This study has aimed to evaluate how osteoporosis affects the quality of life in postmenopausal women and to assess the influence of physical exercise on markers for quality of life in osteoporosis patients. The EQ-5D questionnaire was applied for evaluation of the markers: Mobility, Self-care, Usual Activities, Pain/Discomfort and Anxiety/Depression. In collaboration with the University of Bologna, a 6-month exercise trial of women aged 60-75 with osteoporotic vertebral fractures was analyzed. These osteoporosis patients were divided into two groups; an exercise group and a control group. Markers linked to quality of life were compared for the women with osteoporosis with those of an average female Italian population of similar age. Markers for quality of life, specifically: Mobility, Usual Activities, Pain/Discomfort and Anxiety/Depression were significantly lower in the Italian osteoporosis patients than in the average population. Exercise slightly improved Mobility and Usual Activities for the osteoporosis patients, but the results did not reach statistical significance.

<p> This thesis focuses on an examination of cortical and trabecular bone density and geometry at the radius and tibia in postmenopausal women, primarily women with history of breast carcinoma, while also assessing musculoskeletal changes in postmenopausal breast cancer patients after treatment with the Aromatase Inhibitor, Anastrozole. The first sub-study is an investigation of the reproducibility of the pQCT measurement parameters at the radius and tibia in healthy pre-and postmenopausal women. Results indicated that the reproducibility was good at the radius and even better at the tibia for all parameters measured. The second study is an appraisal of the level of osteoporosis knowledge in a cohort of postmenopausal women. The participants were assessed via the Facts on Osteoporosis Quiz, a well validated questionnaire, and the data revealed significantly lower test scores among the breast cancer subjects in comparison with healthy postmenopausal women. In the remaining group of studies, pQCT technology was utilized to describe trabecular and cortical bone at the radius and tibia in postmenopausal women and women with a history of breast carcinoma whom had been prescribed Anastrozole. The following measurement sites were significantly lower in the breast cancer subjects: TOT_DEN and TOT_CNT at the 4% radius; CRT_DEN, TOT_CNT, and CRT_CNT at the 20% radius; TOT_DEN at the 4% tibia; and CRT_DEN at the 38% tibia. With respect to time on Anastrozole, TOT_CNT at the 4% radius (r=-0.36); TOT_CNT (r=-0.33), CRT_CNT (r=-0.34) and CRT_DEN (r=-0.44) at the 20% radius; and CRT_DEN (r=-0.39) and CRT_CNT (r=-0.27) at the 38% tibia were significantly negatively correlated with days on Anastrozole. Furthermore, after two years of Anastrozole treatment in a small cohort of breast cancer subjects, there was a significant decrease in CRT_DEN (p=0.025) at the 20% diaphyseal radius and also at the 38% diaphyseal tibia (p=0.051). Together, the sub-studies that comprise this thesis demonstrate that there are noteworthy deficiencies in osteoporosis knowledge among postmenopausal women, particularly those with a history of breast carcinoma, and yet, these are the same women that have an increased need to understand the preventative and treatment options regarding this disease as they demonstrate reduced bone density at all measurement sites. It also appears that time on Anastrozole primarily affects cortical bone density in these women. In summary, this thesis provides novel details regarding cortical bone in breast cancer subjects and emphasizes the need for a normative database of bone quality parameters at different skeletal sites in order to gain a better understanding of the utility of each skeletal site with regard to fracture risk prediction. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

Motivation - The burden of cardiovascular diseases (CVD) is increasing in developing countries worldwide, but even more so in sub-Saharan Africa. Due to rapid urbanisation, black populations experience lifestyle changes (e.g. unhealthy diet, increased access to alcohol and tobacco) that predispose them to increased obesity and cardiovascular risk. In this study, attention will be given to cardiovascular alterations, specifically arterial calcification, in lean and overweight/obese women nearing or already experiencing menopause. These include elevated blood pressure, large artery stiffness (indicated by increased central pulse pressure (cPP)) and carotid intima-media thickness (CIMT). Other factors linked to arterial calcification include the level of obesity as well as low bone mineral density. Ectopic calcification plays a significant role in cardiovascular morbidity and mortality, especially in renal failure patients, osteoporotic and elderly women. Factors contributing to the development and progression of arterial calcification include calciotropic hormones and altered bone metabolism, particularly in older postmenopausal women. This is due to the lack of protective effects of oestrogen against vascular alterations and bone loss after menopause. Previous studies have shown that increased bone resorption indicated by elevated levels of c-telopeptide of type I collagen (CTX), parathyroid hormone (PTH), low 25- hydroxycholecalciferol (25(OH)D3) and parathyroid hormone to 25-hydroxycholecalciferol ratio (PTH:25(OH)D3) are independently linked to arterial stiffening, CIMT and vascular calcification. Knowledge on the contribution of altered bone metabolism and associated calciotropic hormones on cardiovascular health in Africans is limited. Previous studies on ectopic calcification in South Africans focused on men and renal failure patients. This study will explore the possible role of altered calcium regulation and bone metabolism in the development of arterial calcification and CVD in older African women. Aim - The aim of this study was to investigate the associations of brachial and central pressures and CIMT with PTH, PTH:25(OH)D3 and CTX, a marker of bone resorption, in lean and overweight/obese African women older than 46 years. Methodology - This sub-study forms part of the Prospective Urban Rural Epidemiology (PURE) study. A total of 434 urban and rural women older than 46 years were included in the study. Women infected with the human immunodeficiency virus (HIV) were excluded from the study. The study was reviewed and approved by the Ethics Committee of the North-West University (Potchefstroom campus) and all participants signed an informed consent form prior to enrolment into the project. Field workers administered demographic, general health and physical activity questionnaires in the participants’ home language. Anthropometric measurements included weight, height and waist circumference, while body mass index (BMI) was calculated in kg/m2. Cardiovascular measurements included brachial and central systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), brachial and central pulse pressure (PP) as well as CIMT and carotid cross-sectional wall area (CSWA). Blood pressure measurements were performed on the right arm with the participant in the sitting position. Blood was drawn after an overnight fasting period. We performed biochemical analyses from serum and plasma samples for follicle stimulating hormone (FSH), PTH, 25(OH)D3, and CTX. HIV testing was performed according to standardised procedures. Since interactions existed for BMI with regards to associations of CIMT and cPP with PTH:25(OH)D3, the study population was divided into the lean (BMI <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) groups. We performed independent T-tests to compare means and used the chi-square test to compare proportions. Single and multiple regression analyses were performed to investigate the associations of markers of vascular structure and function with CTX and calciotropic hormones. Results - In this study, 90% of the women displayed an FSH concentration exceeding the cut-off value of 35 mIu/mL, indicating a postmenopausal state. When comparing lean and overweight/obese African women, we found that lean women had higher levels of CTX and 25(OH)D3 (both p<0.001), while the overweight/obese group was older (p=0.007) and presented with higher PTH and PTH:25(OH)D3 levels (both p<0.001). Brachial and central pressures did not differ between the groups (p≥0.23), except for DBP being higher in the overweight/obese group (p=0.017). Overweight/obese women had higher CIMT (p<0.001) and CSWA (p=0.001) as compared to their lean counterparts. A larger proportion of lean women smoked (63%) and self-reported on alcohol use (37%) than overweight/obese women (41% and 18%, respectively) (both p<0.001). Forty-one percent of overweight/obese women used antihypertensive medication, opposed to 25% in the lean group (p=0.001). In multivariate regression analyses, an independent positive association existed between CIMT and PTH:25(OH)D3 (R2=0.22; β=0.26; p=0.003) in lean women. In the overweight/obese group independent positive associations were confirmed between brachial SBP and PTH (p=0.013) and CTX (p=0.038), and between DBP and PTH (p=0.030). Brachial PP and central SBP remained positively associated with CTX (p=0.016 and p=0.024, respectively), while cPP was independently associated with PTH:25(OH)D3 (R2=0.20; β=0.17; p=0.017) and CTX (R2=0.20; β=0.17; p=0.025). Conclusion - Our results indicate that in older African women, large artery structure and function are associated with calciotropic hormones and bone resorption, suggesting that altered bone metabolism and associated calciotropic hormones play a role in the development of vascular calcification. The different associations in lean and overweight/obese women suggest different mechanisms at work regarding arterial calcification in states of low and high adiposity. These findings need confirmation in larger prospective and experimental studies. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

Motivation - The burden of cardiovascular diseases (CVD) is increasing in developing countries worldwide, but even more so in sub-Saharan Africa. Due to rapid urbanisation, black populations experience lifestyle changes (e.g. unhealthy diet, increased access to alcohol and tobacco) that predispose them to increased obesity and cardiovascular risk. In this study, attention will be given to cardiovascular alterations, specifically arterial calcification, in lean and overweight/obese women nearing or already experiencing menopause. These include elevated blood pressure, large artery stiffness (indicated by increased central pulse pressure (cPP)) and carotid intima-media thickness (CIMT). Other factors linked to arterial calcification include the level of obesity as well as low bone mineral density. Ectopic calcification plays a significant role in cardiovascular morbidity and mortality, especially in renal failure patients, osteoporotic and elderly women. Factors contributing to the development and progression of arterial calcification include calciotropic hormones and altered bone metabolism, particularly in older postmenopausal women. This is due to the lack of protective effects of oestrogen against vascular alterations and bone loss after menopause. Previous studies have shown that increased bone resorption indicated by elevated levels of c-telopeptide of type I collagen (CTX), parathyroid hormone (PTH), low 25- hydroxycholecalciferol (25(OH)D3) and parathyroid hormone to 25-hydroxycholecalciferol ratio (PTH:25(OH)D3) are independently linked to arterial stiffening, CIMT and vascular calcification. Knowledge on the contribution of altered bone metabolism and associated calciotropic hormones on cardiovascular health in Africans is limited. Previous studies on ectopic calcification in South Africans focused on men and renal failure patients. This study will explore the possible role of altered calcium regulation and bone metabolism in the development of arterial calcification and CVD in older African women. Aim - The aim of this study was to investigate the associations of brachial and central pressures and CIMT with PTH, PTH:25(OH)D3 and CTX, a marker of bone resorption, in lean and overweight/obese African women older than 46 years. Methodology - This sub-study forms part of the Prospective Urban Rural Epidemiology (PURE) study. A total of 434 urban and rural women older than 46 years were included in the study. Women infected with the human immunodeficiency virus (HIV) were excluded from the study. The study was reviewed and approved by the Ethics Committee of the North-West University (Potchefstroom campus) and all participants signed an informed consent form prior to enrolment into the project. Field workers administered demographic, general health and physical activity questionnaires in the participants’ home language. Anthropometric measurements included weight, height and waist circumference, while body mass index (BMI) was calculated in kg/m2. Cardiovascular measurements included brachial and central systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), brachial and central pulse pressure (PP) as well as CIMT and carotid cross-sectional wall area (CSWA). Blood pressure measurements were performed on the right arm with the participant in the sitting position. Blood was drawn after an overnight fasting period. We performed biochemical analyses from serum and plasma samples for follicle stimulating hormone (FSH), PTH, 25(OH)D3, and CTX. HIV testing was performed according to standardised procedures. Since interactions existed for BMI with regards to associations of CIMT and cPP with PTH:25(OH)D3, the study population was divided into the lean (BMI <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) groups. We performed independent T-tests to compare means and used the chi-square test to compare proportions. Single and multiple regression analyses were performed to investigate the associations of markers of vascular structure and function with CTX and calciotropic hormones. Results - In this study, 90% of the women displayed an FSH concentration exceeding the cut-off value of 35 mIu/mL, indicating a postmenopausal state. When comparing lean and overweight/obese African women, we found that lean women had higher levels of CTX and 25(OH)D3 (both p<0.001), while the overweight/obese group was older (p=0.007) and presented with higher PTH and PTH:25(OH)D3 levels (both p<0.001). Brachial and central pressures did not differ between the groups (p≥0.23), except for DBP being higher in the overweight/obese group (p=0.017). Overweight/obese women had higher CIMT (p<0.001) and CSWA (p=0.001) as compared to their lean counterparts. A larger proportion of lean women smoked (63%) and self-reported on alcohol use (37%) than overweight/obese women (41% and 18%, respectively) (both p<0.001). Forty-one percent of overweight/obese women used antihypertensive medication, opposed to 25% in the lean group (p=0.001). In multivariate regression analyses, an independent positive association existed between CIMT and PTH:25(OH)D3 (R2=0.22; β=0.26; p=0.003) in lean women. In the overweight/obese group independent positive associations were confirmed between brachial SBP and PTH (p=0.013) and CTX (p=0.038), and between DBP and PTH (p=0.030). Brachial PP and central SBP remained positively associated with CTX (p=0.016 and p=0.024, respectively), while cPP was independently associated with PTH:25(OH)D3 (R2=0.20; β=0.17; p=0.017) and CTX (R2=0.20; β=0.17; p=0.025). Conclusion - Our results indicate that in older African women, large artery structure and function are associated with calciotropic hormones and bone resorption, suggesting that altered bone metabolism and associated calciotropic hormones play a role in the development of vascular calcification. The different associations in lean and overweight/obese women suggest different mechanisms at work regarding arterial calcification in states of low and high adiposity. These findings need confirmation in larger prospective and experimental studies. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

Le risque cardiométabolique (RCM) représente l’ensemble de tous les facteurs de risque pour les maladies cardiovasculaires et le diabète de type 2, incluant les facteurs de risque traditionnels et ceux émergents. Les évidences indiquent que la résistance à l’insuline, l’inflammation et le stress oxydant jouent un rôle clé dans le RCM, bien que l’acteur initiateur des altérations métaboliques caractéristiques du RCM reste encore à définir. Les femmes post-ménopausées constituent un sous-groupe important de la population puisque le risque de complications cardiométaboliques augmente après la ménopause. Les facteurs de RCM peuvent être modulés par l’alimentation, l’activité physique et la perte de poids. Alors que l’étude de nutriments / aliments spécifiques a permis de mieux comprendre l’implication de l’alimentation dans le RCM, celle de la qualité de l’alimentation est prometteuse. L’activité physique a des effets bénéfiques sur le RCM bien démontrés chez des personnes actives. Cependant, la relation entre la dépense énergétique et le RCM chez des individus sédentaires a été moins investiguée. De même, peu ou pas de données existent quant à une interaction synergique possible entre l’alimentation et l’activité physique sur le RCM. L’objectif de la présente thèse est d’investiguer les relations entre l’alimentation, l’activité physique, le stress oxydant et le RCM chez des femmes post-ménopausées en surpoids ou obèses, sédentaires et sans autres complications métaboliques. Les résultats montrent que d’une part, chez ces femmes sédentaires, une dépense énergétique active (DÉAP) élevée est associée à un meilleur profil inflammatoire, indépendamment de l’adiposité. D’autre part, il existe une relation synergique entre la qualité alimentaire et la DÉAP associée à un meilleur RCM. Une qualité alimentaire élevée combinée à une DÉAP élevée est associée à un meilleur profil lipidique et lipoprotéique et à une inflammation sub-clinique moindre, indépendamment de l’adiposité. Par ailleurs, dans une étude pilote, seuls des effets indépendants des changements de la qualité alimentaire et de la DÉAP sur les changements dans les facteurs de RCM ont été observés suite à cette diète hypocalorique de 6 mois, indépendamment du changement de l’adiposité encouru. En effet, au-delà de la réduction de l’adiposité et de l’amélioration du profil lipoprotéique induites par l’intervention, l’amélioration de la qualité alimentaire et de la DÉAP est associée, indépendamment l’une de l’autre, à une meilleure pression artérielle et un meilleur profil lipidique. Par ailleurs, une modification du système glutathion, un des systèmes antioxydants les plus communs de l’organisme, est associée à un RCM élevé. Une activité élevée de la glutathion peroxydase est associée à une résistance à l’insuline et à une épaisseur plus importante de l’intima-media de la carotide. Ces relations pourraient être médiées par un stress réducteur. En conclusion, l’adoption d’une saine alimentation et la pratique d’activités physiques doivent être encouragées dans les interventions visant à contrer l’obésité et ses complications, même en absence d’un changement d’adiposité. D’autre part, l’activité de la glutathion peroxydase pourrait être un paramètre impliqué dans le développement de désordres cardiométaboliques sub-cliniques et asymptomatiques chez des femmes obèses. D’autres investigations sont requises pour confirmer ces observations et élucider les mécanismes d’action impliqués. / The cardiometabolic risk represents all risk factors for cardiovascular diseases and type 2 diabetes, including the traditional and the emerging risk factors. Accumulating evidences indicate that insulin resistance, inflammation and oxidative stress are key players in the cardiometabolic risk, although the main cause initiating the metabolic alterations associated with the cardiometabolic risk has to be identified. Postmenopausal women are an important sub-group of the general population because the risk of developing cardiometabolic complications increases after menopause. The cardiometabolic risk factors can be modulated by dietary intake, physical activity and weight loss. Despite the fact that the study of specific nutrients or foods provided a better understanding of the implication of nutrition in the cardiometabolic risk, the relationship between diet quality and cardiometabolic risk has been less studied. Beneficial effects of physical activity on the cardiometabolic risk have been demonstrated in physically active individuals. However, the relationship between energy expenditure and the cardiometabolic risk in sedentary individuals has been less investigated. Similarly, it is unknown whether dietary intake interacts with physical activity in order to have greater beneficial effects on the cardiometabolic risk. The objective of this thesis is to determine the relationships between diet quality, physical activity and oxidative stress on the cardiometabolic risk in sedentary postmenopausal overweight and obese women without cardiometabolic complications. The results showed that, in these sedentary women, physical activity energy expenditure is associated with reduced inflammation, independently of adiposity. Moreover, there is a synergistic relationship between quality and physical activity energy expenditure (PAEE) which is associated with a reduced cardiometabolic risk compared to their separate effects. Indeed, high diet quality combined to high PAEE levels is associated with a better lipid and lipoprotein profile and a lower inflammatory status, independently of adiposity. However, in a pilot study, only independent effects of changes in diet quality and PAEE on the changes in cardiometabolic risk factors was observed following a 6-month hypocaloric diet. Indeed, beyond the reduction of adiposity and improvement of the lipoprotein profile induced by this diet, improved diet quality and increased PAEE are associated with beneficial changes in blood pressure and lipid profile. On the other hand, modification in the glutathione system, which is one of the most common antioxidant systems in the body, is associated with a higher cardiometabolic risk. Greater glutathione peroxidase activity is associated with insulin resistance and greater intima-media thickness of blood vessels. These relationships may be mediated through a reductive stress. In conclusion, a healthy diet and physical activity should be emphasized in interventions aimed to reduce obesity and its related complications, even in absence of change in adiposity. Moreover, glutathione peroxidase activity may be a parameter contributing to the development of sub-clinical but clinically relevant asymptomatic cardiometabolic abnormalities in obese women. Further investigations are needed to confirm these results and to elucidate the underlying mechanisms.

Le risque cardiométabolique (RCM) représente l’ensemble de tous les facteurs de risque pour les maladies cardiovasculaires et le diabète de type 2, incluant les facteurs de risque traditionnels et ceux émergents. Les évidences indiquent que la résistance à l’insuline, l’inflammation et le stress oxydant jouent un rôle clé dans le RCM, bien que l’acteur initiateur des altérations métaboliques caractéristiques du RCM reste encore à définir. Les femmes post-ménopausées constituent un sous-groupe important de la population puisque le risque de complications cardiométaboliques augmente après la ménopause. Les facteurs de RCM peuvent être modulés par l’alimentation, l’activité physique et la perte de poids. Alors que l’étude de nutriments / aliments spécifiques a permis de mieux comprendre l’implication de l’alimentation dans le RCM, celle de la qualité de l’alimentation est prometteuse. L’activité physique a des effets bénéfiques sur le RCM bien démontrés chez des personnes actives. Cependant, la relation entre la dépense énergétique et le RCM chez des individus sédentaires a été moins investiguée. De même, peu ou pas de données existent quant à une interaction synergique possible entre l’alimentation et l’activité physique sur le RCM. L’objectif de la présente thèse est d’investiguer les relations entre l’alimentation, l’activité physique, le stress oxydant et le RCM chez des femmes post-ménopausées en surpoids ou obèses, sédentaires et sans autres complications métaboliques. Les résultats montrent que d’une part, chez ces femmes sédentaires, une dépense énergétique active (DÉAP) élevée est associée à un meilleur profil inflammatoire, indépendamment de l’adiposité. D’autre part, il existe une relation synergique entre la qualité alimentaire et la DÉAP associée à un meilleur RCM. Une qualité alimentaire élevée combinée à une DÉAP élevée est associée à un meilleur profil lipidique et lipoprotéique et à une inflammation sub-clinique moindre, indépendamment de l’adiposité. Par ailleurs, dans une étude pilote, seuls des effets indépendants des changements de la qualité alimentaire et de la DÉAP sur les changements dans les facteurs de RCM ont été observés suite à cette diète hypocalorique de 6 mois, indépendamment du changement de l’adiposité encouru. En effet, au-delà de la réduction de l’adiposité et de l’amélioration du profil lipoprotéique induites par l’intervention, l’amélioration de la qualité alimentaire et de la DÉAP est associée, indépendamment l’une de l’autre, à une meilleure pression artérielle et un meilleur profil lipidique. Par ailleurs, une modification du système glutathion, un des systèmes antioxydants les plus communs de l’organisme, est associée à un RCM élevé. Une activité élevée de la glutathion peroxydase est associée à une résistance à l’insuline et à une épaisseur plus importante de l’intima-media de la carotide. Ces relations pourraient être médiées par un stress réducteur. En conclusion, l’adoption d’une saine alimentation et la pratique d’activités physiques doivent être encouragées dans les interventions visant à contrer l’obésité et ses complications, même en absence d’un changement d’adiposité. D’autre part, l’activité de la glutathion peroxydase pourrait être un paramètre impliqué dans le développement de désordres cardiométaboliques sub-cliniques et asymptomatiques chez des femmes obèses. D’autres investigations sont requises pour confirmer ces observations et élucider les mécanismes d’action impliqués. / The cardiometabolic risk represents all risk factors for cardiovascular diseases and type 2 diabetes, including the traditional and the emerging risk factors. Accumulating evidences indicate that insulin resistance, inflammation and oxidative stress are key players in the cardiometabolic risk, although the main cause initiating the metabolic alterations associated with the cardiometabolic risk has to be identified. Postmenopausal women are an important sub-group of the general population because the risk of developing cardiometabolic complications increases after menopause. The cardiometabolic risk factors can be modulated by dietary intake, physical activity and weight loss. Despite the fact that the study of specific nutrients or foods provided a better understanding of the implication of nutrition in the cardiometabolic risk, the relationship between diet quality and cardiometabolic risk has been less studied. Beneficial effects of physical activity on the cardiometabolic risk have been demonstrated in physically active individuals. However, the relationship between energy expenditure and the cardiometabolic risk in sedentary individuals has been less investigated. Similarly, it is unknown whether dietary intake interacts with physical activity in order to have greater beneficial effects on the cardiometabolic risk. The objective of this thesis is to determine the relationships between diet quality, physical activity and oxidative stress on the cardiometabolic risk in sedentary postmenopausal overweight and obese women without cardiometabolic complications. The results showed that, in these sedentary women, physical activity energy expenditure is associated with reduced inflammation, independently of adiposity. Moreover, there is a synergistic relationship between quality and physical activity energy expenditure (PAEE) which is associated with a reduced cardiometabolic risk compared to their separate effects. Indeed, high diet quality combined to high PAEE levels is associated with a better lipid and lipoprotein profile and a lower inflammatory status, independently of adiposity. However, in a pilot study, only independent effects of changes in diet quality and PAEE on the changes in cardiometabolic risk factors was observed following a 6-month hypocaloric diet. Indeed, beyond the reduction of adiposity and improvement of the lipoprotein profile induced by this diet, improved diet quality and increased PAEE are associated with beneficial changes in blood pressure and lipid profile. On the other hand, modification in the glutathione system, which is one of the most common antioxidant systems in the body, is associated with a higher cardiometabolic risk. Greater glutathione peroxidase activity is associated with insulin resistance and greater intima-media thickness of blood vessels. These relationships may be mediated through a reductive stress. In conclusion, a healthy diet and physical activity should be emphasized in interventions aimed to reduce obesity and its related complications, even in absence of change in adiposity. Moreover, glutathione peroxidase activity may be a parameter contributing to the development of sub-clinical but clinically relevant asymptomatic cardiometabolic abnormalities in obese women. Further investigations are needed to confirm these results and to elucidate the underlying mechanisms.

Le syndrome génito-urinaire de la ménopause (SGUM) engendre des symptômes importants et des impacts considérables sur la qualité de vie et la fonction sexuelle des femmes post-ménopausées. Les traitements actuels sont efficaces pour soulager un grand nombre de femmes. Toutefois, dans certains cas, ils ne pas soulagent pas tous les symptômes, peuvent entraîner des effets indésirables et être contre-indiqués. Il apparaît alors nécessaire d’identifier des traitements alternatifs ou complémentaires pour le SGUM. Ce projet avait pour but d’approfondir les connaissances sur l’utilisation d’un programme d’exercices des muscles du plancher pelvien (EMPP) pour le traitement du SGUM chez des femmes post-ménopausées. Les objectifs principaux étaient: 1) évaluer les qualités psychométriques d’outils de mesure nécessaires à l’étude du SGUM, 2) étudier la faisabilité et les effets d’un programme d’EMPP auprès de femmes post-ménopausées atteintes du SGUM et 3) investiguer les mécanismes d’action potentiels des EMPP sur le SGUM. Trois projets distincts ont été élaborés dans le cadre de cette thèse. Le premier a permis d’explorer les effets des EMPP sur le SGUM au moyen de l’étude du cas d’une femme post-ménopausée. Suite à l’intervention, les signes et symptômes du SGUM du cas à l’étude se sont améliorés, en plus de leurs impacts sur la qualité de vie et la fonction sexuelle. À la lumière de ces résultats, des hypothèses sur les mécanismes d’action responsables des effets positifs ont été émises, dont une était l’amélioration de la vascularisation vulvovaginale. Le deuxième projet visait donc à évaluer la fidélité de la mesure de la vascularisation d’artères liées aux tissus vulvovaginaux, soit les artères pudendale interne et dorsale du clitoris, à l’aide de l’échographie Doppler. Les résultats recueillis auprès de 20 femmes sans condition urogynécologique ont appuyé la fidélité test-retest de ces mesures. Pour le troisième projet, 32 femmes post-ménopausées atteintes du SGUM ont participé à deux évaluations pré-intervention, un programme d’EMPP de 12 semaines et une évaluation post-intervention. Les évaluations pré-intervention ont permis de confirmer les qualités psychométriques d’outils de mesure du SGUM (Most Bothersome Symptom Approach et Atrophy Symptom questionnaire) en plus de confirmer la fidélité test-retest de la mesure de la vascularisation des artères pudendale interne et dorsale du clitoris à l’aide de l’échographie Doppler chez cette population. Suite à l’intervention, les résultats supportaient la faisabilité d’un programme d’EMPP auprès de femmes post-ménopausées atteintes du SGUM, de par des taux élevés de ii participation à l’intervention et de complétion de l’étude. Les résultats supportaient également l’effet positif de cette intervention en démontrant une diminution significative de la sévérité des symptômes du SGUM, de certains signes du SGUM et de leurs impacts sur leur qualité de vie et leur fonction sexuelle. Les résultats de cette étude suggèrent également l’augmentation de la vascularisation vulvovaginale, l’amélioration de la capacité de relâchement des MPP et l’augmentation de l’élasticité des tissus vulvovaginaux comme mécanismes d’actions potentiels d’un programme d’EMPP chez les femmes post-ménopausées atteintes du SGUM. Des études ultérieures devront confirmer nos résultats. / Genitourinary syndrome of menopause (GSM) causes significant symptoms and considerable impacts on the quality of life and sexual function of postmenopausal women. Current treatments are effective in alleviating the symptoms of many women. However, in some cases, they do not relieve all symptoms, and may cause side effects and be contraindicated. In these cases, it is necessary to identify alternative or complimentary treatments for GSM. The purpose of this project was to increase knowledge on the use of a pelvic floor muscle exercise (PFME) program for the treatment of GSM in postmenopausal women. The main objectives were to: 1) evaluate the psychometric qualities of the measurement tools needed to study GSM, 2) study the feasibility and effects of a PFME program in postmenopausal women with GSM, and 3) investigate the potential mechanisms of action of PFME on GSM. Three separate projects were developed for this thesis. The first project was a case study involving a postmenopausal woman, which provided an exploration of the effects of PPME on GSM. In this case study, the woman’s signs and symptoms of GSM improved, as well as her quality of life and sexual function. Considering these results, hypotheses were proposed on the mechanisms of action responsible for the positive effects of PPME on GMS, one of which was the improvement of vulvovaginal vascularization. The second project aimed to assess the accuracy of the measurement of the vascularization of arteries related to vulvovaginal tissues, namely the internal pudendal and dorsal arteries of the clitoris, using Doppler ultrasound. Results from 20 women without urogynecological conditions supported the test-retest reliability of these measurements. For the third project, 32 postmenopausal women with GSM participated in two pre-intervention assessments, a 12-week PFME program, and a post-intervention assessment. The pre-intervention assessments confirmed the psychometric qualities of GSM measurement tools (the Most Bothersome Symptom Approach and the Atrophy Symptom Questionnaire) and the test-retest reliability of the measurement of the vascularization of the internal pudendal and dorsal clitoral artery in this population using Doppler ultrasound. Following the intervention, the results supported the feasibility of a PFME program in postmenopausal women with GSM, due to high rates of participation in the intervention and completion of the study. The results also supported the positive effect of this intervention by demonstrating a significant reduction in the severity of GSM symptoms, certain signs of GSM, and their impact on their quality of life and sexual function. Finally, the results of this study suggest an increase in vulvovaginal vascularization, an improvement in the ability to relax the pelvic floor muscles and an increase in the elasticity of vulvovaginal tissues as potential mechanisms of action of a PFME program in postmenopausal women with GSM. Further studies are needed to confirm these findings.

CONTEXTE: L'inefficacité de captation des acides gras libres (AGL) par le tissu adipeux blanc (TAB) est connue pour favoriser la résistance à l'insuline (RI) dans les tissus périphériques, mais dans le foie, elle favorise également la production accrue de lipoprotéines contenant l'apolipoprotéine B100 (lipoprotéines apoB). Nous avons récemment démontré que les femmes post-ménopausées obèses avec un nombre élevé de lipoprotéines apoB à jeun (apoB plasmatique > 1,2 g/L) avaient plus de RI que les femmes avec un taux d’apoB normal. Notre objectif était donc d'examiner si l'inefficacité de captation des AGL pourrait être un mécanisme expliquant la RI, in vivo dans cette population. HYPOTHÈSES: Les femmes ménopausées en surpoids/obèses avec un taux d’apoB élevé ont moins d'efficacité à capter les AGL par le TAB que les femmes avec un taux d’apoB faible. MÉTHODES/RÉSULTATS: L'efficacité de captation des AGL a été examinée dans 22 femmes non diabétiques en surpoids/obèses. La population a été séparée selon la médiane d’apoB (0.9 g/L) en 2 groupes; les femmes ayant un taux d’apoB inférieur vs supérieur à la médiane (N=11/groupe). L'efficacité de captation des AGL par le TAB a été indirectement évaluée en suivant le sort d'un repas riche en gras (0.0162g 13C-trioléine/g de matières grasses, 66% de gras, 47g gras/m2 surface corporelle) marqué au 13C-trioléine, sur 6h en circulation ([13C]TG et [13C]AGL plasmatiques) et en oxydation (13CO2 dans l’air expiré [AE]). L’enrichissement en 13C des échantillons d’AE et du plasma a été mesuré par spectrométrie de masse pour ratio isotopique. Les femmes ayant un apoB élevé avaient une clairance plasmatique totale postprandiale des TG (p <0,05) réduite sans diminuer de la clairance plasmatique totale des AGL, par rapport aux femmes ayant un faible taux d’apoB. Cependant, en examinant le sort du 13C-trioléine, les femmes ayant un apoB élevé avait une réduction de la clairance des [13C]TG plasmatiques (44,78 μM vs 7,81 μM; p <0,05) et des [13C]AGL plasmatiques (2,64 uM vs 0,06 uM; p <0,05) à 6h, sans aucune différence en % récupéré de 13C-trioléine dans le CO2 de l’AE. Ces données suggèrent que les femmes ayant un taux d’apoB élevé ont une réduction postprandiale de la clairance et de la captation de 13Ctrioléine par le TAB. CONCLUSION: La captation inefficace des AGL par le TAB des femmes post-ménopausées en surpoids et obèses avec un surplus d’apoB peut être un mécanisme sousjacent à la RI chez ces sujets. / BACKGROUND: Inefficiency of fatty acid (FA) trapping in white adipose tissue (WAT) is known to promote insulin resistance (IR) in peripheral tissue, but in the liver, it also promotes increased secretion of apolipoprotein B100-lipoproteins (apoB-lipoproteins). We recently demonstrated that post-menopausal obese women with high numbers of fasting apoB-lipoproteins (plasma apoB> 1.2 g/L) had higher IR than women with normal apoB. Our aim was thus to examine whether inefficiency of FA trapping was a mechanism explaining IR in vivo in this population. HYPOTHESES: Postmenopausal overweight and obese women with high apoB have lower efficiency of FA trapping in WAT than women with low apoB. METHODS/RESULTS: The efficiency of FA trapping was examined in 22 non-diabetic overweight and obese women, and the group was separated around median apoB (0.9 g/L) into women with higher vs lower apoB (N=11 per group). The efficiency of FA trapping in WAT was indirectly assessed by following the fate of a 13C-triolein labelled high-fat meal (0.0162g 13C-triolein/g of fat, 66% fat, 47 g fat/m2 body surface area) over 6 hours in circulation (plasma [13C]TG and [13C]FA) and oxidation (breath 13CO2). 13Cenrichment of breath and plasma samples was measured by isotope ratio mass spectrometry. Women with higher apoB had delayed total postprandial plasma TG clearance (p<0.05) but not total plasma free FA clearance compared to women with lower apoB. However, examining the fate of 13C-triolein revealed that women with higher apoB had delayed plasma [13C]-TG clearance (44.78 μM vs 7.81 μM; p<0.05) and plasma [13C]-FA clearance (2.64 μM vs 0.06 μM; p<0.05) at 6 hours, without any differences in % recovered 13C-triolein in breath CO2. This data suggests that women with higher apoB have lower postprandial 13C-triolein clearance and trapping in WAT. CONCLUSION: Ineffective FA trapping in WAT in post-menopausal overweight and obese women with higher apoB may be a mechanism underlying IR in these subjects.

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