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.

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.

abstract: Women are exposed to numerous endogenous and exogenous hormones across the lifespan. In the last several decades, the prescription of novel hormonal contraceptives and hormone therapies (HTs) have resulted in aging women that have a unique hormone exposure history; little is known about the impact of these hormone exposures on short- and long- term brain health. The goal of my dissertation was to understand how lifetime hormone exposures shape the female cognitive phenotype using several innovative approaches, including a new human spatial working memory task, the human radial arm maze (HRAM), and several rodent menopause models with variants of clinically used hormone treatments. Using the HRAM (chapter 2) and established human neuropsychological tests, I determined males outperformed females with high endogenous or exogenous estrogen levels on visuospatial tasks and the spatial working memory HRAM (chapter 3). Evaluating the synthetic estrogen in contraceptives, ethinyl estradiol (EE), I found a high EE dose impaired spatial working memory in ovariectomized (Ovx) rats, medium and high EE doses reduced choline-acetyltransferace-immunoreactive neuron population estimates in the basal forebrain following Ovx (chapter 4), and low EE impaired spatial cognition in ovary-intact rats (chapter 5). Assessing the impact of several clinically-used HTs, I identified a window of opportunity around ovarian follicular depletion outside of which the HT conjugated equine estrogens (CEE) was detrimental to spatial memory (chapter 6), as well as therapeutic potentials for synthetic contraceptive hormones (chapter 9) and bioidentical estradiol (chapter 7) during and after the transition to menopause. Chapter 6 and 7 findings, that estradiol and Ovx benefitted cognition after the menopause transition, but CEE did not, are perhaps due to the negative impact of ovarian-produced, androstenedione-derived estrone; indeed, blocking androstenedione’s conversion to estrone prevented its cognitive impairments (chapter 8). Finally, I determined that EE combined with the popular progestin levonorgestrel benefited spatial memory during the transition to menopause, a profile not seen with estradiol, levonorgestrel, or EE alone (chapter 9). This work identifies several cognitively safe, and enhancing, hormonal treatment options at different time points throughout female aging, revealing promising avenues toward optimizing female health. / Dissertation/Thesis / Doctoral Dissertation Psychology 2015

Submitted by THAIS REIS SILVA DE PAULO null (thais.reis.silva@hotmail.com) on 2017-08-23T00:24:36Z No. of bitstreams: 1 Tese Doutorado Unesp - Thais Reis Silva de Paulo.pdf: 3840818 bytes, checksum: d10d7b154e545727960214291e390e95 (MD5) / Approved for entry into archive by Monique Sasaki (sayumi_sasaki@hotmail.com) on 2017-08-23T17:54:15Z (GMT) No. of bitstreams: 1 paulo_trs_dr_rcla.pdf: 3840818 bytes, checksum: d10d7b154e545727960214291e390e95 (MD5) / Made available in DSpace on 2017-08-23T17:54:15Z (GMT). No. of bitstreams: 1 paulo_trs_dr_rcla.pdf: 3840818 bytes, checksum: d10d7b154e545727960214291e390e95 (MD5) Previous issue date: 2017-08-17 / Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) / Introdução: O câncer de mama é uma doença multifatorial com vários tipos de tratamento, dentre eles, a quimioterapia, radioterapia e a hormonioterapia. Os inibidores de aromatase fazem parte do tratamento endócrino e são considerados medicamentos efetivos para o câncer de mama, que promovem menos chances de recidiva e metástase. No entanto, efeitos colaterais do tratamento para o câncer são vários, dentre eles mudanças na composição corporal (diminuição da densidade mineral óssea e aumento do percentual de gordura), disfunção metabólica e piora da qualidade de vida. Sendo assim, o treinamento combinado (resistido + aeróbio) pode ser uma estratégia interessante para minimizar os efeitos colaterais do tratamento para o câncer de mama e promover melhoras nestas variáveis. Objetivo: Analisar o efeito crônico do treinamento combinado sobre a composição corporal, variáveis metabólicas e qualidade de vida de mulheres pós menopáusicas, que fazem tratamento para o câncer de mama com inibidores da aromatase. Métodos: A amostra foi formada por mulheres pós menopáusicas que tiveram câncer de mama e que usavam inibidores de aromatase distribuídas em dois grupos: grupo intervenção (treinamento combinado) e grupo controle (alongamento). Foram realizadas as seguintes avaliações: composição corporal estimada pelo DEXA – Absorciometria de Raios-X de Dupla Energia, para as variáveis gordura corporal, massa magra e densidade mineral óssea, análises bioquímicas de sangue: colesterol total e frações (HDL, LDL, não HDL), triacilglicerol, glicemia, PCR, marcadores ósseos (CTX e osteocalcina) e qualidade de vida. A intervenção foi com treinamento combinado (aeróbio e resistido), três vezes semanais, com exercícios resistidos realizados em máquinas (40 minutos/sessão), seguido do treinamento aeróbio em esteira elétrica (30 minutos/sessão). A intervenção durou nove meses e as avaliações foram feitas nos momentos inicial, três, seis e nove meses após iniciada a intervenção. As análises estatísticas foram realizadas de Anova Two-way - medidas repetidas, utilizando software estatístico SPSS versão 24.0, com significância em 5%. Resultados: De acordo com as análises, o treinamento combinado foi efetivo para promover alterações na composição corporal (diminuição da massa total; da gordura corporal total, % gordura total e de tronco), variáveis metabólicas (diminuição do LDL), além de promover benefícios na qualidade de vida. Quando comparado com o grupo controle, não foram observadas diferenças nas variáveis relacionadas a densidade mineral óssea com o treinamento. Conclusão: Concluiu-se que o treinamento combinado deve ser recomendado como forma de tratamento não-farmacológico para mulheres pós menopáusicas com câncer de mama em uso de inibidores da aromatase. O treinamento combinado, também pode ser considerado uma estratégia importante para melhorar a saúde e qualidade de vida, como também, minimizar os efeitos colaterais do tratamento para o câncer de mama e diminuir os impactos causados pela menopausa e pelo processo de envelhecimento. / Introduction: Breast cancer is a multifactorial disease with several types of treatment, including chemotherapy, radiation therapy and hormone therapy. Aromatase inhibitors are part of endocrine therapy and are considered effective medicines for breast cancer, which promote less chance of relapse and metastasis. However, side effects of cancer treatment are several, including changes in body composition (decreased bone mineral density and increased fat percentage), metabolic dysfunction and worsening of quality of life. Thus, combined (strength plus aerobic) training may be an interesting strategy to minimize the side effects of treatment for breast cancer and to promote improvements in these variables. Objective: To analyze the chronic effect of combined training on body composition, metabolic variables and quality of life of postmenopausal women who are being treated for breast cancer with aromatase inhibitors. Methods: The sample consisted of postmenopausal women who had breast cancer and who used aromatase inhibitors distributed in two groups: intervention group (combined training) and control group (stretching). The following evaluations were performed: body composition by DXA (body fat, lean mass and bone mineral density), blood biochemical analyzes: total cholesterol and fractions (HDL, LDL, non HDL), triglycerides, glycemia, C-reactive protein, bone markers (CTX and osteocalcin), and quality of life. The intervention was with combined training (strength plus aerobic), three times weekly, with resistance exercises performed on machines (40 minutes / session), followed by aerobic training on an electric treadmill (30 minutes / session). The intervention lasted nine months and the evaluations were done at the initial moments, three, six and nine months. Statistical analyzes were performed from Anova Two-way - repeated measures, using statistical software SPSS version 24.0, with significance at 5%. Results: According to the analysis, combined training was effective to promote changes in body composition (decrease of total body fat, total body fat, total body fat and trunk), metabolic variables (LDL decrease) Quality of life. When compared to the control group, no differences were observed in the variables related to bone mineral density with the training. Conclusion: Concluded that combined training should be recommended as a form of non-pharmacological treatment for postmenopausal women with breast cancer. Combined training can also be considered an important strategy for improving health, and quality of life, as well as minimizing the side effects of treatment for breast cancer and reducing the impact caused by menopause and the aging process.

Background: In recent years, compounded bioidentical hormone therapy (CBHT) has emerged as a popular alternative to manufactured, FDA approved hormone therapy (HT)-despite concerns within the medical community and the availability of new FDA approved "bioidentical" products. This study aims to characterize the motivations for using CBHT in a U.S. sample of ordinary midlife women. Methods: We analyze data collected from 21 current and former users of CBHT who participated in a larger qualitative study of menopausal decision-making among U.S. women. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed thematically using an iterative inductive and deductive process. Results: Although women's individual motivations varied, two overarching themes emerged: "push motivations" that drove women away from conventional HT and from alternative therapies, and "pull motivations" that attracted women to CBHT. Push motivations focused on (1) fear and uncertainty about the safety of conventional HT, (2) an aversion to conjugated estrogens in particular, and (3) and overarching distrust of a medical system perceived as dismissive of their concerns and overly reliant on pharmaceuticals. Participants also voiced dissatisfaction with the effectiveness of herbal and soy supplements. Participants were attracted to CBHT because they perceive it to be (1) effective in managing menopausal symptoms, (2) safer than conventional HT, (3) tailored to their individual bodies and needs, and (4) accompanied by enhanced clinical care and attention. Conclusions: This study finds that women draw upon a range of "push" and "pull" motivations in their decision to use CBHT. Importantly, we find that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care where their menopausal experience is solicited, their treatment goals are heard, and they are engaged as agents in managing their own menopause. The significance of this finding goes beyond understanding why women choose CBHT. Women making menopause treatment decisions of all kinds would benefit from greater shared decision-making in the clinical context in which they are explicitly invited to share their experiences, priorities, and preferences. This would also provide an opportunity for clinicians to discuss the pros and cons of conventional HT, CBHT, and other approaches to managing menopause.

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. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

Context: The Women’s Health Initiative (WHI) study, published in July 2002, had a significant impact on the prescribing of hormone replacement therapy (HRT). The controversy surrounding the findings, however, has led to much uncertainty regarding the prescription of HRT. Aims and Objectives: The aim of this study is to determine both the initial and the continued impact of the WHI study on the prescribing of HRT in a defined South African population and to determine whether HRT was appropriately individualised based on recommendations published subsequent to the WHI study. Setting: Claims data from a Managed Healthcare Organisation (MHO) that administers for a number of medical aid schemes in South Africa. Method: A retrospective drug utilisation review (DUR) was conducted to identify HRT-related prescribing patterns in the defined populations. The time-frame of the dataset included January 2002, to assess prescribing patterns prior to the publication of the WHI study, January 2003 to determine the initial impact of the WHI study, and January 2005 to assess the continued impact. An extensive, additional dataset of all the HRT users in the defined populations was utilised to conduct a sub-group analysis and determine whether HRT had been appropriately individualised. Key Findings: The percentage of patients in the dataset using HRT decreased from 30.05 percent in January 2002 to 28.30 percent in January 2003 and to 23.24 percent in January 2005, with the latter decrease reaching statistical significance. Although sex hormones and modulators (G03) of the genital system were the most frequently prescribed drug class in all three years of the study period, the prescribing frequency decreased significantly from 10.40 percent in January 2002 to 9.32 percent in January 2003 and 7.44 percent in January 2005. The most noteworthy change in the prescribing of HRT was a 3.95 percent decrease in the prescribing of conjugated equine estrogen (CEE), with a corresponding 2.53 percent increase in the prescribing of estradiol between January 2002 and January 2003. However, less pronounced changes were observed in the prescribing frequencies of other types of HRT, including medroxyprogesterone and estrogen (the HRT type investigated in the estrogen plus progestin phase of the WHI study). Patients initiating HRT post-WHI publication were generally found to be in the younger menopausal age categories (40 to 49 years). These patients were more likely to have been initiated on HRT types other than those investigated in the WHI study and were at a higher risk for disease states for which HRT use is beneficial, such as osteoporosis. Patients discontinuing HRT post-WHI publication were generally found to be in the older menopausal age categories (60 to 69 years), were more likely to have been combined HRT users (although not necessarily the type investigated in the WHI study) and were at a higher risk for disease states for which HRT use is considered harmful or has an uncertain effect, such as diseases affecting the cardiovascular system. Conclusion: It can be concluded that the WHI study did have an impact on the prescribing of HRT in the defined South African population of this study, but that the impact was considerably less than the impact reported in global studies. It was also determined that HRT was appropriately individualised according to recommendations made subsequent to publication of the WHI study.

Orientadores: Cristina Laguna Benetti Pinto, Rose Luce Gomes do Amaral / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T09:13:50Z (GMT). No. of bitstreams: 1 GiraldoSouza_HelenaPatriciaDonovan_M.pdf: 2305470 bytes, checksum: add3640d7732bc5676b5b9eb414466b0 (MD5) Previous issue date: 2015 / Resumo: Introdução: Insuficiência Ovariana Prematura 46XX (IOP) é um estado de hipogonadismo, caracterizado por oligoamenorréia, infertilidade e deficiência estrogênica em mulheres abaixo de 40 anos. Mulheres com IOP deveriam ser tratadas com reposição estrogênica até pelo menos a idade da menopausa, para reduzir os sinais e sintomas do hipoestrogenismo e se possível, preservar a massa mineral óssea. Objetivos: Avaliar se Terapia Hormonal (TH) com baixa dose estrogênica é adequada para reduzir a perda de massa óssea de mulheres com IOP. Métodos: Estudo de corte transversal. Foram avaliadas 239 mulheres com IOP: 132 usando TH baixa dose (17-Beta-Estradiol 1mg + Noretisterona ou estrogênio conjugado 0,625mg + acetado de Medroxiprogesterona) e 107 mulheres sem TH. Todas responderam anamnese detalhada (idade, idade na última menstruação e idade no início de tratamento) e foram submetidas a avaliação de densidade mineral óssea (DMO) na coluna lombar (CL), colo femoral (CF) e fêmur total (FT) através da técnica DEXA. Resultados: As médias de idade, idade na última menstruação e de IMC para o grupo sem tratamento e para o grupo com TH foram 38,1 ± 6,1 e 36,8 ± 7,3 anos; 31,4 ± 7,3 e 30,7 ± 7,2 anos; 26,6 ± 7,1 e 25,8 ± 4,6, respectivamente (p=NS). A DMO média na CL foi 1,06 ± 0,15 e 1,00 ± 0,17g/cm2 (p=0,003), para CF 0,92 ± 0,15 e 0,89 ± 0,14 (p=0,0479) e FT de 0,92 ± 0,19 e 0,91 ± 0,13 g/cm2 (p=0,039), respectivamente para os grupos. Verificou-se DMO alterada na CL em 45,1% (35,2% Osteopenia e 9,8% Osteoporose) das mulheres sem tratamento e 60,1% (38,1 Osteopenia e 22% Osteoporose) quando usavam TH baixa dose (p=0,01). No CF 25,4% (21,5% Osteopenia e 3,9% Osteoporose) das mulheres sem tratamento e 29,6% (22,8% Osteopenia e 6,7% Osteoporose) quando usavam TH baixa dose (p=0,38) mostravam alteração e, para FT, em 32,35% (19,6% Osteopenia e 12,7% Osteoporose) das sem tratamento e 36,4% (21,2% Osteopenia e 15,2% Osteoporose) para TH de baixa dose (p=0,34). Conclusão: A TH de baixa dose não parece ser adequada para reduzir a perda de massa óssea de coluna lombar, colo de fêmur e fêmur total em mulheres com IOP / Abstract: Introduction: Premature Ovarian Insufficiency (POI) is a hypogonadism state, characterized by oligoamenorhea, infertility and estrogen deficiency in women below the age of 40. Women with POI should be treated with estrogen replacement until at least the age of menopause, in order to reduce the signs and symptoms of hypoestrogenism and if possible, preserve bone mineral density (BMD). Aim: To assess whether hormone therapy (HT) with low estrogen dose is sufficient to avoid bone mass loss in women with POI. Methods: Cross-sectional study. Two hundred and thirty nine women were evaluated: 132 using low dose TH (1 mg of 17-Beta-Oestradiol + Norethisterone or 0.625 mg of conjugated estrogen + medroxyprogesterone acetate) and 107 women without HT. Detailed history was obtained from the studied women (age, age of last menstrual period and age of onset of treatment) and were subjected to evaluation of bone mineral density (BMD) in the lumbar spine (LS), femoral neck (FN) and total femur (TF) through DEXA technique. Results: The mean age, age at last menstrual period and BMI for the untreated group and the group with HT were 38.1 ± 6.1 and 36.8 ± 7.3 years; 31.4 ± 7.3 and 30.7 ± 7.2 years; 26.6 ± 7.1 and 25.8 ± 4.6 respectively (p = NS). The mean LS BMD was 1.06 ± 0.15 and 1.00 ± 0,17g / cm2 (p = 0.003), CF 0.92 ± 0.15 and 0.89 ± 0.14 (p = 0.0479) and FT 0.92 ± 0.19 and 0.91 ± 0.13 g / cm2 (p = 0.039) respectively for the groups. BMD at LS was compromised in 45.1% (35.2% osteopenia and osteoporosis 9.8%) for women without treatment and 60.1% (38.1% osteopenia and 22% osteoporosis) low dose HT (p = 0.01). For the FN 25.4% (21.5% Osteopenia and Osteoporosis 3.9%) of women without treatment and 29.6% (22.8% Osteopenia and Osteoporosis 6.7%) for the ones in use of TH low dose, were compromised (p = 0 38). For TF compromise was found in 32.35% (19.6% osteopenia and 12.7% osteoporosis) of the untreated women and 36.4% (21.2% and 15.2% osteoporosis osteopenia) for low dose HT (p = 0.34). Conclusion: The low dose HT seems to be inadequate to reduce bone loss in the lumbar spine, femoral neck and total femur in women with IOP / Mestrado / Fisiopatologia Ginecológica / Mestra em Ciências da Saúde

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