WHI
Trial question
What is the role of estrogen plus progestin in healthy postmenopausal women?
Study design
Multi-center
Double blinded
RCT
Population
16608 female patients.
Inclusion criteria: healthy postmenopausal women aged 50-79 years with an intact uterus at baseline.
Key exclusion criteria: any medical condition likely to be associated with a predicted survival of < 3 years, prior breast cancer, other prior cancer within the last 10 years except nonmelanoma skin cancer, low hematocrit or platelet counts, alcoholism, or dementia.
Interventions
N=8506 estrogen plus progestin (conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet).
N=8102 placebo (matching placebo tablet).
Primary outcome
Nonfatal MI or CV death
0.37%
0.3%
0.4 %
0.3 %
0.2 %
0.1 %
0.0 %
Estrogen plus
progestin
Placebo
Borderline significant
increase ▲
Borderline significant increase in nonfatal MI or CV death (0.37% vs. 0.3%; HR 1.29, 95% CI 1.02 to 1.63).
Secondary outcomes
No significant difference in stroke (0.29% vs. 0.21%; HR 1.41, 95% CI 0.81 to 1.07).
Borderline significant increase in venous thromboembolic disease (0.34% vs. 0.16%; HR 2.11, 95% CI 1.58 to 2.82).
Borderline significant decrease in osteoporotic fractures (1.47% vs. 1.91%; HR 0.76, 95% CI 0.69 to 0.85).
Safety outcomes
No significant difference in death and cause of death.
Significant difference in invasive breast cancer (0.38% per year vs. 0.30% per year).
Conclusion
In healthy postmenopausal women aged 50-79 years with an intact uterus at baseline, estrogen plus progestin was inferior to placebo with respect to nonfatal MI or CV death.
Reference
Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33.
Open reference URL