MIAMI BEACH — The risk of Alzheimer's disease declines by almost half among postmenopausal nonsmokers who use estrogen therapy, but nearly doubles among those who both smoke and use estrogen therapy, Rosebud O. Roberts, M.B., said in a poster presented at the annual meeting of the American Academy of Neurology.
Dr. Roberts, an epidemiologist at the Mayo Clinic, Rochester, Minn., also found that early estrogen therapy might be a predictor for Alzheimer's in postmenopausal women; in contrast, estrogen therapy taken later in life appears to be more protective. But these conclusions may have more to do with premenopausal estrogen levels than postmenopausal estrogen therapy, she said in an interview.
“What I suspect is that smoking may lead to lower estrogen levels premenopausally, which could lead to brain neurons that are less viable and more likely to die early. Those who initiate therapy earlier probably have less [endogenous] estrogen, and more symptoms, while those who initiate therapy at a later age—because they had fewer symptoms or less severe symptoms—probably had more premenopausal estrogen.”
She and her associates conducted a case-control study that included 216 women with natural menopause who developed Alzheimer's disease during 1985–1989. They were compared with 210 cognitively intact controls who had similar ages at menarche and menopause.
A similar percentage of women in both groups used estrogen therapy for at least 6 months (11.6% of cases, 14% of controls). Of the 54 women on estrogen, the 25 with Alzheimer's started estrogen therapy earlier than the 29 controls (50 years vs. 53 years), and had a shorter lag time between menopause and the initiation of estrogen therapy (1 year vs. 4 years). Estrogen users had a 20% reduced risk of Alzheimer's disease, but this was not statistically significant.
The investigators did see significant differences in estrogen therapy and the risk of Alzheimer's disease between smokers and nonsmokers, however. The odds ratio of Alzheimer's was 1.93 in smokers who used estrogen therapy and only 0.54 in nonsmokers who used estrogen therapy. In nonsmokers, estrogen therapy of more than 3 years' duration showed a significant protective effect, reducing the risk of Alzheimer's by almost 70%.
“It is in women who don't smoke where we see the beneficial effects of [estrogen therapy],” she said.