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
> 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.
The damage the Women’s Health Initiative did to women’s health by conducting the flawed research that got HRT black boxes 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.
> 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.
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.
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.
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.
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.
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...
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
> 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.
The damage the Women’s Health Initiative did to women’s health by conducting the flawed research that got HRT black boxes 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.
> 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.
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...
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".
Eh, are you citing sone peer-reviewed research or are you making stuff up?
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.
Eh, have you seen any research on this or are you quoting own experience?
I'm a bit confused about the claims 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...