Study Finds Link Between Estradiol and Depression, Anxiety

A study from the University of Albany found that the administration of the hormone estradiol to aged female mice decreased anxiety-like and depression-like behaviors. This finding may help explain the onset of depression during and after menopause.

Previous research found that estradiol had an anti-anxiety and anti-depressive effect on young mice, but whether the same was true of old mice, which have significant differences in hormone levels, remained uncertain. Estradiol is a sex hormone which is most prevalent in females, but also occurs in males. A synthetic version of estradiol (ethinylestradiol) is also used in many hormonal contraceptives.

Eighteen mice, which were between 20 and 28 months old, were injected with either sesame oil or estradiol, and then put through a variety of anxiety and depression tests. Why 20 to 28 year old mice? As the authors of this research note,”female reproductive aging in mice is similar, but not analogous to that of women” After 20-26 months, the production of sex hormones in the ovaries of mice decreases, similar to what occurs during menopause in women.

The tests included the open field, elevated plus maze, mirror chamber, light-dark transition task, and the Vogel conflict-task to assess anxiety levels and the forced swim task to assess depression levels. These tests are commonly used to assess depressive and anxiety-like behaviors in lab rats and mice.

The results of the study found that mice injected with estradiol had lower levels of anxiety in three of the five tests as compared to the mice injected with sesame oil. Although the other two tests also indicated that the mice injected with estradiol had reduced levels of anxiety, the results of these tests were not statistically significant. (In other words, there was not enough evidence to confirm that the results of these two tests were not due to chance.) The mice injected with estradiol also showed lower levels of depression.

This research provides evidence for the effectiveness of hormone replacement therapy as a treatment for menopausal and post-menopausal depression. Although the results of this study may sound promising, it is far from conclusive. Until more research is conducted on the mechanism by which estradiol influences depression and anxiety, the clinical significance of hormone replacement therapy for these symptoms will remain questionable.

Furthermore, anyone considering the use of hormone replace therapy should be aware of its side effects. According to Medline Plus, hormone replacement therapy “can increase your risk of breast cancer, heart disease and stroke.”


Walf. A.A, & Frye C.A. (2009) Estradiol reduces anxiety- and depression-like behavior of aged female mice, Physiology & Behavior. doi:10.1016/j.physbeh.2009.09.017

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