In our last blog post on 7-15-21, we discussed the effects of high estrogen levels in males after injectable testosterone therapy. One of the commonly accepted beliefs is elevated estrogen causes an increased risk of stroke in males.*  However, if you research the validity of this statement, you will find quite the opposite.

In fact, a paper in 2014 supported the use of estrogen as a therapy for stroke! Estrogen Replacement Therapy for Stroke, Cell Med 2014.** The article presented an animal model to identify potential therapeutic effects of estrogen for stroke and stroke prevention using an animal model.  This concept pushed me to focus on researching……

Benefits of Estrogen in the Brain!

Estrogen and Stroke: A Review of the Current Literature

A 2009 paper, Estrogen and Stroke: A Review of the Current Literature looked at estrogen and/or estrogen hormone replacement therapy in relationship to stroke.

‘Fifty-seven articles met the criteria for inclusion in the review:

  • 19 articles supported the use of estrogen and/or an estrogen-related compound in the prevention or treatment of stroke,
  • 6 articles claim estrogen and/or estrogen-related compounds are risk factors for stroke
  • 11 articles remain inconclusive with regard to an estrogen and stroke relationship****

Estrogens, Neuroinflammation and Neurodegeneration

While researching high estrogen and stroke, an excellent 2016 review article entitled Estrogens, Neuroinflammation and Neurodegeneration, was brought to my attention. This article delineated specific critical actions estrogens play in the microglia of the brain.***

Estrogens support Microglia Function 

Microglia are Neuroprotective Immune Cells in the Brain.  Microglia play a large role in maintaining nerve conductivity and health of the Central Nervous System (CNS) in the brain.

‘Microglia are responsible for:

  • Synthesizing and releasing inflammatory molecules such as inflammatory cytokines when needed to fight exposure to pathogens or brain damage.
  • Signaling the brain and anti-inflammatory immune cells in the brain to help decrease inflammation.
  • Clearing debris in brain tissue such as damaged neurons and infections. Our ability to clear ‘brain debris’ decreases with age contributing to dementia and other neurodegenerative processes.
  • Providing nutrients to repair damage when inflammation occurs.’

“Failure of microglia to work properly can lead to chronic pain, epilepsy, neurodegeneration disorders, and psychiatric disorders”. ***

Estrogens are Hugely Neuroprotective for the Brain

All nerve cells, including microglia, are capable of expressing estrogen receptors.  Therefore, estrogens play a major role in controlling microglia activity and hence are hugely neuroprotective for the brain.***

“Estrogens appear to play a role in the neurodegenerative processes, conditioning the incidence of these pathological processes as well as the course of their progression”.

Lack of estrogens are, “part of a multifactorial effect on cellular neurodegeneration. The impairment of estrogenic signaling in combination with a lack of other elements relevant for neuronal health may facilitate the initiation of the neurodegenerative process as shown by the studies on the correlation between ER signaling and ApoE4.” (305)** ApoE4 is the most prevalent genetic risk factor of Alzheimer’s.

Therefore, bioidentical estrogen hormone replacement for deficient natural hormones in the brain may be able to help stave off neurodegenerative disorders from occurring.

Could bioidentical hormones be targeted for the brain as a treatment for neurodegenerative disorders?

‘In the near future, efforts should be mainly aimed at a better understanding of the physiology of estrogen actions in the microglia of males and females.  This knowledge is vital for the design of appropriate hormone replacement therapies that can overcome the lack of the natural hormone in targeted areas such as the brain’**


In conclusion, there is a large body of experimental evidence indicating microglia are positively influenced by neuroprotective actions of estrogen, and repleted estrogens may aid in the recovery from strokes and brain injury.

Estrogen is still not seen as playing a primary role in preventing neurodegeneration cell programming but is definitely seen as part of a conglomerate of elements that can help prevent neurodegeneration and help recovery of injured brain tissue.

Estrogen is important for brain functioning in both men and women.  A big reason for men on testosterone therapy to NOT take estrogen blockers unless estrogen blockers are needed for other reasons.

*  Estrogen Replacement Therapy for Stroke ** Estrogens, Neuroinflammation, and Neurodegeneration 305. Neurobiol Aging. 2008;29(12):1783–1794. Brown CM, Choi E, Xu Q, Vitek MP, Colton CA. The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol. ****  Estrogen and Stroke: A Review of the Current Literature * Estradiol and risk of stroke in elderly men 2007

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