Specifically, taking estrogen around the time of menopause is linked to a lowered risk of dementia for women as they enter old age, but estrogen therapy in late life is associated with a higher risk for dementia, according to a retrospective study led by Dr. Kristine Yaffe, chief of geriatric psychiatry at the San Francisco VA Medical Center.
Yaffe wanted to probe the opposing evidence on whether or not estrogen is neuroprotective.
“In animal models and molecular studies, it looked as if estrogen had beneficial effects on the brain, especially if administered early,” said Yaffe. “While at the same time, research in humans indicated that estrogen therapy was associated with an increased risk of dementia.”
Yaffe analyzed the health data of 5,504 post-menopausal women who were members of the Kaiser Permanente Medical Care Program of Northern California.
In particular, the Women’s Health Initiative, a nationwide study funded by the National Institutes of Health, showed strong links between estrogen therapy and dementia, as well as a multitude of other serious health problems, including breast cancer, stroke and cardiovascular disease, she said.
“Nonetheless,” said Yaffe, “some scientists have wondered if the problem with estrogen and dementia is that you have to expose women to hormones at a certain critical period, during and just after menopause — and that older age is too late.”
She wanted to test this “critical window” theory by observing more than 40 years of data on the members of Kaiser, a health survey given in the years between 1964 and 1973 (the women were middle aged); then the women’s pharmacy records from 1994 to 1998; and finally their patient diagnoses from 1998 to 2008.
“It was the best way I could conceive of to look at the question of mid-life versus late-life exposure to hormone therapy,” said Yaffe, “since no one is going to fund a 30-year trial on this question.”
The results, she said, “seem to confirm the critical window hypothesis.” Women who participated in estrogen therapy in mid-life but not in late life had 26 percent decreased risk of dementia in old age as opposed to women who had never taken estrogen in their lifetime.
However, women who took estrogen in old age but not in mid-life had a 48 percent greater risk of dementia compared to non-estrogen-taking women.
Interestingly, those who took estrogen in both mid-life and old age had the same risk for dementia as women who never took it at all.
Yaffe believes the study is significant for two reasons.
“First, it replicates the results of the Women’s Health Initiative, in that it shows that estrogen exposure in late life increases your risk of dementia, and that women should not take estrogen at that time in hopes of reducing dementia.”
Second, she said, “it suggests that if you’re exposed to estrogen only around menopause, and not in later life, it may be protective. We aren’t sure why, but studies in animal models indicate that during menopause, estrogen may increase neuronal health and reduce the changes in the brain seen with Alzheimer’s disease.”
But she cautioned against reaching premature conclusions from her research.
“This was an observational study, not a drug trial,” she said, “so we cannot say for sure that mid-life estrogen is responsible for the protective effects we observed. It is suggestive, but it is not proof.”
Yaffe noted that “while the known health risks of hormone therapy must be acknowledged, I will note that cancer, stroke and cardiovascular disease tend to be age-related. It may be that if we restrict hormone therapy to a year or two around the menopause transition, and then stop it, it may not increase the risk for these other things. We just don’t know.”
“We need to go back and think carefully about estrogen, “ she said. “My hope is that this study will help open the door to other studies — that it will tell funding agencies that the question is more complicated than we thought.”
The study is found in the January 2011 issue of Annals of Neurology and was supported by funds from the National Institute on Aging.
Source: University of California