I'm a bit confused about exactly what's novel here. Here's an article from at least a year earlier talking about memory decline after menopause being linked to lower estrogen: https://health.clevelandclinic.org/memory-loss-in-middle-age...

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...