Research Confirms Lower Rate of Alzheimer's in Women on Long-term Hormone Therapy

SEATTLE -- In perhaps the most definitive study to-date on the topic, researchers report in the Nov. 6 Journal of the American Medical Association that hormone replacement therapy (HRT) may prevent Alzheimer's disease in women, but the benefit accrues only when the therapy lasts 10 years or more. No protective benefit was seen from HRT that had not begun at least several years prior to the onset of mental decline.

"Our findings, along with other recent work, suggest that HRT may be effective for the primary prevention of Alzheimer's disease--if not for its treatment," write the authors, from the Department of Veterans Affairs (VA) Puget Sound Health Care System, Johns Hopkins University, Duke University, University of Washington and Banner Health System in Phoenix.

The researchers compared the rates of Alzheimer's disease between 1995 and 2000 in 1,357 men and 1,889 women, all elderly, in Cache County, Utah. They found that women who had taken HRT for at least a decade were 2.5 times less likely than women who had never used HRT to develop Alzheimer's. This lower rate among the long-term HRT users was comparable to that of the men in the study.

The study, funded by the National Institutes of Health, also looked at the use of calcium supplements and multivitamins to see if these had a preventive effect, but none was found. But the researchers do not rule out the possibility that the lower Alzheimer's rate among the long-term HRT users was due to some factor other than the HRT.

HRT, using estrogen and progestin, was the treatment of choice until very recently for millions of menopausal women seeking to halt the bone loss that causes osteoporosis, and to help with other symptoms, such as hot flashes and mood swings. Based on brain-imaging studies, the therapy had also been thought to slow mental decline and stall the onset of Alzheimer's disease, although clinical trials on this issue had produced mixed results. The therapy was associated with a small increase in the risk for uterine and breast cancer, but the benefits were thought to outweigh the risks.

This belief was challenged in July 2002 when the National Heart, Lung and Blood Institute stopped a major clinical trial after finding significantly increased rates of breast cancer and cardiovascular disease in women taking HRT, compared to women on placebo. Soon after, a report in the British journal The Lancet showed an increased risk of breast cancer, stroke and blood clots for women on HRT.

The new JAMA study shows that HRT may in fact help prevent mental decline, but raises questions about the window of effectiveness. In an editorial accompanying the research report, Drs. Susan Resnick and Victor Henderson point out that the results offer hope as to a brain-protective effect of HRT, but show it may be difficult to determine the best timing of treatment.

According to the authors: "A new finding in this study is an apparent limited window of time during which sustained HRT exposure seems to reduce the risk of Alzheimer's disease. We found that, in contrast with [use earlier in life], HRT exposures within 10 years of Alzheimer's onset yielded little, if any, apparent benefit." They theorize that estrogen, like non-steroidal anti-inflammatory drugs (NSAIDS), may exert a protective effect against Alzheimer's only before extensive damage occurs in the brain.

---U.S. Dept. of Veterans Affairs