But the new risks for other cancers, particularly lung tumors, in women who'd taken estrogen-progestin pills for about five years puzzled the researchers and outside experts.
Those risks "were completely unanticipated," said Dr. Gerardo Heiss of the University of North Carolina in Chapel Hill, lead author of the follow-up analysis.
The analysis focused on participants' health in the first two to three years after the study's end. During that time, those who'd taken hormones but stopped were 24 percent more likely to develop any kind of cancer than women who'd taken dummy pills during the study.
"There's still a lot of uncertainty about the cause of the increased cancer risk," said analysis co-author Dr. JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital.
The cancers included breast tumors, which also occurred more frequently in hormone users during the study.
The researchers noted that the increased risks for all cancers amounted to only three extra cases per year for every 1,000 women on hormone pills, compared with nonusers.
Still, Heiss said the results suggest that former hormone users need to be vigilant about getting cancer screening including mammograms.
"Vigilance is justified," he said. "No alarm, but vigilance."
The initial study of 16,608 postmenopausal women was designed to examine pros and cons of taking pills long thought to benefit women's health. It was halted in 2002 when more breast cancers, heart attacks and related problems were found in hormone users versus nonusers.
There were some health benefits -- decreased risks for hip fractures and colorectal cancer -- but the follow-up found those also faded after women stopped the pills.
Some data suggest that U.S. breast cancer rates have declined since the study's end. But that likely reflects fewer women starting on the pills rather than any decline in breast cancer risk among past users, said Dr. Michael Lauer of the National Heart, Lung and Blood Institute at the National Institutes of Health, which conducted and funded the landmark research.
The authors said the new results send the same message they've been advocating ever since the study ended: Health risks from estrogen-progestin pills outweigh their benefits, and they should only be used to relieve hot flashes and other menopause symptoms, in the lowest possible dose for the shortest possible duration.
The new analysis appears in Wednesday's Journal of the American Medical Association.
A spokesman for Wyeth Pharmaceuticals, maker of the Prempro estrogen-protestin pills used in the study, voiced a criticism frequently cited by scientists, too -- that participants were in their 60s on average, at least 10 years older than typical hormone users. The latest results thus may not apply to typical users because older women have different health risks than younger ones, including more cancers in general, said Wyeth's Dr. Joseph Camardo.
Prempro's packaging information already recommends routine breast exams and mammograms for users, and Camardo said the follow-up results are "not anything that's particularly new that should change guidance."
Manson, the co-author, said it's possible the initial study results prompted hormone-using participants to see their doctors more often than nonusers after the study ended, which could have resulted in more cancers detected.
It's also possible hormones either triggered new tumors or fueled the growth of existing ones, the researchers said.
"Once a tumor gets started, you might think of it as a train is out of the station and it might be more difficult to stop it," Lauer said.
The follow-up involved 15,730 participants tracked through March 2005.
The authors said the decline in heart problems was not surprising, since harmful effects of hormones on blood vessels could be expected to fade after women stopped taking the pills. Also, heart risks during the study were highest soon after women started taking hormones.
Dr. Sherry Nordstrom, an obstetrician-gynecologist at the University of Illinois at Chicago, said the lung cancers were a surprising finding but called hormones "still very appropriate therapy" for women with bad symptoms.
Study participant Geraldine Boggs, a Washington, D.C. nurse with three daughters and four granddaughters, said women should pay attention to the new findings.
"I initially joined the study to make sure that my daughters and granddaughters had informed choices about taking them when they got to be my age," said Boggs, 64.
Boggs, in her early 50s when she enrolled, was assigned to take hormones. Still, she said she developed no health problems during the study or afterward, other than hot flashes for about a year after quitting the pills.
Dr. Nieca Goldberg, a New York University women's heart specialist, said the study underscores that in addition to cancer screening, women who stop taking hormones need to find other ways to keep their bones strong, including getting more calcium and exercise.