Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 15082697 · doi:10.1001/jama.291.14.1701
What was done
A multicenter, randomized, double-blind, placebo-controlled trial across 40 US clinical centers evaluated the effect of daily conjugated equine estrogen (CEE, 0.625 mg/d) versus placebo on chronic disease incidence in 10,739 postmenopausal women aged 50-79 years with prior hysterectomy (23% minority race/ethnicity). The primary efficacy outcome was coronary heart disease (nonfatal myocardial infarction or CHD death), the primary safety outcome was invasive breast cancer, and a global index tracked overall risks and benefits over an average follow-up of 6.8 years.
What was found
Compared with placebo, CEE showed no significant effect on coronary heart disease (HR 0.91, 95% CI 0.75-1.12; 376 cases) or invasive breast cancer (HR 0.77, 95% CI 0.59-1.01; 218 cases). CEE significantly increased risk of stroke (HR 1.39, 95% CI 1.10-1.77; 276 cases; absolute excess of 12 per 10,000 person-years) and total cardiovascular disease (HR 1.12, 95% CI 1.01-1.24). CEE significantly reduced risk of hip fracture (HR 0.61, 95% CI 0.41-0.91; 102 cases; absolute reduction of 6 per 10,000 person-years) and total fractures (HR 0.70, 95% CI 0.63-0.79). No significant differences were seen for pulmonary embolism (HR 1.34, 95% CI 0.87-2.06), colorectal cancer (HR 1.08, 95% CI 0.75-1.55), total cancer (HR 0.93, 95% CI 0.81-1.07), total mortality (HR 1.04, 95% CI 0.88-1.22), or the global index (HR 1.01, 95% CI 0.91-1.12).
Why it matters
This landmark trial demonstrated that estrogen-alone therapy does not reduce coronary heart disease and increases stroke risk, establishing that CEE should not be recommended for chronic disease prevention in postmenopausal women with prior hysterectomy.
Limits
The intervention phase was terminated early by the NIH. The findings are specific to oral conjugated equine estrogen (0.625 mg/d) in postmenopausal women with prior hysterectomy aged 50-79, and do not directly evaluate other formulations, lower doses, non-oral routes, or women with an intact uterus.
Cited by
- supports The Women's Health Initiative stopped an estrogen-based hormone therapy trial early because it was not reducing cardiovascular risk and appeared to increase risk.