That's what a new study presented yesterday at a scientific session of the American College of Cardiology in Atlanta discovered: In research involving monkeys, scientists found the animals that received hormone replacement therapy (HRT) when fatty deposits had only begun to accumulate in their blood vessels showed the greatest benefit.
Heart disease is the leading cause of death among American men and women, although it tends to develop a decade later in women because of factors relating to menopause. Coronary heart disease claims the lives of 250,000 women a year.Lead investigator Mary S. Anthony, an assistant professor of pathology at Wake Forest University Baptist Medical Center, says the findings follow a wealth of medical research suggesting HRT has benefits for cardiovascular disease and atherosclerosis.
However, after reading two recent studies that claimed HRT had no effect on either disease, Anthony noted those women had fairly advanced atherosclerosis.
She decided to turn her attention to the effect of HRT at an early stage of the artery disease.
Anthony and her colleague, Thomas Clarkson, fed female cynomolgus monkeys an atherosclerosis-inducing diet for two years, then surgically removed the animals' ovaries to cause menopause. At that time, the degree of atherosclerosis was measured in each monkey.
The animals were randomly assigned to one of two groups. For the next three years, one group received no treatment, the other got HRT at a dose comparable to that consumed by the average woman on HRT. All the animals continued on the same diet.
At the end of the study, the researchers measured the extent of atherosclerosis in each monkey. Overall, the animals that received HRT had less atherosclerosis. However, the greatest benefit was seen in monkeys with the earliest stages of disease at the study's start.
Among animals that had the least atherosclerosis at the beginning of the three-year period, those that received HRT had 85 percent fewer fatty deposits than the monkeys that received a placebo. Animals with intermediate levels of atherosclerosis when their ovaries were removed who received HRT had deposits that were 25 percent smaller than the monkeys that received a placebo. There was no difference between the two groups in animals that started the study with high levels of atherosclerosis.
"The implication of that for us is that you should start individuals at earlier stages, rather than at later stages," Anthony says. "As soon as women start to have hot flashes and experience some symptoms of menopause would be the right time to start thinking about some sort of estrogen therapy."
Dr. Karen P. Alexander, an assistant professor of cardiology at Duke University Medical Center, says the findings are interesting.
"If you start hormone replacement before disease has progressed, you might get more of the benefit," she says.
Although the mechanism behind these findings hasn't been confirmed, there are several theories on why early HRT is a better weapon against atherosclerosis. Anthony thinks it may be that estrogen receptors become less responsive to estrogen as atherosclerosis progresses, or it's possible that estrogen increases levels of proteins that increase the size of large lesions.
"That doesn't happen if you start out with very small lesions," Anthony explains.
However, a recent advisory from the American Heart Association warns women not to rely on HRT as their sole method for protecting their cardiovascular system.
"You can't rely on it to the exclusion of eating a healthy diet and doing other things that we know have benefits for lowering cardiovascular disease, like exercise," Anthony says. "It has to be part of a healthy package."
Alexander agrees, saying that "all women ought to remember to do the simple and free things, which are [a healthy] diet and exercise."
She adds doctors can also treat patients with statins, aspirin, beta blockers and ACE inhibitors as a secondary line of prevention.
"We have a lot of proven therapies that do reduce risk," she says.
A study in the July 2001 issue of Fertility and Sterility found that even low doses of HRT reduces levels of LDL, the form of cholesterol linked to atherosclerosis. In addition, a study of alternatives to hormonal therapy found that a component of soy called isoflavone, along with calming various symptoms of menopause, also reduced cholesterol levels.
Anthony is currently studying whether soy-based therapies have an effect similar to HRT. Overall, she says that while soy lowers atherosclerosis levels some, the effects are not as great as with HRT. However, she stresses this area needs further study.
What To Do
Read about coronary heart disease and HRT from the National Heart, Lung, and Blood Institute.