses com Trifolium pratense, na dose de 40mg/dia, não promoveu melhora significante dos sintomas menopausais e na satisfação sexual.

OBJECTIVE: To evaluate effects of treatment with Trifolium pratense on climacteric symptoms and sexual satisfaction in postmenopausal women. METHODS: This study was prospective, randomized, double-blind and placebo-controlled. We selected 120 women, aged between 45 and 65 years with climacteric symptoms, with absence of menstruation (amenorrhea) for more then one year and without any treatment in the last six months. After selection, women were divided into two groups: GT received 40 mg of Trifolium pratense (one capsule per day); GP received placebo (control, one capsule of lactose per day). Treatment lasted 12 months and women were evaluated before and after four, eight and twelve months of treatment by clinical (Kupperman Menopausal Index -KMI and the Golombok Rust Inventory of Sexual Satisfaction) and laboratory exams. At study end, each group had 50 patients. RESULTS: There was a significant decrease of symptoms after four months of treatment according to the KMI, mainly of hot flashes in relation to baseline data for both groups, but not between both groups. Evaluation of sexual satisfaction did not disclose any difference in both groups before and after treatment. CONCLUSION: The 40mg/day Trifolium pratense treatment may not ameliorate menopausal symptoms or improve sexual satisfaction.

Estradiol transdérmico e perfil lipídico: efeitos em um grupo específico de mulheres brasileiras pós-menopausadas / Transdermal estradiol and lipid profile: effects on a specific group of brazilian postmenopausal women / Estradiol transdérmico y perfil lipídico: efectos en un grupo específico de mujeres brasileñas posmenopáusicas

Fundamento: Em mulheres pós-menopausadas, mudanças significantes ocorrem, que podem induzir doenças cardiovasculares, tais como o perfil lipídico aterogênico devido a um aumento nos níveis de colesterol total e LDL, e uma diminuição nos níveis de HDL. A terapia de reposição hormonal (TRH) pode evitar essas mudanças no perfil lipídico. Objetivo: Determinar os efeitos da TRH constituída por estradiol transdérmico e acetato de medroxiprogesterona nos parâmetros bioquímicos e lipídicos de mulheres brasileiras pós-menopausadas. Métodos: Este é um estudo prospectivo, longitudinal, aberto, no qual trinta mulheres pós-menopausadas receberam estradiol em gel transdérmico (1 mg/dia) de forma contínua, combinado com acetato de medroxiprogesterona (MPA) (5 mg/dia) por 12 dias/mês. Os seguintes parâmetros foram determinados: colesterol total, triglicérides, lipoproteína de alta densidade (HDL-colesterol), lipoproteína de baixa densidade (LDL-colesterol), lipoproteína de muito baixa densidade (VLDL-colesterol), glicose, aspartato aminotransferase (AST), alanina aminotransferase (ALT), gama-glutamil transferase (GGT) e hormônio folículo estimulante (FSH). Resultados: Os parâmetros do perfil lipídico mostraram uma diminuição não-significante, enquanto os níveis de GGT e FSH apresentaram uma diminuição estatisticamente significante. Conclusões: O tratamento com estradiol em gel transdérmico não mostrou um impacto significante no perfil lipídico, de forma que não resultou em um efeito benéfico nos marcadores de doenças cardiovasculares, sugerindo que a dose, modo de administração e o tempo de tratamento foram importantes para esses resultados. Além disso, o tratamento com dose baixa e modo de administração transdérmico também demonstrou um significante efeito hepático nessa população. Dessa forma, esse tratamento pode fornecer efeitos interessantes sobre o perfil lipídico em mulheres brasileiras pós-menopausadas.

Background: In postmenopausal women, significant changes occur that can induce cardiovascular diseases, such as atherogenic lipid profile, due to an increase in total cholesterol and LDL levels, and a decrease in HDL cholesterol levels. The hormone replacement therapy (HRT) can prevent these changes in lipid profile. Objective: Verify the effects of HRT consisting of transdermal estradiol gel associated with medroxyprogesterone acetate on the lipid profile and biochemical parameters in Brazilian postmenopausal women. Methods: This study is an open prospective longitudinal study, in which thirty postmenopausal women received transdermal estradiol gel (1 mg/day) continuously combined with oral medroxyprogesterone acetate (MPA) (5 mg/day) for 12 days/month. The following parameters were determined: total cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gama glutamyl transferase (GGT) and follicle-stimulating hormone (FSH). Results: The parameters of the lipid profile did not show a significant decrease, while the levels of GGT and FSH had a statistically significant decrease. Conclusions: the treatment with transdermal estradiol gel did not have a significant impact on the lipid profile, thus not resulting in a beneficial effect on cardiovascular disease markers, suggesting that the dose, administration route and the time of treatment were important for these results. Moreover, the treatment using small dose and the transdermal administration route also had a significant hepatic effect in this population. Therefore, this treatment might provide interesting effects on the lipid profile in Brazilian postmenopausal women.

Fundamento: Cambios significantes ocurren en las mujeres posmenopáusicas que pueden inducir enfermedades cardiovasculares, tales como el perfil lipídico aterogénico debido a un aumento en los niveles de colesterol total y LDL y una disminución en los niveles de HDL. La terapia de reemplazo hormonal (TRH) puede evitar esos cambios en el perfil lipídico. Objetivo: Determinar los efectos de la TRH constituida por estradiol transdérmico y acetato de medroxiprogesterona en los parámetros bioquímicos y lipídicos de mujeres brasileñas posmenopáusicas Métodos: Este es un estudio prospectivo, longitudinal, abierto, en el que treinta mujeres posmenopáusicas recibieron estradiol en gel transdérmico (1 mg/día) de forma continua, combinado con acetato de medroxiprogesterona (MPA) (5 mg/día) por 12 días/mes. Se determinaron los seguientes parámetros: colesterol total, triglicéridos, lipoproteína de alta densidad (HDL-colesterol), lipoproteína de baja densidad (LDL-colesterol), lipoproteína de muy baja densidad (VLDL-colesterol), glucosa, aspartato transaminasa (AST), alanina aminotransferasa (ALT), Gammaglutamiltranspeptidasa (GGT) y hormona foliculoestimulante (FSH). Resultados: Los parámetros del perfil lipídico mostraron una disminución insignificante, mientras los niveles de GGT y FSH presentaron una disminución estadísticamente significante. Conclusiones: El tratamiento con estradiol en gel transdérmico no mostró un impacto significante en el perfil lipídico, causando un efecto benéfico en los marcadores de enfermedades cardiovasculares, sugiriendo que la dosis, el modo de administración y el tiempo de tratamiento fueron importantes para esos resultados. Además, el tratamiento con dosis baja y modo de administración transdérmico también demostró un significante efecto hepático en esa población. Así pues, ese tratamiento puede surtir efectos interesantes sobre el perfil lipídico en las mujeres brasileñas posmenopáusicas.

Effects of isoflavones on the skin of postmenopausal women: a pilot study

OBJECTIVE: The aim of this study was to evaluate the effects of isoflavones on the skin of postmenopausal women. DESIGN: A prospective study was performed with 30 postmenopausal women before and immediately after the end of treatment with 100 mg/day of an isoflavones-rich, concentrated soy extract for six months. A skin punch was performed in the gluteal region for sample collection before and immediately after the treatment program. Morphometric determination of epidermal thickness, the papillary index (wrinkling), and the amount of dermal elastic and collagen fibers was assessed. In addition, the number of blood vessels in the sample was also evaluated. The paired Student¡¯s t-test was used for statistical analysis (P ¡Ü 0.05). RESULTS: Isoflavone treatment resulted in a 9.46% increase in the thickness of the epidermis in 23 patients. In addition, the papillary index was reduced in 21 women. The papillary index was inversely proportional to skin wrinkling, i.e., there were a large number of papillae after treatment. The amount of collagen in the dermis was increased in 25 women (86.2%). In 22 women (75.8%) we observed that the number of elastic fibers increased. The number of dermal blood vessels was significantly increased in 21 women.CONCLUSION: Our data show that the use of a concentrated, isoflavone-rich soy extract during six consecutive months caused significant increases in epithelial thickness, the number of elastic and collagen fibers, as well as the blood vessels.