Durante a transição menopausal e a pós-menopausa cerca de 75% das mulheres apresentam sintomas de hipoestrogenismo, tais como fogachos. O emprego de terapia hormonal (TH) para alívio dos sintomas da menopausa está bem estabelecido, mas seus efeitos cardiovasculares (CV) permanecem controversos. Dados de estudos recentes indicam a presença de duas populações distintas quanto aos efeitos CV da TH. Essa diferenciação estaria relacionada principalmente com a idade e o tempo de pós-menopausa. Evidências sugerem também que a presença de fatores de risco cardiovascular antes do início do TH, ou de uma associação de fatores de risco, podem ser determinantes dos efeitos CV do TH. Dose de medicação, via de administração e o tipo de progestogênio utilizado em associação com estrogênio para TH também vem sendo estudados como possíveis fatores relacionados ao impacto CV do TH. O presente trabalho é composto por: 1) Ensaio clínico randomizado, comparando os efeitos da via oral baixa dose e via não oral sobre variáveis relacionadas com risco CV em uma população de mulheres saudáveis na pósmenopausa recente; 2) Ensaio clínico randomizado, onde foram avaliados os efeitos da adição de progesterona natural micronizada ao estrogênio não oral durante TH em mulheres na pós-menopausa recente; e 3) Revisão sistemática e meta-análise, onde foram sistematicamente buscados todos os artigos com TH baixa dose que avaliassem os efeitos desta terapia sobre variáveis relacionadas com risco cardiovascular: peso, índice de massa corporal, pressão arterial, proteína C reativa e lipídios. Desenvolvemos ensaio clínico randomizado, cross-over, com objetivo de avaliar os efeitos de dois tipos de tratamento hormonal na menopausa: oral baixa dose, estradiol 1 mg e drospirenona 2 mg diário e não oral, estradiol 17 β gel 1.5 mg (ou nasal 300 mcg) diário e progesterona micronizada vaginal, 200 mg, 14 dias por mês, sobre peptídeo natriurético atrial, variáveis relacionadas com inflamação e função endotelial, perfil antropométrico e metabólico em mulheres na pós-menopausa recente e sem doença clínica evidente. 101 mulheres na pós-menopausa foram alocadas aleatoriamente para iniciar o TH por um dos dois grupos de tratamento: via oral baixa dose (n=50) ou via não oral (n=51). Todas as pacientes utilizaram ambos os TH de forma seqüencial. Após o primeiro período de 2 a 3 meses de TH a paciente passava para o segundo tratamento, sem período de washout. A avaliação laboratorial foi realizada antes e após cada um dos tratamentos. A amostra do estudo foi composta por mulheres com média etária de 51 ± 3 anos e tempo de amenorréia de 22 ± 10 meses. Oitenta e seis pacientes concluíram o estudo. Peso e índice de massa corporal não se modificaram, enquanto que a circunferência da cintura reduziu de forma similar em ambos os grupos de tratamento. Colesterol total e LDL-C reduziram após ambos os TH, e triglicerídeos reduziram somente após a TH não oral. Insulina e glicemia de jejum não se modificaram. Não foram observadas modificações nos níveis de fibrinogênio, fator von Willebrand (FvW) e proteína C reativa (PCR) após TH oral. Após TH não oral, observou-se redução significativa de fibrinogênio e FvW. Níveis de PCR não se modificaram. Houve redução do número de pacientes no maior tertil de PCR (alto risco CV) após TH não oral. Essas pacientes passaram a integrar os grupos de risco intermediário e baixo. Níveis de peptídeo natriurético atrial (PNA) mantiveram-se inalterados após os ambos os TH. Não houve modificações significativas na pressão arterial e esta não se correlacionou com valores de PNA. Realizamos análise adicional do TH não oral, quanto às diferenças entre a via nasal e a percutânea e quanto aos efeitos da adição de progesterona natural micronizada ao estrogênio. Não houve diferenças significativas para todas as variáveis estudadas entre a via nasal e a via percutânea. A adição de progesterona natural micronizada não modificou os efeitos metabólicos e CV do estrogênio não oral. Foi realizada busca sistemática de todos os artigos que incluíssem como TH estrogênio baixa dose e avaliassem os efeitos deste tratamento sobre as variáveis de interesse: peso, índice de massa corporal, pressão arterial, proteína C reativa e lipídeos. Foram consultadas as bases MEDLINE, Cochrane CENTRAL, EMBASE. Foram revisadas todas as referências dos artigos de interesse e revisões e metaanálises no assunto, em busca de artigos relevantes. Após exclusão dos artigos em duplicata, 8610 artigos foram revisados. Destes, 28 artigos foram selecionados para meta-análise. Desta análise foi possível concluir que pacientes em uso de TH baixa dose apresentaram em média menor peso corporal, colesterol total e LDL-C do que não usuárias. A TH baixa dose não apresentou efeitos deletérios sobre demais variáveis estudadas. Em conclusão, ambos os TH apresentaram efeitos neutros ou benéficos sobre variáveis relacionadas com risco CV em uma população de mulheres na pósmenopausa recente e sem evidência de doença CV. A adição de progesterona natural micronizada não modificou os efeitos do estrogênio não oral. Os resultados da metaanálise sobre TH baixa dose e variáveis relacionadas com risco CV também permitem concluir que a TH baixa dose não exerceu efeitos deletérios sobre lipídeos e pressão arterial, e foi observado um possível efeito benéfico deste tratamento sobre o peso corporal. / During the menopausal transition and postmenopause about 75% of women have symptoms of hypoestrogenism symptoms such as hot flushes. The use of hormone therapy (HT) for relief of menopausal symptoms is well established, but its cardiovascular effects (CV) remain controversial. Data from more recent studies suggest the presence of two distinct populations regarding the cardiovascular effects of HT. This differentiation is related mainly to age and time after menopause. Evidence also suggests that the presence of cardiovascular risk factors before the onset of HT, or a combination of risk factors may be determinants of CV effects of HT. Medication dose, route of administration and type of progestin used in combination with estrogen for HT has also been studied as possible factors related to the CV impact of HT. This work consists of: 1) Randomized clinical trial, comparing the effects of low dose oral and non-oral route of variables related to CV risk in a population of healthy women in early postmenopausal; 2) A randomized clinical trial, which we assessed the effects of the addition of natural micronized progesterone to non-oral estrogen for HT in women in early postmenopausal; and 3) systematic review and meta-analysis, which were systematically searched all items with low-dose HT to assess the effects of this therapy on variables related to cardiovascular risk: weight, body mass index, blood pressure, C-reactive protein and lipids. A cross-over, randomized clinical trial was designed in order to evaluate the effects of two types of HT: low dose oral treatment, estradiol oral 1 mg and drospirenone 2 mg, by day and non-oral treatment, estradiol 1.5 mg 17 β gel by percutaneous route (or nasal route 300 mcg) by day and vaginal micronized progesterone, 200 mg/d, 14 days by month on atrial natriuretic peptide, variables associated with inflammation and endothelial function, anthropometric and metabolic variables on early and healthy postmenopausal women. One hundred one women were randomly allocated to start with one of the treatments: low dose oral treatment (n=50) or non-oral treatment (n=51). At the end the first three months period, the patients were crossed over without washout for an additional three months. Laboratory evaluated were carried before and after oral and non-oral HT. The sample of the study included postmenopausal women with a mean age of 51 years and duration of amenorrhea of 22±10 months. Eighty-six patients completed the study. Weight and body mass index remained unchanged, while the waist circumference decreased similarly in both treatment groups. Total cholesterol and LDL-cholesterol reduced after both the HT and triglycerides reduced only after nonoral HT. Insulin and fasting glucose did not change. No changes were observed in the levels of fibrinogen, von Willebrand factor (vWF) and C-reactive protein (CRP) after oral HT. After non-oral HT, there was a significant reduction of fibrinogen and vWF. CRP levels did not change. There was a reduction in the number of patients in the highest tertile of CRP (high CV risk) after non-oral HT. These patients have joined the groups of intermediate and low risk. Levels of atrial natriuretic peptide, ANP, were unchanged after both HT. There were no significant changes on blood pressure and did not correlate with values of ANP. We performed additional analysis of nonoral HT, for the differences between nasal and percutaneous and about the effects of addition of natural micronized progesterone to estrogen. There were no significant differences for all the variables studied between the nasal and percutaneously. The addition of micronized natural progesterone did not modify the metabolic and CV effects of non-oral estrogen. Systematic search of all articles that include as TH low dose estrogen and evaluate the effects of this treatment on the variables of interest was taken: weight, body mass index, blood pressure, C-reactive protein and lipids. The MEDLINE, Cochrane CENTRAL, EMBASE databases were consulted. All references of interest and reviews and meta-analyzes on the subject, in search of relevant articles were reviewed. After removing duplicate articles, 8610 articles were reviewed. Of these, 28 articles were selected for meta-analysis. From this analysis it was concluded that patients using low-dose TH had on average lower body weight, total cholesterol and LDL-C than non-users. The TH low dose showed no deleterious effects on other variables. In conclusion, low-dose oral and non-oral treatments had neutral or beneficial effects on variables related to CV risk in a population of women in early post menopausal and without evidence of CV disease. The addition of micronized natural progesterone did not modify the effects of non-oral estrogen. The results of the metaanalysis of low dose and TH variables related CV risk also showed that the TH low dose did not exert deleterious effects on lipids and blood pressure, and a possible beneficial effect of this treatment on body weight was observed.

La contraception hormonale combinée (CHC) est la contraception la plus utilisée en France. La maladie veineuse thromboembolique (MVTE), constitue le principal effet délétère de ces CHC. Des recommandations de bonnes pratiques sont publiées pour guider les prescripteurs. La meilleure compréhension des modifications biologiques associées aux différents types de CHC, les caractéristiques cliniques des femmes ayant eu une MVTE, la place de la recherche d’antécédents familiaux de MVTE (AFVTE) et d’une thrombophilie biologique avant la prescription d’une CHC constituent des pistes de recherche qui permettrait potentiellement d’optimiser la balance bénéfice-risque des CHC. Enfin l’impact de l’utilisation d’une contraception hormonale après un 1er épisode de MVTE reste peu évalué. Ce travail de thèse a été réalisé à la fois à l’aide de données biologiques d’utilisatrices de contraceptions hormonales (Etude EDGAR) et aussi à partir des données de l’étude de cohorte française COREVE (COntraception and REcurrent Venous Event). Cette étude a inclus 3121 femmes de moins de 45 ans au moment de leur 1er épisode de MVTE. Nous nous sommes particulièrement intéressés à l’analyse des caractéristiques de ces femmes en fonction du type de contraception utilisée, à la prévalence des facteurs de risque vasculaires et notamment les AFVTE. La fréquence d’épisode de MVTE associé à une prescription inadaptée de CHC, variait ainsi de 8.8 à 25.9 %. Par ailleurs, à l’aide d’une méthodologie de type cas versus cas, l’interaction entre l’utilisation d’une CHC et la présence d’une mutation du facteur V Leiden sur le risque de MVTE diffère significativement en fonction du progestatif combiné des CHC. / Combined hormonal contraception (CHC) is the most widely used contraception in France in which venous thrombosis embolism (VTE) is the main deleterious effect. Best practice recommendations are published in order to guide prescribers.The better understanding of the biological changes associated with different types of CHC, the clinical characteristics of women with VTE, the place of family history of VTE (FHVTE) and for biological thrombophilia before prescribing a CHC constitute research paths that could potentially optimize the risk-benefit balance of CHCs. Finally, the impact of hormonal contraception use after a first episode of VTE remains rarely evaluated.This work was carried out both using biological data from hormonal contraception users (EDGAR study) and also using data from the French cohort study COREVE (COntraception and REcurrent Venous Event).This study included 3121 women under 45 at the time of their 1st episode of VTE. We were particularly interested in analyzing the characteristics of these women according to the type of contraception used, the prevalence of vascular risk factors and especially the FHVTE.The frequency of VTE episode associated with an inadequate CHC prescription varied from 8.8 to 25.9%. Moreover, using a case-only methodology, the interaction between the use of CHC and the presence of a mutation of the factor V Leiden on the risk of VTE differs significantly depending on the progestin combined of the CHCs.

In the theoretical part of my thesis I define the illness, venous thromboembolic disease. The theoretical principles are used to determine the risks of the disease onset in women, primarily focused on the risk related to the hormonal contraception usage and the hormone replacement therapy. Attention is paid to the diagnosis, treatment and prevention of the DVT as well. In the following chapters the readers will be apprised with the treatment procedures, primarily from the nursing care perspective. The theoretical part of the thesis will be concluded with the casuistry of patient who suffers the thromboembolic disease and who was in my personal nursing care. The empirical part of my thesis is aimed on the qualitative and related quantitative research, which will be carry out by the help of the questionnaire. The questionnaire is based on the outcoume of the data analysis (casuistry) gained at the Clinic of Cardiology, FN Motol. The questionnaire is distributed and determined for wide group of women from non-medical environment (layman). The results of my research are giving the respons on the thesis's goals and hypotheses. The maion goal of my thesis is to define the women awareness of thromboembolic disease risks, in connection with the hormonal contraception usage and the hormone replacement...

Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The diploma thesis is focused on the social aspects of women's oral hormonal contraception in the lives of two generations of women - daughters and their mothers. The theoretical part introduces the fundamental concepts of contraception research based on gender perspective. It also highlights the important historical milestones related to so-called birth control pill. Furthermore, the development of the contraceptive behavior of the Czech population since the 50s of the 20th century is analyzed. The empirical part of this thesis includes the description of methodology and the analysis of semi-structured interviews with ten women - mothers who were born in the 1960s and their daughters born around the turn of the 80s and 90s. The aim of the analysis is to discover how a generally accepted theory about contraception as the emancipation mechanism that helps women to control their own body and decide about their own reproduction is expressed in the lives of interviewed women. I ask the reason why, when and under what conditions these women decided to use birth control pills and the role of other circumstances in their decision-making. Moreover, I focus on the way how the birth control pills affect the relationship to own body and self-esteem of my respondents. And also, how birth control pills affect...

In der vorliegenden Arbeit wird die Anwendung der Lewis-Säure vermittelten Cycloadditionen von Allylsilanen an alpha,beta-ungesättigte Carbonylverbindungen beschrieben. Das Sesquiterpen Isocomen wurde unter Anwendung der [3+2]-Cycloaddition an Enone synthetisch hergestellt. Die [2+2]-Cycloaddition an Acrylsäurederivate wurde angewandt für einen Einstieg zur Totalsynthese des Oleander Scale Pheromons. Im zweiten Teil der Arbeit wird die Synthese hormonell aktiver Cholesterinderivate dargestellt. Ausgehend von kommerziell erhältlichen Substanzen wurden verschiedene Substituenten in das Steroidgerüst eingeführt.

Hormones influence life of all animals. Not only they affect physiological changes in organisms, but also impact their behaviour. This work focuses at two main groups of steroid hormones: glucocorticoids and androgens. Glucocortiods are activated in response to stress. Their levels can be measured using non-invasive methods, which have a range of advantages. The main advantage is the feedback-free sample collection for enzyme immunoassay. As the measurement involves metabolites of the hormones rather than the hormones themselves, prior validation of the method is, however, necessary. This work reports on a study aiming to validate non-invasive measurement on the Madagascar Ground Gecko (Paroedura Picta). The validation was based on ACTH challenge test: Synacthen Depot was injected, which should lead to increased blood level of glucocorticoids. The validation, however, was not successful. The measurement did not discover significant increase in the levels of the metabolites of glucocorticoids. In addition, the work focuses on behavioural effects of testosterone, the primary androgen. Hormonal manipulations have been carried out on several male and female specimens. The results have discovered differences in sexual behaviour between control groups. On the other hand, the hormonal manipulations had no...

Moral aspects of contraception from the perspective of present catholic couples Most women in productive age choose any form of conception control. Catholic Church accepts only natural contraceptive methods. Fertility awareness-based methods are cheap, ecological but for necessity of managing the method more complicated forms of contraception. It is also little promoted and by doctors mostly considered to be less reliable and that's why it is not often recommended by gynecologists in contrast to widely promoted and used hormonal contraception. The topic of this dissertation is how do present catholic couples cope with this problem. The aim of the work is to give comprehensive description of basic types of in present used contraception and after that bring the view of particular contraception methods from the perspective of the Catholic Church doctrine. By the questionnaire survey in practical part is evaluated what are the attitudes of present catholic coulpes to contraception in comparison with official Catholic Church doctrine. Keywords catholic couples, contraception, fertility awareness-based methods, symptothermal method, hormonal contraception