Tenth Anniversary of Initial Women’s Health Initiative (WHI) Report
Richard Santen, MD
University of Virginia
12/2/11
Tenth Anniversary of Initial Women’s Health Initiative (WHI) Report
• What have we learned?
• How should the public be informed?
• What should a post-menopausal woman do, based on what we now know?
WHI
• First report 2002• Two arms
– Placebo versus conjugated equine estrogen plus MPA (E+P)
– Placebo versus conjugated equine estrogen alone (E)
• 80% reduction in menopausal hormone use over the next five years
WHI 10 years later:key conclusions after a decade of reflection
• Need to consider all information based on excess risk and benefit and not relative risk and benefit
• Only women just entering menopause are candidates for menopausal hormone therapy
Initial WHI Report 2002major finding
26% increasein risk of breast cancer
Do I have a 26% chance of getting breast cancer since I have taken hormones for more than 5 years? That is a
one in four chance. Is this really true?
My wife immediately asked me
My answer No, the 26% increase represents only relative risk.
Her reply What does that mean for me?
Important Issue
• We need to distinguish between: –relative risk –absolute risk –excess risk
This is how I explain this to my wife
One Million Women who marched in Washington
120,000 of these women or 12% will develop breast cancer in their lifetimes
This is absolute risk
12,000 or 1% will develop breast cancer in five years
Absolute risk
Lets consider just 1000 of these marchers
How many of these women will get breast cancer within five years?
18 Women not receiving MHT will develop breast cancer over a five year period
Absolute risk
26% increase in relative risk in WHI
If these 1000 women take MHT for five years,
22 women will develop breast cancer
18 with breast cancer without MHT22 with breast cancer with MHT
Excess risk 4
My Answer: Based on the WHI study, you will only have a 4 in 1000 chance of getting a breast cancer
that you would not otherwise have gotten if you take MHT for 5 years
WHI 10 years later
• Relative risk is only important when absolute risk is high
• Example from common experience
Example of relative vs absolute risk
• If you take one plane flight your chances of crashing are one in ten million (absolute risk)
• Your relative risk of crashing is increased by 500% if you take five plane flights .
• Your excess risk by taking five flights rather than one is four per ten million
• Bottom line: relative risk means little when absolute risk is low• This is the reason to convert all WHI data to excess risk or
benefit
WHI 10 years later
• Need to consider all risk and benefit data consistently
• The Endocrine Society has expressed all risks and benefits as the number of women per 1000 using MHT for 5 years who will experience event
What are the major excess risks reported in the original WHI study?
WHI Estrogen plus Progestin MHT
Excess Risks
# w
omen
/1,0
00/5
yrs
0
2
4
6
8
10 E+P
Risks
Benefits
WHI E+P
Average age 63
What are the under-reported benefits?
Reduction in Mortality
Under-reported Benefits (WHI)#
pre
vent
ion
/1,0
00
/5 y
rs
0
5
10
15
20
25
30EE+P
Timing HypothesisEarly vs. late treatment
Early Late5
4
3
2
1
0
5
4
3
2
1
EE+P
EE+P
5
4
3
2
1
0
5
4
3
2
1
Timing HypothesisEarly vs. late treatment
Early Late
4
2
0
6
4
2
8
6
8
EE+P
4
2
0
6
4
2
8
6
8EE+P
VTE and Stroke
Similar relative increase in risk but younger women experience these problems less commonly
MHT 10 years after WHIonly used at start of menopause
RisksBenefits
For Some in Menopause, Hormones May Be Only Option
By TARA PARKER-POPE
New York TimesAugust 15, 2011
MHT 10 years after WHIwomen with severe symptoms
Risks
Benefits
What to do about breast cancer risk?
Benefit
Low risk of breast cancer
Risk
High risk of breast cancer
Assess risk of breast cancer and only treat those at low risk
• Low risk (i.e. 0.5% chance of breast cancer in 5 year) excess risk is 2.5/1000 per 5 years
• High risk (i.e. 4% chance of breast cancer in 5 years) excess risk 20/1000/5 years
RR
Estrogen Related Risk Factors
0
1
2
3
4
5
6Bre
ast
Den
sity
Breast Cancer Risk Factors by Group
Plas
ma
E2Age
at
Men
opau
seAge
at
1st L
ive
birt
h
BM
IAge
at
Men
arch
e
MH
T
RR
Estrogen Related Risk Factors
0
1
2
3
4
5
6Other Risk
FactorsBre
ast
Den
sity
Plas
ma
E2Age
at
Men
opau
seAge
at
1st L
ive
birt
h
BM
IAge
at
Men
arch
e
MH
T1
o Rel
ativ
e2
o Rel
ativ
e
Alc
ohol
Breast Cancer Risk Factors by Group
Calculation of Breast Cancer Risk
• Gail Model (http://www.cancer.gov/bcrisktoolmobile)
• Tyrer-Cuzick Model (http://pulsescreening.co.uk/Corporate/Breast_cancer_prediction_model-1.pdf)
For Some in Menopause, Hormones May Be Only Option
By TARA PARKER-POPE
New York TimesAugust 15, 2011
WHI after 10 years
The Ultimate Goal is to provide the most benefit
to the patient while avoiding the most risks
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