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www.menopausetoday.comWomen’s Health Initiative - Summary of results
DISCLAIMER
• Menopausetoday gives the following presentation for your information and to promote discussion.
• We welcome your comments
• We advise you if you have concerns to consult your doctor or local health department for further information.
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
National Institutes of Health (NIH)
Women’s Health Initiative (WHI)
The Results
JAMA, July 17, 2002 - Vol 288, No.3
www.menopausetoday.comWomen’s Health Initiative - Summary of results
WHI Study Design
Two study arms:
1. Combined HRT vs Placebo TerminatedConjugated equine oestrogens (0.625mg) + medroxyprogesterone acetate (2.5mg) vs placebo
2. Oestrogen vs Placebo Ongoing Conjugated equine oestrogens (0.625mg) vs placebo
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Combined HRT vs Placebo Study Design
• n=16,608 women with an intact uterus
• Age range= 50-79yrs (Average age = 63 yrs)
Recruited from 40 US centres between 1993-1998
Follow-up of 5.2 years (8.5 years planned)
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Main FindingsRELATIVE AND ABSOLUTE RISK OR BENEFIT SEEN IN OESTROGEN
PLUS PROGESTOGEN ARM OF WHI(n =16,608, placebo and study drug)
Health Event Relative Riskvs. Placebo
Groupat 5.2 Years
(Nominal 95% CI)
IncreasedAbsolute Risk
per 10,000Women/Year
IncreasedAbsoluteBenefit
per 10,000Women/Year
Heart AttacksStrokesBreast CancerThromboembolic EventsColorectal CancerHip 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)
788
1865
Adapted from JAMA 2002; 288: 321-
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Composite Outcomes for E+P
Outcome Hazard Ratio (95% CI)
Total Cardiovascular Disease 1.22 (1.09-1.36)
Total Cancer 1.03 (0.90-1.17)
Combined Fractures 0.76 (0.69-0.85)
Total Mortality 0.98 (0.82-1.18)
Global Index 1.15 (1.03-1.28)
No difference in mortality and no overall increase in cancers
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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)
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Main Findings: the Benefits
Per 10,000 women after 5 years there were reductions in:
• Colorectal Cancer (from 16 to 10 cases)
• Hip Fracture (from 15 to 10 cases)
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Absolute Excess RisksAbsolute excess risks per 10,000 person years
attributable to oestrogen+progestin were:
• 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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Absolute Risk Reductions
Absolute risk reductions per 10,000 person years attributable to oestrogen+progestin were:
• 6 fewer colorectal cancers
• 5 fewer hip factures
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
• 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.
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Other issues not covered
• Quality of life
• Vaginal Health
• Cognition
• Gallbladder
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Benefits of HRT
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Established Benefits
• Eliminates hot flushes, night sweats, dry vagina, and palpitations.
• Reduces osteoporotic bone fracture (?P)
• Reduces colorectal cancer (?P)
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Possible Benefits
• May increase mood and feeling of well-being –quality of life
• May reduce risk of Alzheimer’s disease
• May reduce arthritis
• May maintain dental health
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Contraindications for HRT
• Active hepatitis- acute
• Previous DVT (?)
• MI in the last 6 months
• Undiagnosed vaginal bleeding
www.menopausetoday.comWomen’s Health Initiative - Summary of results
RISKS of HRT
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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).
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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
www.menopausetoday.comWomen’s Health Initiative - Summary of results
Possible Risks
• There may be an increased risk of breast cancer after taking HRT for five years or more (?P)
www.menopausetoday.comWomen’s Health Initiative - Summary of results
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