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Kawas and colleagues from johns hopkins investigated the relationship between postmenopausal estrogen therapy and the risk of developing Alzheimer’s disease in the Baltimore Longitudinal Study of Aging. This study is a prospective study of normal aging conducted by the National Institute of Aging. From this study, 514 women who had been followed for up to 16 years were available for analysis. Every two years, the subjects returned for an extensive evaluation. About 45% of the women used estrogen, and there was a total of 34 cases of Alzheimer’s diseaseonly nine in the estrogen-user group. The relative risk for the development of Alzheimer’s was 0.46 (CI = 0.209-0.997). No increase in protection was found with increasing duration of estrogen use (contrary to data in some case-control studies).
Each new study examining the relationship between postmenopausal estrogen therapy and the risk of developing Alzheimer’s disease finds a significant beneficial effect of estrogen. This new study has the strength of being a prospective cohort investigation; nevertheless, the impressive positive effect of estrogen will have to be confirmed by the currently on-going randomized clinical trials. However, the results of the recent case-control and cohort studies have been so impressive that estrogen therapy is being recommended in many geriatric centers and in many dementia clinics. This is supported by the findings that women who already have Alzheimer’s disease demonstrate improvement in cognitive function with estrogen therapy.
An important unanswered question is whether the addition of a progestational agent has a positive or negative influence on this effect of estrogen. I know of at least one dementia center that believes adding a progestin subtracts from estrogen’s beneficial effect. This question, too, is being addressed in the on-going clinical trials.
In the meantime, this is another powerful argument in favor of long-term estrogen therapy and an argument supporting the initiation of estrogen treatment in elderly women. It is also another good reason to consider raising estrogen levels in men. (Dr. Speroff is Professor of Obstetrics and Gynecology, Oregon Health Sciences University, Portland.)