The women were participants in the Women's Health Initiative, halted abruptly in 2002 when researchers found that the doses of estrogen and progestin increased patients' risk for heart disease, stroke and breast cancer.
"Menopausal women really need to think through whether using estrogen-progestin is the right thing to do, particularly if continued for more than a few years," said Marcia L. Stefanick, a professor of medicine at Stanford University and one of the authors of a paper appearing in the Journal of the American Medical Assn.
Physicians taking the medical history of a new patient past menopausal age should "ask specific questions about past use of hormone therapy" and be alert for possible problems, said Dr. Robert W. Rebar, executive director of the American Society for Reproductive Medicine, who was not involved in the study.
"The important message is women really need to make sure they continue getting their mammograms," Stefanick said.
Some experts noted that hormone use had changed dramatically since 2002, with physicians prescribing lower doses for shorter periods of time. They are also giving the drugs to younger women -- a group that the Women's Health Initiative found was less likely to suffer adverse effects.
"We really don't believe this latest article provides any new guidance," said Dr. Gary Stiles, chief medical officer of Wyeth Pharmaceuticals, which manufactures the Prempro used in the study. "We continue to recommend it be used at the lowest effective dose for the shortest duration of time possible."
The Women's Health Initiative originally enrolled 16,608 women with an average age of 63 who were given either Prempro -- a mix of estrogen and progestin -- or a placebo. The goal was to determine whether the hormones could protect against heart disease.
But the study was stopped prematurely after an average of 5.6 years when it was determined that women taking the hormones had a 26% higher risk of breast cancer as well as an increased risk of stroke, blood clots and heart attack.
Subsequent analysis, however, showed that younger women beginning treatment at menopause about 50 did not share the increased risk.
Since 2002, sales of Prempro have dropped from $2 billion a year to a little more than $1 billion. Breast cancer rates also have fallen, and many experts attribute the decrease to lower rates of hormone replacement therapy.
The new study, funded by the National Heart, Lung and Blood Institute, followed 15,730 of the original trial participants for an average of three years after they stopped taking hormones.
The researchers found 281 cancers in the group receiving Prempro, compared with 218 in the placebo group, a difference driven primarily by breast cancers. The rate of deaths from all causes was 15% higher in the Prempro group, but the difference was not considered statistically significant.
There were 343 heart attacks, strokes and blood clots in the Prempro group and 323 in the placebo group, a statistically insignificant difference.
At a news conference sponsored by Wyeth, Dr. Hugh S. Taylor of the Yale University School of Medicine cautioned that, with the uproar over possible harm from hormone replacement therapy, physicians should not lose sight of the hot flashes, vaginal atrophy, sexual problems and insomnia associated with menopause.
"They can have a dramatic effect on women. Careers and relationships suffer," he said.
"It's important that we don't trivialize quality of life."