Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pathology. Title from title-page of electronic thesis. Includes bibliographical references.

Abstract Altogether 406 patients were included in five studies, and all patients were examined and controlled in the Oulu University Hospital during the years 1991–1998. Twenty-nine patients with mixed-type erectile dysfunction (ED) were recruited into a randomized, controlled, double-blind crossover comparison of placebo and high-dose yohimbine hydrochloride (36 mg per day orally). Positive clinical responses were obtained in 44% of the patients during yohimbine treatment and in 48% during placebo treatment. Thirty patients with ED underwent an intracavernosal injection test (ICI) using three different active agents (prostaglandin E1(PGE1), papaverine hydrochloride (PV), moxisylyte (MS)) and physiological saline. PGE1 produced significantly better rigidity than either PV or MS. Sixty-nine patients with ED who had started ICI therapy with PGE1 at least three years previously were invited to a control examination to find out the long-term outcome of this treatment and to evaluate the patients' overall satisfaction with their sexual life. 46.4% of the patients had discontinued PGE1 therapy, the mean time of using PGE1 having been 23.3 months (range 0–48 months). 34.8% of the patients reported that their own spontaneous erections had improved during the PGE1 therapy. The sexual functions of 155 patients with benign prostatic hyperplasia (BPH) were evaluated before TURP and 6 and 12 months afterwards with questionnaires. Only 26% of the patients had completely satisfactory erections before TURP, while 22% had satisfactory erections 6 months later and 24% 12 months later. The majority of patients (about 70%) were satisfied with their sexual life both before and after the procedure. 123 men with symptoms of andropause participated in a randomized, placebo-controlled study to assess the effects of dihydrotestosterone (DHT) gel in men with andropausal symptoms. The drug was administered transdermally once a day during six months. Early morning erections improved significantly (p < 0.003) in the DHT group by the three-month control, the ability to maintain erections was better, and there was also a positive effect on libido. In the patients with a elevated (> 12) international index of the prostatic symptoms score (I-PSS) before DHT treatment, I-PSS decreased from 17.7 to 12.3 points. As a conclusion yohimbine hydrochloride is no better than placebo in the treatment of patients with mixed-type ED. PGE1, PV and MS are well tolerated, and PGE1 was shown to be the most effective drug of the three. ICI therapy with PGE1 in long-term use is safe and effective. Sexual functions in men did not change after TURP, and this group of aging men were fairly satisfied with their sexual life despite of the fact that they had some ED and one third of the patients had not had intercourse during the previous year. Transdermal administration of DHT in aging men improves sexual function.

Objectif : Identifier les déterminants physiques et métaboliques de la rigidité artérielle mesurée par tonométrie de l'amplitude du pouls (PAT) digital chez l'homme et la femme ménopausée. Méthodes : La rigidité artérielle, exprimée par l'index d'hyperémie réactive (RHI), a été mesurée par PAT digitale (EndoPAT2000, Itamar Medical, Caesarea, Israël) suite à l'obstruction de l'artère brachiale pendant 5 minutes chez un groupe de 88 hommes (âge moyen ± écart type : 57.9 ± 6.7 ans) et 135 femmes ménopausées (59.2 ± 5.2 ans). Le profil cardiométabolique a été déterminé et des mesures anthropométriques effectuées pour chaque participant. Résultats : Les valeurs de RHI étaient significativement plus basses chez les hommes comparativement aux femmes ménopausées (1.86 ± 0.56 vs. 2.26 ± 0.72 respectivement, p<0.0001). Des corrélations significatives ont été notées entre le RHI et l'indice de masse corporelle (r=-0.22, p=0.0001), la circonférence de la taille (r=- 0.22, p=0.002) ainsi qu'avec les concentrations plasmatiques de cholestérol-HDL (r=0.33, p<0.0001) et le ratio cholestérol total/cholestérol-HDL (r=-0.24, p=0.0006). Par ailleurs, les individus présentant un syndrome métabolique (SMet) affichaient des valeurs de RHI plus faibles (-15.8%, p=0.0003) et des concentrations plasmatiques de molécules d'adhésion ICAM-1 plus élevées (+28.6%, p=0.0003) que les sujets ne présentant pas de SMet. Conclusion : Nos résultats démontrent que, comparativement aux femmes ménopausées, les hommes affichent une rigidité artérielle plus importante et que celle-ci semble être modulée par la présence d'obésité abdominale et d'un profil lipidique altéré. Par ailleurs, nos résultats indiquent que les individus affichant un SMet sont caractérisés par une dysfonction endothéliale pouvant contribuer à l'accroissement du risque d'atteinte cardiovasculaire. Des études supplémentaires sont nécessaires afin de mieux comprendre comment une condition dysmétabolique favorise le développement de la rigidité artérielle et de la dysfonction endothéliale chez l'homme et la femme.

Estudos em animais e humanos sugerem que níveis adequados de testosterona são necessários para preservar a integridade do tecido eretor peniano. Nenhum estudo prévio confirmou se as mudanças estruturais são reversíveis após longo período de deprivação hormonal. Foi proposto a avaliação, através de métodos quantitativos, as alterações estruturais no corpo cavernoso de ratos submetidos à castração cirúrgica; bem como o papel da reposição hormonal tardia na reversão das possíveis alterações estruturais. Foram usados 25 ratos Sprague-Dawley machos com aproximadamente 12 semanas de idade. Os animais foram divididos em 5 grupos compostos por 5 animais em cada grupo e tratados da seguinte forma: ORQ1 = Grupo submetido à orquiectomia e sacrificado após 1 mês. C1- Grupo controle morto após 1 mês. ORQ2 - Grupo orquiectomizado e morto após 2 meses. C2 - Grupo controle morto após 2 meses. T Grupo orquiectomizado que recebeu, após 1 mês, suplementação com undecanoato de testosterona na dose de 100mg/ Kg subcutâneo. Após 1 mês de reposição hormonal os animais foram mortos.No Resultado Houve uma redução significativa no valor absoluto do colágeno, músculo liso, espaço sinusoidal e área total do corpo cavernoso após 2 meses no grupo castrado, quando comparado ao controle. Em termos gerais a densidade não apresentou nenhuma diferença significativa entre os grupos. A reposição hormonal com testosterona foi capaz de reverter as alterações observadas, demonstrando um aumento dos elementos estudados. A metodologia utilizada permitiu mostrar que valores absolutos demonstram melhor o que de fato ocorre com os elementos observados, eliminando um víeis de análise, quando se consideram os valores relativos. Esses resultados sugerem que a reposição, mesmo quando realizada tardiamente, foi eficaz na reversibilidade das alterações geradas pela castração / Introduction. Studies in animals and humans have suggested that adequate levels of testosterone are necessary to preserve the integrity of penile erectile tissue. No previously reported studies have confirmed if these structural changes are reversible following long-term hormonal deprivation. To evaluate, through quantitative methods, the structural alterations in the corpora cavernosa of rats submitted to surgical castration as well as the role of late hormone replacement in reversing the possible structural alterations. We used 25 male Sprague-Dawley rats who were approximately 12 weeks of age. The animals were divided into 5 groups composed of 5 animals each and treated as follows. ORCHIEC-1 = group that underwent orchiectomy and were sacrificed after 1 month, C-1 = control group sacrificed after 1 month, ORCHIEC-2 = group that underwent orchiectomy and were sacrificed after 2 months, C-2 = control group sacrificed after 2 months, T = group that underwent orchiectomy, and after 1 month underwent testosterone replacement with a subcutaneous single dose of testosterone undecanoate at 100 mg/kg (T); after 1 month of hormonal replacement, the animals were sacrificed. Quantification of smooth muscle, collagen and elastic system fibers in controls and rats submitted to orchiectomy alone and with late hormonal replacement. There were a significant decrease in the absolute values of collagen, smooth muscle, sinusoidal space and total area of corpora cavernosa after 2 months in the castrated group when compared with controls. Overall, as regards density, no significant differences were observed among the groups. The hormonal replacement with testosterone was able to reverse the alterations observed, demonstrating an increase in the elements studied. The method used for this research allowed demonstrating that absolute values are reliable to quantify the structural alterations of corpora cavernosa structures. The results suggest that hormonal replacement, even when instituted at a late stage, is effective in reversing the corpora cavernosa alterations produced by castration

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo dessa dissertação é explorar a reformulação da antiga andropausa no diagnóstico de Deficiência Androgênica do Envelhecimento Masculino (DAEM) e seu tratamento farmacológico, que é a reposição de testosterona. Essa "nova" patologia se localiza dentro do escopo da Medicina Sexual, e faz parte, juntamente com a disfunção erétil e a ejaculação precoce, de um avanço da medicalização sobre corpos masculinos. Realizei entrevistas semi-estruturadas com alguns médicos envolvidos no estabelecimento do DAEM. Esses profissionais são urologistas ou endocrinologistas, ou ainda andrologistas, acadêmicos, mas que também mantêm um consultório. A entrevista pode ser dividida em dois grandes grupos, um relativo à definição e diagnóstico do DAEM, e a centralidade do sexo nas queixas do paciente. O outro analisa a terapia de reposição hormonal em si, e as conseqüências para a masculinidade da deficiência de testosterona. Elenquei ainda um terceiro tema, relativo às disputas entre as duas especialidades médicas, e as diferenças nas abordagens dos problemas colocados, que encobriam diferentes concepções de corpo e doença. Por fim, tentei manter gênero e envelhecimento como eixos transversais, que atravessassem toda a entrevista. O objetivo desse roteiro era perceber, sob a ótica desses médicos, como o DAEM é construído tanto na academia quanto na clínica médica, e quais as idéias subjacentes ao seu diagnóstico e tratamento. Portanto, nessa dissertação, pretendo analisar como o DAEM parece se localizar numa encruzilhada, unificando novos ideais de masculinidade e envelhecimento, sob a égide da medicina sexual e seus tratamentos farmacológicos. Porém, para isso, foi preciso antes investigar as mudanças na masculinidade e na velhice, o que as definia antes, e quais os novos desenhos que elas apresentam, para poder vislumbrar sua articulação com a medicalização e/ou farmacologização da sexualidade masculina.

Estudos em animais e humanos sugerem que níveis adequados de testosterona são necessários para preservar a integridade do tecido eretor peniano. Nenhum estudo prévio confirmou se as mudanças estruturais são reversíveis após longo período de deprivação hormonal. Foi proposto a avaliação, através de métodos quantitativos, as alterações estruturais no corpo cavernoso de ratos submetidos à castração cirúrgica; bem como o papel da reposição hormonal tardia na reversão das possíveis alterações estruturais. Foram usados 25 ratos Sprague-Dawley machos com aproximadamente 12 semanas de idade. Os animais foram divididos em 5 grupos compostos por 5 animais em cada grupo e tratados da seguinte forma: ORQ1 = Grupo submetido à orquiectomia e sacrificado após 1 mês. C1- Grupo controle morto após 1 mês. ORQ2 - Grupo orquiectomizado e morto após 2 meses. C2 - Grupo controle morto após 2 meses. T Grupo orquiectomizado que recebeu, após 1 mês, suplementação com undecanoato de testosterona na dose de 100mg/ Kg subcutâneo. Após 1 mês de reposição hormonal os animais foram mortos.No Resultado Houve uma redução significativa no valor absoluto do colágeno, músculo liso, espaço sinusoidal e área total do corpo cavernoso após 2 meses no grupo castrado, quando comparado ao controle. Em termos gerais a densidade não apresentou nenhuma diferença significativa entre os grupos. A reposição hormonal com testosterona foi capaz de reverter as alterações observadas, demonstrando um aumento dos elementos estudados. A metodologia utilizada permitiu mostrar que valores absolutos demonstram melhor o que de fato ocorre com os elementos observados, eliminando um víeis de análise, quando se consideram os valores relativos. Esses resultados sugerem que a reposição, mesmo quando realizada tardiamente, foi eficaz na reversibilidade das alterações geradas pela castração / Introduction. Studies in animals and humans have suggested that adequate levels of testosterone are necessary to preserve the integrity of penile erectile tissue. No previously reported studies have confirmed if these structural changes are reversible following long-term hormonal deprivation. To evaluate, through quantitative methods, the structural alterations in the corpora cavernosa of rats submitted to surgical castration as well as the role of late hormone replacement in reversing the possible structural alterations. We used 25 male Sprague-Dawley rats who were approximately 12 weeks of age. The animals were divided into 5 groups composed of 5 animals each and treated as follows. ORCHIEC-1 = group that underwent orchiectomy and were sacrificed after 1 month, C-1 = control group sacrificed after 1 month, ORCHIEC-2 = group that underwent orchiectomy and were sacrificed after 2 months, C-2 = control group sacrificed after 2 months, T = group that underwent orchiectomy, and after 1 month underwent testosterone replacement with a subcutaneous single dose of testosterone undecanoate at 100 mg/kg (T); after 1 month of hormonal replacement, the animals were sacrificed. Quantification of smooth muscle, collagen and elastic system fibers in controls and rats submitted to orchiectomy alone and with late hormonal replacement. There were a significant decrease in the absolute values of collagen, smooth muscle, sinusoidal space and total area of corpora cavernosa after 2 months in the castrated group when compared with controls. Overall, as regards density, no significant differences were observed among the groups. The hormonal replacement with testosterone was able to reverse the alterations observed, demonstrating an increase in the elements studied. The method used for this research allowed demonstrating that absolute values are reliable to quantify the structural alterations of corpora cavernosa structures. The results suggest that hormonal replacement, even when instituted at a late stage, is effective in reversing the corpora cavernosa alterations produced by castration

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O objetivo dessa dissertação é explorar a reformulação da antiga andropausa no diagnóstico de Deficiência Androgênica do Envelhecimento Masculino (DAEM) e seu tratamento farmacológico, que é a reposição de testosterona. Essa "nova" patologia se localiza dentro do escopo da Medicina Sexual, e faz parte, juntamente com a disfunção erétil e a ejaculação precoce, de um avanço da medicalização sobre corpos masculinos. Realizei entrevistas semi-estruturadas com alguns médicos envolvidos no estabelecimento do DAEM. Esses profissionais são urologistas ou endocrinologistas, ou ainda andrologistas, acadêmicos, mas que também mantêm um consultório. A entrevista pode ser dividida em dois grandes grupos, um relativo à definição e diagnóstico do DAEM, e a centralidade do sexo nas queixas do paciente. O outro analisa a terapia de reposição hormonal em si, e as conseqüências para a masculinidade da deficiência de testosterona. Elenquei ainda um terceiro tema, relativo às disputas entre as duas especialidades médicas, e as diferenças nas abordagens dos problemas colocados, que encobriam diferentes concepções de corpo e doença. Por fim, tentei manter gênero e envelhecimento como eixos transversais, que atravessassem toda a entrevista. O objetivo desse roteiro era perceber, sob a ótica desses médicos, como o DAEM é construído tanto na academia quanto na clínica médica, e quais as idéias subjacentes ao seu diagnóstico e tratamento. Portanto, nessa dissertação, pretendo analisar como o DAEM parece se localizar numa encruzilhada, unificando novos ideais de masculinidade e envelhecimento, sob a égide da medicina sexual e seus tratamentos farmacológicos. Porém, para isso, foi preciso antes investigar as mudanças na masculinidade e na velhice, o que as definia antes, e quais os novos desenhos que elas apresentam, para poder vislumbrar sua articulação com a medicalização e/ou farmacologização da sexualidade masculina.

No description available.

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.

Although the female menopause has been extensively characterized as a well-defined symptomatic state of oestrogen deficiency, which responds relatively well to oestrogen replacement therapy, the symptomatic state of androgen deficiency in men is poorly defined and uncertainty exists whether it responds to testosterone replacement. It has been proposed that hypothalamic-pituitary-testicular (HPT)-axis function (responsible for the production of androgens) and regulation could be viewed as a ‘barometer’ of health status in older men and that potential alterations in HPT-axis function and regulation reflect subclinical and clinical deficits in function and health, which may result in an aged phenotype of human health and disease in older men. The HPT-axis constitutes a well-defined, tractable, clinically-relevant, biological system, which may permit insight into the mechanisms underlying the expression of ageing-related phenotypes of human health and disease. By using a different lens – such as the genetic background; the compensatory responses within the HPT-axis; the syndromes of androgen deficiency; the ethnic background of an individual or the life course trajectory of function and health from conception into older age – to magnify potential dysregulation in the HPT-axis will it be possible to visualize and understand the phenotypic expression of human male ageing as a gradient of functional and health outcomes. This will allow for a better understanding of the physiological mechanics underlying symptomatic expression of dysregulation in the HPT-axis.