Estrogen Therapy and Coronary Artery Calcification

June 2007

Findings Summary

Calcified plaque in the coronary arteries that provide blood flow to the heart predicts risk of future heart attacks. Other randomized trials have not looked at the effect of estrogen therapy on the amount of coronary artery calcium.
The Women’s Health Initiative (WHI) included a randomized trial of estrogen-alone in women with hysterectomy. Women in this trial were randomly assigned to take either conjugated equine estrogens (CEE) 0.625 mg or a placebo pill each day. We measured coronary artery calcium (CAC) as a sub-study of the WHI estrogen-alone trial.
Cardiac CT (computed tomography) scans were used to measure CAC in 1,064 estrogen-alone participants who were aged 50-59 years when they joined the WHI. Scans were done at 28 of 40 WHI centers an average of 8.7 years after joining (7.4 years after they started study pills and 1.3 years after study pills were stopped). CAC was scored at a central reading center, which did not have information about which women were in the estrogen or placebo groups.
CAC scores were lower in women in the CEE (estrogen) group compared to those in the placebo group. The mean CAC score was 83.1 for CEE and 123.1 for placebo. After taking into account other heart disease risk factors, the risk of having mild-to-moderate CAC was 20-30% lower and the risk of severe CAC was 40% lower in the CEE group compared to placebo. When we looked only at women who were taking their study pills regularly (at least 80% of the time), the risk of mild-to-moderate CAC was 40-50% lower and the risk of severe CAC was 60% lower in the CEE group compared to placebo.
In summary, we looked at the effect of estrogen on coronary artery calcium among women who were aged 50-59 when they joined the WHI estrogen-alone trial. After the trial was stopped, the calcium plaque build-up in the coronary arteries was lower in women randomized to estrogen compared to placebo. However, estrogen has complex biological effects and may affect a woman’s risk of heart disease and other health outcomes in many different ways.

Questions and Answers

What is the “bottom-line” message of the WHI-CACS study?
WHI-CACS suggests that women aged 50-59 who were assigned to take estrogen (CEE) had lower amounts of coronary artery calcium after the trial ended compared to women assigned to placebo. These findings provide some reassurance about heart disease risks in younger women with hysterectomy who are taking estrogen-alone. When taken for an average of 7.4 years, estrogen-alone is not likely to increase heart disease risk in recently menopausal women who are considering hormone therapy for menopausal symptoms.
Do the WHI-CACS results mean that hormone therapy guidelines should be changed?
No. Hormone therapy should not be started (or continued) to prevent heart disease or other cardiovascular diseases in either younger or older postmenopausal women. Current guidelines remain—hormone therapy should be limited to the treatment of moderate-to-severe menopausal symptoms, and the lowest effective dose should be used for the shortest duration possible.