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
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.
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.
That image you linked shows a testosterone level 9X higher than the upper limit. I'm assuming that's unrelated to the values in your post because there is no way that 200mg/week produces those numbers.
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.
Same here. My cis-male body and brain really does strongly prefer high E2 levels. Just below “growing breast tissue” seems to be the sweet spot. Testosterone / DHT levels matter much less.
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.
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.
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
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.
E2 as a libido regulator is a cross-species conserved effect.
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]:
> "Both estradiol (E) and dihydrotestosterone (DHT) contribute to the activation of mating, although E is more important for copulation and DHT, for genital reflexes."
> "We show here that a single injection of estradiol (500 μg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone behaviorally ineffective by itself."
The underlying theme is that across animal species, estrogens are regulators of sexual desire/libido while androgens support the necessary biological functions (erection) required.
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.
It will depend exactly which anti androgen is used. I think you're describing the effects of cyproterone. Spironolactone has other side effects (a lot of them), while triptoreline targets the production of LH and FSH directly and seems to have fewer effects on other systems (though honestly it's a bit hard to tell)
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
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.
> 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)
Hard to find more protein per dollar than $2/lb of canned chicken with an equal or even similar Protein Digestibility-Corrected Amino Acid Score (PDCAAS).
Yeah, this was the first thing that came to mind, how does this compare to the Truffle WASM implementation. The Graal Polyglot API is pretty incredible, we've been using it for a JavaScript/Python plugin system in a JVM app, and it's been amazing.
Agree about Graal being really good. there are some different use cases for embedding wasm in an application. chicory / endive is not just for embedding another language. the main use case was always secure plugin-systems. but there are other use cases. also it's not controlled by Oracle and works well outside of their ecosystem, which i think some people value. this question came up a few times and were addressed in talks and blog articles:
I think "They wanted an engineer to build a chatbox that called ChatGPT with company documents as prompt context" fits the term "AI Engineer", personally - see https://www.latent.space/p/ai-engineer which uses it for "applied"
AI.
You don't call someone who integrates the Twilio API a "Twilio Engineer", or Mailchimp a "Mailchimp engineer"
Integrating third-party libraries to build an application is a significant chunk of the work in any SaaS product and the expectation is you can read the vendor docs and figure it out
I think the difference here is that it's possible to know bowering there is to know about the Twilio API. Read the docs, build a few things and you can consider yourself to have mastered that entirely.
Nobody on earth can tell you that they've "mastered" the art of building software on top of LLMs.
They're weird. They don't behave like other APIs. They're non-deterministic and unpredictable and not even the people who created them fully understand what they can and cannot do.
(For one thing, if someone claims to have mastered LLMs ask them how they would 100% protect against prompt injection attacks...)
Why would a self-described "AI Engineer" be any more capable of building that sort of functionality over any other backend engineer, especially one who is familiar with agent-assisted development?
Because building on top of LLMs is really tricky. You need to understand things like writing evals, configuring agentic loops, creating and iterating on system prompts, designing tools that work well with LLMs.
It's a speciality, just like being a payments engineer who integrates with systems like Stripe is a speciality.
Being familiar with agent-assisted development helps a little bit because at least you understand prompts, but there's a whole lot more to building software on top of LLMs than that.
Any engineer can get familiar with these things of course, just like any engineer can figure out what it takes to work on payment systems.
> It's a speciality, just like being a payments engineer who integrates with systems like Stripe is a speciality.
At $PREV_JOB, we had physical Point-of-Sales systems as well as a mobile app, and provided multi-merchant marketplace functionality with things like disbursement reports and support for multiple bank accounts for vendors.
I had to migrate all of this from Braintree to Stripe. It probably encompasses the most complex payment system I've worked on in my career.
But that's not a job title, it's just part of "make the app work"
This is such a sad story most of the way through, but it's amazing you were able to eventually get to the bottom.
I also got diagnosed with OSA (AHI 32) after crashing my car falling asleep at the wheel in stop-and-go traffic. It tooks years of progressively feeling worse to get there, though.
I had not considered the allergies angle, it might be worth adding some portable filters inside of my apartment...
So, the general architecture described here is solid, and I support it, but I take issue with the "Lakebase" naming thing.
Disaggregated storage and disaggregated compute have been an open trend in DBMS development for the last half-decade. This is an obvious move with modern computing paradigms, and the academic literature has a standard name for it.
This feels like "JAMStack" from Netlify happening all over again.
I tweeted about this in 2022, as a general trend, and also from the RocksDB meetup emphasizing disaggregated storage:
I don't think it should be surprising that vendors are not going to lead with "disaggregated storage". I don't see that taking off either. This isn't a paper in a journal. Aurora doesn't call it that either. But yes, it is not a new idea.
Lakebase is referring to the fact that in addition to disaggregated storage s3 is authoritative storage for older data.
Since data is on s3 (or lake) you can perform direct to s3 type operations like data loading, reading this data by engines that are not Postgres and more
> in addition to disaggregated storage s3 is authoritative storage for older data
Suppose a person retrives cold data from another Object Storage protocol rather than S3. This is no longer a "Lakebase", so we have to come up with a different name to avoid confusion.
But if you say "Disaggregated Storage on S3" then you have the flexibility to change that to "Disaggregated Storage on FOOBAR" to avoid confusion.
> Suppose a person retrives cold data from another Object Storage protocol rather than S3. This is no longer a "Lakebase", so we have to come up with a different name to avoid confusion.
I've never seen "lake" or adjacent terminology refer to S3 specifically like that vs other object storage. A data lake on Ceph would still be a data lake.
(My quibble would be that "lake" often refers to inconsistent or unstructured, and itself has always been a bit handwavy compared to "warehouse," whereas this is very structured data on object storage.)
Maybe I’m wrong, but AFAICT this is block (page) storage backed by S3, tuned for Postgres with some paxos-linked storage/caching servers sitting in front? Sounds good, but I’m not sure “lake” or “warehouse” is a word I’d choose… much closer to Litestream-with-reads, or the somewhat-famous “I ran out of RAM so I downloaded some more” blog article.
Yes! I was just about to comment the same thing. I sank so many hours into that Dragon Ball Z game. Was called Dragon Ball Z Tournament. And its background music was an instrumental version of Sisqo's Thong Song. Wild.
The difference with Woozle is that people don't have an (vague, but still existing) idea of what consciousness is, or direct lived experience of it, that they can tap into for recognizing it in others.
>What makes you so sure any of us have an idea of what it means to be conscious?
I know we have an idea. It might not be right or accurate, but we very well have an idea.
>Human cognition also provides the experiencer the illusion of free will.
And I'm fine with it, as I also consider it an open question. We could very well have free will, the mechanistic view of the universe is too 18th century.
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
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