More Shots Against Long-Term HRT 

Two new reviews of combination hormone replacement therapy and its effect on heart disease and other problems, published in August in two leading medical journals, strongly support the recent conclusions of the Women's Health Initiative (WHI) study, which finds more harm than benefit in long-term HRT use.

The WHI clinical trial of estrogen used with progestin was halted last month, 5.2 years into the planned eight-year study, because it found that women using the combination HRT (specifically, Prempro) were more likely to have breast cancer, heart attack, stroke, and blood clots even though they were protected against osteoporosis and colon cancer.

The new analyses, published in a recent issue of the Annals of Internal Medicine and a recent issue of the Journal of the American Medical Association (JAMA), lend more support to the findings in the WHI study, the researchers say.

The Annals of Internal Medicine review addresses primarily cardiovascular disease risk, while the JAMA review also considers other potential effects of long-term HRT use, such as osteoporosis and colon cancer prevention, and includes in its analysis the WHI study.

In both reviews, the researchers combed through medical literature from 1966 to 2000 or 2001 and kept only the most scientific studies of HRT to review.

"For prevention of chronic conditions, there aren't a lot of reasons to take it," says Dr. Heidi D. Nelson, an author of the JAMA review and an associate professor of medicine and medical informatics and outcome research at the Oregon Health & Science University in Portland.

"I want to make clear we were only looking at HRT for the prevention of chronic conditions," she adds, and not for short-term relief of hot flashes and other menopausal symptoms, which is what HRT is often used for.

The Annals of Internal Medicine review, led by Dr. Linda L. Humphrey, associate professor of medicine at Oregon Health & Science University and the Portland Veterans Affairs Medical Center, concludes that HRT has no benefit in the primary or secondary prevention of coronary heart disease.

The findings from the new analyses contradict common wisdom, the authors acknowledge.

"The thing so exciting a few years ago is that everyone thought [HRT] helped your heart," Nelson says. "Our review found no benefit for the heart. That takes a huge bit of the luster away from taking something long-term. It does help your bones. That's been consistent in all the studies. But there are other things you can do [to preserve bone density]. What really has changed over the past few years is the realization that there is more evidence for harm."

"The harms are not common," she adds. "When you calculate the number of people who are harmed, it is not a large number. For instance, 1.5 women per year per 10,000 women will have a blood clot. All the studies agree. That's 1.5 more women than you would expect [without HRT]."

The decision of whether or not to take HRT today, Nelson says, "is a different decision than it was before" for prevention of chronic conditions.

She is talking, she stresses, only about combination therapy using estrogen plus progestin. The arm of the WHI study that is evaluating estrogen-only, given to women who do not have a uterus, is continuing. (Women with an intact uterus are given combination therapy because taking estrogen alone raises the risk of endometrial cancer.)

For women deciding whether to continue on HRT for heart disease prevention, the decision should be straightforward, says Humphrey.

"When you put all the data together about heart disease prevention and HRT, there was no benefit for primary prevention," she says. That is, women without heart disease can't expect HRT to prevent them from getting it.

Both researchers say some women may have quality-of-life issues for continuing to take HRT for more than a few years. Some say they simply feel better on the therapy, having fewer mood swings, less vaginal dryness, and better libido.

The new analyses probably will not change the advice physicians are giving women on a case-by-case basis about HRT based on their risks, says Dr. William Parker, a gynecologist at Santa Monica-UCLA Medical Center who is very familiar with HRT research. These new analyses, he says, echo "what has already been said." And the WHI study, he says, was the more scientifically sound one.

The analyses, he said, are what experts call meta-analyses, or an evaluation of previous studies that may differ in scientific quality in reaching their conclusions.

"Meta-analyses have inherent flaws," Parker says. "It's kind of like comparing apples and oranges."

But the meta-analyses done by Humphrey and Nelson will be used by the US Preventive Services Task Force, an independent panel of experts, which is in the process of updating its HRT recommendations.

The US Department of Health and Human Services has already announced it will hold a series of public forums to consider the future of HRT, beginning in the fall.

Always consult your physician for more information.

In Other Heart Health News For Women:

Heartening News on Vitamin E

If you are a woman who is not getting enough vitamin E in your diet, you could be increasing your risk of cardiovascular disease.

A study in the September issue of the American Journal of Clinical Nutrition found that low vitamin E intake in middle-aged women is a risk factor for early atherosclerosis.

The study included 307 southern Italian women, average age 56, with no clinical history of cardiovascular disease. The women did not take any vitamin supplements containing the antioxidant vitamins A, C, or E.

Their average daily intakes and plasma concentrations of antioxidants were assessed, using questionnaires and blood samples. They were also given ultrasound examinations of the carotid arteries and branches.

The researchers found that 66 percent of the women had atherosclerotic plaques at one or more sites in the carotid arteries. Women with the lowest vitamin E intake were more than twice as likely to have plaque in their carotid branches.

There was no connection between such plaque in the women's carotid arteries or branches and their intake of vitamins A and C, the study found.

The women in the study reported their main sources of dietary vitamin E were legumes, vegetables, and olive oil.

The study authors say only people with low intakes of vitamin E could benefit from increasing their intake of the vitamin. Before anyone alters their diet or takes antioxidant supplements, they need to assess their daily vitamin E intake with their physician, the authors say.

Always consult your physician for more information.