The millions of women who abandoned hormone replacement six years ago when research showed it increased the risk of serious illness are more likely to develop breast cancer than women who didn't take the hormones, research published today suggests.
But the increased risk of heart disease associated with hormone therapy seems to dissipate, according to a long-anticipated follow-up study published in the Journal of the American Medical Association.
Benefits of the pills, including decreased risk of hip fractures and colorectal cancer, also disappeared when women stopped the medications.
Women who took the hormones over the long term should not necessarily be worried today, but they should watch their health carefully, said Dr. Gerardo Heiss, an epidemiologist at the University of North Carolina School of Public Health and one of the study's authors.
"There's a reason to be vigilant," Heiss said. "There's no reason for alarm."
After the original, critical study of the Women's Health Initiative appeared in 2002, prescriptions for hormone replacement therapy drugs dropped sharply.
The Food and Drug Administration and groups such as the American College of Obstetricians and Gynecologists began recommending that hormones be given only to women actively experiencing symptoms of menopause - and then only at the smallest possible dose for the shortest period of time.
Today's report in JAMA reaffirms what researchers learned in 2002, supporting the decision to halt the original trial.
"This is further confirmation about the danger of long-term combination hormone therapy," said Dr. Michael Lauer, prevention chief at the National Heart, Lung and Blood Institute of the National Institutes of Health, which sponsored the study. "Even after stopping therapy, the harms do not just plain disappear."
For a half-century, hormone replacement therapy was pitched to women as a path to staying young, beautiful and healthy. Women took HRT for many years, believing it helped protect against the ills of aging - particularly cardiovascular disease.
They were often given estrogen in combination with a synthetic form of progesterone - two female sex hormones the body no longer produced.
Animal experiments with estrogen backed up the theories; observational studies showed that women who took estrogen and progestin were healthier than those who did not.
At HRT's peak, an estimated 15 million women were on hormone replacement therapy. But no one had conducted a large clinical trial to test its use.
"It was very frequently prescribed and taken for long periods of time because there was insufficient awareness of the risk," Heiss said. "It was not uncommon for women to take it for 10 years or more."
The publication of the unexpected Women's Health Initiative results in 2002 upended the conventional medical wisdom. Hormones went from being prescribed liberally for older women to being recommended only for those experiencing the acute hot flashes, night sweats and sleep disturbances of menopause.
"Before this study, there was the thought that hormone therapy might be beneficial to all woman post-menopause," said Dr. May Hsieh Blanchard, an obstetrician/gynecologist at the University of Maryland Medical Center. Now, she said, "the only reason to be on hormone therapy is for short-term symptom management."
The latest findings are from a follow-up study of more than 15,700 post-menopausal women - ages 50 to 79 at enrollment - who participated in the WHI trial. They had received either a combination of estrogen and progestin or a placebo for an average of 5.6 years.
The women in the study were instructed to stop taking the hormone therapy in July 2002, while researchers followed them for an average of 2.4 years after that.
Although the increased risk of heart attack dropped after the women stopped taking hormones, Lauer said, the risk of stroke and blood clots remained about the same.
But breast cancer remained the largest risk. Women who took estrogen and progestin during the study but stopped in 2002 were still about 27 percent more likely to develop breast cancer than the women who did not take the hormones at all.
Researchers also noted a 24 percent increased risk in developing any form of cancer, chiefly lung cancer, among women who had been in the hormone group. Overall, there were 63 more diagnoses of cancer during the follow-up study, or three per 1,000 participants per year, according to the NIH.
Breast cancer rates in the United States dropped in 2003, the year after the WHI was halted, and authors of a 2007 study linked the drop in breast cancer to the decrease in hormone therapy prescriptions.
Dr. Kala Visvanathan, a medical oncologist at the Johns Hopkins Kimmel Cancer Center, said women should talk to their doctors about their history of hormone use so the physicians can make more informed decisions about treatment.
"You don't want everyone on it all the time, for long periods of time, and you don't want people to be scared," she said. "There needs to be a discussion."
The average age of menopause is 51, and most women in the study were significantly older than that, raising some questions about whether the risks apply to younger women as well. Still, the basic message is the same: HRT doesn't protect against chronic disease.
Although she doesn't prescribe hormones for that reason, occasionally Blanchard will get a new patient in her 70s who says she takes hormones.
That begins a conversation about why. Blanchard notes that there are other drugs to protect against osteoporosis and other treatments for cardiovascular disease - though not as many for symptoms of menopause.
stephanie.desmon@baltsun.com