By Jackie Jadrnak, Albuquerque Journal Staff
SANTA FE -- Suppose a 55-year-old woman has no evidence of heart disease, but has a family history of heart disease and a couple of risk factors to develop it herself.
Should she take estrogen to help her heart since she has passed menopause?
The question used to be a no-brainer. Early studies showed overwhelmingly that post-menopausal women who got estrogen in hormone replacement therapy had far fewer problems with heart disease.
But when the question was placed to some physicians on a panel at a recent cardiology conference here, the first answer was an uneasy silence. The picture isn't so clear any more.
The Heart and Estrogen/Progestin Replacement Study (HERS) published in the August 1998 Journal of the American Medical Association has given many physicians pause. For four years, HERS researchers followed 2,763 post-menopausal women who already had heart disease. Not only did it show that those on hormone replacement therapy had no difference in the number of "events" such as a heart attack, but it showed they had a tendency to have more heart attacks in the first year of the hormone treatment.
Also last year, researchers at Duke University Medical Center looked back at a 1996 study of aspirin use in heart attack patients. An analysis of data in that study showed that 37 percent of the women who started hormone therapy after their heart attack were hospitalized for unstable angina (heart pain) within a year, compared with only 17 percent of the women who never used hormones and 21 percent of those who had used hormones before their heart attack.
Physicians have divided into two camps after those studies, according to David Herrington, associate professor of internal medicine at Wake Forest University in North Carolina. He spoke at the American College of Cardiology's Santa Fe Colloquium on Cardiovascular Therapy earlier this month.
One group says the HERS study applies only to women who already have heart disease, and estrogen use still might help women to avoid getting it in the first place, he said. The other group has serious questions about whether estrogen really can prevent heart disease.
Elizabeth Barrett-Connor, professor and chief of the division of epidemiology at the University of California-San Diego, said she has tried to think of a medical intervention that can prevent a disease (primary prevention) but not help prevent recurrences (secondary prevention). "I can't come up with one," she said.
"It's possible estrogen has so many different effects that we didn't expect that maybe it's a good primary but not a secondary preventive," she said. "It may be -- but it gives me pause."
Jonathan Abrams, cardiologist and professor of medicine at the University of New Mexico, said his conclusion had been to put all post-menopausal women on estrogen replacement therapy if they had any risk factors for cardiovascular disease.
While recent studies question that approach, he added, "I have a concern we're throwing the baby out with the bath water. There are many positive effects of hormone replacement therapy."
Giving women estrogen is believed to help avoid osteoporosis, Alzheimer's disease, and general symptoms of menopause such as hot flashes, irritability and vaginal dryness. Since estrogen tends to increase the risk of uterine cancer, women often combine it with some form of progesterone to protect the uterus.
It's easy to see why even doctors have a hard time deciding what is best.
Twenty-five studies have shown a 33 percent reduced risk of heart disease in women who take replacement estrogen, Barrett-Connor said. Another group of studies, which studied women taking the estrogen-progesterone combination, showed a 35 percent risk reduction.
However, since those studies simply looked at women after the fact, they may have had a selective bias. "Women on hormone replacement therapy are healthier, wealthier and wiser," said Herrington. More educated women are more likely to ask for estrogen and are more able to pay for it.
"You reduce your risk of heart disease 50 percent by having a college education," Barrett-Connor said.
Also, many women have been denied estrogen therapy if they had heart disease, high blood pressure or diabetes, she said, so those taking estrogen probably were healthier in the first place.
The HERS study was the first clinical trial to actually separate women randomly -- so both groups had similar backgrounds -- and follow and compare those taking estrogen/progesterone with those not taking it. And it tracked actual heart disease, instead of looking at estrogen's influence on some of the risk factors for heart disease.
Estrogen's positive effects on some of those risk factors has been clear in past studies. It helps walls of the artery stay thinner and more flexible; it lowers the bad cholesterol and raises the good cholesterol; it lowers levels of one substance that causes clotting.
In listing those findings, Herrington added that other effects are less clear. Estrogen also appears to play a role in encouraging blood to clot -- it might depend on a woman's specific type of blood platelets -- and in encouraging inflammation, he said.
"It doesn't mean it's always a pro-inflammatory compound," Herrington said. "It suppresses some mediators of inflammation. The whole story of estrogen and inflammation is a very complicated one."
The good news is that the conflicting results have stimulated a lot of good, new research on estrogen and heart disease, Herrington said.
"There is reason to be circumspect about excessive use of estrogen with the expectation it will reduce women's risk of heart disease," he said. "This does point out that our understanding of estrogen is limited still."
