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108 Current Topics in Menopause Eef Hogervorst
Recall of use would also be required retrospectively to an average of 15 years
before the symptoms of dementia would have become apparent at the earliest, as
most AD symptoms do not appear until 65 years of age [10] and, on average,
women experience menopause around 51 years of age [11]. It was indeed found
that women with dementia were twice more likely to forget that they took
hormones when their self report was compared to that of their pharmaceutical
records [12]. This “recall bias” is thus inherent to the very nature of the morbidity
under investigation. Substantiating the importance of this bias is that studies
which used pharmaceutical records, rather than self report, could also not replicate
the earlier reported protective association of self reported estrogen use with lower
dementia risk [8]. This bias would not affect prospective studies, where women
would not have had dementia symptoms at baseline. However, these are also
tainted by bias, albeit in a different form.
Women who decided to use sex hormones around the menopause were already
healthier before they started hormone use [13]. This bias is referred to as the
“healthy user bias”. These women already had lower blood pressure, less diabetes
risk, lower weight, lower cholesterol levels and exercised more, as well as usually
being better educated than those women who would not use hormones for
menopausal complaints or other indications. It was postulated [8] that using
hormones was part of a “healthy lifestyle” choice for these women at a time when
negative effects of hormones (breast cancer risk, possible risk for stroke and
dementia etc). were not as highlighted as they are today. All these healthy lifestyle
related factors in midlife have been implicated in reduced dementia risk in later
life and could provide bias for the association between the decision to use
hormones and a lower risk of dementia found in the observational studies [14].
Despite the biological plausibility as indicated by the animal and cell culture
studies, these forms of bias make it difficult to promote hormone use to prevent
dementia in women.
THE NEGATIVE EFFECTS OF LONG TERM EXPOSURE TO
ELEVATED ESTROGEN LEVELS ON DEMENTIA RISK
In addition, in contrast to the basic sciences and observational data, several large well
controlled treatment trials actually showed negative effects on dementia and cognition