Maguire G Justin, July 2022. 


Inflammation is arguably the biggest contributing factor toward cellular ageing, yet most are unaware of how to negate excessive inflammatory outcomes within their bodies. Glycans are chain-like structures that are composed of single sugar molecules linked together by chemical bonds1, which are also associated with the early signs of age-related diseases. Estrogen has the ability to reduce glycans2, an ability in which estrogen’s roles in modulating neurotransmitters and hormones may be contributing to its anti-ageing effect. This article serves to provide insight into the important role estrogen plays in influencing behaviour, focusing on the diverse impacts that different estrogen types and respective receptors have upon physiology. Additionally, further resources are explained how one may improve the functionality of estrogen by supporting hepatic and gastrointestinal health.
 
Properties of Estrogen 
 
The physiological properties and reactions of estrogen fall into a wide category of effects, some of which we will discuss in greater detail later in the article. To gain an appreciation of the importance of estrogen, it is necessary to look at the huge range of its effects on the human body, which are highlighted below.

In women, estrogen:

  • creates the endometrium
  • regulates the menstrual cycle
  • reduces vaginal dryness

In both men and women, estrogen:

  • Slows bone loss
  • Anti-ageing 
  • Uplifts mood
  • Lowers LDL
  • Increases HDL
  • Reduces Lipoprotein (a) and homocysteine
  • Positive effect on neurotransmitters
  • Supports memory and motivation 
  • Supports puberty development
  • Reduces incidence of heart attack
  • Increases progesterone receptor sensitivity
  • Increases sexual desire

Signs and symptoms of low estrogen

As a man, I never used to think that estrogen deficiency was something I needed to consider yet it is important to know that a deficiency of estrogen influences both men and women, in particular as regards cardiovascular and psychological health. A few common symptoms of low estrogen are as follows :

  • hot flashes/night sweats (in both men and women!!!)
  • sleep disturbance
  • anxiety
  • depression 
  • memory loss/lapses
  • emotional instability
  • brain fog
  • vaginal dryness
  • low libido (in both men and women!!!!)
  • headaches (one of the biggest neglected contributing factors to migraines!)
  • weight gain 
  • heart palpitations
  • hair loss
  • painful intercourse 
  • elevated blood pressure
  • dry skin/wrinkles
  • joint pain 

Types of estrogen and estrogen receptors 

There are three types of estrogen in human physiology:

  • estradiol 
  • estrone; and
  • estriol 

Additionally, there are two types of estrogen receptors (ER) in the human body:

  • ER beta; and
  • ER alpha 

At particular stages of a woman’s life, specific types of estrogen predominate, specifically::

  • estriol during times of pregnancy 
  • estradiol in pre-menopausal women; and 
  • estrone in post-menopausal women

The activity of the different estrogen receptors produces a wide variety of effects on physiology and neuroendocrine activity. Increased activity of ER alpha has been shown to induce carcinogenic cell growth in breast tissue3 therefore to avoid oncogenesis it is paramount to modulate levels of estrogens likely to activate ER alpha.

Each estrogen exhibits a unique affinity for specific ER receptors, namely:

  • estradiol binds to both ER alpha and beta
  • estrone binds predominantly to ER alpha; and
  • estriol binds predominantly to ER beta.

When considering bio-identical hormone therapy in those who have a history or family history of cancer, it is, therefore, safer to opt for estriol given its lack of affinity for ER alpha receptors.

Estrogen’s influence on neurochemistry and neurological health

Estradiol has been shown to reduce neuroinflammation and to protect the cortex, striatum and hippocampus of the brain4.
Given that:

  1. the cortex is responsible for perception and awareness
  2. the striatum is responsible for maintaining motivation and the reward link associated with neuroplasticity and
  3. the hippocampus is largely responsible for memory recall

It is clear that estrogen plays a pivotal role in sustaining and preserving the optimal functionality of the brain.  

ER alpha also serves an important purpose in promoting the output of gamma amino butyric acid (GABA), dopamine, neuropeptide Y, glutamate, neurotensin and even somatostatin5. Potential for neuronal excitation is therefore closely linked to the activity of ER alpha and the respective availability of estrogens associated with that receptor. 

Every action has a reaction, a cause and an effect: and in any situation where we excite the nervous system, some level of inflammation will ensue. ER beta then steps in to modulate any potential excessive ER alpha activity by promoting the inhibitory neurotransmitters oxytocin and serotonin6, which put the brakes on to reduce neuroinflammation and stop the brain from burning itself up.

Both ER alpha and beta are essential in modulating NMDA receptors7 which facilitates glutamate’s role within the hippocampus to improve memory recall. Where excessive glutamate activity causes neuroinflammation and the associated depletion of antioxidants, GABA acts as an antagonist to excessive glutamate activity, thereby neutralizing the likelihood of neurodegeneration. ER beta activity modulates the activity of GABAb receptors8, and this balanced activity of ER alpha and beta receptors serves to facilitate improved cognitive function in addition whilst negating the potential of excitotoxicity. 

Estrogen metabolites through hydroxyl pathway

Depending on the health and activity of the liver, estrogen can be metabolized into either beneficial or detrimental metabolites. Sulfation and glucuronidation form vital conjugation pathways of hormonal metabolism and when the function of these pathways becomes compromised DNA damage can result. 

There are three hydroxylated estrogen metabolites:

  • 4-OH-E1: most toxic estrogen metabolite which may instigate DNA damage/mutation (Often estrone is metabolized through this pathway) 
  • 2-OH-E1: aids in DNA repair, anti-inflammatory properties and modulates glycan activity. 
  • 16-OH-E1: Increases protein binding, may render other hormones ineffective and reduce receptor activation throughout endocrine complexes.

In order to support the liver’s ability to optimally metabolise estrogen the following nutrients are essential:

Phase one liver detoxification nutrients (Modification)

  • B-complex
  • Vitamin A, C, E, D3
  • Folinic acid
  • Milk thistle
  • Citrus bioflavonoids
  • Antioxidants
  • Thiols (garlic/onions)
  • Copper, Selenium, Zinc and Manganese

Phase two liver detoxification nutrients (conjugation)

  • Calcium  d-glucarate
  • Amino acids
  • Cruciferous vegetables 
  • MSM
  • N-acetyl-Cysteine 

High estrogen does not mean estrogen efficiency, on the contrary, high estrogen levels may be associated with unwanted xenoestrogens – foreign chemicals with a similar structure to estrogen –  being present within the body, Xenoestrogens disrupt natural feedback mechanisms, which instruct regulatory outcomes of optimal and healthy hormone production. Essentially, therefore you can have a situation of high total estrogen yet still exhibit symptoms of estrogen deficiency. It is therefore very important to support the detoxification of harmful estrogens.

Some possible causes of high  estrogen are as follows:

  • obesity
  • Type 2 diabetes
  • peri-menopause
  • liver disease
  • high-fat diet
  • estrogen replacement (not moderated correctly!!!)
  • ovarian tumours
  • high beef consumption (if not organic or grass-fed)
  • medication 

Assessing the state of your estrogen health takes more than simply looking into blood tests. Although blood chemistry analysis is useful to determine total hormone levels,  hormone metabolism and activity are best understood through the utilization of a dried hormone urine analysis. Both blood chemistry and dried hormone analysis are therefore required to capture the full picture of estrogen activity and concentration in the body.

For those living in the UK I would suggest the following two tests through Omnos 

https://app.omnos.me/all-tests/blood/bloods-sex-hormone-female

https://app.omnos.me/all-tests/blood/bloods-sex-hormore-male

https://app.omnos.me/all-tests/hormones/hormones
Use this code to receive a 5% discount on the tests once you check out:  AUTONOMIC

For those looking for nutrient support to aid the liver I recommend the following:

Integrative therapeutics Lipotropic formula/complex 

  1. Protocol’s Protoclear
  2. Designs for health’s LV&GB complex

along with one of the following:

  1. Integrative therapeutic’s blue heron
  2. Metagenics Metafiber
  3. Allergy Research Group Gastrocleanse 

For those looking to help eliminate high xenoestrogens and restore optimal health estrogen production I recommend one of the following:

  1. Designs for health: Fem guard and balance
  2. Vitamia: Fem Balance
  3. Vital Nutrients: Hormone balance 

For more information as to how you can restore your mental and physical health through rectifying hormonal imbalances, reach out to info@autonomiccoaching.com or visit www.autonomiccoaching.com

References 

  1. GlyTech Inc., 2018. What are glycans. Available at: https://www.glytech-inc.com/glycan/what-are-glycans/ (sourced 20 July 2022) 
  2. Jurić, J., Kohrt M, W., Kifer, D., Pezer, M.,  Nigrovic A, P.,  Lauc, G. June 2020. Effects of estradiol on biological age measured using the glycan age index. Available at: https://www.medrxiv.org/content/10.1101/2020.06.25.20138503v1.full (accessed 20 July 2022)
  3. Liu, Y., Ma, H. and Yao, J. March 2020. ERalpha, a key target for cancer therapy: A review. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073439/#:~:text=Estrogen%20receptor%20%CE%B1%20(ER%CE%B1)%20is,as%20well%20as%20cancer%20inhibition. (sourced 20 July 2022)
  4. Bryant D, N. and Dorsa D, M. Aug 2010. Roles of estrogen receptors alpha and beta in sexually dimorphic neuroprotection against glutamate toxicity. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949441/ (accessed 20 July 2022) 
  5. Kelly M, J., and Ronnekleiv O, K. Mar 2009. Control of CNS neuronal excitability by estrogens via membrane initiated signalling. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701913/ (sourced 20 July 2022)
  6. Walf A, A., Frye A, C. Jun 2006. A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behaviour. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624621/ (sourced 20 July 2022) 
  7. Tang, B., Ji, Y., Traub R, J. Feb 2008. Estrogen alters spinal NMDA receptor activity via PKA signalling pathway in a visceral pain model in the rat. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2543943/ (sourced 20 July 2022) 
  8. Saleh M, T. and Connel B, J. Jun 2003. Estrogen-induced autonomic effects are mediated by NMDA and GABA(a) receptors in the parabrachial nucleus. Available at: https://www.researchgate.net/publication/10768012_Estrogen-induced_autonomic_effects_are_mediated_by_NMDA_and_GABAA_receptors_in_the_parabrachial_nucleus (sourced 20 July 2022) 
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