For the second time in two years, the National Institutes of Health has halted a massive women’s health study, telling postmenopausal participants to stop taking estrogen because it does not protect them from heart disease even as it increases the risk of stroke.
Preliminary review of the study’s findings indicates that estrogen does protect women from hip fractures, but also may slightly increase the risk of developing dementia or mild cognitive impairment, NIH officials said.
In July 2002, the study known as the Women’s Health Initiative halted research into the other form of hormone replacement therapy, estrogen coupled with progestin, after researchers determined the combination increased risks of breast cancer, strokes, heart attacks and blood clots in postmenopausal women.
Together, the findings turn what had long been conventional medical wisdom on its ear, puncturing the myth of hormone replacement as an elixir of youth and healthfulness for women.
“This reinforces the previous recommendation that women should not take hormone therapy to prevent heart disease,” said Dr. Barbara Alving, director of the Women’s Health Initiative and acting director of the National Heart, Lung and Blood Institute of the NIH.
If women are considering estrogen therapy for relief of severe menopausal symptoms such as hot flashes, she said, “they should use it at the lowest doses, for the shortest period of time.”
Hormone replacement had been commonly recommended not just as effective therapy to ease the transition to menopause but as a long-term preventive health measure believed to confer a wide array of health benefits, from preventing heart disease and osteoporosis to possibly protecting cognitive function.
At its peak, some 15 million American women were taking some form of estrogen or combination pills. More than 8 million continue to take estrogen or the combination formula, the majority on estrogen only. Officials with Wyeth-Ayerst, maker of Premarin, said that before 2002, 6.4 million women were taking Premarin, its brand of estrogen pills, while 3.4 million took its brand of estrogen-progestin, Prempro. The numbers have fallen to 4 million on Premarin and 700,000 on Prempro.
Responding to news of the study results yesterday, Cynthia Pearson, executive director of the National Women’s Health Network, a nonprofit health organization that pressed for the trials in 1990, said, “The era of replacement therapy is over. It was a theory that made a lot of sense biologically but there wasn’t all that much data to back it up.”
Hormone treatments are still approved for relief from moderate to severe hot flashes and symptoms of vulvar and vaginal wasting. And though it is effective for preventing osteoporosis, yesterday NIH officials discouraged it for women unless they are at high risk and cannot take other medications.
The estrogen-only study followed 11,000 healthy postmenopausal women, aged 50 to 79, who had previously undergone hysterectomy. It became apparent fairly early that women taking estrogen faced a slightly higher risk of stroke than the control group taking a placebo pill, NIH officials said, and participants were warned about the increased risk.
Women taking estrogen had eight more strokes a year for every 10,000 women, an increase in risk similar to the increased risk of women taking a combination of estrogen plus progestin, NIH officials said.
And estrogen did not confer the promised protection against heart disease.
“This is a sea change from the beliefs in the early 1990s when we got started on the trials,” said Dorothy Lane, principal investigator for the Stony Brook University Hospital Women’s Health Initiative Clinical Center. “Since the results came out on estrogen plus progestin, it’s less surprising, but there still was the hope that the estrogen alone findings would be different.”
But, she said, “Estrogen, and estrogen plus progestin, are not the answer.”
Some 125 women are enrolled in the estrogen-only part of the trial at the Stony Brook center, according to Lane. They are among 11,000 participants nationwide who have received letters telling them to stop taking the pills. They were randomly assigned to either Premarin, a daily dose of 0.625 mg of conjugated equine estrogen, or a placebo.
Only women who have undergone hysterectomy are treated with estrogen alone, because so-called unopposed estrogen increases the risk of uterine cancer.
The NIH decided to stop the estrogen alone study on Feb. 2, after the initiative’s Data and Safety Monitoring Board, an independent advisory committee that regularly reviews data and oversees safety, reviewed the latest data. The advisory committee was split about whether the study should continue or be stopped, but the NIH decided to halt it, Alving said.
One intriguing finding was that estrogen alone, long suspected as a culprit in breast cancer, did not increase the risk during the time period of the study. “We were surprised,” Alving said. “There was a great deal of conjecture about this.”
More detailed analysis of data from the study will be reported in the next two months and published in medical journals, NIH officials said.
“I wasn’t surprised about the results,” said Sydell Urdang- Pizzo, 74, of Shirley, who has participated in the study since 1995. “I had a hysterectomy at 45 and was put on Premarin.”
But her doctor discontinued it after three months, she said, and Vitamin E helped her with the estrogen depletion.
She learned yesterday that she had been taking a placebo during the study.
“I think it’s a beautiful thing for all the women yet to be,” she said of the Women’s Health Initiative. “It’s the only study in this country that’s exclusively for postmenopausal women.”
A separate report will have information on women 65 and over who took part in the WHI Memory Study (WHIMS), an ancillary study of the hormone trials. Preliminary data suggest those on estrogen face a “trend toward increased risk of probable dementia and/or mild cognitive impairment.” In 2003, WHIMS reported an increased risk of dementia in women 65 and over taking estrogen plus progestin.
Wyeth-Ayerst Research provided the active hormone for the estrogen alone study and funded the WHIMS study.
The Women’s Health Initiative has involved more than 160,000 postmenopausal women at 40 clinical sites across the country.
Other ongoing WHI trials are studying a low-fat eating pattern and calcium and Vitamin D supplements.