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SOBRAF

DIRETRIZES PARA A UTILIZAO DE HORMNIOS


HOMLOGOS HUMANOS POR MLTIPLAS
ESPECIALIDADES MDICAS NA PRTICA CLNICA
A- INTRODUO:
As diretrizes aqui elencadas representam a posio oficial da Sociedade
Brasileira Para Estudos da Fisiologia SOBRAF - com relao ao uso de
hormnios homlogos humanos por mltiplas especialidades mdicas na prtica
clnica, e esto fundamentadas no Projeto Diretrizes, iniciativa conjunta da
Associao Mdica Brasileira e Conselho Federal de Medicina, que tem por
objetivo conciliar informaes da rea mdica a fim de padronizar condutas que
auxiliem o raciocnio e a tomada de deciso do mdico.
As informaes contidas neste documento devem ser submetidas avaliao e
crtica do mdico, responsvel pela conduta a ser seguida, frente realidade e ao
estado clnico de cada paciente.
B- DESCRIO DO MTODO DE COLETA DE EVIDNCIA:
A reviso bibliogrfica de artigos cientficos destas diretrizes foi realizada na
base de dados MEDLINE.
A busca de evidncias partiu de cenrios clnicos 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 alzheimers disease AND cancer risk AND cancer prevention
AND low hormone levels .
C- GRAU DE RECOMENDAO E FORA DE EVIDNCIA:
A: Estudos experimentais e observacionais de melhor consistncia.

B: Estudos experimentais e observacionais de menor consistncia.


C: Relatos de casos (estudos no controlados).
D: Opinio desprovida de avaliao crtica, baseada em consensos, estudos
fisiolgicos ou modelos animais.
D- OBJETIVOS:
Estabelecer a definio, interferncias do uso de hormnios no metabolismo
lipoproteico, na vida sexual, na baixa densidade mineral ssea, nas mamas, na
reduo do percentual de gordura corporal, na reduo dos riscos de
hipertenso arterial sistmica, na reduo dos riscos de diabetes, na reduo do
risco de demncia de Alzheimer, na melhora da massa muscular, na promoo
de bem estar fsico e mental, na reduo dos riscos de doenas, na melhora da
qualidade de vida, na preveno das perdas funcionais da velhice, na melhora da
capacidade laboral, fsica e funcional, na melhora da libido, na melhora da
qualidade do sono, na melhora da depresso, na melhora da ansiedade, na
melhora do estresse, na atenuao da formao de espcies oxignio-reativas, na
reduo do estresse oxidativo celular, na preservao da integridade celular, na
preservao da integridade mitocondrial, na otimizao metablica, na
otimizao imunolgica, na reduo e ou reverso da placa ateromatosa, na
reduo do risco cardiovascular, na preveno de doenas crnicas, na
preveno do cncer, na reduo do risco de cncer e na promoo de um
envelhecimento saudvel e determinar as indicaes da teraputica hormonal
baseadas nas melhores evidncias atuais.
E- CONFLITO DE INTERESSE:
Nenhum conflito de interesse declarado.

1. MENOPAUSA
a. Quadro clnico
i. Amenorria secundria em mulheres com mais de 35 anos
ou amenorria secundria em mulheres, por perodo
superior a seis meses;
ii. Fogachos, sudorese noturna, insnia, labilidade emocional,
secura vaginal, dispareunia, declnio cognitivo, fragilidade
imunolgica, ressecamento da pele, queda de cabelos,
aumento do peso total, aumento do percentual de gordura,

perda de massa magra, perda de massa ssea, reduo da


libido e comprometimento da qualidade de vida.

b.

Quadro Laboratorial
i. FSH > 15 u/L
ii. LH > 8 u/L

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da menopausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de menopausa ser confirmado
tomando-se como referncia as manifestaes e o quadro
clnico apresentados pelo paciente e devidamente avaliados
e registrados pelo mdico. Tal conduta se justifica pela
baixa acurcia dos mtodos de diagnstico laboratorial das
deficincias hormonais, falhas de tcnicas intrnsecas aos
mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a menopausa, a SOBRAF recomenda que seus mdicos associados
utilizem-se do termo de consentimento padro adotado pela
mesma e que dever ser devidamente assinado pelo mdico e pelo
seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA MENOPAUSA

i. Aps criteriosa reviso da literatura cientfica, discusses


com mdicos representantes de todos os continentes e
discusses entre mdicos brasileiros, todos profissionais
versados e adequadamente qualificados em utilizar e
prescrever hormnios em seres humanos com a
finalidade primria de promoo da sade e, ainda, em
total consonncia 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, ns, mdicos membros da SOBRAF,


conclumos haver chegado o momento de reconsiderar os
conceitos atualmente vigentes acerca da reposio
hormonal na menopausa.
A presente controvrsia acerca da reposio hormonal na
menopausa, teve incio aps a publicao dos resultados
do chamado estudo WHI ( Womens Health Iniciative ),
publicado em 2002, bem como do British One Million
Women Study, publicado em 2003. Em ambos os estudos,
o uso de hormnios em mulheres na ps-menopausa foi
associado a uma maior incidncia de cncer de mama,
quando comparadas ao grupo placebo-controle ou ao de
no usurias. No estudo WHI, o uso de hormnios em
mulheres foi associado a um aumento no risco de doenas
cardiovasculares e cerebrovasculares. Para os mdicos
membros da SOBRAF, ambos os estudos apresentam,
dentre outras, duas falhas graves de desenho que
consistem, respectivamente, em primeiro lugar: estas
mulheres estavam utilizando estrognios conjugados de
urina equina. Consiste em um coquetel de 38 hormnios
obtidos da urina de guas prenhes, portanto, um dejeto
animal, sendo que nenhum destes hormnios existe em
seres humanos ou produzido pelos mesmos, tendo,
portanto, propriedades farmacolgicas e comportamento
completamente distintos do 17-beta-estradiol, hormnio
que deixa de ser produzido por mulheres na fase psmenopausal. Em segundo lugar, esta combinao, foi
associado o acetato de medroxiprogesterona, molcula
que consiste em um progestognio sinttico, igualmente
no existente em seres humanos, e, consequentemente,
substncia com propriedades qumicas e fisiolgicas
diferentes da progesterona humana.
Revisando
cuidadosamente a literatura cientfica existente,
possvel encontrar vrios outros estudos que
demonstram, de maneira inquestionvel, a potencial
toxicidade e os riscos inerentes ao uso destas substncias.
De acordo com as recentes recomendaes de um grupo
cada vez maior de sociedades mdicas ao redor de todo o
mundo, ns, igualmente, no recomendamos o uso de
hormnios no-homlogos humanos a reposio
hormonal da menopausa. Em contraste com as
recomendaes de algumas sociedades, que no
recomendam a reposio hormonal na menopausa, ou
ainda, algumas outras que a recomendam por um perodo
limitado a cinco anos, no mximo, ns recomendamos o
uso de hormnios em mulheres antes e aps a
menopausa, por tanto tempo quanto se fizer necessrio,
desde que as indicaes e as necessidades clnicas

justifiquem e que nenhum evento adverso ocorra que


contraindique o seu uso.
Contudo, ns recomendamos o uso da combinao de
estradiol e estriol homlogos humanos, associados
progesterona homloga humana para a correo da
deficincia ovariana da menopausa, exceto para casos
especficos e bem pontuais e por um perodo de tempo
limitado, aonde o uso de hormnios no-homlogos
humanos possa apresentar resultados clnicos melhores,
com o caso de algumas metrorragias e sangramentos da
perimenopausa. A via de administrao , , igualmente,
parmetro de considervel importncia. A via
transdrmica, , sem dvida bem mais segura e fisiolgica
do que a via oral. Esta via no oferece risco de elevao
do cncer de mama, e, quando se associa progesterona
homloga humana reposio de estradiol e estriol,
vrios estudos, na verdade, demonstram uma clara
reduo dos riscos para aquela patologia.
A mulher que teve cncer de mama, pode fazer reposio
hormonal? A tendncia observada na atualidade de se
evitar a administrao de hormnios em mulheres que
tiveram cncer de mama. Esta observao pode no se
justificar nas mulheres em que a leso foi removida
cirurgicamente de
forma completa. Revendo
cuidadosamente todos os estudos cientficos atuais que
envolvem mulheres que tiveram cncer de mama e
receberam reposio hormonal na menopausa, nenhum
risco de recorrncia foi reportado ou identificado. Ao
contrrio, a reposio hormonal na menopausa est
associada a uma notria reduo do risco de recorrncia
do cncer, bem como uma clara diminuio das taxas
gerais de mortalidade na maioria dos estudos. Mesmo a
despeito de fartas evidncias em contrrio, ainda muito
cedo para recomendar-se a reposio hormonal para
mulheres em menopausa portadoras de cncer de mama.
Ns recomendamos que estudos em larga escala placebocontrole sejam efetivados com a finalidade de identificar
com a maior clareza possvel, em quais mulheres que
tiveram cncer de mama a terapia de reposio hormonal
da menopausa estaria mais indicada.
Ns recomendamos aos mdicos que fazem a reposio
hormonal da menopausa, que submetam suas clientes
propedutica e monitorao mamria peridicos, antes e
durante o perodo de durao da reposio, obedecendo
aos intervalos regulares preconizados e consensuados,
consistindo de inspeo, palpao e mamografia de alta
resoluo,
acompanhada
de
ultrassonografia
complementar de alta resoluo. Importante, igualmente,
ressaltar a necessidade de vigilncia peridica do

endomtrio, atravs de monitoramento ultrassonogrfico


transvaginal.
CONCLUSO DO CONSENSO:
Tendo em vista as enormes repercusses biopsicossociais
da menopausa e os crescentes e exorbitantes gastos para
o tratamento e controle das doenas chamadas
inevitveis da velhice, ns recomendamos aos mdicos
estimularem a reposio hormonal da menopausa,
sempre observando os bons preceitos da prtica mdica e
utilizando-se de hormnios homlogos humanos,
preferencialmente administrados pela via transdrmica,
no caso da associao estradiol-estriol, e, no caso da
progesterona, via transdrmica ou transvaginal. Para os
casos anteriores, a via oral tambm pode ser uma
alternativa, desde que os hormnios administrados sejam,
igualmente, homlogos humanos.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.
6.
7.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

2. ANDROPAUSA
a. Quadro clnico

i. Cansao, reduo da libido e do desempenho sexual,


reduo da fora muscular, adinamia, fragilidade
imunolgica, ginecomastia, reduo da capacidade fsica,
ressecamento da pele, dficit de memria, averso ao
convvio social, aumento da circunferncia abdominal,
queda de cabelos, aumento do percentual de gordura
corporal, alteraes do sono, alteraes do humor, perda
de massa ssea, e comprometimento da qualidade de vida.

b.

Quadro Laboratorial
i.
ii.
iii.
iv.
v.

FSH > 5 u/L


LH > 8 u/L
Testosterona Total < 700 ng/dL
ndice de Andrognio Livre < 0,7
Testosterona livre < 2%

vi. Testosterona biodisponvel < 400 ng/dL

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da andropausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de andropausa ser confirmado
tomando-se como referncia as manifestaes e o quadro
clnico apresentados pelo paciente e devidamente avaliados
e registrados pelo mdico. Tal conduta se justifica pela
baixa acurcia dos mtodos de diagnstico laboratorial das
deficincias hormonais, falhas de tcnicas intrnsecas aos
mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a andropausa, a SOBRAF recomenda que seus mdicos associados
utilizem-se do termo de consentimento padro adotado pela
mesma e que dever ser devidamente assinado pelo mdico e pelo
seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA ANDROPAUSA
Aps criteriosa reviso da literatura cientfica, discusses com
mdicos representantes de todos os continentes e discusses
entre mdicos brasileiros, todos profissionais versados e
adequadamente qualificados em utilizar e prescrever
hormnios em seres humanos com a finalidade primria de
promoo da sade e, ainda, em total consonncia 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, ns,
mdicos membros da SOBRAF, conclumos haver chegado o
momento de considerar a deficincia hormonal masculina, e o

conseqente
andropausa.

tratamento

de

reposio

hormonal

da

Desde que a estrutura qumica da testosterona e a tcnica de


obt-la de forma sinttica foram descobertos na dcada de 30,
um grande nmero de estudos tm demonstrado, de forma
indubitvel, ser a testosterona um hormnio indispensvel
para a manuteno de um estado timo de sade na populao
masculina. Na medida em que os homens envelhecem, as
fraes biodisponveis da testosterona e de outros andrognios
declinam crnica e cumulativamente. O declnio gradual da
testosterona biodisponvel responde por uma vasta e
multivariada gama de sinais e sintomas, tais como fadiga,
depresso, mudanas 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 imunolgica,
ginecomastia, perda de massa ssea e muitas outras
manifestaes que so, invariavelmente, atribudas a achados
normais da idade. A persistncia da deficincia hormonal
masculina pode aumentar os riscos das comorbidades
associadas ao envelhecimento, tais como obesidade, depresso,
diabetes, osteoporose e doenas cardiovasculares. Embora o
declnio hormonal no afete de maneira to 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 sade e, muito provavelmente, a sua
prpria expectativa de vida. O declnio andrognico masculino
recebe uma vasta sinonmia: distrbio andrognico do
envelhecimento masculino (DAEM ), andropausa, climatrio
masculino, menopausa masculina, partial androgen deficiency
in aging men ( PADAM ), hipogonadismo relacionado idade,
penopausa, dentre outros tantos.
A quantidade de homens que recebe ateno e tratamento no
transcurso da deficincia hormonal incomparavelmente
menor do que a quantidade de mulheres que recebe reposio
e tratamento na menopausa. Isto se deve, principalmente, ao
fato de que, ao contrrio do declnio feminino, o declnio
hormonal masculino ainda no um fato plenamente aceito
por boa parte da medicina tradicional. Com base na fisiologia
do envelhecimento hormonal, ns acreditamos no haver
qualquer justificativa vlida para tal discriminao.
Os oponentes da reposio hormonal da andropausa amparamse em estudos conflitantes e com srios erros de desenho
existentes na literatura, que demonstram diferenas no
significativas entre os nveis sricos hormonais de homens
jovens e homens velhos, outros sugerem que a testosterona
pode aumentar a incidncia de cncer de prstata, enquanto
outros sugerem que a reposio de testosterona no apresenta

efeitos clnicos significativos. Estes estudos atpicos so


fartamente contrapostos por um imenso nmero de estudos
que so claros e unnimes em demonstrar exatamente o
oposto, destacando-se, principalmente, um indubitvel efeito
protetor da testosterona contra o cncer de prstata.
Uma reviso global da literatura corrente no consegue
fornecer qualquer evidncia de que a reposio com
testosterona ou seus derivados possa aumentar os riscos de
cncer de prstata in vivo. Ao contrrio, homens com baixos
nveis de testosterona biodisponvel so exatamente os que
apresentam no s os maiores riscos de cncer de prstata,
como a ocorrncia de tumores de comportamento muito mais
agressivo, aumento do processo de deposio aterosclertica
das artrias e piora gradual e cumulativa da qualidade de
sade. Alm do mais, pacientes portadores de cncer de
prstata que tm os seus nveis circulantes de testosterona
drasticamente reduzidos por conta das terapias antiandrognicas, no apresentam qualquer aumento ou melhora
da sobrevivncia.
Com a finalidade de detectar com o maior grau de preciso
possvel a deficincia hormonal masculina, ns recomendamos
no somente uma detalhada avaliao clnica, levando-se em
conta os sinais e sintomas fsicos e mentais sugestivos do
declnio masculino, como a realizao de testes laboratoriais
que auxiliem e quantifiquem o diagnstico, dentre os quais:
dosagem da testosterona total, testosterona livre, SHBG,
proteinograma, DHT, testosterona biodisponvel, FSH, LH, e o
ndice de andrognio livre. Igualmente importante avaliar os
nveis sricos de estradiol, uma vez que a elevao destes
nveis pode provocar um bloqueio da ao da testosterona nos
homens.
Levando-se em considerao o enorme impacto para a sade
masculina oriundo da queda de testosterona, ns
recomendamos aos mdicos que estimulem o tratamento desta
deficincia para todos os casos, utilizando-se da testosterona
homloga humana ou de seus derivados quimicamente mais
semelhantes possveis, excetuando-se alguma contraindicao
absoluta. Todos os homens que avanam na idade, devem
expectar, cedo ou tarde, declnio dos seus nveis timos de
testosterona, sendo, portanto, potenciais candidatos terapia
de reposio. A maioria dos homens ir experimentar declnio
entre os 30 e 45 anos de idade. Vale, entretanto, salientar, que
excees a esta regra podem ocorrer, fazendo com que alguns
homens venham a necessitar da reposio hormonal abaixo ou
acima daquela faixa etria.
Somente doses fisiolgicas de testosterona devem ser
administradas, objetivando-se manter os nveis sricos
comparveis ao de adultos jovens e saudveis, na faixa etria
dos 25 a 30 anos.

As melhores vias de administrao para este hormnio so a


transdrmica e a intramuscular.
Nveis excessivos de estradiol devem ser evitados durante o
tratamento de reposio com testosterona, por conta do efeito
biolgico neutralizador e alm de responder pela ocorrncia de
ginecomastia, hipertrofia prosttica benigna e, possivelmente
infarto agudo do miocrdio. Ajustes no padro alimentar, evitar
lcool e cafena, alm da prtica regular de atividade fsica so
importantes medidas de suporte para reduo dos nveis
excessivos de estradiol. Evitar a obesidade um ponto
importantssimo neste contexto, uma vez que o tecido adiposo
rico em aromatase, enzima que catalisa a transformao de
testosterona em estradiol. Quando estas medidas no surtirem
o efeito desejado, o uso de inibidores da aromatase ou de
pequenas doses de progesterona podem estar indicados. A
progesterona aumenta a transformao de estradiol em
estrona, diminuindo, portanto, as suas concentraes sricas.
O cncer de prstata em atividade pode ser considerado como
uma contraindicao para o uso de testosterona. Contudo, ao se
rever cuidadosamente a literatura atual, parece haver uma
inconsistente base de evidncias para dar suporte a esta
afirmao. Muitos estudos, ao contrrio, demonstram que
portadores de cncer de prstata que tambm possuem
deficincia hormonal masculina tm a sua qualidade de sade
severamente comprometida e podem ser beneficiados com a
reposio de doses pequenas de testosterona, trazendo
benefcios suplementares que em muito superam qualquer
suposto risco de estimulo ao crescimento tumoral.
CONCLUSO DO CONSENSO:
Ns no conseguimos identificar na literatura atual qualquer
evidncia de que repor doses fisiolgicas de testosterona
deponha contra ou traga riscos sade de homens portadores
de declnio nos nveis daquele hormnio. Ao contrrio. Uma vez
que so mltiplos e multivariados os benefcios advindos da
reposio hormonal masculina, ns recomendamos o uso de
doses fisiolgicas de testosterona ou de seu derivado qumico
mais prximo possvel, com o intuito de corrigir esta
deficincia, submetendo este homem em reposio a um
programa de acompanhamento clnico peridico e regular.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1. Professora Doutora Ana Cristina Vendramini, PhD
2. Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
3. Professora Doutora Andrea Thomaz Soccol, PhD

4.
5.
6.
7.

Professor Doutor Eduardo Faria, PhD


Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

3. SOMATOPAUSA
a. Quadro clnico

i. Deteriorao da composio corporal, reduo da massa


muscular, aumento do percentual de gordura corporal
total, aumento do percentual de gordura visceral, cansao,
reduo do desempenho sexual, reduo da fora muscular,
adinamia, fragilidade imunolgica, reduo da capacidade
fsica, ressecamento e enrugamento da pele, dficit de
memria, baixa autoestima, alteraes do sono, alteraes
do humor, perda de massa ssea, 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

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da somatopausa. Por outro
lado, nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de somatopausa ser
confirmado tomando-se como referncia as manifestaes e
o quadro clnico apresentados pelo paciente e devidamente
avaliados e registrados pelo mdico. Tal conduta se justifica
pela baixa acurcia dos mtodos de diagnstico laboratorial
das deficincias hormonais, falhas de tcnicas intrnsecas
aos mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.

d. No momento da instituio da proposta teraputica hormonal para


a somatopausa, a SOBRAF recomenda que seus mdicos
associados utilizem-se do termo de consentimento padro adotado
pela mesma e que dever ser devidamente assinado pelo mdico e
pelo seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA SOMATOPAUSA
Aps criteriosa reviso da literatura cientfica, discusses
com mdicos representantes de todos os continentes e
discusses entre mdicos brasileiros, todos profissionais
versados e adequadamente qualificados em utilizar e
prescrever hormnios em seres humanos com a finalidade
primria de promoo da sade e, ainda, em total
consonncia com os preceitos e guidelines da Sociedade
Brasileira Para Estudos da Fisiologia SOBRAF, da
International Hormone Society e da World Society of AntiAging Medicine, ns, mdicos membros da SOBRAF,
conclumos haver chegado o momento de considerar a
reposio com o hormnio do crescimento humano
recombinante no s em adultos portadores de patologias
que impeam ou dificultem a sua produo, como nos
adultos que esto envelhecendo e decaindo a sua
capacidade inata de sntese endgena. Ns concordamos e
aprovamos os consensos j estabelecidos e consagrados em
muitos pases, que aconselham a reposio com o hormnio
do crescimento humano recombinante em adultos
portadores de patologias que impeam ou dificultem a sua
produo. Nestas situaes, existe histria pregressa de
remoo, trauma, radiao, tumores ou severa inativao
da hipfise, fatos que impedem a produo endgena do
hormnio do crescimento.
Pensamos j haver na literatura cientfica atual uma base
suficiente de dados que demonstram e confirmam os
mltiplos benefcios e segurana do uso clnico do
hormnio do crescimento. Desta forma, tornou-se uma
necessidade mdica estendermos a indicao de reposio
tambm aos adultos que esto envelhecendo e decaindo a
sua capacidade inata de sntese endgena, por conta da
progressiva reduo funcional, consequente ao processo de
envelhecimento.
A evidncia de que o hormnio do crescimento essencial
no apenas para o crescimento de crianas, mas tambm
essencial para a sade fsica e mental de adultos,

particularmente na manuteno da integridade dos


sistemas muscular, adiposo, sseo, imunolgico e
cardiovascular. A deficincia do hormnio do crescimento
frequentemente acompanhada de fadiga, ansiedade e
depresso, alm de um progressivo e cumulativo
comprometimento da qualidade de vida. Por outro lado, a
reposio com o hormnio do crescimento nestes casos tem
demonstrado ser capaz de promover a parada e, por muitas
vezes reverso da progresso de todos aqueles processos.
A falta da reposio do hormnio do crescimento nos
adultos que esto envelhecendo e decaindo a sua
capacidade inata de sntese endgena, ao contrrio do que
se imagina, pode trazer consequncias verdadeiramente
desastrosas. Aumento considervel da velocidade de
deposio da placa ateromatosa, aumento das taxas de
mortalidade cardiovascular, deteriorao da composio
corporal atravs da perda de massa muscular e
concomitante aumento da deposio de gordura corporal
total e gordura intra-abdominal, fragilidade imunolgica,
perda de massa ssea, depresso, distrbios progressivos
do sono e reduo da sntese de protenas so, dentre
outros, alguns dos fenmenos que se sucedem ao declnio
da capacidade de manuteno da sntese de nveis
fisiolgicos do hormnio do crescimento, e que so parcial
ou totalmente reversveis atravs da reposio do mesmo.
Ns recomendamos aos mdicos submeterem os clientes
em uso do hormnio do crescimento a um regime de
avaliaes regulares e aprazados. Isto inclui: anamnese,
exame fsico e exames laboratoriais complementares
obedecendo a um intervalo de um a doze meses,
dependendo da necessidade individual de cada cliente.
Em relao a um eventual aumento no risco de
desenvolvimento de certos tipos de cncer com o uso do
hormnio do crescimento, os estudos mais srios e
respeitados realizados em pacientes que receberam o
hormnio, comparados ao grupo controle de indivduos
no-tratados,
mostram
uma
clara
reduo
de
aproximadamente 50% na incidncia de cncer e na
mortalidade por cncer no grupo de indivduos que
receberam o hormnio. Na realidade, inexiste qualquer
argumento consistente ou fundamentao razovel para se
acreditar que repor o hormnio do crescimento possa
elevar o risco de cncer.
De qualquer forma, uma pesquisa de rotina a cada seis a 12
meses para o cncer de prstata e mama, complementadas

por ultrassom e mamografia quando necessrio, constitui


conduta essencial, segundo este grupo de consenso. Alm
do mais, ns tambm recomendamos que o tratamento de
reposio seja programado de modo a se respeitar as doses
fisiolgicas preconizadas. Em casos clnicos muito
especficos e pontuais, como, por exemplo, os grandes
obesos e indivduos com grande superfcie corporal, pode
ser justificvel o uso de doses maiores, que devero ser
mantida por perodo de tempo no superior a 90 dias.
Doses acima dos limites fisiolgicos no so recomendadas
por esta sociedade e fogem t ao escopo deste protocolo de
consenso.
Desta forma e seguindo estes princpios, o mdico estar
assegurando no s a eficcia como a segurana do
tratamento.
CONCLUSO DO CONSENSO:
Na atualidade inexiste qualquer base cientfica de dados
que contraindique a reposio do hormnio do crescimento
humano recombinante em adultos que esto envelhecendo
e decaindo a sua capacidade inata de sntese endgena. Ao
contrrio, uma multiplicidade de sinais, sintomas e
problemas adversos e deletrios sade humana tem sido
abundantemente reportada em indivduos portadores de
nveis endgenos infra fisiolgicos do hormnio do
crescimento, bem como tem sido fartamente reportada
melhora, desaparecimento ou mesmo reverso dos
problemas aludidos ao se promover a adequada reposio
do mesmo.
Ressaltamos, mais uma vez, a importncia de se observar as
doses fisiolgicas do hormnio, bem como a realizao de
avaliaes clnico-laboratoriais peridicas.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.
6.
7.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

4. TIREOPAUSA
a. Quadro clnico

i. Deteriorao da composio corporal, reduo da massa


muscular, aumento do percentual de gordura corporal
total, aumento do percentual de gordura visceral, cansao,
depresso marcadamente matinal, apatia, incapacidade de
concentrao, dificuldade de perder peso, unhas fracas,
queda de cabelos, dislipidemia, hipercolesterolemia,
ateromatose precoce, intolerncia ao frio, adinamia,
fragilidade imunolgica, constipao, reduo da
capacidade fsica, zumbidos, ressecamento e enrugamento
da pele, dficit de memria, alteraes do sono, alteraes
do humor, e comprometimento da qualidade de vida.

b.

Quadro Laboratorial
i.
ii.
iii.
iv.

c.

TSH ultrassensvel > 2,0 pg/mL


T3 livre < 0,37 ng/dL
T4 livre < 0,7 ng/mL
Mdia da Temperatura Basal < 36,5o C em cinco aferies
matinais consecutivas.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da tireopausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de somatopausa ser
confirmado tomando-se como referncia as manifestaes e
o quadro clnico apresentados pelo paciente e devidamente
avaliados e registrados pelo mdico. Tal conduta se justifica
pela baixa acurcia dos mtodos de diagnstico laboratorial
das deficincias hormonais, falhas de tcnicas intrnsecas
aos mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.

d. No momento da instituio da proposta teraputica hormonal para


a tireopausa, a SOBRAF recomenda que seus mdicos associados
utilizem-se do termo de consentimento padro adotado pela
mesma e que dever ser devidamente assinado pelo mdico e pelo
seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA TIREOPAUSA
Aps criteriosa reviso da literatura cientfica, discusses
com mdicos representantes de todos os continentes e
discusses entre mdicos brasileiros, todos profissionais
versados e adequadamente qualificados em utilizar e
prescrever hormnios em seres humanos com a finalidade
primria de promoo da sade e, ainda, em total
consonncia com os preceitos e guidelines da Sociedade
Brasileira Para Estudos da Fisiologia SOBRAF, da
International Hormone Society e da World Society of AntiAging Medicine, ns, mdicos membros da SOBRAF,
conclumos existir um slido conjunto de evidncias de
ordem clnica, prtica e terica que j permitem expandir o
tratamento do hipotireoidismo alm dos parmetros
correntes convencionais.
Existe, na atualidade, uma controvrsia entre grupos de
mdicos. Um grupo essencialmente define o diagnstico do
hipotireoidismo baseado em testes de laboratrio,
enquanto o outro toma como base parmetro
essencialmente clnicos. Uma slida base de evidncias
cientficas no d suporte ideia de que o diagnstico do
hipotireoidismo deva ou possa ser baseado apenas em
testes laboratoriais. Isto implica em que a existncia do
hipotireoidismo s se confirma quando os nveis sricos de
TSH encontram-se acima dos limites superiores atuais de
referncia, e os nveis sricos de tiroxina (T4) e
triiodotireonina (T4), encontram-se abaixo dos limites
inferiores atuais de referncia, negligenciando os sinais e
sintomas clnicos.
Esta sociedade adota a posio intermediria. A deciso de
iniciar a reposio com o hormnio tireoidiano deve ser
baseada tanto em achados clnicos quanto laboratoriais, e
no 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 informaes clnicas so


essenciais no diagnstico de deficincias hormonais. Os
dados necessrios ao diagnstico do hipotireoidismo
incluem a pesquisa das queixas fsicas e emocionais dos
pacientes, sinais fsicos e coleta de histria pregressa
pessoal e familiar sugestivas de deficincia tireoidiana, bem
como eventuais anormalidades no volume glandular,
expressos pela presena de hipertrofia ou bcio e/ou
tireoidite autoimune.
As seguintes evidncias do suporte existncia de
hipotireoidismo clnico, em indivduos erroneamente
considerados laboratorialmente normais, e que so
candidatos ao tratamento de reposio hormonal
tireoidiana:
Os nveis de referencia da normalidade so excessivamente
largos e ignoram e existncia dos nveis timos de
referncia. Estes nveis incluem largas margens de
referncia de normalidade para os nveis de T3, T4 e TSH,
que so, na realidade, plenamente compatveis com
mltiplas disfunes tireoidianas. No existe qualquer
evidncia atual que d suporte persistncia do uso destes
parmetros, uma vez que so 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 nveis de
referencia incomparavelmente mais estreitos e especficos
para esta situao. Os nveis convencionais de referncia
para deteco do hipotireoidismo sofrem variao de mais
de 30 vezes ( 0.2 a 6.5 mUI/L ).
Em muitos estudos clnicos atuais, nveis sricos de TSH
acima de 1.5 a 2.0 mUI/L tem sido associados com
dislipidemia, inflamao crnica subclnica, nveis elevados
de homocistena, protena C reativa, hipercolesterolemia,
depresso, pobre resposta ao tratamento com
antidepressivos, maiores ndices de massa corprea, maior
incidncia de hipertenso arterial sistmica, elevao dos
triglicrides e hiperglicemia. Do mesmo modo, aqueles
nveis tem sido associados a anormalidades cardacas e
vasculares, que incluem ateromatose acelerada e perda da
elasticidade vascular. Neonatos com baixo peso e partos
prematuros tem sido relatados em mes 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 mltiplos estudos, existem


evidncias que do suporte a adoo de nveis 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 populao de indivduos saudveis e com a
atividade tireoidiana normal exibem nveis sricos de TSH
dentro do intervalo de 0.4 a 2.0 mUI/L.
Um outro ponto de capital importncia, que os estudos
demonstram resultados clnicos incomparavelmente
superiores quando se utiliza no tratamento a associao
entre T3 e T4, ao invs do tratamento isolado com T4. Isto
se deve ao fato de que uma boa parte do T4 administrado
isoladamente, sofre converso para T3 reverso, forma
hormonal inativa biologicamente. Alm do mais, para que o
estado de eutireoidismo seja alcanado, o organismo
humano necessita de ambos os hormnios, T4, que tem a
finalidade principal de atrair molculas de TBG ( thyroid
binding globulin ) e T3, que, livre do atrelamento da TBG,
pode ligar-se rapidamente aos receptores celulares do
hormnio tireoidiano nas clulas-alvo. A combinao
fisiolgica entre T3 e T4, obedecendo s propores de uma
parte de T3 para cinco partes de T4 , produz resultados
clnicos inequivocamente superiores.
Ns recomendamos aos mdicos que excluam
cuidadosamente outras patologias ou estados clnicos que
produzam sintomatologia semelhante ao hipotireoidismo
antes de iniciar a reposio do hormnio tireoidiano. Ao se
iniciar o tratamento, utilizar doses menores e programar
elevao gradual, de acordo com a necessidade clnica,
visando evitar a presena de superdosagem, e,
consequentemente,
um
possvel
quadro
de
hipertireoidismo iatrognico, efeito adverso mais frequente
no tratamento do hipotireoidismo.
Intolerncia ao
tratamento pode ser causada por excessiva converso de T4
em T3, acelerando, desta forma, a atividade tireoidiana.
Devemos lembrar que a principal causa deste problema a
deficincia no diagnosticada de outros hormnios,
principalmente a hipocortisolemia e a deficincia de
estradiol na menopausa. Os mdicos devem dedicar
especial ateno aos nveis de cortisol. A fadiga adrenal
crnica, que leva queda excessiva dos nveis de cortisol
provoca uma baixa tolerncia ao tratamento do
hipotireoidismo, principalmente quando a opo foi pela
combinao T4/T3. A deficincia de cortisol provoca

hiperatividade do sistema nervoso ortossimptico e uma


excessiva e rpida converso de T4 em T3. Desta forma, em
pacientes com fadiga adrenal crnica, ns recomendamos
que os mdicos tratem a deficincia de cortisol antes de
iniciarem o tratamento do hipotireoidismo ou, no mnimo,
de forma concomitante ao incio do mesmo. A segurana 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
necessrios.
CONCLUSO DO CONSENSO:
Hipotireoidismo clnico, em indivduos erroneamente
considerados laboratorialmente normais, constitui, sem
nenhuma dvida uma racional justificativa para se
promover a incluso destas pessoas no grupo de candidatos
ao tratamento com os hormnios tireoidianos. Estes
indivduos podem se beneficiar com um programa de
reposio com baixas dosagens, em que estejam associados
T4 e T3 em propores fisiolgicas. Avaliao clnica e
laboratorial aprazados, utilizando-se parmetros mais
estreitos para os nveis de referncia do TSH, alm de um
cuidadoso monitoramento individual de cada caso, so as
bases que conduzem a resultados clnicos favorveis.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.
6.
7.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

5. FADIGA ADRENAL CRNICA


a. Quadro clnico

i. Cansao marcadamente matinal, apatia, incapacidade de


concentrao,
adinamia,
fragilidade
imunolgica,
compulso massas e doces, irritabilidade, intolerncia ao

estresse, dficit de memria, alteraes do sono, alteraes


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

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da fadiga adrenal crnica. Por
outro lado, nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico da fadiga adrenal crnica ser
confirmado tomando-se como referncia as manifestaes e
o quadro clnico apresentados pelo paciente e devidamente
avaliados e registrados pelo mdico. Tal conduta se justifica
pela baixa acurcia dos mtodos de diagnstico laboratorial
das deficincias hormonais, falhas de tcnicas intrnsecas
aos mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a fadiga adrenal crnica, a SOBRAF recomenda que seus mdicos
associados utilizem-se do termo de consentimento padro adotado
pela mesma e que dever ser devidamente assinado pelo mdico e
pelo seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA FADIGA ADRENAL CRNICA
Aps criteriosa reviso da literatura cientfica, discusses
com mdicos representantes de todos os continentes e
discusses entre mdicos brasileiros, todos profissionais
versados e adequadamente qualificados em utilizar e
prescrever hormnios em seres humanos com a finalidade
primria de promoo da sade e, ainda, em total

consonncia com os preceitos e guidelines da Sociedade


Brasileira Para Estudos da Fisiologia SOBRAF, da
International Hormone Society e da World Society of AntiAging Medicine, ns, mdicos membros da SOBRAF,
conclumos ter chegado o momento de reconsiderar os
conceitos atualmente vigentes acerca do tratamento da
deficincia adrenal, em particular a deficincia de cortisol,
no apenas nas pessoas afetadas por severas deficincias,
mas tambm nos portadores de fadiga adrenal crnica.
Ns concordamos plenamente e aprovamos o consenso
mundial que foi atingido no que concerne ao tratamento
com glicocorticoides para adultos portadores de severa
deficincia de cortisol. Geralmente, naquela condio, existe
uma deficincia total ou quase total da produo de cortisol,
que ocorre por conta de remoo total ou parcial ou
inativao total ou parcial das glndulas adrenais, as
estruturas responsveis pela produo de cortisol.
Acreditamos que a quantidade de evidncias existentes na
atualidade demonstrando os efeitos benficos do cortisol,
bem como os seus eventuais efeitos adversos suficiente
para promover a extenso da recomendao da reposio
de cortisol tambm para os portadores da condio clnica
conhecida como fadiga adrenal crnica.
Entre os quadros de deficincia de cortisol deve tambm
ser includo a forma que incide ao longo do processo do
envelhecimento, ocasionada pela progressiva deteriorao
do eixo hipofisrio-adrenal.
A evidncia de que o cortisol essencial no s para os
portadores de estados de severa depleo, como tambm
para a manuteno do equilbrio fsico e mental dos adultos
que esto envelhecendo e declinando a sua capacidade de
produo. Uma quantidade adequada de cortisol essencial
para o normal funcionamento de uma multiplicidade de
rgos e sistemas: crebro, pele, articulaes, msculos,
trato digestrio, sistemas imunolgico e cardiovascular. A
deficincia de cortisol encontra-se clinicamente relacionada
com fadiga, baixa tolerncia ao estresse, confuso 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.
Consequncias adversas da deficincia de cortisol variam
desde potenciao dos efeitos debilitantes de doenas
inflamatrias ( artrite reumatoide, gastrenterite, colite,
desordens imunolgicas e alergias ), at o aumento da
mortalidade em condies de alto risco como o choque
sptico. Os estados de deficincia leve de cortisol podem,

igualmente, causar mais repercusses danosas sade


humana do que se imaginava antes.
Como a suplementao de cortisol e de outros
glicocorticoides tem sido associada com importantes efeitos
adversos, dentre os quais: imunossupresso, osteoporose,
ganho de peso, atrofia cutnea, hipertenso, supresso
adrenal e fcies cushingide, ns recomendamos aos
mdicos que a reposio de cortisol deva ser pautada pela
observncia de guidelines de segurana. Acreditamos
firmemente que os efeitos colaterais so consequentes ao
uso de doses excessivas, bem como pelo fato de que a
reposio de cortisol no pode ocorrer na ausncia da
correo dos desequilbrios nos nveis de hormnios
anablicos (pausas humanas ), principalmente a queda dos
nveis de DHEA. e T3. A presena de nveis fisiolgicos de
hormnios anablicos pode bloquear os efeitos catablicos
da presena de doses excessivas de glicocorticoides. Em
vrios casos de deficincia de cortisol, reposio de
derivados sintticos produz efeitos clnicos muito menos
efetivos do que a reposio do cortisol na sua forma
homloga humana.
Em termos de diagnstico laboratorial, pode-se lanar mo
das dosagens sricas de cortisol total matinal, cortisol livre,
transcortina ( CBG= cortisol binding globulin ), ACTH, bem
como dosagens dos 17-hidroxiesterides em urina de 24
horas, pela tcnica de cromatografia a gs.
O tratamento de reposio com cortisol nas formas leves
pode ser feito observando-se os limites dirios das doses
fisiolgicas. Em casos mais severos, as doses recomendadas
podem sofrer um acrscimo de at 30-50%.
Lembramos que os homens necessitam de doses maiores
porque fisiologicamente secretam quantidades dirias
cerca de 50% maiores do que as mulheres. Apenas 50 % da
dose diria administrada absorvida pelo trato
gastrintestinal. Em situaes de agravamento das condies
de estresse, como: infeces, procedimentos cirrgicos e
abalo emocional intenso, recomendamos que as doses
sejam temporariamente aumentadas.
Importante lembrar que a reposio com cortisol pode
agravar deficincias j existentes na produo dos
hormnios tireoidianos e DHEA. Desta forma,
recomendamos aos mdicos corrigirem concomitantemente
aquelas deficincias.
CONCLUSO DO CONSENSO:
Com base na literatura cientfica atual, inexistem quaisquer
justificativas
plausveis
que
contraindiquem
ou
desestimulem o tratamento de reposio com cortisol em

adultos com baixos nveis. Efeitos colaterais adversos


podem ser evitados seguindo-se os guidelines j propostos,
bem como utilizando-se doses fisiolgicas da forma
homloga humana do cortisol. Novamente ressaltamos a
capital importncia da correo concomitante de outras
deficincias na produo de hormnios anablicos,
particularmente DHEA e o hormnio tireoidiano. Monitorar
os pacientes atravs de um programa regular de
acompanhamento clnico-laboratorial.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.
6.
7.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

6. ADRENOPAUSA
a. Quadro clnico
i. Depresso e cansao em pessoas jovens, adinamia, apatia,
fragilidade imunolgica, ateromatose, irritabilidade, dficit
de memria, alteraes do sono, alteraes do humor,
ressecamento vaginal, queda de cabelos, rarefao de pelos
pubianos, reduo da libido, hipercolesterolemia,
dislipidemia, perda de massa ssea e comprometimento da
qualidade de vida.

b.

Quadro Laboratorial

i. SDHEA < 350 ug/mL em homens


ii. SDHEA < 300 ug/mL em mulheres

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da adrenopausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e

laboratoriais, o diagnstico de adrenopausa ser


confirmado tomando-se como referncia as manifestaes e
o quadro clnico apresentados pelo paciente e devidamente
avaliados e registrados pelo mdico. Tal conduta se justifica
pela baixa acurcia dos mtodos de diagnstico laboratorial
das deficincias hormonais, falhas de tcnicas intrnsecas
aos mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a adrenopausa, a SOBRAF recomenda que seus mdicos associados
utilizem-se do termo de consentimento padro adotado pela
mesma e que dever ser devidamente assinado pelo mdico e pelo
seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA ADRENOPAUSA
Aps criteriosa reviso da literatura cientfica, discusses
com mdicos representantes de todos os continentes e
discusses entre mdicos brasileiros, todos profissionais
versados e adequadamente qualificados em utilizar e
prescrever hormnios em seres humanos com a finalidade
primria de promoo da sade e, ainda, em total
consonncia com os preceitos e guidelines da Sociedade
Brasileira Para Estudos da Fisiologia SOBRAF, da
International Hormone Society e da World Society of AntiAging Medicine, ns, mdicos membros da SOBRAF,
conclumos ter chegado o momento de considerar a
deficincia de dehidroepiandrosterona, bem como a sua
reposio.
At o presente momento, as sociedades mdicas
convencionais relacionadas endocrinologia, ainda no
reconheceram a necessidade e a importncia clnica de
tratar
e
repor
a
deficincia
adrenal
de
dehidroepiandrosterona
(DHEA).
Algumas
poucas
sociedades mdicas convencionais ao redor do mundo, tem
expressado de forma pontual e tmida a importncia da

reposio de DHEA. Em geral, se identifica a concluso de


que ainda no existe base de dados suficiente que d
suporte reposio deste hormnio. Eles so da opinio de
que a literatura cientifica sobre o DHEA ainda muito
escassa e sua eficcia clnica ainda no est suficientemente
comprovada.. Eles, igualmente, expressam a preocupao
de que a reposio de DHEA poderia estar relacionada a
uma maior incidncia do cncer genital e a uma reduo do
HDL colesterol.
Aps uma cuidadosa e exaustiva reviso da literatura
cientifica atual, bem como ler e discutir os relatrios
negativos institucionais, conclumos no existir qualquer
base de dados cientfica razovel que d suporte ideia de
que o uso de DHEA possa trazer riscos sade humana.
Ns reconhecemos e corroboramos um grande nmero de
estudos aonde homens e mulheres com deficincia de
DHEA tem sido tratados e tem apresentado significativa
melhora em mltiplos aspectos fsicos e mentais.
Ao nos detalharmos com estudos que demonstram efeitos
pouco significativos no tratamento com DHEA possvel
observar que uma falha de desenho importante
frequentemente perceptvel: o tempo excessivamente curto
em que estas pessoas tem passado recebendo o hormnio,
perodos inferiores a duas semanas, em boa parte das
vezes, tempo notoriamente insuficiente para que resultados
consistentes sejam alcanados.
Ao lado de uma minoria de estudos que demonstram
resultados negativos ou no significativos, existe um grande
nmero de estudos que atesta de maneira inquestionvel a
importncia e, mais ainda, uma multivariedade de
benefcios oriundos da reposio com DHEA. Alm do mais,
estes estudos no s confirmam a eficcia como chegam
concluso que a reposio de DHEA, o mais abundante
hormnio esteroide produzido no corpo humano, uma das
formas de reposio mais seguras e eficientes que existem.
Estudos randomizados, placebo-controle e duplo-cego,
confirmam inexistirem quaisquer efeitos danosos sade
humana, quando nveis fisiolgicos de DHEA so
suplementados. Efeitos colaterais porventura existentes,
encontram-se completamente vinculados ao emprego de
doses excessivas. Os sinais mais caractersticos de doses
excessivas de DHEA so: pele oleosa, acne e leve hirsutismo,
efeitos reversveis atravs do devido ajuste nas dosagens.
Em muitos estudos que analisam a reposio de DHEA,
significativos benefcios foram obtidos no ganho de massa
ssea, qualidade da pele, sistema imunolgico,
sensibilidade glicose, sensibilidade insulina e perfil
lipdico. Benefcios tambm foram evidenciados na
performance mental e emocional, qualidade de vida, fadiga,

depresso, reduo do risco cardiovascular, diabetes e


obesidade.
a opinio deste grupo que os seguintes argumentos do
suporte e justificam plenamente o tratamento de reposio
com DHEA em adultos com baixos nveis sricos:
1. DHEA um hormnio natural aos seres humanos,
est plenamente configurado para atender s nossas
demandas metablicas, e, na verdade, o hormnio
presente em maior quantidade no corpo humano.
2. DHEA exerce mais de 150 funes anablicas no
metabolismo humano.
3. Apresenta uma multiplicidade de benefcios quando
usando em indivduos adultos que apresentam
baixos nveis, sendo uma valiosa ferramenta no
combate
s
doenas
relacionadas
ao
envelhecimento.
4. Reposio de DHEA segura.
5. Reposio de DHEA tem um custo acessvel.
Com o intuito de elevar a segurana do tratamento de
reposio com DHEA, ns recomendamos que os mdicos
submetam seus clientes a um programa de avaliaes
peridicas, incluindo anamnese, exame fsico 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 avaliaes clnico-laboratoriais para o cncer de
prstata e mama, obedecendo a um intervalo de seis a 12
meses, dependendo de cada caso.
Na nossa experincia, os melhores mtodos para o
diagnstico da deficincia de DHEA so a avaliao srica
dos nveis do sulfato de dehidroepiandrosterona e a
avaliao da excreo dos metablitos 17-cetoesteridesDHEA em urina de 24 horas, pela tcnica de cromatografia
a gs.
As doses de segurana so as chamadas doses fisiolgicas,
que devem ser seguidas e observadas pelos membros da
sociedade.
Ressaltamos que nos casos em que clinicamente
relevante evitar a converso de DHEA para Testosterona
ou Estradiol, pode-se lanar mo da reposio de 7-KetoDHEA, principal metablito ativo do DHEA, que possui
exatamente as mesmas propriedades do DHEA, porm, no
sofre converso para outros hormnios. Neste caso, devese, igualmente, observar as doses fisiolgicas de segurana.
CONCLUSO DO CONSENSO:

Com base na literatura cientfica atual, inexistem


justificativas
plausveis
que
contraindiquem
ou
desestimulem o tratamento de reposio de DHEA em
adultos com baixos nveis, exceto para as mulheres que
encontram-se na ps-menopausa e no esto fazendo a
reposio hormonal da menopausa. Ao contrrio, benefcios
em quantidade e intensidade suficientes j tem sido
demonstrados e servem como base para nos permitir
recomendar o uso de doses fisiolgicas de DHEA para
corrigir as deficincias bem estabelecidas e previamente
diagnosticadas em adultos, submetendo-os, da por diante,
a um programa regular de acompanhamento clnicolaboratorial. A reposio de DHEA encontra-se
especialmente justificada em indivduos portadores de
condies de sade tratadas com corticoides, uma vez que o
seu uso pode neutralizar com segurana os efeitos
catablicos excessivos da corticoterapia.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.
6.
7.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD
Professor Doutor Marcos Renato Scholz, PhD
Dr. talo Emmanuel Valeriano Rachid

7. MELATOPAUSA
a. Quadro clnico
i. Depresso, cansao, adinamia, apatia, fragilidade
imunolgica, irritabilidade, dficit de memria, alteraes
do sono, alteraes do humor, alteraes gastrointestinais e
comprometimento da qualidade de vida.

b.

Quadro Laboratorial

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

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da melatopausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de melatopausa ser
confirmado tomando-se como referncia as manifestaes e
o quadro clnico apresentados pelo paciente e devidamente
avaliados e registrados pelo mdico. Tal conduta se justifica
pela baixa acurcia dos mtodos de diagnstico laboratorial
das deficincias hormonais, falhas de tcnicas intrnsecas
aos mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a melatopausa, a SOBRAF recomenda que seus mdicos associados
estaro, concomitantemente, utilizem-se do termo de
consentimento padro adotado pela mesma e que dever ser
devidamente assinado pelo mdico e pelo seu paciente.
e.

CONSENSO DA SOBRAF PARA O TRATAMENTO


HORMONAL DA MELATOPAUSA
Aps criteriosa reviso da literatura cientfica, discusses com
mdicos representantes de todos os continentes e discusses
entre mdicos brasileiros, todos profissionais versados e
adequadamente qualificados em utilizar e prescrever
hormnios em seres humanos com a finalidade primria de
promoo da sade e, ainda, em total consonncia com os
preceitos e guidelines do Grupo Longevidade Saudvel, da
International Hormone Society e da World Society of AntiAging Medicine, ns, mdicos membros do Grupo de Consenso
do Grupo Longevidade Saudvel, conclumos ter chegado o
momento de considerar o tratamento da deficincia de
melatonina em adultos.
At o presente momento, nenhuma sociedade mdica
convencional no mundo reconheceu a necessidade e a

importncia de tratar a deficincia da glndula pineal atravs


da reposio de melatonina.
Como de costume quando se trata do assunto reposio
hormonal, a controvrsia tambm no foge regra na
reposio de melatonina. Para algumas escolas constitui-se em
um hormnio essencial, com importantes repercusses para a
sade humana. J para outras escolas, no passa de um placebo
sem qualquer importncia clnica. Em contraste com esta
controvrsia, existe uma unanimidade completa acerca da
segurana e importncia da reposio de melatonina entre
pesquisadores renomados e mdicos ao redor de todo o mundo
que acumularam vasta experincia no uso e aplicaes clnicas
deste hormnio em seres humanos. A melatonina tem se
mostrado to segura, que at o presente momento no foi
possvel determinar os limites de doses txicas para humanos e
para animais. Doses extremamente elevadas tem sido
utilizadas em experimentos com animais com o intuito de
estabelecer aqueles nveis, sem que se consiga produzir efeitos
danosos ou mesmo a morte dos animais.
Aps exaustiva reviso da literatura e troca de experincias
entre grupos versados no emprego clnico da melatonina, o que
se pode concluir que a sua reposio capaz de produzir
consistentes e significativos benefcios sade humana. Os
efeitos mais notrios so observados na qualidade do sono,
controle do Jet Lag, varredura de radicais livres, metabolismo
da glicose, ossos, sistema cardiovascular, metabolismo
cerebral, melhora do perfil lipdico e manuteno da ciclicidade
e responsividade dos receptores celulares para hormnios
anablicos.
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 notria melhora da qualidade do sono, por
ser a melatonina capaz de encurtar o tempo de induo do
sono, encurtar o incio da fase REM do sono profundo e
provocar um relaxamento muscular e nervoso atravs da
estimulao do sistema parassimptico. O conjunto destas
aes facilita o sono e melhora a sua qualidade, alm de
contribuir diretamente para o processo de reparo e
recuperao metablica ao longo do perodo de permanncia
no sono.
Com base na literatura e experincia mundial atuais, inexistem
quaisquer justificativas plausveis de ordem cientfica ou
mdica que contraindiquem ou desestimulem o tratamento de
reposio com melatonina. Sua segurana e eficcia clnica so
motivos mais do que suficientes para ressegurar s autoridades
de sade a validade e aceitao do seu uso, desde de que tal
seja feito sob criteriosa prescrio e superviso mdica.
As doses de segurana so as chamadas doses fisiolgicas, 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 crnica devese iniciar o tratamento com doses menores e tambm corrigir a
deficincia de cortisol de forma concomitante.
Na opinio deste grupo, os seguintes argumentos do suporte e
fundamentam o tratamento de reposio de melatonina em
adultos:
Melatonina uma substncia natural ao organismo
humano e sua presena abundante, principalmente no
perodo noturno.
Melatonina est completamente adaptada ao corpo
humano.
Melatonina exerce uma multiplicidade de benefcios na
manuteno da sade fsica e mental, bem como contra
o desenvolvimento das doenas degenerativas da
velhice.
Melatonina segura.
Melatonina tem custo acessvel.
O diagnstico da deficincia de melatonina baseado
em critrios essencialmente clnicos. Pode-se,
entretanto, em casos que se faam necessrios, recorrer
dosagem da excreo em urina de 24 horas da 6sulfatoxi-melatonina,
principal
metablito
da
melatonina, como parmetro diagnstico laboratorial.
CONCLUSO DO CONSENSO:
Com base na literatura cientfica atual, inexistem
quaisquer justificativas plausveis que contraindiquem
ou desestimulem o tratamento de reposio com
melatonina em adultos com baixos nveis. Ao contrrio,
uma vasta base de dados e evidncias do suporte e
validam o seu emprego em indivduos com deficincia e
com baixos nveis, submetendo-os a um programa
regular de acompanhamento mdico.
So Paulo, 12 de Novembro de 2012
Grupo de Consensos da SOBRAF
1.
2.
3.
4.
5.

Professora Doutora Ana Cristina Vendramini, PhD


Professora Doutora Andreia Conceio Milan B. Antoniolli, PhD
Professora Doutora Andrea Thomaz Soccol, PhD
Professor Doutor Eduardo Faria, PhD
Professor Doutor Marcelo Alexandre de Mattos, PhD

6. Professor Doutor Marcos Renato Scholz, PhD


7. Dr. talo Emmanuel Valeriano Rachid

8. ELETROPAUSA

a. Quadro clnico
i. Depresso, cansao, adinamia, apatia, fragilidade
imunolgica, irritabilidade, dficit de memria, alteraes
do sono, alteraes do humor e comprometimento da
qualidade de vida.

b.

Quadro Laboratorial

i. Dosagem do Sulfato de Pregnenolona no lquor


ii. Sulfato de pregnenolona < 90 ng/mL.

c.

Observaes
complementares
diagnstico clnico-laboratorial:

acerca

do

i. Quando o diagnstico laboratorial mostrar-se coerente e


compatvel com o quadro clnico, este ser considerado na
confirmao do diagnstico da eletropausa. Por outro lado,
nas situaes em que ocorrer clara discrepncia,
divergncia ou distores entre os dados clnicos e
laboratoriais, o diagnstico de eletropausa ser confirmado
tomando-se como referncia as manifestaes e o quadro
clnico apresentados pelo paciente e devidamente avaliados
e registrados pelo mdico. Tal conduta se justifica pela
baixa acurcia dos mtodos de diagnstico laboratorial das
deficincias hormonais, falhas de tcnicas intrnsecas aos
mtodos, uso de metodologia inadequada na coleta da
amostra de sangue, horrio em que a amostra foi colhida,
nvel de hidratao do paciente no momento da coleta e
limitaes tcnicas dos mtodos laboratoriais. A coleta de
uma amostra matinal de sangue para dosar um dado
hormnio, expressa um retrato esttico de um fenmeno
intensamente dinmico e complexo, que sofre influncia de
mltiplas variveis, o que torna
qualquer mtodo
diagnstico potencialmente falho, limitado e pouco
confivel, at que sejam desenvolvidas tecnologias e
mtodos mais eficazes.
d. No momento da instituio da proposta teraputica hormonal para
a eletropausa, a SOBRAF recomenda que seus mdicos associados
utilizem-se do termo de consentimento padro adotado pela
mesma e que dever ser devidamente assinado pelo mdico e pelo
seu paciente.

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1. Higashi Y, Sukhanov S, Anwar A, Shai SY, Delafontaine P. IGF-1, oxidative
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Iwasaki Y, Asai M, Yoshida M, Nigawara T, Kambayashi M, Nakashima N.


Dehydroepiandrosterone-sulfate inhibits nuclear factor-kappaB-dependent
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Atividade Antioxidante do Estradiol


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Bokov AF, Ko D, Richardson A. The effect of gonadectomy and estradiol on


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Atividade Antioxidante da Progesterona


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Tam NN, Ghatak S, Ho SM. Sex hormone-induced alterations in the activities of


antioxidant enzymes and lipid peroxidation status in the prostate of Noble
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2- OTIMIZAO DA IMUNIDADE MEDIADA PELA


MODULAO HORMONAL
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3- OTIMIZAO DO BEM
QUALIDADE DE VIDA
MODULAO HORMONAL

ESTAR FSICO E
MEDIADOS PELA

Baixa Qualidade de Vida e Fadiga: Correlao Com Baixos Nveis de


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Baixa Performance: A Correlao Com Baixos Nveis de Testosterona


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CONTROLE DA ANSIEDADE ATRAVS DA


MODULAO HORMONAL
4

Ansiedade: Associao Com Baixos Nveis de DHEA


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Ansiedade: A Melhora Com a Reposio dos Hormnios Tireoidianos


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Ansiedade: A Melhora Com a Reposio do Hormnio do Crescimento

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Ansiedade: Associao Com Baixos Nveis de Pregnenolona

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Ansiedade: A Melhora Com a Reposio de Pregnenolona


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Ansiedade: A Melhora Com a Reposio de Estradiol e Progesterona


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CONTROLE DA QUALIDADE DO SONO


ATRAVS DA MODULAO HORMONAL
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Distrbios do Sono: A Correlao Com Baixos Nveis de Melatonina

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Distrbios do Sono: A Correlao Com Baixos Nveis de Estradiol

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Sleep quality, estradiol levels, and behavioral factors in late reproductive age
women. Obstet Gynecol. 2001 Sep;98(3):391-7

Distrbios do Sono: A Melhora Com a Reposio de Estradiol

1- Antonijevic IA, Stalla GK, Steiger A. Modulation of the sleep


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Distrbios do Sono: A Melhora Com a Reposio de Estradiol e Progesterona

1- Hachul H, Bittencourt LR, Andersen ML, Haidar MA, Baracat EC, Tufik S.
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104 ESTUDOS PLACEBO-CONTROLADOS DEMONSTRANDO OS BENEFCIOS


E CONTROLE EXERCIDOS PELA REPOSIO DE MELATONINA NOS
MECANISMOS E QUALIDADE DO SONO EM CRIANAS E ADULTOS

Crianas

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Distrbios do Sono: A Correlao Com Baixos Nveis de Testosterona

1- Andersen ML, Tufik S. The effects of testosterone on sleep and sleepdisordered breathing in men: its bidirectional interaction with erectile function.
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1- Davis A, Gilbert K, Misiowiec P, Riegel B. Perceived effects of testosterone


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CONTROLE DA PRESSO ARTERIAL


ATRAVS DA MODULAO HORMONAL
6

Hipertenso Arterial: A Associao Com Baixos Nveis de Melatonina


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Hipertenso Arterial: A Associao Com Baixos Nveis do Hormnio do


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Hipertenso Arterial: A Associao Com Baixos Nveis de IGF-1

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Hipertenso Arterial: A Associao Com Baixos Nveis de Estradiol

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Hipertenso Arterial: A Melhora Com a Reposio de Estradiol

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Hipertenso Arterial: A Associao Com Baixos Nveis de Testosterona

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CONTROLE DA GORDURA CORPORAL E


PROFILAXIA E TRATAMENTO DA OBESIDADE
ATRAVS DA MODULAO HORMONAL
7

Obesidade: A Associao Com Baixos Nveis de Melatonina

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Obesidade: A Associao Com Baixos Nveis dos Hormnios Tideoidianos

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5-

6-

7-

8-

9-

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Obesidade: A Associao Com Baixos Nveis de DHEA


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Obesidade e Adiposidade Visceral: A Associao Com Baixos Nveis do
Hormnio do Crescimento
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MELHORA DA APARNCIA FSICA, COMPOSIO


CORPORAL E MASSA MUSCULAR ATRAVS DA
MODULAO HORMONAL
8

Hormnio do Crescimento e Composio Corporal


Sarcopenia: A Associao Com Baixos Nveis de GH/IGF-1

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Perda de Massa Muscular e Aumento da Massa Gordurosa: A Associao Com


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PREVENO
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OSTEOPOROSE
ATRAVS
HORMONAL
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TRATAMENTO
DA
DA
MODULAO

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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):16874
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 postmenopausal 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, placebocontrolled 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 postmenopausal 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 Associao Com Baixos Nveis 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 Preveno Com a Reposio de Estradiol e


Progesterona

1- Michaelsson K, Baron JA, Farahmand BY, Persson I, Ljunghall S. Oralcontraceptive 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 Associao Com Baixos Nveis 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
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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 Reposio 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):4751

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 Associao Com Baixos Nveis 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

PREVENO DO CNCER E REDUO DO


RISCO DE CNCER ATRAVS DA MODULAO
HORMONAL
10

Proteo 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

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

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

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

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

Proteo na ANDROPAUSA:

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.

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 cncer

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

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 mans life when testosterone levels decline.

o
o

TESTOSTERONE therapy in men with untreated PCa


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!

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 testosterones 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.*

HORMNIO DO CRESCIMENTO E CNCER:


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

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.

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

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.

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%

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.

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 antitumorgenic actions.
IGFBP 3 may be considered The Guardian of the Genome.

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.

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

.
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
Declnio IGF-1 diretamente correlacionado com aumento do
risco de cncer de prstata
Queda 55% de IGF-1, representa aumento de 48% no
risco de ca prstata

Cncer: Efeito Protetor da Reposio 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):23942
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. Antiangiogenic 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):31923
Cncer: A Associao Com Baixos Niveis do Hormnio 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 populationbased 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 Nveis de GH/IGF-1 em Pacientes


Com Cncer

Baixos Nveis de IGF-1 no Glioma


1.

Lnn 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 Nveis de IGF-1 no Cncer de Prstata

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, Schnemann 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):10915
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 insulinlike growth factor I, insulin-like growth factor binding protein 3, and insulin.
Cancer. 2005 Jan 1;103(1):76-84

Baixos Nveis de IGF-1 no Cncer 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 Nveis de IGF-1 no Cncer Pancretico

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 Nveis de IGF-1 no Cncer Cervical

1- Schaffer A, Koushik A, Trottier H, Duarte-Franco E, Mansour N, Arseneau J,


Provencher D, Gilbert L, Gotlieb W, Ferenczy A, Coutle 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, Snchez-Gmez 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 Ausncia de Correlao ou Associao dos


Nveis de IGF-1 e Cncer

Cncer de Prstata

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
Cncer 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

Cncer 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 IGFBP1 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)

Cncer: Possvel Melhora da Evoluo Com Reposio do Hormnio do


Crescimento

12-

3-

Torosian MH. Growth hormone and prostate cancer growth and metastasis in
tumor-bearing animals. J Pediatr Endocrinol. 1993 Jan-Mar;6(1):93-7
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
Bartlett DL, Charland S, Torosian MH. Growth hormone, insulin, and
somatostatin therapy of cancer cachexia. Cancer. 1994 Mar 1;73(5):1499504

Cncer: A Associao Com Baixos de DHEA

1- Herman WA, Seko A, Korczowska I, acka K. Could serum DHEA and


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Cncer: Possvel Melhora da Evoluo Com Reposio de DHEA

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Cncer de Mama: Melhora Com a Reposio de DHEA

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ESTUDOS EM HUMANOS

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Leucemia, Metstases e Cncer do Ovrio

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Cncer: A Associao Com Baixos Nveis de Estradiol

1- Holmberg L, Norden T, Lindgren A, Wide L, Degerman M, Adami HO. Preoperative oestradiol levels - relation to survival in breast cancer. Eur J Surg
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States African-American and white women? Cancer Res. 2001 Apr
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Recorrncia em Mulheres Com Histria Prvia de Cncer de Mama Submetidas
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Postmenopausal hormone therapy and mortality. N Engl J Med. 1997;
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8- Mohammed SN, Smith P, Hodgson SV, Fentiman IS, Miles DW, Barnes DM,
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15- Willis DB, Calle EE, Miracle-McMahill HL, Heath CW Jr. Estrogen
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postmenopausal women in the United States. Cancer Causes Control. 1996
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Carrero JJ, Qureshi AR, Parini P, Arver S, Lindholm B, Brny P, Heimbrger


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Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone
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Cncer em Homens: Possvel Proteo Com a Reposio de Testosterona

1- Dimitrakakis C, Jones RA, Liu A, Bondy CA. Breast cancer incidence in


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Morales A, Connolly JG, Bruce AW. Androgen therapy in advanced carcinoma


of the prostate. Can Med Assoc J. 1971;105(1):71-2
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 Reposio Com Testosterona Promove Inibio da


Proliferao do Cncer de Prstata 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

2-

3-

human prostate cancer cell line LNCaP. J Steroid Biochem Mol Biol 1995
Oct;55(1):67-76
Wolf DA, Schulz P, Fittler F. Synthetic androgens suppress the transformed
phenotype in human prostate carcinoma cell line LNCaP. Br J Cancer. 1991
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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 Reposio de Testosterona Reduz Queixas Prostticas Como


Disria e Nictria

1-

2-

34567-

8-

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
Kearns WM. Testosterone in the treatment of testicular deficiency and prostatic
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Meltzer M. Male hormone therapy of prostatic hypertrophy. Lancet. 1939; 59:
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Trasoff A. The treatment of benign prostatic hypertrophy with testosterone
propionate. J Lab Clin Med. 1940; 25: 377
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Laqueur E. Behandlung der Prostathypertropie mit mnnlichen Hormone
(Hombreol) une experimentell Begrndung dieser Therapie. Schweiz Med
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South Med J, 1939, 32: 154

Estudos Onde a Reposio de Testosterona Reduziu o Volume da Prstata e


as Queixas Prostticas
123-

4-

South Med J, 1939, 32: 154


de Lignieres B. Transdermal dihydrotestosterone treatment of 'andropause.
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Estudos de Reviso Onde os Autores No Acharam Associao Entre Os


Nveis de Testosterona e o Risco de Cncer de Prstata e Demonstram
Claramente Que No Existem Dados ou Evidncias Que Dem Suporte a Viso
de Que a Reposio de Testosterona Esteja Correlacionada Com o Risco de
Cncer

1-

2-

3-

4-

567-

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.)
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)
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)
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)
Wirth MP, Hakenberg OW Testosterone and the prostate. Urologe A 2000
Sep;39(5):418-20
Rolf C, Nieschlag E. Potential adverse effects of long-term testosterone
therapy. Baillieres Clin Endocrinol Metab. 1998 Oct;12(3):521-34.
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 Reposio de Testosterona em Homens Com Cncer de


Prstata No Exerce Qualquer Efeito Adverso na Progresso ou Recorrncia
do Cncer e, Ao Mesmo Tempo, Melhora a Qualidade de Vida e Os Parmetros
Gerais de Sade

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testosterone
therapy
..no
adverse
effects
from
testosterone
supplementation)
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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 Reposio de Testosterona No Demonstra Efeitos Adversos


No Risco de Cncer de Prstata

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Estudos Onde a Reposio de Testosterona No Demonstra Quaisquer Efeitos


Nos Nveis de PSA ou do Volume da Prstata

3.

4.

5.

6.

7.

8.

9.

10.

11.

Rhoden EL, Morgentaler A. Influence of demographic factors and biochemical


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Monath JR, McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum
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antigen. Urology. 1995 Jul;46(1):58-61

EXPANSO DA LONGEVIDE E MELHORA DA


QUALIDADE DE VIDA ATRAVS DA MODULAO
HORMONAL
11

Longevidade em Homens: A Associao Com Baixos Nveis de Testosterona

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Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A,


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Longevidade em Homens: A Melhora da Sobrevida Com A Reposio de


Testosterona

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Longevidade em Homens: A Associao Com Baixos Nveis de GH

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Stochholm K, Christiansen J, Laursen T, Gravholt CH. Mortality and reduced


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Besson A, Salemi S, Gallati S, Jenal A, Horn R, Mullis PS, Mullis PE..


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Longevidade: A Melhora Com a Reposio de GH

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2-

3-

4-

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
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6- Rasmuson T, Grankvist K, Jacobsen J, Olsson T, Ljungberg B. Serum


insulin-like growth factor-1 is an independent predictor of prognosis in
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Longevidade: A Melhora Com a Reposio de IGF-1

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Longevidade: A Associao Com Baixos Nveis de DHEA

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Cappola AR, O'Meara ES, Guo W, Bartz TM, Fried LP, Newman AB.
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Enomoto M, Adachi H, Fukami A, Furuki K, Satoh A, Otsuka M, Kumagae S,


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Longevidade: A Associao Com os Nveis de Progesterona

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Mohr PE, Wang DY, Gregory WM, Richards MA, Fentiman IS. Serum
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Longevidade: A Melhora Com a Reposio de Estradiol


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2-

3-

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Petitti DB, Perlman JA, Sidney S. Noncontraceptive estrogens and


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Longevidade: A Melhora Com a Reposio de Progesterona

1-

Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M,


Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery
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Longevidade: A Possvel Associao Com a Persistncia do Ritmo Cirdadiano


da Melatonina em Idosos

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Longevidade: A Melhora Com a Reposio de Melatonina

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Longevidade: A Associao Com Baixos Nveis dos Hormnios Tireoidianos

1-

2-

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Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic
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Iervasi G, G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L'Abbate A,


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Longevidade: A Melhora Com a Reposio dos Hormnios Tireoidianos


1-

Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The Incidence of Ischemic
Heart Disease and Mortality in People with Subclinical Hypothyroidism:
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12PROFILAXIA E TRATAMENTO DA
DEPRESSO
ATRAVS
DA
MODULAO HORMONAL:
Depresso: A Associao Com Baixos Nveis de Melatonina

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Depresso: A Associao Com Baixos Nveis do Hormnio do Crescimento

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Depresso: A Melhora Com a Reposio do Hormnio do Crescimento

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Depresso: A Associao Com Baixos Nveis dos Hormnios Tireoidianos

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Depresso: A Associao Com Baixos Nveis de Cortisol


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Depresso: A Associao Com Baixos Nveis de DHEA

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Depresso: A Melhora Com a Reposio de DHEA


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Depresso: A Melhora Com a Reposio de Estradiol

1- Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS.
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Depresso: A Associao Com Baixos Nveis de Testosterona

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Depresso: A Melhora Com a Reposio de Testosterona

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