A PRIMAVERA VEM AÍ. Aproveitem melhores tempos!

A PRIMAVERA

VEM AÍ…

Aproveitem melhores

tempos !

estamos hoje expostos a

vulcões

de

estudos explosivos

que derramam as cinzas

das

notícias erradas

como a conferência de

imprensa sobre o WHI:

com notícias muitíssimo

quentes…

e…, só mais tarde… a primeira

publicação do WHI (JAMA)…

Os manifestos panfletários…

Os seus manifestos panfletários não

foram transmitidos em primeira mão

aos responsáveis pela saúde das

mulheres. Ao contrário,

comunicaram-nos à Imprensa que os aceitou

erróneamente como verdadeiros e os

publicou em títulos de caixa alta !

Assim conseguiram gerar o pânico nas

populações, e a confusão de riscos

WHI and breast cancer

Once again, it is apparent that the

alarmist

reports that spread world-wide

when the

first results of the WHI study were

published in 2002

were unjustified based

on the more recent further analyses,

particularly in peri- and early

postmenopausal women.

As encíclicas…

“O que é especialmente

preocupante acerca das

declarações e encíclicas das

prescrições é

a aceitação cega da

infalibilidade do WHI e do MWS”

Sturdee D and MacLennan A –(Editorial) Should epidemiology, the media and

“

Baseado no grupo de estudo do

WHI

, a

implementação dos resultados

para a clínica tem pouca base

científica, se é que tem alguma…

”

Adam Ostrzenski and Katarzyna M Ostrzenska. Am J Obst Gynecol 2005;193:1599-604

The women enrolled in WHI and HERS

initiated EPT more than a decade after

menopause on average

, and the majority

of events that produced this pattern

occurred in older women.

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

Data from large studies such as the

WHI and HERS should not be

extrapolated to symptomatic

postmenopausal women younger than

50 years of age who initiate HT at that

time as these women were not

studied in those trials

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

It is not possible to extrapolate

conclusions from the study of one

compound, dose, and route of

administration directly to another.

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

The WHI study was not designed, and

therefore was not powered, to

investigate the consequences of

hormone therapy (HT) in women below

60 years of age.

e ….

os investigadores do WHI

não sabem interpretar os seus resultados…

a pesar de os apresentarem

como

a verdade…

“O Estudo da Saúde das

Enfermeiras (NHS) e outros

semelhantes podem estar

correctos e o WHI estar

equivocado, ou vice-versa”

”Pode suceder também que cada um

deles esteja equivocado.

Talvez o estrogénio das pastilhas não

seja a molécula em que nos devamos

concentrar”

“ Se os dois estudos estiverem certos

então pode ter sucedido que as

mulheres estudadas em ambos fossem

diferentes nalgum aspecto que os

investigadores não decifraram”.

WHI

(Women´s Health Initiative)

O que é que mudou?

por

Manuel Neves-e-Castro

XII Jornadas Minhotas de Ginecologia

Março 2007

NADA!

e por quê?...

porque só agora é que a comunidade científica percebeu

o que é o WHI

desde há 4 anos…

a SPM soube e sabe ler o WHI !

e por isso se pode verificar que sempre

estivemos na vanguarda da leitura

correcta (que agora se confirma), nos

concensos e artigos publicados !

O que é que o WHI é ?

e

O WHI

não foi desenhado para

estudar o efeito da THM

• em mulheres menopáusicas sintomáticas

• durante os primeiros 10 anos após a

WHI

• O WHI foi um estudo desenhado apenas para se

verificar se a THM tinha efeitos protectores das doenças cardiovasculares:

- em mulheres sem os sintomas frequentes da pós-menopausa (afrontamentos, suores nocturnos, etc)

- com mais de 10 anos após a menopausa (a média de idades foi de 63 anos)

- submetidas a uma única terapêutica hormonal

contínua (0,625mg de estrogéneos equinos conjugados e 2,5 mg de acetato de medroxiprogesterona) que não

era ajustada em função da idade (até 80 anos!...) nem dos seus efeitos secundários !

Por que motivo se fez o estudo

WHI?

Para determinar o efeito a longo prazo dos tratamentos hormonais na:

prevenção de

doenças cardíacas e

fracturas do colo do fémur, e possíveis aumentos de risco para

cancro da mama e cancro do cólon.

Mensagem do Presidente do Estudo WHI

Press Statement IMS

The WHI study was not designed, and

therefore was not powered, to investigate the consequences of hormone therapy (HT) in women below 60 years of age. Therefore,

any attempt to present the results of the study as indicating that HT may inflict damage to the

heart in general – a message that was accepted

by many medical societies and regulatory Authorities

WHI

Uma chamada de atenção para

em termos gerais de THM

- se estudarem doses mais baixas do E e P - se estudar o benefício/risco

a) das vias de administração

b) das moléculas de P e E usadas c) da duração das THM

- se determinar qual a idade pós-menopáusica

A forma como se interpretaram

os resultados em termos de:

- Risco Absoluto (RA ou AR)

- Risco Relativo (RR ou RR)

- Risco Atribuível (RAt ou AtR)

- Número Necessário para Causar Dano

A MENOPAUSA FOI ATACADA

POR UM

O Terrorista Hormonal

O Terrorista Hormonal

Quero tomar TH !

O Terrorista Hormonal Quero tomar TH ! Mas alguns médicos dizem que NÃO !...

Homem

Homem

WHI

O que se disse e ...

O que não se disse...

Quais foram as conclusões do

WHI no que se refere a:

cancro da mama?

Efeito sobre o risco de

cancro da mama

WHI

aumento do risco

:

RR 1.26 (CI 1.00-1.59); 26% aumento de risco

AR 0.38% vs 0.30% (ie, 38 vs 30 casos anualmente por

10.000 mulheres)

NÃO SIGNIFICATIVO !

HERS

aumento do risco

:

RR 1.27 (CI 0.84-1.94); 27% aumento de risco

AR 0.59% vs 0.47% (ie, 59 vs 47 casos anualmente por

10.000 mulheres)

WHI

(JAMA 2002;288:321-331)

Results:

“the difference reaches “almost nominal

statistical significance”

(i.e. not

statistically different!)

Discussion:

“the substantial risks for CVD and breast

cancer” (?!...)

Se os resultados do WHI se

calcularem, por ano, como

NNT

NNH

Neves-e-Castro M. Menopause in crisis post-Women’s Health Initiative? A

view based on personal clinical experience. Human Reproduction

Women’s Health Initiative (WHI)

per

1000

pts over

5 years

Event

Coronary Heart Disease 17 13 +4

Stroke 13 9 +4

Pulmonary Embolism 8 4 +4

Invasive Breast Cancer 17 13 +4

Colorectal Cancer 5 8 -3

Hip Fracture 4 6 -2

Then, why all this

noise?...

Mainly because

the conclusions of

recent trials were severely

misinterpreted

by the medical

professionals, the media and by the

women, themselves

Are

Women

in a

crisis

?

YES !

Because

We have a tendency to accept as valid

the headlines that circulate in the

media without having critically read the

full papers to which they refer

We are not able to explain to our

patients the meaning of those risks and

how small they are compared to other

risks to which they are expose

To begin with, and

i

n the light of the present evidence,

doctors and women should be

reassured that the suggested HT’s for

the relief of symptoms in the

menopause

Medicina Baseada na Evidência

e/ou

Evidência Baseada na Medicina

?

Medicina Baseada na Evidência

e/ou

Medicina Baseada na Inteligência

?

Evidence informed practice

(A Clínica Informada pela Evidência)

• It is clearly time to change “evidence based

medicine” to “evidence informed practice”.

• I suggest the era of evidence informed rather

than evidence based medicine has arrived

Glasziou P. Centre for Evidence-Based Medicine. University of Oxford OX3 7LF. BMJ 2005;330:92

Evidence-Based Medicine

implies that

recommendations should be limited to the

women for whom the studies are relevant.

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

The practice of medicine is ultimately

based on the interpretation at any one

time of the entire body of evidence

currently available.

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

e …

eis um exemplo de um

Effects of conjugated Equine Estrogen in Postmenopausal Women with Hysterectomy. JAMA, 2004;291:1701-1712

Stroke

“In women 50-59 years

not taking HT

,

ischemic stroke is expected to occur in

3 out of 1000 women during 5 years.

Five years use of HT would yield

1

additional case of stroke/

1000 women”

“Estamos afogados

em

informação

mas famintos de

sabedoria

”

O que é que parece ter mudado na

interpretação dos resultados de

WHI?

No que se refere a:

–Cancro da mama?

O cérebro é como um

paraquedas…

ambos funcionam melhor

quando se abrem !

A Mortalidade Cardiovascular

é o dobro da

BENEFITS OF HORMONE THERAPY

menopausal and without prevalent

cardiovascular disease, the initiation of HT does not cause early harm and may reduce cardiovascular morbidity and mortality.

Continuation of HT beyond the age of 60 should be decided as a part of the overall risk–benefit analysis.

Clinica Cardiovascular da Mulher

• 13% das mulheres com idade superior a 45 anos teve uma síndrome coronária aguda

• 55% da mortalidade na mulher é devido a doença cardiovascular (cardíaca, cerebral) • As mulheres, representam 62% da

mortalidade por Insuficiência Cardíaca

• A doença coronária na mulher pré-menopausa é menos prevalente, mantendo-se assim

durante 10 a 15 anos até aos 70 anos, altura em que iguala o homem

Hormone replacement therapy and risk

for coronary heart disease

Long-term HRT use is not associated

with increased risk for CHD in the CORA-study.

This research even supports the notion that HRT can positively affect a number of risk factors like central adiposity, insulin resistance and blood pressure.

HRT may even protect from CHD, but adverse lifestyle habits like heavy smoking and a not sufficiently healthy nutrition can offset the beneficial effects of HRT.

Hormones and the Heart

1 in 3

women will die from coronary

heart disease (CHD) in the USA.

1 in 25

women will die from breast

cancer

Causes of Death Among Women*

*Percentage of total deaths in 1999 among women aged 65 years and older. Anderson RN. Natl Vital Stat Rep. 2001;49:1-13.

Heart Disease Other Cancers Other Diabetes Chronic Lower Respiratory Disease Cerebrovascular Disease Breast Cancer 34% 10% 6% 3% 15% 28% 4%

NNH

/ Year

(

N

umber

N

eeded to

H

arm)

(the reciprocal of the AtR, the atributable risk)

Coronary Heart Disease

WHI (RR

1.29

)

1428

HERS (RR

0.99

)

5000

Breast Cancer

WHI (RR

1.26

)

1250

HERS (RR

1.27

)

833

“Not everything that can

be counted

counts

;

and not everything that

counts

can be counted”

“HRT is associated with a

35%

reduction in mortality

for women who suffered

myocardial infarction”.

Doenças cardiovasculares (WHI )

O que estava oculto

- com terapêutica combinada (E+P)?

Younger Women May Receive Heart Protection From Estrogen Therapy

In women ages 50-59 who had undergone a

hysterectomy, a significant protective effect of estrogen treatment, when both primary (heart

attacks and heart attack death) and secondary (coronary artery bypass surgery, angioplasty, confirmed angina pectoris) cardiac endpoints

were considered.

Dr. S. Mitchell Harman, director and president of Phoenix-based Kronos Longevity Research Institute (KLRI) in Archives of Internal Medicine 2006;106:357-363

An update of the WHI Study !

WHI investigators reported (Feb 2006) a

statistically significant (34%) lower risk for the combined endpoint of myocardial infarction

(heart attack), coronary death, coronary

revascularization and confirmed angina among

women who were between the ages of 50 and 59 at the start of the study (RR 0.66; 95% CI 0.45-0.96).

Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

Press Statement IMS

The estrogen plus progestogen arm of the WHI and the estrogen-alone arm actually showed that

HT does not

increase the risk of coronary heart disease in the peri- and early menopause,

and may even carry beneficial effects.

Hormonas

e

Menopausal women

and their

doctors

are scared about the side

effects of HRT

mainly about breast cancer

Cancro da mama (WHI)

o que concluiu o WHI ?

WHI ...

O fluxo da Verdade

corre através dos seus

canais de enganos ...

POTENTIAL SERIOUS ADVERSE

EFFECTS OF HORMONE THERAPY

Women should be reassured that the

possible risk of breast cancer

associated with HT is small (less than

0.1% per annum).

POTENTIAL SERIOUS ADVERSE

EFFECTS OF HORMONE THERAPY

Data from the WHI and Nurses’ Health Study suggest that long-term estrogen-only

administration for 7 and 15 years, respectively, does not increase the risk of breast cancer in American women.

Recent European observational studies suggest that risk may increase after 5 years.

Breast Cancer Risk in Postmenopausal

Women Using Estrogen-Only Therapy

Our nationwide study shows that the use of oral or

transdermal estradiol for less than 5 years does not increase the risk of breast cancer, but such a risk

appears with increasing duration of use in 2 to 3 extra

cases of breast cancer per 1.000 women in 10 years of follow-up.

The EMAS 2006/2007 update on

clinical recommendations on

postmenopausal hormone therapy

suggest the absence of increased risk of breast cancer using estrogen only therapy after short periods of time (less than 10

year). An increased risk may exist thereafter, however.

Estrogen and progestogen use in peri-

and postmenopausal

women

In absolute terms,

this increased risk

was rare in the WHI, being 4 to 6

additional invasive cancers per 10,000

women per year who used EPT for 5 or

more years.

March 2007 position statement of The North American Menopause Society.Menopause 2007;14(2):1-17

Cancro da Mama

WHI

Cancro da Mama

HERS

Breast cancer and the use of HRT

Considering

10.000 women on the

combination HRT then

for each year

there would be:

Seven additional cases of heart attacks Eight cases of stroke,

Eight cases of pulmonary embolus,

Eight cases of invasive breast cancer,

Six fewer cases of hip fractures

O Cancro da Mama

O risco de cancro da mama com os

E+P combinados contínuos é

mínimo

.

É necessário tratar

1250 mulheres

(NNH) durante 1 ano até que se

diagnostique 1 cancro da mama

(o que

é equivalente ao risco relativo de 23%!)

Cancro da Mama

O Risco Relativo aumentado de Cancro

da Mama com os estrogénios mais

progestagénios durante 5, 6 anos é

comparável ao aumento de risco de

Cancro da Mama para uma mulher que

consome uma bebida alcoólica por dia ou

que tem um Indice de Massa Corporal de

24, em comparação com 22.

It must be emphasized that we are

talking about an

increased incidence of

the disease

, which does not

automatically translate into an increase

in deaths from the disease.

Almost

2/3

of women now diagnosed with

breast cancer are likely to survive at least 20

years

• Cancer Research UK researchers estimate that 64% of women newly diagnosed with breast cancer in

England and Wales will live for at least 20 years -

compared with 44% in the early 1990s.

• More than 7 out of 10 women (72%) are now

predicted to survive for at least 10 years, compared

with 54% diagnosed in the early 1990s.

• Survival in women aged 50 to 69 - the age group in

which breast cancer is most commonly diagnosed - was even better, with 80% predicted to live for at

least 10 years while 72% survived to at least 20

years.

Prof. Michel Coleman, London School of Hygiene and Tropical Medicine told reports; Oct.10, 2005.

Source: Eurocare study 53.6 40.5 49.2 51.0 84.3 76.1 65.4 EUROPE 56.7 43.5 55.0 56.3 91.0 80.0 67.0 Switzerland 57.6 42.5 52.2 54.4 90.6 82.6 67.4 Sweden 57.1 43.9 55.0 55.8 89.8 78.0 65.5 Spain 47.0 31.2 34.8 38.8 70.0 67.4 48.8 Slovenia N/A N/A 49.0 43.5 68.9 71.9 44.0 Portugal 40.5 25.2 26.3 28.7 57.9 63.1 38.6 Poland 54.9 40.0 51.4 53.6 88.4 77.2 62.1 Norway 55.7 42.7 51.9 54.0 87.7 78.2 68.4 Netherlands N/A N/A 35.9 53.3 65.0 74.8 39.4 Malta 55.6 41.2 51.2 52.1 82.5 80.6 63.9 Italy N/A N/A 45.9 55.2 90.9 79.6 76.2 Iceland 55.6 44.1 50.5 54.5 89.9 75.4 75.9 Germany 57.9 44.5 55.9 58.7 85.3 81.3 75.2 France 55.8 41.4 54.0 52.7 84.0 81.4 66.5 Finland 51.2 33.5 43.2 47.6 88.0 74.9 41.5 Denmark 46.0 32.3 38.1 36.4 78.1 64.0 50.1 Czech Rep. 57.9 47.5 N/A 58.4 88.2 75.4 83.6 Austria 47.3 34.7 40.1 36.5 79.1 69.5 48.8 WALES 49.5 35.6 45.3 47.2 90.1 72.3 53.6 SCOTLAND 50.8 37.1 45.7 46.2 85.6 73.6 53.8 ENGLAND All (F) All (M) Colon (M) Colon (F) Skin* Breast Prostate

% of patients alive five years after diagnosis

Extended use of estrogen for

10 years

increases risks by

0,5%

, and by

15 years

increases risks by

0,9%

but..

upon cessation of HRT

,

the

relative risk quickly returns to 1.0 !

Coombs N J, Taylor R, Wilcken N. and Boyages J. BMJ 2005;331:347-349

Breast Cancer

• The diagnosis of a breast cancer after the

initiation of a HRT (with a duration of less than 5

years) is only a proof of its growth stimulatory

effect (not of its carcinogenic effect)

• Therefore, the reversal of the risk to 1 after the

cessation of HRT confirms again only its growth

promoting effect and denies a carcinogenic

effect.

Breast Cancer

• The doubling time of an initial cancer cell,

up to the diagnosis of a resultant 1cm

tumor, is most likely greater than 10 years.

• This is why

many dormant cancer cells

may exist in a “normal” breast !

Occult Breast Cancer

Clinically occult

in situ

BC’s are

frequent

in

young and middle-aged

women.

Occult Breast Cancer

Breast

malignancy was

found in

22 women

(20%)

Thus…

• Mammographies

give more false

negative

than false positive results

!

• A “normal” mammography does not

exclude the presence of cancer cells

that may “explode” a few months later…

Estrogen replacement therapy in

patients with early breast cancer

The mortality rates from breast cancer for

the

ERT users was

4.28%

compared with

22.3% in the nonusers.

HRT in Breast Cancer Survivors:

results:Matched Analysis

174 breast cancer cases taking estrogen

matched 4:1 controls with cancer not taking Estrogen.

Cases (ERT/HRT) Controls (no ERT/HRT) recurrence 17/1000 30/1000 Br cancer deaths 5/1000 16/1000 Total deaths 16/1000 30/1000

“Recurrent breast cancer was

found in

9% of HRT

users

and

15% of nonuser

”.

Mortality following development of

breast cancer

while using

oestrogen or oestrogen plus progestin:

W Chen, DB Petitti and AM Geiger.

British Journal of Cancer 2005;93:392– 398

This study explored survival after

exposure to oestrogen or oestrogen

plus progestin at or in the year prior to

breast cancer diagnosis

oestrogen plus progestin users

had lower all-cause mortality

and breast cancer mortality

Chen W, Petitti DB and Geiger AM. British Journal of Cancer

Breast cancer survival after hormone

exposure

Overall survival after hormone

exposure

Breast Cancer

Estrogens and Progestagens

• No significant increases in risk was observed in users of estrogens used alone (RR 1.1; 95%

CI=0.8-1.6) compared with non exposed women but it was greater in combination with oral

progestagens (RR 1.3; CI 1.1-1.5)

• The risk was significantly greater (p <0.001)with HRT containing synthetic progestagens (RR 1.69; CI 1.5-1.9) than with HRT containing micronized

progesterone (RR 1.0; CI 0.83-1.22)

Fournier A et al. Int J Cancer 2005;114:448-454 Fournier A et al. Breast Cancer Res Treat.2007,Feb 27 in press

Reduced hormone therapy use

might be cause of steep decline in

breast cancer cases

A report presented December 14, 2006, at the 29th San Antonio Breast Cancer Symposium in Houston shows a 7% drop in US breast cancer rates. The analysis suggests a link between the decline in breast cancer and hormone therapy (HT) use.

December 2006 position statement of The North American Menopause Society

Recent declines in hormone therapy

utilization and breast cancer incidence:

clinical and population-based evidence

Reduced hormone therapy use

might be cause of steep decline in

breast cancer cases

Greatest decrease in breast cancer was in the number of ER+/PR+ breast cancers. There was little change in other breast cancers. The

greatest decrease also occurred in the women aged 50 to 69, those most likely to be using HT.

Reduced hormone therapy use

might be cause of steep decline in

breast cancer cases

Their data most likely

reflect existing

cancers just below the detection limit in

2002 that slowed or stopped their

growing.

December 2006 position statement of The North American Menopause Society

Reduced hormone therapy use

might be cause of steep decline in

breast cancer cases

Another finding that is consistent with an effect on preexisting tumors is the fact that not a single study thus far has reported a risk increase for

noninvasive disease. If HT were initiating

(causing) new tumor formation, one would expect to see an increase in in situ disease.

December 2006 position statement of The North American Menopause Society

Analisemos então os

Riscos

Há riscos?

É indispensável que seja dada

informação sobre as diferenças

entre

riscos relativos

e

riscos absolutos

uma

vez que os primeiros são a principal causa

de desinformação e alarmismo, sendo os

favoritos dos media…

E então ...

Como saber

Qual é a verdade

e

Explain the

risks

in a way that is

understandable....

Compare the

risks

of HRT with other

better known risks....

Increase incidence Relative risk Risk factor + 20% 1 : 1.2

Physical activity – activate : inactive

+ 60% 1 : 1.6

Serum lipids – normal : raised

+ 30% 1 : 1.3

Alcohol consumption-none:≥20 g daily

+ 30% 1 : 1.3 Hormone replacement-never:5 or more yrs + 10% 1 : 1.1

Oral contraceptives – never user:ever user

+ 40%

1 : 1.4

Age at first birth – 20 yrs : 35 yrs

+ 30%

1 : 1.3

Parity – multiparous : nulliparous

+ 30% 1 : 1.3

Age at menarche – 14 yrs: 11 yrs

+ 100% 1 : 2.0

Age at menopause - 42yrs : 52 yrs

+ 150%

1 : 2.5

Body weight-normal weight : obesity

BREAST CANCER

Exemplos de

Risco Absoluto

,

Risco Relativo

,

Risco Atribuível

• Se comprar um número da lotaria, terá 1

oportunidade em um milhão de ganhar.

(risco absoluto).

• Se comprar cinco números da lotaria, a oportunidade será cinco vezes maior, ou

simplesmente 5 em um milhão.

• As oportunidades de ganhar aumentam 5

vezes, (risco relativo).

• A diferença entre os dois riscos é de 4 em

Risco atribuível, ou de excesso

(que é o mais importante para a clínica)

A diferença entre o risco de

base, subjacente, e o risco após

receber TH é denominada

Não confunda…

Risco Relativo

com

Intervalo de Confiança (C.I.)

Um C.I. de 95% significa que há 95% de

probabilidades de que os “valores

verdadeiros” da população estejam entre

os dois limites.

Se o C.I. cruza a linha de “diferença

nula

” ao ponto de que o benefício se

converta num risco (i.e.1), pode

concluir-se que os resultados não são

Manson J et al. Menopause2006;13(1):139.147

Linha de diferença nula Linha de diferença nula Linha de diferença nula

Efeito sobre o risco de

cancro da mama

WHI

aumento do risco

:

RR 1.26 (CI 1.00-1.59); 26% aumento de risco

AR 0.38% vs 0.30% (ie, 38 vs 30 casos anualmente por

10.000 mulheres)

NÃO SIGNIFICATIVO !

HERS

aumento do risco

:

RR 1.27 (CI 0.84-1.94); 27% aumento de risco

AR 0.59% vs 0.47% (ie, 59 vs 47 casos anualmente por

10.000 mulheres)

Ao ler estudos

Epidemiológicos

POR FAVOR !

Não leiam só os títulos… Não leiam só os resumos…

Há que ler os artigos completos!!

Devemos ser críticos!

Devemos construir os nossos próprios

conceitos!

Assessment of the

understanding of the risks and

benefits of hormone

replacement therapy (HRT) in

primary care physicians

Williams RS, Christie D and Sistrom C.

Respondents that overestimate the

increase or decrease in risk were making

the error of confusing

relative risk

with

absolute risk difference

.

There is a great need for physician

education about the attributable

risks and benefits of HRT

Strategies to help patients

understand risks

Risks of women medicated with E+P (5.2 years)

Risks of women medicated with E only (6.8 years)

Risks of Breast Cancer

Podem reduzir-se

There are no really “safe”

biological active drugs...

There are only “safe” physicians !

Kaminetzy HA 1993

“Aquele que

aprende

mas

não pensa

está

perdido.

O que pensa mas

não aprende

é

perigoso…

mas…

se

aprendermos

e

pensarmos

…

nem estaremos perdidos

nem seremos perigosos

para as nossas doentes

pós-menopáusicas

Conhecer

a doença que uma mulher tem

é tão importante como

conhecer

a mulher que tem a doença

Os médicos devem dar a

informação

a mulher deve

acatar

a

sua decisão

Os médicos devem dar a

informação

a mulher

deve fazer o

que decidiu

Qual é o melhor tratamento ?

• As necessidades e preferências da mulher são

decisivas baseadas no conselho do médico

• Não deve esquecer-se que apesar de haver muitos tratamentos hormonais disponíveis

não são no entanto indispensáveis

• Os médicos têm o dever de dar a sua melhor

informação independente às suas doentes de modo a que elas possam fazer as escolhas acertadas e assim aderir aos tratamentos

• A mulher é quem toma a decisão se o médico não vir contraindicações

• Portanto o melhor tratamento é aquele que a mulher escolher

I personally believe that for the healthy

early post menopausal woman the long term

HT’s, other than relieving vasomotor

symptoms, may play an important role in

improving QoL and in the prevention of CVD, osteoporosis and Alzheimer, under surveillance.

Systemic (parenteral) estrogens, added when needed to vaginal progesterone or progestagen loaded IUD’s, may be very beneficial, largely overpassing minimal risks.

The conclusions of the WHI trial suggest

that the

“

safe

“ woman

(NNH between

600-1000

women)

to initiate HT is

- between 50-59 years of age - with vasomotor symptoms

- less than 10 years after the menopause - being treated with statins

- with a good lipid profile and - with a Body Mass Index >25

E...

que tal com os

produtos

Evitar que uma Mulher

beneficie de uma

correcta terapêutica hormonal

na pós-menopausa

pelo receio de raros efeitos

secundários

não me parece ser uma

Medicina satisfatória…

O que é que temos

aprendido sobre a

Menopausa ?

“Each time we

learn something new

,

the astonishment comes from the

recognition that

we were wrong before.

In truth,

whenever we discover a

new fact

,

it involves the

elimination

of old ones.

WE ARE ALWAYS

,

as it turns

out

, fundamentally

IN ERROR

.”

As convicções são inimigos

mais perigosos da verdade do

que as mentiras

What has been learned from the

major observational studies and

clinical trials?

the first lesson

systematically administered

progestagens may in part suppress

some of the beneficial effects of

estrogens and may also slightly increase

the risk of breast cancer after treatments

with duration greater than five years.

What has been learned from the

major observational studies and

clinical trials?

the second lesson

estrogens, when given alone to

histerectomized women, did not appear to

minimally affect the risk for breast cancer

when compared with controls

What has been learned from the

major observational studies and

clinical trials?

the third lesson

Metabolic effects of estrogens and progestagens, as a whole, can differ

depending on the route of administration, i.e.

oral vs. parentheral, and on the combination of both, in a sequential regimen or in continuous combined administration.

What has been learned from the

major observational studies and

clinical trials?

the fourth lesson

Hormonal treatments are the first

choice for vasomotor symptom relief as

long as they are needed (on and off

assessment).

They should not be used for

the secondary prevention of CVD

, when

atheroma plaques are already present.

What has been learned from the

major observational studies and

clinical trials?

the fourth lesson

(cont.)

Conversely,

they may protect from CVD

if started early during the transition into

the post menopause.

Hormonal treatments are preventive of

osteopenia and osteoporosis at

any

stage in life

The take-home message is:

(1)

Prescribe postmenopausal

hormonal treatments

when clinically indicated

,

if not contraindicated

!

The take-home message is:

(2)

The prescription of long-term

hormonal treatments must

depend always on a benefit/risk

analysis

in comparison with other

non-hormonal

medications and

strategies

.

The take-home message is:

(3)

No answers from ongoing clinical

trials are indispensable to practice

today a good Medicine !

BENEFITS OF HORMONE THERAPY

• HT remains the most effective therapy for vasomotor and estrogen-deficient urogenital symptoms.

• Quality of life and sexuality are key factors to be

considered in the management of the aging individual. • The administration of individualized HT (including

androgenic preparations when appropriate)

improves both sexuality and overall quality of life.

Recommendations on

postmenopausal hormone therapy

limitations on the length of treatment.

• Whether or not to continue therapy should be decided at the discretion of the well-informed hormone user and her health professional, dependent upon the specific goals and an

objective estimation of benefits and an objective estimation of benefits and risks.

IMS reaction to recent breast cancer

data

The use of hormones in early menopause

and

up to age 60 years has a very minor

potential for harm, but may carry

substantial benefits.

Women should

decide annually if they wish to continue

with treatment after consultation with their

caregivers.

The new American way …

or …

a

180º rotation ! …

NAMS position statement on

estrogen and progestagen use in

peri-and postmenopausal women

No single trial should be used to set

public health policy.

The practice of

medicine must ultimately be based on the

interpretation of the entire body of

evidence currently available, given that

there will never be adequate clinical

trials to cover all populations,

NAMS position statement on

estrogen and progestagen use in

peri-and postmenopausal women

Place no limit on ET/EPT treatment

duration,

provided it is consistent with

treatment goals; if monitored regularly,

no

stipulation is made regarding when to

reduce or stop therapy

Key Points:

NAMS March 2007

Position Statement

on Hormone Therapy

The North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007; In press.

HT and Vasomotor Symptoms

Treatment of moderate to severe

vasomotor symptoms (ie, hot flashes,

night sweats) remains primary

indication for systemic ET/EPT

With few exceptions, every systemic ET/EPT

product is government

approved for this indication

Copyright 2007 NAMS position statement. Menopause 2007.

EPT and Breast Cancer Risk

Breast cancer risk increases with EPT

use beyond 5 years

Increased absolute risk in WHI

is viewed as rare (4-6 additional

invasive cancers/10,000 women/yr

when use EPT for ≥5 yrs)

(cont’d)

Copyright 2007 NAMS position statement. Menopause 2007.

ET and Breast Cancer Risk

(cont’d)

Women in WHI’s ET arm had 8 fewer

cases of invasive breast cancer/10,000

women/yr of ET use

Available evidence suggests ET for

<5 yr has little breast cancer risk impact

Limited observational data suggest

ET for >15 yr may increase risk

Copyright 2007 NAMS position statement. Menopause 2007.

3rd International Symposium

of the

Portuguese Menopause Society

In Celebration of the World Menopause Day

The Transatlantic Controversies - The State of the Art

A equipe U.S.A.

1 2 3 4

A equipe Europeia

1. D.Barlow 2. H. Kuhl 4.P.Kenemans 4. A.Pines

As estrelas da Menopausa !

1.D.Barlow, 2.H.Kuhl, 3.P.Kenemans, 4.A.Pines, 5 F.Al-Azzawi, 6.J.Rossouw,

7.J.Stevenson, 8.R.Chlebowski, 9.S.Palacios, 10.Th.Clarkson, 11.M.Sousa, 12.M.Neves-e-Castro, 13.A.Genazzani, 14.J.Calaf, 15.R.Lobo

3rd International Symposium

of the

Portuguese Menopause Society

In Celebration of the World Menopause Day

The Transatla

Algumas das

NCLUSÕES

the Art

October 23, 2004 Fundação Engº António Almeida Oporto – Portugal

KEEPS

K

ronos

E

arly

E

strogen

P

revention

S

tudy

10 anos após a menopausa

ELITE

Early vs. Late Intervention Trial with Estradiol

Não há melhor tratamento para

os sintomas do climatério do

•Se és um clínico tens que acreditar que sabes o que ajuda os teus doentes.

Caso contrário não podes nem aconselhar nem receitar.

•Porém, se és um cientista tens que ter

incertezas: um cientista que deixa de fazer perguntas é um mau cientista…

George Pickering;”Physician and scientist”

UMA MULHER

no Outono da sua vida

merece um Verão de S.Martinho

em vez de um triste Inverno

Como

Este não é o fim,

nem sequer o princípio do fim,

mas talvez seja

o fim do princípio ...

Esperando por

mais...

IV Simpósio Internacional

da Sociedade Portuguesa de Menopausa

The Improvement of Health and Disease Prevention

for the Mid-aged Woman: The State of the Art

20 Outubro 2007

Lisboa . Portugal Pestana Palace Hotel

visite o nosso website www.spmenopausa.ptem 4th International Symposium Sociedade Portuguesa de Menopausa

Av. Almirante Reis nº 62 – 1º Esq. 1150-020 Lisboa - Portugal

Telf: (+351) 21 3174356 – (+351) 93 6016522 Fax: (+351) 21 3156658 e.mail: internationalsymposium@socportmenopausa.mail.pt

Hotel venue:

Pestana Palace – Hotel e Monumento Nacional

www.pestana.com

Participantes, até 31 Maio 2007:

Sócios da SPM e EMAS: € 200,00 Não - Sócios: € 250,00

Participantes, a partir de 31 Maio 2007:

Sócios da SPM e EMAS: € 250,00 Não - Sócios: € 300,00

Inscrições

Para mais informação:

que vão encontrar

aqui !