Reduced Risk of Alzheimer Disease: a Possible Benefit of Hormone Replacement Therapy?
Several factors may contribute to a person’s risk of developing Alzheimer disease (AD), including hormonal factors. Scientists are currently studying what effects, if any, hormones have on the risk of AD and if the use of hormone replacement therapy (HRT) by women during menopause exerts any protective effect on that risk.
The results of such studies have been mixed, but a recent one, published in the Journal of the American Medical Association , found that women who took HRT had a lower risk of developing AD later in life compared with both women who did not use HRT and men. The comparison with men is important, say the researchers, because after the ages of 80 to 85, women appear to have a greater risk for AD than similarly aged men.
About the Study
Researchers from several institutions used data from a study of the effects of genetic and lifestyle factors on risk for AD in elderly men and women residing in Cache County, Utah. Data on a total of 3246 subjects were evaluated: 1357 men (average age 73) and 1889 women (average age 75).
From 1995-1997, subjects were assessed to see how many of them had AD. Several commonly used and well-accepted methods for diagnosing AD were used, including screening questionnaires and detailed examinations by geriatric psychiatrists and neuropsychologists. Three years later, during 1998-2000, subjects were re-evaluated to see how many new cases of dementia had developed.
Researchers also interviewed the female subjects to find out how many had used HRT at any time in their lives. They classified HRT users as “former” or “current,” and also classified use based on duration, including less than 3 years, 3 to 10 years, and more than 10 years. They then calculated the subjects’ risks of developing AD and used statistical analyses to relate it to use of HRT.
Of the 3246 subjects studied, 35 men (2.6%) and 88 women (4.7%) developed AD during the 3-year period between initial assessment and follow-up. Women who used HRT had a 59% lower risk of developing AD compared with women who did not use HRT and had a 23% lower risk compared with men. The risk reduction was seen mainly in women who were former users of HRT (as opposed to current users) and in those who used it for more than 10 years. This leads the researchers to hypothesize that the potential protective effect of HRT on AD risk in late life is dependent upon women taking it earlier in life (at menopause), before AD has begun to develop.
In doing the statistical analyses, the researchers controlled for certain other factors (known as “confounding factors”) that could have influenced AD risk, including age and education level.
Like many observational studies, however, this one has certain limitations, including the following:
- The subjects studied were a very homogenous group—that is, they had similar socioeconomic and sociocultural characteristics, and they all resided in the same county. Therefore, the results cannot necessarily be generalized to the public at large.
- This study relied on the subjects’ own recollections of their exposure to HRT. The results would have been biased if the subjects unintentionally misreported their actual HRT exposure, a not uncommon occurrence in these kinds of studies.
- There could have been some other, unknown characteristics of the women who took HRT (other than the confounding factors that were controlled for) that may have influenced their AD risk.
How Does This Affect You?
So, do the results of this study mean that doctors should begin prescribing HRT as a means to prevent Alzheimer disease? Not yet. More research, including clinical trials, is necessary, especially in light of the findings released this summer from the Women’s Health Initiative study showing that HRT slightly increases the ]]>risk of breast cancer, heart attack, and stroke]]> . It is important to note that the majority (72%) of current users of HRT in the present study were receiving therapy consisting of estrogen alone, which is still being studied by the WHI.
As research continues to unfold, talk to your doctor about your individual potential risks and benefits of taking HRT. As for preventing Alzheimer disease—a number of studies suggest that certain dietary factors and medications, along with exercising both the body and the mind, have the potential for reducing risk. But further data are necessary before general recommendations can be made.
National Heart, Lung, and Blood Institute, National Institutes of Health
Postmenopausal Hormone Therapy
Alzheimer’s Disease Education & Referral Center
Zandi PP, Carlson MC, Plassman BL, et al. Hormone replacement therapy and incidence of Alzheimer disease in older women: The Cache County Study. JAMA . 2002;288:2123-2129.
Resnick SM, Henderson VW. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA . 2002;288:2170-2172.
Last reviewed Nov 7, 2002 by ]]>Richard Glickman-Simon, MD]]>
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