Yale Study Suggests Estrogen Does Not Prevent Heart Attack Death in Postmenopausal Women

Short-term estrogen withdrawal or replacement produces no effects likely to influence heart attack death in postmenopausal women, a Yale study shows.

“If you take women who go into menopause and give them estrogen, it has no effect on their ability to survive a heart attack,” said Patrick McNulty, M.D., associate professor of cardiology in the Department of Internal Medicine at Yale School of Medicine. He is the lead investigator of the study published in the April issue of the American Journal of Physiology: Heart and Circulatory Physiology.

McNulty said the finding bolsters a landmark study published 18 months ago, the HERS Trial, in which it was found that estrogen replacement was not effective in preventing heart attack deaths in postmenopausal women who already had coronary heart disease.

The landmark trial, and the research by McNulty and his colleagues, was intended to investigate years of anecdotal information that premenopausal women, who naturally have high blood estrogen levels, have much lower rates of death from coronary artery disease than postmenopausal women or than men.

Although it was not known by what mechanism estrogen provided this protection, there were three main hypotheses: one, that estrogen taken over many years lowers cholesterol and prevents the development of coronary blockages; two, that estrogen turns on genes that might protect the heart from heart attacks; and three, that estrogen prevents fatal arrhythmias.

The Yale study, using an animal model, found no evidence to support the latter two hypotheses. Estrogen replacement therapy or withdrawal over a six-week period was associated with neither any protection nor any particular adverse risk.

“Millions of women in this country are taking postmenopausal hormone replacement in an attempt to reduce their risk of dying of heart disease,” McNulty said. “Our results suggest stopping estrogen for six weeks, for example, because of a side-effect, would not increase this risk.”

The other authors of the study are Dinesh Jagasia, M.D., cardiology fellow; Jennifer Whiting, research assistant, and Teresa Caulin-Glaser, M.D., assistant professor of Internal Medicine, Cardiology, in the Yale School of Medicine.