Memory decline after menopause linked to loss of estrogen production in brain

https://news.northwestern.edu/stories/2026/05/memory-decline-after-menopause-linked-to-loss-of-estrogen-production-in-brain-tissue

by gmays • 2 months ago

161 69 2 months ago

news.northwestern.edu

thridmddi9e93• 2 months ago

Nearly two-thirds of Americans with Alzheimer’s disease (AD) are women, but the reasons why women are more vulnerable are still not fully understood.

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

jona-f• 2 months ago

Well, I went out to disprove your thesis, thinking we can easily look at countries where men live longer than women in another country.

For example, women in the US have a lower life expectancy than men in Australia (go figure). Now women are less than 1.4 times more likely than men to get dementia in australia, but about 2 times more likely to get alzheimer in the US. So that kind of points in your direction, but that is of course wildly inaccurate, cause one is mentioning dementia the other only alzheimer and whatnot.

https://www.worldometers.info/demographics/life-expectancy/ https://www.aihw.gov.au/reports/dementia/dementia-in-aus/con... https://www.alz.org/getmedia/ef8f48f9-ad36-48ea-87f9-b740346...

Edit: qwen and glm seem to also agree with parent. "Age is the dominant risk factor".

phoronixrly3• 2 months ago

Eh, are you citing sone peer-reviewed research or are you making stuff up?

throw8394jrjr2• 2 months ago

It is just a bro science, sorry. Correlation and simple statistics is not real scientific method, and does not fit into modern research!

mirabilis4• 2 months ago

US life expectancy in 2024 for women was 81.4 years; for men, 76.5 [1]; “non-early” symptoms of Alzheimer's typically begin after 65 [2]. I don’t think that the life expectancy average offset of ~5 years is the main factor here.

1. https://www.cdc.gov/nchs/products/databriefs/db548.htm 2. https://www.mayoclinic.org/diseases-conditions/alzheimers-di...

throw8394jrjr2• 2 months ago

It also said "comfortable lives".

Also compare retirement ages, years worked, income (hard mental work)... it is well known that alzhaimer is corellated with brain activity (like solving suduku puzzles). Watching tv all day is not very healthy for brain...

bee_rider• 2 months ago

No idea what the main factor is. But, it could be a contribution, right? If the life expectancy is ~10 more years after 65 for men, and ~15 for women, then the offset of 5 years seems… somewhat significant?

analog83742• 2 months ago

Memory is environment-associated. Which is to say, these memories that you have are connected to the environment that you find yourself in. Change your environment and your memory, to a degree proportional to the environment change, breaks.

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.

phoronixrly3• 2 months ago

Eh, have you seen any research on this or are you quoting own experience?

stevenhuang• 2 months ago

All of the claims above wrt memory reads quite mundane and adequately non assertive, but I'm a layperson.

I do believe it's well established that memory is associative. It's why roses are associated with love, because of Valentine's Day. If you see roses or smell roses, you will recall memories of your loved ones maybe, especially if you have given them roses.

Whether the decline in estrogen content of a room can be the dominant mechanism for momentary memory loss is a separate claim and more dubious sounding to me though (estrogen behaving like a pheromone??), but it's not like I have looked into this deeply so idk.

derektank• 2 months ago

The damage the Women’s Health Initiative did to women’s health by conducting the flawed research that got HRT black boxed for twenty years really cannot be overstated. We went from a quarter of women being on estrogen replacement therapy post-menopause at the turn of the millennium to ~5% in 2020. A real case study in institutional failure.

bethekidyouwant2• 2 months ago

The institution of science?

leoqa• 2 months ago

If I remember correctly they linked it to breast cancer, causing all research and prescribing to basically disappear over night. It took 20 years before the study was revisited and the link dismissed.

sandworm101• 2 months ago

At the time, there was also real concern about what that estrogen was doing to other people too, people around women who were on supplements. I used to be a competitive swimmer. There was a real debate in the 90s/2000s about how much of that estrogen was ending up in pool water. The question was whether it was healthy for children, boys and girls, to be literately swimming in a not-insignificant amount of supplemental estrogen. Testosterone patches were also an issue in pools, but they were much less common. With the change in treatment the debate is now largely moot.

The exposure for lap swimmers was significant. A competitive kid would regularly spend 10+ hours a week in that water (at my peak it was closer to 20+) not to mention the amount of water swallowed and inhaled as vapor/droplets.

There is a line in a Doctor Who episode (Torchwood?) where a character comments that he could recognize 20th century earth because he could taste estrogen in the rain. In real life, it was detected in rainwater.

jhoechtl• 2 months ago

Is there any line between your statement, women's contraceptive pill and an ongoing decline in human intelligence?

Qem4• 2 months ago

Nearly two-thirds of Americans with Alzheimer’s disease (AD) are women, but the reasons why women are more vulnerable are still not fully understood. Scientists have long theorized that the loss of estrogen after menopause may reduce the brain’s natural protection against memory loss and neurodegeneration.

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.

zulux• 2 months ago

Men have significant estrogen:

Men: roughly 10–40 pg/mL Women (not at ovulation): roughly 30–40 pg/mL

At Ovulation, women spike. Hence, libido changes. If you know, you know.

Qem4• 2 months ago

Think you. I didn't know there was such overlap in the levels between both genders. Do men's levels also take a hit with age?

Supernaut3• 2 months ago

baldness, and the downside of the condition for sexual attractiveness of its bearers

Just a guess, and I highly doubt there are any reliable statistics on this, but perhaps balding men are less likely to be tempted to abandon their family unit, thereby making it more likely that their children will thrive and carry on their genes?

I base this theory on my own experience, which is that I went completely bald in my early thirties and haven't had a second look from a woman ever since. Even if I were the sort to want to cheat on my wife, there wouldn't be any takers![0]

[0] I'm not claiming that bald men are necessarily sexually unattractive. I just know that it didn't work for me, looks-wise.

XorNot• 2 months ago

This seems like an odd conclusion to draw. I'm married with a full head of hair and I couldn't tell you whether or not any woman has ever been interested because I'm not paying attention nor am I trying to draw it.

ericskiff• 2 months ago

Just chiming in for anyone else reading this and worried about their hair thinning, this is a thing men worry about much more than women. Bruce Willis, Patrick Stewart, Michael Jordan, Vin Diesel - there have been plenty of bald sex symbols and plenty of women who enjoy that look (and the look of many average men of various builds and ages)

The factors of attractiveness are by far more related to basic self care (hygine and being fit enough to care for yourself and others), kindness and the ability to share in others' joy, and passionate interest in something, and a lightness or humor in your manner.

I started balding at 18, shaved it all at 22. Its not an issue. Height, hair, etc might get immediate reaction and attention, but hardly matter for real connections.

clickety_clack• 2 months ago

I think you’d want to reconsider the assumption that there is a big downside to baldness for sexual attractiveness.

Qem4• 2 months ago

Just anedoctal evidence, but I have a group of older coworkers, most in late 40s-early 50s, all divorced, and by their reports on their attempts at getting back at dating, success pretty much track how much hair is left. That made me a bit upset, as I'm slowly getting bald myself.

octoberfranklin• 2 months ago

This fails to control for the fact that women, on average, live to older ages before dying.

Qem4• 2 months ago

IIRC in other studies where it's controlled for age, a difference still remains.

yieldcrv2• 2 months ago

I suspect we will still discover some strong unexpected upside to explain why this trait was selected for regardless.

Its not selected for, it merely isn’t selected against

anything that occurs after reproduction starts isn't given the opportunity to be weeded out of the population

in this case, genes are passed into new humans overwhelmingly by men in their teens and twenties and thirties (with some stark outliers)

zahlman• 2 months ago

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.

My understanding was that they have lower incidence specifically of Alzheimer's, but greater incidence of other forms of dementia.

ASalazarMX• 2 months ago

sunlight exposure in the scalp have neuroprotective effects?

Two days late to participate, but thank you for putting this strange idea in my mind.

rendaw• 2 months ago

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...

gavinray7• 2 months ago

Estrogen (specifically Estradiol, E2) is one of the most important systemic hormones in both men and women

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

ranger2072• 2 months ago

Re #2, in the mtf trans experience high estrogen and low testosterone are correlated with low libido, with some individuals even temporarily stopping antiandrogen medications in order to get some back

nostrademons• 2 months ago

Yeah, your comment squares with (and the GP's point #2 contradicts) what I learned in my college Science & Gender class, which was a combined neuroscience/psychology offering where we read a bunch of papers. Most of them supported that testosterone was the primary driver of libido in both men and women, with higher T levels corresponding to higher sexual desire and lower T levels corresponding to the opposite.

gavinray7• 2 months ago

Unfortunately, anti-androgens have myriad effects beyond basic T suppression.

There are two primary drivers behind why anti-androgens would cause loss of libido beyond effect on T:

1) AA's cause androgen receptor blockade systemically. This blocks action at the AR that would be residual across systems from adrenal production. Most important for libido are the AR activity that occurs inside of neurons and astrocytes in the brain

2) AA's have a two-punch effects on the Prolactin/Dopamine system + Progesterone system. Chronically elevated prolactin causes down-regulation of dopamine, which by itself is enough to kill libido. Progestins modulate GABA, which can cause "flat affect" and "emotional flatlining".

The combo punch of neuronal/adrenal AR blockade + Prolactin/Dopamine dysregulation + GABA dysregulation would require a miracle to have preserved libido on.

zparky2• 2 months ago

libido is fixed with progesterone (which is commonly taken ~1-2 years into hrt) for better breast growth. anecdotally it makes you completely f*king feral

toisanji• 2 months ago

Any remedies to reverse this?

Aurornis2• 2 months ago

Estrogen becomes a real problem for people experimenting with anabolic steroids or even taking some of the TRT regimens which go past replacement doses and into performance enhancing territory.

Testosterone is converted into estradiol by aromatase, so people who boost their testosterone up to high levels get more estradiol as a result.

As an aside: Aromatase is present in body fat, so higher body fat will produce more sites for testosterone to convert to estradiol. This is one reason why higher body fat is correlated with lower testosterone. It’s also one reason why the decline of testosterone levels are correlated with the rise of obesity and you shouldn’t trust anyone who rants about declining testosterone levels without acknowledging that major correlation.

Back on topic: The increased estradiol production from excess testosterone can go above the normal range in men, which can cause a wide range of mental and physical problems. It can even promote growth of breast tissue that when left unchecked needs to be surgically removed later. Surgeons who deal with gynecomastia are seeing booming business right now due to all of the men going to TRT clinics and getting blasted with crazy doses of testosterone.

There are medications which reduce aromatase activity but they are very hard to get right. It’s a common story for men to suffer from excess estradiol after manipulating their testosterone, so they assume they can fix it with an aromatase inhibitor. They take slightly too much (which is very easy due to the dosing and duration of action) and crash their estradiol levels too low. Between the sudden swing in levels and the low level they can find themselves feeling a different kind of terrible. Someone I know become suicidal after taking an aromatase inhibitor at the ‘normal’ recommending broscience dosage. It took weeks to clear due to the dynamics of how everything returns to equilibrium. Very scary time.

Estradiol is highly active in the brain including regulation of key functions like MAO (the enzyme inhibited by MAOI antidepressants). One of many reasons why out-of-range levels or sudden fluctuations can make people feel bad in various ways.

gavinray7• 2 months ago

This is anecdata, but as someone who has used exogenous testosterone for the past 10 years, I feel significantly better with low T + high E2 than high T + low E2.

I've had E2 levels as high as the low end of female ovulatory range (see attached image at bottom) and felt fantastic, though personal response varies.

I stopped using aromatase inhibitors after the first few years due to having a worse sense of wellbeing compared to using none at all.

Now, I typically let my E2 sit around 60-90pg/mL (roughly x2-3 upper end of male reference range), which is where lands on 200mg/wk Testosterone, when doing TRT.

https://i.imgur.com/b3MjwDh.png

swat535• 2 months ago

Anything that increases Testosterone will increase E2 , you don't even need TRT!

For example I'm on HCG treatment due to Secondary Hypogonadism causing low Testosterone levels.

My urologist prescribed on a _moderate_ of HCG instead of TRT. I have to do regular blood checks every 3 months just to make sure all is in order.

The treatment was successful, as in my Testosterone and Free Testosterone returned to normal and all my side effects disappeared. My sperm count also doubled which was great.

However, even with a _moderate_ dose, it caused a spike in my Estradiol! Luckily, not enough that would require medication to counter that.

It's been 3+ years now. My recommendation to all men is to get checked, but don't self inject yourself with Testosterone without professional medical oversight.

cmurf• 2 months ago

We need a synthetic or phytoestrogen that provides some (or all) of the benefits of natural estrogen, without at all stimulating Er/Pr receptive cancer.

gavinray7• 2 months ago

This exists! Estetrol (E4) is a very strange estrogen that acts as an ERR antagonist in breast tissue but normally in most other receptors.

https://pmc.ncbi.nlm.nih.gov/articles/PMC8658652/

  > Recent studies indicate that E4 is an estrogen with a distinctive profile of ERα activation. E4 activates the nuclear ERα, but it is an antagonist of the membrane ERα, in contrast to other estrogens [14,15,16]. Based on its pharmacological profile, E4 can be classified as the first Natural Estrogen with Selective Action in Tissues (NEST) [17]. NEST activities of E4 are the consequence of its unique dual role.

  > On breast tumor tissue it acts as an estrogen antagonist in the presence of E2 [21,22]. The estrogen-antagonistic effect of E4 in the breast has been further supported by a recent pre-clinical study that has been performed in women with breast cancer, finding that E4 reduces breast cancer cells proliferation [21,23,24,25,26]. These features could suggest a future role of E4 as a selective estrogen receptor modulator (SERM), but with less adverse effect than tamoxifen (hot flushes, nausea, hypertension, thromboembolic events, endometrial hyperplasia)

polskibus• 2 months ago

What should be done to keep it on the right level forever ?

gavinray7• 2 months ago

There's no magic secret beyond eating well and being physically active

Scroll_Swe2• 2 months ago

So they should drink more beer then?

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

grvdrm2• 2 months ago

And for me - total stomach mess too.

Scroll_Swe2• 2 months ago

For sure, beer is a great cure for constipation in that it causes liquid stools.

systemBuilder• 2 months ago

Strangely, estrogen bathes the male brain in the womb to remove connections and make it masculine. To think of it as "the female hormone" is to misunderstand physiology.

Memory decline after menopause linked to loss of estrogen production in brain

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