Estrogen therapy does not protect women age 65 and older against Alzheimer's disease or other forms of dementia, as scientists once hoped -- and may in fact slightly hasten senility, according to the latest results of a large women's health study.
These results, reported today in the Journal of the American Medical Assn., may be the final nail in the coffin of scientists' hopes for estrogen replacement therapy in older women. The treatment was once thought to be a panacea that reduced many of the ravages of age, such as strokes and dementia, but it now seems instead to promote those problems.
The results mirror those reported last year from a study of the more widely used combination of estrogen and progestin. For the new report, researchers studied 2,947 women, ages 65 to 79, for eight years. Half were taking estrogen.
The team found that 28 of those women developed dementia, compared with only 19 of those who were not taking the hormone -- a 49% increase. The researchers found that trend troubling, but noted that the numbers were too small to be statistically significant.
Dementia is an uncommon condition, so the overall risk is still low, even though the risk is higher for women on hormones. Stephen R. Rapp, a project investigator from Wake Forest University, said that, extrapolating from the study, estrogen might cause 12 new cases of dementia per 10,000 women each year.
Despite the findings of the research, called the Women's Health Initiative Memory Study, hormone replacement therapy is still safe for treating menopausal symptoms like hot flashes in younger women, but the drugs should be taken in low doses for the shortest time possible, Rapp said.
Some doctors still think that the drug confers a protective effect in younger women if the therapy is started during menopause, before any age-related damage has happened to the brain. "Estrogen is not a repairer of function; it's a preserver of function," said Dr. Alan M. Altman, a gynecologist at Brigham and Women's Hospital in Boston.
Most estrogen replacement therapy prescriptions are for women ages 47 through 55 to relieve the symptoms of menopause. But at the beginning of the Women's Health Initiative, scientists thought that estrogen might also help older women stay sharp as they aged.
This theory now appears completely debunked. "I can't see a case for an older woman being on it, and neither can the FDA," Rapp said.
But the study cannot address the risks -- or the benefits -- for younger women, who are the largest group taking hormones. "This still leaves quite open the possibility that an intervention at an early age, before the damage has happened, could be protective," said Dr. Philip M. Sarrel, a gynecologist at Yale-New Haven Hospital.
Study participants who took a daily dose of estrogen, distributed by Wyeth Pharmaceuticals as Premarin, were all healthy women with no signs of mental problems, and all had undergone hysterectomies. (Because they no longer have a uterus, the women do not need to take progestin, which is usually given with estrogen to protect the uterus against estrogen-induced cancers.)
Besides dementia, those taking estrogen also developed "mild cognitive impairment" -- basically, greater than normal forgetfulness, but not full-fledged dementia -- faster than the others, and also showed a small decrease in overall mental acuity, the study found.
Pooling the current results with the previous ones examining estrogen plus progestin showed that older women taking hormones had a 40% greater risk of developing some type of memory problem, Rapp said.
Scientists suspect that the increase in dementia may be caused by small strokes, undetected by the women or their doctors. That speculation is supported by a previous Women's Health Initiative study that found an increase in strokes.