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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
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.
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
Given that those levels are crazy high, you should probably mention that your experience is in the context of a lot of extreme hormone manipulation. Who knows what your body's baseline even is any more. I wouldn't expect your experiences to extend to normal people. I also really, really would not recommend that any men try to keep their E2 at 3X the upper end of the reference range.
Raising E2 a bit basically cured lifelong suicidal ideation and major depressive disorder for me overnight. And it’s been working for 6 years now.
Libido is still fine - my girlfriends are satisfied unless i’m having a very stressful week.
The landmark study in humans for this is the Finkelstein 2013 paper [0] -- they gave humans Testosterone with and without AI to block aromatization to E2. In the AI group, sexual desire and erectile function declined markedly across the board, even when they were given high doses of testosterone.
Then you have studies like [1] and [2]:
The underlying theme is that across animal species, estrogens are regulators of sexual desire/libido while androgens support the necessary biological functions (erection) required.[0] https://www.nejm.org/doi/full/10.1056/NEJMoa1206168
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC1952538/
[2] https://www.sciencedirect.com/science/article/abs/pii/S01664...
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.
There is a line in a Doctor Who episode (Torchwood?) where a character comments that he can taste estrogen in the rain. In real life it was being detected in rainwater.
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.
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.
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.
Good grooming, a good sense of humor, and most importantly, generally being a good person, are what really matter.
My understanding was that they have lower incidence specifically of Alzheimer's, but greater incidence of other forms of dementia.
nobody wants to see a guy in denial clinging onto something, lean in fully
and yes it is unfortunate that different people are attracted to the bald variant than the ones you already know, but you gotta show resolve and confidence
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.
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)
Women live much longer and more comfortable lives. Men are more likely to die before alzheimer can even manifest.
1. https://www.cdc.gov/nchs/products/databriefs/db548.htm 2. https://www.mayoclinic.org/diseases-conditions/alzheimers-di...
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...
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".
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...
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.
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.
btw guys, stop drinking beer. Makes you so so fat and give you tits. The more you know.