Estrogen and Motivation

[cyanide_sunshine]

I've been battling significant fatigue that I could describe as a burning sensation near the brainstem. Serendipitously, I was able to decrease this sensation by 80% using small doses of letrozole despite previously physiological estrogen levels.

Unfortunately, this also induced an incredible depletion of motivation. For those familiar, it is eerily similar to SSRI-induced apathy. I am unable to do housework, read texts or even turn the remote on the television. Dopamine agonists and D-AMP allow me to focus on tasks but the incorrect ones. Like this, this is incorrect.

Letrozole is known to deplete DHEA and E2 peripherally. Estrogen, in general, is supposed to have MAOI activity. In the brain, however:

To determine the effect of in vivo treatment of guinea pigs with a non-steroidal aromatase inhibitor (CGS 20267; letrozole), we treated subjects with subcutaneous Silastic implants containing crystalline letrozole. We studied four treatment groups: intact, intact letrozole-treated, castrate and castrate letrozole-treated. After treatment for 1 week, brain tissues (preoptic area, septum, medial basal hypothalamus, amygdala and parietal cortex) were removed, and microsomal aromatase activity (AA) was determined by an in vitro 3H2O assay using 1beta-3H-androstenedione as substrate. Kinetic experiments were performed to determine the competitive nature of letrozole and an approximate Ki was calculated. Letrozole appears to be a reversible, competitive inhibitor of aromatase activity with an apparent Ki of 1.2 nM. Aromatase activity in intact letrozole-treated animals was elevated compared to untreated controls in all brain areas tested (P< 0.05). Letrozole also stimulated AA in the brains of letrozole-treated castrated guinea pigs compared to untreated castrated animals (P< 0.05). These data indicate that letrozole administered in vivo causes an increase in AA. Possible mechanisms include an autoregulatory mechanism which is interrupted by enzyme inhibition, or an effect of the inhibitor on turnover rates of P450 aromatase.

PMID: 8903425

I do not know which receptors to hit to increase motivation, essentially. Even if you can't help me, I hope you find this marginally interesting.

 

[sekio]

I am not a fan of these sort of "my brain is broken, I take compound X, everything is fixed!!!!!" threads.

I also think playing with endogenous steriod systems is just asking for trouble. Do remember that this study was in guinea pigs.

I do not know which receptors to hit to increase motivation, essentially.

There are lots of neurotransmitters that influence attention and motivation. However, there is no central "motivation receptor", nor does any one of those receptors work alone. Sure, some compounds like amphetamines will appear to increase motivation and attention in individuals, but they are by no means a panacea, and most of them lose efficacy after long-term treatment.

If you have problems with attention, focus, and fatigue, and diet/excercise/lifestyle modification do nothing, see a doctor.

 

[cyanide_sunshine]

I am not a fan of these sort of "my brain is broken, I take compound X, everything is fixed!!!!!" threads.

Understandable.

I also think playing with endogenous steriod systems is just asking for trouble. Do remember that this study was in guinea pigs.

This is four months post administration.

There are lots of neurotransmitters that influence attention and motivation. However, there is no central "motivation receptor", nor does any one of those receptors work alone. Sure, some compounds like amphetamines will appear to increase motivation and attention in individuals, but they are by no means a panacea, and most of them lose efficacy after long-term treatment.

Yes.

 

[sekio]

For reference, what kind of dosing regimen did you take up?