Hormone therapy may improve heart health in some women
Published: Tuesday, January 24, 2006 at 2:29 p.m.
Last Modified: Tuesday, January 24, 2006 at 2:29 p.m.
In a sharp reversal in thinking about the risks and benefits of menopause hormones, new research shows that early use of the drugs may actually lower a woman's risk for heart disease.
The finding, published this week in the Journal of Women's Health, contradicts warnings issued nearly four years ago that hormone use increases risk for heart attack and stroke. That widely publicized warning, based on the government-funded Women's Health Initiative study, caused millions of women to abandon hormone replacement therapy. The government had halted the study early, citing concern over the risk posed to trial participants, and sales of hormone drugs plummeted.
Since that 2002 warning, a number of researchers have questioned the WHI findings, and pointed out that the design of the study didn't necessarily apply to the typical hormone user - women who turn to the drugs to treat menopause symptoms. Most of the 27,000 participants in the WHI clinical trial were older women who started hormones 10 or more years past menopause.
But while there has been evidence that some menopausal women are starting to return to hormone use at lower doses, overall hormone use continues to decline. And women and their doctors remained confused about the risks.
This latest research, which, like the WHI study, was funded by the National Institutes of Health, takes a significant step toward untangling the science. The newest study bolsters the theory that with hormones, timing is everything. Younger women who use the drugs at the onset of menopause likely face fewer risks and more benefits. But the drugs are far more risky if started in older women long past menopause, according to the new research.
The results are based on the well-established database of the Nurses Health Study, research that began in 1976 and now follows 120,000 nurses. The new analysis found that nurses who began hormone therapy near menopause had about a 30 percent lower risk for heart disease than women who didn't use hormones. By comparison, older nurses who started taking hormones at least 10 years after menopause didn't have any benefit. Whether the women took estrogen alone or a combination of estrogen and progestin didn't make a marked difference in heart risk.
To be sure, menopause hormones still have been found to carry risks, including blood clots and possibly breast cancer (risks found in the WHI that weren't examined in this new analysis). And the researchers and others say the new findings shouldn't change the general recommendation from the Food and Drug Administration that hormones be used in the lowest dose for the shortest period of time possible.
But while the results don't mean a woman should take hormones solely to prevent heart attacks, they do suggest that women suffering from hot flashes and other severe symptoms of menopause shouldn't be fearful about heart risk if they decide to use hormones.
Wyeth, the company that makes Premarin and Prempro, the hormone drugs studied in the WHI, was cautious about the latest study results. The company was particularly hard hit in recent years by the decline in hormone sales. "I think the study itself is reassuring," said James H. Pickar, Wyeth's assistant vice president of clinical research and development. He said that menopause hormones "should not be used for the prevention of cardiovascular disease, but they continue to be valuable treatments for the relief of menopausal symptoms."
What is so surprising about the latest hormone news is where it comes from. While hormone advocates have long criticized the findings of the WHI, the new Journal of Women's Health report doesn't come from the anti-WHI camp. It's co-written by Harvard Medical School researcher JoAnn Manson, who was also the lead author on the WHI report linking hormones with higher heart-attack risk. Dr. Manson, who stands by the original findings of the WHI heart study, nevertheless believes the results have been too broadly interpreted and that more research on younger women is necessary.
"It's an oversimplification to say hormone therapy is good for all women or bad for all women," says Dr. Manson, an endocrinologist at Harvard's Brigham and Women's hospital. "Clearly the truth is somewhere in between."
In addition to the nurse data, the Journal of Women's Health article also detailed another analysis that Dr. Manson's group conducted - this time of data from the WHI. In that analysis, researchers found that risk of heart problems among hormone users increased the more time that had passed since the woman experienced menopause. Estrogen and progestin users who started hormones within 10 years of menopause showed an 11 percent lower risk of heart problems than nonusers, while those women who started hormones 10 to 19 years past menopause had a 22 percent higher risk for heart attack.
In yet another analysis by Dr. Manson's group - of the estrogen-only arm of the WHI study - women who started hormones between the ages of 50 and 59 had a 44 percent lower risk of heart troubles. But women who started hormones between the ages of 70 and 79 had a 4 percent higher risk of heart attack.
While all of these findings clearly support the idea that timing of hormone use makes a difference in terms of its safety, numerous questions remain about the data.
First, though the Nurses Health Study is large and well-established, it is an observational study in which the women are simply observed over time. A randomized clinical trial, such as the WHI, often is viewed as more conclusive because it's designed to answer specific questions. Another concern is that even with the reanalysis of both the Nurses Health Study data and the WHI data, the results aren't a perfect match. The older women in the WHI showed far higher risk for heart problems than the older nurses, suggesting that the latest reanalysis of the nurses data may be overstating the heart benefit, says Jacques Rossouw, project officer for the Women's Health Initiative and the NIH official who first announced the WHI results.
In addition, even if everyone agrees there is a heart benefit with early use of hormones, it remains an open question whether there is a point when hormone use, even if started early, becomes risky in a woman with naturally aging arteries.
More answers are expected in the next few months, when WHI researchers are expected to publish a reanalysis of their data focusing on the younger women in the study who started hormones soon after menopause.
In addition, another study - the Kronos Early Estrogen Prevention Study, or KEEPS - is recruiting women for a randomized clinical trial that hopes to better answer the question of whether timing of hormone use makes a difference in terms of risks and benefits, particularly to the heart. Women can learn more at http://www.kronosinstitute.org/keeps.html.
"It's like some of the other things in science and medicine - it's not that the studies were wrong, it's the way we have interpreted them," says Hugh S. Taylor, associate professor in the Yale School of Medicine department of obstetrics, gynecology and reproductive sciences, who is also an investigator on the KEEPS trial. "I think we're going to see a theme developing here that estrogen is good if you start it early and use it appropriately. It may be one of the biggest flip-flops in medicine that we've seen."
Some findings from a new report:
- Women who began hormone therapy near menopause had about a 30 percent lower risk for heart disease than women who didn't use hormones.
- Older women who started taking hormones at least 10 years after menopause didn't have any heart benefit.
- Whether the women took just estrogen or a combination of estrogen and progestin didn't make a marked difference in risk.
Source: The Journal of Women's Health
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