Acid-base regulation, as reflected by hydrogen ion concentration ([H+]), and the chemoreflex control of breathing were examined in healthy pre- (PRE; n=20) and postmenopausal (POST; n=15) women of a comparable age (45 ± 2.7 vs. 52 ± 1.8 years). [H+] behaviour was examined in both groups at rest and during exercise above the ventilatory threshold using Stewart’s physicochemical approach to acid-base analysis. Ventilatory chemoreflex characteristics were assessed using Duffin’s modified rebreathing protocol that includes 5 min of prior hyperventilation and maintenance of either hyperoxic (150 mmHg) or hypoxic (50 mmHg) iso-oxia. As expected, the ovarian hormones progesterone ([P4]) and estrogen ([E2]) were significantly lower in the POST group. [H+] was unaffected by menopausal status at rest or during exercise. At rest the POST group exhibited significantly higher PaCO2 and [SID] values relative to the PRE group. In general, the acidifying effects of increased PaCO2 were offset by the alkalizing effect of increases in [SID] (or vice versa) in the POST group such that [H+] did not differ between PRE and POST groups. The central ventilatory chemoreflex also differed between groups with the POST group exhibiting a significantly higher threshold and a lower sensitivity in the response to CO2 relative to the PRE group. [P4] was found to partially account for the significant group differences in acid-base and central ventilatory chemoreflex control characteristics supporting the role of [P4] as an important determinant of acid-base status and the chemical control of ventilation in healthy women. Findings of the current study may have potential relevance in understanding the increased occurrence of various health conditions such as osteoporosis and sleep disordered breathing in females following the onset of menopause. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2007-09-21 08:53:00.841

AIMS. To determine the cardio-metabolic risk profile and incidence of low bone mineral density in African and Indian postmenopausal women attending the IALCH menopause clinic and to determine whether there is a correlation between cardio-metabolic parameters and low bone mineral density. METHODS. A retrospective, descriptive study involving all Indian and African postmenopausal women, above the age of 40, referred to the menopause outpatient clinic at IALCH from 01 July 2009 to 31 December 2010 was conducted. Data was collected from the medi-com database using a structured questionnaire. Cardio-metabolic data was analysed as continuous variables and summarized using means and standard deviations. Bone mineral density was treated as a quantitative variable and correlation analysis was used to assess relationships between the variables. This was done for each race group separately. The Students T-test was used to compare cardio-metabolic variables between the two ethnic groups. SPSS version 18.0 was used to analyse data. RESULTS. The records of 106 women were analysed (51 African and 55 Indian). In African and Indian women, the prevalence of hypertension was 54.9% vs 65.5%, the prevalence of diabetes was 31.4% vs 56.4%, the prevalence of dyslipidaemia was 17.6% vs 32.7% and the prevalence of ischaemic heart disease was 5.9% vs 14.9% respectively. The prevalence of low bone mineral density was higher in Indian women (40%) compared to African women (23.5%). The mean body mass index (BMI) of African women was significantly higher than Indian women, (33 vs 29). There were no significant differences between African and Indian postmenopausal women regarding their lipid profile, fasting glucose, fasting insulin and thyroid profile. The mean bone mineral density (BMD) in the hip and spine was lower in Indian women compared to African women, however the prevalence of osteopaenia and osteoporosis, as defined by T-scores, was not statistically significant. Statistically significant positive correlations were observed between an increasing BMI and BMD (p<0.001) and increases in weight and BMD (p<0.001). A statistically significant correlation were observed between serum LDL-cholesterol values and BMD (p=0.03), where serum LDL-cholesterol values were inversely proportional to BMD. There were no significant correlations between BMD and the remaining cardio-metabolic variables (ie blood pressure; waist-hip ratio; clinical stigma of dyslipidaemia; clinical stigma of insulin resistance; cholesterol; HDL; triglycerides; fasting glucose; fasting insulin and thyroid function). CONCLUSIONS. There is a high prevalence of cardiovascular risks and low BMD amongst the local menopausal population, irrespective of ethnicity. African and Indian postmenopausal women had a high prevalence of hypertension (60%), diabetes (44%), dyslipidaemia (25%) and obesity (54%). In African women, the incidence of low BMD was 35% in the hip, 53% in the neck of femur and 55% in the lumbar spine. In Indian women, the incidence of low BMD was 55% in the hip, 67% in the neck of femur and 69% in the lumbar spine. BMI and weight showed a positive correlation with bone mineral density. Regarding the cardio-metabolic variables, an increasing LDL value was negatively correlated with bone mineral density. It thus is apparent that a screening lipid profile during the peri-menopausal years, coupled with early and appropriate lifestyle management regarding body mass index/ weight may limit the burden of morbidity in later life. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2013.

Women seem to be largely protected against certain ‘welfare disorders’ such as cardiovacular disease and osteoporosis, during their fertile years.The metabolic changes observed during women’s non-menstrual states, i.e. during pregnancy, after the menopause and during use of oral contraceptives, indicate the importance of sex steroids and an undisturbed biological rhythm. Treatment with monophasic, combined oral contraceptives constitutes a model for the non-cyclic state.Growth hormone (GH) is a pituitary hormone that has major metabolic effects. The pattern of GH exposure to the target organ is of vital importance for the effects and changes in rhythm could possibly induce metabolic changes.Growth hormome, cholecystokinin (CCK), osteocalcin and angiotensinogen were used as markers for metabolic effects and the concentrations in serum were recorded in women during non-menstrual states. The clinical material comprised a total of 60 women: 18 healthy non-pregnant, 25 pregnant, one lactating woman and 16 postmenopausal women. Using a portable pump and a non-thrombogenic venous catheter, blood samples could be collected at 30-min intervals during 24-h periods. Furthermore, the effects of estrogen and GH in the regulation of angiotensinogen were investigated in an experimental model in the rat.Oral contraceptives were found to alter the secretion of GH towards a pattern of lower and more frequent peaks, though the total amount secreted during 24 h was unchanged. Oral contraceptives seem to induce a suppression of the 24-h concentrations of CCK, which may be important with respect to weight gain in some women. Osteocalcin in serum display a significant circadian variation. This emphasizes the need for careful timing of single point measurements and the value of continuous blood sampling. Oral contraceptives may reduce osteocalcin serum concentrations. The long-term effects on bone are unknown. During late pregnancy osteocalcin levels are extremely low, which could indicate osteoblast inhibition and reduced bone turnover. The mode of GH administration is important for the plasma concentration of angiotensinogen in the non-pregnant rat. Estrogen effects on this protein may be mediated via a modification of GH secretion. Oral contraceptives not only increase angiotensinogen concentrations in serum but also markedly enhance their variability. Further studies are needed to elucidate the relation between the individual pattern of angiotensinogen and hypertension. / <p>S. 1-42: sammanfattning, s. 43-88: 6 uppsatser</p> / digitalisering@umu

A major cause of morbidity and early death in the Western societies is cardiovascular disease (CVD) secondary to atherosclerotic disease. Metabolic aberrations have been linked to CVD. Particular combinations of these so-called risk markers are common and (central) obesity, Type 2 diabetes, impaired glucose tolerance, hypertension, dyslipidemia, dysfibrinolysis and hyperinsulinemia are often associated. This has been entitled the Insulin Resistance Syndrome (1RS), due to underlying insulin resistance. Moreover, aberrations in circulating levels of androgens and IGF-binding proteins are associated with 1RS. The main hypothesis in this thesis was that increased levels of leptin, the recently discovered adipocyte derived hormone in combination with obesity may be an important factor in the link between 1RS and the development of CVD. The association between leptin levels and variables associated with the Insulin Resistance Syndrome was studied in a healthy sample (n=163) of middle-aged men and women from the northern Sweden MONICA health survey. Central obesity was associated with high levels of leptin and insulin in men and women. In contrast, central obesity was linked to low testosterone levels in men, whereas in women, central obesity was associated with high testosterone but low SHBG levels. Furthermore, in males and postmenopausal women central obesity was a major determinant for circulating leptin. Leptin levels were associated with biochemical androgenicity in non-obese men and women. The direction of this association was dependent on gender and body fat distribution. Specifically, testosterone was inversely associated to leptin in non-obese men and in normal weight women whereas testosterone was positively associated to leptin in non-obese women. In contrast, adiposity and insulin levels, but not testosterone, were associated to leptin in obese men and women. Similarly, leptin was associated to IGFBP-1 and proinsulin in non-obese men and premenopausal women. Hyperleptinemia was significantly associated to high PAI-1 levels in men and in centrally obese women. In a multivariate model, high leptin levels predicted PAI-1 levels in men but not in women. Finally, leptin levels were related to blood pressure in obese men. The impact of hyperleptinemia on future risk for development of CVD was tested in a nested case-referent study based on the MONICA and the Västerbotten Intervention Program surveys. It was found that hyperleptinemia and high total cholesterol levels were associated with increased risk for development of myocardial infarction whereas high levels of apolipoprotein A-l were protective. Hyperleptinemia together with hypertension remained as significant risk markers for hemorrhagic stroke whereas hypertension alone predicted ischemic stroke. The combinations of hyperleptinemia on one hand and low apolipoprotein A- 1 and high blood pressure on the other were associated with a pronounced increased risk for myocardial infarction and hemorrhagic stroke, respectively. In conclusion, hyperleptinemia is independently associated with several risk markers for CVD included in the insulin resistance syndrome. Furthermore, high leptin levels predict the development of CVD. / <p>Härtill 5 uppsatser</p> / digitalisering@umu

The purpose of this research study was to examine the effects of consumption of beverages (caffeinated and alcoholic) and physical activity on the frequency and severity of hot flashes in peri-menopausal, menopausal, and post-menopausal women by conducting an on-line survey of women over the age of 40 employed at a Midwestern University. One-hundred ninety-six women participated in this study. Majority of participants were age 50-59 (n=104, 53.1%), and were in the naturally post-menopausal reproductive stage (n=81, 41.3%). Overall, results revealed that the effects of self-reported physical activity, average daily caffeine and alcohol intake were not significant in predicting the frequency of hot flashes (R2=.043, F(6, 184) = 1.39, p= .221). However, results revealed a small, but statistically significant effect of physical activity, caffeine, and alcohol intake on severity of hot flashes (R2=.068, F(6,180) = 2.195, p = .046). Additionally, relatively more participation in aerobic physical activity increased frequency of hot flashes (p= .031); while higher intensity of aerobic physical activity had an inverse relationship on both frequency and severity of hot flashes (p=.011, p=.003, respectively). / Department of Family and Consumer Sciences

The purpose of this study was to investigate the effects of: 1) caffeine consumption; 2) Body Mass Index (BMI); and 3) frequency and intensity of physical activity on the frequency and severity of hot flashes, in pre-menopausal, peri-menopausal, menopausal and post-menopausal Hispanic women. Ordinary Least Squares regressions indicated there was a statistical significant correlation between daily total estimated caffeine intake with frequency (R2=0.078 (F(8, 207)=2.2, P=0.029) and severity of hot flashes (R2=0.086 (F(8, 208)=2.45, P=0.015). Analysis of variance revealed that and increase in frequency of 30 min strength physical activity reduced severity of hot flashes by 0.72 on a hedonic scale (p<0.05). Conversely, caffeine intake of 100 mg increased frequency and severity of hot flashes (p<0.001, p=0.004, respectively). / Department of Family and Consumer Sciences

Syftet med denna studie var att beskriva unga kvinnors upplevelser av förtidig menopausefter cytostatika- och/eller hormonbehandling. Ett ytterligare syfte var att beskriva hursexualiteten upplevdes efter dessa behandlingar. Undersökningen genomfördes i två etapper med fenomenologisk metod. Öppna individuella intervjuer valdes i delstudie 1. I delstudie 2 användes fokusgrupp. Sammanlagt deltog nio kvinnor i studien. Dessa kvinnor var yngre än 45 år vid diagnosen och hade slutat att menstruera pga. behandling. Essensen befanns vara: Att inte känna igen sig själv, med delkomponenterna den fertila sexuella kroppen, den åldrande kroppen, sårbarhet och bekräftelse. I fokugruppsintervjun utvecklades essensen: Utanförskap med delkomponenterna att inte vara hemma i sin egen ålder, stigma, sexuell lust och intima relationer, existentiell oro samtbekräftelse. Slutsatsen som dras är att man inom sjukvården bör utveckla samtalsformer som riktar uppmärksamhet mot dessa kvinnors upplevelser av identitetsförvirring och utanförskap. Vissa data tydde på att kunskap omsexualitet samt kroppskännedom mildrade de upplevda svårigheterna. / The purpose of this study was to describe young women’s experiences of premature menopause after chemotherapy and/or treatment of hormones. A further purpose was to describe the women’s experiences of sexuality due to these treatments. The study was conducted in two steps with phenomenological method. Unstructured individual interviews were chosen in part 1. In part 2 focus group interviews were used. Nine women in all participated in the study. These women were younger than 45 years at time of diagnoses and had stopped menstruate due to treatment. The essence that emerged: Not recognizing oneself consisting of the following components: the fertile body, the aging body, vulnerability and confirmation. In the focus group the essence turned out to be: feeling marginalized consisting of the following components: not being at home in your own age, stigma, desire and intimate relationships, existential anxiety and confirmation. The conclusion was that health care services should provide room for the women to discuss feelings of identity confusion and marginalization. Some data indicated that beeing knowledgable about sexuality and the functioning of one’s own body helped in coping with the difficulties caused by drug-induced menopaus / <p>ISBN 91-7997-104-0</p>

In den letzten Jahren wurden die westlichen Industrienationen vermehrt mit Wohlstandserkrankungen konfrontiert, welche durch Überernährung und gleichzeitigem Bewegungsmangel hervorgerufen werden. Dabei gilt es besonders die Fettsucht und das meist damit vergesellschaftete Metabolische Syndrom (MetS) zu nennen. Bei dem MetS handelt es sich um eine multifaktorielle Erkrankung, die laut „International Diabetes Foundation" (IDF) unter anderem durch erhöhte Triglyceride, ein niedrigeres HDL-Cholesterin, einen erhöhten Blutdruck und einen pathologischen Nüchternblutzucker gekennzeichnet ist. Eine wichtige Subpopulation von Betroffenen des MetS sind Frauen in den Wechseljahren, von denen ca. 40 % Symptome des MetS zeigen. In Studien zeigte sich, dass die Hormonersatztherapie (HRT) Parameter des Stoffwechsels in postmenopausalen Frauen unterschiedlich beeinflusst, je nachdem, ob sie gleichzeitig Symptome des MetS zeigen oder nicht. So werden z. B. Probleme der Insulinresistenz durch HRT von postmenopausalen Frauen zwar prinzipiell verbessert, aber nur, wenn diese Frauen nicht gleichzeitig weitere Symptome des MetS aufweisen wie z. B. Adipositas. Um sowohl die Folgen für die Gesundheit des betroffenen Individuums zu minimieren als auch die sozioökonomischen Folgen in Schranken halten zu können, sollten präventive Behandlungsmaßnahmen den kurativen deutlich zu bevorzugen sein. Voraussetzung für eine effektive chemische Prävention des MetS und seiner Folgen für die Gesundheit ist die genaue Kenntnis der molekularen Grundlagen der pathophysiologischen Veränderungen, die als Folge der Östrogendefizienz zur verstärkten Ausprägung der Symptome des MetS bzw. der Adipositas führen. Ein erster plausibler mechanistischer Ansatzpunkt schien dabei durch das Wechselspiel von Östrogenen und Leptin gegeben zu sein. So ist z. B. der Leptin-Spiegel in Frauen gegenüber Männern dreifach höher. Ein „cross-talk“ zwischen den beiden Hormonen im Hypothalamus gilt als nachgewiesen. Die Aromatase-knockout (ArKO)-Maus ist ein Mausmodell, das als Phänotyp die Östrogendefizienz mit den Symptomen des MetS vergesellschaftet. Durch die Deletion des Cyp19-Gens (Aromatase-Gen) sind diese Tiere nicht in der Lage, Östrogene zu synthetisieren. Dies äußert sich phänotypisch durch eine Infertilität beider Geschlechter und im zunehmenden Lebensalter durch die Ausprägung einer exzessiven Adipositas. Durch diese Eigenschaft scheint die ArKO-Maus ein adäquates Modell zur Erforschung von Folgen der Östrogendefizienz einschließlich des MetS zu sein. Aus diesem Grund war es interessant zu prüfen, ob und in welchem Umfang die ArKO-Maus a) ein adäquates Modell für hormonelle Prüfungen bei Zuständen der Östrogendefizienz im Allgemeinen und b) im Zusammenhang mit der Östrogendefizienz vergesellschaftete Fettsucht darstellt. Symptome der Wechseljahre sind ein Problem des alternden Organismus. Diese Tatsache wird in vielen tierexperimentellen Studien zu Erscheinungen der Östrogendefizienz nicht berücksichtigt. Deshalb war es weiterhin interessant, den Einfluss des Alters zu Beginn der Behandlung der ArKO-Maus zu untersuchen. Ein weiterer Schwerpunkt dieser Arbeit lag in der Prüfung östrogenähnlicher Substanzen im ArKO-Mausmodell. Hier war es zusätzlich von Interesse neben dem Einfluss der östrogenen Substanzen auf ausgewählte Gewebe in der ArKO-Maus auch die Bedeutung der Behandlungsdauer zu untersuchen. Zur Beantwortung der ersten Frage die östrogene Empfindlichkeit betreffend wurden ArKO-Mäuse mit der ihren Wildtyp (WT)-Wurfgeschwister verglichen. Dabei wurden jeweils die östrogendefizienten Tiere, ArKO-Maus und ovariektomierte (ovx) WT-Maus, sowie die unter Östrogeneinfluss stehenden Tiere, E2-supplementierten ArKO-Mäuse und intakte WT-Mäuse miteinander verglichen. Basierend auf den physiologisch, biochemisch und molekularbiologisch erhobenen Daten ist das Fazit der ersten tierexperimentellen Studie: Die ArKO-Maus scheint anders als die ovx WT-Maus kein adäquates experimentelles Modell für reine Östrogenprüfungen zu sein. Sie scheint aber geeignet für molekulare Untersuchungen im Zusammenhang von Östrogendefizienz und MetS zu sein. Zwischen den beiden Mausmodellen ArKO und WT fand sich auf physiologischer und molekularer Ebene eine Vielzahl von Unterschieden. Die ArKO-Mäuse waren signifikant schwerer und auch der Verfettungsgrad war bei den ArKO-Mäusen stärker ausgeprägt als bei den ovx WT-Mäusen. Bei der Regulation Genexpression durch Östrogene zeigte ein Teil der untersuchten Gene sogar ein entgegengesetztes Expressionsmuster. Zur Untersuchung, inwiefern das Lebensalter Einfluss auf physiologische und molekulare Eigenschaften der Östrogenwirkung nimmt, wurden weibliche ArKO-Mäuse aus zwei unterschiedlichen Altersgruppen untersucht. Mit der zweiten tierexperimentellen Studie konnte eine Reihe von Parametern identifiziert werden, die in ihrer östrogenen Regulation eine Abhängigkeit vom Alter aufweisen. So unterscheidet sich die Regulation des Körpergewichts signifikant zwischen beiden Altersgruppen, ebenso wie die des Uterusfeuchtgewichts. Auf molekularer Ebene konnte gezeigt werden, dass diese sich altersabhängig verändert und zum Teil im Vergleich der beiden untersuchten Lebensalter sogar entgegengesetzte Muster der östrogenabhängigen Regulation der Genexpression ausbildeten. Als Resümee der zweiten Studie kann daher festgehalten werden, dass bei den ArKO-Mäusen das Lebensalter der Tiere eine entscheidende Determinante für die Östrogensensitivität ist. Dies scheint insofern wichtig, wenn die Endpunkte auf Ebene von Geweben und Genen betrachtet werden, die besonders dem Alterungsprozess unterliegen bzw. die für gealterte Populationen relevant sind. Bei der HRT wird oft die Verwendung von Phytoöstrogenen als sichere „Alternativtherapie“ propagiert. Um zu überprüfen welche Effekte E2, Raloxifen und pflanzliche Sekundärmetaboliten auf physiologische Parameter und die Regulation der Expression ausgewählter Gene in relevanten Zielgeweben der ArKO-Mäuse haben, wurde eine Tiergruppe für drei Tage und eine andere Tiergruppe für 21 Tage mit Raloxifen, Genistein und 8-Prenylnaringenin behandelt. Raloxifen ist eine in der HRT verwendete synthetisch hergestellte östrogene Substanz, die ein bekannter Selektiver-Östrogenrezeptor-Modulator (SERM) ist. Das Soja-Isoflavonoid Genistein und das im Hopfen vorkommende Flavanon 8-Prenylnaringenin (8-PN) sind dagegen natürlich vorkommende sekundäre Pflanzenmetabolite. In den durchgeführten Untersuchungen konnte festgestellt werden, dass es zu einer Verringerung des Fettgewebes durch alle östrogene Substanzen kam. Für die Regulation der Expression östrogener Zielgene kann zusammenfassend festgestellt werden, dass sich nach einer 21-tägigen Behandlungszeit ein anderes Muster der Regulation der Genexpressionsmuster im Uterus ergab als nach einer dreitägigen Behandlung. Dies bestätigt die Annahme, dass auch die Dauer der Behandlung einen großen Einfluss auf die Genexpression und die dadurch vermittelten Veränderungen der Physiologie und des Stoffwechsels hat. Weiter konnte belegt werden, dass Raloxifen, Genistein und 8-PN auf den Uterus und die beiden Fettgewebe ähnliche Effekte zeigten wie E2. In der Expression der untersuchten Gene konnte dies allerdings nicht so deutlich nachgewiesen werden. Schlussfolgernd kann anhand dieser Studien festgehalten werden, dass die ArKO-Maus kein adäquater Ersatz der ovx WT-Maus zur hormonellen Prüfung östrogener Substanzen ist. Sie scheint aber ein geeignetes, ergänzendes experimentelles Modell für Fragestellungen zu sein, die sich mit Untersuchungen der Zusammenhänge von Östrogendefizienz und MetS beschäftigen. Ebenso zeigten die Daten, dass das Lebensalter zu Beginn des Experiments eine entscheidende Determinante für die Qualität der östrogenen Wirkung ist. Darüber hinaus konnte im Rahmen dieser Arbeit gezeigt werden, dass die verwendeten östrogenen Substanzen keine eindeutigen SERM-Eigenschaften, sondern eher östrogene Wirkeigenschaften in den ArKO-Mäusen aufweisen.

Objective: To explore the informational and behavioural factors, that affect women’s participation in physical activity (PA) and body weight changes during perimenopause. Methods: An environmental scan of online health websites to determine availability and quality of information for women about body weight changes during transition to menopause. An interpretive descriptive qualitative study of women age 40 – 60 to explore factors influencing their PA. Descriptive and inductive qualitative analysis were used. Results: Six of 52 websites (11.5%) contained information specific to perimenopausal women, with one site citing evidence. For 26 women interviewed, the most common enabling factors were daily structure, positive feelings, and accountability; while common barriers were disruptions in daily structure, competing demands, and self - sacrifice. Conclusions: There is a lack of information regarding body weight changes for perimenopausal women. Perimenopausal women attribute their PA participation to psychosocial factors, and not the physiology of menopause.

Graduation date: 2000