Estrogen Effects on Serotonergic and Dopaminergic Neurotransmission (Estrogen in the Brain)

I'm just throwing this together now, figured it would be helpful.

This is a summary of how estrogen, including that derived from or converted from testosterone, by means of aromatase, affects central 5-HT (Serotonin) and dopaminergic neurotransmission.

In the references you will find specific brain region alterations induced by estrogen, and how this may correlate to brain function.
This is all relevant if you want to achieve optimal brain health - including intellectual capacity and general cognition.(!)

• Estrogen downregulates somatodendritic 5-HT1A (!) autoreceptors (presynaptic) in the raphe nuclei, leading to enhanced serotonin release in these areas, however, it also increased cortical post-synaptic 5-HT1A receptors - which can induce cortisol and prolactin release and blunt sexual functions(!). (However, estrogen decreases hypothalamic 5-HT1A receptors(!)

• Estrogen also downregulated 5-HT1A in the limbic areas(!).
• Estrogen also downregulates 5-HT1A receptors in the amygdala, hippocampus, perirhinal cortex, and motor cortex (!) , but when combined with progesterone, the 5-HT1A receptors in the hippocampus increased, with no change in other areas.
• Estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine2A (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior(!) (!). This can lead to excitation, anxiety, and potentiation of hallucinogenic drugs.
• Estrogen increases SERT (serotonin reuptake transporter) (!) - leading to enhanced reuptake and less serotonin activity in the synapse - this means that although estrogen may increase serotonin through the above autoreceptor modulation , it ends up not mattering too much in the face of less usability. Thus , high estrogen levels rapidly deplete serotonin from the synapse, leading to reduced efficiency and activity of serotonin. Low estrogen levels would create higher serotonin in the synapse, but less receptors , mainly of the excitory types to bind to. One could presume, that both high and low estrogen would reduce positive effects of SSRI-antidepressants, and increase negative side-effects.
• Estrogen competitively inhibits serotonin 5-HT3 receptor activity.(!)(!)
• Estrogen stimulates the expression of serotonin 5-HT4 (causing excitation and prolactin release), 5-HT5A (can disrupt sleep patterns), and 5-HT6 receptor mRNA (causing cognitive disruptions).(!)
• Estrogen increases dopamine D(2) receptors in the striatum(!).

Thus, estrogen is largely ANTI-COGNITIVE, ANTI-INTELLECTUAL, and does not really provide much benefit at all in terms of these two areas of neurotransmission ......

However, a small amount of estrogen may be necessary to maintain dopamine receptor expression in men and women.
Varying amounts of estrogen per gender, of course....

The greek and roman warriors of old certainly didn't have estrogen dominance - and they were master strategists and intellectuals ---- though I s'pose some of them could be dumb on occasion!

Therefore in terms of serotonergic activity, low estrogen would equate to the following changes.
The fields marked in blue are positive effects of low estrogen, while red is negative, generally.
Purple is neutral, or determined more so by the person.

• More serotonin in the synapse, due to less SERT (transporters), and thus , lessened reuptake of serotonin.
• Increased 5-HT1A receptors in many brain regions, including the hypothalamus, leading to decreased central nitrergic and dopaminergic activity as well as serotonergic neuron activity.
• Decreased serotonin 5-HT2A receptor expression. (leading to less cortisol and prolactin, generally good thing)
• Decreased 5-HT4, 5-HT6, 5-HT5A receptors, especially in pituitary.
• Decreased dopamine D2 in the striatum.
• Increased 5-HT3 receptor binding and activity. (can cause nausea, excitation,pain)
• Decreased serotonin production from tryptophan.
• MORE MONOAMINE OXIDASE (MAO-A)

THUS ALL ROUND LESS SEROTONIN PRODUCTION AND ACTIVITY WITH LOW ESTROGEN HOWEVER.......IN THE PRESENCE OF NORMALIZING TRYPTOPHAN HYDROXYLASE ACTIVITY  - SEROTONIN MAY BE EASIER CHRONICALLY ENHANCED BY LOW ESTROGEN , EXCEPT THAT THE MAIN RECEPTORS SEROTONIN WOULD THEORETICALLY BIND TO WHEN ONE HAS LOW ESTROGEN WOULD BE.


LOW ESTROGEN WOULD MEAN THESE RECEPTORS BELOW WOULD BE MORE AVAILABLE WHILE ALL OTHERS ARE DECREASED.

• 5-HT1A
• 5-HT1B
• 5-HT1D
• 5-HT3
• 5-HT7

THUS, LOW  ESTROGEN RESULTS IN DECREASED.

• 5-HT2A/2C
• 5-HT4
• 5-HT5A
• 5-HT6

Thus, low estrogen by means of all above may have very broad effects, there may be an increase in some forms of intellectual capacity, but a central reduction in glutamatergic tone and a generally lethargic state - which is more pronounced in women ....however, in men, DHT and other androgens can modulate thinking and cognitive function - however, low estrogen in men, may in some, still lead to depression or the need for caffeine and other stimulants............


IN MY EXPERIENCE, BOTH HIGH AND LOW ESTROGEN CHANGES THE TYPE OF FOOD I LIKE.


When estrogen is on the lower side , nearly undetectable, as with when I was on a cut or aromatase inhibitor, I eat more salty and spicy foods, but when estrogen became high in my large experiments with prohormones, I seemed to cling to carbohydrate type foods and sugary foods!

I do find it easier to eat cleaner with lower estrogen, and also alcohol is not desirable not one bit when estrogen is on the lower side, however, my need for caffeine and stimulants increases at times when estro goes into the undetectable or near undetectable range.

( how does estrogen affect men's brains human )