At present, the issue of occurrence of female sex hormones, estrogens and progestogens, in aquatic ecosystems is often discussed by experts and the general public. These substances of steroid structure can be difficult to remove completely by conventional wastewater and drinking water treatment technologies. In given context advanced oxidation processes based on in situ generation of highly reactive hydroxyl radicals can be a suitable technique. This thesis deals with the study of kinetics and degradation products of photocatalytic decomposition of seven female sex hormones (estrone, -estradiol, estriol, ethinylestradiol, diethylstilbestrol, progesterone and norethindrone). Experiments were conducted in a laboratory glass reactor, which was equipped with an energy efficient UV-A LED light source (365 nm emission wavelength) and an immobilised photocatalyst in a form of TiO2 five-layer film deposited on glass. Model samples of water with the initial hormone concentration of 1 mg·L-1 were used and the degradation process was monitored by an HPLC-MS method. In the given system all compounds of interest except estriol had very significant tendency to be adsorb. In the case of estriol the formal rate constant of photocatalytic decomposition was determined based on the Langmuir-Hinshelwood model for two different initial concentrations, 0.5527 hour-1 (1 mg·L-1) and 0.1929 hour-1 (5 mg·L-1), and by comparison of these values it was found that the higher degraded compound concentration, the slower decomposition (fivefold increase of the initial concentration resulted in the constant decrease to almost one-third). Moreover nine degradation products of estriol photocatalytic decomposition were recorded and their structure was designed based on mass spectra. In the second thematic part of the thesis attention was paid to development of a SPE-HPLC-MS method for simultaneous determination of female sex hormones in water ecosystems, with emphasis on an extraction part optimization. The final samples treatment process included besides extraction with Supel™ Select HLB 200 mg SPE cartridges also mechanical impurities removal, hormones extraction from solids trapped on filtration material, sample acidification and extract purification with Supelclean™ ENVI-Florisil® cartridges. Optimised method was used for determination of female sex hormones in two Brno rivers, Svitava and Svratka. In the most cases the concentration was below the detection or quantification limit.

Emotion, as well as cognition, are often understood as a manifestation of brain activity. However, bodily processes are also involved in mental functioning, referring to the concept of embodiment. Embodied emotion, traditionally, implies that experiencing an emotion involves perceptual, somato-visceral, and motor aspects. Within the frame of the Research Training Group “Situated Cognition”, we here extend the concept of embodiment by considering the role of hormones in the processing of emotional content. Importantly, hormones allow a bidirectional body-to-brain and brain-to-body coupling. The endocrine system, e.g., steroid sex hormones, produced in the gonads, send feedback to the brain by binding at their receptors. These receptors are relatively abundant in the brain regions associated with emotional processing, memory, and executive functions (i.e., amygdala, hippocampus, and prefrontal cortex). Moreover, peripheral hormone secretion is modulated via actions from the central nervous system. We intended to characterize the role of sex hormones, and partly also of stress hormones, on different components of emotion as a hormonal embodiment of emotion. Thus, we examined emotional processing in different sex hormone-status groups. To account for different levels of sex hormones, we used a quasi-experimental approach by comparing women in different cycle phases, women using hormonal oral contraceptives (Study 1), and additionally men (in Study 2). The female menstrual cycle is characterized by fluctuating sex hormone levels. On the peripheral gonadal level, these are 17β-estradiol and progesterone. These hormones are low at the beginning of the cycle (early follicular phase). Estradiol rises towards the middle of the cycle (mid-cycle) and stays moderately high until the next cycle. Progesterone levels are high after mid-cycle in the luteal phase until the end of the cycle. Hormonal contraceptives suppress the endogenous production of estradiol and progesterone, keeping the hormone levels low during the whole cycle. Estradiol and progesterone are also present in males, however, at low levels with no sign of cyclical fluctuations. In Study 1, we examined three independent groups of women in the mid-cycle (n = 24), in the luteal phase (n = 24), and women using hormonal oral contraceptives (n = 24). We assessed different measures of emotional processing, i. e. emotional memory, cognitive and affective empathy-related measures (emotion recognition and ratings for feeling with a protagonist´s emotion, respectively), as well as mimic and skin-conductance responses to affective stimuli. Additionally, we addressed interactions of experimental stress (cold pressor test vs. control) with sex hormones in emotional memory. Our data demonstrated the role of hormones in empathy-related measures and skin-conductance responses depending on the stimulus characteristics (valence, the gender of the protagonist). Emotional memory was not affected by hormone status, stressor or salivary hormone levels. In the cognitive empathy-related measure, women in the luteal phase, as well as oral contraceptive users, identified emotions depicted by female protagonists more accurately than those by male protagonists. On the other hand, estradiol correlated positively with recognition of emotions depicted by males in the total sample. In the affective empathy-related measure, oral contraceptive users rated negative emotions higher than the positive ones. Finally, in the luteal phase skin-conductance responses to negative stimuli were heightened, also supported by a positive correlation with the salivary progesterone levels. The mimic responses remained unaffected. None of the remaining associations with the salivary hormone levels were significant. These results indicate that sex hormones modulated emotional processing by interacting with the stimulus features, as evident in the negativity bias under oral contraceptive use and in the luteal phase in the affective empathy-related measure and sympathetic autonomous reactivity, respectively. However, emotional memory and mimic activity to affective stimuli were not affected. In Study 2, we extended the initial scope to examine the role of sex hormones and olfaction in empathy-related measures. Reports of female advantage in empathy-related measures suggest a role for sex hormones, although data are inconsistent. Studies also report similar sex differences in human olfactory perception. In rodents, olfaction is involved in detecting and integrating socially-relevant information and is modulated by the brain-actions of estrogens. Based on this background, we hypothesized that olfaction may untangle the mixed evidence regarding the relationship between sex hormones and empathy-related measures (cognitive, affective). Thus, we measured odor discrimination ability, empathy-related measures, and facial mimic activity (also associated with affective empathy-related measures) in free-cycling women in high sex-hormone phases (n = 20), oral contraceptive users (n = 19), and men (n = 21). Free-cycling women outperformed only men in the recognition of emotions depicted from the eye region. Oral contraceptive users showed higher scores in the affective empathy-related measure towards negative emotions. Free-cycling women exhibited the strongest facial mimicry (viewing female, but not male protagonists), positively associated with progesterone. Finally, the groups differed in odor discrimination, with free-cycling women outperforming men. However, odor discrimination ability and empathy-related performance were not correlated. Our results support the role of sex hormones in odor perception and empathy-related measures, to a certain extent. However, no common underlying mechanism was found. Finally, we conducted a systematic review (Study 3) aiming to elucidate factors contributing to the inconsistent results concerning the role of sex hormones in the two most addressed areas of emotional processing, emotion recognition (empathy-related measure) and emotional memory. Thereby, we extended previous reviews that address single areas of emotion processing. Moreover, we systematically addressed the role of situational features (mainly emotion-type and/or stimulus valence). All studies included healthy women of reproductive age either in stages of their natural menstrual cycle or using oral contraceptives, and measured or at least estimated levels of ovarian sex hormones. We document the methodological diversity in the field, presumably contributing to the heterogeneity of results. We recognized the need for studies explicitly contrasting the early follicular, mid-cycle, and mid-luteal phases, as well as OC-intake and using standardized tasks. Research would take advantage of using within-subject design more frequently and account for the recognition of complex emotions. In sum, our data suggest that sex hormones differentially modulate the cognitive and affective empathy-related performance and skin-conductance responses by interacting with situational variables, such as the emotional valence of the stimuli and the gender of the protagonist. Women in the luteal phase and under oral contraceptive use demonstrated better recognition of emotions depicted by female protagonists. By contrast, estradiol levels positively correlated with the recognition of emotions depicted by male protagonists. Sex-hormone status main effects only manifested in the emotion recognition advantage of free-cycling women over men (Reading the Mind in The Eyes Test; Study 2). In both studies, affective empathy ratings towards negative emotions were higher in the oral contraceptive users. Moreover, although mimic activity was not associated with sex hormones, skin-conductance responses to negative stimuli were heightened in the luteal phase. On the other hand, the performance in empathy-related measures in different hormone-status groups was not related to odor discrimination ability. Additionally, the inconsistencies of the sex hormone and emotion research could be the result of variations of designs and tasks used across studies from a similar field. This is also indicated in our findings from the empathy-related measures differing in tasks and hormone-status groups in two studies. Finally, our findings provide evidence that emotional processes under sex-hormone modulation are situated, i.e., subject to the influence of the stimulus valence. Furthermore, they are embodied via coupling between the endocrine system and the brain as evident in hormone status and valence interactions in empathy-related measures and sympathetic reactivity.

Les corrélats de la cognition sexuellement dimorphique demeurent partiellement compris puisque plusieurs variables de nature psychosociale et biologique modulent de façon synergique ces habiletés cognitives. Les corrélats du sexe et du genre dans le fonctionnement cognitif sexuellement dimorphique ont été évalués dans un échantillon d’individus âgés de 18 à 45 ans (N=87) et d’orientations sexuelles diverses. Les hormones sexuelles (estradiol, testostérone et progestérone) ont été mesurées par le biais d’échantillons de salive à quatre temps de mesure différents lors du paradigme expérimental. Les rôles de genre, l’orientation sexuelle et les variables sociodémographiques ont été évalués par l’entremise de questionnaires auto-rapportés. La contraception étant source importante de variation, a été prise en compte via des questionnaires auto-rapportés. Les participants ont complété une tâche de rotation mentale, de fluidité verbale ainsi que le Trier Social Stress Test par la suite. Le volet de réactivité au stress était un volet des de ce paradigme de recherche, mais pas un objectif de la présente étude puisque cette question a été investiguée dans des études précédentes. Les hommes ont mieux performé à la tâche de rotation mentale que les femmes alors qu’aucune différence significative n’a été démontrée pour la tâche de fluidité verbale. Des associations significatives et positives ont été observées entre l’estradiol et la performance de fluidité verbale pour les femmes naturellement cyclées comparativement à celle utilisant des contraceptifs oraux, mais pas pour la progestérone et la testostérone. En contrôlant pour les hormones sexuelles, un effet d’interaction significatif entre le sexe et les rôles de genre a été identifié démontrant que les femmes s’identifiant comme masculines performaient mieux à la tâche de rotation mentale que les autres groupes de femmes. Ces résultats exploratoires suggèrent un effet principalement conduit par le sexe et les hormones sexuelles sur la performance cognitive qui pourrait également être influencé par des facteurs psychosociaux. / The correlates of sexually dimorphic cognition are not yet fully understood since many biological and psychosocial variables modulate these cognitive abilities in synergy. Sex and gender correlates of sexually dimorphic cognition were assessed in a sample of individuals ages 18-45 years (N=87) from diverse sexual orientations. Sex hormones (estradiol, testosterone and progesterone) were assessed via saliva samples at four timepoints throughout testing. Gender-roles, sexual orientation and socio-demographics were measured via self-report questionnaires. Contraception being an important variability factor was assessed via self-report questionnaires. Participants completed mental rotation and verbal fluency tasks as well as the Trier Social Stress Test afterwards. The stress reactivity aspect was evaluated but was not one of the main objectives of the current study as previous publications have investigated this already. Men performed better than women at mental rotation, while no significant difference was found for verbal fluency. Significant positive associations were observed between estradiol and word fluency for the naturally cycling women compared to the women using oral contraception but not for progesterone and testosterone. While controlling for sex hormones, a significant interaction effect of sex and gender-roles was identified showing that masculine women performed better than other women groups at the mental rotation task. These exploratory results suggest an effect principally driven by sex and sex hormones on cognitive performance that may also be influenced by psychosocial factors.

Clinical and experimental studies have shown that estradiol (E2) can enhance protection against sexually transmitted infections such as HSV-2 and HIV-1. Antigen presenting cells (APCs) such as Dendritic cells (DCs) are critical for generating immune responses against these infections, and it is unclear whether unique factors present in the genital mucosa can influence immune responses by directly modulating the phenotype and function of local APCs. To address this, I hypothesized that sex hormones, such as E2 and innate factors in the local microenvironment can regulate the phenotype and function of vaginal APCs. The work summarized in this thesis addressed this central hypothesis. In the first section of the thesis, I examined whether vaginal APCs were distinct in their phenotype and function compared to those in other mucosal tissues or spleen. The results show that the vagina was enriched in CD11c+ CD11b+ MHCII− DCs. Functionally, vaginal tissue cells (TC) and CD11c+ DCs were more potent inducers of Th17 responses in co-cultures with CD4+ T cells, compared to lung, small intestine or spleen APCs. E2 was critical for the conditioning of vaginal DCs to prime these Th17 responses through an IL-1-dependent pathway, indicating that sex hormones such as E2 can directly influence the function of vaginal APCs. In the next section, I determined whether other co-factors in the genital microenvironment such as microflora and innate lymphocytes could also influence vaginal APC functions. We found that while microflora was not essential, IL-17 produced by innate lymphocytes was critical for the induction of IL-1 from DCs, and consequently for potentiating Th17 responses. Finally, I attempted to develop an in vivo mouse model where the effect of E2 on vaginal APCs could be examined in the context of genital HSV-2 infection. I tested a 7-day injectable E2 and a 21-day E2 pellet delivery model, and found that both regimes had limitations for examining E2-effects on anti-viral responses. Yet, subsequent to the work done in this thesis, we were able to confirm our observations of E2-conditioned Th17 responses in vivo in an intranasal immunization model utilizing E2 pellet delivery, and thereby addressed the mechanism underlying enhanced anti-viral protection following E2-treatment. In conclusion, this is the first study to show the effect of E2 on genital tract APCs and their ability to prime Th17 responses. It provides future avenues to examine whether modulation of this microenvironment can help optimize vaccine-induced immune responses against STIs. On a more fundamental level, it highlights the need to consider the inherent distinctions in APC populations among different mucosal tissues. / Dissertation / Doctor of Philosophy (PhD)

Objectives: To investigate the organisation of asthma care in primary care and evaluate outcomes for patients attending primary care centres with and without asthma clinics. Other objectives were to study the association between quality of life and asthma control in patients in primary care and to analyse sex differences regarding asthma outcomes related to menopausal status. Material and methods: Cross-sectional surveys and a patient record study. Results: Of all the primary health care centres, 77% had a spirometer and 53% an asthma clinic. At centres with asthma clinics 77% of the patients reported sufficient knowledge of asthma as compared with 65% at centres without asthma clinics (p<0.001). With more time allocated for the nurse, 44% of patients achieved asthma control as compared with 27% at asthma clinics with less time (p<0.003). Patients using short-acting beta-2 agonists more than twice in the last week had clinically significant lower MiniAQLQ scores (5.17 versus 5.91). This finding also held for night awakenings during the previous week (4.42 versus 5.86), courses of oral corticosteroids (5.26 versus 5.64) and reported emergency consultations during the last six months (4.85 versus 5.71). Premenopausal women had significantly lower total MiniAQLQ scores than men in the same age group (5.44 versus 5.89, p<0.001), while no difference was found between postmenopausal women and men of similar ages. The adjusted odds for premenopausal women for asthma exacerbations was 2.0 (95%CI 1.22-3.43) as compared with men in the same age group. No differences were found when comparing postmenopausal women with men of similar ages. Conclusions: Half the primary health care centres had an asthma clinic and the majority had access to a spirometer. Patients at primary health care centres with asthma clinics reported better knowledge of their disease, and asthma control is more often achieved if the nurse is allocated more time. Achieving asthma control is associated with better quality of life in patients in primary care. Premenopausal women had lower quality of life and less often asthma control then men of the same ages, while no corresponding difference was found between postmenopausal women and men of similar ages.

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN. / Erythropoietin-producing hepatocyte (EPH) kinases are the largest family of receptor tyrosine kinases. Their ligands, ephrins (EFNs), are also cell surface molecules. Ephs/EFNs are implicated in many biological processes. Hypertension is a chronic medical condition of high arterial blood pressure (BP). New hypertension therapeutic treatments are of great importance for public health. Until recently, there are only a few studies related to the role of EPHs/EFNs in vascular smooth muscle cell (VSMC) function. In our previous studies, we have found that EPHB6 and EFNB1 function in concert with sex hormones to regulate BP. In the present investigation, we found that different EPH/EFN family members can either positively or negatively regulate the VSMC contractility and BP: while EPHB4 and EFNB2 belong to the former category, EFNB1, EFNB3 and EPHB6, the latter. In vivo, male but not female smooth muscle-specific EPHB4 knockout (KO) mice presented decreased BP, compared to WT controls. VSMCs from EPHB4 KO mice in the presence of testosterone showed reduced contractility. EFNB2 is the major ligand of EPHB4. As expected, smooth muscle-specific EFNB2 KO mice had a similar although not identical BP phenotype as EPHB4 KO mice. Male but not female EFNB2 KO mice on regular or high-salt diet presented reduced BP, compared to WT counterparts. At the cellular level, the KO VSMCs showed reduced contractility compared to WT controls. In a human genetic study, we identified in the EFNB2 gene six SNPs that were significantly associated with hypertension risk in a sex-dependent way, corroborating our findings in mice. On the other hand, EFNB3 gene KO in female mice resulted in elevated BP and small artery resistance in vivo, enhanced small arterial contractility ex vivo, and augmented VSMC contractility in vitro. Male KO mice had normal BP, but castration led to significant BP elevation in KO but not in WT mice. VSMCs from female KO mice showed heightened MLC phosphorylation and reduced MLC kinase phosphorylation. This signaling change was mediated through an adaptor protein Grip1. Indeed, in a genome-wide association study by the International Consortium for Blood Pressure, an SNP in the GRIP1 gene approached the significant threshold p-value for its association with diastolic BP. Our research for the first time revealed that EPHs/EFNs are novel components in the BP regulation system. Members of the EPH/EFN family may act as Yin and Yang forces to finely tune the vessel tone for BP homeostasis and regulation. Such effects of EPHs/EFNs depend on sex and sex-hormone levels. Based on this new knowledge, we could develop novel personalized hypertension therapy using sex hormone antagonists or sex hormone replacement therapy, depending on the sex hormone levels of the patients and mutations in EPH/EFN genes.

Este estudo teve por objetivo avaliar a influência da terapia hormonal sobre a pressão ocular de mulheres na pós-menopausa. A amostra foi constituída por 58 olhos de 58 pacientes no período da pós-menopausa, com indicação de terapia hormonal, com idade entre 41 e 65 anos, que não tenham utilizado hormônio nos últimos três meses. As pacientes foram randomizadas (por sorteio) em dois grupos: terapia hormonal contínua (n=32) com comprimidos de estradiol 2 mg e acetato de noretisterona 1 mg, diário durante três meses e grupo controle placebo (n=26). O estudo foi realizado de forma cega pela investigadora principal. As pacientes foram avaliadas quanto à pressão ocular, paquimetria, ceratometria e dosagens dos hormônios sexuais pré e pós-tratamento. A média de idade foi de 54,21 anos ± 4,95, sendo 53,66 anos ± 5,60 no grupo com terapia hormonal e de 54,88 anos ± 4,01 no grupo placebo. Não houve diferença significativa entre os grupos com relação a idade (p= 0,352), índice de massa corporal (p= 0,818), pressão ocular (p=0,697), ceratometria (p > 0,05), paquimetria central (p=0,580), e dosagens dos hormônios sexuais (p>0,05) no pré-tratamento. A pressão ocular média pré-tratamento foi de 14,08 mmHg ± 1,96 no grupo terapia hormonal e de 13,81 mmHg ± 3,28 no grupo placebo. Houve redução significativa da pressão ocular média entre o pré e o pós-tratamento (p=0,0009) no grupo terapia hormonal e redução não significativa no grupo placebo (p=0,108). Na avaliação entre os grupos, não houve diferença estatística nos valores de pressão ocular média no pós-tratamento. Na avaliação entre os grupos, não houve diferença estatisticamente significativa para os valores de paquimetria e ceratometria. O grupo com terapia hormonal apresentou aumento significativo dos níveis hormonais de estradiol e redução significativa nas dosagens hormonais médias de LH e FSH no pós-tratamento com 30, 60 e 90 dias (p=0,000). As dosagens hormonais no grupo placebo não apresentaram variação estatisticamente significante. No grupo terapia hormonal, houve correlação diretamente proporcional entre as pressões oculares médias e níveis hormonais de LH e FSH, e correlação inversamente proporcional com níveis hormonais de estradiol. Em resumo, houve redução da pressão ocular média no grupo terapia hormonal entre o pré e o pós-tratamento e os níveis pressóricos neste grupo se correlacionaram com os níveis hormonais de LH, FSH e estradiol / This trial aimed to assess the influence of hormonal therapy on intraocular pressure in post-menopausal women. The sample had 58 eyes of 58 patients during menopause period, indicated for hormonal therapy, they were between the age of 41 and 65 years, who have not taken hormone in the past three months. Patients were randomized (raffle) in two groups: continuous hormonal therapy (n=32) with 2 mg of estradiol and 1 mg daily of norethisterone acetate for three months and controlled placebo group (n=26). It was a blind study carried out by the main investigator. Patients were assessed regarding ocular pressure, pachymetry, keratometry and sex hormone\'s dosages, pre and post treatment. The average was 54.21 years old ± 4.95, where 53.66 years old ± 5.60 in the group with hormonal therapy and 54.88 years old ± 4.01 in the placebo group. There was no significant difference between the groups regarding age (p= 0.352), body mass index (p= 0.818), ocular pressure (p=0.697), keratometry (p > 0.05), central pachymetry (p=0.580), and sex hormone dosages (p>0.05) during pre treatment. The average pre treatment pressure was 14.08 mmHg ± 1.96 in the hormonal therapy group and 13.81 mmHg ± 3.28 in the placebo group. There was a significant reduction in the average ocular pressure between the pre and post treatment (p=0.0009) in the hormonal therapy group and not a significant reduction in the placebo group, (p=0.108). There was no statistically difference between the groups in the average ocular pressure values after treatment. There were no statistically significant differences between the two groups in the values of pachymetry and keratometry. The hormonal therapy group showed a significant increase in estradiol hormonal levels and a significant reduction in the average hormonal dosages of LH e FSH in the post treatment after 30, 60 and 90 days (p=0.000). The hormonal dosages in the placebo group no showed significant changed. In the hormonal group, there was a direct and proportional relation between the average ocular pressure and LH and FSH hormonal levels and a proportional contrariwise correlation with estradiol hormonal levels. In summary, there was a reduction in the ocular pressure average in the hormonal therapy group between the pre and post treatment and the pressure levels in this group were correlated with the hormonal levels of LH, FSH and estradiol

O uso de álcool entre mulheres é uma questão atual e preocupante, face a maior vulnerabilidade destas aos danos hepáticos, cerebrais, entre outros, quando comparadas aos homens com padrões semelhantes de consumo. Sendo assim, investigaram-se as possíveis variações na farmacocinética do etanol em mulheres, considerando duas fases do ciclo menstrual (pré-folicular e lútea), bem como o uso de anticoncepcionais orais (AO). Participaram voluntários dos sexos feminino (n=22) e masculino (n=14), administrando-lhes 0,3 g/kg de etanol, na forma de uísque. Os resultados indicaram: a) os parâmetros farmacocinéticos do etanol não variam em função do ciclo menstrual (fase pré-folicular e lútea); b) as mulheres que tomavam AO levam menos tempo para atingir a concentração máxima e eliminam o etanol mais rapidamente do que as que não faziam uso; c) não houve diferença nos parâmetros farmacocinéticos entre o grupo de homens e o de mulheres que utilizavam AO, porém os homens apresentam maior velocidade de eliminação do que as mulheres que não faziam uso e d) os parâmetros farmacocinéticos relacionados com a biodisponibilidade (área sob a curva) e com o volume de distribuição não apresentaram diferenças entre os grupos analisados. / After drinking equivalent amounts of alcohol, women appear to be more vulnerable than men to many adverse consequences of alcohol use, including liver and brain damage. This study investigated the influence of menstrual cycle and female sex steroids levels on ethanol pharmacokinetics, as a possible mechanism for these effects. Twenty-two female and 14 male volunteers were given a moderate dose of ethanol (0.3 g/kg) in the morning after an overnight fast. The results indicated: a) no evidence that the tested menstrual cycle phases (pre-follicular and luteal) significantly influence ethanol pharmacokinetics; b) the time required to reach peak BAC was shorter and the ethanol elimination rate was increased for women taking oral contraceptives (OC) as compared to women not taking them; c) there is no difference on ethanol pharmacokinetics between men and women taking OC, but men showed increased ethanol elimination rate compared to women not taking OC; d) no gender-related differences relating to bioavailability of ethanol were found.

The aim of this diploma thesis was to summarize the topic of the anterior cruciate ligament (LCA) injury dependency on the menstrual cycle phase of young women with regular sport activity. The general part describes basic knowledge about connective tissue, LCA, issues of LCA injury and related risk situations. Large chapter is dedicated to sex hormones and menstrual and ovarian cycle, which is crucial for understanding the whole topic. The main part is focused on impact of sex hormones and hormonal contraception on connective tissue, but also on muscle and nervous tissues, which might be as well important for LCA injury incidence. Next part of the thesis consists of a questionnaire survey. 52 respondents aged 15-35 with rupture or partial rupture of LCA answered the non-standardized questionnaire compiled specially for this thesis and the results were statistically processed. 14 respondents were using hormonal contraception, remaining 38 had physiological menstrual cycle. Based on the theoretical findings we expected highest incidence of LCA injuries among women without contraception in phases of menstrual cycle with highest levels of oestrogen (10th -15th day). That was confirmed (P-value: 0,0218) as well as overall lower incidence among women using contraception (P-value: 0,0006). Expected higher...

O uso de álcool entre mulheres é uma questão atual e preocupante, face a maior vulnerabilidade destas aos danos hepáticos, cerebrais, entre outros, quando comparadas aos homens com padrões semelhantes de consumo. Sendo assim, investigaram-se as possíveis variações na farmacocinética do etanol em mulheres, considerando duas fases do ciclo menstrual (pré-folicular e lútea), bem como o uso de anticoncepcionais orais (AO). Participaram voluntários dos sexos feminino (n=22) e masculino (n=14), administrando-lhes 0,3 g/kg de etanol, na forma de uísque. Os resultados indicaram: a) os parâmetros farmacocinéticos do etanol não variam em função do ciclo menstrual (fase pré-folicular e lútea); b) as mulheres que tomavam AO levam menos tempo para atingir a concentração máxima e eliminam o etanol mais rapidamente do que as que não faziam uso; c) não houve diferença nos parâmetros farmacocinéticos entre o grupo de homens e o de mulheres que utilizavam AO, porém os homens apresentam maior velocidade de eliminação do que as mulheres que não faziam uso e d) os parâmetros farmacocinéticos relacionados com a biodisponibilidade (área sob a curva) e com o volume de distribuição não apresentaram diferenças entre os grupos analisados. / After drinking equivalent amounts of alcohol, women appear to be more vulnerable than men to many adverse consequences of alcohol use, including liver and brain damage. This study investigated the influence of menstrual cycle and female sex steroids levels on ethanol pharmacokinetics, as a possible mechanism for these effects. Twenty-two female and 14 male volunteers were given a moderate dose of ethanol (0.3 g/kg) in the morning after an overnight fast. The results indicated: a) no evidence that the tested menstrual cycle phases (pre-follicular and luteal) significantly influence ethanol pharmacokinetics; b) the time required to reach peak BAC was shorter and the ethanol elimination rate was increased for women taking oral contraceptives (OC) as compared to women not taking them; c) there is no difference on ethanol pharmacokinetics between men and women taking OC, but men showed increased ethanol elimination rate compared to women not taking OC; d) no gender-related differences relating to bioavailability of ethanol were found.