4 ms·

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

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

ranger207 4mo 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
- zparky 4mo 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
  - ranger207 4mo ago
    well, here's hoping lol
    - zparky 4mo ago
      if this is about you, good luck :) starting prog helps a lot!
- nostrademons 4mo 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.
  - gavinray 4mo ago
    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. [0] https://www.nejm.org/doi/full/10.1056/NEJMoa1206168 https://www.nejm.org/doi/full/10.1056/NEJMoa1206168 [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC1952538/ https://pmc.ncbi.nlm.nih.gov/articles/PMC1952538/ [2] https://www.sciencedirect.com/science/article/abs/pii/S0166432805003372 https://www.sciencedirect.com/science/article/abs/pii/S01664...
- gavinray 4mo 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.
  - shiandow 4mo ago
    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)
toisanji 4mo ago
Any remedies to reverse this?
Aurornis 4mo 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.
- gavinray 4mo 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 https://i.imgur.com/b3MjwDh.png
cmurf 4mo 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.
- gavinray 4mo 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/ 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 4mo ago
What should be done to keep it on the right level forever ?
- gavinray 4mo ago
  There's no magic secret beyond eating well and being physically active

ranger207 4mo 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

zparky 4mo 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
- ranger207 4mo ago
  well, here's hoping lol
  - zparky 4mo ago
    if this is about you, good luck :) starting prog helps a lot!
nostrademons 4mo 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.
- gavinray 4mo ago
  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. [0] https://www.nejm.org/doi/full/10.1056/NEJMoa1206168 https://www.nejm.org/doi/full/10.1056/NEJMoa1206168 [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC1952538/ https://pmc.ncbi.nlm.nih.gov/articles/PMC1952538/ [2] https://www.sciencedirect.com/science/article/abs/pii/S0166432805003372 https://www.sciencedirect.com/science/article/abs/pii/S01664...
gavinray 4mo 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.
- shiandow 4mo ago
  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)

toisanji 4mo ago

Any remedies to reverse this?

Aurornis 4mo 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.

gavinray 4mo 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 https://i.imgur.com/b3MjwDh.png

cmurf 4mo 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.

gavinray 4mo 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/ 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 4mo ago

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

gavinray 4mo ago
There's no magic secret beyond eating well and being physically active