Contexte : Il est établi que les traitements hormonaux de la ménopause à base d’estroprogestatifs augmentent le risque de cancer du sein, mais ce risque pourrait varier selon les types de progestatifs utilisés. Par ailleurs, le rôle des traitements à base de progestatifs seuls dans le cancer du sein a été peu étudié. Du fait des particularités françaises dans la prescription de ces traitements, nous avons analysé le risque de cancer du sein en fonction des types de traitement hormonaux prescrits chez les femmes en France.Le surpoids et l’obésité sont associés à une diminution du risque de cancer du sein en préménopause, mais augmentent le risque en période post-ménopausique. Les mécanismes sous-jacents ne sont pas complètement élucidés et des questions restent en suspens quant au rôle du gain de poids à différentes périodes de la vie. Méthodes : Ce travail porte sur les données d’une étude cas-témoins réalisée en population générale en France, incluant 1232 cas et 1317 témoins recrutés chez les femmes des deux départements d’Ille-et-Vilaine et de Côte d’Or, entre 2005 et 2007. Des informations détaillées sur l'utilisation des traitements hormonaux, sur le poids à différentes périodes de la vie et sur diverses caractéristiques reproductives et médicales ont été obtenues au cours d'entretiens en face-à-face. Les odds ratios et intervalles de confiance à 95% après ajustement sur les facteurs de risque du cancer du sein ont été calculés à l’aide de modèles de régression logistique. Des analyses de trajectoires d’indice de masse corporelle entre l’âge de 20 ans et l’âge au moment du diagnostic ont été pratiquées.Résultats : Le risque de cancer du sein était augmenté chez les utilisatrices de progestatifs de synthèse combinés ou non avec un estrogène. Ce risque était restreint à la prise récente du traitement hormonal et augmentait avec la durée d’utilisation. A l’inverse, les traitements à base de progestérone naturelle n’étaient pas associés à une augmentation du risque de cancer du sein. Chez les femmes non ménopausées, un IMC élevé et un gain de poids antérieur étaient associés à une diminution du risque de cancer du sein. Chez les femmes ménopausées, seul un gain de poids dans la période précédant la ménopause (entre 40 et 50 ans) était associé à une augmentation du risque de cancer du sein. Cette association était plus marquée chez les femmes maigres à 20 ans (IMC≤ 18,5 kg/m²), ou chez les femmes plus âgées. Conclusion : Ce travail confirme d’une part les effets cancérogènes des traitements hormonaux à base de progestatifs de synthèse, et d’autre part l’absence d’effet délétère de la progestérone naturelle sur le risque de cancer du sein. L’utilisation de progestérone naturelle doit toutefois être évaluée au regard des bénéfices et des risques qu’elle peut entraîner. Nous avons également pu préciser les relations existant entre le gain de poids et le risque de cancer du sein, et suggéré qu’un gain de poids pendant la période précédant la ménopause pouvait être plus favorable à la survenue de cancer du sein en post-ménopause. / Background: There is evidence that menopausal combined estrogen-progestagen therapy increases the risk of breast cancer, but the risk may vary depending on the types of progestagen used. Moreover, the role of progestagen-only therapy in breast cancer has been little studied. Because of French specificities in prescribing these treatments, we analyzed the risk of breast cancer based on these different types of hormone treatment prescribed among women in France.Overweight and obesity are associated with a reduced risk of premenopausal breast cancer, but increase the risk in postmenopausal period. The underlying mechanisms are not fully understood, and questions remain about the role of weight gain in different periods of life.Methods: This work relates on data from a case-control study in the general population in France, including 1232 cases and 1317 controls recruited among women in two departments of Ille-et-Vilaine and Côte d'Or, between 2005 and 2007. Detailed information on hormonal treatments use, on weight at different periods of life and various reproductive and medical characteristics were obtained during a face-to-face interview. Odds ratios and 95% confidence intervals after adjustment for breast cancer risk factors were calculated using logistic regression models. Analyzes of BMI trajectories between the age of 20 and the age at diagnosis were performed.Results: The risk of breast cancer was increased in users of synthetic progestagen combined or not combined with an estrogen. This risk was restricted to the recent use of the hormone treatment and increased with the duration of use. Conversely, the natural progesterone based treatment was not associated with an increased risk of breast cancer.In premenopausal women, higher BMI and a previous weight gain were associated with a decreased risk of breast cancer. In postmenopausal women, only weight gain in the period preceding the menopause (40 to 50 years) was associated with an increased risk of breast cancer. This association was stronger among women who were lean women at the age of 20 (IMC≤ 18.5 kg / m²), or in older women.Conclusion: This study confirms the carcinogenic effects of hormonal treatments with synthetic progestagen, and the absence of deleterious effects of natural progesterone on breast cancer risk. However, the use of natural progesterone must be evaluated according to the benefits and risks that may result. We could also clarify the relationship between weight gain and the risk of breast cancer, and suggested that weight gain during the period before menopause could be more favorable to the occurrence of breast cancer in post-menopausal .

A deficiência androgênica acomete um percentual de homens idosos ainda não bem definido na literatura. São usados parâmetros séricos hormonais de homens jovens, e apesar disto, a terapia de reposição da testosterona vem sendo defendida e utilizada largamente por muitos autores. Várias vias de reposição são usadas tentando simular o ciclo fisiológico de produção das testosteronas. Parece que a transdérmica é a que mais se aproxima do ideal. A relação câncer de próstata e testosterona é pouco compreendida. O receio do estímulo de um câncer oculto pela terapia de reposição não foi devidamente afastado. O tratamento deve ser instituído quando o quadro clínico e laboratorial for evidente. / The androgenic deficiency attacks a percentage of elderly men not well defined in literature yet. Hormonal serum parameters of young men are used and, in spite of that, the testosterone replacement therapy has been widely supported and used by many authors. Various ways of replacement are used trying to simulate the physiological cycle of the testosterone production. It seems that the transdermic is the one closest to the ideal. The relation of prostate cancer and testosterone is little understood. The fear of the stimulation of a concealed cancer by the replacement therapy has not been properly eliminated. The treatment should be indicated when the clinical and laboratorial was defined.

Arapaima gigas is the largest scaled freshwater fish in the world reaching over 250 kg. With growth rates of 10 kg+ within 12 months, A. gigas is considered as a promising candidate species for aquaculture development in South America. However, the lack of reproductive control in captivity is hindering the industry expansion. The work carried out in this doctoral thesis therefore aimed to better understand the species’ reproductive physiology, develop tools to identify gender and monitor gonad development, test hormonal therapies to induce ovulation and spawning and characterise the cephalic secretion for its potential roles in pheromone release and during parental care. Initially, a genomic study investigated the overall extent of polymorphism in A. gigas, which was found to be surprisingly low, with only 2.3 % of identified RAD-tags (135 bases long) containing SNPs. Then, a panel with 293 single nucleotide polymorphism (SNP) was used to characterise the genetic diversity and structure of a range of Amazon populations. Results revealed populations from the Amazon and Solimões appeared to be genetically different from the Araguaia population, while Tocantins population comprised individuals from both stocks. This data provided a tool for broodstock identification and future management. The PhD then aimed to evaluate the effects of slow-release mGnRH implants and different broodstock size pairings on maturation and spawning. Results showed that the implants stimulated the brain-pituitary-gonad axis resulting in increased plasma levels of testosterone (females) and 11-ketotestosterone in males, respectively regardless of pairing sizes. However, no spawning was observed. Results also showed the release of sex steroids with potential pheromonal action through the cephalic secretion, a biological fluid released from the adult head along the reproductive period. Thereafter, a non-surgical field endoscopy method was developed and validated for ovarian assessment and gender identification. The method was then used to describe the female gonopore and obtain biopsy of the ovary through cannulation which allowed the description of oogenesis in A. gigas. Importantly, oocytes obtained by cannulation confirmed that adult females under investigation were maturing with oocytes in final maturation stage but failed to ovulate/spawn. Another hormonal induction trial was therefore performed in which a combination of GnRHa (mGnRHa/sGnRHa) was used by injection to induce ovulation and spawning in selected maturing females with effects on oocyte maturation monitored post-induction through biopsy. However, this trial appeared to not be successful at inducing ovulation or spawning. Finally, the peptidome and proteome of the cephalic secretion was further characterised through the comparison between parental and non-parental fish. Results highlighted the complex role of this biological fluid including potential roles on the developing offspring during the parental care period. Overall, this doctoral thesis provided new basic and applied data on A. gigas reproduction and tools that can be used in future studies to better understand the environmental and hormonal control of oogenesis and spawning.

Made available in DSpace on 2016-04-28T14:16:24Z (GMT). No. of bitstreams: 1 Joelma Ramos Santana.pdf: 1423651 bytes, checksum: 8780200329c93a76a016c2383c8ba409 (MD5) Previous issue date: 2016-03-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present study sought to analyze contextual and historiographical aspects related with the diffusion of oral contraception, particularly among women, along the period of its introduction and initial commercialization in Brazil (1962-1972). Therefore we analyzed how the information on the mode of action of the pill on the female body, related implications and alleged risks and benefits was divulgated. For that purpose the sources used were magazines and journals commonly read at that time and the biology textbooks used in secondary schools. The result was a mapping of the contemporary scientific ideas on oral contraception and the socio-historical framework that circumscribed its divulgation. Our study shows that while the arrival of the pill in Brazil was a cause of heated debate, it dealt less with scientific than with moral, political and religious issues. The school textbooks, in turn, continued to convey information on reproductive anatomy and physiology outdated in more than 50 years. If mentioned at all, the possibility to control fertility was discussed within the context of eugenic, hygienist or religious ideas / O objetivo do presente trabalho foi explorar aspectos contextuais e historiográficos relacionados à difusão da pílula anticoncepcional, sobretudo entre as mulheres, no período de sua introdução e comercialização, que abrange de 1962 a 1972. Dessa forma, buscou-se analisar como se deu o processo de divulgação da informação sobre o modo de ação do contraceptivo hormonal no organismo feminino, quais eram as implicações associadas e seus supostos riscos e benefícios. A fonte desta pesquisa foram revistas e jornais grande circulação na época e os livros didáticos de biologia destinados ao ensino colegial, resultando num mapeamento das ideias ou argumentos científicos sobre o uso da contracepção oral, assim como do marco sócio-histórico que contornou a divulgação desta. Nosso estudo permitiu conferir que a chegada da pílula causou um intenso debate, menos acerca de questões científicas, que de problemas morais, políticos e religiosas. Quanto aos livros didáticos, continuaram a transmitir conhecimentos sobre anatomia e fisiologia reprodutivas ultrapassados em mais de meio século. O controle da reprodução, quando citado, estava ao serviço de ideias eugenistas e higienistas ou religiosas

Made available in DSpace on 2014-06-11T19:30:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-19Bitstream added on 2014-06-13T19:19:35Z : No. of bitstreams: 1 barbosa_vrn_dr_rcla.pdf: 532811 bytes, checksum: 315204810b83c3ff4321b7490a1779c9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O período de pós-menopausa tem sido associado com maior risco para o ganho de peso e acúmulo de gordura abdominal em mulheres o que pode levar à alta incidência de doenças cardiometabólicas. O exercício físico promove efeitos benéficos sobre esses transtornos. Até o presente momento não foram encontrados na literatura estudos avaliando o efeito do treinamento intervalado em variáveis relacionadas à saúde da mulher. Assim a adiponectina tem sido estudada em diferentes estados patológicos, porém poucos estudos existem avaliando os níveis plasmáticos de adiponectina em mulheres na pós-menopausa. Além disso, o risco de doença cardiovascular aumenta após a menopausa, o qual pode estar relacionado com a resistência à insulina e à rigidez arterial que é um significante preditor da aterosclerose. Portanto, o objetivo deste trabalho foi avaliar o efeito do treinamento físico aeróbio intervalado, por doze semanas, sobre as alterações nas concentrações plasmáticas de nitrito/nitrato e adiponectina em mulheres na pós-menopausa. Foram selecionadas vinte e três mulheres com idade de 55±5 anos, na pós-menopausa, com sobrepeso. As voluntárias foram submetidas a treinamento aeróbio intervalado que foi composto por três ciclos de 10 minutos de duração (totalizando 30 min/sessão) divididos em três momentos: 4 min a 60% da FCreserva; 4 min a 70% da FCreserva; e 2 min com 80% da FCreserva, que consistiu em um treinamento de três dias por semana durante doze semanas; a intensidade foi reajustada na 6ª semana do período de treinamento. Foram realizadas avaliações antropométricas (Índice de Massa Corpórea e Circunferência Abdominal), hemodinâmicas (Pressão Arterial Sistólica, Pressão Arterial Diastólica e Frequência Cardíaca), e cardiorespiratórias com o teste de uma milha, para mensurar a potência aeróbia. As concentrações plasmáticas de... / Post menopause period has been associated with increased risk for weight gain and accumulation of abdominal fat in women which can lead to high incidence of cardiometabolic disease. On the other hand, physical exercise promotes beneficial effects on this disorder. Regarding the influence of intermittent physical exercise on the cardio-metabolic parameters in women after menopause, no studies exist at the present time. Therefore, the purpose of this study was to evaluate the effect of aerobic interval training for twelve (12) weeks, on the plasma nitrite/nitrate and adiponectin levels in postmenopausal women. Twenty-three overweight women were selected with mean age of 55 ± 5 years old. They were submitted to aerobic training intervals consisting of twelve (12) weeks, with a frequency of three sessions per week during 30 minutes of aerobic exercise intensity between 60% and 80% heart rate reserve. The training program was adjusted at 6-week. Anthropometric data were evaluated (body mass index and waist circumference) and hemodynamics parameters (systolic blood pressure, diastolic blood pressure, heart frequency). One mile walking test was also performed to evaluate the cardio-respiratory capacity at the initial and final time of the study. Plasma nitrite/nitrate and adiponectin levels were determined. All data was analyzed before and after aerobic exercise. Our data show that postmenopausal women present a significant reduction in waist circumference (3.8%) without changing in body mass index. The exercise protocol was effective in reducing diastolic blood pressure by 6.7% as well as the time to perform the one mile walking test (3.8%) indicating an improvement in physical fitness. Moreover, there was an increase in VO2max values (baseline: 25.1 ± 0.8, trained: 26.5 +0.9 ml / kg / min) approximately 5.5%, p <0.002. Similarly, plasma adiponectin levels after intermittement aerobic ... (Complete abstract click electronic access below)

Made available in DSpace on 2016-08-19T18:15:54Z (GMT). No. of bitstreams: 1 Ana Maria Nogueira Silva.pdf: 441134 bytes, checksum: 7fdca83931c0bdbbdf8528fe5b39b167 (MD5) Previous issue date: 2007-12-22 / Objetives: To assess the effects between non-treatment (placebo group) and a low dosage estrogen-progestin regimen with norgestimate on changes in mammographic breast density (BD) in postmenopausal women after 12 months of hormone therapy. Methods: A prospective study was performed with 40 postmenopausal patients from Materno-Infantil University Hospital (São Luís, Maranhão), divided into two groups: treated ( n=20) using 1 mg of beta-estradiol (E2) and 1mg of E2 + 90mcg norgestimate (NMG); and control (placebo). One-hundred sixty mammograms were done before and after a 12-month period of hormone therapy and BD between the two exams in each group was compared. BD was measured by two qualitative methods (Wolfe and Breast Image Reporting and Data System BI-RADS classification) by two different observers. Data were analysed using Epi- Info program, with statistical significance of 5%. Interobserver variability from mammograms was considered low in both classifications, as well as there were a high percentage of agreement between the two methods. T-student test was used for means and Fisher test for binomial variables. Results: Both groups were considered homogeneous. Body mass index (BMI) did not change during the study period in both groups. Mammographic breast density s classification according to Wolfe was respectively in treated and placebo groups, N1=12, P1=5, P2=3, DY=0; and N1=11, P1=6, P2=3, DY=0, before and after low dose hormone therapy, with no significant differences. A similar pattern was observed at placebo group using Wolfe classification. There were no significant changes in BD according to BI-RADS category in both groups. Conclusion: Low dosage hormone therapy with norgestimate was not associated with increased BD after 12 months of treatment, supporting current literature. Further studies using devices with better technology in analyzing BD are needed to confirm a stability of breast epithelium with different types of low dosage hormone therapy. / Objetivos: Avaliar mudanças no padrão da densidade mamográfica (DM) com a utilização da terapia estro-progestativa de baixa dose com norgestimato entre mulheres na pós-menopausa durante um período de 1 ano. Metodologia: Realizado estudo prospectivo com 40 pacientes menopausadas do Hospital Universitário Materno-Infantil (São Luís, Maranhão), divididas em dois grupos: tratado (n=20) usando 1 mg de beta-estradiol (E2) e 1mg de E2 + 90mcg de norgestimato (NMG); e controle (placebo). Cento e sessenta mamografias foram realizadas antes e depois de 12 meses de acompanhamento. A DM foi aferida por dois métodos qualitativos (classificação de Wolfe e do Breast Image Reporting and Data System BI-RADS) por dois observadores. Os dados foram analisados e tabulados utilizando-se o programa Epi-Info (alfa=5%). A variabilidade interobservador foi considerada baixa nas duas classificações, assim como houve ótima concordância entre os dois métodos. Os testes t de Student e Fisher foram utilizados para, respectivamente, médias e variáveis binomais. Resultados: Ambos os grupos foram considerados homogêneos. O índice de massa corpórea (IMC) não se alterou durante o período do estudo tanto no grupo A como no B. A classificação de DM no grupo tratado, de acordo com Wolfe foi, respectivamente: N1=12, P1=5, P2=3, DY=0; e N1=11, P1=6, P2=3, DY=0, respectivamente antes e depois da terapia hormonal de baixa dose, sem diferenças estatísticas. Um padrão similar foi também observado no grupo controle. Não houveram mudanças significativas na densidade mamária de acordo com a classificação BI-RADS nos dois grupos. Conclusão: A terapia hormonal de baixa dose com norgestimato não foi associada com aumento de DM após 12 meses de tratamento, ratificando literatura corrente. Há necessidade de melhores tecnologias para avaliar a DM e confirmar a estabilidade do epitélio mamário com diferentes tipos de terapia hormonal de baixa dose.

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.

OBJETIVO: Analisar a sintomatologia climatérica, a função hepática e a hemostasia das pacientes com hepatite crônica pelo vírus C, durante o uso da terapia hormonal. METODOLOGIA: As pacientes foram divididas em dois grupos: Grupo TH (Grupo caso) - 25 pacientes com terapia hormonal transdérmica (50mcg de estradiol e 170 mcg de noretisterona/dia) por 9 meses, e Grupo NT (Grupo controle) - 25 pacientes sem terapia hormonal, ambos com sintomas climatéricos. A menopausa foi confirmada pela dosagem do FSH, LH e estradiol, e a hepatite C foi diagnosticada pela sorologia, PCR (reação em cadeia de polimerase) e biópsia hepática (grau histológico variando de I-IV). Os dois grupos foram avaliados no mês 0, 1,4,7 e 9; sendo a sintomatologia climatérica mensurada através do Índice Menopausal de Kupperman, a função hepática e a hemostasia pelos exames: alanina aminotransferase, aspartato aminotransferase, gama glutamiltransferase, fosfatase alcalina, bilirrubinas, albumina, tempo de protrombina, fator V, fibrinogênio e plaquetas. ANÁLISE ESTATÍSTICA: realizada através do teste t de Student, teste de Mann Whitney e análises de variâncias com medidas repetidas com dois fatores. Após a realização das análises de variâncias, para os efeitos estatisticamente significantes foram realizadas comparações múltiplas através de contrastes ou do método de Dunnett. RESULTADOS: A média da idade das pacientes foi de 53,72 e a da menopausa foi de 47,3 anos. Os escores médios dos sintomas vasomotores, fraqueza, palpitação e a somatória dos valores atribuídos ao índice menopausal de Kupperman sofreram alteração no comportamento ao longo do tempo (p<0,05). Os valores da fosfatase alcalina apresentaram alteração no comportamento ao longo do tempo (p<0,05), entretanto, as demais medidas da função hepática e hemostasia, não apresentaram diferença entre os grupos. CONCLUSÕES: Houve melhora da sintomatologia climatérica. Não houve alteração na hemostasia e na função hepática, exceção feita à fosfatase alcalina que apresentou melhora significativa no Grupo TH a partir do 4º mês; portanto, houve melhora na qualidade de vida, sem interferência na função hepática e na hemostasia. / OBJECTIVE: To analize climacteric symptoms, liver function, hemostasis in patients with chronic viral hepatitis C, during hormone therapy. DESIGN: Patients were divided in two groups: Group TH (Case Group) - 25 patients on transdermal hormone therapy (50mcg of estradiol and 170 mcg of norethisterone/day) for 9 months, and Group NT (Control Group) - 25 hormone-untreated patients, both with climacteric symptoms. Menopause was confirmed by measuring FSH, LH and estradiol, and hepatitis C was diagnosed by serology, PCR (Polymerase Chain Reaction) and liver biopsy (histological type stages I to IV). Both groups were evaluated in the months 0, 1, 4, 7 and 9; and the climacteric symptoms measured by using Kupperman menopausal index, liver function and hemostasis by the following laboratory tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase, alkaline phosphatase, bilirubin, albumin, prothrombin time (PT), factor V, fibrinogen and platelets. STATISTICAL ANALYSIS: Student\'s t test, Mann-Whitney test and two-factor analysis of variance with repeated measures were applied. After analysis of variance, multi-factor analysis of variance was applied for the statistically significant effects using contrasts or Dunnett?s test. RESULTS: The mean age of patients was 53.72 and the mean age of menopause was 47.3 years. The total mean scores for vasomotor symptoms, fatigue, palpitations and the sum of the values attributed to Kupperman menopausal index do change throughout time (p<0.05). Levels of alkaline phosphatase show alteration throughout time (p<0.05), although, other measures for liver function and hemostasis present no mean difference between the groups. CONCLUSION: There was an improvement in climacteric symptoms. No change was found in hemostasis levels or liver function. However, alkaline phosphatase levels significantly improved in Group TH starting in month 4; therefore, an increase in quality of life was observed.

Weaning is one of the most critical periods in pig production due to a high susceptibility to gut disorders and infections induced by psychological, social, environmental and dietary stresses interfering with gut development and adaptation. This period was managed for decades by incorporating antibiotics in the diet. However, the European Union implemented a full ban on in-feed antibiotics since 1 January 2006. In this context, many alternatives are studied. We chose to study bovine colostrum for its richness in essential nutrients but also in bioactive peptides known for their growth promoting and antimicrobial properties in the calf but also in other species (poultry, pig, human). It was also selected for its high disponibility (Banque de colostrum, CER, Marloie, Belgium). The objective of this thesis is to investigate the potential of the use of bovine colostrum in the newly-weaned piglet diet and its mechanism of action. This thesis is composed of two parts : In the first part, the effects of bovine colostrum on growth performances, feed intake and physiological parameters were studied in two experiments. In the first experiment, 24 newly weaned piglets were fed daily a diet supplemented with 0, 1 or 5 g of defatted bovine colostrum. Our measures on the immune system showed that bovine colostrum could influence the development of the IgA response by potentiating a Th2 response in the ileal Peyer patch. In the digestive tract, no effects were shown on the morphology of the intestinal wall but a local anti-colostral immunisation was observed. In a second experiment, we demonstrated the efficiency of a 2 % bovine colostrum whey supplementation in weaning piglet diet to reduce the post-weaning growth check and undernutrition. The blood parameters showed a systemic IgA response, confirming previous results, and a higher IGF-I level in the colostrum-fed piglets the first week post-weaning. No effects on the faecal E. coli population were recorded. In the second part of this thesis, different ways to make the use of bovine colostrum more cost-effective for pig production were studied. It was shown that it was possible to maintain the same efficiency while reducing the dose of supplementation from 2 to 1 % and the period of administration from 28 to 10 days and replacing bovine colostrum whey by defatted bovine colostrum, a product 50 % less expensive to produce. Le sevrage est une des périodes les plus critiques en production porcine à cause d'une plus forte sensibilité des animaux aux problèmes intestinaux et aux infections suite aux stress psychologique, social, environnemental et alimentaire interférant avec le développement du tube digestif. Cette période délicate a été maîtrisée durant des décennies par l'incorporation d'antibiotiques dans l'aliment. Cependant, depuis le 1er Janvier 2006, cette pratique est totalement interdite dans l'Union Européenne. Dans ce contexte, de nombreuses alternatives sont étudiées. Nous avons choisi le colostrum bovin pour sa richesse en éléments essentiels et surtout en peptides bioactifs connus pour leurs propriétés promotrices de croissance et antimicrobiennes chez le bovin mais également chez d'autres espèces (poulet, porc, homme). Il a également été retenu pour sa grande disponibilité (banque de colostrum, CER, Marloie, Belgique). L'objectif de cette thèse est d'évaluer l'intérêt d'utiliser du colostrum bovin dans l'alimentation du porcelet au sevrage et d'étudier son mécanisme d'action. La thèse se compose de deux parties : Dans la première partie, les effets d'une supplémentation en colostrum bovin sur les performances, l'ingestion et certains paramètres physiologiques ont été étudiés au cours de deux expériences. Au cours d'une première expérience, un aliment supplémenté quotidiennement avec 0, 1 ou 5 g de colostrum bovin dégraissé a été testé. Au niveau immunitaire, nos mesures ont montré une influence du colostrum bovin sur le développement de la réponse en IgA en induisant une réponse de type Th2 au niveau de la plaque de Peyer iléale. Dans le tube digestif, aucun effet n'a été observé sur la morphologie de la paroi intestinale, mais une immunisation locale anti-colostrale a été mise en évidence. Une seconde expérience a démontré l'efficacité d'une supplémentation de 2 % de sérum de colostrum dans l'aliment pour réduire la perte de poids et la sous-alimentation provoquées par le sevrage. Les paramètres sanguins ont montré une augmentation des IgA, confirmant nos résultats précédents, et un taux en IGF-I plus important chez les porcelets recevant le colostrum. Par contre, aucun effet n'a été observé sur la population d'E. Coli fécale. Dans la seconde partie de la thèse, différents moyens de réduire le coût de la supplémentation en colostrum bovin ont été étudiés. Il a été démontré qu'il était possible de maintenir l'efficacité du colostrum tout en réduisant la dose (de 2 % à 1 %) et la durée de supplémentation (de 28 à 10 jours) et en remplaçant le sérum de colostrum par du colostrum dégraissé, un produit 50 % moins cher.

Contexte  Le cancer colorectal, deuxième par ordre de fréquence chez les femmes françaises, se développe principalement à partir de lésions précancéreuses, des adénomes. Les facteurs associés à l'obésité sont multiples, incluant des événements de début de vie, le niveau socio-économique et le comportement alimentaire ; l'obésité a aussi été associée de façon assez constante au risque de cancer colorectal. Cependant les associations entre des facteurs anthropométriques spécifiques ou au cours de la vie et le risque de tumeurs colorectales selon la filiation adénome-cancer ou selon le site sont moins claires. La ménopause est un événement de vie majeur et est associée à des modifications anthropométriques, tandis que le traitement hormonal de la ménopause (THM) est susceptible d'interagir avec les aspects anthropométriques mais aussi directement avec le risque de tumeur. De plus, la prescription du THM dépend de plusieurs paramètres, dont l'importance du suivi médical. Enfin, si le dépistage des tumeurs colorectales est conseillé à partir de 50 ans (soit aux environs de la ménopause) les attitudes vis-à-vis du dépistage varient selon de nombreux paramètres incluant les antécédents familiaux de cancer, le niveau socio-économique et les comportements de santé. Objectif  Le risque de tumeurs colorectales dépend ainsi de nombreux facteurs étroitement liés, parmi lesquels nous avons choisi d'étudier les relations complexes entre facteurs anthropométriques au cours de la vie, utilisation de THM et antécédents personnels de coloscopie, et le risque d'adénomes et de cancers colorectaux. Population  Les analyses ont été effectuées sur les données de la cohorte de femmes françaises E3N, comportant environ 1400 cas d'adénomes diagnostiqués parmi 17000 femmes ayant passé une coloscopie au cours du suivi (1993-2002) et 690 cas de cancers diagnostiqués parmi 92000 femmes au cours du suivi (1990-2008). Résultats  Notre étude a mis en évidence plusieurs aspects originaux. Tout d'abord, nous avons mis en évidence que les trois facteurs d'exposition principaux étudiés étaient associés au risque de tumeurs colorectales de façon significativement hétérogène en fonction du site, renforçant l'hypothèse selon laquelle il existe trois entités bien distinctes le long du cadre colorectal. Les caractéristiques anthropométriques typiquement occidentales (IMC et tour de taille élevés) étaient associées à un risque accru de tumeurs du côlon gauche, tandis que les associations originales que nous avons décrites entre taille assise et risque d'adénomes du côlon droit, et entre corpulence dans l'enfance et plus faible risque d'adénomes du rectum suggèrent de nouvelles pistes de recherche pour ces sites à l'étiologie mal connue. La mise en évidence d'une association positive entre prise de THM de type estrogènes seul (habituellement prescrit aux femmes hystérectomisées) et risque d'adénomes, en particulier du côlon gauche, et d'une association inverse entre le même type de THM et le risque de cancer, en particulier du côlon gauche, n'étant pas cohérentes avec les associations décrites dans la littérature, nous a conduit a explorer un éventuel biais de dépistage. La pratique de coloscopie était effectivement plus fréquente chez les femmes utilisant des estrogènes seuls (et donc aux antécédents d'hystérectomie), tandis que les antécédents de fibrome utérin étaient associés à un risque accru d'adénomes. De leur côté, les antécédents personnels de coloscopie étaient associés à une diminution de risque de cancer, surtout du côlon gauche, tandis que la réduction de risque des cancers du rectum devenait semblable à celle observée pour le côlon gauche dans la période la plus récente. Conclusion  En conclusion, nos résultats suggèrent qu'il existe des moyens efficaces de prévention des tumeurs distales, mais que la prévention des tumeurs du côlon droit demande des études spécifiques et peut-être de nouveaux paradigmes.