Transcript AOTEAROA WOMEN’S HEALTH INITIATIVE:

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Women’s Health Initiative - Summary of results
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Dr Beverley Lawton Dr Jill Shepherd
18/7/2002 comment on WHI study
• The following is a presentation covering the
results of the recent WHI study. This is
designed primarily for a medical audience
• Please feel free to send comments to
[email protected] and discussion
will be reported under book exerpt
Women’s Health Initiative - Summary of results
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National Institutes of Health (NIH)
Women’s Health
Initiative (WHI)
The Results
JAMA, July 17, 2002 - Vol 288, No.3
Women’s Health Initiative - Summary of results
WHI Study Design
Two study arms:
1. Combined HRT vs Placebo Terminated
Conjugated equine oestrogens (0.625mg) +
medroxyprogesterone acetate (2.5mg) vs placebo
2. Oestrogen vs Placebo
Ongoing
Conjugated equine oestrogens (0.625mg) vs placebo
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Combined HRT vs Placebo
Study Design
• n=16,608 women with an intact uterus
• Age range= 50-79yrs (Average age = 63 yrs)
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Recruited from 40 US centres between 19931998
Follow-up of 5.2 years (8.5 years planned)
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Main Findings
RELATIVE AND ABSOLUTE RISK OR BENEFIT SEEN IN OESTROGEN
PLUS PROGESTOGEN ARM OF WHI
(n =16,608, placebo and study drug)
Health Event
Relative Risk
vs. Placebo
Group
at 5.2 Years
(Nominal 95% CI)
Increased
Absolute Risk
per 10,000
Women/Year
Heart Attacks
Strokes
Breast Cancer
Thromboembolic Events
Colorectal Cancer
Hip Fractures
1.29 (1.02-1.63)
1.41 (1.07-1.85)
1.26 (1.00-1.59)
2.11 (1.58-2.82)
0.63 (0.43-0.92)
0.66 (0.45-0.98)
7
8
8
18
Increased
Absolute
Benefit
per 10,000
Women/Year
6
5
Adapted from JAMA 2002; 288: 321-
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Composite Outcomes for E+P
Outcome
Total Cardiovascular Disease
Total Cancer
Combined Fractures
Total Mortality
Global Index
Hazard Ratio (95% CI)
1.22 (1.09-1.36)
1.03 (0.90-1.17)
0.76 (0.69-0.85)
0.98 (0.82-1.18)
1.15 (1.03-1.28)
 No difference in mortality and no overall increase in
cancers
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Main Findings: the Risks
Per 10,000 women after 5 years there was an
increased risk of:
• Breast Cancer
(from 30 to 38 cases)
• Coronary Heart Disease (from 30 to 37 cases)
• Stroke
(from 21 to 29 cases)
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Main Findings: the Benefits
Per 10,000 women after 5 years there were
reductions in:
• Colorectal Cancer
• Hip Fracture
Women’s Health Initiative - Summary of results
(from 16 to 10 cases)
(from 15 to 10 cases)
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Absolute Excess Risks
Absolute excess risks per 10,000 person years
attributable to oestrogen+progestin were:
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7 more CHD events
8 more strokes
8 more PEs
8 more invasive breast cancers
The absolute excess risk of events included in the
global index was 19 per 10,000 person years
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Absolute Risk Reductions
Absolute risk reductions per 10,000 person years
attributable to oestrogen+progestin were:
• 6 fewer colorectal cancers
• 5 fewer hip factures
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DSMB recommendation
• Study terminated because the test statistic for
invasive breast cancer exceeded the stopping
boundary for this adverse effect
• The global index statistic supported risks
exceeding benefits
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Study Conclusions
• Overall the health risks exceeded benefits from
use of combined estrogen+progestin among
healthy postmenopausal US women
• Results indicate that this regimen should not be
initiated or continued for the primary prevention
of CHD
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Discussion points
• Significant study
• Breast cancer “strong trend” as rates not
statistically significant
• Study stopped on breast Ca, and global
trend not CHD events
• Trial could not distinguish the effects of
oestrogen from progestin
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Discussion points
• Older women – average age 63 years
• Not taking HRT for symptoms
• Large dropout rate – 42 % HRT group and
38% of placebo
• What is the significance of Progestin?
• Oestrogen arm had NO increased breast
cancer rate and is continuing
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• The risk to an individual is small for
example the increased risk for a women for
1 year for breast cancer is less than 1tenth
of a per cent.
• Oestrogen alone appears to be safer as this
arm is continuing.
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Other issues not covered
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Quality of life
Vaginal Health
Cognition
Gallbladder
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Benefits of HRT
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Established Benefits
• Eliminates hot flushes, night sweats, dry
vagina, and palpitations.
• Reduces osteoporotic bone fracture
(?P)
• Reduces colorectal cancer (?P)
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Possible Benefits
• May increase mood and feeling of wellbeing –quality of life
• May reduce risk of Alzheimer’s disease
• May reduce arthritis
• May maintain dental health
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Contraindications for HRT
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Active hepatitis- acute
Previous DVT (?)
MI in the last 6 months
Undiagnosed vaginal bleeding
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RISKS of HRT
Women’s Health Initiative - Summary of results
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Established Risks
• HRT increases the risk of VTE (?P)
• HRT increases the risk of non-fatal
stroke (?P)
• HRT increases the rate of non-fatal MI
(?P).
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Established Risks 2
• Estrogen increases the risk of
endometrial cancer when it is taken
without a progestin.
• HRT increases the incidence of
gallbladder disease in some women
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Possible Risks
• There may be an increased risk of
breast cancer after taking HRT for five
years or more (?P)
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What to say to patients
• The risk to individual women is small and
includes a small risk in DVT, stroke, CHD.
• No increased breast cancer risk in first 4
years of use (?P)
• Safe and effective for symptoms
• Effective for osteoporosis; but other
medications longterm
Women’s Health Initiative - Summary of results
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