The roles of the ovarian hormones, estrogen and progesterone, in cognition and
neuroprotection continue to be highly controversial. Despite a wealth of
information that estrogen can affect learning and memory and promote neuronal
survival in non-primate models, the therapeutic benefits of hormone replacement
therapy are not supported by the recent findings of the longitudinal Women's
Health Initiative Memory Study (WHIMS) of over 4500 women. WHIMS results
released to date indicate that women between ages 65 to 79 taking a daily
combination treatment of estrogen and a synthetic progesterone, progestin,
actually had a higher incidence of dementia over the course of the study
compared to controls. There are several caveats regarding the WHIMS results.
First, the synthetic progestin used in the combination therapy is not typically
administered in non-human experiments and there is evidence that this form of
progestin may counteract some effects of estrogen. Second, many of the hormonal
effects reported in non-primates have been found with estrogen alone, given in the
absence of progesterone or other progestins. WHIMS results from women taking
estrogen alone will be released in the coming years. Therefore, the treatment
conditions in the WHIMS project differ in important ways from treatments typically
administered in non-primate studies.
In rodent experiments from our laboratory as well as other laboratories, estrogen
has been shown to affect performance on appetitive and aversive tasks, on spatial
and non-spatial tasks, on conditioning, and on acquisition, consolidation, and
retention. These effects are complex and vary with task, gender, and age, as
well as the regimens of estrogen exposure. Furthermore, the effects of estrogen
on learning and memory can improve, impair, or not affect performance on various
measures of learning and/or memory. We have also found that estrogen can limit
cognitive impairments in female rats induced by administration of neurotoxins
associated with human dementias. Consequently, the biological and behavioral
significance of estrogen modulation of cognitive performance warrants further
investigation. A better understanding of the mechanisms of estrogen action and
cognitive function may lead to the development of new steroid treatment regimens
to improve neuronal functions that has been compromised by trauma, age, or disease.