Estrogen May Lower Heart Disease Risk For Some Menopausal Women

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Main Category: Menopause
Also Included In: Endocrinology;  Heart Disease;  Cardiovascular / Cardiology
Article Date: 22 Jun 2007 - 0:00 PDT

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New results from a follow up study of the US federally funded Women's Health Initiative (WHI) suggest that among women in their 50s who have had hysterectomies, estrogen was associated with a significantly lower risk of coronary artery calcification which is a known predictor of future heart attacks.

The study is published in the New England Journal of Medicine (NEJM).

The WHI Coronary Artery Calcium Study found that younger menopausal women (aged 50 to 59) who were given a standard dose of oral conjugated estrogens had significantly less coronary artery calcification at the end of the study period compared with women who took a placebo.

These findings should allay one concern for younger postmenopausal women who have had a hysterectomy and are considering taking estrogen to relieve hot flashes, but researchers wanted to remind women that hormone replacement therapy (HRT) still carries other health risks such as increased risk of blood clots and strokes. And under no circumstances should these findings be interpreted to mean that estrogen could be used to guard against heart disease.

Dr Elizabeth G Nabel, Director of the National Heart, Lung, and Blood Institute (NHLBI), which is part of the National Institutes of Health and sponsor of the WHI study, said that:

"These new results offer some reassurance to younger women who have had a hysterectomy and who would like to use hormone therapy on a short-term basis to ease menopausal symptoms."

"We must emphasize, however, that these findings do not alter the current recommendations that when hormone therapy is used for menopausal symptoms, it should only be taken at the smallest dose and for the shortest time possible, and hormone therapy should never be used to prevent heart disease," she cautioned.

The senior author of the study, and a a Stanford University School of Medicine researcher confirmed that the study offered some reassurance to some women considering HRT:

"Heart disease is complex, and the effect of estrogen on one risk factor does not adequately predict the risk of having a heart attack," said Dr Marcia Stefanick, who is professor of medicine at the Stanford Prevention Research Center at the Stanford University School of Medicine and chair of the national steering committee for the overall WHI study.

"But this study offers some reassurance for women of menopausal age that it's not unsafe, in terms of the risk of heart attack, to take estrogen, at least for a few years," she added.

Until the results of the WHI study published in 2002 showed otherwise, observational studies had earlier suggested that hormone therapy not only relieved hot flashes and other menopause symptoms but also protected women against heart disease, weak bones and dementia. After the 2002 results there was a big drop in women taking HRT and some groups are still critical of the WHI study findings.

For instance, the UK's International Menopause Society (IMS) asks why the WHI researchers didn't find out earlier that the heart disease risk of estrogen only therapy was age related. This is not the only WHI follow up study to show it, they said in a prepared statement.

One of the problems is the view that researchers take about the studies that were ongoing before the WHI, such as the long term Nurses' Health Studies. Because these were observational as opposed to randomized controlled studies, they are considered of a lower quality. However, the IMS suggest that as more post hoc findings emerge from the WHI study, they appear to be confirming the conclusions of the earlier observational studies, the results of which have been known for 10 years. They suggest that doctors consider all the evidence, and not just the WHI findings, when advising their patients about HRT.

There were two arms to the HRT part of the WHI placebo-controlled study. One, for women who still had their uteruses, assigned them to take either placebo or a combination of estrogen and progestin. The other, for women who had had hysterectomies, assigned them to take either placebo or estrogen alone, in the form of conjugated equine estrogens.

The combined estrogen and progestin arm was stopped in 2002 when early results showed that the women were at higher risk of breast cancer, stroke, blood clots and, in the first year of treatment, heart attack.

The estrogen only arm continued until 2004 when it was stopped because of concerns that this group was at higher risk of stroke and blood clots, with no benefits in terms of heart disease.

Researchers have continued to analyse the data from both trials, and this latest study is one such analysis.

The initial analysis looked at the overall risk of heart attack among all women aged 50 to 79, regardless of age. More recent studies have broken the groups down by age.

In this latest study the researchers found there might some benefit from estrogen only therapy for women in their 50s and those within 10 years of menopause, but there is no evidence that it benefits heart health for older women or those who started HRT more than 10 years after the menopause.

The researchers invited women who were aged 50 to 59 at the time they entered the WHI trial to have cardiac computed tomography (CT) scans to assess their levels of coronary artery calcium, one indicator of heart disease. Calcified plaque builds up in arteries and can rupture, resulting in blockage of arterial blood flow that can cause heart attacks and strokes. The participants came from 28 of the original 40 centres involved in the WHI trial.

The scans were done nearly 9 years after the women were assigned to take either estrogen or placebo, and just over a year after the estrogen only arm was stopped.

The results showed that calcified artery plaque was 20 to 40 per cent lower in women who were on estrogen compared to those on placebo. The reduction was even greater, between 50 and 60 per cent, for those women on estrogen who took 80 per cent of their pills during the trial, compared to the women who completed the same dosage of placebos.

Stefanick and her team were very cautious about their findings. There is no way of knowing, for example, whether the reduced plaque levels will remain a reliable indicator of coronary artery disease as the women get older. They pointed out that researchers studying heart disease in women in their 50s and looking at other areas such as the role played by the smaller heart vessels could bring up other findings.

"Regardless, we have to keep in mind that heart disease is only one potential health risk of hormone therapy. When women are thinking about taking estrogen, they should consider the overall risk/benefit balance, which includes an increased risk of stroke and blood clots, regardless of age," said Stefanick.

An accompanying editorial suggests that this latest study supports the notion that estrogen is beneficial if therapy starts before the ovaries have stopped producing the hormone, or that it could be harmful if started some time afterwards.

But the authors said this study did not address this "timing hypothesis" because, as Stefanick put it:

"Only younger women were studied, so we don't know whether coronary artery calcium was higher or lower in the older women assigned to estrogen vs. placebo. Furthermore, without a baseline CT scan, we have no data about changes over time."

Stefanick and colleagues said that this study should not alter the medical advice for women who want to relieve hot flashes and other symptoms of the menopause. If they choose to start on estrogen therapy they should take the lowest dose for their symptoms and limit the duration of the treatment.

These comments and observations show how important it is not to generalize from specific results, and that doctors and their patients should consider how the detail of each study applies in a specific case in order to calculate the benefit-risk profile for an individual patient and not be tempted to avoid the discussion because it is too complex.

"Estrogen Therapy and Coronary-Artery Calcification."
Manson, JoAnn E., Allison, Matthew A., Rossouw, Jacques E., Carr, J. Jeffrey, Langer, Robert D., Hsia, Judith, Kuller, Lewis H., Cochrane, Barbara B., Hunt, Julie R., Ludlam, Shari E., Pettinger, Mary B., Gass, Margery, Margolis, Karen L., Nathan, Lauren, Ockene, Judith K., Prentice, Ross L., Robbins, John, Stefanick, Marcia L., the WHI and WHI-CACS Investigators.
N Engl J Med 2007 356: 2591-2602.
Volume 356:2591-2602, June 21, 2007, Number 25.

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Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today
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