July 2, 2002 -- Hormone replacement therapy does not reduce the risk of heart attack and death from coronary events in older women with existing heart disease, findings from a widely anticipated study suggest.
Experts say data from the Heart and Estrogen/Progestin Replacement Study Follow-Up (HERS II) trial offer definitive evidence that hormone therapy is not protective against heart disease progression in postmenopausal women with pre-existing heart disease. And it casts further doubt on its heart-protective value in women without heart disease.
"It is fair to say that there is a growing dark cloud surrounding this treatment," says Diana B. Petitti, MD. "There is growing uncertainty regarding the risks and benefits of hormone replacement therapy. I think more and more women who are on it for prevention will begin to [say no to HRT]."
Millions of menopausal and postmenopausal women take hormone replacement therapy (HRT). It remains the most effective treatment for the symptoms of menopause, but it has also been widely prescribed for protection against heart disease and bone-thinning osteoporosis. There is also some evidence of a protective benefit against Alzheimer's disease. On the negative side, HRT has been linked to an increased risk of breast cancer, ovarian cancer, blood clots, and gallbladder disease.
The original HERS trial involved almost 2,800 postmenopausal women with heart disease who were followed for four years. Women on HRT were found to have an increased risk of coronary events during the first year of treatment and a decreased risk in subsequent years, compared with women on placebo treatment.
At the time, researchers speculated that longer follow-up would make the heart-protective benefits of hormone therapy more obvious, but the newly released report does just the opposite. The new findings, published in the July 3 issue of TheJournal of the American Medical Association, showed that women on HRT for almost seven years were just as likely to have heart attacks and die of heart disease as women who were not on the therapy.
"Despite the fact that almost half of the women originally assigned to hormone therapy were still taking hormones at the end of follow-up, there was no evidence of overall benefit for any cardiovascular outcome," lead researcher Deborah Grady, MD, and colleagues wrote.
There was also no evidence that hormone therapy protected against bone fractures associated with osteoporosis, but women on HRT were found to be at increased risk for blood clots and gallbladder disease.
Petitti, who wrote an editorial assessing the new findings, tells WebMD that though there is mounting evidence showing hormone replacement does not protect the heart, the jury is still out on its ability to protect against bone loss and related fractures. In addition, she says, research on the protective role of hormones against age-related dementia has only just begun.
Clinicians are looking to a major study to help provide more answers. More than 27,000 women on hormone replacement therapy are taking part in the federally funded Women's Health Initiative. Final results from the trial are scheduled for release in 2006, but Petitti says interim reports may help clarify the risks and benefits of HRT sooner.
"Right now we can say that (menopausal) symptom relief is the main established benefit of hormone replacement therapy," says Petitti, who is director of research for Kaiser Permanente California. "I think that all of the other benefits remain to be established."
Lori Mosca, MD, says there are still a lot of good reasons for women to be on hormone replacement therapy. Mosca wrote a revised American Heart Association position statement on HRT published last July. The group now says that HRT should not be recommended solely for the prevention of heart disease and that women with a history of one or more heart attacks should avoid hormone replacement if not already on it.
Mosca tells WebMD that a major benefit of hormone replacement therapy -- improved quality of life -- is rarely measured in clinical trials. She says there is no reason women should stop taking HRT if it relieves their menopausal symptoms.
"So many women on this therapy feel better," she says. "There is still a role for hormone replacement in the treatment of menopausal symptoms and the prevention of thinning bones. And there is nothing in these new studies to indicate that women should stop taking (HRT), with the exception of those with existing heart disease who are taking it solely to prevent a second heart attack."