Estrogen replacement increases risk factors for arrhythmia and sudden death

Women who use estrogen replacement therapy to relieve menopausal symptoms are more likely to develop risk factors for potentially fatal irregular heartbeats (arrythmias) and heart attacks than women who take hormone therapy combining estrogen and progestin.

Prior to the early termination of the estrogen plus progestin arm of a nationwide women’s health study, postmenopausal hormone replacement therapy was the most commonly prescribed medication in the United States, based on its alleged cholesterol-lowering and cardioprotective effects.

As a result, according to a study in the August issue of Annals of Epidemiology, a large number of women who used hormone replacement therapy may have been at increased risk — and women who continue to use “unopposed” estrogen replacement remain at risk — for developing heart problems.

Northwestern University researcher Mercedes Carnethon, who led the nine-year study of 3,100 postmenopausal women selected from the Atherosclerosis Risk in Communities Study, said that estrogen replacement therapy prolongs a segment of the electrocardiogram called the QT interval, a part of the repeating electrical pattern of the heart that is measured in fractions of a second. Prolongation of the QT interval is associated with an increased risk for arrhythmia, coronary heart disease and sudden cardiac death.

Carnethon is assistant professor of preventive medicine at the Feinberg School of Medicine at Northwestern University. Carnethon and her research group found that odds of QT prolongation were 50 percent higher among women who used hormone therapy as compared with women who never used hormones.

However, when hormone use was compared separately by formulation, risk for QT prolongation was nearly twice that in women who used estrogen replacement therapy compared with those who never used it. There was no difference in risk in women taking progestin plus estrogen vs. those who were not using hormone replacement therapy.

Women are known to have longer QT intervals – especially during childbearing years — than men and that the QT interval varies over the course of a woman’s life. It is believed that QT length may be controlled, at least in part, by sex hormones, particularly estrogen. Women also are at higher risk for QT prolongation from various drugs, including antipsychotics and heart medications.

Carnethon said it is possible that hormone therapy acts to lengthen QT intervals and increase risk for arrhythmia, heart attack and sudden death.

This research represents the largest observational study of postmenopausal women with the longest follow-up to date to estimate the effects of hormone therapy on QT length. The potential for QT prolongation associated with estrogen replacement therapy in the women studied, and the possible impact on a great number of women, make this an important concern that should be further explored in randomized trials, Carnethon said.