diretrizes_sobraf

SOBRAF

DIRETRIZES PARA A UTILIZAÇÃO DE HORMÔNIOS HOMÓLOGOS HUMANOS POR MÚLTIPLAS

ESPECIALIDADES MÉDICAS NA PRÁTICA CLÍNICA

A- INTRODUÇÃO: As diretrizes aqui elencadas representam a posição oficial da Sociedade Brasileira Para Estudos da Fisiologia – SOBRAF - com relação ao uso de hormônios homólogos humanos por múltiplas especialidades médicas na prática clínica, e estão fundamentadas no Projeto Diretrizes, iniciativa conjunta da Associação Médica Brasileira e Conselho Federal de Medicina, que tem por objetivo conciliar informações da área médica a fim de padronizar condutas que auxiliem o raciocínio e a tomada de decisão do médico. As informações contidas neste documento devem ser submetidas à avaliação e à crítica do médico, responsável pela conduta a ser seguida, frente à realidade e ao estado clínico de cada paciente.

B- DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIA: A revisão bibliográfica de artigos científicos destas diretrizes foi realizada na base de dados MEDLINE. A busca de evidências partiu de cenários clínicos reais, e utilizou palavras-chaves (MeSH terms): (aging hormone replacement therapy) OR (gynecology hormone replacement therapy) OR (endocrinology hormone replacement therapy) (hormones OR Estradiol OR Testosterone OR Progesterone OR Thyroid Hormones OR DHEA OR Pregnenolone OR Melatonin OR Growth Hormone OR IGF-1 OR deficiency OR therapeutic OR replacement) AND quality of life AND risk factors AND bone density AND osteoporosis AND osteopenia, (hormone replacement therapy OR hormones) AND (cancer) AND (Monitoring) AND (sexual function) AND glucose metabolism AND plasma lipids AND inflammatory factors AND visceral fat) AND cardiovascular disease AND antioxidant activity AND immune function AND fatigue AND depression AND sleep disorders AND anxiety AND hypertension AND obesity AND body composition AND lean mass AND muscle mass AND sarcopenia AND longevity AND alzheimer´s disease AND cancer risk AND cancer prevention AND low hormone levels .

C- GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A: Estudos experimentais e observacionais de melhor consistência.

B: Estudos experimentais e observacionais de menor consistência. C: Relatos de casos (estudos não controlados). D: Opinião desprovida de avaliação crítica, baseada em consensos, estudos fisiológicos ou modelos animais.

D- OBJETIVOS: Estabelecer a definição, interferências do uso de hormônios no metabolismo lipoproteico, na vida sexual, na baixa densidade mineral óssea, nas mamas, na redução do percentual de gordura corporal, na redução dos riscos de hipertensão arterial sistêmica, na redução dos riscos de diabetes, na redução do risco de demência de Alzheimer, na melhora da massa muscular, na promoção de bem estar físico e mental, na redução dos riscos de doenças, na melhora da qualidade de vida, na prevenção das perdas funcionais da velhice, na melhora da capacidade laboral, física e funcional, na melhora da libido, na melhora da qualidade do sono, na melhora da depressão, na melhora da ansiedade, na melhora do estresse, na atenuação da formação de espécies oxigênio-reativas, na redução do estresse oxidativo celular, na preservação da integridade celular, na preservação da integridade mitocondrial, na otimização metabólica, na otimização imunológica, na redução e ou reversão da placa ateromatosa, na redução do risco cardiovascular, na prevenção de doenças crônicas, na prevenção do câncer, na redução do risco de câncer e na promoção de um envelhecimento saudável e determinar as indicações da terapêutica hormonal baseadas nas melhores evidências atuais.

E- CONFLITO DE INTERESSE: Nenhum conflito de interesse declarado.

1. MENOPAUSA a. Quadro clínico

i. Amenorréia secundária em mulheres com mais de 35 anos ou amenorréia secundária em mulheres, por período superior a seis meses;

ii. Fogachos, sudorese noturna, insônia, labilidade emocional, secura vaginal, dispareunia, declínio cognitivo, fragilidade imunológica, ressecamento da pele, queda de cabelos, aumento do peso total, aumento do percentual de gordura,

perda de massa magra, perda de massa óssea, redução da libido e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. FSH > 15 u/L

ii. LH > 8 u/L

c. Observações complementares acerca do diagnóstico clínico-laboratorial:

i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da menopausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de menopausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a menopausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA MENOPAUSA

i. Após criteriosa revisão da literatura científica, discussões

com médicos representantes de todos os continentes e

discussões entre médicos brasileiros, todos profissionais

versados e adequadamente qualificados em utilizar e

prescrever hormônios em seres humanos com a

finalidade primária de promoção da saúde e, ainda, em

total consonância com os preceitos e diretrizes da

Sociedade Brasileira Para Estudos da Fisiologia – SOBRAF,

da International Hormone Society e da World Society of

Anti-Aging Medicine, nós, médicos membros da SOBRAF,

concluímos haver chegado o momento de reconsiderar os

conceitos atualmente vigentes acerca da reposição

hormonal na menopausa.

A presente controvérsia acerca da reposição hormonal na menopausa, teve início após a publicação dos resultados do chamado estudo WHI ( Women’s Health Iniciative ), publicado em 2002, bem como do British One Million Women Study, publicado em 2003. Em ambos os estudos, o uso de hormônios em mulheres na pós-menopausa foi associado a uma maior incidência de câncer de mama, quando comparadas ao grupo placebo-controle ou ao de não usuárias. No estudo WHI, o uso de hormônios em mulheres foi associado a um aumento no risco de doenças cardiovasculares e cerebrovasculares. Para os médicos membros da SOBRAF, ambos os estudos apresentam, dentre outras, duas falhas graves de desenho que consistem, respectivamente, em primeiro lugar: estas mulheres estavam utilizando estrogênios conjugados de urina equina. Consiste em um coquetel de 38 hormônios obtidos da urina de éguas prenhes, portanto, um dejeto animal, sendo que nenhum destes hormônios existe em seres humanos ou é produzido pelos mesmos, tendo, portanto, propriedades farmacológicas e comportamento completamente distintos do 17-beta-estradiol, hormônio que deixa de ser produzido por mulheres na fase pós-menopausal. Em segundo lugar, à esta combinação, foi associado o acetato de medroxiprogesterona, molécula que consiste em um progestogênio sintético, igualmente não existente em seres humanos, e, consequentemente, substância com propriedades químicas e fisiológicas diferentes da progesterona humana. Revisando cuidadosamente a literatura científica existente, é possível encontrar vários outros estudos que demonstram, de maneira inquestionável, a potencial toxicidade e os riscos inerentes ao uso destas substâncias. De acordo com as recentes recomendações de um grupo cada vez maior de sociedades médicas ao redor de todo o mundo, nós, igualmente, não recomendamos o uso de hormônios não-homólogos humanos a reposição hormonal da menopausa. Em contraste com as recomendações de algumas sociedades, que não recomendam a reposição hormonal na menopausa, ou ainda, algumas outras que a recomendam por um período limitado a cinco anos, no máximo, nós recomendamos o uso de hormônios em mulheres antes e após a menopausa, por tanto tempo quanto se fizer necessário, desde que as indicações e as necessidades clínicas

justifiquem e que nenhum evento adverso ocorra que contraindique o seu uso. Contudo, nós recomendamos o uso da combinação de estradiol e estriol homólogos humanos, associados à progesterona homóloga humana para a correção da deficiência ovariana da menopausa, exceto para casos específicos e bem pontuais e por um período de tempo limitado, aonde o uso de hormônios não-homólogos humanos possa apresentar resultados clínicos melhores, com é o caso de algumas metrorragias e sangramentos da perimenopausa. A via de administração , é, igualmente, parâmetro de considerável importância. A via transdérmica, é, sem dúvida bem mais segura e fisiológica do que a via oral. Esta via não oferece risco de elevação do câncer de mama, e, quando se associa progesterona homóloga humana à reposição de estradiol e estriol, vários estudos, na verdade, demonstram uma clara redução dos riscos para aquela patologia. A mulher que teve câncer de mama, pode fazer reposição hormonal? A tendência observada na atualidade é de se evitar a administração de hormônios em mulheres que tiveram câncer de mama. Esta observação pode não se justificar nas mulheres em que a lesão foi removida cirurgicamente de forma completa. Revendo cuidadosamente todos os estudos científicos atuais que envolvem mulheres que tiveram câncer de mama e receberam reposição hormonal na menopausa, nenhum risco de recorrência foi reportado ou identificado. Ao contrário, a reposição hormonal na menopausa está associada a uma notória redução do risco de recorrência do câncer, bem como uma clara diminuição das taxas gerais de mortalidade na maioria dos estudos. Mesmo a despeito de fartas evidências em contrário, ainda é muito cedo para recomendar-se a reposição hormonal para mulheres em menopausa portadoras de câncer de mama. Nós recomendamos que estudos em larga escala placebo-controle sejam efetivados com a finalidade de identificar com a maior clareza possível, em quais mulheres que tiveram câncer de mama a terapia de reposição hormonal da menopausa estaria mais indicada. Nós recomendamos aos médicos que fazem a reposição hormonal da menopausa, que submetam suas clientes à propedêutica e monitoração mamária periódicos, antes e durante o período de duração da reposição, obedecendo aos intervalos regulares preconizados e consensuados, consistindo de inspeção, palpação e mamografia de alta resolução, acompanhada de ultrassonografia complementar de alta resolução. Importante, igualmente, ressaltar a necessidade de vigilância periódica do

endométrio, através de monitoramento ultrassonográfico transvaginal. CONCLUSÃO DO CONSENSO: Tendo em vista as enormes repercussões biopsicossociais da menopausa e os crescentes e exorbitantes gastos para o tratamento e controle das doenças chamadas “inevitáveis” da velhice, nós recomendamos aos médicos estimularem a reposição hormonal da menopausa, sempre observando os bons preceitos da prática médica e utilizando-se de hormônios homólogos humanos, preferencialmente administrados pela via transdérmica, no caso da associação estradiol-estriol, e, no caso da progesterona, via transdérmica ou transvaginal. Para os casos anteriores, a via oral também pode ser uma alternativa, desde que os hormônios administrados sejam, igualmente, homólogos humanos. São Paulo, 12 de Novembro de 2012

Grupo de Consensos da SOBRAF

1. Professora Doutora Ana Cristina Vendramini, PhD

2. Professora Doutora Andreia Conceição Milan B. Antoniolli, PhD 3. Professora Doutora Andrea Thomaz Soccol, PhD 4. Professor Doutor Eduardo Faria, PhD

5. Professor Doutor Marcelo Alexandre de Mattos, PhD 6. Professor Doutor Marcos Renato Scholz, PhD 7. Dr. Ítalo Emmanuel Valeriano Rachid

2. ANDROPAUSA

a. Quadro clínico i. Cansaço, redução da libido e do desempenho sexual,

redução da força muscular, adinamia, fragilidade imunológica, ginecomastia, redução da capacidade física, ressecamento da pele, déficit de memória, aversão ao convívio social, aumento da circunferência abdominal, queda de cabelos, aumento do percentual de gordura corporal, alterações do sono, alterações do humor, perda de massa óssea, e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. FSH > 5 u/L

ii. LH > 8 u/L iii. Testosterona Total < 700 ng/dL iv. Índice de Androgênio Livre < 0,7 v. Testosterona livre < 2%

vi. Testosterona biodisponível < 400 ng/dL


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da andropausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de andropausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a andropausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA ANDROPAUSA

Após criteriosa revisão da literatura científica, discussões com

médicos representantes de todos os continentes e discussões

entre médicos brasileiros, todos profissionais versados e

adequadamente qualificados em utilizar e prescrever

hormônios em seres humanos com a finalidade primária de

promoção da saúde e, ainda, em total consonância com os

preceitos e guidelines diretrizes da Sociedade Brasileira Para

Estudos da Fisiologia – SOBRAF, da International Hormone

Society e da World Society of Anti-Aging Medicine, nós,

médicos membros da SOBRAF, concluímos haver chegado o

momento de considerar a deficiência hormonal masculina, e o

conseqüente tratamento de reposição hormonal da

andropausa.

Desde que a estrutura química da testosterona e a técnica de obtê-la de forma sintética foram descobertos na década de 30, um grande número de estudos têm demonstrado, de forma indubitável, ser a testosterona um hormônio indispensável para a manutenção de um estado ótimo de saúde na população masculina. Na medida em que os homens envelhecem, as frações biodisponíveis da testosterona e de outros androgênios declinam crônica e cumulativamente. O declínio gradual da testosterona biodisponível responde por uma vasta e multivariada gama de sinais e sintomas, tais como fadiga, depressão, mudanças do humor, labilidade emocional, irritabilidade, perda de massa muscular, aumento da gordura corporal total, aumento da gordura intra-abdominal, perda do desejo e da performance sexual, fragilidade imunológica, ginecomastia, perda de massa óssea e muitas outras manifestações que são, invariavelmente, atribuídas a achados normais da idade. A persistência da deficiência hormonal masculina pode aumentar os riscos das comorbidades associadas ao envelhecimento, tais como obesidade, depressão, diabetes, osteoporose e doenças cardiovasculares. Embora o declínio hormonal não afete de maneira tão aguda e incisiva os homens como a queda hormonal da menopausa, de todo modo, compromete, pela sua cronicidade e efeito cumulativo, a sua qualidade de vida, sua saúde e, muito provavelmente, a sua própria expectativa de vida. O declínio androgênico masculino recebe uma vasta sinonímia: distúrbio androgênico do envelhecimento masculino (DAEM ), andropausa, climatério masculino, menopausa masculina, partial androgen deficiency in aging men ( PADAM ), hipogonadismo relacionado à idade, penopausa, dentre outros tantos. A quantidade de homens que recebe atenção e tratamento no transcurso da deficiência hormonal é incomparavelmente menor do que a quantidade de mulheres que recebe reposição e tratamento na menopausa. Isto se deve, principalmente, ao fato de que, ao contrário do declínio feminino, o declínio hormonal masculino ainda não é um fato plenamente aceito por boa parte da medicina tradicional. Com base na fisiologia do envelhecimento hormonal, nós acreditamos não haver qualquer justificativa válida para tal discriminação. Os oponentes da reposição hormonal da andropausa amparam-se em estudos conflitantes e com sérios erros de desenho existentes na literatura, que demonstram diferenças não significativas entre os níveis séricos hormonais de homens jovens e homens velhos, outros sugerem que a testosterona pode aumentar a incidência de câncer de próstata, enquanto outros sugerem que a reposição de testosterona não apresenta

efeitos clínicos significativos. Estes estudos atípicos são fartamente contrapostos por um imenso número de estudos que são claros e unânimes em demonstrar exatamente o oposto, destacando-se, principalmente, um indubitável efeito protetor da testosterona contra o câncer de próstata. Uma revisão global da literatura corrente não consegue fornecer qualquer evidência de que a reposição com testosterona ou seus derivados possa aumentar os riscos de câncer de próstata in vivo. Ao contrário, homens com baixos níveis de testosterona biodisponível são exatamente os que apresentam não só os maiores riscos de câncer de próstata, como a ocorrência de tumores de comportamento muito mais agressivo, aumento do processo de deposição aterosclerótica das artérias e piora gradual e cumulativa da qualidade de saúde. Além do mais, pacientes portadores de câncer de próstata que têm os seus níveis circulantes de testosterona drasticamente reduzidos por conta das terapias anti-androgênicas, não apresentam qualquer aumento ou melhora da sobrevivência. Com a finalidade de detectar com o maior grau de precisão possível a deficiência hormonal masculina, nós recomendamos não somente uma detalhada avaliação clínica, levando-se em conta os sinais e sintomas físicos e mentais sugestivos do declínio masculino, como a realização de testes laboratoriais que auxiliem e quantifiquem o diagnóstico, dentre os quais: dosagem da testosterona total, testosterona livre, SHBG, proteinograma, DHT, testosterona biodisponível, FSH, LH, e o índice de androgênio livre. Igualmente importante é avaliar os níveis séricos de estradiol, uma vez que a elevação destes níveis pode provocar um bloqueio da ação da testosterona nos homens. Levando-se em consideração o enorme impacto para a saúde masculina oriundo da queda de testosterona, nós recomendamos aos médicos que estimulem o tratamento desta deficiência para todos os casos, utilizando-se da testosterona homóloga humana ou de seus derivados quimicamente mais semelhantes possíveis, excetuando-se alguma contraindicação absoluta. Todos os homens que avançam na idade, devem expectar, cedo ou tarde, declínio dos seus níveis ótimos de testosterona, sendo, portanto, potenciais candidatos à terapia de reposição. A maioria dos homens irá experimentar declínio entre os 30 e 45 anos de idade. Vale, entretanto, salientar, que exceções a esta regra podem ocorrer, fazendo com que alguns homens venham a necessitar da reposição hormonal abaixo ou acima daquela faixa etária. Somente doses fisiológicas de testosterona devem ser administradas, objetivando-se manter os níveis séricos comparáveis ao de adultos jovens e saudáveis, na faixa etária dos 25 a 30 anos.

As melhores vias de administração para este hormônio são a transdérmica e a intramuscular. Níveis excessivos de estradiol devem ser evitados durante o tratamento de reposição com testosterona, por conta do efeito biológico neutralizador e além de responder pela ocorrência de ginecomastia, hipertrofia prostática benigna e, possivelmente infarto agudo do miocárdio. Ajustes no padrão alimentar, evitar álcool e cafeína, além da prática regular de atividade física são importantes medidas de suporte para redução dos níveis excessivos de estradiol. Evitar a obesidade é um ponto importantíssimo neste contexto, uma vez que o tecido adiposo é rico em aromatase, enzima que catalisa a transformação de testosterona em estradiol. Quando estas medidas não surtirem o efeito desejado, o uso de inibidores da aromatase ou de pequenas doses de progesterona podem estar indicados. A progesterona aumenta a transformação de estradiol em estrona, diminuindo, portanto, as suas concentrações séricas. O câncer de próstata em atividade pode ser considerado como uma contraindicação para o uso de testosterona. Contudo, ao se rever cuidadosamente a literatura atual, parece haver uma inconsistente base de evidências para dar suporte a esta afirmação. Muitos estudos, ao contrário, demonstram que portadores de câncer de próstata que também possuem deficiência hormonal masculina têm a sua qualidade de saúde severamente comprometida e podem ser beneficiados com a reposição de doses pequenas de testosterona, trazendo benefícios suplementares que em muito superam qualquer suposto risco de estimulo ao crescimento tumoral. CONCLUSÃO DO CONSENSO: Nós não conseguimos identificar na literatura atual qualquer evidência de que repor doses fisiológicas de testosterona deponha contra ou traga riscos à saúde de homens portadores de declínio nos níveis daquele hormônio. Ao contrário. Uma vez que são múltiplos e multivariados os benefícios advindos da reposição hormonal masculina, nós recomendamos o uso de doses fisiológicas de testosterona ou de seu derivado químico mais próximo possível, com o intuito de corrigir esta deficiência, submetendo este homem em reposição a um programa de acompanhamento clínico periódico e regular.

São Paulo, 12 de Novembro de 2012



2. Professora Doutora Andreia Conceição Milan B. Antoniolli, PhD 3. Professora Doutora Andrea Thomaz Soccol, PhD

4. Professor Doutor Eduardo Faria, PhD


3. SOMATOPAUSA a. Quadro clínico

i. Deterioração da composição corporal, redução da massa muscular, aumento do percentual de gordura corporal total, aumento do percentual de gordura visceral, cansaço, redução do desempenho sexual, redução da força muscular, adinamia, fragilidade imunológica, redução da capacidade física, ressecamento e enrugamento da pele, déficit de memória, baixa autoestima, alterações do sono, alterações do humor, perda de massa óssea, e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. IGF-1 < 300 ng/dL em homens

ii. IGF-1 < 280 ng/dL em mulheres


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da somatopausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de somatopausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a somatopausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA SOMATOPAUSA

Após criteriosa revisão da literatura científica, discussões com médicos representantes de todos os continentes e discussões entre médicos brasileiros, todos profissionais versados e adequadamente qualificados em utilizar e prescrever hormônios em seres humanos com a finalidade primária de promoção da saúde e, ainda, em total consonância com os preceitos e guidelines da Sociedade Brasileira Para Estudos da Fisiologia – SOBRAF, da International Hormone Society e da World Society of Anti-Aging Medicine, nós, médicos membros da SOBRAF, concluímos haver chegado o momento de considerar a reposição com o hormônio do crescimento humano recombinante não só em adultos portadores de patologias que impeçam ou dificultem a sua produção, como nos adultos que estão envelhecendo e decaindo a sua capacidade inata de síntese endógena. Nós concordamos e aprovamos os consensos já estabelecidos e consagrados em muitos países, que aconselham a reposição com o hormônio do crescimento humano recombinante em adultos portadores de patologias que impeçam ou dificultem a sua produção. Nestas situações, existe história pregressa de remoção, trauma, radiação, tumores ou severa inativação da hipófise, fatos que impedem a produção endógena do hormônio do crescimento.

Pensamos já haver na literatura científica atual uma base suficiente de dados que demonstram e confirmam os múltiplos benefícios e segurança do uso clínico do hormônio do crescimento. Desta forma, tornou-se uma necessidade médica estendermos a indicação de reposição também aos adultos que estão envelhecendo e decaindo a sua capacidade inata de síntese endógena, por conta da progressiva redução funcional, consequente ao processo de envelhecimento.

A evidência é de que o hormônio do crescimento é essencial não apenas para o crescimento de crianças, mas também essencial para a saúde física e mental de adultos,

particularmente na manutenção da integridade dos sistemas muscular, adiposo, ósseo, imunológico e cardiovascular. A deficiência do hormônio do crescimento é frequentemente acompanhada de fadiga, ansiedade e depressão, além de um progressivo e cumulativo comprometimento da qualidade de vida. Por outro lado, a reposição com o hormônio do crescimento nestes casos tem demonstrado ser capaz de promover a parada e, por muitas vezes reversão da progressão de todos aqueles processos.

A falta da reposição do hormônio do crescimento nos adultos que estão envelhecendo e decaindo a sua capacidade inata de síntese endógena, ao contrário do que se imagina, pode trazer consequências verdadeiramente desastrosas. Aumento considerável da velocidade de deposição da placa ateromatosa, aumento das taxas de mortalidade cardiovascular, deterioração da composição corporal através da perda de massa muscular e concomitante aumento da deposição de gordura corporal total e gordura intra-abdominal, fragilidade imunológica, perda de massa óssea, depressão, distúrbios progressivos do sono e redução da síntese de proteínas são, dentre outros, alguns dos fenômenos que se sucedem ao declínio da capacidade de manutenção da síntese de níveis fisiológicos do hormônio do crescimento, e que são parcial ou totalmente reversíveis através da reposição do mesmo.

Nós recomendamos aos médicos submeterem os clientes em uso do hormônio do crescimento a um regime de avaliações regulares e aprazados. Isto inclui: anamnese, exame físico e exames laboratoriais complementares obedecendo a um intervalo de um a doze meses, dependendo da necessidade individual de cada cliente.

Em relação a um eventual aumento no risco de desenvolvimento de certos tipos de câncer com o uso do hormônio do crescimento, os estudos mais sérios e respeitados realizados em pacientes que receberam o hormônio, comparados ao grupo controle de indivíduos não-tratados, mostram uma clara redução de aproximadamente 50% na incidência de câncer e na mortalidade por câncer no grupo de indivíduos que receberam o hormônio. Na realidade, inexiste qualquer argumento consistente ou fundamentação razoável para se acreditar que repor o hormônio do crescimento possa elevar o risco de câncer.

De qualquer forma, uma pesquisa de rotina a cada seis a 12 meses para o câncer de próstata e mama, complementadas

por ultrassom e mamografia quando necessário, constitui conduta essencial, segundo este grupo de consenso. Além do mais, nós também recomendamos que o tratamento de reposição seja programado de modo a se respeitar as doses fisiológicas preconizadas. Em casos clínicos muito específicos e pontuais, como, por exemplo, os grandes obesos e indivíduos com grande superfície corporal, pode ser justificável o uso de doses maiores, que deverão ser mantida por período de tempo não superior a 90 dias.

Doses acima dos limites fisiológicos não são recomendadas por esta sociedade e fogem t ao escopo deste protocolo de consenso.

Desta forma e seguindo estes princípios, o médico estará assegurando não só a eficácia como a segurança do tratamento.

CONCLUSÃO DO CONSENSO:

Na atualidade inexiste qualquer base científica de dados que contraindique a reposição do hormônio do crescimento humano recombinante em adultos que estão envelhecendo e decaindo a sua capacidade inata de síntese endógena. Ao contrário, uma multiplicidade de sinais, sintomas e problemas adversos e deletérios à saúde humana tem sido abundantemente reportada em indivíduos portadores de níveis endógenos infra fisiológicos do hormônio do crescimento, bem como tem sido fartamente reportada melhora, desaparecimento ou mesmo reversão dos problemas aludidos ao se promover a adequada reposição do mesmo.

Ressaltamos, mais uma vez, a importância de se observar as doses fisiológicas do hormônio, bem como a realização de avaliações clínico-laboratoriais periódicas.






4. TIREOPAUSA a. Quadro clínico

i. Deterioração da composição corporal, redução da massa muscular, aumento do percentual de gordura corporal total, aumento do percentual de gordura visceral, cansaço, depressão marcadamente matinal, apatia, incapacidade de concentração, dificuldade de perder peso, unhas fracas, queda de cabelos, dislipidemia, hipercolesterolemia, ateromatose precoce, intolerância ao frio, adinamia, fragilidade imunológica, constipação, redução da capacidade física, zumbidos, ressecamento e enrugamento da pele, déficit de memória, alterações do sono, alterações do humor, e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. TSH ultrassensível > 2,0 pg/mL

ii. T3 livre < 0,37 ng/dL iii. T4 livre < 0,7 ng/mL iv. Média da Temperatura Basal < 36,5o C em cinco aferições

matinais consecutivas.


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da tireopausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de somatopausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a tireopausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA TIREOPAUSA

Após criteriosa revisão da literatura científica, discussões




prescrever hormônios em seres humanos com a finalidade

primária de promoção da saúde e, ainda, em total

consonância com os preceitos e guidelines da Sociedade

Brasileira Para Estudos da Fisiologia – SOBRAF, da

International Hormone Society e da World Society of Anti-

Aging Medicine, nós, médicos membros da SOBRAF,

concluímos existir um sólido conjunto de evidências de

ordem clínica, prática e teórica que já permitem expandir o

tratamento do hipotireoidismo além dos parâmetros

correntes convencionais.

Existe, na atualidade, uma controvérsia entre grupos de médicos. Um grupo essencialmente define o diagnóstico do hipotireoidismo baseado em testes de laboratório, enquanto o outro toma como base parâmetro essencialmente clínicos. Uma sólida base de evidências científicas não dá suporte à ideia de que o diagnóstico do hipotireoidismo deva ou possa ser baseado apenas em testes laboratoriais. Isto implica em que a existência do hipotireoidismo só se confirma quando os níveis séricos de TSH encontram-se acima dos limites superiores atuais de referência, e os níveis séricos de tiroxina (T4) e triiodotireonina (T4), encontram-se abaixo dos limites inferiores atuais de referência, negligenciando os sinais e sintomas clínicos. Esta sociedade adota a posição intermediária. A decisão de iniciar a reposição com o hormônio tireoidiano deve ser baseada tanto em achados clínicos quanto laboratoriais, e não somente em resultados de um simples teste laboratorial, como se encontra atualmente expresso nos jornais JAMA e Thyroid, conduta que representa o atual consenso da Sociedade Americana de Tireoide.

Entendemos que achados e informações clínicas são essenciais no diagnóstico de deficiências hormonais. Os dados necessários ao diagnóstico do hipotireoidismo incluem a pesquisa das queixas físicas e emocionais dos pacientes, sinais físicos e coleta de história pregressa pessoal e familiar sugestivas de deficiência tireoidiana, bem como eventuais anormalidades no volume glandular, expressos pela presença de hipertrofia ou bócio e/ou tireoidite autoimune. As seguintes evidências dão suporte à existência de hipotireoidismo clínico, em indivíduos erroneamente considerados laboratorialmente normais, e que são candidatos ao tratamento de reposição hormonal tireoidiana: Os níveis de referencia da normalidade são excessivamente

largos e ignoram e existência dos níveis ótimos de

referência. Estes níveis incluem largas margens de

referência de normalidade para os níveis de T3, T4 e TSH,

que são, na realidade, plenamente compatíveis com

múltiplas disfunções tireoidianas. Não existe qualquer

evidência atual que dê suporte à persistência do uso destes

parâmetros, uma vez que são completamente incapazes de

definir e diferenciar de maneira clara e adequada os

estados de eutireoidismo e hipotireoidismo. A base de

dados atuais sugere que sejam utilizados níveis de

referencia incomparavelmente mais estreitos e específicos

para esta situação. Os níveis convencionais de referência

para detecção do hipotireoidismo sofrem variação de mais

de 30 vezes ( 0.2 a 6.5 mUI/L ).

Em muitos estudos clínicos atuais, níveis séricos de TSH

acima de 1.5 a 2.0 mUI/L tem sido associados com

dislipidemia, inflamação crônica subclínica, níveis elevados

de homocisteína, proteína C reativa, hipercolesterolemia,

depressão, pobre resposta ao tratamento com

antidepressivos, maiores índices de massa corpórea, maior

incidência de hipertensão arterial sistêmica, elevação dos

triglicérides e hiperglicemia. Do mesmo modo, aqueles

níveis tem sido associados a anormalidades cardíacas e

vasculares, que incluem ateromatose acelerada e perda da

elasticidade vascular. Neonatos com baixo peso e partos

prematuros tem sido relatados em mães com TSH acima de

2.0 mUI/L. Mais importante, iniciar o tratamento do

hipotireoidismo nestes casos, tem demonstrado ser uma

medida capaz de minimizar ou reverter aqueles problemas.

Com base ainda nestes múltiplos estudos, existem

evidências que dão suporte a adoção de níveis de referencia

bem mais estreitos para o TSH, cujos valores devem se

situar entre 0.4 a 2.0 mUI/L. Torna-se importante ressaltar

que 95% da população de indivíduos saudáveis e com a

atividade tireoidiana normal exibem níveis séricos de TSH

dentro do intervalo de 0.4 a 2.0 mUI/L.

Um outro ponto de capital importância, é que os estudos

demonstram resultados clínicos incomparavelmente

superiores quando se utiliza no tratamento a associação

entre T3 e T4, ao invés do tratamento isolado com T4. Isto

se deve ao fato de que uma boa parte do T4 administrado

isoladamente, sofre conversão para T3 reverso, forma

hormonal inativa biologicamente. Além do mais, para que o

estado de eutireoidismo seja alcançado, o organismo

humano necessita de ambos os hormônios, T4, que tem a

finalidade principal de atrair moléculas de TBG ( thyroid

binding globulin ) e T3, que, livre do atrelamento da TBG,

pode ligar-se rapidamente aos receptores celulares do

hormônio tireoidiano nas células-alvo. A combinação

fisiológica entre T3 e T4, obedecendo às proporções de uma

parte de T3 para cinco partes de T4 , produz resultados

clínicos inequivocamente superiores.

Nós recomendamos aos médicos que excluam cuidadosamente outras patologias ou estados clínicos que produzam sintomatologia semelhante ao hipotireoidismo antes de iniciar a reposição do hormônio tireoidiano. Ao se iniciar o tratamento, utilizar doses menores e programar elevação gradual, de acordo com a necessidade clínica, visando evitar a presença de superdosagem, e, consequentemente, um possível quadro de hipertireoidismo iatrogênico, efeito adverso mais frequente no tratamento do hipotireoidismo. Intolerância ao tratamento pode ser causada por excessiva conversão de T4 em T3, acelerando, desta forma, a atividade tireoidiana. Devemos lembrar que a principal causa deste problema é a deficiência não diagnosticada de outros hormônios, principalmente a hipocortisolemia e a deficiência de estradiol na menopausa. Os médicos devem dedicar especial atenção aos níveis de cortisol. A fadiga adrenal crônica, que leva à queda excessiva dos níveis de cortisol provoca uma baixa tolerância ao tratamento do hipotireoidismo, principalmente quando a opção foi pela combinação T4/T3. A deficiência de cortisol provoca

hiperatividade do sistema nervoso ortossimpático e uma excessiva e rápida conversão de T4 em T3. Desta forma, em pacientes com fadiga adrenal crônica, nós recomendamos que os médicos tratem a deficiência de cortisol antes de iniciarem o tratamento do hipotireoidismo ou, no mínimo, de forma concomitante ao início do mesmo. A segurança do tratamento do hipotireoidismo pode ser aumentada se o iniciarmos com doses menores, promovendo um aumento gradual nos casos em que tais ajustes se fizerem necessários.

CONCLUSÃO DO CONSENSO: Hipotireoidismo clínico, em indivíduos erroneamente

considerados laboratorialmente normais, constitui, sem

nenhuma dúvida uma racional justificativa para se

promover a inclusão destas pessoas no grupo de candidatos

ao tratamento com os hormônios tireoidianos. Estes

indivíduos podem se beneficiar com um programa de

reposição com baixas dosagens, em que estejam associados

T4 e T3 em proporções fisiológicas. Avaliação clínica e

laboratorial aprazados, utilizando-se parâmetros mais

estreitos para os níveis de referência do TSH, além de um

cuidadoso monitoramento individual de cada caso, são as

bases que conduzem a resultados clínicos favoráveis.






5. FADIGA ADRENAL CRÔNICA a. Quadro clínico

i. Cansaço marcadamente matinal, apatia, incapacidade de concentração, adinamia, fragilidade imunológica, compulsão massas e doces, irritabilidade, intolerância ao

estresse, déficit de memória, alterações do sono, alterações do humor, e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. Cortisol matinal < 15 mcg/dL

ii. Cortisol livre < 10 ng/ml iii. Transcortina > 30 mg/L


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da fadiga adrenal crônica. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico da fadiga adrenal crônica será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a fadiga adrenal crônica, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA FADIGA ADRENAL CRÔNICA











concluímos ter chegado o momento de reconsiderar os

conceitos atualmente vigentes acerca do tratamento da

deficiência adrenal, em particular a deficiência de cortisol,

não apenas nas pessoas afetadas por severas deficiências,

mas também nos portadores de fadiga adrenal crônica.

Nós concordamos plenamente e aprovamos o consenso mundial que foi atingido no que concerne ao tratamento com glicocorticoides para adultos portadores de severa deficiência de cortisol. Geralmente, naquela condição, existe uma deficiência total ou quase total da produção de cortisol, que ocorre por conta de remoção total ou parcial ou inativação total ou parcial das glândulas adrenais, as estruturas responsáveis pela produção de cortisol. Acreditamos que a quantidade de evidências existentes na atualidade demonstrando os efeitos benéficos do cortisol, bem como os seus eventuais efeitos adversos é suficiente para promover a extensão da recomendação da reposição de cortisol também para os portadores da condição clínica conhecida como fadiga adrenal crônica. Entre os quadros de deficiência de cortisol deve também ser incluído a forma que incide ao longo do processo do envelhecimento, ocasionada pela progressiva deterioração do eixo hipofisário-adrenal. A evidência é de que o cortisol é essencial não só para os portadores de estados de severa depleção, como também para a manutenção do equilíbrio físico e mental dos adultos que estão envelhecendo e declinando a sua capacidade de produção. Uma quantidade adequada de cortisol é essencial para o normal funcionamento de uma multiplicidade de órgãos e sistemas: cérebro, pele, articulações, músculos, trato digestório, sistemas imunológico e cardiovascular. A deficiência de cortisol encontra-se clinicamente relacionada com fadiga, baixa tolerância ao estresse, confusão mental e comprometimento da qualidade de vida. O tratamento com glicocorticoides tem se mostrado capaz de melhorar a qualidade de vida, humor e status mental dos pacientes. Consequências adversas da deficiência de cortisol variam desde potenciação dos efeitos debilitantes de doenças inflamatórias ( artrite reumatoide, gastrenterite, colite, desordens imunológicas e alergias ), até o aumento da mortalidade em condições de alto risco como o choque séptico. Os estados de deficiência leve de cortisol podem,

igualmente, causar mais repercussões danosas à saúde humana do que se imaginava antes. Como a suplementação de cortisol e de outros glicocorticoides tem sido associada com importantes efeitos adversos, dentre os quais: imunossupressão, osteoporose, ganho de peso, atrofia cutânea, hipertensão, supressão adrenal e fácies cushingóide, nós recomendamos aos médicos que a reposição de cortisol deva ser pautada pela observância de guidelines de segurança. Acreditamos firmemente que os efeitos colaterais são consequentes ao uso de doses excessivas, bem como pelo fato de que a reposição de cortisol não pode ocorrer na ausência da correção dos desequilíbrios nos níveis de hormônios anabólicos (pausas humanas ), principalmente a queda dos níveis de DHEA. e T3. A presença de níveis fisiológicos de hormônios anabólicos pode bloquear os efeitos catabólicos da presença de doses excessivas de glicocorticoides. Em vários casos de deficiência de cortisol, reposição de derivados sintéticos produz efeitos clínicos muito menos efetivos do que a reposição do cortisol na sua forma homóloga humana. Em termos de diagnóstico laboratorial, pode-se lançar mão das dosagens séricas de cortisol total matinal, cortisol livre, transcortina ( CBG= cortisol binding globulin ), ACTH, bem como dosagens dos 17-hidroxiesteróides em urina de 24 horas, pela técnica de cromatografia a gás. O tratamento de reposição com cortisol nas formas leves pode ser feito observando-se os limites diários das doses fisiológicas. Em casos mais severos, as doses recomendadas podem sofrer um acréscimo de até 30-50%. Lembramos que os homens necessitam de doses maiores porque fisiologicamente secretam quantidades diárias cerca de 50% maiores do que as mulheres. Apenas 50 % da dose diária administrada é absorvida pelo trato gastrintestinal. Em situações de agravamento das condições de estresse, como: infecções, procedimentos cirúrgicos e abalo emocional intenso, recomendamos que as doses sejam temporariamente aumentadas. Importante lembrar que a reposição com cortisol pode agravar deficiências já existentes na produção dos hormônios tireoidianos e DHEA. Desta forma, recomendamos aos médicos corrigirem concomitantemente aquelas deficiências.


Com base na literatura científica atual, inexistem quaisquer

justificativas plausíveis que contraindiquem ou

desestimulem o tratamento de reposição com cortisol em

adultos com baixos níveis. Efeitos colaterais adversos

podem ser evitados seguindo-se os guidelines já propostos,

bem como utilizando-se doses fisiológicas da forma

homóloga humana do cortisol. Novamente ressaltamos a

capital importância da correção concomitante de outras

deficiências na produção de hormônios anabólicos,

particularmente DHEA e o hormônio tireoidiano. Monitorar

os pacientes através de um programa regular de

acompanhamento clínico-laboratorial.






6. ADRENOPAUSA a. Quadro clínico

i. Depressão e cansaço em pessoas jovens, adinamia, apatia, fragilidade imunológica, ateromatose, irritabilidade, déficit de memória, alterações do sono, alterações do humor, ressecamento vaginal, queda de cabelos, rarefação de pelos pubianos, redução da libido, hipercolesterolemia, dislipidemia, perda de massa óssea e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. SDHEA < 350 ug/mL em homens

ii. SDHEA < 300 ug/mL em mulheres


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da adrenopausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e

laboratoriais, o diagnóstico de adrenopausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a adrenopausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA ADRENOPAUSA











concluímos ter chegado o momento de considerar a

deficiência de dehidroepiandrosterona, bem como a sua

reposição.

Até o presente momento, as sociedades médicas convencionais relacionadas à endocrinologia, ainda não reconheceram a necessidade e a importância clínica de tratar e repor a deficiência adrenal de dehidroepiandrosterona (DHEA). Algumas poucas sociedades médicas convencionais ao redor do mundo, tem expressado de forma pontual e tímida a importância da

reposição de DHEA. Em geral, se identifica a conclusão de que ainda não existe base de dados suficiente que dê suporte à reposição deste hormônio. Eles são da opinião de que a literatura cientifica sobre o DHEA ainda é muito escassa e sua eficácia clínica ainda não está suficientemente comprovada.. Eles, igualmente, expressam a preocupação de que a reposição de DHEA poderia estar relacionada a uma maior incidência do câncer genital e a uma redução do HDL – colesterol. Após uma cuidadosa e exaustiva revisão da literatura cientifica atual, bem como ler e discutir os relatórios negativos institucionais, concluímos não existir qualquer base de dados científica razoável que dê suporte à ideia de que o uso de DHEA possa trazer riscos à saúde humana. Nós reconhecemos e corroboramos um grande número de estudos aonde homens e mulheres com deficiência de DHEA tem sido tratados e tem apresentado significativa melhora em múltiplos aspectos físicos e mentais. Ao nos detalharmos com estudos que demonstram efeitos “pouco significativos” no tratamento com DHEA é possível observar que uma falha de desenho importante é frequentemente perceptível: o tempo excessivamente curto em que estas pessoas tem passado recebendo o hormônio, períodos inferiores a duas semanas, em boa parte das vezes, tempo notoriamente insuficiente para que resultados consistentes sejam alcançados. Ao lado de uma minoria de estudos que demonstram resultados negativos ou não significativos, existe um grande número de estudos que atesta de maneira inquestionável a importância e, mais ainda, uma multivariedade de benefícios oriundos da reposição com DHEA. Além do mais, estes estudos não só confirmam a eficácia como chegam à conclusão que a reposição de DHEA, o mais abundante hormônio esteroide produzido no corpo humano, é uma das formas de reposição mais seguras e eficientes que existem. Estudos randomizados, placebo-controle e duplo-cego, confirmam inexistirem quaisquer efeitos danosos à saúde humana, quando níveis fisiológicos de DHEA são suplementados. Efeitos colaterais porventura existentes, encontram-se completamente vinculados ao emprego de doses excessivas. Os sinais mais característicos de doses excessivas de DHEA são: pele oleosa, acne e leve hirsutismo, efeitos reversíveis através do devido ajuste nas dosagens. Em muitos estudos que analisam a reposição de DHEA, significativos benefícios foram obtidos no ganho de massa óssea, qualidade da pele, sistema imunológico, sensibilidade à glicose, sensibilidade à insulina e perfil lipídico. Benefícios também foram evidenciados na performance mental e emocional, qualidade de vida, fadiga,

depressão, redução do risco cardiovascular, diabetes e obesidade. É a opinião deste grupo que os seguintes argumentos dão suporte e justificam plenamente o tratamento de reposição com DHEA em adultos com baixos níveis séricos:

1. DHEA é um hormônio natural aos seres humanos,

está plenamente configurado para atender às nossas

demandas metabólicas, e, na verdade, é o hormônio

presente em maior quantidade no corpo humano.

2. DHEA exerce mais de 150 funções anabólicas no

metabolismo humano.

3. Apresenta uma multiplicidade de benefícios quando

usando em indivíduos adultos que apresentam

baixos níveis, sendo uma valiosa ferramenta no

combate às doenças relacionadas ao

envelhecimento.

4. Reposição de DHEA é segura.

5. Reposição de DHEA tem um custo acessível.

Com o intuito de elevar a segurança do tratamento de reposição com DHEA, nós recomendamos que os médicos submetam seus clientes a um programa de avaliações periódicas, incluindo anamnese, exame físico e exames laboratoriais complementares a cada 3 a 12 meses, dependendo das necessidades individuais de cada um. Entendemos ser igualmente relevante promover uma rotina de avaliações clínico-laboratoriais para o câncer de próstata e mama, obedecendo a um intervalo de seis a 12 meses, dependendo de cada caso. Na nossa experiência, os melhores métodos para o diagnóstico da deficiência de DHEA são a avaliação sérica dos níveis do sulfato de dehidroepiandrosterona e a avaliação da excreção dos metabólitos 17-cetoesteróides-DHEA em urina de 24 horas, pela técnica de cromatografia a gás. As doses de segurança são as chamadas doses fisiológicas, que devem ser seguidas e observadas pelos membros da sociedade. Ressaltamos que nos casos em que é clinicamente relevante evitar a conversão de DHEA para Testosterona ou Estradiol, pode-se lançar mão da reposição de 7-Keto-DHEA, principal metabólito ativo do DHEA, que possui exatamente as mesmas propriedades do DHEA, porém, não sofre conversão para outros hormônios. Neste caso, deve-se, igualmente, observar as doses fisiológicas de segurança.


Com base na literatura científica atual, inexistem

justificativas plausíveis que contraindiquem ou

desestimulem o tratamento de reposição de DHEA em

adultos com baixos níveis, exceto para as mulheres que

encontram-se na pós-menopausa e não estão fazendo a

reposição hormonal da menopausa. Ao contrário, benefícios

em quantidade e intensidade suficientes já tem sido

demonstrados e servem como base para nos permitir

recomendar o uso de doses fisiológicas de DHEA para

corrigir as deficiências bem estabelecidas e previamente

diagnosticadas em adultos, submetendo-os, daí por diante,

a um programa regular de acompanhamento clínico-

laboratorial. A reposição de DHEA encontra-se

especialmente justificada em indivíduos portadores de

condições de saúde tratadas com corticoides, uma vez que o

seu uso pode neutralizar com segurança os efeitos

catabólicos excessivos da corticoterapia.






7. MELATOPAUSA a. Quadro clínico

i. Depressão, cansaço, adinamia, apatia, fragilidade imunológica, irritabilidade, déficit de memória, alterações do sono, alterações do humor, alterações gastrointestinais e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. 6-Sultatoxi-Melatonina < 40 ng/dia em urina de 24 horas


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da melatopausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de melatopausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a melatopausa, a SOBRAF recomenda que seus médicos associados estarão, concomitantemente, utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

e. CONSENSO DA SOBRAF PARA O TRATAMENTO HORMONAL DA MELATOPAUSA

Após criteriosa revisão da literatura científica, discussões com

médicos representantes de todos os continentes e discussões

entre médicos brasileiros, todos profissionais versados e

adequadamente qualificados em utilizar e prescrever

hormônios em seres humanos com a finalidade primária de

promoção da saúde e, ainda, em total consonância com os

preceitos e guidelines do Grupo Longevidade Saudável, da


Aging Medicine, nós, médicos membros do Grupo de Consenso

do Grupo Longevidade Saudável, concluímos ter chegado o

momento de considerar o tratamento da deficiência de

melatonina em adultos.

Até o presente momento, nenhuma sociedade médica convencional no mundo reconheceu a necessidade e a

importância de tratar a deficiência da glândula pineal através da reposição de melatonina. Como é de costume quando se trata do assunto reposição hormonal, a controvérsia também não foge à regra na reposição de melatonina. Para algumas escolas constitui-se em um hormônio essencial, com importantes repercussões para a saúde humana. Já para outras escolas, não passa de um placebo sem qualquer importância clínica. Em contraste com esta controvérsia, existe uma unanimidade completa acerca da segurança e importância da reposição de melatonina entre pesquisadores renomados e médicos ao redor de todo o mundo que acumularam vasta experiência no uso e aplicações clínicas deste hormônio em seres humanos. A melatonina tem se mostrado tão segura, que até o presente momento não foi possível determinar os limites de doses tóxicas para humanos e para animais. Doses extremamente elevadas tem sido utilizadas em experimentos com animais com o intuito de estabelecer aqueles níveis, sem que se consiga produzir efeitos danosos ou mesmo a morte dos animais. Após exaustiva revisão da literatura e troca de experiências entre grupos versados no emprego clínico da melatonina, o que se pode concluir é que a sua reposição é capaz de produzir consistentes e significativos benefícios à saúde humana. Os efeitos mais notórios são observados na qualidade do sono, controle do Jet Lag, varredura de radicais livres, metabolismo da glicose, ossos, sistema cardiovascular, metabolismo cerebral, melhora do perfil lipídico e manutenção da ciclicidade e responsividade dos receptores celulares para hormônios anabólicos. Foram revistos mais de 350 estudos sobre o uso de melatonina e o sono, sendo que a quase totalidade dos mesmos (98,6%) deixa evidente uma notória melhora da qualidade do sono, por ser a melatonina capaz de encurtar o tempo de indução do sono, encurtar o início da fase REM do sono profundo e provocar um relaxamento muscular e nervoso através da estimulação do sistema parassimpático. O conjunto destas ações facilita o sono e melhora a sua qualidade, além de contribuir diretamente para o processo de reparo e recuperação metabólica ao longo do período de permanência no sono. Com base na literatura e experiência mundial atuais, inexistem quaisquer justificativas plausíveis de ordem científica ou médica que contraindiquem ou desestimulem o tratamento de reposição com melatonina. Sua segurança e eficácia clínica são motivos mais do que suficientes para ressegurar às autoridades de saúde a validade e aceitação do seu uso, desde de que tal seja feito sob criteriosa prescrição e supervisão médica. As doses de segurança são as chamadas doses fisiológicas, que devem ser seguidas e observadas pelos membros da sociedade.

Lembramos que a melatonina pode reduzir a atividade do cortisol, de modo que, em casos de fadiga adrenal crônica deve-se iniciar o tratamento com doses menores e também corrigir a deficiência de cortisol de forma concomitante. Na opinião deste grupo, os seguintes argumentos dão suporte e fundamentam o tratamento de reposição de melatonina em adultos:

Melatonina é uma substância natural ao organismo

humano e sua presença é abundante, principalmente no

período noturno.

Melatonina está completamente adaptada ao corpo

humano.

Melatonina exerce uma multiplicidade de benefícios na

manutenção da saúde física e mental, bem como contra

o desenvolvimento das doenças degenerativas da

velhice.

Melatonina é segura.

Melatonina tem custo acessível.

O diagnóstico da deficiência de melatonina é baseado em critérios essencialmente clínicos. Pode-se, entretanto, em casos que se façam necessários, recorrer à dosagem da excreção em urina de 24 horas da 6-sulfatoxi-melatonina, principal metabólito da melatonina, como parâmetro diagnóstico laboratorial.

CONCLUSÃO DO CONSENSO: Com base na literatura científica atual, inexistem

quaisquer justificativas plausíveis que contraindiquem

ou desestimulem o tratamento de reposição com

melatonina em adultos com baixos níveis. Ao contrário,

uma vasta base de dados e evidências dão suporte e

validam o seu emprego em indivíduos com deficiência e

com baixos níveis, submetendo-os a um programa

regular de acompanhamento médico.





5. Professor Doutor Marcelo Alexandre de Mattos, PhD

6. Professor Doutor Marcos Renato Scholz, PhD 7. Dr. Ítalo Emmanuel Valeriano Rachid

8. ELETROPAUSA

a. Quadro clínico i. Depressão, cansaço, adinamia, apatia, fragilidade

imunológica, irritabilidade, déficit de memória, alterações do sono, alterações do humor e comprometimento da qualidade de vida.

b. Quadro Laboratorial i. Dosagem do Sulfato de Pregnenolona no líquor

ii. Sulfato de pregnenolona < 90 ng/mL.


i. Quando o diagnóstico laboratorial mostrar-se coerente e compatível com o quadro clínico, este será considerado na confirmação do diagnóstico da eletropausa. Por outro lado, nas situações em que ocorrer clara discrepância, divergência ou distorções entre os dados clínicos e laboratoriais, o diagnóstico de eletropausa será confirmado tomando-se como referência as manifestações e o quadro clínico apresentados pelo paciente e devidamente avaliados e registrados pelo médico. Tal conduta se justifica pela baixa acurácia dos métodos de diagnóstico laboratorial das deficiências hormonais, falhas de técnicas intrínsecas aos métodos, uso de metodologia inadequada na coleta da amostra de sangue, horário em que a amostra foi colhida, nível de hidratação do paciente no momento da coleta e limitações técnicas dos métodos laboratoriais. A coleta de uma amostra matinal de sangue para dosar um dado hormônio, expressa um retrato estático de um fenômeno intensamente dinâmico e complexo, que sofre influência de múltiplas variáveis, o que torna qualquer método diagnóstico potencialmente falho, limitado e pouco confiável, até que sejam desenvolvidas tecnologias e métodos mais eficazes.

d. No momento da instituição da proposta terapêutica hormonal para a eletropausa, a SOBRAF recomenda que seus médicos associados utilizem-se do termo de consentimento padrão adotado pela mesma e que deverá ser devidamente assinado pelo médico e pelo seu paciente.

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Baixa Qualidade de Vida, Baixa Performance e Fadiga: A Melhora Com a

Reposição do Hormônio do Crescimento

1. Okamoto I, Munakata M, Miyazaki M, Satoh T, Takahata T, Takamatsu Y, Muto O, Koike K, Ishitani K, Mukaiyama T, Sakata Y, Nakagawa K, Tamura K. Disturbance of the Growth Hormone-Insulin-like Growth Factor-1 Axis Associated with Poor Performance Status in Patients with Solid Tumors. Jpn J Clin Oncol. 2010 Mar;40(3):222-6.


Níveis de DHEA

2. Morgan CA 3rd, Rasmusson A, Pietrzak RH, Coric V, Southwick SM. Relationships among plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate, cortisol, symptoms of dissociation, and objective performance in humans exposed to underwater navigation stress. Biol Psychiatry. 2009 Aug 15;66(4):334-40

3. Ahboucha S, Pomier-Layrargues G, Vincent C, Hassoun Z, Tamaz R, Baker G, Butterworth RF. Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis. Neurochem Int. 2008 Mar-Apr;52(4-5):569-74

4. Téllez N, Comabella M, Julià E, Río J, Tintoré M, Brieva L, Nos C, Montalban X. Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone. Mult Scler. 2006 Aug;12(4):487-94

5. O'Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB. Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. . J Clin Endocrinol Metab. 2006 Feb;91(2):425-31

6. Maes M, Mihaylova I, De Ruyter M. Decreased dehydroepiandrosterone sulfate but normal insulin-like growth factor in chronic fatigue syndrome (CFS): relevance for the inflammatory response in CFS. Neuro Endocrinol Lett. 2005 Oct;26(5):487-92

7. Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab 1994 Jun;78(6):1360-7

8. Arlt W, Callies F, Allolio B. DHEA replacement in women with adrenal insufficiency - pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. Endocr Res. 2000;26(4):505-11

9. Cawood EH, Bancroft J. Steroid hormones, the menopause, sexuality and well-being of women. Psychol Med. 1996 Sep;26(5):925-36

10. Rigaud AS, Pellerin J. Neuropsychic effects of dehydroepiandrosterone. Ann Med Interne (Paris). 2001 Apr;152 Suppl 3:IS43-9

11. Piketty C, Jayle D, Leplege A, Castiel P, Ecosse E, Gonzalez-Canali G, Sabatier B, Boulle N, Debuire B, Le Bouc Y, Baulieu EE, Kazatchkine MD. Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease. Clin Endocrinol (Oxf). 2001 Sep;55(3):325-30


Reposição de DHEA

1. Alkatib AA, Cosma M, Elamin MB, Erickson D, Swiglo BA, Erwin PJ, Montori VM. A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. . J Clin Endocrinol Metab. 2009 Oct;94(10):3676-81

2. Nordmark G, Bengtsson C, Larsson A, Karlsson FA, Sturfelt G, Rönnblom L. Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity. 2005 Nov;38(7):531-40

3. Calabrese V. DHEA in multiple sclerosis: positive effects in a non-randomized study. In: The biological role of DHEA, edited by Regelson W, Kalimi M, De Gruyter-Berlin, 1990: 95-100

4. Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR. Dehydroepiandrosterone treatment of midlife dysthymia. Biol Psychiatry. 1999;45(12):1533-41

5. Hunt PJ, Gurnell EM, Huppert FA, Richards C, Prevost AT, Wass JA, Herbert J, Chatterjee VK. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab. 2000;85(12):4650-6

6. van Vollenhoven RF, Engleman EG, McGuire JL. Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheum. 1995 Dec;38(12):1826-31


Níveis de Estradiol

1. Studer DW. Clinical symptoms of estrogen deficiency in Estrogen Deficiency: Causes and consequence, 1996, Ed. RW Staw, The Parthenon Publishing Group, New-York, USA

2. Freedman MA. Quality of life and menopause: the role of estrogen. J Womens Health (Larchmt). 2002 Oct;11(8):703-18

3. Carette S, Dessureault M, Belanger A. Fibromyalgia and sex hormones. J Rheumatol. 1992 May;19(5):831


Reposição de Estradiol

1. Serrano D, Mariani L, Mora S, Guerrieri-Gonzaga A, Cazzaniga M, Daldoss C, Ramazzotto F, Feroce I, Decensi A, Bonanni B. Quality of life assessment in a chemoprevention trial: fenretinide and oral or transdermal HRT. Maturitas. 2006 Aug 20;55(1):69-75

2. Czarnecka D, Klocek M, Betkowska-Korpala B, Jankowski P, Olszanecka A, Kawecka-Jaszcz K. Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension. Przegl Lek. 2000;57(7-8):397-401

3. Burger HG, Hailes J, Menelaus M, Nelson J, Hudson B, Balazs N. The management of persistent menopausal symptoms with oestradiol-testosterone implants: clinical, lipid and hormonal results. Maturitas. 1984 Dec;6(4):351-8

4. Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women. J Clin Endocrinol Metab. 2002 Apr;87(4):1509-16

5. Nathorst-Boos J, Wiklund I, Mattsson LA, Sandin K, von Schoultz B. Is sexual life influenced by transdermal estrogen therapy? A double blind placebo controlled study in postmenopausal women. Acta Obstet Gynecol Scand. 1993 Nov;72(8):656-60

6. Wendlova J. Effect of Kliogest on bone metabolism, bone mineral density and quality of life in postmenopausal patients. Vnitr Lek 1998 Aug;44(8):464-8

7. Gorins A, Espie M, Bedairia N, Perret F, Tournant B, Novak H, Lucchi-Angelier E, Marty M. Hormone replacement therapy in breast cancer patients: a study of 230 patients, with a case-control study. Gynecol Obstet Fertil. 2003 Jul-Aug;31(7-8):614-9

8. Gambacciani M, Ciaponi M, Cappagli B, Monteleone P, Benussi C, Bevilacqua G, Genazzani AR. Effects of low-dose, continuous combined estradiol and noretisterone acetate on menopausal quality of life in early postmenopausal women. Maturitas. 2003 Feb 25;44(2):157-63

9. Derman RJ, Dawood MY, Stone S. Quality of life during sequential hormone replacement therapy – a placebo-controlled study. Int J Fertil Menopausal Stud. 1995 Mar-Apr;40(2):73-8

10. Collins A, Hanson U, Eneroth P, Hagenfeldt K, Lundberg U, Frankenhaeuser M. Psychophysiological stress responses in postmenopausal women before and after hormonal replacement therapy. Hum Neurobiol. 1982;1(2):153-9

11. Ulrich LG, Barlow DH, Sturdee DW, Wells M, Campbell MJ, Nielsen B, Bragg AJ, Vessey MP. Quality of life and patient preference for sequential versus continuous combined HRT: the UK Kliofem multicenter study experience. UK Continuous Combined HRT Study Investigators. Int J Gynaecol Obstet. 1997 Oct;59 Suppl 1:S11-7

12. Gelfand MM, Moreau M, Ayotte NJ, Hilditch JR, Wong BA, Lau CY. Clinical assessment and quality of life of postmenopausal women treated with a,new intermittent progestogen combination hormone replacement therapy: a placebo-controlled study. Menopause. 2003 Jan-Feb;10(1):29-36

13. Barrett-Connor E, Young R, Notelovitz M, Sullivan J, Wiita B, Yang HM, Nolan J. A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. J Reprod Med. 1999 Dec;44(12):1012-20

14. Bech P, Munk-Jensen N, Obel EB, Ulrich LG, Eiken P, Nielsen SP. Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures. Psychother Psychosom. 1998 Jul-Oct;67(4-5):259-65

15. Wu MH, Pan HA, Wang ST, Hsu CC, Chang FM, Huang KE. Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy. Climacteric. 2001 Dec;4(4):314-9

16. Pornel B.Efficacy and safety of Menorest in two positive-controlled studies. Eur J Obstet Gynecol Reprod Biol. 1996 Apr;64 Suppl:S35-7

17. Karlberg J, Mattsson LA, Wiklund I. A quality of life perspective on who benefits from estradiol replacement therapy. Acta Obstet Gynecol Scand. 1995 May;74(5):367-72

18. Limouzin-Lamothe MA, Mairon N, Joyce CR, Le Gal M. Quality of life after the menopause: influence of hormonal replacement therapy. Am J Obstet Gynecol. 1994 Feb;170(2):618-24

19. Iversen OE, Eid AB, Johannesen KH, Nyland B, Lovset T. Transdermal estrogen treatment. A placebo controlled study. Tidsskr Nor Laegeforen. 1991 Aug 30;111(20):2544-6

20. Wiklund I, Karlberg J, Mattsson LA. Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study. Am J Obstet Gynecol. 1993 Mar;168(3 Pt 1):824-30

21. Wiklund I, Berg G, Hammar M, Karlberg J, Lindgren R, Sandin K. Long-term effect of transdermal hormonal therapy on aspects of quality of life in postmenopausal women. Maturitas. 1992 Mar;14(3):225-36

22. Wiklund I, Holst J, Karlberg J, Mattsson LA, Samsioe G, Sandin K, Uvebrant M, von Schoultz B.A new methodological approach to the evaluation of quality of life in postmenopausal women. Maturitas. 1992 Mar;14(3):211-24

23. Hilditch JR, Lewis J, Ross AH, Peter A, van Maris B, Franssen E, Charles J, Norton P, Dunn EV.A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17 beta combined with an oral progestin on quality of life in postmenopausal women. Maturitas. 1996 Jul;24(3):177-84

24. Hall G, Pripp U, Schenck-Gustafsson K, Landgren BM. Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease. Maturitas. 1998 Jan 12;28(3):235-42

25. Rigano A, Rigano M, Cancellieri F, Pulle C. Sexually and well-being in early menopause. Effect of transdermal estradiol therapy. Panminerva Med. 2001 Jun;43(2):115-8.

26. Adamson DL, Webb CM, Collins P. Esterified estrogens combined with methyltestosterone improve emotional well-being in postmenopausal women with chest pain and normal coronary angiograms. Menopause. 2001 Jul-Aug;8(4):233-8

27. Collins A, Hanson U, Eneroth P, Hagenfeldt K, Lundberg U, Frankenhaeuser M. Psychophysiological stress responses in postmenopausal women before and after hormonal replacement therapy. Hum Neurobiol. 1982;1(2):153-9

28. Best NR, Rees MP, Barlow DH, Cowen PJ. Effect of estradiol implant on noradrenergic function and mood in menopausal subjects. Psychoneuroendocrinology. 1992;17(1):87-93

29. Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977 Apr;4(1):31-47


Níveis de Testosterona 1. Salminen E, Portin R, Korpela J, Backman H, Parvinen LM, Helenius H, Nurmi

M. Androgen deprivation and cognition in prostate cancer. Br J Cancer. 2003 Sep 15;89(6):971-6

2. van Andel G, Kurth KH. The impact of androgen deprivation therapy on health related quality of life in asymptomatic men with lymph node positive prostate cancer. Eur Urol. 2003 Aug;44(2):209-14

3. Pether M, Goldenberg SL, Bhagirath K, Gleave M. Intermittent androgen suppression in prostate cancer: an update of the Vancouver experience. Can J Urol. 2003 Apr;10(2):1809-14

4. Segal RJ, Reid RD, Courneya KS, Malone SC, Parliament MB, Scott CG, Venner PM, Quinney HA, Jones LW, D'Angelo ME, Wells GA. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2003 May 1;21(9):1653-9

5. Potosky AL, Reeve BB, Clegg LX, Hoffman RM, Stephenson RA, Albertsen PC, Gilliland FD, Stanford JL. Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy. J Natl Cancer Inst. 2002 Mar 20;94(6):430-7

6. Novak A, Brod M, Elbers J. Andropause and quality of life: findings from patient focus groups and clinical experts. Maturitas. 2002 Dec 10;43(4):231-7

7. Fowler FJ Jr, McNaughton Collins M, Walker Corkery E, Elliott DB, Barry MJ. The impact of androgen deprivation on quality of life after radical prostatectomy for prostate carcinoma. Cancer. 2002 Jul 15;95(2):287-95

8. Seidman SN, Araujo AB, Roose SP, Devanand DP, Xie S, Cooper TB, McKinlay JB. Low testosterone levels in elderly men with dysthymic disorder. Am J Psychiatry. 2002 Mar;159(3):456-9

9. Lubeck DP, Grossfeld GD, Carroll PR. The effect of androgen deprivation therapy on health-related quality of life in men with prostate cancer. Urology. 2001 Aug;58(2 Suppl 1):94-100

10. Herr HW, O'Sullivan M. Quality of life of asymptomatic men with nonmetastatic prostate cancer on androgen deprivation therapy. J Urol. 2000 Jun;163(6):1743-6

11. Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS. Testosterone replacement therapy improves mood in hypogonadal men - a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3578-83

12. van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ. Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals. Arch Sex Behav. 1989 Jun;18(3):217-28


Reposição de Testosterona

1. Knapp PE, Storer TW, Herbst KL, Singh AB, Dzekov C, Dzekov J, LaValley M, Zhang A, Ulloor J, Bhasin S. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E1135-43

2. Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006 Feb;63(2):177-85

3. Katznelson L, Robinson MW, Coyle CL, Lee H, Farrell CE. Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men. Eur J Endocrinol. 2006 Dec;155(6):867-75 (“Improved quality of life with testosterone treatment if the treatment was associated with exercise”)

4. Arver S, Dobs AS, Meikle AW, Caramelli KE, Rajaram L, Sanders SW, Mazer NA. Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men. Clin Endocrinol (Oxf) 1997 Dec;47(6):727-37

5. Park NC, Yan BQ, Chung JM, Lee KM. Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency. Aging Male. 2003 Jun;6(2):86-93

6. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation. 2000 Oct 17;102(16):1906-11

7. Rabkin JG, Wagner GJ, Rabkin R. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry. 2000 Feb;57(2):141-7

8. Rabkin JG, Wagner GJ, Rabkin R. Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism. J Clin Psychopharmacol. 1999 Feb;19(1):19-27

9. Rabkin JG, Wagner GJ, McElhiney MC, Rabkin R, Lin SH. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol. 2004 Aug;24(4):379-85

10. O'Connor DB, Archer J, Hair WM, Wu FC. Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men. Physiol Behav. 2002 Apr 1;75(4):557-66

11. Rozenek R, Rahe CH, Kohl HH, Marple DN, Wilson GD, Stone MH. Physiological responses to resistance-exercise in athletes self-administering anabolic steroids. J Sports Med Phys Fitness. 1990 Dec;30(4):354-60.

12. Wagner GJ, Rabkin JG, Rabkin R. Testosterone as a treatment for fatigue in HIV+ men. Gen Hosp Psychiatry. 1998 Jul;20(4):209-13

13. Wagner G, Rabkin J, Rabkin R. Exercise as a mediator of psychological and nutritional effects of testosterone therapy in HIV+ men. Med Sci Sports Exerc. 1998 Jun;30(6):811-7

14. Okun MS, McDonald WM, DeLong MR. Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity. Arch Neurol. 2002 May;59(5):807-11

15. Crawford BA, Liu PY, Kean MT, Bleasel JF, Handelsman DJ. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab. 2003 Jul;88(7):3167-76

16. Grinspoon S, Corcoran C, Askari H, Schoenfeld D, Wolf L, Burrows B, Walsh M, Hayden D, Parlman K, Anderson E, Basgoz N, Klibanski A. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998 Jul 1;129(1):18-26

17. Howell SJ, Radford JA, Adams JE, Smets EM, Warburton R, Shalet SM. Randomized placebo-controlled trial of testosterone replacement in men with mild Leydig cell insufficiency following cytotoxic chemotherapy. Clin Endocrinol (Oxf). 2001 Sep;55(3):315-24

18. Gruenewald DA, Matsumoto AM.Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003 Jan;51(1):101-15

19. van Basten JP, van Driel MF, Jonker-Pool G, Sleijfer DT, Schraffordt Koops H, van de Wiel HB, Hoekstra HJ. Sexual functioning in testosterone-supplemented patients treated for bilateral testicular cancer. Br J Urol. 1997 Mar;79(3):461-7

Baixa Performance: A Correlação Com Baixos Níveis de Testosterona

1. Orwoll E, Lambert LC, Marshall LM, Blank J, Barrett-Connor E, Cauley J, Ensrud K, Cummings SR; Osteoporotic Fractures in Men Study Group. Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med. 2006 Oct 23;166(19):2124-31

2. Cardinale M, Stone MH.Is testosterone influencing explosive performance? J Strength Cond Res. 2006 Feb;20(1):103-7

3. O'Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB. Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. . J Clin Endocrinol Metab. 2006 Feb;91(2):425-31

Baixa Performance: A Melhora Com a Reposição de Testosterona

1. Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol. 2009 Sep 1;54(10):919-27

2. Sattler FR, Castaneda-Sceppa C, Binder EF, Schroeder ET, Wang Y, Bhasin S, Kawakubo M, Stewart Y, Yarasheski KE, Ulloor J, Colletti P, Roubenoff R, Azen SP. Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab. 2009 Jun;94(6):1991-2001

3. Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MD, Adams JE, Oldham JA, Wu FC. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010 Feb;95(2):639-50

4- CONTROLE DA ANSIEDADE ATRAVÉS DA

MODULAÇÃO HORMONAL

Ansiedade: Associação Com Baixos Níveis de DHEA

1- Ritsner M, Maayan R, Gibel A, Strous RD, Modai I, Weizman A. Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients. Eur Neuropsychopharmacol. 2004 Aug;14(4):267-73

2- Ritsner M, Gibel A, Ram E, Maayan R, Weizman A. Alterations in DHEA metabolism in schizophrenia: Two-month case-control study. Eur Neuropsychopharmacol. 2006 Feb;16(2):137-46

3- Goyal RO, Sagar R, Ammini AC, Khurana ML, Alias AG. Negative correlation between negative symptoms of schizophrenia and testosterone levels. Ann N Y Acad Sci. 2004 Dec;1032:291-4

Ansiedade: Associação Com Baixos Níveis de Androgênios

1- Diamond P, Brisson GR, Candas B, Peronnet F. Trait anxiety, submaximal physical exercise and blood androgens. Eur J Appl Physiol Occup Physiol. 1989;58(7):699-704

Ansiedade: A Melhora Com a Reposição de DHEA

1- Arlt W, Callies F, van Vlijmen JC, Koehler I, Reincke M, Bidlingmaier M, Huebler D, Oettel M, Ernst M, Schulte HM, Allolio B. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999;341(14):1013-20

2- Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, Weizman A. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry. 2003 Feb;60(2):133-41

3- Morales AJ, Nolan JJ, Nelson JC, Yen SS. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. 1994 Jun;78(6):1360-7

4- Sharma AN, Chopde CT, Hirani K, Kokare DM, Ugale RR Chronic progesterone treatment augments while dehydroepiandrosterone sulphate prevents tolerance to ethanol anxiolysis and withdrawal anxiety in rats. Eur J Pharmacol. 2007 Jul 19;567(3):211-22

5- Maayan R, Touati-Werner D, Ram E, Strous R, Keren O, Weizman A. The protective effect of frontal cortex dehydroepiandrosterone in anxiety and depressive models in mice. Pharmacol Biochem Behav. 2006 Oct;85(2):415-21

6- Melchior CL, Ritzmann RF. Dehydroepiandrosterone is an anxiolytic in mice on the plus maze. Pharmacol Biochem Behav. 1994 Mar;47(3):437-41

7- Ovsiukova MV, Kudriavtseva NN, Obut TA, Amikishieva AV. Anxiolytic effect of the dehydroepiandrosterone sulfate: mu-opioid mechanism. Ross Fiziol Zh Im I M Sechenova. 2003 May;89(5):598-604

Baixa Resistência Ao Estresse: A Associação Com Baixos Níveis de DHEA

1- Morgan CA 3rd, Rasmusson A, Pietrzak RH, Coric V, Southwick SM. Relationships among plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate, cortisol, symptoms of dissociation, and objective performance in humans exposed to underwater navigation stress. Biol Psychiatry. 2009 Aug 15;66(4):334-40 (“DHEA and DHEAS were significantly and negatively related to stress-induced symptoms of dissociation during performance of the task”)

Ansiedade: A Melhora Com a Reposição de Melatonina

1- Ovanesov KB, Ovanesova IM, Arushanian EB. Effects of melatonin and motherwort tincture on the emotional state and visual functions in anxious subjects. Eksp Klin Farmakol. 2006 Nov-Dec;69(6):17-9

2- Acil M, Basgul E, Celiker V, Karagoz AH, Demir B, Aypar U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol. 2004 Jul;21(7):553-7

3- Lissoni P, Barni S, Meregalli S, Fossati V, Cazzaniga M, Esposti D, Tancini G. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone Br J Cancer. 1995 Apr;71(4):854-6

4- Nelson E, Panksepp J, Ikemoto S. The effects of melatonin on isolation distress in chickens. Pharmacol Biochem Behav. 1994 Oct;49(2):327-33Nava F, Carta G. Melatonin reduces anxiety induced by lipopolysaccharide in the rat. Neurosci Lett. 2001 Jul 6;307(1):57-60

5- Naranjo-Rodriguez EB, Osornio AO, Hernandez-Avitia E, Mendoza-Fernandez V, Escobar A. Anxiolytic-like actions of melatonin, 5-metoxytryptophol, 5-hydroxytryptophol and benzodiazepines on a conflict procedure. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Jan;24(1):117-29

Ansiedade: Associação Com Baixos Níveis dos Hormônios Tireoidianos

1- Constant EL, Adam S, Seron X, Bruyer R, Seghers A, Daumerie C. Anxiety and depression, attention, and executive functions in hypothyroidism. J Int Neuropsychol Soc. 2005 Sep;11(5):535-44

2- Kikuchi M, Komuro R, Oka H, Kidani T, Hanaoka A, Koshino Y. Relationship between anxiety and thyroid function in patients with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):77-81

3- Bauer M, Priebe S, Kurten I, Graf KJ, Baumgartner A. Psychological and endocrine abnormalities in refugees from East Germany: Part I. Prolonged stress, psychopathology, and hypothalamic-pituitary-thyroid axis activity. Psychiatry Res. 1994 Jan;51(1):61-73

4- Magliozzi JR, Maddock RJ, Gold AS, Gietzen DW. Relationships between thyroid indices and symptoms of anxiety in depressed outpatients Ann Clin Psychiatry. 1993 Jun;5(2):111-6

5- Sait Gonen M, Kisakol G, Savas Cilli A, Dikbas O, Gungor K, Inal A, Kaya A. Assessment of anxiety in subclinical thyroid disorders. Endocr J. 2004 Jun;51(3):311-5

6- Larisch R, Kley K, Nikolaus S, Sitte W, Franz M, Hautzel H, Tress W, Muller HW.. Depression and anxiety in different thyroid function states. Horm Metab Res. 2004 Sep;36(9):650-3


8- Landen M, Baghaei F, Rosmond R, Holm G, Bjorntorp P, Eriksson E. Dyslipidemia and high waist-hip ratio in women with self-reported social anxiety. Psychoneuroendocrinology. 2004 Sep;29(8):1037-46 (Serum levels of free thyroxin (14+/-2 versus. 16+/-4, P=0.04) were lower in subjects confirming social anxiety)

Ansiedade: A Melhora Com a Reposição dos Hormônios Tireoidianos

1- Saravanan P, Simmons DJ, Greenwood R, Peters TJ, Dayan CM. Partial substitution of thyroxine (T4) with tri-iodothyronine in patients on T4 replacement therapy: results of a large community-based randomized controlled trial. J Clin Endocrinol Metab. 2005 Feb;90(2):805-12

2- Venero C, Guadano-Ferraz A, Herrero AI, Nordstrom K, Manzano J, de Escobar GM, Bernal J, Vennstrom B. Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor alpha1 can be ameliorated by T3 treatment. Genes Dev. 2005 Sep 15;19(18):2152-63

Ansiedade: Associação Com Baixos Níveis do Hormônio do Crescimento

1- Stouthart PJ, Deijen JB, Roffel M, Delemarre-van de Waal HA. Quality of life of growth hormone (GH) deficient young adults during discontinuation and restart of GH therapy. Psychoneuroendocrinology. 2003 Jul;28(5):612-26

2- Malberg JE, Platt B, Rizzo SJ, Ring RH, Lucki I, Schechter LE, Rosenzweig-Lipson S. Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects. Neuropsychopharmacology. 2007 Nov;32(11):2360-8

3- Uhde TW, Malloy LC, Slate SO. Fearful behavior, body size, and serum IGF-I levels in nervous and normal pointer dogs. Pharmacol Biochem Behav. 1992 Sep;43(1):263-9

4- Tancer ME, Stein MB, Uhde TW. Growth hormone response to intravenous clonidine in social phobia: comparison to patients with panic disorder and healthy volunteers. Biol Psychiatry. 1993 Nov 1;34(9):591-5

5- Cameron OG, Abelson JL, Young EA. Anxious and depressive disorders and their comorbidity: effect on central nervous system noradrenergic function. Biol Psychiatry. 2004 Dec 1;56(11):875-83

6- Stabler B. Impact of growth hormone (GH) therapy on quality of life along the lifespan of GH-treated patients. Horm Res. 2001;56 Suppl 1:55-8

7- Abelson JL, Glitz D, Cameron OG, Lee MA, Bronzo M, Curtis GC. Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatry. 1991 Feb;48(2):157-62

Ansiedade: A Melhora Com a Reposição do Hormônio do Crescimento

1- Thompson JL, Butterfield GE, Gylfadottir UK, Yesavage J, Marcus R, Hintz RL, Pearman A, Hoffman AR. Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. : J Clin Endocrinol Metab. 1998 May;83(5):1477-84

2- Darnaudéry M, Perez-Martin M, Bélizaire G, Maccari S, Garcia-Segura LM. Insulin-like growth factor 1 reduces age-related disorders induced by prenatal stress in female rats. Neurobiol Aging. 2006 Jan;27(1):119-27

3- Arwert LI, Deijen JB, Muller M, Drent ML. Long-term growth hormone treatment preserves GH-induced memory and mood improvements: a 10-year follow-up study in GH-deficient adult men. Horm Behav. 2005 Mar;47(3):343-9

4- Lasaite L, Bunevicius R, Lasiene D, Lasas L. Psychological functioning after growth hormone therapy in adult growth hormone deficient patients: endocrine and body composition correlates. Medicina (Kaunas). 2004;40(8):740-4

Ansiedade: Associação Com Baixos Níveis de Pregnenolona 1. Ritsner M, Maayan R, Gibel A, Weizman A. Differences in blood pregnenolone

and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects. Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65

2. Heydari B, Le Melledo JM. Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia. Psychol Med. 2002 Jul;32(5):929-33

3. Semeniuk T, Jhangri GS, Le Melledo JM. Neuroactive steroid levels in patients with generalized anxiety disorder. J Neuropsychiatry Clin Neurosci. 2001 Summer;13(3):396-8

4. Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy RH, Biggio G. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABA(A) receptor function in rat brain. J Neurochem. 2000 Aug;75(2):732-40

Ansiedade: A Melhora Com a Reposição de Pregnenolona

1- Reddy DS, Kulkarni SK. Neurosteroid coadministration prevents development of tolerance and augments recovery from benzodiazepine withdrawal anxiety and hyperactivity in mice. Methods Find Exp Clin Pharmacol. 1997 Jul-Aug;19(6):395-405

2- Reddy DS, Kulkarni SK. Differential anxiolytic effects of neurosteroids in the mirrored chamber behavior test in mice. Brain Res. 1997 Mar 28;752(1-2):61-71

3- Jorge JC, Gonzalez L, Fortis A, Cruz ND. Sex-specific modulation of anxiety and locomotion after neonatal exposure to pregnenolone sulfate. Physiol Behav. 2005 Jan 17;83(5):779-86

4- Melchior CL, Ritzmann RF. Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav. 1994 Aug;48(4):893-7

Ansiedade: A Melhora Com a Reposição de Estradiol e Progesterona

1- Collins A, Hanson U, Eneroth P, Hagenfeldt K, Lundberg U, Frankenhaeuser M. Psychophysiological stress responses in postmenopausal women before and after hormonal replacement therapy. Hum Neurobiol. 1982;1(2):153-9

Ansiedade: A Melhora Com a Reposição de Estradiol

1- Best NR, Rees MP, Barlow DH, Cowen PJ. Effect of estradiol implant on noradrenergic function and mood in menopausal subjects. Psychoneuroendocrinology. 1992;17(1):87-93

2- Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977 Apr;4(1):31-47

3- Montgomery JC, Appleby L, Brincat M, Versi E, Tapp A, Fenwick PB, Studd JW. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. Lancet. 1987 Feb 7;1(8528):297-9

4- Nathorst-Boos J, von Schoultz B, Carlstrom K. Elective ovarian removal and estrogen replacement therapy - effects on sexual life, psychological well-

being and androgen status. J Psychosom Obstet Gynaecol. 1993 Dec;14(4):283-93

5- Walf AA, Paris JJ, Frye CA. Chronic estradiol replacement to aged female rats reduces anxiety-like and depression-like behavior and enhances cognitive performance. Psychoneuroendocrinology. 2009 Jul;34(6):909-16

6- Walf AA, Frye CA. Estradiol decreases anxiety behavior and enhances inhibitory avoidance and gestational stress produces opposite effects. Stress. 2007 Aug;10(3):251-60

Ansiedade: A Melhora Com a Reposição de Progesterona

1- Wieland S, Lan NC, Mirasedeghi S, Gee KW. Anxiolytic activity of the progesterone metabolite 5 alpha-pregnan-3 alpha-o1-20-one. Brain Res. 1991 Nov 29;565(2):263-8

2- Picazo O, Fernandez-Guasti A. Anti-anxiety effects of progesterone and some of its reduced metabolites: an evaluation using the burying behavior test. Brain Res. 1995 May 22;680(1-2):135-41.

3- Bitran D, Shiekh M, McLeod M. Anxiolytic effect of progesterone is mediated by the neurosteroid allopregnanolone at brain GABAA receptors. J Neuroendocrinol. 1995 Mar;7(3):171-7

4- Baker ER, Best RG, Manfredi RL, Demers LM, Wolf GC. Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome. J Assist Reprod Genet. 1995 Mar;12(3):205-9

5- Bitran D, Purdy RH, Kellogg CK. Anxiolytic effect of progesterone is associated with increases in cortical allopregnanolone and GABAA receptor function. Pharmacol Biochem Behav. 1993 Jun;45(2):423-8

Ansiedade: Associação Com Baixos Níveis de Testosterona 13. Werner AA. The male climateric JAMA. 1946;132(4):188-94 14. Diamond P, Brisson GR, Candas B, Peronnet F. Trait anxiety, submaximal

physical exercise and blood androgens. Eur J Appl Physiol Occup Physiol. 1989;58(7):699-704

Ansiedade: A Melhora Com a Reposição de Testosterona 15. Cooper MA, Ritchie EC. Testosterone replacement therapy for anxiety. Am J

Psychiatry. 2000 Nov;157(11):1884 16. Aikey JL, Nyby JG, Anmuth DM, James PJ. Testosterone rapidly reduces

anxiety in male house mice (Mus musculus). Horm Behav. 2002 Dec;42(4):448-60

5- CONTROLE DA QUALIDADE DO SONO

ATRAVÉS DA MODULAÇÃO HORMONAL

Distúrbios do Sono: A Correlação Com Baixos Níveis de Melatonina

1- Rahman SA, Marcu S, Kayumov L, Shapiro CM. Altered sleep architecture

and higher incidence of subsyndromal depression in low endogenous melatonin secretors. Eur Arch Psychiatry Clin Neurosci. 2010

2- Blaicher W, Speck E, Imhof MH, Gruber DM, Schneeberger C, Sator MO, Huber JC. Melatonin in postmenopausal females. Arch Gynecol Obstet. 2000 Feb;263(3):116-8

3- Riemann D, Klein T, Rodenbeck A, Feige B, Horny A, Hummel R, Weske G, Al-Shajlawi A, Voderholzer U. Nocturnal cortisol and melatonin secretion in primary insomnia. Psychiatry Res. 2002 Dec 15;113(1-2):17-27

4- Rodenbeck A, Huether G, Ruther E, Hajak G. Nocturnal melatonin secretion and its modification by treatment in patients with sleep disorders. Adv Exp Med Biol. 1999;467:89-93

5- Hajak G, Rodenbeck A, Staedt J, Bandelow B, Huether G, Ruther E. Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. J Pineal Res. 1995 Oct;19(3):116-22

6- Hansen T, Bratlid T, Lingjarde O, Brenn T. Midwinter insomnia in the subarctic region: evening levels of serum melatonin and cortisol before and after treatment with bright artificial light. Acta Psychiatr Scand. 1987 Apr;75(4):428-34

Distúrbios do Sono: A Melhora Com a Reposição de Melatonina

1- Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-136

2- Bendz LM, Scates AC. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann Pharmacother. 2010 Jan;44(1):185-91

3- Aeschbach D, Lockyer BJ, Dijk DJ, Lockley SW, Nuwayser ES, Nichols LD, Czeisler CA. Use of transdermal melatonin delivery to improve sleep maintenance during daytime. Clin Pharmacol Ther. 2009 Oct;86(4):378-82

4- Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-49

5- Megwalu UC, Finnell JE, Piccirillo JF. The effects of melatonin on tinnitus and sleep. Otolaryngol Head Neck Surg. 2006 Feb;134(2):210-3

6- Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605

7- Skene DJ, Arendt J. Circadian rhythm sleep disorders in the blind and their treatment with melatonin. Sleep Med. 2007 Sep;8(6):651-5

8- Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). 1996 Jul;126(2):179-81

9- Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995 Aug 26;346(8974):541-4

10- Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M. Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuroendocrinol Lett. 2002 Apr;23 Suppl 1:17-9

11- Monti JM, Cardinali DP. A critical assessment of the melatonin effect on sleep in humans. Biol Signals Recept. 2000 Nov-Dec;9(6):328-39

Distúrbios do Sono: A Melhora Com a Reposição dos Hormônios Tireoidianos

1- Jha A, Sharma SK, Tandon N, Lakshmy R, Kadhiravan T, Handa KK, Gupta R, Pandey RM, Chaturvedi PK. Thyroxine replacement therapy reverses sleep-disordered breathing in patients with primary hypothyroidism. Sleep Med. 2006 Jan;7(1):55-61

2- Misiolek M, Marek B, Namyslowski G, Scierski W, Zwirska-Korczala K, Kazmierczak-Zagorska Z, Kajdaniuk D, Misiolek H. Sleep apnea syndrome and snoring in patients with hypothyroidism with relation to overweight. J Physiol Pharmacol. 2007 Mar;58 Suppl 1:77-85

3- Ruiz-Primo E, Jurado JL, Solis H, Maisterrena JA, Fernandez-Guardiola A, Valverde C. Polysomnographic effects of thyroid hormones primary myxedema. Electroencephalogr Clin Neurophysiol. 1982 May;53(5):559-64

4- Orr WC, Males JL, Imes NK. Myxedema and obstructive sleep apnea. Am J Med. 1981 May;70(5):1061-6

Distúrbios do Sono: A Correlação Com Baixos Níveis do Hormônio do

Crescimento

1- Ismailogullari S, Tanriverdi F, Kelestimur F, Aksu M. Sleep architecture in Sheehan's syndrome before and 6 months after growth hormone replacement therapy. Psychoneuroendocrinology. 2009 Feb;34(2):212-9

2- Astrom C, Lindholm J. Growth hormone-deficient young adults have decreased deep sleep. Neuroendocrinology. 1990 Jan;51(1):82-4

Distúrbios do Sono: A Melhora Com a Reposição do Hormônios do

Crescimento

1- Verrillo E, Bruni O, Franco P, Ferri R, Thiriez G, Pavone M, Petrone A, Paglietti MG, Crinò A, Cutrera R. Analysis of NREM sleep in children with Prader-Willi syndrome and the effect of growth hormone treatment. Sleep Med. 2009 Jun;10(6):646-50

2- Ismailogullari S, Tanriverdi F, Kelestimur F, Aksu M. Sleep architecture in Sheehan's syndrome before and 6 months after growth hormone replacement therapy. Psychoneuroendocrinology. 2009 Feb;34(2):212-9

3- Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab. 2006 Feb;91(2):413-7

4- Peker Y, Svensson J, Hedner J, Grote L, Johannsson G. Sleep apnoea and quality of life in growth hormone (GH)-deficient adults before and after 6 months of GH replacement therapy. Clin Endocrinol (Oxf). 2006 Jul;65(1):98-105

5- Astrom C, Pedersen SA, Lindholm J. The influence of growth hormone on sleep in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1990 Oct;33(4):495-500

Distúrbios do Sono: A Correlação Com Baixos Níveis de Estradiol

1- Merklinger-Gruchala A, Ellison PT, Lipson SF, Thune I, Jasienska G. Low

estradiol levels in women of reproductive age having low sleep variation. Eur J Cancer Prev. 2008 Oct;17(5):467-72

2- Hollander LE, Freeman EW, Sammel MD, Berlin JA, Grisso JA, Battistini M. Sleep quality, estradiol levels, and behavioral factors in late reproductive age women. Obstet Gynecol. 2001 Sep;98(3):391-7

Distúrbios do Sono: A Melhora Com a Reposição de Estradiol

1- Antonijevic IA, Stalla GK, Steiger A. Modulation of the sleep electroencephalogram by estrogen replacement in postmenopausal women. Am J Obstet Gynecol. 2000 Feb;182(2):277-82.

2- Schiff I, Regestein Q, Tulchinsky D, Ryan KJ. Effects of estrogens on sleep and psychological state of hypogonadal women. JAMA. 1979 Nov 30;242(22):2405-4

Distúrbios do Sono: A Melhora Com a Reposição de Progesterona

1- Montplaisir J, Lorrain J, Denesle R, Petit D. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause. 2001 Jan-Feb;8(1):10-6

2- Schüssler P, Kluge M, Yassouridis A, Dresler M, Held K, Zihl J, Steiger A. Progesterone reduces wakefulness in sleep EEG and has no effect on cognition in healthy postmenopausal women. Psychoneuroendocrinology. 2008 Sep;33(8):1124-31

Distúrbios do Sono: A Melhora Com a Reposição de Estradiol e Progesterona

1- Hachul H, Bittencourt LR, Andersen ML, Haidar MA, Baracat EC, Tufik S. Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women. Int J Gynaecol Obstet. 2008 Dec;103(3):207-12

2- Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause. 2006 Sep-Oct;13(5):780-6

3- Keefe DL, Watson R, Naftolin F. Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study. Menopause. 1999 Fall;6(3):196-200.

4- Sarti CD, Chiantera A, Graziottin A, Ognisanti F, Sidoli C, Mincigrucci M, Parazzini F; Gruppo di Studio IperAOGOI. Hormone therapy and sleep quality in women around menopause. Menopause. 2005 Sep-Oct;12(5):545-51

104 ESTUDOS PLACEBO-CONTROLADOS DEMONSTRANDO OS BENEFÍCIOS

E CONTROLE EXERCIDOS PELA REPOSIÇÃO DE MELATONINA NOS MECANISMOS E QUALIDADE DO SONO EM CRIANÇAS E ADULTOS

Crianças

1. Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA.

Melatonin for chronic sleep onset insomnia in children: a randomised placebo-controlled trial. J Child Neurol. 2001 Feb;16(2):86-92

2. Smits MG, van Stel HF, van der Heijden K, Meijer AM, Coenen AM, Kerkhof GA. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1286-93

3. Jan JE, Hamilton D, Seward N, Fast DK, Freeman RD, Laudon M. Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders. J Pineal Res. 2000 Aug;29(1):34-9

4. Jan JE, Espezel H, Appleton RE. The treatment of sleep disorders with melatonin. Dev Med Child Neurol. 1994 Feb;36(2):97-107

5. Dodge NN, Wilson GA .Melatonin for treatment of sleep disorders in children with developmental disabilities. J Child Neurol. 2001 Aug;16(8):581-4

6. McArthur AJ, Budden SS.Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol. 1998 Mar;40(3):186-92

7. Coppola G, Iervolino G, Mastrosimone M, La Torre G, Ruiu F, Pascotto A. Melatonin in wake-sleep disorders in children, adolescents and young adults with mental retardation with or without epilepsy: a double-blind, cross-over, placebo-controlled trial. Brain Dev. 2004 Sep;26(6):373-6

8. Niederhofer H, Staffen W, Mair A, Pittschieler K. Brief report: melatonin facilitates sleep in individuals with mental retardation and insomnia. J Autism Dev Disord. 2003 Aug;33(4):469-72

Adultos 1- Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in

the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-136

2- Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-49

3- Van Den Heuvel CJ, Kennaway DJ, Dawson D. Effects of daytime melatonin infusion in young adults. Am J Physiol. 1998 Jul;275(1 Pt 1):E19-26

4- Lushington K, Pollard K, Lack L, Kennaway DJ, Dawson D. Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency. Sleep. 1997 Dec;20(12):1135-44

5- Mishima K, Satoh K, Shimizu T, Hishikawa Y. Hypnotic and hypothermic action of daytime-administered melatonin. Psychopharmacology (Berl). 1997 Sep;133(2):168-71

6- Krauchi K, Cajochen C, Wirz-Justice A. A relationship between heat loss and sleepiness: effects of postural change and melatonin administration. J Appl Physiol. 1997 Jul;83(1):134-9

7- Hughes RJ, Badia P. Sleep-promoting and hypothermic effects of daytime melatonin administration in humans. Sleep. 1997 Feb;20(2):124-31

8- Reid K, Van den Heuvel C, Dawson D. Day-time melatonin administration: effects on core temperature and sleep onset latency. J Sleep Res. 1996 Sep;5(3):150-4

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10- Cajochen C, Krauchi K, von Arx MA, Mori D, Graw P, Wirz-Justice A. Daytime melatonin administration enhances sleepiness and theta/alpha activity in the waking EEG. Neurosci Lett. 1996 Apr 5;207(3):209-13

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12- Deacon S, Arendt J. Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res. 1995 Aug 7;688(1-2):77-85

13- Nave R, Iani C, Herer P, Gopher D, Lavie P. Residual effects of daytime administration of melatonin on performance relevant to flight. Behav Brain Res. 2002 Apr 1;131(1-2):87-95

14- Matsumoto M. The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry Clin Neurosci. 1999 Apr;53(2):243-5

15- Gilbert SS, van den Heuvel CJ, Dawson D. Daytime melatonin and temazepam in young adult humans: equivalent effects on sleep latency and body temperatures. J Physiol. 1999 Feb 1;514 ( Pt 3):905-14

16- Rogers NL, Kennaway DJ, Dawson D. Neurobehavioral performance effects of daytime melatonin and temazepam administration. J Sleep Res. 2003 Sep;12(3):207-12

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18- Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA. 1994 Mar 1;91(5):1824-8

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21- Wright J, Aldhous M, Franey C, English J, Arendt J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf). 1986 Apr;24(4):375-82

22- Harris AS, Burgess HJ, Dawson D. The effects of day-time exogenous melatonin administration on cardiac autonomic activity. J Pineal Res. 2001 Oct;31(3):199-205

23- Rajaratnam SM, Middleton B, Stone BM, Arendt J, Dijk DJ. Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities in humans. J Physiol. 2004 Nov 15;561(Pt 1):339-51

24- Holmes AL, Gilbert SS, Dawson D. Melatonin and zopiclone: the relationship between sleep propensity and body temperature. Sleep. 2002 May 1;25(3):301-6

25- Paul MA, Gray G, Kenny G, Pigeau RA. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003 Dec;74(12):1263-70

26- Paul MA, Gray G, MacLellan M, Pigeau RA. Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam. Aviat Space Environ Med. 2004 Jun;75(6):512-9

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30- Tzischinsky O, Lavie P. Melatonin possesses time-dependent hypnotic effects. Sleep. 1994;17(7):638-45

31- Nave R, Peled R, Lavie P. Melatonin improves evening napping. Eur J Pharmacol. 1995 Mar 6;275(2):213-6

32- Stone BM, Turner C, Mills SL, Nicholson AN. Hypnotic activity of melatonin. Sleep. 2000 Aug 1;23(5):663-

33- Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL.Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995 May;57(5):552-8

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35- Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl). 1990;100(2):222-6

36- Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000 Nov;29(4):193-200

37- Pires ML, Benedito-Silva AA, Pinto L, Souza L, Vismari L, Calil HM. Acute effects of low doses of melatonin on the sleep of young healthy subjects. J Pineal Res. 2001 Nov;31(4):326-32

38- Pinto LR Jr, Seabra Mde L, Tufik S. Different criteria of sleep latency and the effect of melatonin on sleep consolidation. Sleep. 2004 Sep 15;27(6):1089-92

39- 123. Attenburrow ME, Cowen PJ, Sharpley AL. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). 1996 Jul;126(2):179-81

40- Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995 Aug 26;346(8974):541-4

41- Garfinkel D, Laudon M, Zisapel N. Improvement of sleep quality by controlled-release melatonin in benzodiazepine-treated elderly insomniacs. Arch Gerontol Geriatr. 1997 Mar-Apr;24(2):223-31

42- Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995 Sep;18(7):598-603

43- Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30

44- Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep. 1998;21(1):52-68

45- MacFarlane JG, Cleghorn JM, Brown GM, Streiner DL. The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. Biol Psychiatry. 1991 Aug 15;30(4):371-6

46- Andrade C, Srihari BS, Reddy KP, Chandramma L. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2001 Jan;62(1):41-5

47- Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999 Nov 8;159(20):2456-60

48- Dahlitz M, Alvarez B, Vignau J, English J, Arendt J, Parkes JD. Delayed sleep phase syndrome response to melatonin. Lancet. 1991 May 11;337(8750):1121-4

49- Kayumov L, Brown G, Jindal R, Buttoo K, Shapiro CM. A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom Med. 2001 Jan-Feb;63(1):40-8

50- Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC. Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep. 2005 Oct 1;28(10):1271-8

51- Nagtegaal JE, Kerkhof GA, Smits MG, Swart AC, Van Der Meer YG. Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res. 1998 Jun;7(2):135-43

52- Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004 Jan;89(1):128-34

53- 148. Suhner A, Schlagenhauf P, Johnson R, Tschopp A, Steffen R. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int. 1998 Nov;15(6):655-66

54- Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry. 1993 Apr 1;33(7):526-30

55- Paul MA, Gray G, Sardana TM, Pigeau RA. Melatonin and zopiclone as facilitators of early circadian sleep in operational air transport crews. Aviat Space Environ Med. 2004 May;75(5):439-43

56- Revell VL, Burgess HJ, Gazda CJ, Smith MR, Fogg LF, Eastman CI. Advancing human circadian rhythms with afternoon melatonin and morning intermittent bright light. J Clin Endocrinol Metab. 2006 Jan;91(1):54-9

57- Jorgensen KM, Witting MD. Does exogenous melatonin improve day sleep or night alertness in emergency physicians working night shifts? Ann Emerg Med. 1998 Jun;31(6):699-704

58- Dawson D, Encel N, Lushington K. Improving adaptation to simulated night shift: timed exposure to bright light versus daytime melatonin administration. Sleep. 1995 Jan;18(1):11-21

59- Folkard S, Arendt J, Clark M. Can melatonin improve shift workers' tolerance of the night shift? Some preliminary findings. Chronobiol Int. 1993 Oct;10(5):315-20

60- Sharkey KM, Fogg LF, Eastman CI. Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res. 2001 Sep;10(3):181-92

61- Yoon IY, Song BG. Role of morning melatonin administration and attenuation of sunlight exposure in improving adaptation of night-shift workers. Chronobiol Int. 2002 Sep;19(5):903-13

62- Yang CM, Spielman AJ, D'Ambrosio P, Serizawa S, Nunes J, Birnbaum J. A single dose of melatonin prevents the phase delay associated with a delayed weekend sleep pattern. Sleep. 2001 May 1;24(3):272-81

63- Middleton B, Arendt J, Stone BM. Complex effects of melatonin on human circadian rhythms in constant dim light. J Biol Rhythms. 1997 Oct;12(5):467-77

64- Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth. 1999 Jun;82(6):875-80

65- Acil M, Basgul E, Celiker V, Karagoz AH, Demir B, Aypar U. Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance. Eur J Anaesthesiol. 2004 Jul;21(7):553-7

66- Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry. 1998 Aug;155(8):1119-21

67- Leppamaki S, Partonen T, Vakkuri O, Lonnqvist J, Partinen M, Laudon M. Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behavior. Eur Neuropsychopharmacol. 2003 May;13(3):137-45

68- Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry. 2000 May;61(5):373-7

69- Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch. 2003 Aug;70(4):334-41

70- O'Callaghan FJ, Clarke AA, Hancock E, Hunt A, Osborne JP.Use of melatonin to treat sleep disorders in tuberous sclerosis. Dev Med Child Neurol. 1999 Feb;41(2):123-6

71- Rosenberg SI, Silverstein H, Rowan PT, Olds MJ. Effect of melatonin on tinnitus. Laryngoscope. 1998 Mar;108(3):305-10

72- Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ. Melatonin for sleep disturbances in Parkinson's disease. Sleep Med. 2005 Sep;6(5):459-66.

73- Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000 Oct 12;343(15):1070-7

74- Sack RL, Lewy AJ, Blood ML, Stevenson J, Keith LD. Melatonin administration to blind people: phase advances and entrainment. J Biol Rhythms. 1991 Fall;6(3):249-61

75- Fischer S, Smolnik R, Herms M, Born J, Fehm HL. Melatonin acutely improves the neuroendocrine architecture of sleep in blind individuals. J Clin Endocrinol Metab. 2003 Nov;88(11):5315-20

76- Hack LM, Lockley SW, Arendt J, Skene DJ. The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects. J Biol Rhythms. 2003 Oct;18(5):420-9

77- Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily night-time melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004 Feb;43(2):192-7

78- Campos FL, da Silva-Junior FP, de Bruin VM, de Bruin PF. Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2004 Nov 1;170(9):947-51

79- Shilo L, Dagan Y, Smorjik Y, Weinberg U, Dolev S, Komptel B, Shenkman L. Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study. Chronobiol Int. 2000 Jan;17(1):71-6

Distúrbios do Sono: A Correlação Com Baixos Níveis de Testosterona

1- Andersen ML, Tufik S. The effects of testosterone on sleep and sleep-disordered breathing in men: its bidirectional interaction with erectile function. Sleep Med Rev. 2008 Oct;12(5):365-79

2- Barrett-Connor E, Dam TT, Stone K, Harrison SL, Redline S, Orwoll E; Osteoporotic Fractures in Men Study Group. The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing. Clin Endocrinol Metab. 2008 Jul;93(7):2602-9

3- Penev PD. Association between sleep and morning testosterone levels in older men. Sleep. 2007 Apr 1;30(4):427-32

Distúrbios do Sono: A Melhora Com a Reposição de Testosterona

1- Davis A, Gilbert K, Misiowiec P, Riegel B. Perceived effects of testosterone replacement therapy in perimenopausal and postmenopausal women: an internet pilot study. Health Care Women Int. 2003 Nov;24(9):831-48

6- CONTROLE DA PRESSÃO ARTERIAL

ATRAVÉS DA MODULAÇÃO HORMONAL

Hipertensão Arterial: A Associação Com Baixos Níveis de Melatonina

1- Cui HW, Zhang ZX, Gao MT, Liu Y, Su AH, Wang MY. Circadian rhythm of melatonin and blood pressure changes in patients with essential hypertension. Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Jan;36(1):20-3

2- Zeman M, Dulková K, Bada V, Herichová I. Plasma melatonin concentrations in hypertensive patients with the dipping and non-dipping blood pressure profile. Life Sci. 2005 Mar 4;76(16):1795-803

3- Cagnacci A, Arangino S, Angiolucci M, Melis GB, Tarquini R, Renzi A, Volpe A. Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy. J Pineal Res. 2000 Oct;29(3):152-8

4- Rapoport SI, Shatalova AM, Malinovskaia NK, Vettenberg L. Melatonin production in hypertensive patients. Klin Med (Mosk). 2000;78(6):21-4

5- Rapoport SI, Shatalova AM, Oraevskii VN, Malinovskaia NK, Vetterberg L. Melatonin production in hypertonic patients during magnetic storms. Ter Arkh. 2001;73(12):29-33

6- Tetsuo M, Polinsky RJ, Markey SP, Kopin IJ. Urinary 6-hydroxymelatonin excretion in patients with orthostatic hypotension. J Clin Endocrinol Metab. 1981 Sep;53(3):607-10

Hipertensão Arterial: A Melhora Com a Reposição de Melatonina

1- Rechciński T, Trzos E, Wierzbowska-Drabik K, Krzemińska-Pakuła M, Kurpesa M. Melatonin for nondippers with coronary artery disease: assessment of blood pressure profile and heart rate variability. Hypertens Res. 2010 Jan;33(1):56-61

2- Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens. 2009 Aug;27 Suppl 6:S17-20.

3- Rechciński T, Kurpesa M, Trzos E, Krzeminska-Pakuła M. The influence of melatonin supplementation on circadian pattern of blood pressure in patients with coronary artery disease--preliminary report. Pol Arch Med Wewn. 2006 Jun;115(6):520-8

4- Cagnacci A, Arangino S, Angiolucci M, Maschio E, Melis GB. Influences of melatonin administration on the circulation of women. Am J Physiol. 1998 Feb;274(2 Pt 2):R335-8

5- Cagnacci A, Arangino S, Angiolucci M, Maschio E, Longu G, Melis GB. Potentially beneficial cardiovascular effects of melatonin administration in women. J Pineal Res. 1997 Jan;22(1):16-9

6- Cagnacci A, Arangino S, Angiolucci M, Melis GB, Facchinetti F, Malmusi S, Volpe A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf). 2001 Feb;54(2):261-6

7- Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999 May 1;83(9):1417-9

8- Burgess HJ, Sletten T, Savic N, Gilbert SS, Dawson D. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol. 2001 Sep;91(3):1214-22

9- Nishiyama K, Yasue H, Moriyama Y, Tsunoda R, Ogawa H, Yoshimura M, Kugiyama K. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am Heart J. 2001 May;141(5):E9

10- Lusardi P, Preti P, Savino S, Piazza E, Zoppi A, Fogari R. Effect of bedtime melatonin ingestion on blood pressure of normotensive subjects. Blood Press Monit. 1997 Apr;2(2):99-103

11- Kitajima T, Kanbayashi T, Saitoh Y, Ogawa Y, Sugiyama T, Kaneko Y, Sasaki Y, Aizawa R, Shimisu T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci. 2001 Jun;55(3):299-300

12- Zaslavskaia RM, Biiasilov NS, Akhmetov Kzh, Teiblium MM. Capozide-50 alone and in combination with melatonin in therapy of hypertension. Klin Med (Mosk). 2000;78(11):39-41

13- Zaslavskaia RM, Komarov FI, Shakirova AN, Teiblium MM, Akhmetov KZh. Effect of moxonidine monotherapy and in combination with melatonin on hemodynamic parameters in patients with arterial hypertension. Klin Med (Mosk). 2000;78(4):41-4

14- Zaslavskaia RM, Komarov FI, Goncharov LF, Goncharova ZF, Makarova LA. Comparative study of the effectiveness of Cozaar monotherapy and Cozaar and melatonin combined therapy in aged patients with hypertension. Klin Med (Mosk). 1998;76(12):49-51

15- Zaslavskaia RM, Shakirova AN, Komarov FI, Teiblium MM, Akhmetov KZh. Effects of melatonin alone and in combination with aceten on chronostructure of diurnal hemodynamic rhythms in patients with hypertension stage II. Ter Arkh. 1999;71(12):21-4

16- Zaslavskaia RM, Komarov FI, Makarova LA, Shakirova AN, Narmanova OZh, Biiasilov N. Time-dependent effects of antihypertensive agents and

chronocorrecting action of melatonin in patients with arterial hypertension. Vestn Ross Akad Med Nauk. 2000;(8):36-41

Hipertensão Arterial: A Associação Com Baixos Níveis de DHEA

1- Herman WA, Seńko A, Korczowska I, Łacka K. Could serum DHEA and DHEAS levels be good risk predictors of metabolic syndrome and osteoporosis in the population of ageing men? Pol Merkur Lekarski. 2009 Sep;27(159):197-201

2- Johannes CB, Stellato RK, Feldman HA, Longcope C, McKinlay JB. Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women's Health Study. J Clin Epidemiol. 1999 Feb;52(2):95-103

3- Nowaczynski W, Fragachan F, Silah J, Millette B, Genest J. Further evidence of altered adrenocortical function in hypertension. Dehydroepiandrosterone excretion rate. Can J Biochem 1968;46(9):1031-8

4- Okamoto K, Yagyu K, Sasaki R. The relationship between serum dehydroepiandrosterone sulfate levels and factors associated with cardiovascular diseases: a cross-sectional study in Japan. Nippon Koshu Eisei Zasshi. 1995;42(2):78-83

5- Legrain S, Berr C, Frenoy N, Gourlet V, Debuire B, Baulieu EE. Dehydroepiandrosterone sulfate in a long-term care aged population. Gerontology. 1995;41(6):343-51

6- Suzuki M, Kanazawa A, Hasegawa M, Hattori Y, Harano Y. A close association between insulin resistance and dehydroepiandrosterone sulfate in subjects with essential hypertension. Endocr J. 1999;46(4):521-8

7- Maccario M, Mazza E, Ramunni J, Oleandri SE, Savio P, Grottoli S, Rossetto R, Procopio M, Gauna C, Ghigo E. Relationships between dehydroepiandrosterone-sulphate and anthropometric, metabolic and hormonal variables in a large cohort of obese women. Clin Endocrinol (Oxf). 1999;50(5):595-600

8- Barna I, Feher T, de Chatel R. Relationship between blood pressure variability and serum dehydroepiandrosterone sulfate levels. Am J Hypertens. 1998 May;11(5):532-8

Hipertensão Arterial: A Melhora Com a Reposição de DHEA

1- Dockery F, Bulpitt CJ, Donaldson M, Fernandez S, Rajkumar C. The relationship between androgens and arterial stiffness in older men. J Am Geriatr Soc. 2003 Nov;51(11):1627-32

2- Hampl V, Bibova J, Povysilova V, Herget J. Dehydroepiandrosterone sulphate reduces chronic hypoxic pulmonary hypertension in rats. Eur Respir J. 2003 May;21(5):862-5

3- Bonnet S, Dumas-de-La-Roque E, Begueret H, Marthan R, Fayon M, Dos Santos P, Savineau JP, Baulieu EE. Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension. Proc Natl Acad Sci USA. 2003 Aug 5;100(16):9488-93

Hipertensão Arterial: A Associação Com Baixos Níveis do Hormônio do Crescimento

1- Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, Rosen T, Lundstedt G, Lundberg PA, Bengtssopn BA. Serum insulin-like growth factor 1 in a random population sample of men and women: relation to age, sex, smoking habits, coffee consumption and physical activity, blood pressure and concentrations of plasma lipids, fibrinogen, parathyroid hormone and osteocalcin. Clin Endocrinol (Oxf). 1994 Sep;41(3):351-7

Hipertensão Arterial: A Melhora Com a Reposição do Hormônio do

Crescimento

1- Holmer H, Svensson J, Rylander L, Johannsson G, Rosén T, Bengtsson BA, Thorén M, Höybye C, Degerblad M, Bramnert M, Hägg E, Edén Engström B, Ekman B, Norrving B, Hagmar L, Erfurth EM. Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone. J Clin Endocrinol Metab. 2007 Sep;92(9):3560-7

2- Feldt-Rasmussen B, Lange M, Sulowicz W, Gafter U, Lai KN, Wiedemann J, Christiansen JS, El Nahas M; APCD Study Group. Growth hormone treatment during hemodialysis in a randomized trial improves nutrition, quality of life, and cardiovascular risk. J Am Soc Nephrol. 2007 Jul;18(7):2161-71

3- Graham MR, Baker JS, Evans P, Kicman A, Cowan D, Hullin D, Davies B. Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users. Growth Horm IGF Res. 2007 Jun;17(3):201-9

4- van Dijk M, Bannink EM, van Pareren YK, Mulder PG, Hokken-Koelega AC. Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (sga) and untreated short SGA controls. J Clin Endocrinol Metab. 2007 Jan;92(1):160-5

5- Caidahl K, Eden S, Bengtsson BA. Cardiovascular and renal effects of growth hormone. Clin Endocrinol (Oxf). 1994 Mar;40(3):393-400

Hipertensão Arterial: A Associação Com Baixos Níveis de IGF-1

1- Sesti G, Sciacqua A, Scozzafava A, Vatrano M, Angotti E, Ruberto C, Santillo E, Parlato G, Perticone F. Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy of hypertensive patients. J Hypertens. 2007 Feb;25(2):471-7

2- Hopkins KD, Lehmann ED, Gosling RG, Parker JR, Sönksen PH. Biochemical correlates of aortic distensibility in vivo in normal subjects. Clin Sci (Lond). 1993 Jun;84(6):593-7

3- Lawlor DA, Ebrahim S, Smith GD, Cherry L, Watt P, Sattar N. The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: findings from the prospective British Women's Heart and Health Study. Atherosclerosis. 2008 Nov;201(1):198-204

4- Paolisso G, Tagliamonte MR, Rizzo MR, Rotondi M, Gualdiero P, Gambardella A, Barbieri M, Carella C, Giugliano D, Varricchio M. Mean arterial blood pressure and serum levels of the molar ratio of insulin-like growth factor-1 to its binding protein-3 in healthy centenarians.J Hypertens. 1999 Jan;17(1):67-73.

Hipertensão Arterial: A Associação Com Baixos Níveis dos Hormônios

Tireoidianos

1- Duan Y, Wang X, Peng W, Feng Y, Tang W, Wu X, Mao X, Bo R, Li W, Chen J, Qin Y, Liu C, Liu C. Gender-specific associations between subclinical hypothyroidism and blood pressure in Chinese adults. Endocrine. 2010 (2009 Oct 14: Epub ahead of print)

2- Kileĭnikov DV, Makusheva MV, Volkov VS. Pathogenesis of arterial hypertension in patients with primary hypothyroidism] Klin Med (Mosk). 2009;87(5):30-2

3- Velkoska Nakova V, Krstevska B, Bosevski M, Dimitrovski Ch, Serafimoski V. Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi. 2009 Dec;30(2):93-102

4- Guasti L, Marino F, Cosentino M, Cimpanelli M, Rasini E, Piantanida E, Vanoli P, De Palma D, Crespi C, Klersy C, Maroni L, Loraschi A, Colombo C, Simoni C, Bartalena L, Lecchini S, Grandi AM, Venco A. Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment. Clin J Pain. 2007 Jul-Aug;23(6):518-23

5- Kotsis V, Alevizaki M, Stabouli S, Pitiriga V, Rizos Z, Sion M, Zakopoulos N. Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J Hypertens. 2007 May;25(5):993-9

6- Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004 Jun;24(1):1-13

7- Streeten DH, Anderson GH Jr, Howland T, Chiang R, Smulyan H. Effects of thyroid function on blood pressure. Recognition of hypothyroid hypertension. Hypertension. 1988 Jan;11(1):78-83

8- Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab. 2002 May;87(5):1996-2000

9- Saito I, Ito K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension. 1983 Jan-Feb;5(1):112-5

Hipertensão Arterial: A Melhora Com a Reposição dos Hormônios Tireoidianos

1- Fuller H Jr, Spittell JA Jr, McConahey WM, Schirger A. Myxedema and hypertension. Postgrad Med. 1966 Oct;40(4):425-8

2- Gasiorowski W, Plazinska MT. Arterial hypertension associated with hyper and hypothyroidism. Pol Tyg Lek. 1992 Nov 2-9;47(44-45):1009-10

Hipertensão Arterial: A Associação Com Baixos Níveis de Estradiol

1- Harrison-Bernard LM, Schulman IH, Raij L. Postovariectomy hypertension is linked to increased renal AT1 receptor and salt sensitivity. Hypertension. 2003 Dec;42(6):1157-63

2- Clark JT, Chakraborty-Chatterjee M, Hamblin M, Wyss JM, Fentie IH. Estrogen depletion differentially affects blood pressure depending on age in Long-Evans rats. Endocrine. 2004 Nov;25(2):173-86

3- Peng N, Clark JT, Wei CC, Wyss JM. Estrogen depletion increases blood pressure and hypothalamic norepinephrine in middle-aged spontaneously hypertensive rats. Hypertension. 2003 May;41(5):1164-7

Hipertensão Arterial: A Melhora Com a Reposição de Estradiol

1- Mercuro G, Zoncu S, Piano D, Pilia I, Lao A, Melis GB, Cherchi A. Estradiol-17beta reduces blood pressure and restores the normal amplitude of the circadian blood pressure rhythm in postmenopausal hypertension. Am J Hypertens. 1998 Aug;11(8 Pt 1):909-13

2- Del Rio G, Velardo A, Zizzo G, Avogaro A, Cipolli C, Della Casa L, Marrama P, MacDonald IA. Effect of estradiol on the sympathoadrenal response to mental stress in normal men. J Clin Endocrinol Metab. 1994 Sep;79(3):836-40

3- Pang SC, Greendale GA, Cedars MI, Gambone JC, Lozano K, Eggena P, Judd HL. Long-term effects of transdermal estradiol with and without medroxyprogesterone acetate. Fertil Steril. 1993 Jan;59(1):76-82

4- Angerer P, Stork S, von Schacky C. Influence of 17beta-oestradiol on blood pressure of postmenopausal women at highvascular risk. J Hypertens. 2001 Dec;19(12):2135-42

5- Manhem K, Ahlm H, Dellborg M, Milsom I. Acute effects of transdermal estrogen in postmenopausal women with coronary artery disease. Using a clinically relevant estrogen dose and concurrent antianginal therapy. Cardiology. 2000;94(2):86-90 (“resting diastolic blood pressure was significantly decreased due to estrogen”)

6- Seely EW, Walsh BW, Gerhard MD, Williams GH. Estradiol with or without progesterone and ambulatory blood pressure in postmenopausal women. Hypertension. 1999 May;33(5):1190-4

Hipertensão Arterial: A Melhora Com a Reposição de Estradiol e Progesterona

1- Junge W, El-Samalouti V, Gerlinger C, Schaefers M. Effects of menopausal hormone therapy on hemostatic parameters, blood pressure, and body weight: open-label comparison of randomized treatment with estradiol plus drospirenone versus estradiol plus norethisterone acetate. Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):195-200

2- Ichikawa A, Sumino H, Ogawa T, Ichikawa S, Nitta K. Effects of long-term transdermal hormone replacement therapy on the renin-angiotensin- aldosterone system, plasma bradykinin levels and blood pressure in normotensive postmenopausal women. Geriatr Gerontol Int. 2008 Dec;8(4):259-64

3- Kaya C, Cengiz SD, Cengiz B, Akgun G. Long-term effects of low-dose 17beta-estradiol plus dydrogesterone on 24-h ambulatory blood pressure in healthy postmenopausal women: a 1-year, randomized, prospective study. Gynecol Endocrinol. 2007 Oct;23 Suppl 1:62-7

4- Preston RA, Norris PM, Alonso AB, Ni P, Hanes V, Karara AH. Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide. Menopause. 2007 May-Jun;14(3 Pt 1):408-14

5- Gerhard M, Walsh BW, Tawakol A, Haley EA, Creager SJ, Seely EW, Ganz P, Creager MA. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation. 1998 Sep 22;98(12):1158-63

6- Kornhauser C, Malacara JM, Garay ME, Perez-Luque EL. The effect of hormone replacement therapy on blood pressure and cardiovascular risk factors in menopausal women with moderate hypertension. J Hum Hypertens. 1997 Jul;11(7):405-11

Hipertensão Arterial: A Associação Com Baixos Níveis de Testosterona

1- Ishikura F, Asanuma T, Beppu S. Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic. Hypertens Res. 2008 Feb;31(2):243-8

2- Hughes GS, Ringer TV, Watts KC, DeLoof MJ, Francom SF, Spillers CR. Fish oil produces an atherogenic lipid profile in hypertensive men. Atherosclerosis. 1990 Oct;84(2-3):229-37

3- Tuev AV, Lunegova NV. Several indicators of hormonal homeostasis (hypophysis - gonads) in patients with hypertension. Ross Med Zh. 1992;(3):10-3

4- Phillips GB, Jing TY, Resnick LM, Barbagallo M, Laragh JH, Sealey JE. Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension. J Hypertens. 1993 Jul;11(7):699-702

Hipertensão Arterial: A Melhora Com a Reposição de Testosterona

1- Shapiro J, Christiana J, Frishman WH. Testosterone and other anabolic steroids as cardiovascular drugs. Am J Ther. 1999 May;6(3):167-74

7- CONTROLE DA GORDURA CORPORAL E

PROFILAXIA E TRATAMENTO DA OBESIDADE ATRAVÉS DA MODULAÇÃO HORMONAL

Obesidade: A Associação Com Baixos Níveis de Melatonina

1- Blaicher W, Imhof MH, Gruber DM, Schneeberger C, Sator MO, Huber JC. Endocrinological disorders. Focusing on melatonin's interactions. Gynecol Obstet Invest. 1999;48(3):179-82

2- Birketvedt GS, Florholmen J, Sundsfjord J, Osterud B, Dinges D, Bilker W, Stunkard A. Behavioral and neuroendocrine characteristics of the night-eating syndrome. JAMA. 1999 Aug 18;282(7):657-63

3- Ostrowska Z, Zwirska-Korczala K, Buntner B, Pardela M, Drozdz M. Association of body mass and body fat distribution with serum melatonin levels in obese women either non-operated or after jejunoileostomy. Endocr Regul. 1996 Mar;30(1):33-40

Obesidade: A melhora Com a Reposição de Melatonina

1- Hussein MR, Ahmed OG, Hassan AF, Ahmed MA. Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model. Int J Exp Pathol. 2007 Feb;88(1):19-29

2- Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 1999 Feb;140(2):1009-12

3- Wolden-Hanson T, Mitton DR, McCants RL, Yellon SM, Wilkinson CW, Matsumoto AM, Rasmussen DD. Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology. 2000 Feb;141(2):487-97

4- Rasmussen DD, Mitton DR, Larsen SA, Yellon SM. Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses. J Pineal Res 2001 Aug;31(1):89-94

5- Bartness TJ, Wade GN. Body weight, food intake and energy regulation in exercising and melatonin-treated Siberian hamsters. Physiol Behav. 1985 Nov;35(5):805-8

6- Zeman M, Vyboh P, Jurani M, Lamosova D, Kostal L, Bilcik B, Blazicek P, Juraniova E. Effects of exogenous melatonin on some endocrine, behavioral and metabolic parameters in Japanese quail Coturnix coturnix japonica. Comp Biochem Physiol Comp Physiol. 1993 Jun;105(2):323-8

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1- Rotondi M, Leporati P, La Manna A, Pirali B, Mondello T, Fonte R, Magri F, Chiovato L. Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism? Eur J Endocrinol. 2009 Mar;160(3):403-8

2- Verma A, Jayaraman M, Kumar HK, Modi KD. Hypothyroidism and obesity. Cause or effect? Saudi Med J. 2008 Aug;29(8):1135-8

3- Resta O, Pannacciulli N, Di Gioia G, Stefano A, Barbaro MP, De Pergola G. High prevalence of previously unknown subclinical hypothyroidism in obese patients referred to a sleep clinic for sleep disordered breathing. Nutr Metab Cardiovasc Dis. 2004 Oct;14(5):248-53

4- Jung CH, Sung KC, Shin HS, Rhee EJ, Lee WY, Kim BS, Kang JH, Kim H, Kim SW, Lee MH, Park JR, Kim SW. Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea. Korean J Intern Med. 2003 Sep;18(3):146-53

5- Rimm AA, Werner LH, Yserloo BV, Bernstein RA. Relationship of ovesity and disease in 73,532 weight-conscious women. Public Health Rep. 1975 Jan-Feb;90(1):44-54

Obesidade: A melhora Com a Reposição dos Hormônios Tideoidianos

1- Moore R, Grant AM, Howard AN, Mills IH. Treatment of obesity with triiodothyronine and a very-low-calorie liquid formula diet. Lancet. 1980 Feb 2;1(8162):223-6

2- Gelvin EP, Kenigsberg S, Boyd LJ. Results of addition of liothyronine to a weight-reducing regimen.J Am Med Assoc. 1959 Jul 25;170(13):1507-12

3- Rozen R, Abraham G, Falcou R, Apfelbaum M. Effects of a 'physiological' dose of triiodothyronine on obese subjects during a protein-sparing diet. Int J Obes. 1986;10(4):303-12

4- Pasquali R, Baraldi G, Biso P, Piazzi S, Patrono D, Capelli M, Melchionda N. Effect of 'physiological' doses of triiodothyronine replacement on the

hormonal and metabolic adaptation to short-term semistarvation and to low-calorie diet in obese patients. Clin Endocrinol (Oxf). 1984 Oct;21(4):357-67

5- Koppeschaar HP, Meinders AE, Schwarz F. Metabolic responses in grossly obese subjects treated with a very-low-calorie diet with and without triiodothyronine treatment. Int J Obes. 1983;7(2):133-41

6- Koppeschaar HP, Meinders AE, Schwarz F. The effect of a low-calorie diet alone and in combination with triiodothyronine therapy on weight loss and hypophyseal thyroid function in obesity. Int J Obes. 1983;7(2):123-31

7- Wilson JH, Lamberts SW. The effect of triiodothyronine on weight loss and nitrogen balance of obese patients on a very-low-calorie liquid-formula diet. Int J Obes. 1981;5(3):279-82

8- Moore R, Mehrishi JN, Verdoorn C, Mills IH. The role of T3 and its receptor in efficient metabolisers receiving very-low-calorie diets. Int J Obes. 1981;5(3):283-6

9- Moore R, Grant AM, Howard AN, Mills IH. Treatment of obesity with triioidothyronine and a very low caorie liquid formula diet. Lancet 1980 Feb. 2;223-6

Obesidade: A Associação Com Baixos Níveis de DHEA

1- Rabijewski M, Kozakowski J, Zgliczyński W. The relationship between testosterone and dehydroepiandrosterone sulfate concentrations, insulin resistance and visceral obesity in elderly men] Endokrynol Pol. 2005 Nov-Dec;56(6):897-903

2- Blanchette S, Marceau P, Biron S, Brochu G, Tchernof A. Circulating progesterone and obesity in men. Horm Metab Res. 2006 May;38(5):330-5

3- Savastano S, Belfiore A, Guida B, Angrisani L, Orio F Jr, Cascella T, Milone F, Micanti F, Saldalamacchia G, Lombardi G, Colao A. Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women. J Endocrinol Invest. 2005 Jun;28(6):509-15

4- Diamond P, Cusan L, Gomez JL, Belanger A, Labrie F. Metabolic effects of 12-month percutaneous dehydroepiandrosterone replacement therapy in postmenopausal women. J Endocrinol. 1996;150 Suppl:S43-50

5- Herranz L, Megia A, Grande C, Gonzalez-Gancedo P, Pallardo F. Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men. Int J Obes Relat Metab Disord 1995;19(1):57-60

6- De Pergola G, Zamboni M, Sciaraffia M, Turcato E, Pannacciulli N, Armellini F, Giorgino F, Perrini S, Bosello O, Giorgino R. Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal obese women. Int J Obes Relat Metab Disord. 1996 Dec;20(12):1105-10

7- De Pergola G, Giagulli VA, Garruti G, Cospite MR, Giorgino F, Cignarelli M, Giorgino R. Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index. Metabolism. 1991 Feb;40(2):187-90

8- De Pergola G. The adipose tissue metabolism: role of testosterone and dehydroepiandrosterone. Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S59-63

Obesidade: A melhora Com a Reposição de DHEA

1- Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf). 2000;53(5):561-8

2- Nestler JE, Barlascini CO, Clore JN, Blackard WG. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab. 1988;66(1):57-61

3- Abrahamsson L, Hackl H. Catabolic effects and the influence on hormonal variables under treatment with Gynodian-Depot or dehydroepiandrosterone (DHEA) oenanthate. Maturitas. 1981;3(3-4):225-34

Obesidade e Adiposidade Visceral: A Associação Com Baixos Níveis do

Hormônio do Crescimento

1- Savastano S, Angrisani L, Di Somma C, Rota F, Savanelli MC, Cascella T, Orio F, Lombardi G, Colao A. Relationship between growth hormone/insulin-like growth factor-1 axis integrity and voluntary weight loss after gastric banding surgery for severe obesity. Obes Surg. 2010 Feb;20(2):211-20

2- Irving BA, Weltman JY, Patrie JT, Davis CK, Brock DW, Swift D, Barrett EJ, Gaesser GA, Weltman A. Effects of exercise training intensity on nocturnal growth hormone secretion in obese adults with the metabolic syndrome. J Clin Endocrinol Metab. 2009 Jun;94(6):1979-86

3- Utz AL, Yamamoto A, Hemphill L, Miller KK. Growth hormone deficiency by growth hormone releasing hormone-arginine testing criteria predicts increased cardiovascular risk markers in normal young overweight and obese women. J Clin Endocrinol Metab. 2008 Jul;93(7):2507-14

4- Kelestimur F, Popovic V, Leal A, Van Dam PS, Torres E, Perez Mendez LF, Greenman Y, Koppeschaar HP, Dieguez C, Casanueva FF. Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test. Clin Endocrinol (Oxf). 2006 Jun;64(6):667-71

5- Beshyah SA, Freemantle C, Thomas E, Rutherford O, Page B, Murphy M, Johnston DG. Abnormal body composition and reduced bone mass in growth hormone deficient hypopituitary adults. Clin Endocrinol (Oxf) 1995 Feb;42(2):179-89

6- Attanasio AF, Bates PC, Ho KK, Webb SM, Ross RJ, Strasburger CJ, Bouillon R, Crowe B, Selander K, Valle D, Lamberts SW; Hypoptiuitary Control and Complications Study International Advisory Board. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS Database. J Clin Endocrinol Metab. 2002 Apr;87(4):1600-6

7- Stouthart PJ, de Ridder CM, Rekers-Mombarg LT, van der Waal HA. Changes in body composition during 12 months after discontinuation of growth hormone therapy in young adults with growth hormone deficiency from childhood. J Pediatr Endocrinol Metab. 1999 Apr;12 Suppl 1:335-8

8- Biller BM, Sesmilo G, Baum HB, Hayden D, Schoenfeld D, Klibanski A. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men withadult-onset GH deficiency. J Clin Endocrinol Metab. 2000 Mar;85(3):970-6

9- Kohno H, Ueyama N, Honda S. Unfavourable impact of growth hormone (GH) discontinuation on body composition and cholesterol profiles after the completion of height growth in GH-deficient young adults. Diabetes Obes Metab. 1999 Sep;1(5):293-6

10- Kuromaru R, Kohno H, Ueyama N, Hassan HM, Honda S, Hara T. Long-term prospective study of body composition and lipid profiles during and after

growth hormone (GH) treatment in children with GH deficiency: gender-specific metabolic effects. J Clin Endocrinol Metab. 1998 Nov;83(11):3890-6

11- Vahl N, Juul A, Jorgensen JO, Orskov H, Skakkebaek NE, Christiansen JS. Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study. J Clin Endocrinol Metab. 2000 May;85(5):1874-81

12- Norrelund H, Vahl N, Juul A, Moller N, Alberti KG, Skakkebaek NE, Christiansen JS, Jorgensen JO. Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism. J Clin Endocrinol Metab. 2000 May;85(5):1912-7

13- Johannsson G. What happens when growth hormone is discontinued at completion of growth? Metabolic aspects. J Pediatr Endocrinol Metab. 2000;13 Suppl 6:1321-6

Obesidade e Adiposidade Visceral: A melhora Com a Reposição do Hormônio

do Crescimento

1- Mekala KC, Tritos NA. Effects of recombinant human growth hormone therapy in obesity in adults: a meta analysis. . J Clin Endocrinol Metab. 2009 Jan;94(1):130-7

2- Graham MR, Baker JS, Evans P, Kicman A, Cowan D, Hullin D, Davies B. Evidence for a decrease in cardiovascular risk factors following recombinant growth hormone administration in abstinent anabolic-androgenic steroid users. Growth Horm IGF Res. 2007 Jun;17(3):201-9

3- Beauregard C, Utz AL, Schaub AE, Nachtigall L, Biller BM, Miller KK, Klibanski A. Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008 Jun;93(6):2063-71

4- Lin HY, Lin SP, Tsai LP, Chao MC, Chen MR, Chuang CK, Huang CY, Tsai FJ, Chou IC, Chiu PC, Huang CH, Yen JL, Lin JL, Kuo PL. Effects of growth hormone treatment on height, weight, and obesity in Taiwanese patients with Prader-Willi syndrome. Chin Med Assoc. 2008 Jun;71(6):305-9

5- Follin C, Thilén U, Ahrén B, Erfurth EM. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH-deficient adult survivors of childhood-onset acute lymphoblastic leukemia. . J Clin Endocrinol Metab. 2006 May;91(5):1872-5

6- Halpern A, Mancini MC, Cercato C, Villares SM, Costa AP. Effects of growth hormone on anthropometric and metabolic parameters in android. Obesity. Arq Bras Endocrinol Metabol. 2006 Feb;50(1):68-73

7- Ahn CW, Kim CS, Nam JH, Kim HJ, Nam JS, Park JS, Kang ES, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB. Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control. Clin Endocrinol (Oxf). 2006 Apr;64(4):444-9

8- Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1-6

9- Rudman D, Feller AG, Cohn L, Shetty KR, Rudman IW, Draper MW. Effects of human growth hormone on body composition in elderly men. Horm Res 1991;36 Suppl 1:73-81

10- Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Sjostrom L, Isaksson OG. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab. 1993 Feb;76(2):309-17

11- Munzer T, Harman SM, Hees P, Shapiro E, Christmas C, Bellantoni MF, Stevens TE, O'Connor KG, Pabst KM, St Clair C, Sorkin JD, Blackman MR. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab. 2001 Aug;86(8):3604-10

12- Rodriguez-Arnao J, Jabbar A, Fulcher K, Besser GM, Ross RJ. Effects of growth hormone replacement on physical performance and body composition in GH deficient adults. Clin Endocrinol (Oxf). 1999 Jul;51(1):53-60

13- Soares CN, Musolino NR, Cunha Neto M, Caires MA, Rosenthal MC, Camargo CP, Bronstein MD. Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial. Arq Neuropsiquiatr. 1999 Jun;57(2A):182-9

14- Fernholm R, Bramnert M, Hagg E, Hilding A, Baylink DJ, Mohan S, Thoren M. Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab. 2000 Nov;85(11):4104-12

15- Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J Clin Endocrinol Metab. 1997 Jan;82(1):82-8

16- Beshyah SA, Freemantle C, Shahi M, Anyaoku V, Merson S, Lynch S, Skinner E, Sharp P, Foale R, Johnston DG. Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults Clin Endocrinol (Oxf). 1995 Jan;42(1):73-84

17- Moorkens G, Wynants H, Abs R. Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. Growth Horm IGF Res. 1998 Apr;8 Suppl B:131-3

18- Lo JC, Mulligan K, Noor MA, Schwarz JM, Halvorsen RA, Grunfeld C, Schambelan M. The effects of recombinant human growth hormone on body composition and glucose metabolism in HIV-infected patients with fat accumulation. J Clin Endocrinol Metab. 2001 Aug;86(8):3480-7

19- Christ ER, Cummings MH, Albany E, Umpleby AM, Lumb PJ, Wierzbicki AS, Naoumova RP, Boroujerdi MA, Sonksen PH, Russell-Jones DL. Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study. J Clin Endocrinol Metab. 1999 Jan;84(1):307-16

20- Florkowski CM, Collier GR, Zimmet PZ, Livesey JH, Espiner EA, Donald RA. Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1996 Dec;45(6):769-73

21- Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E. Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults. J Clin Endocrinol Metab. 2002 Jun;87(6):2725-33

22- Weaver JU, Monson JP, Noonan K, John WG, Edwards A, Evans KA, Cunningham J. The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. J Clin Endocrinol Metab. 1995 Jan;80(1):153-9

23- Vahl N, Jorgensen JO, Hansen TB, Klausen IB, Jurik AG, Hagen C, Christiansen JS. The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with

concomitant reductions in adiposity. A 12 month placebo-controlled study. Int J Obes Relat Metab Disord. 1998 Jun;22(6):529-36

24- Hansen TB, Gram J, Jensen PB, Kristiansen JH, Ekelund B, Christiansen JS, Pedersen FB. Influence of growth hormone on whole body and regional soft tissue composition in adult patients on hemodialysis. A double-blind, randomized, placebo-controlled study. Clin Nephrol; 2000 Feb;53(2):99-107

25- Fisker S, Vahl N, Hansen TB, Jorgensen JO, Hagen C, Orskov H, Christiansen JS. Growth hormone (GH) substitution for one year normalizes elevated GH-binding protein levels in GH-deficient adults secondary to a reduction in body fat. A placebo-controlled trial. Growth Horm IGF Res. 1998 Apr;8(2):105-12

26- Baum HB, Biller BM, Finkelstein JS, Cannistraro KB, Oppenhein DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med. 1996 Dec 1;125(11):883-90

27- Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab. 1997 Feb;82(2):550-5

28- Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, Wang J, Bozzette SA, Breitmeyer JB. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group. Ann Intern Med. 1996 Dec 1;125(11):873-82

29- Lee PD, Pivarnik JM, Bukar JG, Muurahainen N, Berry PS, Skolnik PR, Nerad JL, Kudsk KA, Jackson L, Ellis KJ, Gesundheit N. A randomized, placebo-controlled trial of combined insulin-like growth factor I and low dose growth hormone therapy for wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab. 1996 Aug;81(8):2968-75

30- Toogood AA, Shalet SM.Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study. J Clin Endocrinol Metab. 1999 Jan;84(1):131-6

Obesidade e Elevação do Indice de Massa Corpórea: A Associação Com Baixos Níveis de IGF-1

1- Rasmussen MH, Frystyk J, Andersen T, Breum L, Christiansen JS, Hilsted J. The impact of obesity, fat distribution, and energy restriction on insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, insulin, and growth hormone. Metabolism. 1994 Mar;43(3):315-9

2- Lawlor DA, Ebrahim S, Smith GD, Cherry L, Watt P, Sattar N. The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: findings from the prospective British Women's Heart and Health Study. Atherosclerosis. 2008 Nov;201(1):198-204

3- Toledo-Corral CM, Roberts CK, Shaibi GQ, Lane CJ, Higgins PB, Davis JN, Weigensberg MJ, Goran MI. Insulin-like growth factor-I is inversely related to adiposity in overweight Latino children. J Pediatr Endocrinol Metab. 2008 Sep;21(9):855-64

4- Abdulle AM, Gillett MP, Abouchacra S, Sabri SM, Rukhaimi MA, Obineche EN, Singh J. Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients. Mol Cell Biochem. 2007 Aug;302(1-2):195-201

5- Henderson KD, Goran MI, Kolonel LN, Henderson BE, Le Marchand L. Ethnic disparity in the relationship between obesity and plasma insulin-like growth

factors: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2298-302

6- Tong PC, Ho CS, Yeung VT, Ng MC, So WY, Ozaki R, Ko GT, Ma RC, Poon E, Chan NN, Lam CW, Chan JC. Association of testosterone, insulin-like growth factor-I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes. J Clin Endocrinol Metab. 2005 Dec;90(12):6418-23

7- De Pergola G, Zamboni M, Pannacciulli N, Turcato E, Giorgino F, Armellini F, Logoluso F, Sciaraffia M, Bosello O, Giorgino R. Divergent effects of short-term, very-low-calorie diet on insulin-like growth factor-I and insulin-like growth factor binding protein-3 serum concentrations inpremenopausal women with obesity. Obes Res. 1998 Nov;6(6):408-15

8- Mårin P, Kvist H, Lindstedt G, Sjöström L, Björntorp P. Low concentrations of insulin-like growth factor-I in abdominal obesity. Int J Obes Relat Metab Disord. 1993 Feb;17(2):83-9

9- Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J, Skakkebae NE. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab. 1995 Apr;80(4):1407-15

10- Ballerini MG, Ropelato MG, Domené HM, Pennisi P, Heinrich JJ, Jasper HG. Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis. J Pediatr Endocrinol Metab. 2004 May;17(5):749-57

11- Reinehr T, Panteliadou A, de Sousa G, Andler W. Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and growth in obese children before and after reduction of overweight. J Pediatr Endocrinol Metab. 2009 Mar;22(3):225-33

12- Martha PM, Gorman KM, Blizzard RM, Rogol AD, Veldhuis JD. Endogenous growth hormone secretion and clearance rates in normal boys, as determined by deconvolution analysis: relationship to age, pubertal status, and body mass. J Clin Endocrinol Metab. 1992 Feb;74(2):336-44

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3- Hayes VY, Urban RJ, Jiang J, Marcell TJ, Helgeson K, Mauras N. Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects. J Clin Endocrinol Metab. 2001 May;86(5):2211-9

Obesidade: A Associação Com Baixos Níveis de Testosterona 1. Knoblovits P, Costanzo PR, Rey Valzacchi GJ, Gueglio MG, Layus AO, Kozak

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3. Chu LW, Tam S, Kung AW, Lo S, Fan S, Wong RL, Morley JE, Lam KS. Serum total and bioavailable testosterone levels, central obesity, and muscle strength changes with aging in healthy Chinese men. J Am Geriatr Soc. 2008 Jul;56(7):1286-91

4. Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007 Apr;30(4):911-7

5. Kaplan SA, Meehan AG, Shah A. The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men? J Urol. 2006 Oct;176(4 Pt 1):1524-7

6. Osuna JA, Gómez-Pérez R, Arata-Bellabarba G, Villaroel V. Relationship between BMI, total testosterone, sex hormone-binding-globulin, leptin, insulin and insulin resistance in obese men. Arch Androl. 2006 Sep-Oct;52(5):355-61

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Obesidade: A melhora Com a Reposição de Testosterona

1- Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006 Jun;154(6):899-906

2- Bhasin S, Parker RA, Sattler F, Haubrich R, Alston B, Umbleja T, Shikuma CM; AIDS Clinical Trials Group Protocol A5079 Study Team. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. Clin Endocrinol Metab. 2007 Mar;92(3):1049-57

3- Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Clin Endocrinol Metab. 2008 Jan;93(1):139-46

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8- MELHORA DA APARÊNCIA FÍSICA, COMPOSIÇÃO

CORPORAL E MASSA MUSCULAR ATRAVÉS DA MODULAÇÃO HORMONAL

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Sarcopenia: A Melhora Com a Reposição de GH 1- Vahl N, Juul A, Jorgensen JO, Orskov H, Skakkebaek NE, Christiansen JS.

Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study. J Clin Endocrinol Metab. 2000 May;85(5):1874-81

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5- Janssen YJ, Doornbos J, Roelfsema F. Changes in muscle volume, strength, and bioenergetics during recombinant human ,growth hormone (GH) therapy in adults with GH deficiency. J Clin Endocrinol Metab. 1999 Jan;84(1):279-84

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7- ter Maaten JC, de Boer H, Kamp O, Stuurman L, van der Veen EA. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab. 1999 Jul;84(7):2373-80

8- Whitehead HM, Boreham C, McIlrath EM, Sheridan B, Kennedy L, Atkinson AB, Hadden DR. Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol (Oxf). 1992 Jan;36(1):45-52

9- Nam SY, Kim KR, Cha BS, Song YD, Lim SK, Lee HC, Huh KB. Low-dose growth hormone treatment combined with diet restriction decreases insulin resistance by reducing visceral fat and increasing muscle mass in obese type 2 diabetic patients. Int J Obes Relat Metab Disord. 2001 Aug;25(8):1101-7

Massa Muscular: A Associação Com Baixos Níveis de GH/IGF-1 1- De Boer H, Blok GJ, Voerman HJ, De Vries PM, van der Veen EA. Body

composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. J Clin Endocrinol Metab. 1992 Sep;75(3):833-7

Massa Muscular: A Melhora Com a Reposição de GH 1- Feldt-Rasmussen B, Lange M, Sulowicz W, Gafter U, Lai KN, Wiedemann J,

Christiansen JS, El Nahas M; APCD Study Group. Growth hormone treatment during hemodialysis in a randomized trial improves nutrition, quality of life, and cardiovascular risk. J Am Soc Nephrol. 2007 Jul;18(7):2161-71

2- Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Sjostrom L, Isaksson OG. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab. 1993 Feb;76(2):309-17

3- Lombardi G, Luger A, Marek J, Russell-Jones D, Sonksen P, Attanasio AF. Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms. J Clin Endocrinol Metab. 2002 May;87(5):1974-9

4- Vahl N, Juul A, Jorgensen JO, Orskov H, Skakkebaek NE, Christiansen JS. Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study. J Clin Endocrinol Metab. 2000 May;85(5):1874-81

5- Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1-6

6- Davies JS, Obuobie K, Smith J, Rees DA, Furlong A, Davies N, Evans LM, Scanlon MF. A therapeutic trial of growth hormone in hypopituitary adults and its influence upon continued prescription by general practitioners. Clin Endocrinol (Oxf). 2000 Mar;52(3):295-303

7- Olsovska V, Siprova H, Beranek M, Soska V. The influence of long-term growth hormone replacement therapy on body composition, bone tissue and some metabolic parameters in adults with growth hormone deficiency. Vnitr Lek. 2005 Dec;51(12):1356-64

Melhora da Aparência Fìsica e Morfologia Corporal Com a Reposição de GH 1- Hertoghe T. Growth hormone therapy in aging adults. Anti-aging Med Ther.

1997;1:10-28 2- Honda M, Yogi A, Ishizuka N, Genka I, Gatanaga H, Teruya K, Tachikawa N,

Kikuchi Y, Oka S. Effectiveness of subcutaneous growth hormone in HIV-1 patients with moderate to severe facial lipoatrophy. Intern Med. 2007;46(7):359-62

3- Zivicnjak M, Franke D, Ehrich JH, Filler G.Does growth hormone therapy harmonize distorted morphology and body composition in chronic renal failure? Pediatr Nephrol. 2000 Dec;15(3-4):229-35

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Perda de Massa Muscular e Aumento da Massa Gordurosa: A Associação Com Baixos Níveis de GH/IGF-1

1- Engvall IL, Elkan AC, Tengstrand B, Cederholm T, Brismar K, Hafstrom I. Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin-like growth factor. Scand J Rheumatol. 2008 Sep-Oct;37(5):321-8

2- Gómez JM. Serum leptin, insulin-like growth factor-I components and sex-hormone binding globulin. Relationship with sex, age and body composition in healthy population. Protein Pept Lett. 2007;14(7):708-11

3- Axelsson J, Qureshi AR, Divino-Filho JC, Bárány P, Heimbürger O, Lindholm B, Stenvinkel P. Are insulin-like growth factor and its binding proteins 1 and 3 clinically useful as markers of malnutrition, sarcopenia and inflammation in end-stage renal disease? Eur J Clin Nutr. 2006 Jun;60(6):718-26

4- Payette H, Roubenoff R, Jacques PF, Dinarello CA, Wilson PW, Abad LW, Harris T. Insulin-like growth factor-1 and interleukin 6 predict sarcopenia in very old community-living men and women: the Framingham Heart Study. J Am Geriatr Soc. 2003 Sep;51(9):1237-43

5- Waters DL, Yau CL, Montoya GD, Baumgartner RN. Serum Sex Hormones, IGF-1, and IGFBP3 Exert a Sexually Dimorphic Effect on Lean Body Mass in Aging. J Gerontol A Biol Sci Med Sci. 2003 Jul;58(7):648-52

6- Gómez JM, Maravall FJ, Gómez N, Navarro MA, Casamitjana R, Soler J. Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf). 2003 Feb;58(2):213-9

7- Chang S, Wu X, Yu H, Spitz MR. Plasma concentrations of insulin-like growth factors among healthy adult men and postmenopausal women: associations with body composition, lifestyle, and reproductive factors. Cancer Epidemiol Biomarkers Prev. 2002 Aug;11(8):758-66

8- Figueroa A, Going SB, Milliken LA, Blew R, Sharp S, Lohman TG. Body composition modulates the effects of hormone replacement therapy on growth hormone and insulin-like growth factor-I levels in postmenopausal women. Gynecol Obstet Invest. 2002;54(4):201-6

9- Niebauer J, Pflaum CD, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, Coats AJ, Anker SD. Deficient insulin-like growth factor I in chronic heart

failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol. 1998 Aug;32(2):393-7

Deterioração da Composição Corporal: A Melhora Com a Reposição de GH


2- Woods KA, Camacho-Hübner C, Bergman RN, Barter D, Clark AJ, Savage MO. Effects of insulin-like growth factor I (IGF-I) therapy on body composition and insulin resistance in IGF-I gene deletion. J Clin Endocrinol Metab. 2000 Apr;85(4):1407-11

3- Ng EH, Rock CS, Lazarus DD, Stiaino-Coico L, Moldawer LL, Lowry SF. Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia. Am J Physiol. 1992 Mar;262(3 Pt 2):R426-31

4- Hayes VY, Urban RJ, Jiang J, Marcell TJ, Helgeson K, Mauras N. Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects. J Clin Endocrinol Metab. 2001 May;86(5):2211-9

5- Herndon DN, Ramzy PI, DebRoy MA, Zheng M, Ferrando AA, Chinkes DL, Barret JP, Wolfe RR, Wolf SE. Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment. Ann Surg. 1999 May;229(5):713-20

6- Debroy MA, Wolf SE, Zhang XJ, Chinkes DL, Ferrando AA, Wolfe RR, Herndon DN. Anabolic effects of insulin-like growth factor in combination with insulin-like growth factor binding protein-3 in severely burned adults. J Trauma. 1999 Nov;47(5):904-10

Sarcopenia: A Associação Com Baixos Níveis de Estradiol

1- Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci. 2002 Dec;57(12):M772-7

Sarcopenia: A Melhora Com A Reposição de Estradiol

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Massa Muscular: A Melhora Com a Reposição de Estradiol

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2- Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res. 2001 Oct;9(10):622-6

3- Davis SR, Walker KZ, Strauss BJ. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause. 2000 Nov-Dec;7(6):395-401

Envelhecimento Cutâneo: A Melhora Com a Reposição de Estradiol

1- Son ED, Lee JY, Lee S, Kim MS, Lee BG, Chang IS, Chung JH. Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-Beta signaling in aged human skin in vivo. . J Invest Dermatol. 2005 Jun;124(6):1149-61

Sarcopenia Em Homens: A Melhora Com a Reposição de Testosterona 1- Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone

therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. Clin Endocrinol Metab. 2008 Jan;93(1):139-46

2- Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, Bhasin S. Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab. 2004 Feb;89(2):718-26

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6- Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D.Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol. 1989 Jan;66(1):498-503

7- Griggs RC, Halliday D, Kingston W, Moxley RT 3rd. Effect of testosterone on muscle protein synthesis in myotonic dystrophy. Ann Neurol. 1986 Nov;20(5):590-6

8- Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ, Casaburi R. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab. 1997 Feb;82(2):407-13.

Massa Muscular em Homens: A Associação Com Baixos Níveis de

Testosterona

1- Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD,

Urban RJ. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab. 1998 Jun;83(6):1886-92

2- Bhasin S, Tenover JS. Age-associated sarcopenia--issues in the use of testosterone as an anabolic agent in older men. J Clin Endocrinol Metab. 1997 Jun;82(6):1659-60.

Massa Muscular em Homens: A Melhora Com a Reposição de Testosterona

1- Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men - a clinical research center study. J Clin Endocrinol Metab. 1996 Oct;81(10):3469-75

2- Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW. Testosterone dose-response relationships in healthy young men.Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1172-81

3- Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N; Testosterone Gel Study Group. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab. 2000 Aug;85(8):2839-53

4- Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May;89(5):2085-98

5- Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ, Casaburi R. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab. 1997 Feb;82(2):407-13

6- Bhasin S, Storer TW, Asbel-Sethi N, Kilbourne A, Hays R, Sinha-Hikim I, Shen R, Arver S, Beall G. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab. 1998 Sep;83(9):3155-62

9- PREVENÇÃO E TRATAMENTO DA

OSTEOPOROSE ATRAVÉS DA MODULAÇÃO HORMONAL

Osteoporose: A Associação Com Baixos Níveis do Hormônio do Crescimento

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2- Foldes J, Lakatos P, Zsadanyi J, Horvath C. Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism. Eur J Endocrinol. 1997 Mar;136(3):277-81

3- Monson JP, Abs R, Bengtsson BA, Bennmarker H, Feldt-Rasmussen U, Hernberg-Stahl E, Thoren M, Westberg B, Wilton P, Wuster C. Growth hormone deficiency and replacement in elderly hypopituitary adults. KIMS Study Group and the KIMS International Board. Pharmacia and Upjohn International Metabolic Database. Clin Endocrinol (Oxf). 2000 Sep;53(3):281-9

4- Longobardi S, Di Rella F, Pivonello R, Di Somma C, Klain M, Maurelli L, Scarpa R, Colao A, Merola B, Lombardi G. Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients. J Endocrinol Invest. 1999 May;22(5):333-9

5- Beckers V, Milet J, Legros JJ. Prolonged treatment with recombined growth hormone improves bone measures: study of body composition in 21 deficient adults on treatment. Ann Endocrinol (Paris). 2001 Dec;62(6):507-15

6- Gomez JM, Gomez N, Fiter J, Soler J. Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res. 2000 Feb;32(2):66-70

7- Kaufman JM, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab. 1992 Jan;74(1):118-23

8- Calo L, Castrignano R, Davis PA, Carraro G, Pagnin E, Giannini S, Semplicini A, D'Angelo A. Role of insulin-like growth factor-I in primary osteoporosis: a correlative study. J Endocrinol Invest. 2000 Apr;23(4):223-7

9- Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab. 1999 Jun;84(6):1919-24

10- Nakaoka D, Sugimoto T, Kaji H, Kanzawa M, Yano S, Yamauchi M, Sugishita T, Chihara K. Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women. Osteoporos Int. 2001;12(7):548-54

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12- Ljunghall S, Johansson AG, Burman P, Kampe O, Lindh E, Karlsson FA. Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J Intern Med. 1992 Jul;232(1):59-64

Osteoporose: A Melhora Com a Reposição de GH

1- Lopes RF, Coeli CM, Vaisman M, de Farias ML. Additional beneficial effects of recombinant growth hormone in alendronate-treated patients with idiopathic osteoporosis. Endocr J. 2009;56(7):851-8

2- Rota F, Savanelli MC, Tauchmanova L, Savastano S, Lombardi G, Colao A, Di Somma C. Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender. J Endocrinol Invest. 2008 Feb;31(2):94-102

3- Joseph F, Ahmad AM, Ul-Haq M, Durham BH, Whittingham P, Fraser WD, Vora JP. Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis. J Bone Miner Res. 2008 May;23(5):721-9.

4- Clanget C, Seck T, Hinke V, Wuster C, Ziegler R, Pfeilschifter J. Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH-deficient adults. Clin Endocrinol (Oxf). 2001 Jul;55(1):93-9

5- Sartorio A, Ortolani S, Galbiati E, Conte G, Vangeli V, Arosio M, Porretti S, Faglia. Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. J Endocrinol Invest. 2001 Apr;24(4):224-30

6- Biller BM, Sesmilo G, Baum HB, Hayden D, Schoenfeld D, Klibanski A.Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab 2000 Mar;85(3):970-6

7- Gomez JM, Gomez N, Fiter J, Soler J. Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res. 2000 Feb;32(2):66-70

8- Benbassat CA, Wass rman M, Laron Z. Changes in bone mineral density after discontinuation and early reinstitution of growth hormone (GH) in patients with childhood-onset GH deficiency. Growth Horm IGF Res. 1999 Oct;9(5):290-5

9- ter Maaten JC, de Boer H, Kamp O, Stuurman L, van der Veen EA. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab. 1999 Jul;84(7):2373-80

10- Valimaki MJ, Salmela PI, Salmi J, Viikari J, Kataja M, Turunen H, Soppi E. Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 1999 Jun;140(6):545-54

11- Baum HB, Biller BM, Finkelstein JS, Cannistraro KB, Oppenhein DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med. 1996 Dec 1;125(11):883-90

12- Beshyah SA, Thomas E, Kyd P, Sharp P, Fairney A, Johnston DG. The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism. Clin Endocrinol (Oxf). 1994 Mar;40(3):383-91

13- Vandeweghe M, Taelman P, Kaufman JM.Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males. Clin Endocrinol (Oxf). 1993 Oct;39(4):409-15

14- Finkenstedt G, Gasser RW, Hofle G, Watfah C, Fridrich L. Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo- controlled study with open follow-up. Eur J Endocrinol. 1997 Mar;136(3):282-9

15- Erdtsieck RJ, Pols HA, Valk NK, Van OBM, Lamberts SW, Mulder P, Birkenhager JC. Treatment of post-menopausal osteoporosis with a

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combination of growth hormone and pamidronate:a placebo controlled trial. Clin Endocrinol (Oxf). 1995;43:557-565

Osteoporose: A Associação Com Baixos Níveis de IGF-1

1- Liu JM, Zhao HY, Ning G, Chen Y, Zhang LZ, Sun LH, Zhao YJ, Xu MY, Chen JL. IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab. 2008;26(2):159-64

2- Reed BY, Zerwekh JE, Sakhaee K, Breslau NA, Gottschalk F, Pak CY. Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res. 1995 Aug;10(8):1218-24

3- Ljunghall S, Johansson AG, Burman P, Kämpe O, Lindh E, Karlsson FA. Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J Intern Med. 1992 Jul;232(1):59-64

4- Ali O, Shim M, Fowler E, Cohen P, Oppenheim W. Spinal bone mineral density, IGF-1 and IGFBP-3 in children with cerebral palsy. Horm Res. 2007;68(6):316-20

Osteoporose: A Melhora Com a Reposição de IGF-1

1- Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002 Sep;110(6):771-81

2- Stabnov L, Kasukawa Y, Guo R, Amaar Y, Wergedal JE, Baylink DJ, Mohan S. Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density during puberty in IGF-1-deficient MIDI mice. Bone. 2002 Jun;30(6):909-16

Osteoporose: A Associação Com Baixos Níveis de DHEA


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16- Ortego-Centeno N, Munoz-Torres M, Jodar E, Hernandez-Quero J, Jurado-Duce A, de la Higuera Torres-Puchol J. Effect of tobacco consumption on bone mineral density in healthy young males. Calcif Tissue Int 1997;60(6):496-500

Osteoporose: A Melhora Com a Reposição de DHEA

1- Jankowski CM, Gozansky WS, Kittelson JM, Van Pelt RE, Schwartz RS, Kohrt WM. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin Endocrinol Metab. 2008 Dec;93(12):4767-73

2- von Mühlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008 May;19(5):699-707

3- Baulieu EE, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti-Ferrandi H, Trivalle C, de Lacharriere O, Nouveau S, Rakoto-Arison B, Souberbielle JC, Raison J, Le Bouc Y, Raynaud A, Girerd X, Forette F. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of

the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA. 2000;97(8):4279-84

4- Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl). 2002 Mar;115(3):402-4

5- Labrie F, Diamond P, Cusan L, Gomez JL, Belanger A, Candas B. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab. 1997;82(10):3498-505

6- Mortola JF, Yen SS. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab. 1990;71(3):696-704

Osteoporose: A Associação Com Baixos Níveis de Estradiol

1- van Geel TA, Geusens PP, Winkens B, Sels JP, Dinant GJ. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle mass, muscle strength and bone mineral density in postmenopausal women: a cross-sectional study. Eur J Endocrinol. 2009 Apr;160(4):681-7

2- Mastaglia SR, Bagur A, Royer M, Yankelevich D, Sayegh F, Oliveri B. Effect of endogenous estradiol levels on bone resorption and bone mineral density in healthy postmenopausal women: a prospective study. Climacteric. 2009 Feb;12(1):49-58

3- Richelson LS, Wahner HW, Melton LJ 3rd, Riggs BL. Relative contributions of aging and estrogen deficiency to postmenopausal bone loss. N Engl J Med. 1984 Nov 15; 311(20): 12273-5

4- Bourdel A, Mahoudeau JA, Guaydier-Souquieres G, Leymarie P, Sabatier JP, Loyau G. Gonadal function in primary apparent male osteoporosis. 12 cases. Presse Med. 1989 Oct 21;18(34):1691-4

5- Khosla S, Riggs BL, Robb RA, Camp JJ, Achenbach SJ, Oberg AL, Rouleau PA, Melton LJ 3rd. Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women. J Clin Endocrinol Metab. 2005 Sep;90(9):5096-103

6- Tremollieres FA, Pouilles JM, Ribot C. Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women Osteoporos Int. 2001;12(5):385-90

7- Huang JS, Wilkie SJ, Sullivan MP, Grinspoon S. Reduced bone density in androgen-deficient women with acquired immune deficiencysyndrome wasting. J Clin Endocrinol Metab. 2001 Aug;86(8):3533-9

8- Deutsch S, Benjamin F, Seltzer V, Tafreshi M, Kocheril G, Frank A. The correlation of serum estrogens and androgens with bone density in the late postmenopause. Int J Gynaecol Obstet. 1987 Jun;25(3):217-22

9- Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. 2000 Aug;15(8):1526-36

10- Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. Risk factors for hip fracture in Asian men

and women: the Asian osteoporosis study. J Bone Miner Res. 2001 Mar;16(3):572-80

11- van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000 Sep;85(9):3276-82

Osteoporosis: A Melhora Com a Reposição de Estradiol e Progesterona

1- Sorensen MB, Rosenfalck AM, Hojgaard L, Ottesen B. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res. 2001 Oct;9(10):622-6

2- Christiansen C, Christensen MS, Transbol I. Bone mass in postmenopausal women after withdrawal of oestrogen/gestagen replacement therapy. Lancet. 1981 Feb 28;1(8218):459-61.

3- Christiansen C, Christensen MS, McNair P, Hagen C, Stocklund KE, Transbol I. Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females. Eur J Clin Invest. 1980 Aug;10(4):273-9.

4- Bagur A, Wittich A, Ghiringhelli G, Vega E, Mautalen C. Hormone replacement therapy increases trabecular and cortical bone density in osteoporotic women. Medicina (B Aires). 1996;56(3):247-51

5- Tiras MB, Noyan V, Yildiz A, Biberoglu K. Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate. Climacteric. 2000 Jun;3(2):92-101

6- Ringe JD, Meiss F. The avoidance of early postmenopausal bone substance losses by transdermal estrogen substitution. Dtsch Med Wochenschr. 1993 May 28;118(21):769-74

7- Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, Judd HL, Caplan RH, Riggs BL. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992 Jul 1;117(1):1-9

8- Mizunuma H, Taketani Y, Ohta H, Honjo H, GoraiI, Itabashi A, Shiraki M. Dose effects of oral estradiol on bone mineral density in Japanese women with osteoporosis. Climacteric. 2009 Jul 7:1-12

9- Riis BJ, Thomsen K, Strom V, Christiansen C. The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss. Am J Obstet Gynecol. 1987 Jan;156(1):61-5

10- Nielsen TF, Ravn P, Bagger YZ, Warming L, Christiansen C. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study. Osteoporos Int. 2004 Feb;15(2):168-74

11- Notelovitz M, John VA, Good WR. Effectiveness of Alora estradiol matrix transdermal delivery system in improving lumbar bone mineral density in healthy, postmenopausal women. Menopause. 2002 Sep-Oct;9(5):343-53

12- Arrenbrecht S, Boermans AJ.Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Osteoporos Int. 2002;13(2):176-83.

13- Castelo-Branco C, Vicente JJ, Figueras F, Sanjuan A, Martinez de Osaba MJ, Casals E, Pons F, Balasch J, Vanrell JA. Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women. Maturitas. 2000 Feb

14- Cooper C, Stakkestad JA, Radowicki S, Hardy P, Pilate C, Dain MP, Delmas PD. Matrix delivery transdermal 17beta-estradiol for the prevention of bone

loss in postmenopausal women. The International Study Group. Osteoporos Int. 1999;9(4):358-66

15- Evans SF, Davie MW. Low and conventional dose transdermal oestradiol are equally effective at preventing bone loss in spine and femur at all post-menopausal ages. Clin Endocrinol (Oxf). 1996 Jan;44(1):79-84

16- Ribot C, Tremollieres F, Pouilles JM, Louvet JP, Peyron R. Preventive effects of transdermal administration of 17 beta-estradiol on postmenopausal bone loss: a 2-year prospective study. Gynecol Endocrinol. 1989 Dec;3(4):259-67

17- Holland EF, Leather AT, Studd JW. Increase in bone mass of older postmenopausal women with low mineral bone density after one year of percutaneous oestradiol implants. Br J Obstet Gynaecol. 1995 Mar;102(3):238-42

18- Liu JH, Muse KN. The effects of progestins on bone density and bone

metabolism in postmenopausal women: a randomized controlled trial. Am J Obstet Gynecol. 2005 Apr;192(4):1316-23

19- Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss--a 2 year randomized, placebo-controlled trial. Eur J Nutr. 2004 Aug;43(4):246-57

20- Grey A, Cundy T, Evans M, Reid I. Medroxyprogesterone acetate enhances the spinal bone mineral density response to oestrogen in late post-menopausal women. Clin Endocrinol (Oxf). 1996 Mar;44(3):293-6

21- Lee JR. Osteoporosis reversal with transdermal progesterone. Lancet. 1990 Nov 24;336(8726):1327

22- Lee JR. Is natural progesterone the missing link in osteoporosis prevention and treatment? Med Hypotheses. 1991 Aug;35(4):316-8

23- Barengolts EI, Gajardo HF, Rosol TJ, D'Anza JJ, Pena M, Botsis J, Kukreja SC. Effects of progesterone on postovariectomy bone loss in aged rats. J Bone Miner Res. 1990 Nov;5(11):1143-7

Fraturas do Quadril: A Associação Com Baixos Níveis de Estradiol

1- Chapurlat RD, Garnero P, Breart G, Meunier PJ, Delmas PD. Serum estradiol and sex hormone-binding globulin and the risk of hip fracture in elderly women: the EPIDOS study. J Bone Miner Res. 2000 Sep;15(9):1835-41

2- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004 Mar;103(3):440-6(5 years after stopping estrogen use => loss of protection against hip fractures)

Fraturas do Quadril: A Prevenção Com a Reposição de Estradiol e

Progesterona

1- Michaelsson K, Baron JA, Farahmand BY, Persson I, Ljunghall S. Oral-contraceptive use and risk of hip fracture: a case-control study. Lancet. 1999 May 1;353(9163):1481-4 (-50 % less hip fractures)

2- Kiel DP, Felson DT, Anderson JJ, Wilson PW, Moskowitz MA. Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study. N Engl J Med. 1987 Nov 5;317(19):1169-74

3- Kiel DP, Baron JA, Anderson JJ, Hannan MT, Felson DT. Smoking eliminates the protective effect of oral estrogens on the risk for hip fracture among women. Ann Intern Med. 1992 May 1;116(9):716-21

4- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004 Mar;103(3):440-6

Osteoporose: A Associação Com Baixos Níveis de Testosterona

1- Clapauch R, Mattos TM, Silva P, Marinheiro LP, Buksman S, Schrank Y. Total estradiol, rather than testosterone levels, predicts osteoporosis in aging men. Arq Bras Endocrinol Metabol. 2009 Nov;53(8):1020-5

2- Deutsch S, Benjamin F, Seltzer V, Tafreshi M, Kocheril G, Frank A. The correlation of serum estrogens and androgens with bone density in the late postmenopause. Int J Gynaecol Obstet. 1987 Jun;25(3):217-22

3- Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. 2000 Aug;15(8):1526-36

4- Lau EM, Suriwongpaisal P, Lee JK, Das De S, Festin MR, Saw SM, Khir A, Torralba T, Sham A, Sambrook P. Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study. J Bone Miner Res. 2001 Mar;16(3):572-80

5- van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000 Sep;85(9):3276-82

6- Fukui M, Nakamura N. Bone and Men's Health. Association between serum testosterone and bone mineral density in patients with diabetes. Clin Calcium. 2010 Feb;20(2):206-11

7- Foresta C, Zanatta GP, Busnardo B, Scanelli G, Scandellari C. Testosterone and calcitonin plasma levels in hypogonadal osteoporotic young men. J Endocrinol Invest. 1985 Aug;8(4):377-9

8- Jassal SK, Barrett-Connor E, Edelstein SL. Low bioavailable testosterone levels predict future height loss in postmenopausal women. J Bone Miner Res. 1995 Apr;10(4):650-4

Osteoporose em Homens: A Melhora Com a Reposição de Testosterona

1- Welch BJ, Denke MA, Kermani A, Adams-Huet B, Gazmen NM, Gruntmanis U. Comparison of testosterone, alendronate, and a combination of both therapies in men with low bone mineral density. J Investig Med. 2007 May;55(4):168-73

2- Anderson FH, Francis RM, Faulkner K. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Bone. 1996 Feb;18(2):11-7

3- Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65

4- Isaia G, Mussetta M, Pecchio F, Sciolla A, di Stefano M, Molinatti GM. Effect of testosterone on bone in hypogonadal males. Maturitas. 1992 Aug;15(1):47-51

5- Salamano G, Isaia GC, Pecchio F, Appendino S, Mussetta M, Molinatti GM. Effect on phospho-calcium metabolism of testosterone administration in hypogonadal males. Arch Ital Urol Nefrol Androl. 1990 Mar;62(1):149-53

6- Diamond T, Stiel D, Posen S. Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis. J Bone Miner Res. 1991 Jan;6(1):39-43

7- Kenny AM, Prestwood KM, Gruman CA, Marcello KM, Raisz LG. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci. 2001 May;56(5):M266-72

8- Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. 2000 Aug;85(8):2670-7

9- Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad JG Jr, Strom BL. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab. 1999 Jun;84(6):1966-72

Fraturas do Quadril: A Associação Com Baixos Níveis de Testosterona

1- Leifke E, Wichers C, Gorenoi V, Lucke P, von zur Muhlen A, Brabant G. Low serum levels of testosterone in men with minimal traumatic hip fractures. Exp Clin Endocrinol Diabetes. 2005 Apr;113(4):208-13

10- PREVENÇÃO DO CÂNCER E REDUÇÃO DO

RISCO DE CÂNCER ATRAVÉS DA MODULAÇÃO HORMONAL

Proteção na MENOPAUSA:

o Raghvendra K et al. Cardiovascular pharmacology of estradiol metabolites. Journal of Pharmacology and Experimental Therapeutics. 2004; 308-403-409.

Replace E2 = presence of catecholestradiols and methoxyestradiols = not activation of the nuclear estrogen receptors = protection against cancer and other diseases

o Liu ZJ et al. Selective insensitivity of ZR-75-1 human breast cancer

cells to 2-methoxyestradiol: evidence for type II beta-ydroxisteroid dehydrogenase as the underlying cause. Cancer Res. 2005 Jul 1;65(13):5802-11

Metabolism of E2 after replacement by P450 produce 2ME2 and confer protection

2ME2 decreases tumor growth, angiogenesis and growth of cancer cells

2ME2 has strong antiproliferative, apoptotic and antiangiogenic action

o Fournier A. et al. Breast cancer risk in relation to different types

of hormone replacement therapy in the E3N-EPIC cohort study. International Journal of Cancer .2005 Apr 10;114(3):448-54

Progesterone protects, progestins worsen cancer risk The risk was significantly greater ( p < 0.001) with HRT

containing synthetic progestins than with HRT containing bioidentical Progesterone

The RR respectively 1.4 and 0.8 20% decrease in risk with bioidentical progesterone

o Fournier A. et al. Unequal risks for breast cancer associated with

different hormone replacement thearpies: results of the E3N-EPIC cohort study. Breast Cancer Research Treat .2007 Feb 10;104(13):373-91

80.377 postmenopausal women No increase in breast cancer in women on E2 and

Progesterone CEE+MPA had RR of 1.69 or 69% increase in risk of breast

cancer These findings prove that bioidentical hormones are

undoubtedly safer o Campagnoli C. et al. Progesterone and Progestins in relation to

breast cancer risk. Journal of Steroid Biochemistry amd Molecular Biology.2005 441-450

Progesterone decreases breast cancer risk Synthetic progestins increase BC risk Higher P4 during menstrual cycle, 50% reduction risk Higher P4 HRT, 78% reduction in risk

Proteção na ANDROPAUSA: o Morley, J. et al., “Testosterone replacement and the physiologic

aspects of aging in men”, “ Mayo Clinic Proc 2000; 75(suppl):583-7 There is absolutelly no clinical evidence that the risk of either

prostate cancer or BPH increases with transdermal testosterone replacement.

o Stattin, P. et al., “High levels of circulating testosterone are not

associated with increased prostate cancer risk: a pooled prospective study”, “ Intl J Cancer 2004 Jan 20; 108(3):418-24.

Higher T less prostate cancer. Higher E2 more prostate câncer

o Basaria, A. et al., “Anabolic androgenic steroid therapy in the

treatment of chronic diseases”, “ The Journal of Clinical Endocrinology and Metabolism 2004; Vol 86. No. 11:5108-5117

The increase of prostate cancer is not increased by Testosterone administration

o Rhoden, W. et al., “High levels of circulating testosterone are not

associated with increased prostate cancer risk” . New England Journal of Medicine 2004 Mar; 163(3):824-7

No compelling evidence at present to suggest that men with higher testosterone levels are at great risk of prostate cancer or that treating men who have hipogonadism with exogenous androgens increases this risk. In fact, it should be recognized that prostate cancer becomes more prevalent exactly at the time of a man’s life when testosterone levels decline.

o TESTOSTERONE therapy in men with untreated PCa o Morgentaler et al, J Urol 2011

All men experienced symptomatic benefit No increase in PSA No increase in prostate volume No definite cancer progression 54% of biopsies- no cancer seen!

o Muller M, van der Schouw YT, Thijssen JH, Grobbee DE. Endogenous

sex hormones and cardiovascular disease in men. J Clin Endocrinol Metab. 2003; 88 (11): 5076-86.

A report in The Journal of Clinical Endocrinology and Metabolism (November 2003) sheds more light on the beneficial effects of testosterone supplementation in andropausal men. The study authors conducted a rigorous database search of testosterone’s effect on heart disease in men, and identified multiple studies showing that men with low testosterone levels had higher blood pressure, LDL cholesterol levels, triglyceride levels, and body mass index compared to men with optimal testosterone levels. Discussing the potential side effects of testosterone supplementation in elderly men, the authors noted, “the scientific basis for these concerns is scarce.”*

HORMÔNIO DO CRESCIMENTO E CÂNCER:

o Vance M, CJ. et al., “GH Therapy in Adults and Children. The New England Journal of Medicine. October 14, 2000

“No evidence that GH replacement therapy affects the risk of cancer”

o Molitch ME. et al., “Diagnosis of GH deficiency in adults – how good

the criteria need to be ? J Clin Endocrinol Metab 2002 Feb; 87(2):473-6

Although there has been concerns about an increased risk of cancer, reviews of existing well-maintained databases of treated patients have shown this theoretical risk to be nonexistent.

o Fiebig HH et al. No evidence of tumor growth stimulation in human tumors in vitro following treatment with recombinant human growth hormone. Anticancer Drugs J 2000 Sep; 11(8):659-64

GH improves cancer cachexia No evidence of tumor growth stimulation

o Growth Hormone Research Society. J Clin Endo Metab, May 2001.

There is no data to suggest that IGF-1 and IGFBP 3 modulate cancer risk in GH treated patients.

There is no data to support that active malignancy is a contraindication for GH supplementation.

No evidence that GH increases cancer recurrence or de novo cancer or leukemia.

o Swerdlow A. et al. Growth Hormone Treatment of Children with Brain Tumors and Risk of Tumor Recurrence. The Journal of Clinical Endocrinology and Metabolism Vol 85, No. 12, December 2000.

Children with brain tumors -

180 treated with GH

891 not treated with GH In treated patients

Decreased risk of recurrence: 60%

Decreased risk of mortality: 50% o Murray R.D. et al. GH-Deficient Survivors of Chidlhood Cancer: GH

Replacement During Adult Life. The Journal of Clinical Endocrinology and Metabolism 2002 Jan;87(1):129-35

GH Replacement and Cancer Improved QOL “Importantly, during the 12-24 months of GH replacement

therapy, there was absolutely no clinical suggestion of tumor reccurence.

o Hong J et al. IGFBP 3 mutants that do not bind IGFs stimulate

apoptosis in human cancer cells. Journal of Bio Chem 2002 Jan 9. IGFBP 3 Independent Anti-Cancer Actions IGFBP 3 triggers cell cycle and stimulates apoptosis. IGFBP 3 independent mechanisms are major contributors to

IGFBP 3 induced apoptosis in cancer cells. IGFBP 3 plays a wider hole in the anti-proliferative and anti-

tumorgenic actions. IGFBP 3 may be considered “The Guardian of the Genome”.

o Kurek R et al. The significance of serum levels of insulin-like growth

factor 1 in patients with prostate cancer. J Clin Endoc Metab, 2000 Jan;85(1):125-9.

No association between IGF-1, GH and prostate cancer risk. Androgen decline or withdrawal did not change IGF-1.

o Baffa R et al. Low serum insulin-like growth factor 1 : a significant

association with prostate cancer. J Urology, 2000 Sep;6(3):236-239. Low IGF-1 Associated with Prostate Cancer IGF-1 considerably lower in Prostate CA patients than control.

No association of IGF-1, GH levels and PSA increase. IGF-1 decresed with age Prostate cancer risk increased with age .

o Finne P et Al IGf-1 Tumor Marker for cancer prostate ? . Can Research 2004 15;63(14)3991-496 Mar 28;334(13): 800-14

Declínio IGF-1 diretamente correlacionado com aumento do risco de câncer de próstata

Queda 55% de IGF-1, representa aumento de 48% no risco de ca próstata

Câncer: Efeito Protetor da Reposição de Melatonina 177. Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a

systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6

178. Lissoni P, Barni S, Ardizzoia A, Paolorossi F, Crispino S, Tancini G, Tisi E, Archili C, De Toma D, Pipino G, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology. 1992;49(5):336-9

179. Lissoni P, Brivio O, Brivio F, Barni S, Tancini G, Crippa D, Meregalli S. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res. 1996 Nov;21(4):239-42

180. Lissoni P. Is there a role for melatonin in supportive care? Support Care Cancer. 2002 Mar;10(2):110-6

181. Lissoni P, Rovelli F, Malugani F, Bucovec R, Conti A, Maestroni GJ. Anti-angiogenic activity of melatonin in advanced cancer patients. Neuroendocrinol Lett. 2001;22(1):45-7

182. Neri B, de Leonardis V, Gemelli MT, di Loro F, Mottola A, Ponchietti R, Raugei A, Cini G. Melatonin as biological response modifier in cancer patients. Anticancer Res. 1998 Mar-Apr;18(2B):1329-32

183. Lissoni P, Paolorossi F, Tancini G, Barni S, Ardizzoia A, Brivio F, Zubelewicz B, Chatikhine V. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer. 1996 Jul;32A(8):1340-3

184. Gonzalez R, Sanchez A, Ferguson JA, Balmer C, Daniel C, Cohn A, Robinson WA. Melatonin therapy of advanced human malignant melanoma. Melanoma Res. 1991 Nov-Dec;1(4):237-43

185. Bartsch C, Bartsch H. Melatonin in cancer patients and in tumor-bearing animals. Adv Exp Med Biol. 1999;467:247-64

186. Cos S, Fernandez R, Guezmes A, Sanchez-Barcelo EJ. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res. 1998 Oct 1;58(19):4383-90

187. Kossoy G, Ben-Hur H, Popovich I, Zabezhinski M, Anisimov V, Zusman I. Melatonin and colon carcinogenesis. IV. Effect of melatonin on proliferative activity and expression of apoptosis-related proteins in the spleen of rats exposed to 1,2-dimethylhydrazine. Oncol Rep. 2000 Nov-Dec;7(6):1401-5

188. Kumar CA, Das UN. Effect of melatonin on two stage skin carcinogenesis in Swiss mice. Med Sci Monit. 2000 May-Jun;6(3):471-5

189. Lissoni P, Paolorossi F, Ardizzoia A, Barni S, Chilelli M, Mancuso M, Tancini G, Conti A, Maestroni GJ. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res. 1997 Aug;23(1):15-9

190. Lissoni P, Rovelli F, Frassineti A, Fumagalli L, Malysheva O, Conti A, Maestroni G. Oncostatic activity of pineal neuroendocrine treatment with the pineal indoles melatonin and 5-methoxytryptamine in untreatable metastatic cancer patients progressing on melatonin alone. Neuroendocrinol Lett. 2000;21(4):319-23

Câncer: A Associação Com Baixos Niveis do Hormônio do Crescimento

1- Woodson K, Tangrea JA, Pollak M, Copeland TD, Taylor PR, Virtamo J, Albanes D. Serum IGF-1: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Res. 2003 Jul 15;63(14):3991-4

2- Chokkalingam AP, Pollak M, Fillmore CM, Gao YT, Stanczyk FZ, Deng J, Sesterhenn IA, Mostofi FK, Fears TR, Madigan MP, Ziegler RG, Fraumeni JF Jr, Hsing AW. Insulin-like growth factors and prostate cancer: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev. 2001 May;10(5):421-7

3- Baffa R, Reiss K, El-Gabry EA, Sedor J, Moy ML, Shupp-Byrne D, Strup SE, Hauck WW, Baserga R, Gomella LG. Low serum insulin-like growth factor 1 (IGF-1): a significant association with prostate cancer. Tech Urol. 2000 Sep;6(3):236-9

4- Finne P, Auvinen A, Koistinen H, Zhang WM, Maattanen L, Rannikko S, Tammela T, Seppala M, Hakama M, Stenman UH. Insulin-like growth factor I is not a useful marker of prostate cancer in men with elevated levels of prostate-specific antigen. J Clin Endocrinol Metab. 2000 Aug;85(8):2744-7

5- Colombo F, Iannotta F, Fachinetti A, Giuliani F, Cornaggia M, Finzi G, Mantero G, Fraschini F, Malesci A, .Bersani M, et al. Changes in hormonal and biochemical parameters in gastric adenocarcinoma. Minerva Endocrinol. 1991 Jul-Sep;16(3):127-39

Estudos em Humanos Relacionando Baixos Níveis de GH/IGF-1 em Pacientes Com Câncer Baixos Níveis de IGF-1 no Glioma 1. Lönn S, Inskip PD, Pollak MN, Weinstein SJ, Virtamo J, Albanes D. Glioma risk

in relation to serum levels of insulin-like growth factors. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):844-6

Baixos Níveis de IGF-1 no Câncer de Próstata

1- Agurs-Collins T, Adams-Campbell LL, Kim KS, Cullen KJ.Ins ulin-like growth factor-1 and breast cancer risk in postmenopausal African-American women. Cancer Detect Prev. 2000;24(3):199-206

2- Fuhrman B, Barba M, Schünemann HJ, Hurd T, Quattrin T, Cartagena R, Carruba G, Muti P. Basal growth hormone concentrations in blood and the risk for prostate cancer: a case-control study. Prostate. 2005 Jul 1;64(2):109-15

3- Woodson K, Tangrea JA, Pollak M, Copeland TD, Taylor PR, Virtamo J, Albanes D. Serum insulin-like growth factor I: tumor marker or etiologic factor? A prospective study of prostate cancer among Finnish men. Cancer Res. 2003 Jul 15;63(14):3991-4

4- Chen C, Lewis SK, Voigt L, Fitzpatrick A, Plymate SR, Weiss NS. Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin. Cancer. 2005 Jan 1;103(1):76-84

Baixos Níveis de IGF-1 no Câncer Colorretal

1- Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R. Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut. 2002 May;50(5):642-6

Baixos Níveis de IGF-1 no Câncer Pancreático

1- Stolzenberg-Solomon RZ, Limburg P, Pollak M, Taylor PR, Virtamo J, Albanes D. Insulin-like growth factor (IGF)-1, IGF-binding protein-3, and pancreatic cancer in male smokers. Cancer Epidemiol Biomarkers Prev. 2004 Mar;13(3):438-44

Baixos Níveis de IGF-1 no Câncer Cervical

1- Schaffer A, Koushik A, Trottier H, Duarte-Franco E, Mansour N, Arseneau J, Provencher D, Gilbert L, Gotlieb W, Ferenczy A, CoutlÃ©e F, Pollak MN, Franco EL; Biomarkers of Cervical Cancer Risk Study Team . Insulin-like growth factor-I and risk of high-grade cervical intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):716-22

2- Serrano ML, Romero A, Cendales R, SÃ¡nchez-GÃ³mez M, Bravo MM. Serum levels of insulin-like growth factor-I and -II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer. Biomedica. 2006 Jun;26(2):258-68

Estudos em Humanos Reportando Ausência de Correlação ou Associação dos Níveis de IGF-1 e Câncer Câncer de Próstata

1- Weiss JM, Huang WY, Rinaldi S, Fears TR, Chatterjee N, Chia D, Crawford ED, Kaaks R, Hayes RB. IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Int J Cancer. 2007 Nov 15;121(10):2267-73

Câncer Colorrectal

1- Probst-Hensch NM, Yuan JM, Stanczyk FZ, Gao YT, Ross RK, Yu MC. IGF-1,

IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai. Br J Cancer. 2001 Nov 30;85(11):1695-9

Câncer Mama

1- Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ. Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 1998 Jan;47(2):111-20 (No statistically significant differences between breast cancer patients and controls for IGF-I and IGFBP-1 levels in premenopausal women)

2- Kajdaniuk D, Marek B. Influence of adjuvant chemotherapy with cyclophosphamide methotrexate and 5-fluorouracil on plasma insulin-like growth factor-I and chosen hormones in breast cancer pre-menopausal patients. J Clin Pharm Ther 2000 Feb;25(1):67-72 (Plasma IGF-I concentration in breast cancer patients prior to treatment did not differ significantly from that of healthy women)

Câncer: Possível Melhora da Evolução Com Reposição do Hormônio do Crescimento 1- Torosian MH. Growth hormone and prostate cancer growth and metastasis in

tumor-bearing animals. J Pediatr Endocrinol. 1993 Jan-Mar;6(1):93-7 2- Ng EH, Rock CS, Lazarus DD, Stiaino-Coico L, Moldawer LL, Lowry SF.

Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia. Am J Physiol. 1992 Mar;262(3 Pt 2):R426-31

3- Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and somatostatin therapy of cancer cachexia. Cancer. 1994 Mar 1;73(5):1499-504

Câncer: A Associação Com Baixos de DHEA


2- Alberg AJ, Gordon GB, Hoffman SC, Comstock GW, Helzlsouer KJ. Serum dehydroepiandrosterone and dehydroepiandrosterone sulfate and the

subsequent risk of developing colon cancer. Cancer Epidemiol Biomarkers Prev. 2000 May;9(5):517-21

3- Alberg AJ, Gordon GB, Genkinger JM, Hoffman SC, Selvin E, Comstock GW, Helzlsouer KJ. Serum dehydroepiandrosterone and dehydroepiandrosterone sulfate and risk of melanoma or squamous cell carcinoma of the skin. Anticancer Res. 2001 Nov-Dec;21(6A):4051-4

4- Karasek M, Pawlikowski M. Pineal gland, melatonin and cancer. Neuroendocrinol Lett. 1999;20(3-4):139-44

5- Lissoni P, Rovelli F, Giani L, Mandala M, Meregalli S, Barni S, Confalonieri G, Bonfanti A. Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid neoplasms: selective deficiency in metastatic disease. Int J Biol Markers. 1998 Jul-Sep;13(3):154-7

Câncer: Possível Melhora da Evolução Com Reposição de DHEA

1- Luo S, Sourla A, Labrie C, Belanger A, Labrie F. Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz(A)anthracene-induced mammary carcinoma in the rat. Endocrinology. 1997;138(10):4435-44

2- Mcikova-Kalicka K, Bojkova B, Adamekova E, Mnichova-Chamilova M, Kubatka P, Ahlersova E, Ahlers I. Preventive effect of indomethacin and melatonin on 7, 12-dimethybenz/a/anthracene-induced mammary carcinogenesis in female Sprague-Dawley rats. A preliminary report. Folia Biol (Praha). 2001;47(2):75-9

3- Melvin WS, Boros LG, Muscarella P, Brandes JL, Johnson JA, Fisher WE,Schirmer WJ, Ellison EC.. Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo. Surgery. 1997;121(4):392-7

4- Nyce JW, Magee PN, Hard GC, Schwartz AG. Inhibition of 1,2-dimethylhydrazine-induced colon tumorigenesis in Balb/c mice by dehydroepiandrosterone. Carcinogenesis. 1984;5(1):57-62

5- Orner GA, Hendricks JD, Arbogast D, Williams DE. Modulation of aflatoxin-B1 hepatocarcinogenesis in trout by dehydroepiandrosterone: initiation/post-initiation and latency effects. Carcinogenesis. 1998;19(1):161-7

6- Rao KV, Johnson WD, Bosland MC, Lubet RA, Steele VE, Kelloff GJ, McCormick DL. Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone. Cancer Res. 1999 Jul 1;59(13):3084-9

7- McCormick DL, Rao KV, Johnson WD, Bowman-Gram TA, Steele VE, Lubet RA, Kellof GJ. Exceptional chemopreventive activity of low-dose dehydroepiandrosterone in the rat mammary gland. Cancer Res. 1996 Apr 15;56(8):1724-6

8- McCormick DL, Rao KV. Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat. Eur Urol. 1999;35(5-6):464-7

Câncer de Mama: Melhora Com a Reposição de DHEA

1- Boccuzzi G, Aragno M, Brignardello E, Tamagno E, Conti G, Di Monaco M, Racca S, Danni O, Di Carlo F. Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas. Anticancer Res. 1992 Sep-Oct;12(5):1479-83

2- Boccuzzi G, Brignardello E, di Monaco M, Forte C, Leonardi L, Pizzini A. Influence of dehydroepiandrosterone and 5-en-androstene-3 beta, 17 beta-diol on the growth of MCF-7 human breast cancer cells induced by 17 beta-estradiol. Anticancer Res. 1992 May-Jun;12(3):799-803

ESTUDOS EM HUMANOS Estudos Demonstrando Associação Entre Baixos Níveis de DHEA e Aumento do Risco de Câncer de Mama 1. Rose DP, Stauber P, Thiel A, Crowley JJ, Milbrath JR. Plasma DHEAs,

Androstenedione and cortisol, and urinary free cortisol excretion in breast cancer. Europ J Cancer. 1977; 13: 43-7

2. Gomes P, Cassanas G, Halberg F, Hermida R, Robel P, Baulieu EE, Lakatua D, Haus E. Taux sanguin de la DHEA-S et risque de cancer du sein. C R Acad Sci III. 1988;306(7):261-4

3. Brownsey B, Cameron EH, Griffiths K, Gleave EN, Forrest AP, Campbell H.. Plasma dehydroepiandrosterone sulphate levels in patients with benign and malignant breast disease., Eur J Cancer. 1972;8(1):131-7

4. Wang DY, Bulbrook RD, Herian M, Hayward JL. Studies on the sulphate esters of dehydroepiandrosterone and androsterone in the blood of women with breast cancer. Eur J Cancer. 1974;10(8):477-82

5. Cameron EH, Griffiths K, Gleave E, Stewart HJ, Forrest AP, Campbell H., Benign and malignant breast disease in South Wales: a study of urinary steroids., Br Med J. 1970;4(738):768-71

6. Bulbrook RD, Hayward JL, Spicer CC, Thomas BS. Abnormal excretion of urinary steroids by women with early breast cancer. Lancet. 1962; 1238-40

7. Tominaga T, Tei N, Kitamura M, Taguchi T, Kudo Y. Urinary excretion of steroids by Japanese women with breast cancer. Gann 1975 Jun;66(3):305-10

8. Hindy I, Prajda N, Tapolcsanyi L, Sellei C, Eckhardt S. Investigation of 17-ketosteriod excretion in mastopathia and premenopausal breast cancer. Arch Geschwulstforsch 1975;45(5):453-6

9. Tominaga T, Tei N, Kitamura M, Taguchi T, Kudo Y. Urinary excretion of steroids by Japanese women with breast cancer. Gann 1975 Jun;66(3):305-10

10. Hindy I, Prajda N, Tapolcsanyi L, Sellei C, Eckhardt S. Investigation of 17-ketosteriod excretion in mastopathia and premenopausal breast cancer. Arch Geschwulstforsch 1975;45(5):453-6

11. Thijssen JH, van Landeghem AA, Poortman J. Uptake and concentration of steroid hormones in mammary tissues. Ann N Y Acad Sci. 1986;464:106-16.

12. Lissoni P, Rovelli F, Giani L, Mandala M, Meregalli S, Barni S, Confalonieri G, Bonfanti A. Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid neoplasms: selective deficiency in metastatic disease. Int J Biol Markers. 1998;13(3):154-7

13. Labrie F, Luu-The V, Belanger A, Lin SX, Simard J, Pelletier G, Labrie C. Is dehydroepiandrosterone a hormone? J Endocrinol. 2005 Nov;187(2):169-96

14. Cutler SY, Young JL. Third National Cancer Survey: incidence data. Washington DC: National Cancer Institute Monograph; 1975; vol. 41

Baixos Níveis de DHEA Tem Sido Observados em Outros Tipos de Câncer: Leucemia, Metástases e Câncer do Ovário

1- Cuzick J, Bulstrode JC, Stratton I, Thomas BS, Bulbrook RD, Hayward JL. A

prospective study of urinary androgen levels and ovarian cancer. Int J Cancer 1983 Dec 15;32(6):723-6

2- Heinonen PK, Koivula T, Pystynen P. Decreased serum level of dehydroepiandrosterone sulfate in postmenopausal women with ovarian cancer. Gynecol Obstet Invest 1987;23(4):271-4

3- Blaakaer J, Hogdall CK, Hording U, Bennett P, Toftager-Larsen K, Daugaard S,Bock J. Hormonal factors and prognosis in epithelial ovarian cancer: a multivariate analysis. Eur J Obstet Gynecol Reprod Biol 1993 Sep;51(1):21-7

4- Uozumi K, Uematsu T, Otsuka M, Nakano S, Takatsuka Y, Iwahashi M, Hanada S, Arima T. Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers.Am J Hematol 1996;53(3):165-8

5- Lissoni P, Rovelli F, Giani L, Mandala M, Meregalli S, Barni S, Confalonieri G, Bonfanti A. Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid neoplasms: selective deficiency in metastatic disease. Int J Biol Markers. 1998;13(3):154-7

Câncer: A Associação Com Baixos Níveis de Estradiol

1- Holmberg L, Norden T, Lindgren A, Wide L, Degerman M, Adami HO. Pre-operative oestradiol levels - relation to survival in breast cancer. Eur J Surg Oncol 2001 Mar;27(2):152-6

2- MacMahon B, Cole P, Brown JB, Aoki K, Lin TM, Morgan RW, Woo NC. Urine oestrogen profiles of Asian and North American women. Int J Cancer. 1974 Aug 15;14(2):161-7

3- MacMahon B, Cole P, Brown JB, Aoki K, Lin TM, Morgan RW, Woo N. Oestrogen profiles of Asian and North American women. Lancet. 1971 Oct 23;2(7730):900-2

4- Ursin G, Wilson M, Henderson BE, Kolonel LN, Monroe K, Lee HP, Seow A, YuMC, Stanczyk FZ, Gentzschein E Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women? Cancer Res. 2001 Apr 15;61(8):3326-9

5- Ursin G, London S, Stanczyk FZ, Gentzschein E, Paganini-Hill A, Ross RK, Pike MC. Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1999 Jun 16;91(12):1067-72

6- Lemon HM. Pathophysiologic considerations in the treatment of menopausal patients withoestrogens; the role of oestriol in the prevention of mammary carcinoma. Acta Endocrinol Suppl (Copenh) 1980;233:17-27

7- Vorherr H, Messer RH. Breast cancer: potentially predisposing and protecting factors. Role of pregnancy, lactation, and endocrine status. Am J Obstet Gynecol 1978 Feb 1;130(3):335-58

Câncer: A Associação Com Baixos Níveis de Progesterona

1- Cowan LD, Gordis L, Tonascia JA, Jones GS. Breast cancer incidence in women with a history of progesterone deficiency. Am J Epidemiol 1981 Aug;114(2):209-17

2- Adami HO, Bergstrom R, Holmberg L, Klareskog L, Persson I, Ponten J.The effect of female sex hormones on cancer survival. A register-based study in patients younger than 20 years at diagnosis. JAMA. 1990 Apr 25;263(16):2189-93

3- Adami HO, Holmberg L, Persson I. Survival and age at diagnosis in breast cancer. N Engl J Med. 1987 ; 316(12): 750-2

4- Mohr PE, Wang DY, Gregory WM, Richards MA, Fentiman IS. Serum progesterone and prognosis in operable breast cancer. Br J Cancer. 1996 Jun;73(12):1552-5

5- Badwe RA, Wang DY, Gregory WM, Fentiman IS, Chaudary MA, Smith P, Richards MA, Rubens RD. Serum progesterone at the time of surgery and survival in women with premenopausal operable breast cancer.Eur J Cancer. 1994;30A(4):445-8

Câncer: Possível Proteção Com a Reposição de Estradiol

1- . Henderson BE, Paganini-Hill,A, Ross RK. Decreased mortality in users of estrogen replacement therapy. Arch Intern Med 1991; 151:75

Estudos Demonstrando A Redução do Risco do Câncer de Mamam Coma Reposição de Estradiol

1- Plu-Bureau G, Le MG, Thalabard JC, Sitruk-Ware R, Mauvais-Jarvis P. Percutaneous progesterone use and risk of breast cancer: results from a French cohort study of premenopausal women with benign breast disease. Cancer Detect Prev 1999;23(4):290-6

2- Lauritzen C et al. Risks of endometrial and mammary cancer morbidity and mortality in long-term estrogen treatment. In The Climacteric -An Update, ed by van Herendael H & B, Riphagen FE, Goessens L, van der Pars H Lancaster, England, MTP Press Ltd 1984; 207

3- Peters GN, Fodera T, Sabol J, Jones S, Euhus D. Estrogen replacement therapy after breast cancer: a 12-year follow-up. Ann Surg Oncol 2001 Dec;8(10):828-32

4- Gambrell RD Jr. Hormones in the etiology and prevention of breast and endometrial cancer. South Med J.1984 Dec: 77(12): 1509-15.

5- Gambrell RD Jr, Maier RC, Sanders BI. Decreased incidence of breast cancer in postmenopausal estrogen progestogen users.. Obstet Gynecol 1983 Oct;62(4):435-43

6- Wingo PA, Layde PM, Lee NC, Rubin G, Ory HW. The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy. JAMA. 1987 Jan 9; 257(2): 209-15

7- Nachtigall LE, Nachtigall RH, Nachtigall RD, Beckman EM. Estrogen replacement Il: A prospective study in the relationship to carcinoma and cardiovascular and metabolic problems. Obstet Gynecol. 1979; 54: 74-9

8- Davelaar EM, Gerretsen G, Relyveld J.. No increase in the incidence of breast carcinoma with subcutaneous administration of estradiol Ned Tijdsch Geneeskd. 1991 Apr 6 ; 135(14): 613-5

9- Rosenberg L, Miller DR, Kaufman DW, Helmrich SP, Stolley PD, Schottenfeld. D; Shapiro S. Breast cancer and oral contraceptive use. Am J Epidemiol 1984 Feb;119(2):167-76

10- Kaufman DW, Miller DR, Rosenberg, Miller DR, Rosenberg L, Helmrich SP, Stolley P, Schottenfeld D, Shapiro S. Noncontraceptive estrogen use and the risk of breast JAMA 1984 Jul 6;252(1):63-7

11- Hammond CB, Jelovsek FR, Lee KI, WT, Parker. Effects of long term estrogen replacement therapy. II - Neoplasia. Am J Obstet Gynecol. 1979; 133: 537 (Reduced aggressivity of breast cancer if HRT before)

12- Sellers, TA, Mink, PJ, Cerhan, JR, g W, Anderson KE, Kushi LH, Folson AR. The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer. Ann Intern Med 1997; 127:973

Estudos Demonstrando o Aumento da Longevidade e a Redução de Recorrência em Mulheres Com História Prévia de Câncer de Mama Submetidas a Reposição de Estradiol

1- Wile AG, Opfell RW, Margileth DA. Hormone replacement therapy in previously treated breast cancer patients. Am J Surg. 1993 Mar;165(3):372-5

2- O'Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence & mortality. J Natl Cancer Inst. 2001;93(10):754-62

3- Dew JE, Wren BG, Eden JA. Tamoxifen, hormone receptors & hormone replacement therapy in women previously treated for breast cancer: a cohort study. Climacteric. 2002;5(2):151-5

4- Dew J, Eden J, Beller E, Magarey C, Schwartz P, Crea P, Wren B. A cohort study of hormone replacement therapy given to women previously treated for breast cancer. Climacteric.1998;1(2):137-42

5- Durna EM, Wren BG, Heller GZ, Leader LR, Sjoblom P, Eden JA. Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality. Med J Aust. 2002 Oct 7;177(7):347-51

6- Steinberg KK, Thacker SB, Smith SJ, Stroup DF, Zack MM, Flanders WD, Berkelman RL. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA. 1991 Apr 17;265(15):1985-90

7- Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, Rosner B, Fuchs C, Hankinson SE, Hunter DJ, Hennekens CH, Speizer FE. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997; 336:1769-75

8- Mohammed SN, Smith P, Hodgson SV, Fentiman IS, Miles DW, Barnes DM, Millis RR, Rubens RD Family history and survival in premenopausal breast cancer. Br J Cancer. 1998 Jun;77(12):2252-6

9- Gajdos C, Tartter PI, Babinszki A. Breast cancer diagnosed during hormone replacement therapy. Obstet Gynecol. 2000 Apr;95(4):513-8

10- Holli K, Isola J, Cuzick J. Low biologic aggressiveness in breast cancer in women using hormone replacement therapy. J Clin Oncol. 1998 Sep;16(9):3115-20

11- Magnusson C, Holmberg L, Norden T, Lindgren A, Persson I. Prognostic characteristics in breast cancers after hormone replacement therapy. Breast Cancer Res Treat. 1996;38(3):325-34

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9187066&dopt=Abstract


12- Meurer LN, Lena S. Cancer recurrence and mortality in women using hormone replacement therapy: meta-analysis.J Fam Pract. 2002 Dec;51(12):1056-62

13- Ursin G, Tseng CC, Paganini-Hill A, Enger S, Wan PC, Formenti S, Pike MC, Ross RK. Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer? Arch 1: J Clin Oncol 2002 Feb 1;20(3):699-706

14- Nanda K, Bastian LA, Schulz K. Hormone replacement therapy and the risk of death from breast cancer: a systematic review. Am J Obstet Gynecol. 2002 Feb; 186 (2):325-34

15- Willis DB, Calle EE, Miracle-McMahill HL, Heath CW Jr. Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States. Cancer Causes Control. 1996 Jul;7(4):449-57

16- Schairer C, Gail M, Byrne C, Rosenberg PS, Sturgeon SR, Brinton LA, Hoover RN.Estrogen replacement therapy and breast cancer survival in a large screening study. J Natl Cancer Inst. 1999 Feb 3;91(3):264-70

17- Ettinger B, Friedman, GD, Bush, T, Quesenberry CP Jr. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 1996 Jan;87(1):6-12 1140 Jernstrom H, Frenander J, Ferno M, Olsson H. Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients. Br J Cancer. 1999 Jul;80(9):1453-8

18- Hunt K, Vessey M, McPherson K. Long-term surveillance of mortality and cancer incidence in women recieving hormone replacement therapy. Br J Obstet Gynaecol. 1987; 94: 620-35

19- Plu-Bureau G, Le MG, Sitruk-Ware R, Thalabard JC, Mauvais-Jarvis P. Progestogen use and decreased risk of breast cancer in a cohort study of premenopausal women with benign breast disease. Br J Cancer. 1994 Aug;70(2):270-7

20- Lundgren S, Lonning PE. Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer -II. A differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globulin. J Steroid Biochem. 1990 Jun ; 36(1-2): 105-9

´

Câncer: A Associação Com Baixos Níveis de Testosterona 17. Imamoto T, Suzuki H, Fukasawa S, Shimbo M, Inahara M, Komiya A, Ueda T,

Shiraishi T, Ichikawa T. Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol. 2005 Mar;47(3):308-12

18. Meikle AW, Stanish WM. Familial prostatic cancer risk and low testosterone. J Clin Endocrinol Metab 1982 Jun;54(6):1104-8

19. Turkes AO, Turkes A, Read GF, Fahmy DR. A sensitive fluorometric enzyme immunoassay for testosterone in plasma and saliva [proceedings] J Endocrinol. 1979 Oct;83(1):31P.

20. Vestsi Akademii Medicina Navuk USSR 1980; 3: 72-7 (mentioned in The natural prostate cure (Proger Mason 2000 ISBN 1-884820-61-1)°

21. Kumar VL, Wadhwa SN, Kumar V, Farooq A. Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate. J Surg Oncol. 1990 Jun;44(2):122-8

22. Progress in Clinical Biological Research 1975; 6: 143-58 (mentioned in The natural prostate cure, Proger Mason 2000 ISBN 1-884820-61-1)

23. Zhonghua Yixue Zazhi 1993; 73: 489-90 (mentioned in The natural prostate cure (Proger Mason 2000 ISBN 1-884820-61-1)

24. Hulka BS, Hammond JE, DiFerdinando G, Mickey DD, Fried FA, Checkoway H, Stumpf WE, Beckman WC Jr, Clark TD. Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls. Prostate 1987;11(2):171-82

25. Ortega E, Ruiz E, Mendoza MC, Martin-Andres A, Osorio C. Plasma steroid and protein hormone concentrations in patients with benign prostatic hypertrophy and in normal men. Experientia. 1979 Jun 15;35(6):844-5

26. Wright F, Poizat, Bongini M,Bozzolan F Doukani A, Mauvais-Jarvis P. Decreased urinary 5-alpha-androstanediol glucuronide excretion in patients with benign prostatic hyperplasia. J Clin Endocrinol Metab. 1985; 60 (2) 294-8

27. Wu AH, Whittemore AS, Kolonel LN, John EM, Gallagher RP, West DW, Hankin J, Teh CZ, Dreon DM, Paffenbarger RS Jr. Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiol Biomarkers Prev. 1995 Oct-Nov;4(7):735-41

28. Zumoff B, Levin J, Strain GW, Rosenfeld RS, O'Connor J, Freed SZ, Kream J, Whitmore WS, Fukushima DK, Hellman L. Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a " two-disease" theory. Prostate 1982;3(6):579-88

29. Signorello LB, Tzonou A, Mantzoros CS, Lipworth L, Lagiou P, Hsieh C, Stampfer M, Trichopoulos D. Serum steroids in relation to prostate cancer risk in a case-control study (Greece). Cancer Causes Control 1997 Jul;8(4):632-6

30. Gustafsson O, Norming U, Gustafsson S, Eneroth P, Astrom G, Nyman CR. Dihydrotestosterone and testosterone levels in men screened for prostate cancer:a study of a randomized population. Br J Urol. 1996 Mar;77(3):433-40

31. Nomura A, Heilbrun LK, Stemmermann GN, Judd HL. Prediagnostic serum hormones and the risk of prostate cancer. Cancer Res 1988 Jun 15;48(12):3515-7

32. Hoffman MA, DeWolf WC, Morgentaler A.Is low serum free testosterone a marker for high grade prostate cancer? J Urol 2000 Mar;163(3):824-7

33. Wynder EL, Laakso K, Sotarauta M, Rose DP. Metabolic epidemiology of prostatic cancer. Prostate 1984;5(1):47-53

Mortalidade Aumentada em Homens Com Câncer de Próstata e Baixos Níveis

de Testosterona 1- Carrero JJ, Qureshi AR, Parini P, Arver S, Lindholm B, Bárány P, Heimbürger

O, Stenvinkel P. Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol. 2009 Mar;20(3):613-20

2- Tivesten A, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellström D, Ohlsson C. Low serum testosterone and estradiol predict mortality in elderly men. . J Clin Endocrinol Metab. 2009 Jul;94(7):2482-8

3- Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116(23):2694-701

4- Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. . J Clin Endocrinol Metab. 2008 Jan;93(1):68-75

5- Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006 Aug 14-28;166(15):1660-5

6- Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol. 1997 Dec;20(6):605-8

7- Iversen P, Rasmussen F, Christensen IJ. Serum testosterone as a prognostic factor in patients with advanced prostatic carcinoma. Scand J Urol Nephrol Suppl. 1994; 157: 41-7

8- Haapiainen R, Rannikko S, Alfthan O, Adlercreutz H. Pretreatment plasma levels of testosterone and sex hormone binding globulin binding capacity in relation to clinical staging and survival in prostatic cancer patients. Prostate. 1988;12(4):325-32

Câncer em Homens: Possível Proteção Com a Reposição de Testosterona

1- Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause. 2004 Sep-Oct;11(5):531-535

2- Morales A, Connolly JG, Bruce AW. Androgen therapy in advanced carcinoma of the prostate. Can Med Assoc J. 1971;105(1):71-2

3- Prout GR Jr, Brewer WR. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer. 1967 Nov;20(11):1871-8

4- Joly-Pharaboz MO, Soave MC, Nicolas B, Mebarki F, Renaud M, Foury O, Morel Y, Andre JG. Androgens inhibit the proliferation of a variant of the human prostate cancer cell line LNCaP. J Steroid Biochem Mol Biol 1995 Oct;55(1):67-76

5- Wolf DA, Schulz P, Fittler F. Synthetic androgens suppress the transformed phenotype in human prostate carcinoma cell line LNCaP. Br J Cancer. 1991 Jul; 64 (1): 47-53

6- Andrews P, Krygier S, Djakiew D. Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells. Cancer Chemother Pharmacol 2002 Mar;49(3):179-86

Estudos Aonde a Reposição Com Testosterona Parece Conferir Proteção

Contra o Câncer de Próstata 1. Morales A, Connolly JG, Bruce AW. Androgen therapy in advanced carcinoma

of the prostate. Can Med Assoc J. 1971;105(1):71-2 2. Prout GR Jr, Brewer WR. Response of men with advanced prostatic carcinoma

to exogenous administration of testosterone. Cancer. 1967 Nov;20(11):1871-8 Estudos Aonde a Reposição Com Testosterona Promove Inibição da Proliferação do Câncer de Próstata ou Induz a Sua Apoptose 1- Joly-Pharaboz MO, Soave MC, Nicolas B, Mebarki F, Renaud M, Foury O,

Morel Y, Andre JG. Androgens inhibit the proliferation of a variant of the



human prostate cancer cell line LNCaP. J Steroid Biochem Mol Biol 1995 Oct;55(1):67-76

2- Wolf DA, Schulz P, Fittler F. Synthetic androgens suppress the transformed phenotype in human prostate carcinoma cell line LNCaP. Br J Cancer. 1991 Jul; 64 (1): 47-53

3- Andrews P, Krygier S, Djakiew D. Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells. Cancer Chemother Pharmacol. 2002 Mar;49(3):179-86

Estudos Onde a Reposição de Testosterona Reduz Queixas Prostáticas Como Disúria e Nictúria 1- Flamm J, Kiesswetter H, Englisch M. An urodynamic study of patients with

benign prostatic hypertrophy treated conservatively with phytotherapy or testosterone. Wien Klin Wochenschr 1979 Sep 28;91(18):622-7

2- Kearns WM. Testosterone in the treatment of testicular deficiency and prostatic enlargement. Wisconsin Med J. 1941; 40:927 (testosterone proprionate therapy did not reduce the size of the prostate, but reduced the dysuria)

3- Meltzer M. Male hormone therapy of prostatic hypertrophy. Lancet. 1939; 59: 279

4- Trasoff A. The treatment of benign prostatic hypertrophy with testosterone propionate. J Lab Clin Med. 1940; 25: 377

5- Markham MJ. The clinical use of peroral methyltestosterone in benign prostatic hypertrophy. Urol Cutan Rev. 1942; 46: 225

6- Markham MJ. The clinical use of testosterone propionate in benign prostatic hypertrophy. Urol Cutan Rev. 1941; 45: 35

7- Laqueur E. Behandlung der Prostathypertropie mit männlichen Hormone (Hombreol) une experimentell Begründung dieser Therapie. Schweiz Med Wochenschr. 1934; 64: 1116

8- South Med J, 1939, 32: 154

Estudos Onde a Reposição de Testosterona Reduziu o Volume da Próstata e as Queixas Prostáticas 1- South Med J, 1939, 32: 154 2- de Lignieres B. Transdermal dihydrotestosterone treatment of 'andropause.

Ann Med 1993 Jun;25(3):235-41 3- Swerdloff RS, Wang C. Dihydrotestosterone: a rationale for its use as a non-

aromatizable androgen replacement therapeutic agent. Baillieres Clin Endocrinol Metab. 1998 Oct;12(3):501-6

4- Sitruk-Ware R. Contraception, 1989, 39: 1-191 Estudos de Revisão Onde os Autores Não Acharam Associação Entre Os Níveis de Testosterona e o Risco de Câncer de Próstata e Demonstram Claramente Que Não Existem Dados ou Evidências Que Dêem Suporte a Visão de Que a Reposição de Testosterona Esteja Correlacionada Com o Risco de Câncer

1- Rhoden NEJM 2004 (“No compelling evidence at present to suggest that men

with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism with exogenous androgens increases this risk. In fact, it should be recognized that prostate cancer becomes more prevalent exactly at the time of a man's life when testosterone levels decline.“)

2- Morales A. Androgen replacement therapy and prostate safety. Eur Urol 2002 Feb;41(2):113-20 (“To date there is no evidence that exogenous androgens promote development of prostate cancer”)

3- Basaria S, Wahlstrom JT, Dobs AS. Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases. J Clin Endocrinol Metab. 2001 Nov;86(11):5108-17(“..recent reviews suggest that the incidence of prostate cancer is not increased by testosterone administration”)

4- Morley JE. Testosterone replacement and the physiologic aspects of aging in men. Mayo Clin Proc. 2000 Jan;75 Suppl:S83-7 (“There is no clinical evidence that the risk of either prostate cancer or benign prostate hypertrophy increases with testosterone treatment”)

5- Wirth MP, Hakenberg OW Testosterone and the prostate. Urologe A 2000 Sep;39(5):418-20

6- Rolf C, Nieschlag E. Potential adverse effects of long-term testosterone therapy. Baillieres Clin Endocrinol Metab. 1998 Oct;12(3):521-34.

7- Prehn RT. On the prevention and therapy of prostate cancer by androgen administration. Cancer Res. 1999 Sep 1;59(17):4161-4 (“… contrary to prevalent opinion, declining rather than high levels of androgens probably contribute more to human prostate carcinogenesis and ;.. androgen supplementation would probably lower the incidence of the disease. … consider the possibility that the growth of androgen-independent prostate cancers might be reduced by the administration of androgens”)

Estudos Onde a Reposição de Testosterona em Homens Com Câncer de Próstata Não Exerce Qualquer Efeito Adverso na Progressão ou Recorrência do Câncer e, Ao Mesmo Tempo, Melhora a Qualidade de Vida e Os Parâmetros Gerais de Saúde

1- Morales A, Black AM, Emerson LE. Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations. BJU Int. 2009 Jan;103(1):62-4 (n = 5; “Men with testosterone deficiency syndrome after external beam radiotherapy for localised prostate cancer are candidates for testosterone therapy ..no adverse effects from testosterone supplementation”)

2- Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007 Feb 1;109(3):536-41 ( (n = 31; For patients with low serum testosterone levels and symptoms of hypogonadism, testosterone therapy may be used with caution and close follow-up after prostate brachytherapy)

3- Agarwal PK, Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol. 2005 Feb;173(2):533-6 (n = 10 hypogonadal men treated with radical retropubic prostatectomy for organ confined prostate cancer; testosterone replacement therapy can be

administered carefully and with benefit to hypogonadal patients with prostate cancer)

Estudos Onde a Reposição de Testosterona Não Demonstra Efeitos Adversos No Risco de Câncer de Próstata

1- Prout GRJ, Brewer WR. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer (Phila.). 1967;20:1871-8

2- Trunnell JD, Duffy BJ Jr. The influence of certain steroids on the behavior of human prostate cancer. Trans. NY Acad Sci. 1950;II:12:238-41

3- Brendler H, Lowry O, Brock M. Further investigation of hormonal relationships. Arch Surg. 1950,61:433-40

4- Pearson OH. Discussion of Dr. Huggins’ paper: “Control of cancers of man by endocrinological methods." Cancer Res. 1957:17:473-9

5- Morales A, Connolly J, Burr R, Bruce A. The use of radioactive phosphorus to treat bone pain in metastatic carcinoma of the prostate. Can Med Assoc J. 1970;103: 372-3

Estudos Onde a Reposição de Testosterona Não Demonstra Quaisquer Efeitos Nos Níveis de PSA ou do Volume da Próstata 3. Rhoden EL, Morgentaler A. Influence of demographic factors and biochemical

characteristics on the prostate-specific antigen (PSA) response to testosterone replacement therapy. Int J Impot Res. 2005 Sep 22 (No statistical increase: average = 0.31 ng/ml after 1 year of treatment of hypogonadal men)

4. Shibasaki T, Sasagawa I, Suzuki Y, Yazawa H, Ichiyanagi O, Matsuki S, Miura M, Nakada T. Effect of testosterone replacement therapy on serum PSA in patients with Klinefelter syndrome. Arch Androl. 2001 Nov-Dec;47(3):173-6

5. Cooper CS, Perry PJ, Sparks AE, MacIndoe JH, Yates WR, Williams RD. Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol. 1998 Feb;159(2):441-3

6. Cooper CS, MacIndoe JH, Perry PJ, Yates WR, Williams RD. The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men. J Urol. 1996 Aug;156(2 Pt 1):438-41

7. Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf). 1994 Mar;40(3):341-9

8. Douglas TH, Connelly RR, McLeod DG, Erickson SJ, Barren R 3rd, Murphy GP. Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men. J Surg Oncol. 1995 Aug;59(4):246-50

9. Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab. 1997 Jun;82(6):1661-7

10. Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab. 1997 Nov;82(11):3793-6

11. Monath JR, McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum testosterone within the normal range do not affect serum prostate-specific antigen. Urology. 1995 Jul;46(1):58-61

11- EXPANSÃO DA LONGEVIDE E MELHORA DA

QUALIDADE DE VIDA ATRAVÉS DA MODULAÇÃO HORMONAL

Longevidade em Homens: A Associação Com Baixos Níveis de Testosterona 1- Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A,

Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116(23):2694-701

2- Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):1829-37

3- Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006 Aug 14-28;166(15):1660-5

4- Shores MM, Moceri VM, Gruenewald DA, Brodkin KI, Matsumoto AM, Kivlahan DR. Low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit. J Am Geriatr Soc. 2004 Dec;52(12):2077-81

5- Suzuki M. Centenarians in Japan. Nakayamshoten Tokyo (Japan), 1995: 64-78 6- Haapiainen R, Rannikko S, Alfthan O, Adlercreutz H. Pretreatment plasma

levels of testosterone and sex hormone binding globulin binding capacity in relation to clinical staging and survival in prostatic cancer patients. Prostate. 1988;12(4):325-32

Longevidade em Homens: A Melhora da Sobrevida Com A Reposição de

Testosterona

1- Morales A, Connolly JG, Bruce AW. Androgen therapy in advanced carcinoma of the prostate. Can Med Assoc J. 1971;105(1):71-2

2- Prout GR Jr, Brewer WR. Response of men with advanced prostatic carcinoma to exogenous administration of testosterone. Cancer. 1967 Nov;20(11):1871-8

Longevidade em Homens: A Associação Com Baixos Níveis de GH 1- Stochholm K, Christiansen J, Laursen T, Gravholt CH. Mortality and reduced

growth hormone secretion. Horm Res. 2007;68 Suppl 5:173-6 2- Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in

hypopituitarism. Lancet. 1990 Aug 4;336(8710):285-8

3- Besson A, Salemi S, Gallati S, Jenal A, Horn R, Mullis PS, Mullis PE.. Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab. 2003 Aug;88(8):3664-7

4- Bates AS, Van't Hoff W, Jones PJ , Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169-72

Longevidade: A Melhora Com a Reposição de GH 1- Li N, Zhou L, Zhang B, Dong P, Lin W, Wang H, Xu R, Ding H. Recombinant

human growth hormone increases albumin and prolongs survival in patients with chronic liver failure: a pilot open, randomized, and controlled clinical trial. Dig Liver Dis. 2008 Jul;40(7):554-9

2- Sonntag WE, Carter CS, Ikeno Y, Ekenstedt K, Carlson CS, Loeser RF, Chakrabarty S, Lee S, Bennett C, Ingram R, Moore T, Ramsey M. Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span. Endocrinology. 2005;146(7):2920-32

3- Khansari DN, Gustad T. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice. Mech Ageing Dev. 1991 Jan;57(1):87-100

4- Bengtsson BA, Koppeschaar HP, Abs R, Bennmarker H, Hernberg-Stahl E, Westberg B, Wilton P, Monson JP, Feldt-Rasmussen U, Wuster C. Growth hormone replacement therapy is not associated with any increase in mortality. KIMS Study Group. J Clin Endocrinol Metab. 1999;84(11):4291-2

Longevidade: A Associação Com Baixos Níveis de IGF-1

1- Guimarães SM, Lima EQ, Cipullo JP, Lobo SM, Burdmann EA. Low insulin-like growth factor-1 and hypocholesterolemia as mortality predictors in acute kidney injury in the intensive care unit. Crit Care Med. 2008 Dec;36(12):3165-70

2- Arai Y, Takayama M, Gondo Y, Inagaki H, Yamamura K, Nakazawa S, Kojima T, Ebihara Y, Shimizu K, Masui Y, Kitagawa K, Takebayashi T, Hirose N. Adipose endocrine function, insulin-like growth factor-1 axis, and exceptional survival beyond 100 years of age. J Gerontol A Biol Sci Med Sci. 2008 Nov;63(11):1209-18

3- Brugts MP, van den Beld AW, Hofland LJ, van der Wansem K, van Koetsveld PM, Frystyk J, Lamberts SW, Janssen JA. Low circulating insulin-like growth factor I bioactivity in elderly men is associated with increased mortality. J Clin Endocrinol Metab. 2008 Jul;93(7):2515-22

4- Petretta M, Colao A, Sardu C, Scopacasa F, Marzullo P, Pivonello R, Fontanella L, de Caterina M, de Simone A, Bonaduce D. NT-proBNP, IGF-I and survival in patients with chronic heart failure. Growth Horm IGF Res. 2007 Aug;17(4):288-96


6- Rasmuson T, Grankvist K, Jacobsen J, Olsson T, Ljungberg B. Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma. Acta Oncol. 2004;43(8):744-8

7- Denti L, Annoni V, Cattadori E, Salvagnini MA, Visioli S, Merli MF, Corradi F, Ceresini G, Valenti G, Hoffman AR, Ceda GP. Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly. Am J Med. 2004 Sep 1;117(5):312-7

8- Onenli-Mungan N, Yildizdas D, Yapicioglu H, Topaloglu AK, Yüksel B, Ozer G. Growth hormone and insulin-like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock. J Paediatr Child Health. 2004 Apr;40(4):221-6

9- Laughlin GA, Barrett-Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2004 Jan;89(1):114-20

10- Vasan RS, Sullivan LM, D'Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, Wilson PW. Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study. Ann Intern Med. 2003 Oct 21;139(8):642-8

11- Roubenoff R, Parise H, Payette HA, Abad LW, D'Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med. 2003 Oct 15;115(6):429-35

12- Roubenoff R, Parise H, Payette HA, Abad LW, D'Agostino R, Jacques PF, Wilson PW, Dinarello CA, Harris TB. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med. 2003 Oct 15;115(6):429-35

13- Ruiz-Torres A, Soares de Melo Kirzner M. Ageing and longevity are related to growth hormone/insulin-like growth factor-1 secretion. Gerontology. 2002 Nov-Dec;48(6):401-7

14- Fernández-Reyes MJ, Alvarez-Ude F, Sánchez R, Mon C, Iglesias P, Díez JJ, Vázquez A. Inflammation and malnutrition as predictors of mortality in patients on hemodialysis. J Nephrol. 2002 Mar-Apr;15(2):136-43

15- Caregaro L, Alberino F, Amodio P, Merkel C, Angeli P, Plebani M, Bolognesi M, Gatta A. Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis. Nutrition. 1997 Mar;13(3):185-90.

Longevidade: A Melhora Com a Reposição de IGF-1

1- Serose A, Salmon A, Fiszman MY, Fromes Y. Short-term treatment using insulin-like growth factor-1 (IGF-1) improves life expectancy of the delta-sarcoglycan deficient hamster. J Gene Med. 2006 Aug;8(8):1048-55

Longevidade: A Associação Com Baixos Níveis de DHEA 1- Cappola AR, O'Meara ES, Guo W, Bartz TM, Fried LP, Newman AB.

Trajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study. J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1268-74

2- Enomoto M, Adachi H, Fukami A, Furuki K, Satoh A, Otsuka M, Kumagae S, Nanjo Y, Shigetoh Y, Imaizumi T. Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow-up study in a community-based cohort (Tanushimaru study). J Am Geriatr Soc. 2008 Jun;56(6):994-8

3- Glei DA, Goldman N. Dehydroepiandrosterone sulfate (DHEAS) and risk for mortality among older Taiwanese. Ann Epidemiol. 2006 Jul;16(7):510-5


5- Mazat L, Lafont S, Berr C, Debuire B, Tessier JF, Dartigues JF, Baulieu EE. Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: relationship to gender, subjective health, smoking habits, and 10-year mortality. Proc Natl Acad Sci USA. 2001;98(14):8145-50

6- Feldman HA, Johannes CB, Araujo AB, Mohr BA, Longcope C, McKinlay JB. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2001 Jan 1;153(1):79-89

Longevidade: A Associação Com os Níveis de Progesterona

1- Mohr PE, Wang DY, Gregory WM, Richards MA, Fentiman IS. Serum progesterone and prognosis in operable breast cancer. Br J Cancer. 1996 Jun;73(12):1552-5

Longevidade: A Melhora Com a Reposição de Estradiol

1- Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and mortality: long-term follow-up of women in the Walnut Creek Study. Obstet Gynecol. 1987 Sep;70(3 Pt 1):289-93

2- Natrajan PK, Soumakis K, Gambrell RD Jr. Estrogen replacement therapy in women with previous breast cancer. Am J Obstet Gynecol. 1999;181(2):288-95

3- DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H. Breast cancer survival and hormone replacement therapy: a cohort analysis. Am J Clin Oncol. 2000 Dec;23(6):541-5

4- Jernstrom H, Frenander J, Ferno M, Olsson H. Hormone replacement therapy before breast cancer diagnosis significantly reduces the overall death rate compared with never-use among 984 breast cancer patients. Br J Cancer. 1999;80(9):1453-8

Longevidade: A Melhora Com a Reposição de Progesterona

1- Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. ProTECT: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury. Ann Emerg Med. 2007 Apr;49(4):391-402, 402.e1-2

Longevidade: A Possível Associação Com a Persistência do Ritmo Cirdadiano

da Melatonina em Idosos 1- Cugini P, Touitou Y, Bogdan A, Auzeby A, Pellegrino AM, Fontana S, Vacca K,

Siena GD, Di Rosa R, Zannella FP, Zannella P, Zannella A, Sepe FA, Sepe L. Is melatonin circadian rhythm a physiological feature associated with healthy longevity? A study of long-living subjects and their progeny. Chronobiol Int. 2001 Jan;18(1):99-107

Longevidade: A Melhora Com a Reposição de Melatonina 1- Rodríguez MI, Escames G, López LC, López A, García JA, Ortiz F, Sánchez V,

Romeu M, Acuña-Castroviejo D. Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice. Exp Gerontol. 2008 Aug;43(8):749-56

2- Vinogradova IA, Bukalev AV, Zabezhinskiĭ MA, Semenchenko AV, Anisimov VN. [Effect of light regimens and melatonin on homeostasis, life span and spontaneous tumorigenesis in male rats] Vopr Onkol. 2008;54(1):70-7

3- Ayer RE, Sugawara T, Chen W, Tong W, Zhang JH. Melatonin decreases mortality following severe subarachnoid hemorrhage. J Pineal Res. 2008 Mar;44(2):197-204

4- Xu J, Sun S, Wei W, Fu J, Qi W, Manchester LC, Tan DX, Reiter RJ. Melatonin reduces mortality and oxidatively mediated hepatic and renal damage due to diquat treatment. J Pineal Res. 2007 Mar;42(2):166-71

5- Pierpaoli W, Regelson W. Pineal control of aging: effect of melatonin and pineal grafting on aging mice. Proc Natl Acad Sci USA. 1994 Jan 18;91(2):787-91

6- Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, Cordaro S, Corona G, Trimarchi G, Barberi I. Effects of melatonin treatment in septic newborns. Pediatr Res. 2001 Dec;50(6):756-60

7- Barni S, Lissoni P, Cazzaniga M, Ardizzoia A, Meregalli S, Fossati V, Fumagalli L, Brivio F, Tancini G. A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates. Oncology. 1995 May-Jun;52(3):243-5

Longevidade: A Associação Com Baixos Níveis dos Hormônios Tireoidianos 1- Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic

heart disease and mortality in people with subclinical hypothyroidism: Reanalysis of the Whickham Survey Cohort. J Clin Endocrinol Metab. 2010 Apr;95(4):1734-40

2- Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, Bauer DC. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005 Nov 28;165(21):2460-6

3- Cerillo AG, Bevilacqua S, Storti S, Mariani M, Kallushi E, Ripoli A, Clerico A, Glauber M. Free triiodothyronine: a novel predictor of postoperative atrial fibrillation. Eur J Cardiothorac Surg. 2003 Oct;24(4):487-92

4- Iervasi G, G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L'Abbate A, Donato L. Low T3 syndrome: a strong predictor of death in patients with heart disease. Circulation. 2003;107(5):708-13

5- Kozdag G, Ural D, Vural A, Agacdiken A, Kahraman G, Sahin T, Ural E, Komsuoglu B. Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur J Heart Fail. 2005 Jan;7(1):113-8

6- Pingitore A, Landi P, Taddei MC, Ripoli A, L'Abbate A, Iervasi G. Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am J Med. 2005 Feb;118(2):132-6

Longevidade: A Melhora Com a Reposição dos Hormônios Tireoidianos 1- Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The Incidence of Ischemic

Heart Disease and Mortality in People with Subclinical Hypothyroidism: Reanalysis of the Whickham Survey Cohort. J Clin Endocrinol Metab. 2010 Apr;95(4):1734-40

12- PROFILAXIA E TRATAMENTO DA DEPRESSÃO ATRAVÉS DA MODULAÇÃO HORMONAL:

Depressão: A Associação Com Baixos Níveis de Melatonina

1- Rahman SA, Marcu S, Kayumov L, Shapiro CM. Altered sleep architecture and higher incidence of subsyndromal depression in low endogenous melatonin secretors. Eur Arch Psychiatry Clin Neurosci. 2010 (2009, Dec 18 Epub ahead of print)

2- Parry BL, Meliska CJ, Sorenson DL, Lopez AM, Martinez LF, Nowakowski S, Elliott JA, Hauger RL, Kripke DF. Plasma melatonin circadian rhythm disturbances during pregnancy and postpartum in depressed women and women with personal or family histories of depression. Am J Psychiatry. 2008 Dec;165(12):1551-8

3- Fountoulakis KN, Karamouzis M, Iacovides A, Nimatoudis J, Diakogiannis J, Kaprinis G, Demitriadou A, Bech P. Morning and evening plasma melatonin and dexamethasone suppression test in patients with nonseasonal major depressive disorder from northern Greece (latitude 40-41.5 degrees ). Neuropsychobiology. 2001;44(3):113-7

4- Frazer A, Brown R, Kocsis J, Caroff S, Amsterdam J, Winokur A, Sweeney J, Stokes P.Patterns of melatonin rhythms in depression. J Neural Transm Suppl. 1986;21:269-90

5- McIntyre IM, Judd FK, Norman TR, Burrows GD. Plasma melatonin concentrations in depression. Aust N Z J Psychiatry. 1986 Sep;20(3):381-3

6- Steiner M, Brown GM, Goldman S. Nocturnal melatonin and cortisol secretion in newly admitted psychiatric inpatients. Implications for affective disorders. Eur Arch Psychiatry Clin Neurosci 1990;240(1):21-7

7- Bozhko GKh, Tsaritsinskii VI, Kostiukovskaia LS, Kulabukhov VM. The effect of an increased intensity of light on changes in the serotonin and melatonin content in patients with depression. Lik Sprava 1994 Jul-Aug;(7-8):88-90

8- Brown R, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes PE, Frazer A. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am J Psychiatry. 1985 Jul;142(7):811-6

9- Chazot G, Claustrat B, Brun J, Borson F, Dalery J. Melatonin. Chronobiologic peripheral endocrine index in depressive states. Encephale. 1985 May-Jun;11(3):113-6

10- Nair NP, Hariharasubramanian N, Pilapil C. Circadian rhythm of plasma melatonin in endogenous depression. Prog Neuropsychopharmacol Biol Psychiatry. 1984;8(4-6):715-8

11- Claustrat B, hazot G, Brun J, Jordan D, Sassolas G. A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry. 1984 Aug;19(8):1215-28

12- Souetre E, Salvati E, Belugou JL, Pringuey D, Candito M, Krebs B, Ardisson JL, Darcourt G. Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality. Psychiatry Res 1989 Jun;28(3):263-78

13- Brown RP, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes P, Frazer A. Depressed mood and reality disturbance correlate with decreased nocturnal melatonin in depressed patients. Acta Psychiatr Scand. 1987 Sep;76(3):272-5

14- Hariharasubramanian N, Nair NP, Pilapil C, Isaac I, Quirion R. Effect of imipramine on the circadian rhythm of plasma melatonin in unipolar depression. Chronobiol Int. 1986; 3 (1): 65-9

15- Beck-Friis J, Kjellman BF, Aperia B, Unden F, von Rosen D, Ljunggren JG, Wetterberg L. Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 1985 Apr;71(4):319-30

16- Beck-Friis J, von Rosen D, Kjellman BF, Ljunggren JG, Wetterberg L. Melatonin in relation to body measures, sex, age, season and the use of drugs in patients with major affective disorders and healthy subjects. Psychoneuroendocrinology. 1984;9(3):261-77

Depressão: A Melhora Com a Reposição de Melatonina

1- Rahman SA, Kayumov L, Shapiro CM. Antidepressant action of melatonin in the treatment of Delayed Sleep Phase Syndrome. Sleep Med. 2010 Feb;11(2):131-6

2- Zisapel N. Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs Harefuah. 2009 May;148(5):337-41, 348

3- Jean-Louis G, von Gizycki H, Zizi F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J Pineal Res 1998 Oct;25(3):177-83

4- Raghavendra V, Kaur G, Kulkarni SK. Anti-depressant action of melatonin in chronic forced swimming-induced behavioral despair in mice, role of peripheral benzodiazepine receptor modulation. Eur Neuropsychopharmacol. 2000 Dec;10(6):473-81

5- Bellipanni G, Bianchi P, Pierpaoli W, Bulian D, Ilyia E. Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study. Exp Gerontol 2001 Feb;36(2):297-310

6- Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res. 1998 Jan 16;77(1):57-61

7- Ishizaki A, Sugama M, Takeuchi N. Usefulness of melatonin for developmental sleep and emotional/behavior disorders--studies of melatonin trial on 50 patients with developmental disorders. No To Hattatsu; 1999 Sep;31(5):428-37

Depressão: A Associação Com Baixos Níveis do Hormônio do Crescimento

1- Jarrett DB, Miewald JM, Kupfer DJ. Recurrent depression is associated with a persistent reduction in sleep-related growth hormone secretion. Arch Gen Psychiatry. 1990 Feb;47(2):113-8

2- Jarrett DB, Kupfer DJ, Miewald JM, Grochocinski VJ, Franz B. Sleep-related growth hormone secretion is persistently suppressed in women with recurrent depression: a preliminary longitudinal analysis. J Psychiatr Res. 1994 May-Jun;28(3):211-23)

3- Rubin RT, Poland RE, Lesser IM. Neuroendocrine aspects of primary endogenous depression. X: Serum growth hormone measures in patients and matched control subjects. Biol Psychiatry. 1990 May 15;27(10):1065-82

4- Schilkrut R, Chandra O, Osswald M, Ruther E, Baafusser B, Matussek. Growth hormone release during sleep and with thermal stimulation in depressed patients. Neuropsychobiology. 1975;1(2):70-9

5- Barry S, Dinan TG. Neuroendocrine challenge tests in depression: a study of growth hormone, TRH and cortisol release. J Affect Disord. 1990 Apr;18(4):229-34

6- Dinan TG, Barry S. Responses of growth hormone to desipramine in endogenous and non-endogenous depression. Br J Psychiatry. 1990 May;156:680-4

7- Voderholzer U, Laakmann G, Wittmann R, Daffner-Bujia C, Hinz A, Haag C, Baghai T. Profiles of spontaneous 24-hour and stimulated growth hormone secretion in male patients with endogenous depression. Psychiatry Res. 1993 Jun;47(3):215-27

8- Harro J, Rimm H, Harro M, Grauberg M, Karelson K, Viru AM. Association of depressiveness with blunted growth hormone response to maximal physical exercise in young healthy men. Psychoneuroendocrinology. 1999 Jul;24(5):505-17

9- Greden JF. Biological markers of melancholia and reclassification of depressive disorders. Encephale. 1982;8(2):193-202

10- McMillan CV, Bradley C, Gibney J, Healy ML, Russell-Jones DL, Sonksen PH. Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency. Clin Endocrinol. (Oxf). 2003 Oct;59(4):467-75

Depressão: A Melhora Com a Reposição do Hormônio do Crescimento

1- Arwert LI, Deijen JB, Müller M, Drent ML. Long-term growth hormone treatment preserves GH-induced memory and mood improvements: a 10-

year follow-up study in GH-deficient adult men. Horm Behav. 2005 Mar;47(3):343-9

2- Mahajan T, Crown A, Checkley S, Farmer A, Lightman S. Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life. Eur J Endocrinol. 2004 Sep;151(3):325-32

3- Johansson JO, Larson G, Andersson M, Elmgren A, Hynsjo L, Lindahl A, Lundberg PA, Isaksson OG, Lindstedt S, Bengtsson BA. Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters. Neuroendocrinology. 1995 Jan;61(1):57-66 (GH increases endorphins, reduces dopamine)

Depressão: A Associação Com Baixos Níveis dos Hormônios Tireoidianos


2- Pop VJ, Maartens LH, Leusink G, van Son MJ, Knottnerus AA, Ward AM, Metcalfe R, Weetman AP. Are autoimmune thyroid dysfunction and depression related? J Clin Endocrinol Metab. 1998 Sep;83(9):3194-7

3- Haggerty JJ Jr, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ Jr. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry. 1993 Mar;150(3):508-10

4- Gold MS, Pottash AL, Extein I. "Symptomless" autoimmune thyroiditis in depression. Psychiatry Res. 1982 Jun;6(3):261-9

5- O'Shanick GJ, Ellinwood EH Jr. Persistent elevation of thyroid-stimulating hormone in women with bipolar affective disorder. Am J Psychiatry. 1982 Apr;139(4):513-4

6- Howland RH. Thyroid dysfunction in refractory depression: implications for pathophysiology and treatment. J Clin Psychiatry. 1993 Feb;54(2):47-54

7- Kirkegaard C, Norlem N, Lauridsen UB, Bjorum N, Christiansen C. Protirelin stimulation test and thyroid function during treatment of depression. Arch Gen Psychiatry. 1975 Sep;32(9):1115-8

8- Bauer MS, Whybrow PC, Winokur A. Rapid cycling bipolar affective disorder. I. Association with grade I hypothyroidism. Arch Gen Psychiatry. 1990 May;47(5):427-32

9- Haggerty JJ Jr, Evans DL, Golden RN, Pedersen CA, Simon JS, Nemeroff CB. The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders. Biol Psychiatry. 1990 Jan 1;27(1):51-60

10- Cole DP, Thase ME, Mallinger AG, Soares JC, Luther JF, Kupfer DJ, Frank E. Slower treatment response in bipolar depression predicted by lower pre-treatment thyroid function. Am J Psychiatry. 2002 Jan;159(1):116-21

11- Joffe RT, Marriott M. Thyroid hormone levels and recurrence of major depression. Am J Psychiatry. 2000 Oct;157(10):1689-91 (“the time to recurrence of major depression was inversely related to T3 levels but not to T4 levels”)

Depressão: A Melhora Com a Reposição dos Hormônios Tireoidianos

1- Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. Arch Gen Psychiatry. 1990 May;47(5):435-40

2- Afflelou S, Auriacombe M, Cazenave M, Chartres JP, Tignol J. Administration of high dose levothyroxine in treatment of rapid cycling bipolar disorders. Review of the literature and initial therapeutic application apropos of 6 cases. Encephale. 1997 May-Jun;23(3):209-17

3- Bauer M, Baur H, Berghofer A, Strohle A, Hellweg R, Muller-Oerlinghausen B, Baumgartner A. Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders. J Affect Disord. 2002 Apr;68(2-3):285-94

4- Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M. Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine. Am J Psychiatry. 1984 Dec;141(12):1614-6

5- Prange AJ Jr. Novel uses of thyroid hormones in patients with affective disorders. Thyroid. 1996 Oct;6(5):537-43

6- Birkenhager TK, Vegt M, Nolen WA. An open study of triiodothyronine augmentation of tricyclic antidepressants in inpatients with refractory depression. Pharmacopsychiatry. 1997 Jan;30(1):23-6

7- Joffe RT, Singer W, Levitt AJ, MacDonald C. A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry. 1993 May;50(5):387-93

8- Altshuler LL, Bauer M, Frye MA, Gitlin MJ, Mintz J, Szuba MP, Leight KL, Whybrow PC. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001 Oct;158(10):1617-22

Depressão: A Associação Com Baixos Níveis de Cortisol

1- Rocco A, Martocchia A, Frugoni P, Baldini R, Sani G, Di Simone Di Giuseppe B, Vairano A, Girardi P, Monaco E, Tatarelli R, Falaschi P. Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders. Neuro Endocrinol Lett. 2007 Oct;28(5):610-3

2- Mutsuura H, Kanbara K, Fukunaga M, Yamamoto K, Ban I, Kitamura K, Nakai Y. Depression and anxiety correlate differently with salivary free cortisol in the morning in patients with functional somatic syndrome. Appl Psychophysiol Biofeedback. 2009 Dec;34(4):291-8 (“depressive scores showed a significant negative correlation with salivary free cortisol in the morning in patients”)

3- Stetler C, Miller GE. Blunted cortisol response to awakening in mild to moderate depression: regulatory influences of sleep patterns and social contacts. J Abnorm Psychol. 2005 Nov;114(4):697-705 (“Blunted cortisol response to awakening in women with mild to moderate depression”)

Depressão: A Associação Com Baixos Níveis de DHEA

1- Arlt W, Callies F, van Vlijmen JC, Koehler I, Reincke M, Bidlingmaier M, Huebler D, Oettel M, Ernst M, Schulte HM, Allolio B. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999;341(14):1013-20

2- Johannsson G, Burman P, Wiren L, Engstrom BE, Nilsson AG, Ottosson M, Jonsson B, Bengtsson BA, Karlsson FA Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab. 2002 May;87(5):2046-52

3- Nagata C, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K. Serum concentrations of estradiol and dehydroepiandrosterone sulfate and soy product intake in relation to psychologic well-being in peri- and postmenopausal Japanese women. Metabolism. 2000;49(12):1561-4

4- Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C, Cummings S. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry. 1998;43(9):694-700

5- Goodyer IM, Herbert J, Altham PM, Pearson J, Secher SM, Shiers HM. Adrenal secretion during major depression in 8- to 16-year-olds. I. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation. Psychol Med. 1996;26(2):245-56

6- Buckwalter JG, Stanczyk FZ, McCleary CA, Bluestein BW, Buckwalter DK, Rankin KP, Chang L, Goodwin TM. Pregnancy, the postpartum, and steroid hormones: effects on cognition and mood. Psychoneuroendocrinology. 1999;24(1):69-84

7- Heinz A, Weingartner H, George D, Hommer D, Wolkowitz OM, Linnoila M. Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations. Psychiatry Res. 199920;89(2):97-106

8- Berr C, Lafont S, Debuire B, Dartigues JF, Baulieu EE. Dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study. Proc Natl Acad Sci USA. 1996;93(23):13410-5

9- Barrett-Connor E, von Muhlen D, Laughlin GA, Kripke A. Endogenous levels of dehydroepiandrosterone sulfate, but not other sex hormones, are associated with depressed mood in older women: the Rancho Bernardo Study. J Am Geriatr Soc. 1999;47(6):685-91

10- Goodyer IM, Herbert J, Altham PM. Adrenal steroid secretion and major depression in 8- to 16-year-olds, III. Influence of cortisol/DHEA ratio at presentation on subsequent rates of disappointing life events and persistent major depression. Psychol Med. 1998;28(2):265-73

11- Herbert J. Neurosteroids, brain damage, and mental illness. Exp Gerontol. 1998;33(7-8):713-27

12- Fava M, Littman A, Lamon-Fava S, Milani R, Shera D, MacLaughlin R, Cassem E,Leaf A, Marchio B, Bolognesi E, et al. Psychological, behavioral and biochemical risk factors for coronary artery disease among American and Italian male corporate managers. Am J Cardiol. 1992 Dec 1;70(18):1412-6

Depressão: A Melhora Com a Reposição de DHEA

1- Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology (Berl). 2006 Nov;188(4):541-51

2- Stomati M, Rubino S, Spinetti A, Parrini D, luisi S, Casarosa E, Petraglia F, Gennazzani AR. E Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women. Gynecol Endocrinol. 1999;13(1):15-25

Depressão: A Melhora Com a Reposição de Estradiol

1- Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS. Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life. Menopause. 2006 Sep-Oct;13(5):780-6

2- Carranza-Lira S, Valentino-Figueroa ML. Estrogen therapy for depression in postmenopausal women. Int J Gynaecol Obstet. 1999 Apr;65(1):35-8

3- Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol. 1991 Dec;78(6):991-5

4- Lawrie TA, Herxheimer A, Dalton K. Oestrogens and progestogens for preventing and treating postnatal depression. Cochrane Database Syst Rev. 2000;(2):CD001690

5- Rudolph I, Palombo-Kinne E, Kirsch B, Mellinger U, Breitbarth H, Graser T. Influence of a continuous combined HRT (2 mg estradiol valerate and 2 mg dienogest) on postmenopausal depression. Climacteric. 2004 Sep;7(3):301-11

6- Rasgon NL, Altshuler LL, Fairbanks LA, Dunkin JJ, Davtyan C, Elman S, Rapkin AJ. Estrogen replacement therapy in the treatment of major depressive disorder in perimenopausal women. J Clin Psychiatry. 2002;63 Suppl 7:45-8

7- de Lignieres B, Vincens M. Differential effects of exogenous oestradiol and progesterone on mood in post-menopausal women: individual dose/effect relationship. Maturitas. 1982 Apr;4(1):67-72

8- Best NR, Rees MP, Barlow DH, Cowen PJ. Effect of estradiol implant on noradrenergic function and mood in menopausal subjects. Psychoneuroendocrinology. 1992;17(1):87-93

9- Brincat M, Magos A, Studd JW, Cardozo LD, O'Dowd T, Wardle PJ, Cooper D. Subcutaneous hormone implants for the control of climacteric symptoms. A prospective study. Lancet. 1984 Jan 7;1(8367):16-8

10- Sherwin BB, Gelfand MM. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study. Psychoneuroendocrinology. 1985;10(3):325-35

11- Gregoire AJ, Kumar R, Everitt B, Henderson AF, Studd JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet. 1996 Apr 6;347(9006):930-3

12- Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry. 2001 May;62(5):332-6

13- Nathorst-Boos J, von Schoultz B, Carlstrom K. Elective ovarian removal and estrogen replacement therapy--effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol. 1993 Dec;14(4):283-93

14- Soares CN, Almeida OP, Joffe H, Cohen LS. Arch Gen Psychiatry. 2001 Jun;58(6):529-34. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry. 2001 Jun;58(6):537-8.

Depressão: A Associação Com Baixos Níveis de Testosterona



1- Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable

testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999 Feb;84(2):573-7

2- Werner AA. The male climateric JAMA. 1946; 132 (4):188-94 3- Steiger A, von Bardeleben U, Wiedemann K, Holsboer F. Sleep EEG and

nocturnal secretion of testosterone and cortisol in patients with major endogenous depression during acute phase and after remission. J Psychiatr Res. 1991;25(4):169-77

4- 3Unden F, Ljunggren JG, Beck-Friis J, Kjellman BF, Wetterberg L. Hypothalamic-pituitary-gonadal axis in major depressive disorders. Acta Psychiatr Scand 1988 Aug;78(2):138-46

5- Shores MM, MD; Sloan KL, Matsumoto AM, Moceri VM, Felker B, Kivlahan D. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry. 2004;61:162-7

6- Grinspoon S, Corcoran C, Stanley T, Baaj A, Basgoz N, Klibanski A. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab. 2000 Jan;85(1):60-5

Depressão: A Melhora Com a Reposição de Testosterona

1- Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry. 2003 Jan;160(1):105-11

2- Wagner GJ, Rabkin R. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry. 2000 Feb;57(2):141-7

3- Grinspoon S, Corcoran C, Stanley T, Baaj A, Basgoz N, Klibanski A. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab. 2000 Jan;85(1):60-5

4- Schmitz G. Erfahrungen mit dem neuen synthetischen testes-hormon-preparat "Perandren." Deutsche Medizinische Wochenschrift. 1937; 63:230–1

5- Davidoff E, Goodstone GL. Use of testosterone propionate in treatment of involutional psychosis in the male. Arch Neurol Psychiatry. 1942; 48:811–7

6- Altschule MD, Tillotson KJ. The use of testosterone in the treatment of depression. N Engl J Med. 1948; 239:1036–8

7- Lamar CP. Clinical endrocrinology of the male: with special reference to the male climacteric. J Fla Med Assoc. 1940; 26:398–404

8- O'Carroll R, Shapiro C, Bancroft J. Androgens, behavior and nocturnal erection in hypogonadal men: the effects of varying the replacement dose. Clin Endocrinol. 1985; 23:527–538

9- Skakkebaek NE, Bancroft J, Davidson DW, Warner P. Androgen replacement with oral testosterone undeconoate in hypogonadal men: a double-blind controlled study. Clin Endocrinol. 1981; 14:49–61

10- Rabkin JG, Rabkin R, Wagner G: Testosterone replacement therapy in HIV illness. Gen Hosp Psychiatry 1995;17:37–47

11- Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, Channer KS. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart. 2004 Aug;90(8):871-6.

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