The effects of exogenous estrogen administration on aspects of memory and cognition in women were examined in two studies. In Study 1, women receiving estrogen replacement therapy were compared to untreated women on four measures of verbal memory. Those receiving estrogen had significantly better scores on a measure of delayed memory for propositional material. In Study 2, women in the early stages of Alzheimer's Disease (AD) were administered either estrogen or placebo on a double-blind basis for six months. Women given estrogen showed improvement on a measure of verbal memory and spatial attention compared to the placebo controls. The combined results of these studies provide evidence that estrogen enhances aspects of verbal memory in both healthy postmenopausal women and in postmenopausal women in the early stages of AD as measured by neuropsychological tests. These effects might be mediated by actions of estrogen on neuronal morphology and physiology in brain areas important for memory and cognition.

Prostate cancer is frequently diagnosed in elderly men and, despite the largely unproven survival benefits of treatment, the majority receive treatment. Treatment options include surgery, radiation, and/or androgen deprivation therapy (ADT). Risks associated with treatment include hip fracture. Current understanding suggests that hip fracture is a frequent cause of morbidity and mortality in the elderly, and both radiation treatment and ADT can increase the risk of hip fracture. It is important to understand these risks so they can be minimized and the morbidity of treatment reduced. The objectives of this study were to estimate the risk of hip fracture as a major adverse outcome of treatment for prostate cancer among elderly men. The specific objectives include estimating: 1) the risk of hip fracture and the dose-risk relationship among patients receiving curative radiation treatment, and 2) the risk of hip fracture associated with palliative ADT and relapsed ADT compared to curative ADT. The cancer diagnosis and treatment records of 32,673 men were linked to their hospital discharge abstracts. The risk of hip fracture was estimated using Cox regression and the estimates were adjusted for age, comorbidity, income, and year of diagnosis. The risk of hip fracture was 59% higher among men who received curative radiation when compared to men who received curative surgery. The risk of hip fracture fell by 6% with each one Gy increase in radiation dose between 55 and 81 Gy Biological Equivalent Dose to the hip-bone. The risk of hip fracture for subjects in the palliative ADT and relapsed ADT categories was 5.98 and 5.77 times the risk in comparison to men who received curative ADT treatment. Curative radiation treatment is associated with an increased risk of hip fracture when compared to curative surgery. The risk of hip fracture is greater with ADT for palliation and relapsed cancer than with curative treatment. Current treatments for prostate cancer contain significant risk of hip fracture for elderly men and these risks should be considered as part of the treatment decision.

Cancer-treatment-induced bone loss (CTBL) is a well-recognized co-morbidity that affects many cancer patients. Commonly used to treat breast and prostate cancer patients, hormone suppression therapy (HST) may accelerate bone loss, resulting in osteopenia or osteoporosis. Because of their broad clinical utility, lifestyle and dietary modifications, such as regular participation in bone-stressing exercise and calcium supplementation, are starting to play a much larger role in the prevention and treatment of CTBL. However, only limited information is available on the effects that these factors may have on bone mineral density (BMD). Purpose. The purpose of this investigation was to assess the degree of BMD change from the onset of HST to 6 months and to examine the impact that physical activity and calcium intake may have on BMD. Methods. Twelve subjects (8 females and 4 males) undergoing HST for breast or prostate cancer were enrolled in the study. BMD at the spine, dual femur, and total body was assessed by dual-energy x-ray absorptiometry at 0 and 6 months. In addition, subjects wore an accelerometer to assess physical activity level and completed a lifestyle questionnaire at baseline, 3, and 6 months after starting therapy. Aside from the 7 non-exercise subjects, 5 subjects chose to participate in The Cancer Exercise Program at Ball Memorial Hospital or complete bone-stressing exercises at home. Results. No significant changes in BMD were observed after 6 months of HST between the groups at any of the sites. When all subjects were examined together, a significant BMD decrease of 3.2% was observed at the lumbar spine. The accelerometer and lifestyle questionnaires revealed that the males were more active than the females and the exercisers were more active than the non-exercisers at both baseline and after 6 months of HST. Supplementation with calcium did not affect BMD changes at any site;although it is possible this is an effect of gender as all males were included in the same group. Lifestyle factors such as history of smoking and alcoholism were also examined, but were not correlated to changes in BMD. Conclusion. Treatment with HST results in decreases in BMD, particularly at the spine. Bone-stressing exercise helped maintain or improve total body BMD in 3 of the 5 subjects the exercise group. There appears to be no difference in BMD between those who supplemented with calcium and those who did not. / School of Physical Education, Sport, and Exercise Science

Using illustrations of popular media about female hormones that depict and stereotype women, I theorize towards a more positive approach to women's bodies in flux and change that moves away from the conceptualization of women as Hormonal Bodies towards Bodies without Hormones. I challenge biomedical agency, reductionist biology, a predatory pharmaceutical industry and normative social imperatives to question the assumption of women's bodies as a naturalized pathology. To disrupt the disciplining of women socially constructed as deficient and uncontrollable, I point to the conflict between women's naturally fluxing bodies and emotions, and western society's dominant values shaping women, hormones and contemporary health practices. I reframe women's bodies from problem and limitation to resource and possibility. Neo-materialist views of Deleuze and Guattari, nomadic figurations and rhizomatic thinking are contextualized to women and bodies to produce notions of practicing and experiencing a body of choice unbound to female hormones.

Memory function was examined in association with sex hormone levels in women. The results of the first study suggest that self-reports of memory problems were especially prevalent among women attending a menopause clinic compared to a nonpatient sample. In the following investigation, women given placebo after undergoing a bilateral oophorectomy showed decreases in memory performance, specifically on a paired-associate learning task, coincident with declines in estrogen levels. Significant improvements were found in estrogen-treated women pre- to postoperatively in the immediate recall of paragraphs, in association with supraphysiological estrogen levels. A final study on naturally-cycling women found a decline in visual memory performance during the menstrual compared to the luteal phase of the cycle. Visual memory scores were positively correlated with progesterone levels whereas paired-associate recall scores were positively associated with estradiol levels during the luteal phase. These results suggest that certain aspects of memory covary with changes in sex steroid levels in some women.

Prostate cancer is frequently diagnosed in elderly men and, despite the largely unproven survival benefits of treatment, the majority receive treatment. Treatment options include surgery, radiation, and/or androgen deprivation therapy (ADT). Risks associated with treatment include hip fracture. Current understanding suggests that hip fracture is a frequent cause of morbidity and mortality in the elderly, and both radiation treatment and ADT can increase the risk of hip fracture. It is important to understand these risks so they can be minimized and the morbidity of treatment reduced. The objectives of this study were to estimate the risk of hip fracture as a major adverse outcome of treatment for prostate cancer among elderly men. The specific objectives include estimating: 1) the risk of hip fracture and the dose-risk relationship among patients receiving curative radiation treatment, and 2) the risk of hip fracture associated with palliative ADT and relapsed ADT compared to curative ADT. The cancer diagnosis and treatment records of 32,673 men were linked to their hospital discharge abstracts. The risk of hip fracture was estimated using Cox regression and the estimates were adjusted for age, comorbidity, income, and year of diagnosis. The risk of hip fracture was 59% higher among men who received curative radiation when compared to men who received curative surgery. The risk of hip fracture fell by 6% with each one Gy increase in radiation dose between 55 and 81 Gy Biological Equivalent Dose to the hip-bone. The risk of hip fracture for subjects in the palliative ADT and relapsed ADT categories was 5.98 and 5.77 times the risk in comparison to men who received curative ADT treatment. Curative radiation treatment is associated with an increased risk of hip fracture when compared to curative surgery. The risk of hip fracture is greater with ADT for palliation and relapsed cancer than with curative treatment. Current treatments for prostate cancer contain significant risk of hip fracture for elderly men and these risks should be considered as part of the treatment decision.

Asthma is a chronic inflammatory disease of the airways. Using a murine model which replicates many characteristic features of human asthma, this study evaluated the effects of treatment with anti-inflammatory drugs on the lesions of chronic asthma, and investigated potential underlying molecular mechanisms. Treatment with dexamethasone, a glucocorticoid, was compared with roflumilast, a novel phosphodiesterase-4 (PDE4) inhibitor. BALB/c mice sensitised to ovalbumin were challenged with a low mass concentration of aerosolised antigen for 30 min/day, 3 days/week for 6 weeks. In weeks 5 and 6, groups of animals were treated with either dexamethasone or roflumilast. Assessment included changes in acute-on-chronic inflammation, structural remodelling of the airways and airway hyper-responsiveness to a bronchoconstrictor stimulus. These were correlated with the expression of pro-inflammatory cytokines and growth factors. Compared to vehicle-treated control animals, dexamethasone- and roflumilast-treated mice exhibited reduced accumulation of intra-epithelial eosinophils and chronic inflammatory cells, including CD3+ T-lymphocytes in the airways. Similarly, both drugs inhibited subepithelial fibrosis and airway epithelial thickening, although only dexamethasone inhibited goblet cell hyperplasia/metaplasia. Airway hyper-reactivity was not diminished by either drug. Both treatments suppressed production of Th2 cytokines by ovalbumin-restimulated peribronchial lymph node cells. In selectively dissected airway tissue from vehicletreated animals, increased expression of mRNA for several pro-inflammatory cytokines (TNF-α, GM-CSF, IL-6) and cytokines characteristic of Th1 (IFN-γ), Th2 (IL-5, IL-13)and Th17 (IL-17A) cells was demonstrated using real-time PCR. Enhanced expression of growth factors (TGF-β1 and FGF-2) was also demonstrated in airway epithelium isolated by laser capture microdissection. Interestingly, whereas treatment with dexamethasone significantly inhibited expression of mRNA for all of the inflammationrelated cytokines examined, roflumilast inhibited only IL-17A, TNF-α, GM-CSF and IL-6. Both drugs inhibited mRNA expression of growth factors by epithelial cells. Because roflumilast was as effective as dexamethasone in suppressing inflammation and most changes of remodelling, the selective suppression of IL-17A, TNF-α, GM-CSF and IL-6 suggests that these mediators, or the cells that produce them, may have critical roles in pathogenesis. Furthermore, they may be particularly appropriate therapeutic targets in chronic asthma.

Made available in DSpace on 2014-08-13T14:50:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-25Bitstream added on 2014-08-13T18:00:46Z : No. of bitstreams: 1 000754043.pdf: 2158138 bytes, checksum: 7ef7c9ef1a4a3b011dd34994e462754b (MD5) / A atenção integral à saúde da mulher pressupõe assistência em todas as fases de sua vida. O climatério, por compreender um período relativamente longo da vida da mulher, deve merecer atenção crescente da sociedade, pois a expectativa de vida após a menopausa é atualmente equivalente ao período de vida reprodutiva. A presente pesquisa objetivou avaliar a qualidade de vida das mulheres do município de Promissão/SP que estão passando por essa fase, com ou sem uso da terapia de reposição hormonal. Tratou-se de um estudo epidemiológico longitudinal, com amostra de 99 mulheres para cada grupo. Avaliaram-se as características sociodemográficas, clínicas e comportamentais. Aplicou-se Menopause Rating Scale (MRS) para avaliar a intensidade dos sintomas climatéricos, e o questionário Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) para avaliação da qualidade de vida. Na análise dos dados utilizaram-se os testes t de Student, Qui-quadrado e Tukey. As usuárias de TRH apresentaram média etária de 50,76 ± 3,63 anos e as não usuárias de 48,95 ± 6,27anos (p=0,01). Houve diferença estatisticamente significativa em relação ao estado marital (p=<0,001). As usuárias relataram maior frequência de sintomas climatéricos de intensidade leve a moderada. Dos oito domínios de qualidade de vida avaliados, apenas aspectos sociais apresentou escore abaixo de 50 para os dois grupos. Destaca-se o domínio dor com escores por volta de 60. Fenômenos vasomotores com escores também acima de 50 para o MRS foram evidenciados. Houve diferenças entre os grupos em relação aos componentes do SF-36 e MRS para estado geral de saúde, capacidade funcional, menor capacidade, depressão, insônia e fenômenos vasomotores. As mulheres usuárias e não usuárias de TRH apresentaram boa qualidade de vida / The comprehensive care to women's health requires assistance in all phases of his life. The climacteric, it comprises a relatively long period of woman's life, deserves increased attention from society because life expectancy after menopause is currently equivalent to the period of reproductive life. This study aimed to evaluate the quality of life of women in the municipality of Promissão/SP who are going through this phase with or without use of hormone replacement therapy (HRT). This was a longitudinal epidemiological study with a sample of 99 women in each group. We evaluated the sociodemographic, clinical and behavioral. Applied Menopause Rating Scale (MRS) to assess the intensity of climacteric symptoms and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) to assess quality of life. In the data analysis used the Student t test, chi-square and Tukey. HRT users had a mean age of 50.76 ± 3.63 years and nonusers of 48.95 ± 6.27 years (p = 0.01). There was no statistically significant difference in marital status (p = <0.001). Users reported a higher frequency of climacteric symptoms of mild to moderate intensity. Of the eight domains of quality of life assessed only social scored below 50 for the two groups. It stands out with the pain domain scores around 60. Vasomotor phenomena also with scores above 50 were shown to MRS. There were differences between the groups in relation to the components of the SF-36 and MRS to general health, functional capacity, lower capacity, depression, insomnia and vasomotor phenomena. Women users and nonusers of HRT had good quality of life

abstract: Cognitive function is multidimensional and complex, and research indicates that it is impacted by age, lifetime experience, and ovarian hormone milieu. One particular domain of cognitive function that is susceptible to age-related decrements is spatial memory. Cognitive practice can affect spatial memory when aged in both males and females, and in females alone ovarian hormones have been found to alter spatial memory via modulating brain microstructure and function in many of the same brain areas affected by aging. The research in this dissertation has implications that promote an understanding of the effects of cognitive practice on aging memory, why males and females respond differently to cognitive practice, and the parameters and mechanisms underlying estrogen's effects on memory. This body of work suggests that cognitive practice can enhance memory when aged and that estrogen is a probable candidate facilitating the observed differences in the effects of cognitive practice depending on sex. This enhancement in cognitive practice effects via estrogen is supported by data demonstrating that estrogen enhances spatial memory and hippocampal synaptic plasticity. The estrogen-facilitated memory enhancements and alterations in hippocampal synaptic plasticity are at least partially facilitated via enhancements in cholinergic signaling from the basal forebrain. Finally, age, dose, and type of estrogen utilized are important factors to consider when evaluating estrogen's effects on memory and its underlying mechanisms, since age alters the responsiveness to estrogen treatment and the dose of estrogen needed, and small alterations in the molecular structure of estrogen can have a profound impact on estrogen's efficacy on memory. Collectively, this dissertation elucidates many parameters that dictate the outcome, and even the direction, of the effects that cognitive practice and estrogens have on cognition during aging. Indeed, many parameters including the ones described here are important considerations when designing future putative behavioral interventions, behavioral therapies, and hormone therapies. Ideally, the parameters described here will be used to help design the next generation of interventions, therapies, and nootropic agents that will allow individuals to maintain their cognitive capacity when aged, above and beyond what is currently possible, thus enacting lasting improvement in women's health and public health in general. / Dissertation/Thesis / Ph.D. Psychology 2011

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.