Estradiol and the Brain

NewsGuard 100/100 Score

Estradiol is the most potent and most abundant estrogen in females and is the principal growth hormone required for their reproductive development. Estradiol supports the growth of the vagina, the fallopian tubes, the endometrium, and the cervical glands. This hormone is also required to maintain oocytes, which are the eggs that reside in the ovaries, and triggers a series of events that lead to ovulation.

In males, a small amount of estradiol is produced in the testes. Here, estradiol plays a role in facilitating the maturation of sperm, as well as maintaining a healthy libido. Estradiol is one of two active metabolites of the male hormone testosterone. The other active metabolite of testosterone is dihydrotestosterone.

Image Credit: gritsalak karalak /

Estradiol and the brain

The developing brain expresses high levels of estradiol receptors, which are nuclear transcription factors. These receptors regulate gene expression and act at the membrane level to stimulate signaling pathways.

Estradiol is therefore required for many other biological functions in addition to its role in female reproductive processes. In fact, this versatile hormone regulates sexual differentiation of the brain and provides protective effects for the bones, brain, and cardiovascular system.

In the nervous system, estradiol plays an important role in a wide range of neurological functions. To this end, estradiol is involved in fine motor control, learning, memory, sensitivity to pain, motor coordination, and protecting the brain against stroke damage and Alzheimer’s disease.

Image Credit: Double Brain /


Estrogens affect the serotonergic, dopaminergic, noradrenergic, and cholinergic systems, all of which play a role in mood. Research has shown that estrogen is also involved in depressive illness, as it appears to have antidepressant effects in humans and influences the responses of animals to antidepressant medication.

Cognitive function

Verbal memory, spatial ability, and fine motor skills are all influenced by estrogens. Estrogens are also involved in the strategies used to solve spatial or navigational puzzles which, as a result of their differences in estrogen levels, differ between males and females.


Open trials of estrogen therapy in women have demonstrated a prospective benefit of the therapy on cognitive function in women without dementia. Among elderly women who take postmenopausal estrogen replacement therapy, there is a lower incidence of death caused by Alzheimer’s disease as compared to those who do not take ERT.

Understanding Estrogen and its Effect on Cognition


Murine studies have shown that different pain pathways are used in males and females. In women, these pain pathways appear to be regulated by gonadal steroids and, in particular, estrogen.


In experimental models of stroke, estrogens play an important role in protecting against the damage caused by ischemia.

Estradiol and menopause

In the central nervous system (CNS), estrogen has been shown to increase cerebral blood flow, provide anti-inflammatory effects, promote neuronal synapse activity, and exert both neuroprotective and neurotrophic effects on tissues in the brain.

The brain relies solely on blood flow as a source of energy to function; in fact, blood vessels make up around one-third of the brain. Estrogen is known to increase cerebral perfusion by binding to endothelial receptors and stimulating nitric oxide release, which leads to vasodilation.

At the neuronal synapse, estrogen increases the levels of the neurotransmitters serotonin, dopamine, and norepinephrine, as well as the number of receptors that are available for these chemicals. Estrogen has been shown to confer neuroprotective effects against oxidative stress, ischemic damage, and the damage caused by amyloid protein, which is involved in the pathogenesis of Alzheimer’s disease. This hormone also promotes the growth and repair of neurons and stimulates the production of nerve growth factors.

Through these various mechanisms, estrogen has a large influence on emotions, mood, and cognitive function, all of which may be affected during menopause, which is when estrogen levels start to decline. Symptoms that may arise during menopause include mood changes, memory problems, and hot flashes. The prevalence of Alzheimer’s disease, which is more prevalent in women than men, has also been associated with a deficiency in estrogen.

Physicians should be aware of these associations when advising female patients about some of the symptoms they may experience during mid-life. To this end, it may be beneficial for healthcare providers to educate women of this age group about the potential benefits of estrogen replacement therapy. Such benefits may include an overall improved sense of well-being, improved cognitive function, and a reduced risk of Alzheimer’s disease.


Further Reading

Last Updated: Dec 22, 2022

Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Robertson, Sally. (2022, December 22). Estradiol and the Brain. News-Medical. Retrieved on May 29, 2024 from

  • MLA

    Robertson, Sally. "Estradiol and the Brain". News-Medical. 29 May 2024. <>.

  • Chicago

    Robertson, Sally. "Estradiol and the Brain". News-Medical. (accessed May 29, 2024).

  • Harvard

    Robertson, Sally. 2022. Estradiol and the Brain. News-Medical, viewed 29 May 2024,


  1. Nicola Willson Nicola Willson New Zealand says:

    Does it matter how you receive the oestrogen supplement?  i.e. transdermal patch or oral?  My daughter has PMDD and ADHD and we are following the studies by the late Professor John Studd.  She is on 200mcg patches which we are hoping will stop ovulation and stabilise mood but she is worried about ho much trogon actually makes it to the brain to help her ADHD stimulants to work better.  There is definitely a relationship between the two issues; it's just trying to figure out the optimal treatment.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Mouse study finds PFAS exposure in fathers disrupts offspring's gene expression