WHI: Womens Health Initiative

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WHI Womens Health Initiative

• Purpose
• To assess the major health benefits and risks of
  a commonly used combined hormone preparation
  (estrogen plus progestin), with a particular
  focus on the outcomes of coronary heart disease
  and invasive breast cancer.
• Reference
• Writing Group for the Womens Health Initiative
  Investigators. Risks and benefits of estrogen
  plus progestin in healthy postmenopausal women
  Principal results from the Womens Health
  Initiative randomized controlled trial. JAMA
  2002288321333.

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WHI Womens Health Initiative - TRIAL DESIGN -

• Design
• Multicenter, randomized, double-blind,
  placebo-controlled trial.
• Patients
• 16,608 postmenopausal women who were aged 5079
  years old and who had an intact uterus. Women
  were predominantly healthy at baseline just 7.7
  had prior cardiovascular disease.
• Follow-up and primary endpoint
• Primary endpoints coronary heart disease
  (non-fatal myocardial infarction and coronary
  heart disease death) and invasive breast cancer,
  plus a global index that included the two primary
  endpoints plus stroke, pulmonary embolism,
  endometrial cancer, colorectal cancer, hip
  fracture, and death due to other causes. Mean
  follow-up was 5.2 years.
• Treatment
• Conjugated equine estrogens, 0.625 mg/day, plus
  single-tablet medroxyprogesterone acetate, 2.5
  mg/day, or matching placebo.

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WHI Womens Health Initiative - TRIAL DESIGN
continued -
Baseline characteristics

Estrogen progestin(n8506)
Placebo(n8102)
Mean age (years)
63.2
63.3
Race/ethnicity
White
83.9
84.0
Black
6.5
7.1
Hispanic
5.5
5.1
Hormone use
Never
73.9
74.4
Past
19.7
19.6
Current
6.4
6.0
Body mass index mean (kg/m2)
28.5
28.5
Blood pressure mean (mm Hg)
127.6/75.6
127.8/75.8
History of myocardial infarction
1.6
1.9
History of angina
2.8
2.9
History of stroke
0.7
1.0
0.9
0.8
History of deep vein thrombosis or pulmonary
embolism
Female relative with breast cancer
16.0
15.3
Fracture at age 55 years old
13.5
13.6
Data indicate percentages of patients unless
otherwise noted.
WHI Investigators. JAMA 2002288321333.
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WHI Womens Health Initiative - RESULTS -

• The trial was stopped early after an interim
  analysis found an increased risk of invasive
  breast cancer in the estrogen plus progestin arm
  the global index also supported a finding of
  overall harm associated with hormonal therapy.
• Absolute excess risks and benefits per 10,000
  person-years attributable to estrogen plus
  progestin were as follows
• 7 more coronary heart disease events
• 8 more strokes
• 8 more pulmonary embolisms
• 8 more invasive breast cancers
• 6 fewer colorectal cancers
• 5 fewer hip fractures
• The absolute excess risk of events included in
  the global index was 19 per 10,000 person-years.
• All-cause mortality was not affected.

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WHI Womens Health Initiative - RESULTS
continued -
Kaplan-Meier estimates of cumulative hazards for
selected clinical outcomes
WHI Investigators. JAMA 2002288321333
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WHI Womens Health Initiative - RESULTS
continued -
Kaplan-Meier estimates of cumulative hazards for
global index and death
WHI Investigators. JAMA 2002288321333
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WHI Womens Health Initiative - SUMMARY -

• In healthy postmenopausal women, combined
  estrogen plus progestin hormonal therapy is
  associated with increased risks of cardiovascular
  disease and breast cancer but decreased risks of
  hip fracture and colorectal cancer in comparison
  with placebo.
• The overall riskbenefit profile does not
  support the use of combined hormone therapy for
  the primary prevention of coronary heart disease
  in postmenopausal women.