Introdução: O homem transexual (HT) é um indivíduo de sexo genético feminino, com fenótipo feminino normal, que deseja viver e ser aceito como um membro do sexo masculino. O tratamento hormonal que é realizado no processo de redesignação sexual nesses pacientes consiste na administração de testosterona nas suas diversas apresentações, mais comumente ésteres de testosterona de curta ou longa ação. O tratamento hormonal visa induzir virilização, através da produção de um padrão masculino de crescimento dos pelos faciais e corporais, aumento da massa muscular e interrupção dos ciclos menstruais. O efeito da terapia androgênica na saúde cardiovascular de HT é pouco conhecido, principalmente em relação às repercussões em longo prazo. O HT representa um modelo ideal e único para a avaliação das ações da testosterona exógena administrada em doses suprafisiológicas em um organismo geneticamente feminino. Alguns estudos de farmacogenética demonstraram a influência da repetição CAG do gene do receptor androgênico (RA) nos efeitos observados durante terapia com testosterona em homens hipogonádicos e a maioria dos estudos confirmou a modulação desses polimorfismos sobre fatores de risco cardiovascular. Objetivos: avaliar em HT em tratamento androgênico a prevalência de fatores clássicos de risco cardiovascular e as propriedades estruturais e funcionais dos vasos arteriais; correlacionar a distribuição alélica do microssatélite CAG RA com a ocorrência de comorbidades e com as propriedades estruturais e funcionais dos vasos arteriais; comparar os valores das propriedades estruturais e funcionais dos vasos arteriais de HT com uma população controle (feminina e masculina). Pacientes: 46 pacientes com diagnóstico de HT (faixa etária 42 ± 10 anos) acompanhados no Ambulatório da Unidade de Disforia de Gênero do HCFMUSP e em tratamento com ésteres de testosterona há pelo menos um ano (variação de 1 a 38 anos) foram selecionados para o estudo. Métodos: Parâmetros clínicos (IMC, circunferência abdominal, relação cintura quadril, pressão arterial e pressão de pulso, composição corporal por bioimpedância), a presença de comorbidades (hipertensão arterial, dislipidemia, diabetes mellitus, obesidade) e vícios (tabagismo, etilismo e uso de drogas ilícitas), dados laboratoriais (hematócrito, glicemia de jejum, insulina, índice HOMA IR, hemoglobina glicada, colesterol total, HDL colesterol, LDL colesterol, triglicerídeos e creatinina) e parâmetros vasculares (espessura íntima média da carótida, diâmetro da carótida, percentual da variação sisto-diastólica da carótida e velocidade de onda de pulso dos vasos arteriais) foram avaliados no grupo de HT. Os mesmos parâmetros vasculares também foram avaliados em controles saudáveis masculinos e femininos pareados para idade e IMC com os HT. A distribuição alélica do microssatélite CAG RA foi avaliada em 44 HT através da análise do produto amplificado da região de repetições CAG do exon 1 do gene do RA, utilizando o software GeneMapper. Resultados e Conclusões: Neste grupo de HT em terapia com ésteres de testosterona observamos uma prevalência de dislipidemia de 42%, hipertensão arterial sistêmica de 35%, obesidade de 30%, diabetes de 4% e tabagismo de 20%. HT em tratamento androgênico apresentaram maior velocidade de onda de pulso carotídeo-femoral do que controles masculinos, mas não do que controles femininos, embora no subgrupo >= 42 anos os HT tenham apresentado maior VOP do que controles masculinos e femininos. Não houve diferença de diâmetro, distensão relativa e espessura íntima média carotídea entre HT e controles. Maior diâmetro, maior espessura íntima média e menor distensão relativa da carótida foram observados em HT obesos e hipertensos; e maior velocidade de onda de pulso aórtica em HT hipertensos. Os parâmetros correlacionados à medida funcional da artéria aorta foram a idade, o tempo de tratamento androgênico e a relação cintura-quadril, enquanto que as propriedades estruturais e funcionais da carótida se correlacionaram com idade, parâmetros antropométricos e glicêmicos. Não houve influência do trato CAG RA na comparação entre os HT com e sem comorbidades metabólicas. Repetições CAG RA curtas se associaram com níveis significativamente mais elevados de glicemia de jejum, insulina basal e HOMA IR. Em relação aos parâmetros antropométricos, pressóricos, lipídicos e arteriais, não foi identificada associação com o número de repetições CAG RA. Estes achados sugerem um potencial efeito deletério da terapia androgênica prolongada sobre os vasos arteriais e a necessidade de medidas preventivas em HT / Introduction: Transgender men (TM) are 46, XX individuals, with normal female phenotype, who desire to live and be accepted as a male member. Testosterone esters are used in sex reassignment therapy to induce virilization and to adapt the body to the male identity. The effects of androgen therapy on TM cardiovascular function are poorly known, particularly with regard to long-term androgen treatment. TM represents a good model for evaluation of high-dose exogenous testosterone action in biological women. Pharmacogenetic studies have demonstrated the influence of CAG polymorphic tract of the androgen receptor gene (AR) on the androgenic effects observed during testosterone therapy in hypogonadal men, and most studies confirmed the modulation of these polymorphisms on cardiovascular risk factors. Objective: to evaluate the prevalence of cardiovascular risk factors and the structural and functional properties of large arteries in TM on long-term cross sex hormone therapy compared to a male and female healthy control group; to correlate the allelic distribution of CAG AR polymorphic tract with the cardiovascular comorbidities and the structural and functional properties of large arteries in TM. Patients: Forty-six patients with a diagnosis of TM (42 ± 10 years old), followed at the Gender Dysphoria Unit-HCFMUSP, receiving cross-sex hormone treatment with testosterone esters for at least one year (ranging from 1 to 38 years) were selected for the study. Methods: Clinical parameters (BMI, waist circumference, waist-to-hip ratio, blood pressure, pulse pressure, body fat percentage), the presence of cardiovascular comorbidities (hypertension, dyslipidemia, diabetes mellitus, obesity) and addictions (smoking, alcohol and drug abuse), laboratory parameters (hematocrit, fasting plasma glucose, basal insulin, HOMA IR index, glycated hemoglobin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and creatinine) and vascular parameters (carotid intima-media thickness, carotid diameter, carotid relative distensibility and aortic pulse wave velocity - PWV) were evaluated in the TM group. The same vascular parameters were also evaluated in healthy male and female control group, matched for age and BMI. The allelic distribution of the CAG AR polymorphic tract was evaluated in 44 TM using the GeneMapper software. Results and Conclusions: In the TM group, we observed dyslipidemia in 42%, hypertension in 35%, obesity in 30%, diabetes in 4% and smoking habit in 20%. The mean aortic PWV values in TM was higher than in male healthy controls (p=0.005), but not than in female controls (p=0.640). When categorized by age, considering the median age, TM >= 42 years had higher aortic PWV measures than male (p < 0.001) and female (p = 0.024) controls, regardless of their arterial blood pressure values. There was no difference in carotid diameter, carotid relative distensibility and carotid intima-media thickness between TM and controls. Obese and hypertensive TM presented significantly higher values of carotid diameter and carotid intima-media thickness, and lower values of carotid relative distensibility than healthy transgenders. Hypertensive TM showed higher aortic PWV values than non-hypertensive TM. The aortic stiffness correlated significantly and positively with age, androgen treatment duration and waist-to-hip ratio in TM. Properties of the carotid artery correlated with age, anthropometric parameters and glycemic parameters in TM. Shorter CAG polymorphic tracts of TM were associated with higher levels of fasting plasma glucose, basal insulin and HOMA IR index. There was no influence of the CAG polymorphic tract of TM on the presence of cardiovascular comorbidities, anthropometric, pressure, lipid and arterial parameters. These findings suggest a potential deleterious effect of the long-term testosterone therapy on vessels and the need for preventive measures in TM

O dimorfismo sexual relacionado à hipertensão arterial surge na adolescência e persiste por toda vida adulta. Homens apresentam maior incidência de doenças cardiovasculares quando comparados a mulheres de mesma faixa etária. O mesmo perfil é observado em modelos animais de hipertensão, nos quais machos apresentam maiores níveis pressóricos quando comparados a fêmeas. Dessa forma, a testosterona é frequentemente relacionada à hipertensão arterial. Entretanto, os mecanismos pelos quais a testosterona exerce efeitos vasculares ainda não estão esclarecidos. O objetivo deste trabalho foi investigar os efeitos da testosterona sobre a geração de espécies reativas de oxigênio (EROs), importantes mediadores do processo hipertensivo, em células da musculatura lisa vascular (CMLV) de ratos normotensos e espontaneamente hipertensos (SHR). Os receptores para andrógenos, as fontes de EROs (papel da NADPH oxidase), bem como os efeitos funcionais celulares (migração celular) relacionados aos efeitos da testosterona também foram analisados. Para tanto, CMLV do leito mesentérico de ratos Wistar (W), Wistar-Kyoto (WKY) e SHR foram isoladas, cultivadas e estimuladas com testosterona 10-7mol/L em diferentes tempos, de acordo com cada protocolo. Sempre que necessário, as células foram pré-incubadas por 30 minutos com inibidores específicos para o estudo dos mecanismos envolvidos, tais como: flutamida (inibidor do receptor clássico para andrógenos), apocinina (inibidor da NADPH oxidase), PP2 (inibidor da c-Src), actinomicina D (inibidor da transcrição gênica) e cicloheximida (inibidor da síntese protéica). Nossos resultados indicam que a testosterona induz a geração de EROs por mecanismos dependentes do tempo e da linhagem de ratos, de modo que células isoladas de animais SHR são mais sensíveis a testosterona. Esta geração ocorre por dois mecanismos principais: um mediado pelo receptor clássico para andrógenos (AR) e outro mediado pelo receptor de membrana para andrógenos (ARm), resultando em efeitos genômicos e não-genômicos, respectivamente. Enquanto os efeitos genômicos são comuns, isto é, são observados em células de animais normotensos e hipertensos, os efeitos não-genômicos são específicos, e ocorrem exclusivamente em células de animais hipertensos. A geração genômica de EROs, mediada pelo AR, depende da modulação da expressão de subunidades da NADPH oxidase. Por outro lado, a geração não-genômica, é mediada pelo ARm, independe de síntese protéica, e ocorre devido à ativação de vias de sinalização específicas, reguladoras do complexo enzimático NADPH oxidase. As EROs formadas a partir do estímulo com a testosterona tanto por mecanismos genômicos ou não-genômicos levam a migração celular por mecanismos mediados pelo RA. Nossos resultados sugerem que a testosterona tem papel importante na função de células da musculatura lisa vascular, o que pode contribuir para algumas alterações vasculares características do processo hipertensivo. Portanto, nosso trabalho é o primeiro a demonstrar que a testosterona regula vias de sinalização redox em CMLV levando a efeitos funcionais importantes, relacionados ao remodelamento vascular, os quais podem contribuir para o desenvolvimento e manutenção da hipertensão arterial. / Sexual dimorphism related to hypertension begins at childhood and persists through adulthood. The incidence of cardiovascular diseases is higher in men when compared to age-matched women. Although testosterone has been associated to the sexual dimorphism in hypertension, the mechanisms whereby testosterone acts in the vasculature remain unclear. The main objective of this study was to determine whether testosterone induces reactive oxygen species (ROS) generation, key players on hypertension, in vascular smooth muscle cells (VSMC) isolated from normotensive and hypertensive rats. The signaling pathways and the androgen receptors activated by testosterone, the role of NADPH oxidase in ROS generation and the cellular outcomes (cell migration) were also determined. Accordingly, VSMC isolated from the mesenteric bed of Wistar (W), Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were stimulated with testosterone 10-7mol/L for different periods of time, according to each protocol. Whenever appropriate, cells were pre-incubated with specific inhibitors, such as flutamide 10-5mol/L (nuclear androgen receptor antagonist), apocynin 3x10-5mol/L (NADPH oxidase inhibitor), PP2 10-5mol/L (c-Src inhibitor), actinomycin D 10-5mol/L (inhibitor of gene transcription), and cycloheximide 10-5mol/L (protein synthesis inhibitor). Our findings demonstrate that testosterone induces ROS formation in a time and strain-dependent manner. Augmentation of ROS formation is higher in SHR-VSCMC, indicating an increased sensitivity of SHR-VSMC to testosterone stimuli. Testosterone-induced ROS production occurs by two main mechanisms: the first mediated through the classical androgen receptor (AR) and the second mediated through membrane-associated androgen receptor (ARm), leading to genomic and non-genomic effects, respectively. Whereas the genomic effects occur in VSMC from both strains, non-genomic effects are only observed in SHR-VSMC. The genomic ROS production is mediated through AR and depends on modulation of NADPH oxidase subunits. On the other hand, non-genomic ROS formation is mediated through RAm, does not rely on protein synthesis and occurs via specific signaling pathways that regulate NADPH oxidase. Genomic and non-genomic ROS production by testosterone leads to a common final effect: VSMC migration, indicating that testosterone plays a key role in VSMC function. These results indicate that testosterone signals through redox-sensitive pathways, important in c-Src-mediated migration of VSMCs in SHR. Such processes may contribute to vascular remodeling in hypertension.

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.

A manutenção de animais em zoológicos, criadouros e centros de reprodução tem como objetivo auxiliar os programas de conservação in situ e ex situ, além de contribuir para os programas de educação ambiental. A cada dia, torna-se mais clara a importância do bem-estar dos animais cativos, e a redução do estresse é fundamental neste contexto. A contenção manual faz parte do manejo realizado em zoológicos e criatórios para diversos procedimentos, como tratamentos tópicos, colheita de sangue ou sêmen ou mesmo para exames físicos. Sabe-se que este tipo de procedimento provoca resposta do tipo estresse, porém não é claro a intensidade da resposta, ou se este mecanismo fisiológico poderia potencialmente alterar o padrão de secreção de cortisol e/ou testosterona. O objetivo do projeto foi avaliar o efeito da contenção física manual por cinco minutos, sobre os perfis de metabólitos fecais e urinários de testosterona e de cortisol, em cinco machos adultos de sagui-de-tufos-pretos (C. penicillata), mantidos em casais, no Parque Municipal Quinzinho de Barros em Sorocaba, SP. Considerando-se o dia da contenção física, como o dia 0, foram colhidas amostras fecais diárias, sempre pela manhã, a partir do dia -5 até o dia + 4. Para as amostras urinárias, foram realizadas múltiplas colheitas diárias, do dia -5 ao +1. As amostras foram dosadas através de radioimunoensaio. Baseado nos resultados encontrados foi verificado que a contenção física de C. penicillata por cinco minutos pode induzir resposta do tipo estresse, porém não de forma sustentada ou duradoura. Contudo, a variação individual e a adaptação dos animais às condições experimentais possivelmente desempenharam papel relevante na modulação da resposta / The maintaining of animals in Zoo\'s, breeders and reproduction centers have as objective to help in situ and ex situ conservation programs , besides contributing to environmental education programs. Every day, the importance of captive animals well being becomes more clear, and the reduction of stress is fundamental in this context. Manual restraining is part of the handling performed in zoos and breeders for many procedures, such as topic treatments, blood or semen draw or even for physical exams. It is known that this kind of procedure provokes a stress response, however the intensity of the response is not clear, or if this physiological mechanism could potentially alter the cortisol and/or testosterone secretion pattern. The objective of the project was to evaluate the effect of manual physical restraint for five minutes, over the fecal and urinary metabolites profiles of testosterone and cortisol, in five adult males of Black tufted marmosets (C.penicillata), maintained in couples, at the Parque Municipal Quinzinho de Barros in Sorocaba, SP. Considering the day of physical restraint as day 0, daily fecal samples were collected, always in the morning, starting from -5 until +4. For the urine samples, daily multiple collections were done, from day -5 to +1. The samples were measured with radioimmunoassay. Based on the results found, it was verified that the physical restraining of C.penicillata for five minutes can induce a stress response, though not in a sustained or long lasting manner. However, the individual variation and the adaptation of the animals to experimental conditions possibly had a relevant role over the modulation of the response.

Made available in DSpace on 2017-07-10T14:57:30Z (GMT). No. of bitstreams: 1 Claudio Girelli_ Junior.pdf: 1035740 bytes, checksum: 5744f2af3a9cdd7a97647cc399f302df (MD5) Previous issue date: 2015-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Testosterone is the principal male sex steroid hormone involved in differentiation, sexual development and control of male reproductive functions. In addition to its role in reproductive endocrinology and fertility, testosterone is an important hormone in the regulation and functioning of other organs and tissues including the kidney, heart, skeletal muscle, immune system and oral and periodontal tissues. Periodontitis is a disease characterized by inflammation of the periodontal tissues and associated with dental decay, are mainly responsible for the loss of dental elements. The relationship between sex steroids hormones and periodontal disease has been intensively investigated in females, however studies in males are still scarce. Therefore, the aim of the present project is to analyze the influence of testosterone deficiency on bone loss and histological structure of the periodontal tissues of castrated rats and experimental periodontitis. Twenty-eight male Wistar rats, provided by the Central Biotherium of Unioeste were used. At 80 days of age the animals were separated in four experimental groups, with 7 animals per group: no ligature control (CON), ligature control CON + LIG), no ligature castrated (CAST) and ligature castrated (CAST + LIG). At 90 days of age was held orchiectomy in appropriate groups. Sixty days after castration, the periodontal disease was induced by ligature technique. At the end of experimental period (90 days after castration), the animals were weighed and euthanized in a CO2 chamber. The mandible was removed, dissected, separated into left and right, were fixed by immersion in 10% buffered formalin for 24 hours, decalcified and processed for histological and radiological techniques. The results of this study showed that ligature model was effective 13 in inducing periodontitis in the animals. The food intake profile was similar between groups. The animals of CAST and CAST + LIG groups showed significant reduction in body weight at the end of experimental period, when compared with the groups CON and CON + LIG. Castration resulted in a significant bone loss in animals, which was accentuated with the induction of periodontal disease. Animals with periodontal diseases presented increased of gingival epithelium and connective tissue area, compared to animals without the disease. We conclude that testosterone is a physiological regulator important of alveolar bone metabolism. Testosterone deficiency in synergism with periodontal disease increases alveolar bone resorption and alters the thickness of gingival epithelium.Key / A testosterona é o principal hormônio sexual esteróide masculino envolvido na diferenciação, desenvolvimento sexual e controle das funções reprodutivas masculina. Além do seu papel na endocrinologia reprodutiva e fertilidade, a testosterona é um hormônio importante na regulação e funcionamento de outros órgãos e tecidos corporais tais como o rim, coração, músculo estriado esquelético, sistema imunológico e os tecidos orais e periodontais. A periodontite é uma doença caracterizada pelo processo inflamatório dos tecidos periodontais e juntamente com a cárie, são as grandes responsáveis pela perda de elementos dentais. As relações entre os hormônios sexuais esteróides e doença periodontal tem sido intensamente investigado em fêmeas, entretanto os estudos em machos ainda são escassos. Assim, o presente trabalho teve por objetivos analisar a influência da deficiência de testosterona sobre a perda óssea alveolar e estrutura histológica dos tecidos periodontais de ratos castrados e com periodontite experimental. Foram utilizados 28 ratos machos Wistar, fornecidos pelo Biotério Central da Unioeste. Aos 80 dias de idade os animais foram separados em quatro grupos experimentais, com 7 animais por grupo: controle sem ligadura (CON), Controle com ligadura (CON+LIG), castrado sem ligadura (CAST) e castrado com ligadura (CAST+LIG). Aos 90 dias de idade realizou-se a orquidectomia nos devidos grupos. Sessenta dias após a castração a doença periodontal foi induzida através da técnica de ligadura. Ao final do período experimental (90 dias após a castração), os animais foram pesados e sacrificados em câmara de CO2. As mandíbulas foram retiradas, dissecadas, separadas em direita e esquerda, fixada em formalina tamponada a 10% por 24 horas, descalcificada e 11 processadas para técnicas histológicas e radiológicas. Os resultados do presente trabalho demonstraram que o modelo de ligadura foi eficiente em induzir a periodontite nos animais. O perfil de consumo alimentar foi semelhante entre os grupos. Os animais dos grupos CAST e CAST+LIG apresentaram significativa redução do peso corporal ao final do período experimental, quando comparados aos grupos CON e CON+LIG. A castração levou a uma significativa perda óssea nos animais, a qual foi acentuada com a indução da doença periodontal. Os animais com doença periodontal apresentaram aumento de área do epitélio gengival e área de tecido conjuntivo, quando comparado aos animais sem a doença. Concluímos que a testosterona é um importante regulador fisiológico do metabolismo ósseo alveolar. A deficiência de testosterona em sinergismo com a doença periodontal aumenta a reabsorção óssea alveolar e altera a espessura do epitélio gengival.

<p>The purpose of this investigation was to study sexual function in women with neurological disorders at fairly distinct and separate locations. The dissertation comprises descriptive, retrospective, quantitative studies on sexual functioning in women with hypothalamo-pituitary disorders (HPD) (<i>n</i>:48), multiple sclerosis (MS)(<i>n</i>:47), and insulin-dependent diabetes mellitus (IDDM) (<i>n</i>:42). The results werecompared with those in an age-matched control group (C) (<i>n</i>:42), and as reported by representative Swedish women (<i>n</i>:742) in the Swedish sex survey SiS). The studies were based on comprehensive interviews, neurological examinations, incl. Vibration Perception Thresholds (IDDM), concentrations of prolactin and testosterone in serum (HPD), and a checklist on life satisfaction (IDDM, C, and SiS).</p><p>Sexual dysfunction was prevalent in almost all women with HPD and MS, and in 40% of the IDDM group. The problem of insufficient vaginal lubrication was more common in those with neurological disorders than among women in the SiS group. Sexual problems caused by reduced libido and orgasmic difficulties were more commonin the HPD and MS groups than in the SiS group. In the HPD group, women with intrasellar adenomas had better sexual function than women having expansively growing pituitary adenomas with both intra- and suprasellar extension. Normal serum testosterone values correlated to masturbation activity. Amenorrhea and older age werecorrelated with sexual problems in all groups. In the MS group, symptoms of a weak pelvic floor and of bladder and bowel dysfunction were correlated with reduced lubrication and orgasmic ability. In the IDDM group, signs of autonomic neuropathy were correlated with sexual dysfunction. Concerning life satisfaction generally,proportionately fewer women with IDDM were satisfied or very satisfied, though differing significantly from the other two groups in only two domains of life: contacts with friends, and physical health.</p>

How are new scientific concepts of illnesses and disorder formed? The last fifty years have seen a dramatic increase in new diagnoses incorporated into medical manuals. The concept of the male menopause, or the andropause diagnosis, is suitable for studying how medical knowledge is produced, since it has alternated between being and not being part of the acknowledged medical knowledge since the beginning of the 19th century, when it was originally launched. After being rather unnoticed during the 20th century, the concept of the male menopause had a renaissance in the 1990s’. The andropause then became a specific research area, articles about the male menopause were widely published in medical journals, specific therapies were developed, and andropause clinics opened around the world. The thesis explores what combination of circumstances lay behind the establishment of the andropause as a scientific object in the 1990s’. The purpose was to find out what the institutionalization of the (concept of the) andropause shows about the production of science, specifically  medical knowledge. Methodologically, the study can be described as an analysis of ideas, where the ideas contained in the concept of a male menopause are in focus. Accordingly, the research materials were scientific literature, media, and other documents where the idea of a male menopause was expressed. The analysis was structured in four divisions. First, the andropause theory was studied to find any obvious scientific explanations, such as new knowledge or discoveries. “Pure science” could not explain the breakthrough of the andropause diagnosis, since the andropause theory is laden with uncertainties according to the scientific principles of evaluation that the medical science itself supports. Second, the social organization of the medical knowledge production was inquired with focus on the medical profession, and the andropause theory was found to offer new professional arenas. Third, factors outside profession and science were found, the extra scientific dimensions, primarily cultural conditions and social structures. The emergence of feminist theory was found to change the perception of men in the culture, where the male norm no longer is self-evident. Fourth, in the social structure, pharmaceutical companies were found to engage strongly in the andropause concept. Together these factors constituted the andopause as a scientific object. The thesis demonstrates: the advantage of a multi perspective analysis: the complexity of the development of concepts of disease: the weakness of the epistemology of evidence-based medicine: and the social and cultural foundation of science.

The purpose of this investigation was to study sexual function in women with neurological disorders at fairly distinct and separate locations. The dissertation comprises descriptive, retrospective, quantitative studies on sexual functioning in women with hypothalamo-pituitary disorders (HPD) (n:48), multiple sclerosis (MS)(n:47), and insulin-dependent diabetes mellitus (IDDM) (n:42). The results werecompared with those in an age-matched control group (C) (n:42), and as reported by representative Swedish women (n:742) in the Swedish sex survey SiS). The studies were based on comprehensive interviews, neurological examinations, incl. Vibration Perception Thresholds (IDDM), concentrations of prolactin and testosterone in serum (HPD), and a checklist on life satisfaction (IDDM, C, and SiS). Sexual dysfunction was prevalent in almost all women with HPD and MS, and in 40% of the IDDM group. The problem of insufficient vaginal lubrication was more common in those with neurological disorders than among women in the SiS group. Sexual problems caused by reduced libido and orgasmic difficulties were more commonin the HPD and MS groups than in the SiS group. In the HPD group, women with intrasellar adenomas had better sexual function than women having expansively growing pituitary adenomas with both intra- and suprasellar extension. Normal serum testosterone values correlated to masturbation activity. Amenorrhea and older age werecorrelated with sexual problems in all groups. In the MS group, symptoms of a weak pelvic floor and of bladder and bowel dysfunction were correlated with reduced lubrication and orgasmic ability. In the IDDM group, signs of autonomic neuropathy were correlated with sexual dysfunction. Concerning life satisfaction generally,proportionately fewer women with IDDM were satisfied or very satisfied, though differing significantly from the other two groups in only two domains of life: contacts with friends, and physical health.

This study investigated factors associated with two mortality events: avian botulism in waterfowl and mortality associated with hatching asynchrony in prefledgling Franklins gulls (Larus pipixcan). The initial focus of my research was on the spatiotemporal relationship between mortality of Franklins gulls and the onset of botulism outbreaks in waterfowl, and the suitability of gull carcasses for proliferation and toxigenesis of Clostridium botulinum. From 1999 to 2001, dead hatch-year Franklins gulls were by far the most abundant carcasses, and the only source of toxin-laden maggots found on transects prior to the occurrence of avian botulism in waterfowl. Nest density was a significant predictor of hatch-year gull carcass density. High density of toxic material from gull carcasses prior to the onset of botulism in waterfowl coincided with high densities of susceptible birds; hence, mortality of Franklins gulls has the potential to be a major initiating factor for botulism outbreaks at Eyebrow Lake, Saskatchewan. The causes of gull mortality were conditions or diseases associated with starvation, stress, or immunosuppression, and most mortality occurred in third-hatched chicks. To separate effects of laying order from effects of hatching asynchrony on prefledgling survival, a cross-fostering experiment was conducted to create clutches containing asynchronously hatching eggs of the same laying order, and of similar egg mass, egg volume, and female quality. Hatching order, independent of laying order, significantly affected survival to fledging, whereas laying order had no observable effect, indicating that intraclutch variation in egg quality does not predetermine the fate of prefledglings, and may be less important than hatching asynchrony for survival of prefledgling Franklins gulls. Relationships among hatching asynchrony, laying order, mass, corticosterone, immune function, growth, and survival at two stages of development were complex. Hatching asynchrony significantly affected early and late prefledgling survival, and was directly or indirectly associated with mass, corticosterone level, and cell-mediated immune responses at early and later stages of development. Both hatching asynchrony and mass appeared to play key roles in mediating life history trade-offs among cell-mediated immune function, growth, and survival. In contrast to cell-mediated immune responses, primary humoral immune response was not directly affected by hatching order or mass, nor was it associated with survival to fledging. Rather, it was associated with laying order, neonatal testosterone, corticosterone at 2 weeks, growth of leg length, and clutch initiation date, illustrating the importance of examining more than one branch of the immune system in studies of life history trade-offs. This study is a step toward using a multipronged and multidisciplinary approach to demonstrate interactions and trade-offs among life history traits, the physiological mechanisms that produce these relationships, and how these relationships may change depending on stage of development.

<p>Endocrine&ndash / disrupting compounds (EDCs) are exogenous compounds/chemicals which interfere with, or have adverse effects on the production, distribution and function of natural hormones, thereby affecting normal endocrine activity, health and quality of life of both humans and wildlife. The reproductive system is highly susceptible to EDCs due to it being controlled by an array of hormonal signals. The effects of EDCs on the male reproductive system include infertility, decreased sperm count, function and morphology, abnormal development of secondary sex characteristics, reproductive function and sexual behaviour as well as decreased libido. There are various sources by which EDCs enter the environment which include effluents from several industries (mining, agriculture, smelting, hazardous waste sites, manufacturing industries, etc.), sewage treatment effluents, urban and agricultural runoff and effluents which include natural and pharmaceutical chemicals excreted in the urine of humans and domestic livestock, pesticides, polychlorinated biphenyls, dioxins, plasticizers, surfactants, etc. Humans and animals can also be affected by EDCs by consuming food containing endocrine active substances. The growing concern regarding adverse effects due to EDC exposure of humans and wildlife, as well as the increased incidence of EDC contamination has prompted extensive research into the development and validation of screening tests to detect and monitor known EDCs and new substances with endocrine-disrupting capability. These screening tests involve assessing the effect of known and potential EDCs on reproductive function and development as well as&nbsp / hormone production. To assess the effect of EDCs on the reproductive system different methods are employed which include in vitro, in vivo and ex vivo methods. In vitro methods have been suggested as a suitable screening tool for EDC monitoring due to low costs, reduced animal usage, the use of standard and basic equipment as well as the ability to screen a large number of samples with multiple endpoints. Of the available in vitro methods, the minced testes method has been suggested as the most suitable method for screening EDCs and for this reason has been employed in this study. The aim of this study was thus to employ a minced testes method to screen samples for male reproductive toxicity using cell viability and hormone production (testosterone and estradiol) as endpoints.The first objective of this study was to optimize an in vitro testicular cell culture assay by determining both optimal luteinizing hormone (LH)&nbsp / concentration and incubation time needed for testosterone production. Testicular cell cultures were prepared and cells were treated with varying concentrations of LH (10, 1, 0.1, 0.01 and 0 mu/ml) and incubated for 4 hours and 20 hours. Testosterone production was evaluated for each incubation period. Testosterone production was significantly increased for both incubation periods at all LH concentrations tested as compared to the control. For both incubation periods, there was no significant difference in testosterone production between the different LH concentrations tested. From the data obtained, the 4 hour incubation period as well as the LH concentration of 10 mu/ml were selected as optimal for the testicular cell culture assay. The second objective of this study was to determine the effect of Tulbaghia violacea Harv. on the male reproductive system. T. violacea is a plant species indigenous to southern Africa and is used locally as a herbal remedy/medicine to treat several ailments. Cells were treated with varying concentrations of the T. violacea ethanol extract (with/without LH-treatment) and incubated for 4 hours. Hormone production and cell viability were evaluated. The results obtained from this pilot in vitro study demonstrated that the ethanol extract of T.violacea has androgenic properties by significantly increasing LH-induced testosterone production in mouse testes with no significant change in cell viability. The third objective of this study was to assess the effect of Sutherlandia frutescens(L.) R.Br and Artemisia afra Jacq. Ex Willd. on the male reproductive system. S. frutescens and A. afra are also plant species indigenous to southern Africa and used locally as a herbal remedy/medicine to treat several ailments. Ethanol extracts of each plant was prepared and cells were treated with varying concentrations of each extract (0, 156.25, 312.5, 625, 1250,2500 and 5000 &mu / g/ml) with or without LH-treatment and incubated for 4 hours. Cytotoxicity by LDH measurement and hormone production (testosterone and estradiol) were endpoints that were evaluated. The results obtained showed that the ethanol extracts of both plants are not cytotoxic to testicular cells and that A. afra decreases testosterone production at high concentrations. The fourth and final objective of this study was to assess the acute effect of four heavy metals, namely manganese, copper, cadmium and magnesium on the male reproductive system. These heavy metals are used extensively in manufacturing and mining industries. Cells were treated with varying concentrations of each metal salt (200, 100, 50, 25, 12.5, and 6.25&nbsp / &mu / M) with or without LH-treatment and incubated for 4 hours. Endpoints evaluated included cell viability, testosterone and estradiol production. The results obtained showed that manganese, cadmium and copper are highly toxic to testicular cells in vitro and therefore may potentially cause reproductive toxicity.</p>