I've spent a significant amount of my free time for the last 15 years studying androgen physiology and self-experimentation.

Here are a few facts about estradiol that others might find surprising:

1. E2 acts as a master metabolic/energy regulator in humans. ER-alpha and pan-ER agonists are being developed for obesity and metabolic disorders. Example: SLU-PP-332

2. Libido in males is regulated by E2. Androgens like testosterone/DHT seem to be required to support the biology of erectile function, but for mental libido estrogen is the primary component.

3. Estradiol is synergistically anabolic with androgens. This is why cattle hormone implants contain a blend of Trenbolone and E2

Estrogen has so many supporting functions in brain, muscle, adipose tissue, and bone health...

Apologies for no citations and rough formatting but currently on a phone. Happy to provide citations when home

The part that makes no sense for me is men ending with smaller rates of dementia, given they had much less estrogen to begin with. Men have less incidence of dementia. Men also have much lager incidence of baldness. Did somebody already study if baldness and dementia are inversely correlated? I don't know, perhaps sunlight exposure in the scalp have neuroprotective effects?

Given the prevalence of baldness, and the downside of the condition for sexual attractiveness of its bearers, I suspect we will still discover some strong unexpected upside to explain why this trait was selected for regardless.

Women live much longer and more comfortable lives. Men are more likely to die before alzheimer can even manifest.

This is why sometimes you enter a room and forget why you came in.

This can explain the phenomenon referred to in the op. A woman enters a room devoid of estrogen and her memory breaks.

The article keeps bouncing between talking about estrogen loss generally, and the extracellular matrix (ECM), and doesn't connect the two until about halfway through the article where it says estrogen loss was studied in the ECM... but then it goes back to talking about stuff unrelated to the ECM.

I thought "production" might be the key word here, but that's barely mentioned in the article either.

Looking at the actual study: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.70551 the variables were: sex, age, stopping estrogen production in just the brain or the whole body. AFAIU:

1. Memory and social issues: old, female, either stoppage

2. Depression: either age, female, either stoppage

3. ECM changes: either age, either sex, reduced brain estrogen (whole body not tested?)

The article says:

> In mice, ... in females [estrogen] is produced predominantly in the brain.

But the paper says:

> In rodents, aromatase is expressed almost exclusively in the brain and gonads (Bulun et al. 2005; Zhao et al. 2009). Old female mice are thus heavily reliant on estrogen synthesis in the brain after the cessation of estrous cycles (equivalent to menopause in women).

IIUC in humans it's not produced in the brain, so the idea was to replicate that in mice artificially and see what affect it has on brain function. And... it led to decline in memory function in mice.

So I guess we're back to my first question, which is how was this commonly known if this is a new study drawing that link.

TLDR though I think the conclusion isn't that we've established a link, but that we've confirmed there's some other female-male difference that allows estrogen to have this effect.

Edit: no, I'm still confused. The paper concludes:

> Furthermore, brain-specific estrogen deficiency, achieved through targeted deletion of aromatase, led to alterations in hippocampal ECM that correlated with behavioral changes and memory impairment

This is wrong, right? Alterations to ECM happened in males and females, but the behavioral changes and memory impairment were in women only...

btw guys, stop drinking beer. Makes you so so fat and give you tits. The more you know.