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Le cancer du sein est le type de cancer le plus commun chez les femmes, toutefois, certaines tumeurs demeurent difficilement traitables; le développement de métastases et la résistance aux traitements offerts diminuent davantage l’espérance de vie des patients. Il est donc impératif de trouver de nouvelles méthodes pour combattre le cancer. Les virus oncolytiques sont une solution très prometteuse. Ce traitement révolutionne l’oncologie notamment par sa spécificité aux cellules cancéreuses (peu toxique) et l’implication du système immunitaire du patient (protection contre les récidives). Notre virus modèle est un mutant du virus de la stomatite vésiculaire qui cible et détruit les cellules cancéreuses tout en épargnant les cellules saines. Le défi actuel est d’identifier les facteurs influençant l’efficacité du traitement, car ce ne sont pas tous les cancers qui répondent de manière optimale aux virus oncolytiques. De nombreux facteurs présents dans le micro-environnement tumoral ont le potentiel d’influencer la réplication virale et pourraient donc être manipulés au bénéfice de la thérapie, comme les hormones produites par le corps. De nombreux résultats obtenus par notre laboratoire démontrent que l'estrogène promeut la réplication virale et la mort cellulaire des cellules tumorales en sensibilisant la cellule cancéreuse à l’infection virale, et que l’expression du récepteur d’estrogène indique un pronostique positif pour la virothérapie du cancer du sein. Par ailleurs, des résultats cliniques ont démontré le potentiel d’un traitement combinant la testostérone et un inhibiteur d’aromatase (enzyme qui transforme la testostérone en estrogène) dans lequel la tumeur a diminué après seulement deux semaines de traitement et des résultats de notre laboratoire démontrent que la testostérone améliore notre virothérapie. Notre hypothèse est que certaines hormones ont la capacité de moduler l’infection virale et pourront être exploitées pour favoriser la thérapie du cancer par les virus oncolytiques. Nos résultats pourront guider de futures combinaisons de virus oncolytiques avec des traitements ou supplémentations hormonaux afin de maximiser les bénéfices cliniques. / Breast cancer is the most common type of cancer among women in Canada and yet, the treatments that are currently available are aggressive and won’t treat the disease completely, a lot of tumours remain incurable. Therefore, it’s crucial to find new innovative alternatives to fight aggressive forms of breast cancer that remain hardly treatable by current standards of care, and oncolytic viruses are very promising assets. This treatment revolutionizes cancer therapy by directly killing tumour cells (with a high safety profile) and harnesses the patient’s immune system, avoiding future relapses. Unfortunately, not all cancers are sensitive to oncolytic virotherapy, and one important current challenge is to identify factors influencing treatment efficacy. As such, many factors, like hormones, present in the tumour microenvironment have the potential to impact viral replication and could potentially be manipulated to the benefit of the therapy. Data obtained in our laboratory demonstrate that estrogen promotes viral replication and tumour cell killing and that the expression of the estrogen receptor predicts successful outcome upon viral therapy in breast cancer. Furthermore, clinical studies have shown the potential of a combination of testosterone and aromatase inhibitor (inhibits the transformation of testosterone in estrogen), in which significant tumour regression was observed after 2 weeks of treatment and we have data showing that testosterone improves oncolytic virotherapy. Different hormones have been shown to have an impact on either breast cancer or viral replication and could possibly affect our virotherapy’s efficacy. Here, our hypothesis is that different hormones have viral-modulating effects and that these effects could be exploited to improve the efficacy of oncolytic virotherapy against breast cancer.

Berättelsen om testosteronet. En historisk studie av vetenskapen om det manliga könshormonet inom det manliga klimakteriet och homosexualitet. Syftet med denna uppsats är att undersöka hur historien och idéerna om manliga klimakteriet och testosteron är kopplade till de idéer som finns om sexualitet, moral och hur läkarna såg på det manliga klimakteriet. Syftet är också att förstå hur idéerna om det manliga klimakteriet har förändrats från 1920-talet jämfört med idag och hur det har diskuterats under åren av forskare. Vikten av testosteron och vilken roll idéerna om testosteron har spelat är också av betydelse för syftet i denna uppsats. I uppsatsen använder jag sociologen Peter Conrads teori om medikalisering. Conrad beskriver medikalisering genom att säga att det är en process där icke medicinska problem förändras och bli definierade och behandlas som medicinska problem och detta görs vanligen i form av sjukdom och störningar. I den här uppsatsen beskriver jag hur idéer om ett manligt klimakterium utvecklades under perioden 1920-talet – 1960-talet. Jag beskriver de idéer forskarna och läkarna hade om vad ett manligt klimakterium kunde vara. I uppsatsen undersöks även vilken effekt upptäckten av testosteron hade på idéer om det manliga klimakteriet. Debatten som läkarna har haft om det finns ett manligt klimakterium eller inte behandlas även i uppsatsen. I uppsatsen presenterar jag fyra olika svenska läkare och en finsk läkare från perioden 1920-talet – 1960-talet och behandlar deras idéer om det manliga klimakteriet och testosteron. Då diskussionen vänder sig till testosteronet presenterar jag Paul de Kruif som publicerade boken The Male Hormone (1945) och var en av de första att göra reklam för testosteronbehandling. Jag beskriver även medikaliseringen av det manliga klimakteriet och testosteron och varför det manliga klimakteriet och testosteron inte fick samma genomslag som det kvinnliga. I denna uppsats behandlas också förhållandet mellan de manliga könshormonen och homosexualitet. Jag undersöker varför läkare försökte använda testosteron och andra manliga hormon som ”botemedel” av homosexuella män och jag beskriver ett experiment som gjordes på homosexuella av den svenska doktorn Erik Lundberg. / The purpose of this essay is to investigate the history and ideas of the male menopause and testosterone and how they are linked to ideas about sexuality, morality and how the doctors viewed the male menopause. The aim is also to understand how ideas about the male menopause has changed from the 1920’s compared to today and how it has been discussed by scientists. The importance of testosterone and the role the ideas of testosterone have played is also of importance for the purpose of this essay. In the essay, I use the sociologist Peter Conrad's theory of medicalization. Conrad describes medicalization by saying that it is a process where non-medical problems change and become defined and treated as medical problems, and this is usually done in the form of disease and disorders. In this essay, I describe how the ideas of a male menopause evolved in the period 1920’s - 1960’s. I describe the ideas scientists and doctors had about what a male menopause could be. This essay also examines the impact the discovery of testosterone had on ideas about the male menopause. The debate that doctors have had if there is a male menopause or not is also discussed in the essay. In this essay, I present four Swedish doctors and a Finnish doctor from the period 1920’s - 1960’s and their ideas about the male menopause and testosterone. When the discussion turns to testosterone, I present Paul de Kruif who published the book The Male Hormone (1945) and was one of the first to promote testosterone treatment. I also describe the medicalization of male menopause and testosterone and why the male menopause and testosterone did not have the same impact as the female menopause. This essay also discusses the relationship between the male hormone and homosexuality. I examine why doctors tried to use testosterone and other male hormones as a "cure" of gay men and I describe an experiment conducted on homosexuals by the Swedish doctor Erik Lundberg.

Age-related declines of androgens and libido in males have been observed for decades. This dissertation sought to elucidate the mechanisms by which hormones may act differentially upon their receptors in the hypothalamus of aging compared to young males. I also examined how sexual experience modulates the ability of hormones to facilitate sexual behavior with aging. Experiment one measured androgen receptors (AR) and estrogen receptor α (ERα) cells in male rats at young, middle-aged and old age. I found that AR cell numbers in hypothalamic regions studied underwent significant age-related increases. Numbers of heavily ERα labeled cells, but not total ERα cells, increased with age. This study demonstrates that the aging brain has the capacity to synthesize hormone receptors which is increased possibly due to decreased testosterone concentrations. Experiment two examined the effect of sexual experience on serum hormones and cells of AR and ERα in hypothalamic regions in young and middle-aged males. The results showed that AR cell numbers increased with aging but did not change with experience. No age- or experience-related alteration in ERα expression occurred. However, serum testosterone increased and estradiol decreased with age. Experience increased total and free testosterone. Interactions of age and experience on total testosterone, estradiol, and luteinizing hormone were found. These results show long-lasting effects of sexual experience on hormones, but not on their receptors in the hypothalamus. Experiment three investigated effects of exogenous testosterone on sexual behavior in young and middle-aged males. The results showed a decline in sexual behavior parameters with age. After castration with testosterone treatment, there were few differences in sexual behavior measures between young and middle-aged males. AR cell numbers were higher and ERα cell numbers lower in testosterone compared to vehicle-treated males of both ages, and few effects of age occurred. These findings indicate that testosterone and aging interact in a complex manner to control numbers of cells expressing hormone receptors in the brain and on the subsequent control of sexual behavior. This insight provides a better understanding of the relationship between molecular changes in the brain and behavior, and suggests new therapeutic targets to human testosterone treatment. / text

Un animal qui s’approvisionne en groupe peut rechercher soi-même sa nourriture (tactique producteur) ou tenter de se joindre à des parcelles déjà découvertes par un autre individu (tactique chapardeur). Bien que les modèles de jeu producteur-chapardeur partent du principe que les gains moyens à l’équilibre associés à chacune de ces tactiques sont égaux et ne dépendent pas des caractéristiques des individus, de plus en plus d’études démontrent que le gain de chaque tactique est influencé par certaines caractéristiques phénotypiques (agressivité, capacités d’apprentissage,…). Dans cette étude, nous nous intéressons aux effets de la testostérone sur le choix des tactiques d’approvisionnement chez les mâles de diamant mandarin (Taeniopygia guttata). La testostérone est connue pour influencer le développement du cerveau et l’agressivité, nous avons donc testé les effets d’une exposition prénatale à la testostérone ainsi que durant l’âge adulte sur le choix des tactiques d’approvisionnement lorsque la nourriture est cryptique ou défendable. Nous avons réalisé deux expériences : nous avons tout d’abord utilisé la longueur du tarse ainsi que la différence entre les longueurs des doigts 2 et 4 comme des indicateurs de l’exposition prénatale à la testostérone puis testé si ces différences morphologiques se traduisent par des différences dans le choix des tactiques dans une condition défendable et une condition cryptique. Nous avons trouvé que le choix des tactiques chez les diamants mandarins était limité par le phénotype. Une exposition précoce à la testostérone au cours du développement prénatal pourrait donc être la cause d’au moins une part de la variation observée dans le choix des tactiques d’approvisionnement. Ensuite, nous avons manipulé le taux de testostérone plasmatique chez des mâles adultes grâce à des implants hormonaux sous-cutanés puis comparé le comportement des individus lorsqu’ils portaient un implant hormonal et un implant contrôle et ce, dans chacune des deux conditions d’approvisionnement. Nous n’avons mis en évidence aucun effet du taux de testostérone plasmatique sur le choix des tactiques à l’âge adulte. Nos résultats sont en accord avec l’hypothèse que le choix des tactiques d’approvisionnement peut être influencé par les hormones. Notre conclusion est que les hormones stéroïdiennes peut affecter le choix des tactiques via l’existence d’effets maternels dans le jeu producteur-chapardeur. / An animal foraging in groups can search for its own food (producer tactic) or try to join food patches previously discovered by another group member (scrounger tactic). Although producer-scrounger game models assume that the payoffs associated with both tactic are equal at equilibrium and so do not depend on individual characteristics, there is recent evidence that tactic choice is constrained by certain phenotypical traits (aggressivity, learning abilities…). In this study, we examined the effect of testosterone on tactic use in male zebra finches (Taeniopygia guttata). Because testosterone is known to affect both brain development and aggressiveness, we tested whether differences in testosterone exposure either during development or in adulthood had an effect on producer-scrounger tactic use, when food was cryptic or defendable. First, we measured the tarsus length and the distance between the end of the fourth and the end of the second digit as proxies of prenatal exposure to testosterone, and tested whether they were correlated with foraging tactic use under both conditions. We found that tactic choice in zebra finches is phenotypically constrained. We suggest that early exposure to sex hormones during the embryonic period could be responsible for at least a part of the variation in tactic choice. Second, we manipulated the circulating level of testosterone in adult male zebra finches using subcutaneous testosterone implants, and compared the behavior of individuals when they had either a control implant or a testosterone implant. This time we found no effect of plasmatic level of testosterone on tactic choice. Our results are consistent with the hypothesis that tactic choice in zebra finches could be mediated by hormones. Our finding that steroid hormones can affect tactic use provides evidence for maternal effects in producer-scrounger games.

Orientador: Vania dos Santos Nunes Nogueira / Resumo: Introdução: o uso de testosterona em homens obesos tem sido controverso em termos de perda de peso e controle de doenças relacionadas à obesidade. Objetivo: avaliar a efetividade da reposição de testosterona para perda de peso e prevenção de complicações cardiovasculares em homens obesos com baixos níveis séricos de testosterona. Métodos: foi realizada uma revisão sistemática de acordo com a Metodologia Cochrane de estudos randomizados que compararam em homens obesos com baixos níveis de testosterona a reposição de testosterona versus a não reposição. Dois revisores (ASM e LARB) independentemente fizeram a seleção dos estudos, avaliaram o risco de viés e extraíram os dados dos estudos incluídos. Os desfechos primários analisados foram: melhora dos parâmetros antropométricos (peso, índice de massa corpórea, circunferência de cintura e composição corporal), segurança, qualidade de vida, controle de complicações relacionadas a obesidade e melhora dos sintomas de hipogonadismo. As bases de dados eletrônicas para pesquisa foram Embase, Medline, LILACS e CENTRAL. Desfechos semelhantes em pelo menos dois estudos foram plotados na meta-análise usando o software Review Manager 5.3. A qualidade da evidência da estimativa de efeito da intervenção foi gerada de acordo com a metodologia GRADE (Grading of Recommendations Assessment, Development and Evaluation). Resultados: as estratégias de busca elaboradas resultaram em 2535 artigos após a remoção das duplicatas pelo software Endnote. For... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: The use of testosterone replacement therapy in obese men with low testosterone levels has been controversial in relation to weight loss and control of obesity related-diseases. Objective: To analyze the effectiveness of testosterone therapy for weight loss and prevention of cardiovascular complications in obese men with low serum testosterone levels. Methods: A systematic review was conducted according to the Cochrane Methodology of randomized trials comparing testosterone replacement versus non-replacement in obese men with low testosterone levels. Two reviewers (ASM and LARB) independently selected the studies, assessed the risk of bias, and extracted data from the included studies. The main outcomes analyzed were: improvement of anthropometric parameters (weight, body mass index, waist circumference and body composition), safety, quality of life, control of complications related to obesity and improvement of symptoms of hypogonadism. The electronic databases for search were Embase, Medline, LILACS and CENTRAL. Similar outcomes in at least two trials were plotted in the meta-analysis using Review Manager 5.3 software. The quality of the evidence of the intervention effect estimate was generated according to GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). Results: the search strategies elaborated resulted in 2535 articles after the duplicates were removed by Endnote software. A total of 38 articles were selected for reading, ... (Complete abstract click electronic access below) / Mestre

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.

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Introdução: Vários são os fatores que alteram a atividade sexual de homens e mulheres. Com o envelhecimento observa-se aumento das queixas de desejo hipoativo feminino e de disfunção erétil. Visto que o homem e sua parceira constituem um sistema dinâmico, antes do advento dos inibidores da fosfodiesterase eles se adaptavam às condições disfuncionais do casal. A eficácia aliada a poucos efeitos colaterais e à facilidade de administração da sildenafila e, posteriormente, da vardenafila e tadalafila, revolucionou o tratamento da disfunção erétil. Por outro lado, até a presente data, a terapêutica medicamentosa com testosterona para o desejo sexual hipoativo de mulheres, ainda gera controvérsias. Objetivo: Avaliar o uso de androgênio, utilizado para tratamento das queixas de desejo sexual hipoativo em mulheres, comparando dois períodos, ou seja, pré e após o aparecimento iPDE 5. Os efeitos colaterais e as divergências em relação a este tratamento também serão analisados. Método: Foram selecionados estudos em inglês, português e espanhol, publicados entre 1988 e os dias atuais, ou seja, na década pré-advento dos inibidores da fosfodiesterase 5 e após. A busca dos artigos foi feita em periódicos indexados nas bases Lilacs, Cochrane, Embase e Medline/PubMed, utilizando-se os seguintes descritores e suas combinações: sexualidade (sexuality), desejo sexual hipoativo em mulheres (female hypoactive sexual desire disorder), testosterona (testosterone), terapia androgênica em mulheres (androgen therapy in women). Discussão: Embora haja evidência sobre a efetividade do tratamento com testosterona para desejo hipoativo em mulheres, este uso ainda gera muitas controvérsias. Resultados: O número de estudos randomizados sobre uso de testosterona para tratamento de DSH feminino aumentou de 10%, comparando o período compreendido entre 1988 e 1998, para 90% entre 1999 e 2012. Todos os estudos randomizados analisados demonstraram benefícios sobre a resposta sexual, melhorando a libido, a excitação e/ou o orgasmo. Porém, como tiveram seguimento por um período máximo de 24 semanas, os riscos dessa administração não foram esclarecidos. Conclusão: A partir de 1988, ou seja, após a liberação comercial dos inibidores da fosfodiesterase do tipo 5, para tratamento da disfunção erétil, houve um aumento significativo do número de pesquisas com a finalidade de avaliar o uso de testosterona em mulheres com desejo hipoativo. Porém, ainda são necessários estudos de longo prazo para que os riscos e os benefícios, desta administração, sejam esclarecidos / Introduction: There are several factors that alter the sexual activity of both men and women. With age, an increase in complaints about hypoactive feminine desire and erectile dysfunction can be observed. Since the man and his partner constitute a dynamic system, before the advent of phosphodiesterase inhibitors, they would adapt to the dysfunctional conditions of the couple. The efficacy with few collateral effects and the easy administration of sildenafil and later, vardenafil and tadalafil, has revolutionized the treatment of erectile dysfunction. On the other hand, until now, the drug therapy with testosterone for hypoactive sexual desire of women still generates controversies. Objective: Assess the use of androgen, used for treating complaints of hypoactive sexual desire in women, comparing two periods, that is, before and after the emergence of iPDE 5. Side effects and divergences regarding this treatment are also analyzed. Method: Studies in English, Portuguese and Spanish were selected, published between 1988 and the present, that is, in the decade before the advent of phosphodieterase 5 inhibitors and after this fact. The search for papers was made in indexed journals on Lilacs, Cochrane, Embase and Medline/PubMed data bases, using the following descriptors and their combinations: sexuality, female hypoactive sexual desire disorder, testosterone or androgen therapy in women. Discussion: Although there is evidence on the effectiveness of treatment with testosterone for hypoactive desire in women, this use still generates many controversies. Results: The number of randomized studies on the use of testosterone for the treatment of female HSD has increased 10%, comparing the period between 1988 and 1998, to 90% between 1999 and 2012. All randomized studies analyzed showed benefits on the sexual response, improving libido, excitation and/or orgasm. However, since they were followed for a maximum of 24 weeks, the risks of this dosage were not clarified. Conclusion: From 1988, that is, after the commercial release of phosphodiesterase type 5 inhibitors, for the treatment of erectile dysfunction, there was a significant increase in the number of papers with the purpose of evaluating the use of testosterone in women with hypoactive desire. However, there is the need of long-term studies in order to clarify the risks and benefits of this use

Introdução: Estudos experimentais com animais sugerem que a testosterona atua reduzindo a resposta nociceptiva após estímulos inflamatórios e neuropáticos, porém, o mecanismo pela qual este hormônio atua ainda não foi completamente esclarecido. O objetivo deste estudo é avaliar se o bloqueio androgênico com flutamida promove aumento da nocicepção, e ainda, investigar se esta modulação do comportamento doloroso é decorrente de aumento da expressão de canais de sódio voltagemdependente Nav1.7 e Nav1.8 no gânglio da raiz dorsal de ratos após incisão plantar. Método: Os animais estudados foram divididos em um grupo que recebeu flutamida por via subcutânea, e em um grupo controle que recebeu apenas o veículo como placebo. Após o período de indução, foram submetidos a um modelo de incisão plantar, e posteriormente submetidos à avaliação comportamental nos tempos préoperatório, 2 horas após a incisão, 1º, 2º, 3º e 7º dias de pós-operatório. O teste de von Frey foi utilizado para testar o limiar de retirada da pata, e a dor espontânea foi determinada pelo teste da proteção da pata. A expressão dos canais de sódio foi avaliada através da realização de reação de cadeia de polimerase quantitativa em tempo real para os canais Nav1.7 e Nav1.8 em amostra do gânglio da raiz dorsal correspondente à pata operada. Resultados: Os animais tratados com flutamida desenvolveram maior resposta a dor, tanto no teste de dor evocada quanto no teste da proteção da pata em todos os momentos estudados. Os grupos apresentaram diferença estatisticamente significante no 1º, 2º, 3º e 7º dias de pós-operatório para o limiar de retirada da pata. No teste da proteção da pata, foram significantes nos tempos 2 horas, 3º e 7º dia de pós-operatório. Não houve diferença entre os grupos estudados para a expressão de Nav1.7 e Nav1.8, para cada tempo. A análise de variância mostrou que a expressão de Nav1.7 variou em função do tempo em ambos os grupos, o que não ocorreu na expressão de Nav1.8. Conclusão: Neste estudo foi possível demonstrar que o bloqueio androgênico provocou a redução do limiar para retirada da pata após o 1º dia de pós-operatório, e ainda um escore acumulado no teste de proteção do membro que foi mais elevado no tempo 2 horas, no 3º e 7º dia de pós-operatório. Estes dados sugerem que os androgênios apresentaram um efeito antinociceptivo após a incisão plantar, e ainda que este efeito foi independente dos canais Nav1.7 e Nav1.8 no gânglio da raiz dorsal / Introduction: Evidence accumulated over the years has placed sex hormones as key factors of the differences found between males and females. Experimental studies with animals suggest that testosterone acts to reduce the nociceptive response after inflammatory and neuropathic stimuli, but the mechanism by which this hormone acts has not yet been fully elucidated. The objective of this study was to evaluate if androgenic blockade with flutamide promotes increased nociception in rats and to investigate whether this modulation of the painful behavior is due to an increase in the expression of voltage-dependent sodium channels Nav1.7 and Nav1.8 in the Dorsal root ganglion of rats submitted to a postoperative pain model. Methods: The animals studied were divided into a group that received flutamide subcutaneously, and in a control group receiving only placebo. After the induction period, the animals were submitted to a model of plantar incision, and then submitted to behavioral evaluation in the preoperative times, 2 hours after incision, 1st PO, 2nd PO, 3rd PO and 7th PO. The animals were submitted to Von Frey\'s test to determine the evoked pain, and the spontaneous pain was determined by the paw protection test (Guarding Pain). The expression of the sodium channels was evaluated by performing real time quantitative polymerase chain reaction for Nav channels in the dorsal root ganglion sample corresponding to the incised hindpaw. Results: Animals treated with flutamide developed greater nociception in both the evoked pain test and the paw protection test at all times studied. Statistically significant differences were found in the times 1st PO, 2nd PO, 3rd PO and 7th PO for the paw withdrawal threshold. Guarding pain test showed significant results at 2 hours, 3rd PO and 7th PO. No difference was found between the studied groups for the expression of Nav1.7 or Nav1.8 at each time point. Variance analysis showed that Nav1.7 expression was dependent on time in both groups, but Nav1.8 expression did not change over time Conclusions: In this study it was possible to demonstrate that flutamide caused a reduction in the paw withdrawal threshold after the 1st postoperative day, and also a guarding pain score that was higher 2 hours after incision, on the 3rd and 7 th day of postoperative. Data presented in this study suggest an antinociceptive effect of androgens after plantar incision that was independent of Nav channels