A indicação de biópsia para o diagnóstico precoce do câncer prostático baseia-se na dosagem sérica do PSA e nos achados do toque retal. O PSA é uma kalecreina estando seus genes reguladores ligados aos andrógenos. Drogas que afetam o metabolismo dos andrógenos podem afetar a produção de PSA. A finasterida é uma droga sintética que inibe a conversão de testosterona em DHT pela enzima 5 AR. O uso da finasterida na dose de 5mg/dia para o tratamento da HPB causa redução do volume prostático de 20 a 30% e diminuição dos valores dos PSA em aproximadamente 50% do seu valor inicial após 6 meses. O uso da finasterida na dose de 1mg/dia para o tratamento da AAM foi aprovado pelo FDA em 1997. Um estudo realizado em 2007 avaliou a alteração do nível do PSA em homens com mais de 40 anos fazendo uso de finasterida 1mg/dia para tratamento da AAM. Os resultados revelaram redução dos valores do PSA semelhante à verificada nos pacientes portadores de HPB. Não existem estudos prospectivos sobre o tema incluindo pacientes mais jovens. O objetivo do nosso trabalho foi verificar as alterações da dosagem do PSA, da testosterona sérica total e do volume prostático em indivíduos com menos de 40 anos de idade com em uso de finasterida 1mg/dia. Selecionamos 52 pacientes que após avaliação inicial preenchiam os critérios de inclusão. Foram dosados os níveis séricos do PSA e da testosterona, e mensurado o volume prostático através da ultrassonografia transabdominal, no início do estudo (T0) e um ano após o uso da finasterida (T2). No intervalo, 6 meses após o início da droga, foi solicitada apenas nova dosagem de PSA (T1). O valor médio na avaliação inicial (T0) da dosagem do PSA, da testosterona total plasmática e do volume prostático mensurado pela ultrassonografia transabdominal foi de 0,398 ng/ml (0,14- 0,78); 735,77 ng/dl (548-927) e 21,35 ml (15-31ml) respectivamente. Foi observada uma redução do valor médio do PSA de 9,21% após 6 meses do uso da droga (p=0,001). Após 12 meses do uso da finasterida verificamos uma redução de 10,51% do valor do PSA em relação à dosagem inicial (p<0,001) e uma diminuição do valor médio do volume prostático 21,37 ml para 20,03 ml (p<0,001). Não foi detectada alterações nos níveis de testosterona. Diferentemente de estudos anteriores em que, em homens fazendo uso de finasterida 1mg/dia, houve redução de 40% e 50% dos valores do PSA nas faixas etárias de 40 a 49 anos e 50 a 59 anos, nosso trabalho revelou reduções inferiores. Nosso estudo traz importantes questionamentos em relação a como deve ser feita a correção dos valores do PSA nos pacientes que começaram a utilizar finansterida 1mg antes dos 40 anos de idade e que se apresentam para avaliação prostática. Outro ponto de interesse é se a hiperplasia do componente epitelial observada durante envelhecimento masculino poderia ser inibida pelo uso da finasterida desde a juventude, pois sabemos que indivíduos portadores de deficiência congênita de 5AR não apresentam alopecia e nem tão pouco desenvolvem HPB. / The indication of biopsy for early diagnosis of prostate cancer is based on serum PSA levels and digital rectal examination findings. PSA is a kalecreine and its regulatory genes are modulating by androgens. Drugs affecting the androgens metabolism can affect the production of PSA. Finasteride is a synthetic drug, which inhibits the conversion of testosterone to DHT by the enzyme 5 AR. There are two subtypes of 5AR enzymes, Type 1 that predominates in non-prostatic tissues such as liver and skin, and Type 2, which predominates in the prostate and scalp but is also expressed in other tissues. The use of Finasteride 5mg / day for the treatment of BPH is well known. After six months we observe a decrease in prostate volume by 20 to 30% and also a decrease in total serum PSA concentration of approximately 50%. The use of Finasteride at 1mg / day for the treatment of MAA has been approved by the FDA in 1997. In 2007 a study evaluated the change in total serum PSA concentration in men over 40 years taking Finasteride 1 mg / day to treat MAA. The results showed a reduction in PSA values similar to that observed in patients treated of BPH. There are no prospective studies including younger patients. The aim of our study was to assess the changes in total serum PSA concentration, total serum testosterone concentration and prostate volume in patients younger than 40 years of age in use of Finasteride 1mg / day for MAA. We prospectively selected 52 patients with MAA and indication for treatment with Finasteride who met the inclusion criteria. Serum levels of total PSA and total testosterone and prostate volume, measured by transabdominal ultrasound, were obtained at baseline (T0) and one year after started the drug (T2). In the interval, 6 months after started drug, only serum total PSA concentration was measured (T1). The median value at baseline (T0), for total PSA, total testosterone and prostate volume was 0.398 ng / ml (0.14 to 0.78); 735.77 ng / dl (548-927) and 21.35 ml (15-31ml) respectively. A reduction of 9.21% on total PSA concentration was detected 6 months after started the drug (p = 0.001). After 12 months we observed a 10.51% decrease in total serum PSA concentration, when compared with the baseline value, (p <0.001). A reduction in the median value of prostate volume from 21.37 ml to 20.03 ml (p < 0.001) was also detected at the same period. There were no detectable changes in testosterone levels. They reported a decrease of 40% and 50% in total PSA concentration for groups between 40-49 and 50-59 of age respectively. In our study we observed lower reductions. Our finding may be explained by the fact that the epithelial component of the prostate gland has not yet started the hyperplasia process, so the conversion of testosterone into DHT by blocking 5AR by Finasteride would cause less impact. The fact that the values of plasma testosterone not have changed is not surprising since Finasteride is not considered an anti androgenic drug, it means that the synthesis of the testosterone is not affected by its use. Our study highlights important questions about how the adjustment of PSA values should be done in patients who began taking Finasteride 1mg / day before 40 years of age and present for prostate evaluation. Another point of interest is whether the hyperplasia of the epithelial component, observed during the aging process, could be inhibited by the use of Finasteride. This hypothesis can be corroborate by the fact that individuals with congenital deficiency of 5AR do not present alopecia or develop BPH. In conclusion the use of Finasteride 1mg /day reduces the total serum PSA value by 10,51% after one year. Prostate volume is also reduced by 6,3% in the same period.

Many imprinted genes are necessary for normal human development. Approximately 70 imprinted genes have been identified in humans. I developed a novel approach to identify candidate imprinted genes in humans using the premise that imprinted genes are often associated with nearby parent-of-origin-specific DNA differentially methylated regions (DMRs). I identified parent-of-origin-specific DMRs using sodium bisulfite-based DNA (CpG) methylation profiling of uniparental tissues, mature cystic ovarian teratoma (MCT) and androgenetic complete hydatidiform mole (AnCHM), and biparental tissues, blood and placenta. In support of this approach, the CpG methylation profiling led to the identification of parent-of-origin-specific differentially methylated CpG sites (DMCpGs) in known parent-of-origin-specific DMRs. I found new DMRs for known imprinted genes NAP1L5 and ZNF597. Most importantly, I discovered many new DMCpGs, which were associated with nearby genes, i.e., candidate imprinted genes. Allelic expression analyses of one candidate imprinted gene, AXL, suggested polymorphic imprinting of AXL in human blood.

Many imprinted genes are necessary for normal human development. Approximately 70 imprinted genes have been identified in humans. I developed a novel approach to identify candidate imprinted genes in humans using the premise that imprinted genes are often associated with nearby parent-of-origin-specific DNA differentially methylated regions (DMRs). I identified parent-of-origin-specific DMRs using sodium bisulfite-based DNA (CpG) methylation profiling of uniparental tissues, mature cystic ovarian teratoma (MCT) and androgenetic complete hydatidiform mole (AnCHM), and biparental tissues, blood and placenta. In support of this approach, the CpG methylation profiling led to the identification of parent-of-origin-specific differentially methylated CpG sites (DMCpGs) in known parent-of-origin-specific DMRs. I found new DMRs for known imprinted genes NAP1L5 and ZNF597. Most importantly, I discovered many new DMCpGs, which were associated with nearby genes, i.e., candidate imprinted genes. Allelic expression analyses of one candidate imprinted gene, AXL, suggested polymorphic imprinting of AXL in human blood.

A indicação de biópsia para o diagnóstico precoce do câncer prostático baseia-se na dosagem sérica do PSA e nos achados do toque retal. O PSA é uma kalecreina estando seus genes reguladores ligados aos andrógenos. Drogas que afetam o metabolismo dos andrógenos podem afetar a produção de PSA. A finasterida é uma droga sintética que inibe a conversão de testosterona em DHT pela enzima 5 AR. O uso da finasterida na dose de 5mg/dia para o tratamento da HPB causa redução do volume prostático de 20 a 30% e diminuição dos valores dos PSA em aproximadamente 50% do seu valor inicial após 6 meses. O uso da finasterida na dose de 1mg/dia para o tratamento da AAM foi aprovado pelo FDA em 1997. Um estudo realizado em 2007 avaliou a alteração do nível do PSA em homens com mais de 40 anos fazendo uso de finasterida 1mg/dia para tratamento da AAM. Os resultados revelaram redução dos valores do PSA semelhante à verificada nos pacientes portadores de HPB. Não existem estudos prospectivos sobre o tema incluindo pacientes mais jovens. O objetivo do nosso trabalho foi verificar as alterações da dosagem do PSA, da testosterona sérica total e do volume prostático em indivíduos com menos de 40 anos de idade com em uso de finasterida 1mg/dia. Selecionamos 52 pacientes que após avaliação inicial preenchiam os critérios de inclusão. Foram dosados os níveis séricos do PSA e da testosterona, e mensurado o volume prostático através da ultrassonografia transabdominal, no início do estudo (T0) e um ano após o uso da finasterida (T2). No intervalo, 6 meses após o início da droga, foi solicitada apenas nova dosagem de PSA (T1). O valor médio na avaliação inicial (T0) da dosagem do PSA, da testosterona total plasmática e do volume prostático mensurado pela ultrassonografia transabdominal foi de 0,398 ng/ml (0,14- 0,78); 735,77 ng/dl (548-927) e 21,35 ml (15-31ml) respectivamente. Foi observada uma redução do valor médio do PSA de 9,21% após 6 meses do uso da droga (p=0,001). Após 12 meses do uso da finasterida verificamos uma redução de 10,51% do valor do PSA em relação à dosagem inicial (p<0,001) e uma diminuição do valor médio do volume prostático 21,37 ml para 20,03 ml (p<0,001). Não foi detectada alterações nos níveis de testosterona. Diferentemente de estudos anteriores em que, em homens fazendo uso de finasterida 1mg/dia, houve redução de 40% e 50% dos valores do PSA nas faixas etárias de 40 a 49 anos e 50 a 59 anos, nosso trabalho revelou reduções inferiores. Nosso estudo traz importantes questionamentos em relação a como deve ser feita a correção dos valores do PSA nos pacientes que começaram a utilizar finansterida 1mg antes dos 40 anos de idade e que se apresentam para avaliação prostática. Outro ponto de interesse é se a hiperplasia do componente epitelial observada durante envelhecimento masculino poderia ser inibida pelo uso da finasterida desde a juventude, pois sabemos que indivíduos portadores de deficiência congênita de 5AR não apresentam alopecia e nem tão pouco desenvolvem HPB. / The indication of biopsy for early diagnosis of prostate cancer is based on serum PSA levels and digital rectal examination findings. PSA is a kalecreine and its regulatory genes are modulating by androgens. Drugs affecting the androgens metabolism can affect the production of PSA. Finasteride is a synthetic drug, which inhibits the conversion of testosterone to DHT by the enzyme 5 AR. There are two subtypes of 5AR enzymes, Type 1 that predominates in non-prostatic tissues such as liver and skin, and Type 2, which predominates in the prostate and scalp but is also expressed in other tissues. The use of Finasteride 5mg / day for the treatment of BPH is well known. After six months we observe a decrease in prostate volume by 20 to 30% and also a decrease in total serum PSA concentration of approximately 50%. The use of Finasteride at 1mg / day for the treatment of MAA has been approved by the FDA in 1997. In 2007 a study evaluated the change in total serum PSA concentration in men over 40 years taking Finasteride 1 mg / day to treat MAA. The results showed a reduction in PSA values similar to that observed in patients treated of BPH. There are no prospective studies including younger patients. The aim of our study was to assess the changes in total serum PSA concentration, total serum testosterone concentration and prostate volume in patients younger than 40 years of age in use of Finasteride 1mg / day for MAA. We prospectively selected 52 patients with MAA and indication for treatment with Finasteride who met the inclusion criteria. Serum levels of total PSA and total testosterone and prostate volume, measured by transabdominal ultrasound, were obtained at baseline (T0) and one year after started the drug (T2). In the interval, 6 months after started drug, only serum total PSA concentration was measured (T1). The median value at baseline (T0), for total PSA, total testosterone and prostate volume was 0.398 ng / ml (0.14 to 0.78); 735.77 ng / dl (548-927) and 21.35 ml (15-31ml) respectively. A reduction of 9.21% on total PSA concentration was detected 6 months after started the drug (p = 0.001). After 12 months we observed a 10.51% decrease in total serum PSA concentration, when compared with the baseline value, (p <0.001). A reduction in the median value of prostate volume from 21.37 ml to 20.03 ml (p < 0.001) was also detected at the same period. There were no detectable changes in testosterone levels. They reported a decrease of 40% and 50% in total PSA concentration for groups between 40-49 and 50-59 of age respectively. In our study we observed lower reductions. Our finding may be explained by the fact that the epithelial component of the prostate gland has not yet started the hyperplasia process, so the conversion of testosterone into DHT by blocking 5AR by Finasteride would cause less impact. The fact that the values of plasma testosterone not have changed is not surprising since Finasteride is not considered an anti androgenic drug, it means that the synthesis of the testosterone is not affected by its use. Our study highlights important questions about how the adjustment of PSA values should be done in patients who began taking Finasteride 1mg / day before 40 years of age and present for prostate evaluation. Another point of interest is whether the hyperplasia of the epithelial component, observed during the aging process, could be inhibited by the use of Finasteride. This hypothesis can be corroborate by the fact that individuals with congenital deficiency of 5AR do not present alopecia or develop BPH. In conclusion the use of Finasteride 1mg /day reduces the total serum PSA value by 10,51% after one year. Prostate volume is also reduced by 6,3% in the same period.