This document summarizes key learnings from major observational studies and clinical trials on menopause. It discusses that systemically administered progestogens may negate some benefits of estrogens and slightly increase breast cancer risk with treatment durations over 5 years. It notes that isolated estrogens did not impact breast cancer risk in hysterectomized women compared to controls in WHI. It also states that metabolic effects of estrogens and progestogens may differ based on administration route and regimen of sequential vs. continuous combined therapy.

1. Menopausa
o ponto da situação
por
Manuel Neves-e-Castro
Lisboa
XXVI Curso Pós-Graduado de Endocrinologia e
Andrologia
Junho 2005

3. Terrorista
Hormonal

4. Quero fazer
TH !
Terrorista
Hormonal

5. Quero fazer
TH !
Terrorista
Mas todos Hormonal
os médicos
dizem que
NÃO!

6. O que é que temos
aprendido sôbre a
Menopausa?
por
Manuel Neves-e-Castro
Lisboa
Junho 2005

8. As discussões sobre o
climatério são devidas a:
• Uma falta de cultura que impede uma crítica
correcta dos resultados publicados
• Uma má prática da Medicina que ignora a
mulher na sua totalidade
• “Lobbies” politicos do NIH …
• Uma falta de honestidade científica
manifestada por muitos dos relatores do WHI
• “Lobbies” de várias indústrias farmacêuticas
através da actividade de muitos médicos bem
conhecidos que se oferecem… para transmitir
as suas mensagens…
MNC

9. 3rd International Symposium
of the
Portuguese Menopause Society
In Celebration of the World Menopause Day
The Transatlantic Controversies - The State of the Art
October 23, 2004 Fundação Engº António Almeida Oporto – Portugal

10. The Menopausal
“Stars”...
14 15
5 6 7 8 9 10 11 12
13
4
2 3
1
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

11. “MATURITAS” Special Issue
VOL. 51/1.(May 2005)
“Menopausal Health in 2005”
PART 1. Women’s health after WHI.
Reports from the Amsterdam Menopause
Symposium, October 2-4, 2004.
PART 2. Transatlantic confrontation of
options.
Proceedings of the III International Symposium
of the Portuguese Menopause Society
October 23, 2004.
Guest-editor: M. Neves-e-Castro.

12. The U.S.A. “team”
1 2 3 4
1. R. Chlebowski, 2.J.Rossow, 3. R. Lobo, 4. Th.Clarkson

13. The USA Vision
Chair: M.Neves-e-Castro and Mario de Sousa
09.00-09.30 –Controversies about HRT – Lessons from Monkey Models
Th.Clarkson, Wake Forest Univ.
09.30-10.00 – Appropriate Use of Hormones Should Alleviate Concerns
Regarding CV and Breast Cancer Risks
R.Lobo, Columbia Univ
10.00-10.30 –Implications of clinical trials for CVD in younger women
Jacques Rossouw, NIH/NHLBI/WHI
10.30-11.00 Coffee Break
11.00-11.30 – Menopausal Therapy and Cancer Risk in the WHI
R.Chlebowski, WHI
11.30-12.00 - The state of the Art in the USA
L.Speroff,Portland.Or
12.00-13.00 - Debate and Discussion

14. The European “team”
1 2 3 4
1. D.Barlow, 2. H. Kuhl, 3.P.Kenemans, 4. A.Pines

15. The European Vision
Chair: Mario de Sousa and M. Neves-e-Castro
14.30-15.00 – WHI and Cardioprotection: Looking Beyond the Figures
A.Pines, Il
15.00-15.30 – Hormone Therapy and Breast Cancer:
What is the Problem?
P.Kenemans,Nl
15.30-16.00 – Do Estrogens Really Increase Breast Cancer Risk?
H. Kuhl, D
16.00-16.30 –Coffee Break
16.30-17.00 Strategy in Osteoporosis Management Following WHI
D.Barlow, UK
17.00-18.00 Debate and Discussion
Chair:A. Genazzani (I) and J.Calaf (Sp)
18.00 - Conclusions
M.Neves-e-Castro

16. Conclusões

17. Acreditamos que no que se refere às
DCV’s,quer os estudos experimentais
em primatas como a evidência clínica
sugerem fortemente que os TH’s
podem ser preventivos se iniciados
muito precocemente após a
menopausa,de preferência depois de
um regime de contraceptivos orais
durante a premenopausa
Clarkson TB. Fertil Steril 2004;81:1498-1501
Grodstein F et al. N Engl J Med 2000;343:530-537
Stampfer MJ. NAMS 2004;PS#2
Victory R et al. Fertil Steril 2004;82:O-130

18. O grupo de “estrogénios isolados” do WHI
sugere fortemente que uma medicação
apenas com estrogénios é destituida de
riscos como parece até ser protectora em
relação ao cancro da mama.
Resultados idênticos foram verificados em
estudos de gravidez após cancro da mama e
em TH’s nas sobreviventes de cancro da mama.
Gelber s et al. J Clin Oncol 2001;19:1671-1675
WHI Group J Am Med Assoc 2004;291:1701-1712
O’Meara et al. J N C I 2001
DiSaia et al. Am J Clin Oncol 2000
Nananda F Col et al.J Clin Oncol;2001:19:2357-2363

19. Em estudos recentes não se
verificou,nos tratamentos combinados
contínuos qualquer risco aumentado
de DCV’s ou de cancro da mama.
Esta diferença em relação ao WHI deve-
se a que as mulheres eram mais
novas,sintomáticas,e com menor pêso
corporal
Heikkinen J. NAMS 2004, Abstract LB38
Lobo R. Arch Int Med 2004;164:482-484

20. Acentuamos a necessidade de
implementar medidas colaterais muito
importantes tais como:
• normalização do peso corporal
• abstenção de tabaco
• baixo consumo de alcool
• execício
• Dieta Mediterrânica
etc.
MNC

21. Em conclusão,
e à luz da evidência actual,
deve dar-se aos médicos e às
mulheres a garantia de que os TH’s
para o alívio dos sintomas da
menopausa são seguros e muito
eficazes
MNC

23. WHI

24. What Was the WHI Study
designed to do?
Long-term effect of hormone therapy on the
prevention of
heart disease and
hip fractures and
on monitoring possible increases in risk for
breast cancer and
colon cancer.
Message from the President on WHI Study
www.hormone.org

25. White woman’s risk of death between
the ages of 50 and 94 are:
31.0% from heart disease
2.8% from breast cancer
2.8% from hip fracture
Brinton LA, Schairer C. N Engl J Med.1997;336:1769-1775

28. Effect on the risk of breast
cancer
WHI Nonsignificant increased risk
RR 1.26 (CI 1.00-1.59); 26% increased risk
AR 0.38% vs 0.30% (ie, 38 vs 30 events
annually per 10.000 women)
HERS Nonsignificant increased risk
RR 1.27 (CI 0.84-1.94); 27% increased risk
AR 0.59% vs 0.47% (ie, 59 vs 47 events
annually per 10.000 women)

29. 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” (?!...)

30. Thus…
“The breast cancer findings are
reported as statistically
insignificant but are regarded as
clinically relevant !”
Utian W. Menopause Management 2003;12:9-10

31. WHI results calculated as
NNT/1 year NNH/1 year
CHD 1428
Stroke 1250
VTE 588
Breast Cancer 1250
Colon Cancer 1667
Osteoporotic fractures 227
(totals)
Neves-e-Castro M. Menopause in crisis post-Women’s Health Initiative? A
view based on personal clinical experience. Human Reproduction
2003;18:2512-8

32. “Women considering taking CEE should be
counseled about an increased risk of stroke
but can be reassured about no excess risk
of heart disease or breast cancer for at
least 6.8 years of use.”
Effects of conjugated Equine Estrogen in Postmenopausal Women with
Hysterectomy. JAMA 2004;291:1701-1712

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

34. Why Was the Study Stopped?
• Small increase in the risk of strokes, which put
healthy women at risk and made it
unacceptable to continue with the study.
• No increased risk for breast cancer and a
decrease in the risk of hip fractures.
Message from the President on WHI Study
www.hormone.org

35. 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”
EMAS Statement; 2004.

36. NAMS position statement on
estrogen and progestagen use in
peri-and postmenopausal women
Revised breast cancer statements indicate
that the risk of breast cancer probably
increases with EPT use but not with ET
use.

37. Second thoughts on the WHI study: the effect of age on the safety HRT
Studd J. Climacteric 2004;7:412-414

38. O “braço” do WHI com estrogénios
isolados foi interrompido!
Porquê ? ! …

39. • Parece que se tivesse havido mais
um caso de cancro da mama no
grupo placebo os resultados deste
estudo teriam sido considerados
como estatisticamente muito
significativos…
MNC

40. Portanto…
o grupo WHI/NIH teria sido forçado a
declarar que:
• Os estrogénios não induzem o
cancro da mama , e que
• Os estrogénios protegem a mama
contra o cancro !
MNC

41. Porque é que os investigadores
não quiseram que o estudo fosse
terminado e pudesse chegar a
conclusões tão importantes?
Seria pela necessidade de alguns
investigadores continuarem a
receber milhões de dólares?
MNC

42. Million Women Study
The follow-up for breast cancer
diagnosis was just over 2½ years,
meaning that these breast cancers
were almost certainly pre-existent at
the start of the observational period.
Press Release from the British Menopause Society, 2003

45. Occult Breast Cancer
in
medicolegal autopsies
Breast malignancy was
found in 22 women
(20%)
Nielsen M et al-Br J Cancer 1987;56:814-9

46. Occult Breast Cancer
Malignancy was significantly more frequent
among women
. aged more than 40 years
. with late age at first full-term pregnancy
. with alcohol abuse
. with steatosis or cirrhosis of the liver
Nielsen M et al-Br J Cancer 1987;56:814-9

47. Breast Cancer
MWS data compared to other publish data
MWS GPRD Beral Ross Weiss WHI
(2003) (2002) (1997) (2000) (2002) (2003)
EPT 2.00 1.211 1.152 1.243 1.22 1.26
ET 1.30 0.97 0.992 1.063 0.84 ongoing
4
Tibolone 1.45 1.02
1
Seq EPT 2
≤ 5 y use 3
Per 5y 4
>6y
use

48. HRT and RR of DEATH from
BREAST CANCER
(MW Study,2003)
• AR never users 238/2894 = 0.0822
• AR current users 191/3202 = 0.0597
• RR = 0.0597/0.0822 = 0.73
• RR for mortality = 1.22
• RR for morbidity =1.66
• RR for dying from BC = 1.22/1.66 = 0.73

49. Fatal Breast Cancers
Case-death Case-No death
Current use 191 3011 3203
Never use 238 2656 2894
RR=0.71 (95% CI 0.58-0.87)
Million Women Study Collaborators. Breast Cancer and hormone replacement
therapy in the Million Women Study. Lancet 2003;362:419-427

53. “Recurrent breast cancer was
found in 9% of HRT users
and 15% of nonuser”.
O’Meara ES et al

54. 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.
Natrajan PK and Gambrell RD. Am J Obstet Gynecol 2002;187:289-95

55. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
1ª.lição
Os progestagénios administrados por via
sistémica podem em parte suprimir alguns
dos efeitos benéficos dos estrogénios e
podem tambem aumentar ligeiramente o
risco de cancro da mama após
tratamentos com uma duração superior a
cinco anos
MNC

56. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
2ª.lição
Os estrogénios quando administrados
isoladamente em mulheres histerectomizadas
não afectaram minimamente o risco para o
cancro da mama quando comparado com os
controlos
MNC

57. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
3ª.lição
Os efeitos metabólicos dos estrogénios e
progestagénios, como um todo, podem diferir
em função da via de administração i.e. oral vs.
parentérica, e da combinação de ambos em
regimes de administração sequencial ou
combinada contínua
MNC

58. Relative risks associated with use of
different hormones by women
Cases Person/ Age-adjusted RR
Years (CI – 95%)
Estrogens used alone
Transdermal 29 8.961 1.2 (0.8 – 1.8)
Oral 2 1.204 0.6 (0.2 – 2.4)
Estrogens combined with oral progesterone
Estrogens combined with micronized progesterone 55 21.994 0.9 (0.7 – 1.2)
Transdermal 55 20.685 0.9 (0.7 – 1.2)
Oral 0 1.385
Estrogens combined with synthetic progestins
Transdermal 187 46.252 1.4 (1.2 – 1.7)
Oral 80 20.504 1.4 (1.1 – 1.8)
Fournier A et al. Int J Cancer 2005;114:448-54

59. Progesterone and Breast Cancer
Combinations containing micronized
progesterone appeared to be
associated with a significantly lower
breast cancer risk than those
containing synthetic progestagens.
Fournier A et al. Int J Cancer 2005;114:448-54

60. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
4ª.lição
Os tratamentos hormonais são a primeira
escolha para a abolição dos sintomas
vasomotores enquanto necessários. Não
devem ser usados para a prevenção secundária
da DCV, quando já houver placas de ateroma.
MNC

61. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
4ª.lição (continuação)
Os estrogénios podem proteger contra
DCV’s se iniciados precocemente
durante a transição para a pós
menopausa.
Os tratamentos hormonais são
preventivos da osteopenia e osteoporose
em qualquer fase da vida
MNC

62. Postmenopausal hormone therapy: critical
reappraisal and unified hypothesis
83:558-66

63. Postmenopausal former oral contraceptives
users may have lower rates of heart
disease
702 postmenopausal women enrolled in the
WISE.
Use of oral contraceptive in the past was
an independent negative predictor of
CAD severity (p=0.04 after adjustment for
smoking, aspirin use, lipid lowering medication, and
socioeconomic variables )
14th Annual Meeting of the North American Menopause Society. Abstract
P-51

64. Combined effect of oral contraceptive
use and hormone replacement therapy
on breast cancer risk in postmenopausal
women
The increase in risk with CHRT was
stronger in women who had never used
OC’s in the past than in women who had
used OC’s
Norman SA et al. Cancer Causes Control 2003;14(10):933-43

65. Discussion
The results of this study show a strong
association of current HT with reduced
odds of severe coronary artery
calcification, an indicator of
atherosclerotic plaque burden.
Barrett-Connor E et al. Menopause 2005;12:40-48

66. Discussion
The protective association of HT with
CACS was greater in longer versus
shorter duration users and tended to be
stronger in those whose HT use began
early in postmenopause.
Barrett-Connor E et al. Menopause 2005;12:40-48

67. O que é que aprendemos com os
principais estudos observacionais e
ensaios clinicos?
5ª.lição
Os estrogénios podem evitar lesões
degenerativas do SNC uma vez que, até à
data, são os únicos agentes com efeito no
crescimento dos neurónios
MNC

68. Postmenopausal Estrogen Use
Affects Risk for Parkinson Disease
• Estrogen therapy has been associated
with improved cognitive functioning, a
reduced risk of dementia in women
with Parkinson disease (PD), and a
decreased risk of Alzheimer disease.
• Postmenopausal estrogen therapy may be
associated with a reduced risk of PD in
women.
Currie LJ et al. Arch Neurol 2004;61(6):886-8

69. IADRD: Estrogens Exhibits
Neuroprotective effect in preliminary
analysis of Swedish Data
Preliminary analysis of data from the Swedish
Twin Registry suggests that estrogen is
neuroprotective and the effect is not related
to length of estrogen therapy.
Estrogen use was significantly related to better
cognitive functioning (odds ratio [OR]=0.43 95%
confindence interval [CI]=0.26, 0.70)
Peck P. DG News Stockholm, July 24, 2002.

71. Como se podem reduzir os
riscos potenciais ?

72. Dimitrakakis C et al. Menopause 2004;11:531-535

73. A physiologic role for testosterone
in limiting estrogenic stimulation of
the breast.
These findings suggest that treatment with
a balanced formulation including all
ovarian hormones may prevent or reduce
estrogenic cancer risk in the treatment of
girls and women with ovarian failure.
Dimitrakakis C et Al. Menopause 2003;10(4):292-8

74. Quais são os melhores tratamentos
durante e para além do climatério?
Não tem sido prestada a devida
atenção a outras intervenções
farmacológicas (não hormonais) e a
estratégias que se verificou serem
importantes para a prevenção de tais
doenças e para a manutenção ou
melhoria da saúde
MNC

76. A TH não é possivel …
• Quando não é desejada pela mulher
• Quando a mulher não sente a sua
necessidade
• Quando há contraindicações
MNC

77. Intervenções Farmacológicas
• Sintomáticas
• Perventivas
– primárias
– Secundárias
MNC

78. Nurses’s Health Study
from 1980 to 1994 CHD ↓ 31%
↓ Smoking ↓ 13%
↑ Obesity ↑ 8%
↑ THS ↓ 9%
↑ Better nutrition ↓ 16%
Hu FB, Grodstein F et al. Trends in the Incidence of Coronary Heart Disease
and Changes in Diet and Lifestyle in Women. NEJM 2000;343:530-537.

79. “It appears that half of the
benefits in the prevention of
cardiovascular diseases are
not hormone related”!
Mosca L, Grundy SM, Judelson D, et al. Circulation 99;99:2480-4

80. Association between alcohol
consumption and postmenopausal
breast cancer
results of a case-control study in Montreal, Quebec, Canada
Women who started to drink wine on or
before the age of 40 were at a 2.5 times
increased risk (95% CI 1.4-4.4).
CONCLUSIONS: Our findings provide
further support for a positive association
between the risk of postmenopausal
breast cancer and alcohol
consumption.
Lenz SK et al.Cancer Causes Control 2002;13(8):701-10

81. Mediterranean Diet, Lifestyle
Factors, and 10-Year Mortality in
Elderly European Men and Women
The combination of 4 low risk factors lowered
the all-cause mortality rate to 0.35 (95% CI,
0.28-0.44). In total, lack of adherence to this
low-risk pattern was associated with a
population attributable risk of 60% of all
deaths, 64% of deaths from coronary heart
disease, 61% from cardiovascular diseases,
and 60% from cancer.
Knoops K et al. JAMA 2004;292:1433-9

82. The Polymeal
Franco O et al. BMJ 2004;329:1447-50

83. Doctors could retrain as
Polymeal chefs or wine advisers
The Polymeal—an evidence based menu that
includes wine, fish, dark chocolate, fruits,
vegetables, garlic, and almonds—promises to be an
effective, safe, cheap, and tasty solution to reducing
cardiovascular morbidity and increasing life
expectancy.
Polymeal could reduce cardiovascular disease by
more than 75%.
Franco O et al. BMJ 2004;329:1447-50

84. Tea, circulating estrogens and
breast cancer
Levels were
13% lower in regular green-tea drinkers
(25.8 pg/ml)
19% higher in regular black tea drinkers
(35.0 pg/ml).
Wu A. et al. Carcinogenesis 2005.

85. Tea, circulating estrogens and
breast cancer
“We recently provided the first set of human
evidence that breast cancer risk is
significantly inversely associated with tea
intake, largely confined to intake of green tea.”
“Green tea may have down-regulatory effects
on circulating sex-steroid hormones,
whereas black tea may have up-regulatory
effects .”
Wu A. et al. Carcinogenesis 2005

86. RELATIVE RISK OF BREAST CANCER BY
BODY WEIGHT
Weight (Kg)
Age at
Diagnosis <60 60-69 70+
35-49 1.00 0.54 1.16
50-59 1.00 1.22 1.43
60-69 1.00 1.61 1.81
from deWaard et al ,1964,1978

87. HU FB et al. NEJM 2004;351:2694-2703

88. HU FB et al. NEJM 2004;351:2694-2703

89. HU FB et al. NEJM 2004;351:2694-2703

90. Recreational Physical Activity
and the Risk of Breast Cancer in
Postmenopausal Women
Women who engaged in the equivalent of 1.25
to 2.5 hours per week of brisk walking had an
18% decreased risk of breast cancer (RR,
0.82; 95% CI, 0.68-0.97) compared with
inactive women.
McTiernan A et al. JAMA 2003;290:1331-6

91. Aspirin could be used to prevent
cancer
Three recently published studies indicate
that aspirin, already enjoying a second
lease of life in the prevention of heart
disease, may soon become a first line of
defense against cancer.
London O. BMJ 2003;326:565

92. Breast Cancer and Nonsteroidal
Anti-Inflammatory Drugs:
Prospective Results
from the Women’s Health Initiative1
COX-2 induction may promote breast
cancer development by enhancing local
estrogen biosynthesis, and COX-2
inhibition may reverse the process.
Harris R et al. Cancer Research 2003;63:6096-6101

93. Inhibitory effect of statins on the
proliferation of human breast cancer
cells.
Atorvastatin and fluvastatin were able
to inhibit the proliferation of MCF-7
cells in the absence of estradiol.
This effect seems to depend on an
apoptotic statin effect.
Muck AO et al. Int J Clin Pharmacol Ther 2004;42(12):695-700

94. Inhibitory effect of statins on the
proliferation of human breast cancer
cells.
The present data indicate that statins
may possess anticancerogenic
properties concerning the development
of breast cancer in postmenopausal
women.
Muck AO et al. Int J Clin Pharmacol Ther 2004;42(12):695-700

95. The Polypill
Wald N and Law M. BMJ 2003;326:1419-25

96. A strategy to reduce
cardiovascular disease by more
than 80%
One third of people taking this pill from age 55
would benefit, gaining on average about 11
years of life free from an IHD event or
stroke.
Wald N and Law M. BMJ 2003;326:1419-25

97. Wald N and Law M. BMJ 2003;326:1419-25

98. O que pensam os outros?...
Após uma viragem de
180º em dois anos…
a NAMS (North American
Menopause Society)
acaba de concluir…

99. 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,
eventualities, and regimens.

100. 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

101. Há riscos?
É indispensável que seja dada
informação sôbre 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…
MNC

107. Analisem-se
os factores de risco
• Cardiovasculares
• Oncológicos
• Ósseos
• SNC
MNC

108. Years of healthy life can be increased 5-
10 years, W O says
H
W need to concentrate on the
e
major risks if we are to improve
healthy life expectancy by about 10
years, and life expectancy by even
m ore.
A n Lo p e z , Ph. D. , WHO Se nio r Sc ie nc e A v is o r a nd c o -
la d
d ire c to r o f the WHO re p o rt (2 0 0 2 )

109. Welty F. Menopause 2004;11(4):484-94

110. As mulheres não são
estatísticas…

111. Têm que ser tratatadas
individualmente !

112. Evidence based medicine: does it
make a difference?
Like any technology, evidence based
medicine carries risks and benefits and
can be used appropriately or
inappropriately.
Schon CR et al. BMC Health Serv Res 2003;3(1):14

113. Evidence informed practice
• 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

114. Medicina Baseada na Evidência
e/ou
Evidência Baseada na Medicina ?
Manuel Neves-e-Castro

115. Medicina Baseada na Evidência
e/ou
Medicina Baseada na Inteligência ?
Lucas Viana Machado

116. “Aquele que aprende
mas não pensa
está perdido.
O que pensa mas
não aprende
é perigoso…
Confucius

117. Se aprendermos e
pensarmos…
nem estaremos perdidos
nem seremos perigosos
para as nossas doentes pos-
menopausicas
Wenger NK. Am J Geriatr Cardiol 2000;9:204-9

118. “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.”
Lewis Thomas English Biologist (1913-1993)

119. Quais são as melhores recomendações
do médico da mulher climatérica
1. Explicar o que se está passando no seu corpo durante
o climatério e pós menopausa
2. Ocupação mental
3. Exercicio fisico
4. Alimentação adequada (consumo moderado de vinho
tinto e abundante de: peixe, vegetais, frutos, soja,
leite, alho, chocolate, etc)
5. Manter o índice de massa corporal dentro dos limites
normais
6. Manter um perímetro normal da cintura
7. Abstenção do tabaco
8. Manter uma pressão arterial normal
9. Manter os lípidos sanguíneos nos valores normais
(estatinas)
10. Exame mamário (palpação, inspecção mamografia)

120. Qual é o melhor tratamento ?

122. Qual é o melhor tratamento ?
• Em termos gerais é o que estiver sensatamente
indicado, se não contraindicado, após uma
análise de benefícios e riscos, de todas as
estratégias e intervenções, hormonais ou não
hormonais
• Deve estar dirigido a objectivos e alvos
específicos que serão avaliados regularmente
de modo a determinar a sua eficácia e a
verificar a eventual ocorrência de quaisquer
efeitos secundários, uma condição que
determinará a sua duração
MNC

123. 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 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
MNC

124. Mensagens Finais
(1)
• Prescrevam tratamentos
hormonais na pós menopausa
quando clínicamente indicados,
se não houver contraindicações
MNC

125. Mensagens Finais
(2)
• A prescrição de tratamentos
hormonais de longa duração
depende sempre de uma análise
benefício/risco em comparação com
medicações não hormonais e
estratégias não medicamentosas
MNC

126. Mensagens Finais
(3)
• Não são indispensáveis
quaisquer respostas dos
ensaios clínicos em curso para
que se possa hoje praticar uma
boa Medicina
MNC

127. HT appears to be the best form of
pharmacologic treatment
to improve brain function, as well as
to reduce the risk of colon cancer. It is
probably the best preventive strategy
for osteoporosis.
With this in mind …
limiting HT to the treatment of
climacteric symptoms only is
unjustified.
Kopernik G and Shoham Z. Fertil Steril 2004;81(6):1458-1477

128. Evitar que uma mulher
beneficie de
um bom tratamento
hormonal pós menopáusico
só pelo receio de efeitos
secundários raros
não parece ser uma
Medicina satisfatória …
Manuel Neves-e-Castro

129. Mortality Associated with HRT in
younger and older women
Hormone Replacement Therapy reduced
total mortality in trials with mean age of
participants under 60 years.
No change in mortality was seen in trials
with mean age over 60 years.
Salpeter SR et al. J Gen Intern Med 2004;19:791-804

130. Por isso …
Vários ilustres colegas , “especialistas” em
menopausa:
H . Schneider (Alemanha)
A . Genazzani (Itália)
P . Kenemans (Holanda)
e tambem eu próprio,
continuamos a fazer tratamentos hormonais
de longa duração às nossas consortes com
os seguintes resultados:

131. Schneider Genazzani Neves-e-Castro Kenemans

132. Estou muito grato …
por terem tido a paciência
de me ouvirem,
sem dormir…