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How Estradiol Affects Brain Development and Cognition

Written by Puya Yazdi, MD | Last updated:
Jonathan Ritter
Matt Carland
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience) | Written by Puya Yazdi, MD | Last updated:

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Estradiol is the main female sex hormone (estrogen). However, it is important for men as well as for women and is believed to play a variety of roles in reproductive health, brain development, cognitive functioning, bone health, thyroid function, and body weight.

Estradiol levels also decline naturally with age – especially during menopause in women – and some research suggests that this age-related decline may impact certain types of cognitive function. Read on to learn more about this hormone, its roles in the body and brain, and what the current science says about its potential role in age-related cognitive decline!

What is Estradiol?

Estradiol (E2) is the most active estrogen in the body. It is produced mainly in the ovaries; however, the brain, fat cells, immune system cells, and bones can also produce estradiol. It is produced from the sex hormones testosterone, androstenedione, and progesterone [1].

Estradiol helps protect the brain. It also plays a role in the creation of connections between nerve cells in the brain (synaptogenesis) and may inhibit or promote this process depending on where in the brain it is taking place. It also influences the development of nerve cells in the brain by controlling gene expression and calcium release [2, 3].

According to some research, estradiol may also influence certain cognitive functions, including memory, reasoning, and attention. Due to these early findings, some researchers have suggested that estradiol may be one of the main factors responsible for some of the cognitive and psychological differences between the sexes, such as differences in the stress response, anxiety, and even some cognitive functions [3, 4].

Another important function of estradiol is influencing the levels and overall activity of the major neurotransmitter dopamine. Some researchers believe that by stimulating the release of dopamine, estradiol may enhance motivation – especially in the context of sexual behavior [5].

Estradiol levels generally decrease as a person ages. For women especially, estradiol levels decrease sharply during menopause. Some researchers believe that this decrease may contribute to some of the common declines in memory and learning that often occur during aging [3].

Additionally, some research suggests that having relatively lower estradiol levels may be associated with greater vulnerability to stress, as well as an impaired stress response in general [6].

Estradiol Levels May Affect Cognition

There are many notable differences in brain function and psychology between males and females. While men tend to outperform women on spatial tasks, women tend to perform better on tasks related to short-term memory and verbal abilities – including speech development, spelling, and grammar. Some researchers have suggested that these cognitive differences may be attributable to the differences in estrogen levels between women and men [3].

Estradiol Levels May Affect Memory

According to one study of 31 men and 39 women, women with relatively higher salivary estradiol levels were reported to perform better on memory tasks compared to both women with relatively lower estradiol levels, as well as men in general [7].

Relatedly, according to a review of data from four other studies, post-menopausal women were reported to perform worse on verbal memory and fluency tasks compared to pre-menopausal women, who also had higher estradiol levels [8].

Verbal Memory

According to one study in 29 postmenopausal women, treatment with estradiol was reported to lead to slight improvements in verbal memory, specifically [9].

Short-term Memory

In one trial of 14 women, three days of estrogen injections were reported to bring about improvements in short-term memory [10].

Another study looked at 343 women who participated in studies where they had short-term estrogen therapy administered in the early phase of menopause. The hormone therapy group had a 64% decreased risk of later cognitive impairment, including memory deficits [11].

Additionally, according to a number of animal studies in rats and mice, estradiol (most often 17-ß-estradiol) has been associated with enhanced brain function, such as increased object-recognition and working memory abilities [12, 3, 13].

Takeaway

These studies provide suggestive clues that may point the way towards more extensive research on the potential links between estradiol and certain aspects of brain development and cognitive function.

Furthermore, if these early preliminary findings are verified by more research, they could lead the way towards someday using hormone therapies (such as estradiol injections) to prevent or counteract some of the effects of age-related cognitive decline.

However, even if these kinds of treatments were someday medically approved, there might still be some important limitations to consider. For example, a women’s responsiveness to estrogen therapy may decrease with age and time after menopause. In other words, after a certain age, estradiol may stop having protective effects on cognition [12].

Further Reading

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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