Can Hot Flashes Mean Heart Trouble?

Most women describe hot flashes as annoying, embarrassing and uncomfortable, while doctors have always viewed them as relatively benign. However, new research published this week in the Journal of the American Medical Association (JAMA) indicates that women who have lots of bothersome hot flashes or night sweats after menopause may be at increased risk for heart disease. The study also found that older women who still have severe hot flashes turned out to be the hormone-therapy users who were at greatest risk for heart attacks. While there was a correlation between women who had significant hot flashes and those with risk factors like high blood pressure or high cholesterol, this didn't completely explain their increased risk of having a heart attack while on hormone therapy.

The new study also included some relatively good news for younger women. It seemed to confirm earlier research findings that using hormone therapy for a few years right after menopause to deal with moderate to severe hot flashes and night sweats does not increase these women's risk of heart attacks. Researchers say that, generally, the longer it's been since a woman reached menopause, the more likely it is that using hormone therapy to treat hot flashes will increase her risk of having a heart attack. However, the study also confirmed that all postmenopausal hormone users face an increased risk of stroke, and all those using a combination of estrogen and progesterone have an increased risk of breast cancer.

The JAMA study includes the latest refinements on the mammoth federal Women's Health Initiative (WHI) studies. It was the WHI that first alerted women in 2002 that hormone therapy did not prevent heart attacks after menopause as commonly believed, but actually increased the risk of heart problems, stroke, blood clots and breast cancer in many women. To achieve the statistical power required to conduct this latest, detailed analysis, researchers combined data from the estrogen-only as well as the combined hormone therapy arms of the WHI study, which included more than 27,000 women in their 50s, 60s and 70s. While the study had some technical problems, researchers said its implications were still worth serious consideration.

To better understand the new research, NEWSWEEK's Pat Wingert talked to lead author, Dr. Jacques Rossouw, chief of the WHI Branch at the National Heart, Lung and Blood Institute. Excerpts:

NEWSWEEK: This latest analysis seems to add further evidence that using hormone therapy does not prevent heart disease in postmenopausal women.
Dr. Jacques Rossouw:
That's right. Overall, it's very important to say upfront that this study does not change any of our previous major findings. For the overall study population, taking hormone therapy does not reduce your risk of heart attacks and it does increase your risk of stroke. We saw in the original clinical trials, indications that the risk of coronary heart disease and stroke varied by age group and the length of time since they had reached menopause, but the numbers were too small for us to be sure. Recognizing that, we thought we could get a firmer estimate if we combined the data of both original studies.

The results of this new combined analysis still indicate that you should not take hormone therapy for the prevention of heart disease. But it also indicates that there is not much increased risk of heart attack if you start it when you're younger, or start it within 10 years of reaching menopause, as long as you stop within four or five years. This means that if a woman wants to start hormone therapy to relieve really bad symptoms for a few years, immediately or shortly after she reaches menopause, that's a reasonable option. So in a sense, that's good news. But because we found an association between hot flashes and the greater likelihood of having various risk factors, she will need to closely monitor her blood pressure, her cholesterol, her glucose levels and body weight.

One of the most surprising findings of this study was that older women who still have significant hot flashes turned out to be the hormone-therapy users who were at greater risk for heart disease. Can you explain this?
This was an unexpected finding. We knew that there were increased risks for older women using hormone therapy from the original WHI studies, but when we did a sub-analysis of the older women who were still getting hot flashes and night sweats, we were rather surprised to find that they had an increased risk of heart disease. When we looked at that in more detail, they had more risk factors of cardiovascular disease. They were more likely to have high blood pressure, high blood cholesterol, diabetes and to be overweight. We weren't sure that those things totally explained the increased risk of taking hormones, because when we did an adjusted analysis, we found the increased risk was still there. In other words, being an older woman who has severe hot flashes seems to be a marker of something gone wrong.

We think persisting menopausal symptoms (hot flashes or night sweats) in older women may signal the presence of increased risk factors for heart disease or diseased arteries. But it's just an association at this point [i.e. not proof of cause and effect]. As a result of those findings, our advice to older women who have persisting hot flashes and night sweats, is that they try to get off of hormone therapy, and have themselves checked and treated for cardiovascular risk factors.

Women often joke that no one ever died of a hot flash, but you seem to be saying that severe flashes and night sweats may be a warning that your health isn't as good as you think it is.
We're saying this is a potentially important marker. These findings suggest that women with hot flashes and night sweats may have more risk factors that should be measured and monitored, and more risk factors are associated with a higher risk of heart disease.

How common is it for women to continue to experience severe hot flashes into their 60s and 70s?
In our study, overall, 12 to 17 percent of the postmenopausal women aged 50-79 experienced moderate to severe hot flashes. Usually, they end a few years after the menopause. But for some women, they persist into their 70s. Specifically, we found that about 8.6 percent of women in the estrogen trial and about 4.8 percent of women in the estrogen with progestin trial had moderate to severe hot flashes, the kind that interfere with your life, into their 70s. This study reinforces the conclusion that these women need to get off of hormones if they can.

You've been discouraging older women from taking hormone therapy since the WHI studies came out in 2002. But now, you're emphasizing it even more?
Yes. Hormone therapy was an approved indication for all women with moderate to severe hot flashes or night sweats  in the past. But these new findings sharpen the focus. Hormone therapy can be started during the first five or 10 years after menopause, but after that, we think women—even those with severe symptoms—should avoid it. That's one of the new contributions made by this study.

But older women who have been using hormones for decades are usually the women most resistant to stopping, aren't they? Many say it's very hard for them to get off hormones, because their symptoms are so disruptive to their lives?
That is so. But they need to understand that having these [menopausal] symptoms indicates that they are more likely to have risk factors. Luckily, most risk factors are treatable, and presumably, you can lower your risk of heart disease by taking action. If you look at it that way, these symptoms could be seen as a useful clue.

As to the women who really can't get off of hormones, I would urge them to make sure they are taking good care of themselves and are addressing these other risk factors. Lose some weight, get more exercise, monitor your blood pressure and cholesterol and glucose, and get treatment if it's recommended.

People also need to understand that we were never intended to be exposed to reproductive hormones for our whole lives. Estrogen is a general growth factor—it stimulates all types of tissue, including malignant tissue, so this is not all good. There is still this lingering feeling that estrogen reverses the aging process, that it's the elixir of life, and that if you start taking hormones at the right age, you can preserve yourself into old age. But for many diseases, age is the most important risk factor. Even if you're taking hormones, your arteries are getting older as you age. While estrogen is good for the arteries at some stages, at some point, it becomes a bad thing, and no one knows when that happens. But we do know that starting estrogen at older ages is not beneficial to the heart, and we suspect that continuing it for decades is not good either. There are much safer ways to prevent heart disease than taking hormones.  There are safer ways to reduce your cholesterol, for example. You can use statins at any stage, and they're going to be more beneficial, and have less risk overall, than hormones.

If a younger woman starts hormone therapy immediately after menopause, might she preserve healthier arteries for a longer time?
Using hormone therapy might keep your arteries slightly younger, that may well be true. But it would only be for a few years, when the risk of heart attacks is low anyway. It is unlikely in the long term to prevent the risk of cardiovascular disease. These results should not be taken to imply that if someone starts early, and continues to take it until they are much older, that any benefit will persist.  And remember, hormone therapy can come at the cost of increased risk of breast cancer, stroke and blood clots.

Do you think this correlation between increased risk of heart risk factors found in postmenopausal women having hot flashes, also applies to younger women who have hot flashes prior to menopause?
It is a possibility; I am sure this will be investigated now.

Do these results apply to women who take bioidentical hormones?
This study used " synthetic" hormones, and some people think that natural hormones are better. But from a physiological point of view, a substance either works or it doesn't, and the original form of the hormone is quite irrelevant. Whether using estradiol [the form of estrogen used in bioidentical hormones] makes a difference, who knows. But if I had to hazard a guess, I would say that any estrogen taken orally has much the same effect as we found.  The route of administration makes a difference. Transdermal patches do not increase the likelihood of blood clots. In that way, they appear to have an advantage. But there has not been an adequate number of trials on transdermals to know whether it reduces the risk of heart disease and stroke and breast cancer.

What future studies do you expect will be done with the WHI data?
We want to do more refinements and find out whether there's a difference in risk factors between women who start using hormone therapy immediately after they reach menopause, and those who wait four or five years to start it.  We will look at that in a future paper. This is especially important in terms of breast-cancer risk. There are other studies that indicate that if you change your level of hormones—either up or down—your risk of breast cancer goes down for a while, but then comes back up. For example, one approved treatment for breast cancer is to give someone a high dose of Premarin [an oral synthetic form of estrogen]. For some reason, if you have breast cancer and you bump up your estrogen, it retards tumor growth for a while.  If you block the estrogen, the risk also goes down. But both effects stop after a while. We want to know more about that.

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