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November 6, 2002 — A relationship between prior use of hormone replacement therapy (HRT) and a reduced risk of Alzheimer Disease (AD) in older women is reported by researchers in a study in the November 6, 2002, issue of The Journal of the American Medical Association.
Peter P. Zandi, Ph.D., of Johns Hopkins University in Baltimore, Md., and investigators from the Cache County Study, analyzed data on the association between use of HRT and the risk of AD in elderly women. "Compared with men, women appear to be at increased risk of Alzheimer disease (AD) after ages 80 to 85 years," the authors write in background information for the article. They suggest that postmenopausal depletion of endogenous estrogens may contribute to this risk, but point out that previous studies examining the relationship between HRT and AD have provided mixed results.
The Cache County Study is a long-term investigation of the prevalence and incidence of AD and other dementias in relation to genetic and environmental risk factors. The new analyses considered 1,357 men (mean age, 73.2 years) and 1,889 women (mean age, 74.5 years) residing in the Utah county. These individuals were first assessed in 1995 - 1997, and underwent follow-up studies in 1998 - 2000. At the initial contact, the investigators gathered a history of women's current and former use of HRT, as well as of calcium and multivitamin supplements.
The researchers found that 35 men (2.6 percent) and 88 women (4.7 percent) developed AD between the initial interview and time of follow-up three years later. Women who used HRT had a 41 percent reduction in their risk of AD (26 cases among 1,066 women) compared with non-HRT users (58 cases among 800 women).
"We observed a distinct relation between AD risk and duration of HRT use," the authors write. They describe "considerably stronger effects with longer duration of usage. Compared with nonusers, Cache County women who had used HRT for more than 10 years experienced 2.5-fold lower incidence, comparable with the risk observed in men." The researchers continue, "A new finding in this study is an apparent limited window of time during which sustained HRT exposure seems to reduce the risk of AD. We found that, in contrast with earlier use, HRT exposures within 10 years of AD onset yielded little, if any, apparently benefit."
To explore whether the apparent HRT effect simply reflected health-conscious behavior in HRT users, the authors looked for protection from AD in users of calcium or multivitamin supplements. Although they saw no such protection, they caution that studies like theirs cannot offer proof that HRT protects against AD. "We cannot exclude the possibility that HRT users differ from nonusers in other (important) attributes related to health in general and to AD in particular," they write. The investigators add, "the only way definitively to avoid this sort of difficulty is to conduct large-scale randomized prevention trials."
In an accompanying editorial, Susan M. Resnick, Ph.D., of the National Institute on Aging in Baltimore, Md., and Victor W. Henderson, M.D., M.S., of the University of Arkansas for Medical Sciences in Little Rock, Ark., write that the potential role of menopausal hormone therapy in reducing the risk for dementia due to AD is a topic of great concern for women at midlife and beyond.
"...the results reported by Zandi et al indicate that former users of hormone therapy have a greater reduction in the incidence of Alzheimer disease than current users. Among current users, only long-time users (greater than 10 years) appeared to benefit. These findings raise important issues concerning current understanding of the way in which hormone therapy may potentially protect against Alzheimer disease, for the interpretation of existing studies, and for the design of new investigations."
"The current data are insufficient to recommend hormone therapy for prevention of Alzheimer disease. However, many women will continue to consider short-term use of hormone therapy for treatment of menopausal symptoms, and the possibility of a critical period of use suggests that treatment during the climacteric [menopause] might offer some protection against Alzheimer disease. The results reported by Zandi et al offer both hope for a possible neuroprotective effect of hormone therapy and frustration that it could be difficult to determine the optimal timing of treatment," the authors conclude.