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Alzheimer's - High Estrogen Levels Linked To Dementia Netherlands Study of Older Hawaiian Men No Association Found with Testosterone

July 24th 2006

Alzheimer's - High Estrogen Levels Linked To Dementia  Netherlands Study of Older Hawaiian Men  No Association Found with Testosterone

Estrogen Targets

Researchers from the Netherlands have found a link between high estrogen levels and dementia in older men.  Their data came from a group of 2974 Japanese-American men aged 70 to 91 who participated in the Honolulu-Asia Aging Study.  The baseline fasting blood samples were drawn between 1991 and 1993, at which time levels of testosterone and estradiol, the major estrogen in humans were measured.

None of the participants had signs of dementia at the beginning of the study.  The researchers measured cognitive decline or dementia in all the participants in 1994-1996 and 1997-1999 using the Cognitive Abilities Screening Instrument (CASI).  They collected physical, demographic and medical information at each exam. 


Of the 2300 participants who completed the study, 223 were diagnosed with incident dementia during the follow-up period.  There were 134 men who developed Alzheimer's disease, and 44 developed vascular dementia.

The researchers used Cox regression analyses, adjusting for age and other covariates, to see if hormone levels were associated with risk of developing dementia. 

The report found that "Levels of bioavailable testosterone were not associated with risk of cognitive decline and incident dementia. In contrast, higher levels of bioavailable estradiol were associated with an increased risk for cognitive decline and Alzheimer's disease." For each standard deviation increase in estradiol level, the risk for the disease went up by 25 percent. Furthermore, compared with the lowest tertile of estradiol, men in the middle and highest tertile had .24 and .28 points lower CASI scores, respectively, for each year increase in age.


The researchers believe that the estradiol association could be explained by increased aromatase activity in the brain which may be associated with a neurodegenerative process. It is then possible that the high levels of estradiol are a consequence or early marker of Alzheimer's disease rather than a cause.

In conclusion, the authors report, "our findings of an increased risk of cognitive decline and Alzheimer's disease associated with higher estradiol are similar to recent findings in postmenopausal women. Further studies are needed to examine whether there are mechanisms by which estradiol may increase risk of cognitive decline and dementia."

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