Estrogen study uncovers role of age in outcomes
Women not only get some protection from breast cancer while they take estrogen-only hormone replacement, that benefit continues after they stop, according to the latest findings from an expansive national study.
Seattle Times health reporter
Women not only gain some protection from breast cancer while they take estrogen-only hormone replacement, that benefit continues after they stop, according to the latest findings from an expansive national study.
But the findings, released Tuesday in the Journal of the American Medical Association (JAMA), underscore that nothing is ever simple when it comes to women's hormones.
Unlike an earlier study that frightened millions of women, the results of this clinical trial deliver a good — if mixed — message.
For women in this study — who'd had hysterectomies and who used estrogen for several years and then stopped:
• The decreased risk of invasive breast cancer while they took hormones continued for years after they stopped;
• The increased risk of stroke during the years they took hormones dissipated;
• But the protection they had from hip fracture while they were taking hormones disappeared gradually.
And — the really mixed part of the message — these findings vary significantly by age.
The news is the latest from the huge Women's Health Initiative (WHI) study, which for years has studied the hormone-replacement therapy many women take to relieve symptoms of menopause, such as hot flashes.
In 2002, a different part of the study that enrolled almost 17,000 women to look at the effects of estrogen plus progestin was halted abruptly when researchers found increased risks.
To the great alarm of many women and their doctors, that study turned much conventional wisdom about combination hormone therapy on its head.
Contrary to what many doctors had long believed, researchers found those pills did not protect women from heart disease and brittle bones. Worse, they found that five years on the combination therapy doubled a woman's risk of developing breast cancer.
The early end to the estrogen-plus-progestin study and publicity about the findings caused a furor, and women across the country abandoned combination hormone replacements.
By contrast, the news this time is mostly good, depending on a woman's age.
"These are some of the most favorable findings about estrogen alone we've ever published," said the report's lead author, Andrea LaCroix, co-principal investigator of the WHI Clinical Coordinating Center, based at Fred Hutchinson Cancer Research Center. "It's certainly a big contrast to the increasingly risky outcomes of estrogen plus progestin."
Age makes a difference
The Estrogen-Alone Trial enrolled 11,000 women ages 50 to 79 at 40 sites across the country, including Seattle, between 1993 and 1998.
The double-blind trial randomly assigned women either an estrogen pill or a placebo.
When the study was halted in 2004 — a year early, because researchers found women on the hormone had an increased risk of stroke — women stopped taking their study medication. But researchers continued to follow them.
The study reported Tuesday tallied the health "events" experienced by those women, who participated in the trial for an average of about seven years, and were followed up, on average, for an additional four years.
In general, LaCroix said, the findings are good for women in their 50s, neutral for those in their 60s, and start to be increasingly negative for women in their 70s.
For women who were in their 50s when they began using estrogen, there was a significantly lower rate of death compared to non-estrogen users, LaCroix said. But that picture changes drastically by age.
"If I were in my 60s or 70s, I would think these findings argue against the long-term use of hormones," LaCroix said. "For older women, the data clearly argue that there are important risks of being on estrogen alone. Our bodies change with age, and the doctrine 'do no harm' should be taken seriously here."
For women who were in their 70s when they were enrolled in the study and given estrogen, there are "very concerning" results, she said.
Researchers calculated that, for every 10,000 women in their 70s, there would be 48 more cases of serious health events among those who took estrogen, compared to those who didn't take it.
Those health problems included breast cancer, stroke, hip fracture, pulmonary embolism, colorectal cancer or coronary heart disease. And for those older, estrogen-using women, there were 19 more deaths, from all causes.
Other examples of the age differences: Colorectal-cancer rates, for women who began taking estrogen in their 50s, were slightly less. But for women who were in their 70s, rates were nearly double for estrogen users.
And while estrogen use conferred strong protection against coronary heart disease in younger women, it brought slightly more risk for women who began taking it in their 70s.
By age 60, one of every three U.S. women has had a hysterectomy — surgical removal of the uterus. Most of them can take estrogen-only hormones, while those who have an intact uterus are advised to take combination hormones (estrogen plus progestin or progesterone, which is a synthetic progestin) to protect the uterine lining.
The estrogen-alone study used Premarin, a pill made by Wyeth Ayerst, which is made up of equine estrogens. It is not clear whether other types of estrogen or other forms of hormone delivery, such as a patch, would have the same results.
An editorial in JAMA argued that, because the study included many older women who started and stopped hormones after several years of use, it does not reflect the way doctors actually prescribe — often soon after menopause begins — and may not help reach conclusions about estrogen use in younger women.
The study results don't counter "the larger body of evidence" that shows an increased risk from estrogen, the editorial writers added, warning doctors to be careful in extrapolating results from the WHI to individual patients.
When the earlier estrogen-plus-progestin trial was stopped in 2002, worry spilled over into the estrogen-only trial, and a large number of women stopped taking their study medication. By the end of the estrogen-only trial, 54 percent had stopped taking their medication, LaCroix said.
Even so, "I thought the data spoke very clearly," said LaCroix, a professor of epidemiology.
Women can be reassured by the findings of this study that some increased risks of estrogen dissipate after they stop taking it, LaCroix said, and no new safety concerns popped up.
But in making a decision whether to take estrogen, women still should weigh their odds, age and other risk factors with their doctors.
The results of the hormone studies have wiped out any trace of arrogance among those in the medical research field who previously may have believed they had all the answers, LaCroix said.
"I feel grateful (to the women who participated in the trial) and am absolutely in awe of what these studies taught us about what we didn't know before," she said.
Carol M. Ostrom: 206-464-2249