O envelhecimento normal é um processo contínuo, que desencadeia alterações psicossociais e biológicas, não afetadas por patologias. Estas mudanças podem desencadear perdas de ordem neuromuscular e óssea, influenciando o aparelho locomotor dos idosos. A osteoporose é uma doença que afeta sistêmica e progressivamente o esqueleto sendo as fraturas sua principal consequência, especialmente na coluna vertebral. A identificação destas fraturas pode ser realizada através da morfometria vertebral, analisadas através de raios-X (MRX) ou absorciometria de raios-X (MXA), que consideram morfologia da vértebra através da comparação da altura de seus contornos em 6 pontos diferentes. As mulheres, sobretudo na pós-menopausa, estão mais susceptíveis a fraturas. A prescrição de exercício, não deve somente agregar benefícios físicos, mas também deve considerar a predisposição ao surgimento de novos agravos, como as fraturas. Os exercícios de alta intensidade na água podem funcionar como um recurso seguro para uma população normalmente fragilizada pela idade. Assim, o objetivo da pesquisa foi verificar se a sobrecarga mecânica causada por um programa de exercícios aquáticos de alta intensidade é segura para a morfologia da coluna vertebral de mulheres na pós-menopausa. Trata-se de um estudo prospectivo e controlado onde foram analisadas 108 mulheres sedentárias na pós-menopausa, distribuídas em um grupo com fratura (n=20) e outro sem fratura (n=88). O grupo foi classificado em controle (GC) (n = 44) composto por idosas sedentárias e intervenção (GI) (n = 64), formado por aquelas que participaram do protocolo de hidroginástica. Todas as participantes receberam suplementação oral com 500 mg de cálcio e 1000 UI de Vitamina D3 e foram submetidas a uma avaliação inicial e após 24 semanas de intervenção com um programa de hidroginástica. Foram avaliados os dados antropométricos, informações sobre parâmetros de dor, testes aplicados para variáveis neuromusculares e realização de densitometria óssea seguida de morfometria para identificação de fraturas. Os achados apontaram que 18,51% das mulheres presentaram fraturas, predominantemente localizadas na coluna torácica a região anterior da vértebra. Observou-se mudanças significativas para força, flexibilidade e dimuição do número de quedas nos grupos com e sem fratura (p<0,05). A presença de fraturas esteve associada à idade, Índice de Massa Corpórea (IMC) e Conteúdo Mineral Ósseo (CMO) do trocânter do fêmur (p<0,0001). O desempenho nas variáveis estudadas do GI é superior ao GC, mesmo nas mulheres fraturadas inseridas neste grupo. O protocolo utilizado foi seguro para as mulheres pós menopausadas / Normal aging is a continuous process that results in biological and psychosocial changes, unaffected by pathologies. These changes can lead to a loss in neuromuscular and skeletal order, impacting the locomotors system in the elderly. Osteoporosis is a systemic disease that progressively affects the skeleton structure where the fractures its main consequence, mainly in the spine. The gauged of these fractures can be assessed by vertebral morphometry, by using X-ray (MRX) or X-ray absorptiometry (MXA), which consider the vertebra morphology trough comparison between the heights of its contours in 6 different points. The women, especially postmenopausal, are more susceptible to fractures. The exercise prescription should not just add physical benefits, but also consider the predisposition to the rise of new injuries, such as fractures. The high-intensity exercise in the water can act as a safety feature for a population usually weakened by age. The goal of this research was the investigation if a mechanical overload caused by a program of high-intensity water exercise is safe for the spine morphology in postmenopausal women. A prospective and controlled study was made where 108 postmenopausal sedentary women were distributed in a fracture group (n = 20) and one without fracture (n = 88). The group was distributed in control (CG) (n = 44) composed by sedentary elderly and intervention (GI) (n = 64), formed by those who participated in the protocol for water exercises. All participants received oral supplementation with 500 mg calcium and 1000 IU of Vitamin D3 and were submitted to an initial assessment and 24 weeks after intervention of water exercises. Were evaluated anthropometric data, information on ethnicity, pain parameters, neuromuscular tests applied to variables and performing bone densitometry followed by morphometry to identify fractures. The findings showed that 18.51% of the women present fracture, predominantly located in the anterior thoracic spine. Were observed significant changes for strength, flexibility and a reduction of fall´s in a group with and without fracture (p <0.05). The presence of fractures was associated with age, body mass index (BMI) and bone mineral content (BMC) of the femoral trochanter (p <0.0001). The performance variables have best scores in GI than GC, even in fractured women included in this group. The protocol used was safe for postmenopausal women

A pilot clinical trial was conducted after the in-vivo and in-vitro studies: Eight subjects fulfilled the inclusion criteria were recruited. However, the liver function tests of three subjects out of eight were found to be abnormal with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level, which was not reported in previous toxicity test. The trial was suspended immediately and a follow-up test showed that the elevated AST and ALT level had reverted back to normal within one month after termination of OPR intake. Although we could not accomplish a RCT, the pilot study revealed potential hepatotoxicity of OPR on human beings and it would raise the safety awareness of investigators on the use of herbal remedies in future clinical studies. / After the in-vivo and in-vitro studies, a double-blinded, randomized, placebo-controlled clinical trial (RCT) was planned. Due to a lack of a Chinese version of instrument to measure osteoporosis-specific quality of life, an English version of the Osteoporosis-Targeted Quality of Life Questionnaire (OPTQoL) was translated into Chinese and linguistically validated according to the standard guideline. The newly formed Chinese OPTQoL can be used to assess the impact of new interventions on quality of life among Chinese osteoporosis patients. / Association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM was investigated with the aid of a Kidney-Vacuity Syndromes scoring questionnaire. In the study, postmenopausal women, who suffered from deficiency of kidney "qi" and kidney "essence", had a significantly higher incidence of osteoporosis. These findings strongly supported that replenishing kidney qi and kidney essence was a logical therapeutic principle in the formulation of OPR. / In conclusion, this study investigated the use of TCM on the treatment of postmenopausal osteoporosis in a systematic manner. It started from herbal formulation, basic science studies to clinical trial. It revealed beneficial effects of OPR on bones through in-vivo and in-vitro studies and demonstrated certain possible mechanism behind. On the other hand, the hepatotoxicity of OPR on human beings was also exposed and had not been reported in previous toxicity tests. The study provided valuable clinical data for other investigators on the potential hazards of herbal remedies although they had been validated as safe and effective in pre-clinical stage. / In search for safe, effective and low-priced medicine, the public have turned their attention to Traditional Chinese Medicine (TCM). Extensive experience has been accumulated in TCM regarding the diagnosis and treatment of osteoporosis, which often involves the prescription of kidney-tonifying herbs. Therefore, the aim of the study, firstly, was to explore the association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM, so as to formulate a rational kidney-tonifying herbal formula for osteoporosis research (OPR). Secondly, the effect of the formula was evaluated by in-vitro and in-vivo studies. Thirdly, the Osteoporosis-Targeted Quality of Life Questionnaire was linguistically validated from English to Chinese, which was expected to be one of the outcome measurement tools in future clinical trials. Lastly, a pilot clinical study was performed, which revealed some potential hazards of the formula on human beings which have not been shown in previous works. / Osteoporosis is a skeletal disorder which leads to an increased risk of bone fracture, disability or even death. It has become a major public health threat and the worldwide incidence of osteoporotic fracture is projected to increase two fold within the next 50 years. Postmenopausal women, being affected by a lack of estrogen, face a much higher risk of the disease. This study would therefore focus on type I osteoporosis (i.e. postmenopausal osteoporosis). Although current medications can slow down the bone deterioration process, their side effects and high cost had impaired patients' compliance with long term treatment. / The effect of OPR for the treatment of postmenopausal osteoporosis was then evaluated by in-vitro and in-vivo studies. In the in-vivo study, an osteoporosis model was established by performing ovariectomy on the four-week-old C57BL/6 mice. A high bone turnover rate was induced and OPR successfully slowed down the high turnover rate of bones by decreasing bone formation and resorption process without increasing the uterine linings. However, its beneficial effect on bones could not be detected on bone mineral density measurement. / The potential mechanism of action of OPR on bones was explored by in-vitro study. OPR was shown to induce cell proliferation and differentiation of osteoblast-like UMR 106 cells. Furthermore, the estrogenic activity of OPR was detected by MCF-7 cell line, which has been stably transfected with estrogen responsive elements (ERE). OPR was shown to possess an estrogenic activity in a dose dependent manner and was comparable to the positive control at a concentration of 200 and 1000 mug/ml. The induced estrogenic activity by OPR may be associated with the presence of phytoestrogen within the herbal formula. These findings suggested that the beneficial effect of OPR on bones might relate to its direct positive effect on osteoblast and its estrogenic-like activity. / Liong, Ching. / Adviser: Chun-tao Che. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves ). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

La relative immunité des femmes vis-à-vis du risque cardiovasculaire a longtemps été attribuée aux hormones sexuelles. Néanmoins, le rôle protecteur des estrogènes dans le développement de l’athérosclérose et de ses complications a été récemment remis en cause chez les femmes ménopausées. A partir de la cohorte française des Trois Cités incluant environ 10.000 sujets de plus de 65 ans, j’ai évalué l’association entre les estrogènes endogènes et le risque de maladies cardiovasculaires chez des femmes n’utilisant pas de traitement hormonal. J’ai montré pour la première fois que des taux élevés d’estradiol plasmatique étaient associés à une augmentation du risque artériel ischémique à 4 ans, indépendamment des facteurs de risque cardiovasculaire traditionnels, notamment l’obésité ou le diabète. Dans une deuxième partie, j’ai étudié le rôle modulateur des polymorphismes génétiques des récepteurs des estrogènes α (ESR1) et β (ESR2). J’ai montré que le risque cardiovasculaire augmentait avec les taux élevés d’estradiol chez les femmes porteuses du génotype rs9340799-AA mais pas chez celles avec le génotype rs9340799-AG/GG. Des analyses complémentaires m’ont également permis de suggérer que l’effet des estrogènes était lié en partie à une hypercoagulabilité et un état inflammatoire. Dans une dernière étape, j’ai évalué le rôle prédicteur à long terme des estrogènes endogènes. J’ai confirmé la relation indépendante entre les taux élevés d’estrogènes et la survenue d’un évènement cardiovasculaire après 10 ans de suivi. Globalement, ces résultats suggèrent un effet délétère des estrogènes dans le développement des maladies artérielles ischémiques chez les femmes ménopausées après 65 ans . Si ces résultats étaient confirmés, une meilleure stratification du risque artériel pourrait être proposée chez les femmes ménopausées avec des implications potentielles dans la prévention des maladies cardiovasculaires. / The low incidence of coronary heart disease among women has often been attributed to sex hormones. However, adverse effects of estrogens on arterial disease have been recently reported in older postmenopausal women. In the French Three-City prospective cohort study of subjects over 65 years of age, I investigated the association of endogenous estradiol with cardiovascular risk among postmenopausal women who did not use any hormone therapy. In a first part, I showed that high levels of plasma estradiol were related to the 4-year incidence of ischemic arterial disease (IAD), independently of traditional cardiovascular risk factors such as obesity or diabetes. Then, I reported that the relation between estrogens and IAD risk could be modulated by estrogen receptor-α (ESR1) polymorphisms. Indeed, endogenous estrogens were positively associated with IAD risk in women carrying the ESR1 rs9340799-AA genotype but not in those carrying the ESR1 rs9340799-AG/GG genotype. Further analyses revealed that both hypercoagulability and inflammatory state might act as mediators. Finally, I assessed the long-term predictor role of endogenous estrogens in arterial disease. I showed a positive and independent association of estrogens levels with the 10-year incidence of cardiovascular disease. Overall, high plasma levels of endogenous estradiol emerge as a new significant predictor of cardiovascular disease in older postmenopausal women. If confirmed, these findings could have the potential to improve the stratification of IAD risk in postmenopausal women.

A causa mais comum da osteoporose é o declínio do hormônio sexual feminino, o estrógeno, que ocorre após a menopausa. Esse hormônio regula a produção de citocinas que influenciam a proliferação dos osteoclastos, aumentando a reabsorção óssea. Os efeitos da cafeína no metabolismo ósseo são controversos e podem estar associados ao aumento significativo de doenças periodontais, fraturas, aumento do cálcio urinário e redução da densidade mineral óssea, por exercer efeitos inibidores sobre as funções dos osteoblastos. O principal objetivo deste estudo foi avaliar o efeito in vitro de diferentes concentrações de cafeína no metabolismo de células osteoblásticas da medula óssea de ratas osteoporóticas. Após aprovação pela Comissão de Ética no Uso de Animais, ratas Wistar foram divididas em dois grupos experimentais: controle (C) e submetidas à ovariectomia (OVX). Após 60 dias da cirurgia, as ratas foram sacrificadas para coleta dos fêmures e das células mesenquimais da medula óssea, que foram induzidas à diferenciação em osteoblastos com meio osteogênico com três concentrações de cafeína (1, 3 e 5 mM - grupos OVX1, OVX3 e OVX5) e cultivadas em placas de 24 poços (n = 5) para avaliação da proliferação celular, atividade de fosfatase alcalina (ALP) bioquímica e in situ, detecção e quantificação de nódulos mineralizados e análise da expressão de genes relacionados à atividade osteoblástica através de PCR em tempo real. Os ensaios foram realizados em triplicata e analisados por meio do software estatístico GraphPad Prism, com nível de significância fixado em 5%. A proliferação celular foi menor nos grupos osteoporóticos com adição de cafeína, tendo a menor queda o grupo com adição de 1mM. O método bioquímico de ALP não foi significante nos períodos analisados, entretanto, aos 10 e 14 dias, a atividade aumentou quando a concentração de cafeína era maior. Já na atividade de ALP in situ, o grupo OVX1 foi o que apresentou melhor resultado nos períodos avaliados (p < 0,05), com pico aos 14 dias. A quantificação de matriz mineralizada foi maior no grupo OVX comparado ao grupo C; entre as concentrações, a maior quantificação dos nódulos de cálcio se deu no grupo com 1mM de cafeína. Os resultados obtidos no PCR mostraram que o gene para fosfatase alcalina teve maior expressão no grupo OVX, seguido do grupo OVX1 aos 7 e 10 dias; a expressão gênica de osteocalcina foi maior para o grupo OVX1 aos 10 e 14 dias e esse grupo apresentou a maior expressão em todos os períodos para os genes Runx2 e RankL. No caso do Bmp4, o grupo OVX3 foi o mais expresso aos 10 e 14 dias. Os genes osteoprotegerina e osteopontina variaram sua expressão de acordo com o período e grupo avaliado. A expressão de osterix foi similar entre os grupos aos 7 e 10 dias, enquanto a expressão de Bsp, aos 7 e 14 dias, mostrou semelhança entre os grupos controle e OVX1. Frente aos resultados obtidos, sugere-se que a concentração de 1mM de cafeína pareceu ser a menos prejudicial ao metabolismo das células osteoblásticas neste modelo experimental de osteoporose. / The most common cause of osteoporosis is the decrease of estrogen after menopause. This hormone regulates the production of cytokines that influence osteoclast proliferation, increasing bone resorption. The effects of caffeine in bone metabolism are controversial and may be associated to periodontal disease, bone fractures, increase of urinary calcium levels and reduction of mineral bone density due to inhibition of osteoblast activities. Thus, the goal of this investigation was to evaluate the in vitro effect of different caffeine concentrations in the metabolism of bone marrow osteoblastic cells from osteoporotic rats (OVX). After Ethical Committee approval, wistar female rats were divided in two experimental groups: control (C) and submitted to ovariectomy (OVX). After 60 days of surgery, femurs were removed to isolate bone marrow mesenchymal cells, which were induced to osteoblastic differentiation in osteogenic medium along with three different concentrations of caffeine (1, 3 and 5 mM - OVX1, OVX3 e OVX5 respectively) and posteriorly seeded in 24-well plates (n = 5) to evaluate cell proliferation, alkaline phosphatase activity and its in situ detection, detection and quantification of mineralized nodules as well as assess quantitative expression of genes associated to osteoblastic activity by means of real time PCR. All the experiments were performed in triplicate and analyzed by means of the statistical software GraphPad Prism for p<0.05. Cell proliferation was diminished in the all osteoporotic groups that received caffeine, with group OVX1 being the less affected. Biochemical assay of ALP activity did not show differences among the groups in the periods analyzed; nevertheless there was a tendency to a higher activity proportional to the higher concentration of caffeine. The in situ detection of ALP showed better results in group OVX1 after 14 days of culture. Mineralized matrix quantification was higher in OVX groups when compared to control group; among the concentrations, the higher quantification of calcium nodules was in group OVX1. The results obtained with PCR showed that the gene for ALP had its highest expression in OVX group, followed by OVX1 at 7 and 10 days; expression of osteocalcin was higher in OVX1 after 10 and 14 days and this same group presented higher expression in all periods for genes Runx2 e Rankl. Analysis of Bmp4 gene showed that it was expressed in group OVX3 after 10 and 14 days. The genes that code for osteoprotegerin and osteopontin had different expression values in accordance to the period and group evaluated. The expression of osterix was similar between the groups after 7 and 10 days, whereas the expression of Bsp was similar between control and OVX1 groups after 7 and 14 days. The results suggest that the concentration of 1mM of caffeine is the most beneficial to the metabolism of osteoblastic cells in a model of osteoporosis.

O envelhecimento normal é um processo contínuo, que desencadeia alterações psicossociais e biológicas, não afetadas por patologias. Estas mudanças podem desencadear perdas de ordem neuromuscular e óssea, influenciando o aparelho locomotor dos idosos. A osteoporose é uma doença que afeta sistêmica e progressivamente o esqueleto sendo as fraturas sua principal consequência, especialmente na coluna vertebral. A identificação destas fraturas pode ser realizada através da morfometria vertebral, analisadas através de raios-X (MRX) ou absorciometria de raios-X (MXA), que consideram morfologia da vértebra através da comparação da altura de seus contornos em 6 pontos diferentes. As mulheres, sobretudo na pós-menopausa, estão mais susceptíveis a fraturas. A prescrição de exercício, não deve somente agregar benefícios físicos, mas também deve considerar a predisposição ao surgimento de novos agravos, como as fraturas. Os exercícios de alta intensidade na água podem funcionar como um recurso seguro para uma população normalmente fragilizada pela idade. Assim, o objetivo da pesquisa foi verificar se a sobrecarga mecânica causada por um programa de exercícios aquáticos de alta intensidade é segura para a morfologia da coluna vertebral de mulheres na pós-menopausa. Trata-se de um estudo prospectivo e controlado onde foram analisadas 108 mulheres sedentárias na pós-menopausa, distribuídas em um grupo com fratura (n=20) e outro sem fratura (n=88). O grupo foi classificado em controle (GC) (n = 44) composto por idosas sedentárias e intervenção (GI) (n = 64), formado por aquelas que participaram do protocolo de hidroginástica. Todas as participantes receberam suplementação oral com 500 mg de cálcio e 1000 UI de Vitamina D3 e foram submetidas a uma avaliação inicial e após 24 semanas de intervenção com um programa de hidroginástica. Foram avaliados os dados antropométricos, informações sobre parâmetros de dor, testes aplicados para variáveis neuromusculares e realização de densitometria óssea seguida de morfometria para identificação de fraturas. Os achados apontaram que 18,51% das mulheres presentaram fraturas, predominantemente localizadas na coluna torácica a região anterior da vértebra. Observou-se mudanças significativas para força, flexibilidade e dimuição do número de quedas nos grupos com e sem fratura (p<0,05). A presença de fraturas esteve associada à idade, Índice de Massa Corpórea (IMC) e Conteúdo Mineral Ósseo (CMO) do trocânter do fêmur (p<0,0001). O desempenho nas variáveis estudadas do GI é superior ao GC, mesmo nas mulheres fraturadas inseridas neste grupo. O protocolo utilizado foi seguro para as mulheres pós menopausadas / Normal aging is a continuous process that results in biological and psychosocial changes, unaffected by pathologies. These changes can lead to a loss in neuromuscular and skeletal order, impacting the locomotors system in the elderly. Osteoporosis is a systemic disease that progressively affects the skeleton structure where the fractures its main consequence, mainly in the spine. The gauged of these fractures can be assessed by vertebral morphometry, by using X-ray (MRX) or X-ray absorptiometry (MXA), which consider the vertebra morphology trough comparison between the heights of its contours in 6 different points. The women, especially postmenopausal, are more susceptible to fractures. The exercise prescription should not just add physical benefits, but also consider the predisposition to the rise of new injuries, such as fractures. The high-intensity exercise in the water can act as a safety feature for a population usually weakened by age. The goal of this research was the investigation if a mechanical overload caused by a program of high-intensity water exercise is safe for the spine morphology in postmenopausal women. A prospective and controlled study was made where 108 postmenopausal sedentary women were distributed in a fracture group (n = 20) and one without fracture (n = 88). The group was distributed in control (CG) (n = 44) composed by sedentary elderly and intervention (GI) (n = 64), formed by those who participated in the protocol for water exercises. All participants received oral supplementation with 500 mg calcium and 1000 IU of Vitamin D3 and were submitted to an initial assessment and 24 weeks after intervention of water exercises. Were evaluated anthropometric data, information on ethnicity, pain parameters, neuromuscular tests applied to variables and performing bone densitometry followed by morphometry to identify fractures. The findings showed that 18.51% of the women present fracture, predominantly located in the anterior thoracic spine. Were observed significant changes for strength, flexibility and a reduction of fall´s in a group with and without fracture (p <0.05). The presence of fractures was associated with age, body mass index (BMI) and bone mineral content (BMC) of the femoral trochanter (p <0.0001). The performance variables have best scores in GI than GC, even in fractured women included in this group. The protocol used was safe for postmenopausal women

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

Osteoporosis is a serious disease which often brings pain, disability, hospitalization, and even death. An increasing number of studies have been conducted on the prevention and treatment of osteoporosis in White women, yet a paucity of research exists to explain disparities in screening and treatment of osteoporosis in Black women. This narrative study describes the perspectives of Black women regarding individual barriers to osteoporosis screening. The purpose of this study was to better understand the perspectives of Black women regarding prevention of and screening for osteoporosis. Selections included purposive, criterion sampling of 10 Black women who were 50 years and older, could speak and write English, and lived in Southeastern Virginia. Recruitment flyers were distributed to Black women who were members of 3 local churches. The conceptual framework for this study was the behavioral model of health services, which holds that individual's acceptance to use health service is partly controlled by that individual's predisposing, enablement, and need. Data were collected by in-depth face-to-face interviews and analyzed using open, axial, and selective coding. Four major themes emerged in this study including awareness of osteoporosis, knowledge of the screening, health beliefs, and sharing of information. While the narratives indicated positive effects from engaging in osteoporosis screening, there was a discrepancy in understanding the disease and explanations of screening results. This study addresses social change by identifying how awareness and knowledge may help Black women become more effective when they engage in osteoporosis screening, which can help to ensure health and a better quality of life.

The overall aim of this thesis was to elucidate and investigate psychophysiological aspects and effects of acupuncture and needle stimulation. Within this framework emphasis was directed toward the effects of needle stimulation (acupuncture) on muscle blood flow in the tibialis anterior and trapezius muscles in healthy subjects and patients suffering from chronic muscle pain. This study also included evaluation of a new application of photoplethysmography in noninvasive monitoring of muscle blood flow. The evaluation was based on experiments known to provocate skin or muscle blood flow. The psychological aspects studied comprised the effects of manual acupuncture on pain in fibromyalgia patients and the effects of electro-acupuncture on psychological distress and vasomotor symptoms in postmenopausal women in the clinical context. The results showed that photoplethysmography have potential to noninvasively monitor muscle blood flow and to discriminate between blood flow in skin and muscle, although some considerations still have to be accounted for. It was further shown that muscle blood flow change in response to needle stimulation differed between healthy subjects and patients. Deep needle stimulation in the muscle of healthy subjects consistently increased muscle blood flow more than subcutaneous needle stimulation. In the painful trapezius muscle of FMS patients, however, subcutaneous needling was equal or even more effective in increasing muscle blood flow than deep intramuscular stimulation. Generally, needle stimuli had weak effect on blood flow in the trapezius muscle of the severely affected trapezius myalgia patients, possibly depending on older age and lesser number of patients included in the study. The different patterns of blood flow response to needle stimulation between healthy subjects and patients with chronic muscle pain might be a manifestation of altered somatosensory processing in the patients. The clinical studies showed that best pain relief of acupuncture in FMS patients was achieved in the neck-shoulder region, while the effect on the generalised symptoms was of short duration. Well-being and sleep was found to best predict treatment outcome. The results suggest that acupuncture treatment may be used for the alleviation of neck-shoulder pain, primarily, but it is not an alternative as the sole treatment. Electro-acupuncture, significantly decreased psychological distress and climacteric symptoms in postmenopausal women, but not better than a (near-) placebo control, implying pronounced non-specific effects. / Akupunktur ingår som en del i traditionell kinesisk medicin (TCM) och har använts i över 2000 år för att lindra sjukdom och symptom. I Sverige blev akupunktur godkänd som smärtlindringsmetod inom Hälso- och Sjukvården 1984. Sedan nästan 10 år är akupunktur jämställd med övrig behandling i sjukvården vilket innebär, att akupunktur kan användas även för behandling av annat än smärta. Förutsättningen är emellertid, att det finns tillräckligt med vetenskapliga belägg, s.k. evidens, för detta. I de allra flesta fall saknas det idag. För att säkerställa att evidens föreligger krävs omfattande forskning om effekter av akupunktur. Syftet med de olika studierna i avhandlingen var att belysa och studera psykologiska och fysiologiska aspekter och effekter av akupunktur och nålstimulering. Effekt på blodflöde i hud och muskel undersöktes på friska personer och på patienter med kronisk muskelsmärta. Normalt krävs ett mindre kirurgiskt ingrepp för att mäta blodflöde i muskel, men i dessa studier användes en mätmetod, som enkelt och utan ingrepp (icke-invasivt) i normala fall används för att mäta blodflöde i huden, s.k. fotopletysmografi (PPG, eng.). Med hjälp av ny teknik användes PPG i dessa studier för att mäta även muskelblodflöde. En studie för utvärdering av den nya PPG-tekniken ingick också i avhandlingen. Utvärderingen av mätmetoden visade goda möjligheter att mäta muskelblodflöde icke-invasivt med hjälp av PPG. Hos friska personer blev effekten på blodflödet störst vid djup stimulering i muskeln och där den s.k. DeQi-känslan framkallades (som vid klassisk akupunktur). Hos patienter med fibromyalgi var nålstimulering i huden lika, eller t.o.m. mer, effektiv att öka muskelblodflödet i skuldran än den djupa nålstimuleringen. De olika mönstren av blodflödesökning mellan de friska personerna och patienterna kan bero på ett förändrat reaktionssätt i nervsystemet som svar på smärtsam stimulering. I två kliniska studier studerades den smärtlindrande effekten av manuell akupunktur vid fibromyalgi och effekten av elektroakupunktur på stress och klimakteriebesvär hos kvinnor i övergångsåldern. Akupunktur vid fibromyalgi visade sig ha bäst smärtlindrande effekt i nack-skulderområdet, medan effekten på de generella symptomen var kortvarig. Patienter som mådde och sov relativt bra erhöll bäst effekt. Efter en behandlingsserie, bestående av elektroakupunktur, minskade stress och klimakteriebesvär påtagligt hos kvinnorna i övergångsåldern, men inte mer än hos en grupp kvinnor, som fick en kontrollbehandling bestående av mycket ytligt placerade nålar i huden. Detta tyder på att en betydlig del av behandlingsresultatet utgjordes av ospecifika effekter eller, s.k. eller placeboeffekter.

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

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