TUESDAY, March 2, 2004 (HealthDayNews) -- U.S. health officials have halted the third portion of a landmark hormone replacement therapy trial.
The National Institutes of Health (NIH) on Tuesday pulled the plug on the estrogen-only segment of the Women's Health Initiative (WHI), a major 15-year research program on postmenopausal women, because the data suggests estrogen on its own has no impact either way on heart disease.
While that was the main focus of the study, the research found estrogen alone appears to increase the risk of stroke even though it did not appear to increase the risk of breast cancer.
"The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study," an agency statement says. "This is especially true if estrogen alone does not affect (either increase or decrease) heart disease, as appears to be the case in the current study."
Meanwhile, the U.S. Food and Drug Administration says in a statement it will now assess these latest results to determine whether additional label changes for hormone replacement therapy (HRT) are needed.
The trial, cut short after almost seven years, involved 11,000 healthy postmenopausal women between the ages of 50 and 79 who had had their uteruses removed in a hysterectomy. Women without uteruses can take estrogen alone; those who have a uterus increase their risk of uterine cancer if they don't take progestin to counteract the effects of estrogen.
The women in the estrogen-only portion of the trial were taking Premarin, a conjugated equine estrogen, daily.
The decision to stop the trial, according to the NIH statement, was made on Feb. 2.
"In November and December 2003, the WHI Data and Safety Monitoring Board (DSMB), an independent advisory committee which regularly reviews study data and oversees the safety of study participants, reviewed the latest data from the estrogen-alone study. The DSMB was split as to whether the study pills should be stopped or whether the pills should be continued, provided that a letter would be sent to the participants clearly informing them of the stroke risks and other findings," the statement says.
"After careful review, the NIH decided that women in the estrogen-alone study should stop taking their study pills," the agency adds.
The latest halt follows the shutting down of two WHI high-profile studies involving combination hormone therapy, estrogen plus progestin. In July 2002, the first study was halted because of an unexpected increased risk of breast cancer, heart disease, stroke and blood clots. There was also a decreased risk of hip fracture and colon cancer, but that was not enough to merit continuation of that study.
In May 2003, the memory arm of the WHI was stopped when data showed an increased risk of dementia in women aged 65 and older who took the combination therapy.
And the litany of bad news about HRT trials is not limited to the United States.
In October 2002, a major British trial evaluating hormone therapy was also stopped after elevated risks of breast cancer appeared. Last month, a Swedish HRT study on women who have had breast cancer was halted because the risks of a recurrence of cancer were judged to be too great.
If that were not enough, two small studies recently suggested that HRT could raise the risk of asthma and hearing loss in postmenopausal women.
But expert reaction to the newest cutoff was cautious.
"This is not anywhere as exciting or alarming as the last halting of the study [the July 2002 one]," says Dr. Mary Jane Minkin, a clinical professor of obstetrics and gynecology at Yale University School of Medicine.
And despite the latest findings, Minkin sees no reason to universally stop hormone therapy for menopausal women.
"The key thing to remember with any of these studies is that they were not studying women going through menopause," she says. "The average age of women in the WHI is 63 years old upon initiation of therapy, much older than menopausal, and they're not the world's healthiest. These are not typical women going through menopause."
"Is this relevant at all to my patients going through menopause, and the answer is I don't know," she continues. "Does this make me more worried? No. What my patients are really worried about is breast cancer and what they're going to be interested in is this didn't show increased risk of breast cancer."
She says she would like to know exactly how much of an increased risk of stroke was seen, too.
Also unanswered are questions about what form of estrogen is problematic. This study looked only at oral estrogen, leaving open the possibility that hormone patches might be better.
The NIH says full results of the estrogen trial will not be released for two months until researchers can analyze the data. But its statement indicates the findings were similar to those that caused the July 2002 trial to be halted.
In that study, women taking estrogen plus progestin had eight more strokes per year for every 10,000 women than those taking the placebo, it says.
As the disturbing evidence keeps accumulating, the FDA has been working with manufacturers of hormone therapies to update product labeling.
While these products are still available, the FDA advises women and their health-care providers to discuss the benefits and risks of HRT. The agency is also reminding people that hormone therapy has never been approved for preventing heart disease or memory conditions such as Alzheimer's. Hormone products should only be used for the relief of moderate to severe postmenopausal symptoms such as hot flashes, the agency says. And, it adds, products should also be used at the lowest dose and for the shortest duration possible.
Minkin thinks individualized decisions are the way to go.
"Does this scare me? No. Is this going to tell me to tell my patients who are using estrogen and/or progestin you've got to stop? No," she says. "It's got to be evaluated on a case-by-case basis. You have to take into account each patient's risk profile and what the symptoms are."