The Effects of Short Term Estrogen Therapy on Long Term Cognition in Mouse Model

Stephanie Budhan ‘20

Figure 1. One part of the brain controls cognition and memory via estrogen signaling is the hippocampus.

Menopause in women is characterized by the decline in the production of reproductive hormones such as estrogen. Estrogen plays in a major role in maintaining cognition. Thus, post-menopausal estrogen therapy has the potential to enhance cognition in women. However, treatment success, and it appears that estrogen therapy is only effective at a critical time or age in women. Previously, researchers at Tulane University investigated the effect of short-term (40 days) estrogen therapy on “post-menopausal” middle aged rats. They found that estrogen receptor signaling in the hippocampus was stimulated and memory was enhanced over the long term.

Thus, in the current follow-up study, the researchers sought to replicate the current study as well as expand upon it by utilizing a mouse model that was genetically engineered to quantitatively measure the activity of estrogen receptors in the brain. The study was composed of three experiments. Experiment 1 essentially replicates the previous study in order to confirm its results. In Experiment 2, the same experiment was performed but using the genetically engineered mouse line to estrogen signaling in the brain. In Experiment 3, the effects of the estrogen therapy were compared to that of naturally produced estrogen in control mice.

The results study indicated that short-term estrogen therapy in post-menopausal, middle-aged mice did result in enhanced memory and estrogen receptor signaling in not only the hippocampus in other regions of the brain as well. However, when these effects were compare to the control mice, it appeared that estrogen signaling was not enhanced. This may be because estrogen is produced in a cyclical manner in the control mice whereas the post-menopausal mice were continuously given estrogen. So overall the post-menopausal mice were given a larger dose of estrogen compared to control mice. Therefore, study’s control must be redesigned. Nevertheless, this study suggests specific parameters in which estrogen therapy may be a viable option for cognitive enhancement in post-menopausal women.



  1. K. Pollard, H. Wartman, & J. Daniel. Previous estradiol treatment in ovariectomized mice provides lasting enhancement of memory and brain estrogen receptor activity. Hormones and Behavior 98, 1269-1281 (2018). doi:  
  2. Image retrieved from:

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