Estradiol treatment after menopause may protect against effects of stress on memory

Alexandra Ycaza Herrera, Ph.D., a post-doctoral scholar in the Emotion & Cognition Lab, recently published a study on the effects of post-menopausal hormone replacement on cortisol response to stress and the subsequent effects of stress on memory. The study was published Nov. 2 in The Journal of Clinical Endocrinology and Metabolism.

"Stress hinders recall

The researchers found that women taking estrogen-only therapy had lower levels of the stress hormone cortisol and performed better on tests of “working memory” following exposure to stress compared to women taking a placebo.

Working memory allows the brain to keep information immediately available for processing, such as when a shopper uses a mental grocery list to pick up items or when a student keeps specific numbers in mind as a teacher reads a word problem aloud in math class. Studies have documented that stress can impair working memory.

To measure the effect of estrogen therapy on working memory under stress, Ycaza Herrera recruited 42 women with an average age of 66 from the USC Early versus Late Intervention Trial with Estradiol led by Howard Hodis, a professor at the Keck School of Medicine of USC and a co-author of the study.

Half of the postmenopausal women had been on estradiol, a type of estrogen therapy, for approximately five years, while the others had received a placebo.

Each participant visited USC twice. To induce a stress response during one visit, researchers asked participants to submerge their hand in ice water for about three minutes. For the control condition conducted during the other visit, the participants submerged their hand in warm water.

Before and after each visit, the researchers collected saliva to measure the women’s levels of cortisol, estrogen, and progesterone. The researchers also ran a test of working memory called a “sentence span task,” in which the women were each given a series and then asked whether each sentence made sense. They also were asked to recall the last word of each one.

Not right for every woman

All women performed equally well on the sentence span task after the warm water condition. But after the ice bath, women taking the placebo experienced a spike in cortisol levels. They also demonstrated a decrease in working memory function.

By contrast, women receiving estrogen therapy had a smaller increase in cortisol and showed no decrease in working memory function.

“Hormone replacement therapy may not be right for every woman, but women need to be able to have the conversation with their doctors,” Ycaza Herrera said.

The study was also co-authored by Wendy Mack, a Keck School professor of preventive medicine, and Mara Mather, a USC Leonard Davis School professor of gerontology.

The study, along with the larger ELITE trial and other studies investigating stress-hormone relationships, was 100-percent funded by a combined $2 million in grant funds from the National Institute on Aging (grant numbers R01AG-024154, R01AG-038043 and R21AG-048463)."

USC News link:

What can we learn about aging from the resting brain?

What is resting state fMRI (rsfMRI)?

It is a method of functional neuroimaging where a researcher records brain activity while a participant lies down in an MRI scanner and simply rest without engaging in any specific task.  You may think that the brain is not very active at rest. But in fact, the brain is still active and we can learn a lot from the resting brain. rsfMRI is a powerful tool to study brain function.

Why is rsfMRI so valuable?

While you are at rest, a set of brain regions fluctuates spontaneously and coherently at low frequencies – this is known as a ‘resting state network.’ Researchers describe co-activation of a set of brain regions as ‘functional connectivity’ since these regions may not be anatomically connected but functionally connected. Importantly, resting state networks closely match brain networks activated while you are engaged in a task. For example, the right fronto-parietal network fluctuates together at rest as well as when you are engaged in a cognitive task (e.g., n-back task). Thus, resting state and task-related networks go hand in hand.

How do resting-state networks change as we get older?

Previous research suggested that some resting state networks decline with age (i.e., functional connectivity gets weaker with age). This may not be surprising given that cognitive function typically declines as we get older.  But do all resting state networks decline with age, such as those associated with visual, motor and emotion functions? The answer to this question remains unclear. Particularly, little is known about how aging affects emotion networks. 

Our investigation

We examined which types of resting state networks may change with age and how it relates to performance (Nashiro et al., 2017). We were particularly interested in how aging might differently affect cognition vs. emotion networks given previous behavioral research suggesting age-related decline in cognitive domains (Park, 2000; Salthouse, 2010) but preserved emotional processing in aging (Mather, 2016).

Our findings

• Age-related decline was observed in cognitive, motor and visual networks but not in emotion networks (see A below).

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• Greater within-network connectivity was associated with better cognitive performance (see B below).

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• Relative to younger adults, older adults showed increased functional connectivity in regions outside networks (C), which was associated with poorer cognitive performance (D).

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What did we learn about aging from the resting brain? Our results suggest that all types of resting networks decline with age except for the emotion networks identified in our study. Age-related preserved emotional function may be able to facilitate older adults’ cognitive performance. For example, previous research suggests that mindfulness training, which focuses on improving emotional well-being, can also enhance executive function (Tang et al., 2012).



Mather, M. (2016). The Affective Neuroscience of Aging. Annual Review of Psychology, 67(1), 213–238.

Nashiro, K., Sakaki, M., Braskie, M. N., & Mather, M. (2017). Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing. Neurobiology of Aging, 54, 152–162.

Park, D. C. (2000). Cognitive Aging: A Primer. Taylor & Francis.

Salthouse, T. A. (2010). Selective review of cognitive aging. Journal of the International Neuropsychological Society, 16(5), 754–760.

Tang, Y.-Y., Yang, L., Leve, L. D., & Harold, G. T. (2012). Improving Executive Function and its Neurobiological Mechanisms through a Mindfulness-Based Intervention: Advances within the Field of Developmental Neuroscience. Child Development Perspectives, 6(4), 361–366.