DHT, not T, likely the "active" androgen in heart and brain

[haidut]

Interesting study, done on baboons (so should have good relevance for humans), demonstrating that the cardiovascular system (CVS) exclusively accumulates and recognizes (at the receptor level) DHT, instead of testosterone (T). In fact, the androgen receptor in CVS is so structurally different it apparently cannot even bind T. Recent studies with ALS patients suggest the same may be true in humans, not only in the CVS but in the nervous system as well. Namely, ALS patients tend to have high (circulating) T but lower DHT levels, especially in their brains. The hypothesis for a unique role of DHT in tissues is further corroborated by animal ALS studies demonstrating that administration of DHT is therapeutic, while multiple studies with T have produced null or negative effects. Aside from suggesting once again that DHT, instead of T, is the true tissue-active androgen in humans (and most animals) it also suggests that administration of 5-AR drugs such as finasteride / dutasteride may play a direct causative role in CVD and lethal neurodegenerative conditions such as ALS. Such ALS link has already been established for statins, and considering statins' decimating effects on DHT levels, the risks from finasteride / dutasteride use are likely to be much higher.

Error - Cookies Turned Off

"...This study, along with our previous studies (McGill et al., 1980; McGill and Sheridan, 1981; Sheridan et al., 19811, allows us to compare the in vivo nuclear uptake and retention of 3H-androgen in the cardiovascular system after the injection of 3H-testosterone or 3HDHT. This comparison, along with our biochemical data and the data published in the literature, has led us to two main conclusions to be discussed in detail below. First, we interpret the aggregate data to indicate that the main androgen acting on the cardiovascular system of the baboon is circulating DHT. Second, we believe that the androgen receptor in the baboon cardiovascular system is a physically different androgen receptor from that found in the kidney of a number of species and from the androgen receptor found in certain areas of the developing rat brain."

"...In summary, after comparing the uptake and retention and metabolism of 3H-steroid in the cardiovascular system of baboons following the injection of 3H-testosterone in the present study and 3H-DHT in previous studies (McGill et al., 1980; McGill and Sheridan, 1981; Sheridan et al., 1981), we interpret the data to suggest that the physiological important androgen for the cardiovascular system is circulating DHT, not testosterone, even though there is approximately ten times more circulating testosterone than DHT. In addition, in comparing our autoradiographic data, indicative of in vivo nuclear uptake and retention of 3H-androgens, with the published biochemical data dealing with the in vitro binding characteristics of cytosolic receptor, we interpret the discrepancy between in vivo nuclear uptake and retention of unmetabolized testosterone in the kidney and lack of in vivo nuclear uptake and retention of unmetabolized testosterone (DHT is accumulated) in the myocardium to be indicative of separate receptors for testosterone and DHT."

 

[Gûs80]

View: https://youtu.be/ictH1rSOg5w


Dr Rand prescribes aromatase inhibitors with TRT, one of the few doctors I see on the internet who speaks openly of the dangers of high e2. I tried trt twice myself and got terrible results because they left the e2 high. Dr Rand has seen over 10,000 patients and in his experience men feel better with e2 between 15 and 20pg.

His trt regimen is 200mg testosterone per week (IM) + 1mg anastrozole or 25mg exemestane EOD.

For me he is the example of the serenity that Ray Peat talks about that occurs when we have high dht and low E2. I've watched dozens of Dr Rand's videos and his responses on blogs, the guy is a gentleman.

@hidut from your research, what are the optimal DHT levels for men?

 

[cupofcoffee]

View: https://youtu.be/ictH1rSOg5w


Dr Rand prescribes aromatase inhibitors with TRT, one of the few doctors I see on the internet who speaks openly of the dangers of high e2. I tried trt twice myself and got terrible results because they left the e2 high. Dr Rand has seen over 10,000 patients and in his experience men feel better with e2 between 15 and 20pg.

His trt regimen is 200mg testosterone per week (IM) + 1mg anastrozole or 25mg exemestane EOD.

For me he is the example of the serenity that Ray Peat talks about that occurs when we have high dht and low E2. I've watched dozens of Dr Rand's videos and his responses on blogs, the guy is a gentleman.

@hidut from your research, what are the optimal DHT levels for men?

what is his reasoning for using 200 mg of testosterone? It's more than 2 times the amount produced by normal men + one has to take into consideration that esterified testosterone doesn't follow the circadian cycles so even people who use normal doses (like 100 mg) have way higher androgenic activity than regular folks (does to constantly elevated T levels). My point is are we sure he isn't harming his health in the long term?

 

[Gûs80]

what is his reasoning for using 200 mg of testosterone? It's more than 2 times the amount produced by normal men + one has to take into consideration that esterified testosterone doesn't follow the circadian cycles so even people who use normal doses (like 100 mg) have way higher androgenic activity than regular folks (does to constantly elevated T levels). My point is are we sure he isn't harming his health in the long term?

Maybe you are correct. I really don't have enough knowledge to answer your question.

What I wanted to emphasize was just his claims about ideal levels of e2 in men and the serenity of someone with a high dht/e2 ratio. Many men like me abandon TRT precisely because doctors let the e2 float.

Regarding the doses, maybe there is a difference in the metabolization, so that higher doses than those produced endogenously may be necessary.

I believe that D Rand used similar doses of T a few decades ago, as in the 1980s he was Arnold's stunt double in some movies. He also looks pretty good for a man in his late 60s.

 

[Dave_Fit]

what is his reasoning for using 200 mg of testosterone? It's more than 2 times the amount produced by normal men + one has to take into consideration that esterified testosterone doesn't follow the circadian cycles so even people who use normal doses (like 100 mg) have way higher androgenic activity than regular folks (does to constantly elevated T levels). My point is are we sure he isn't harming his health in the long term?

Agree, constantly elevated androgens are likely not good long term for kidneys and heart, and 200 mg week if used for replacement would be more than double normal for all but possibly a few very rare exceptions, I'm sure a lot of guys may like the effect they get from 200 mg week, but it definitely should not be sold as some longevity dosage. Also at that level a decent amount would convert to e2 so at least Dr. Rand is attempting to control for that. You can put nitrous on virtually any car and it will definitely produce a lot more power. While this extra power can be very fun and may even last for a good while, the engine definitely won't last longer. Having said that. If a guy had low T and symptoms, It would probably be a good idea to look into ways to elevate T naturally, get rid of PUFA, increase SF intake, increase carbs, make sure your fat soluble vitamins are up to snuff, natural sources of sodium, calcium, selenium, boron, copper, zinc, as well as b-vitamins. If this fails, likely a lower dose at true replacement level would make more sense. I'm sure @haidut could get most guys a natural protocol that would get their numbers up into respectable territory.

 

[cupofcoffee]

Maybe you are correct. I really don't have enough knowledge to answer your question.

What I wanted to emphasize was just his claims about ideal levels of e2 in men and the serenity of someone with a high dht/e2 ratio. Many men like me abandon TRT precisely because doctors let the e2 float.

Regarding the doses, maybe there is a difference in the metabolization, so that higher doses than those produced endogenously may be necessary.

I believe that D Rand used similar doses of T a few decades ago, as in the 1980s he was Arnold's stunt double in some movies. He also looks pretty good for a man in his late 60s.

good points

 

[cupofcoffee]

Agree, constantly elevated androgens are likely not good long term for kidneys and heart, and 200 mg week if used for replacement would be more than double normal for all but possibly a few very rare exceptions, I'm sure a lot of guys may like the effect they get from 200 mg week, but it definitely should not be sold as some longevity dosage. Also at that level a decent amount would convert to e2 so at least Dr. Rand is attempting to control for that. You can put nitrous on virtually any car and it will definitely produce a lot more power. While this extra power can be very fun and may even last for a good while, the engine definitely won't last longer. Having said that. If a guy had low T and symptoms, It would probably be a good idea to look into ways to elevate T naturally, get rid of PUFA, increase SF intake, increase carbs, make sure your fat soluble vitamins are up to snuff, natural sources of sodium, calcium, selenium, boron, copper, zinc, as well as b-vitamins. If this fails, likely a lower dose at true replacement level would make more sense. I'm sure @haidut could get most guys a natural protocol that would get their numbers up into respectable territory.

Yeah, focusing on natural T production should always definitely be the first step!

 

[Gûs80]

Another interesting claim of his is that "roid rage" is caused by the lack of aromatase inhibition and the consequent increase in estrogen. As Peat always says: there is a clear link between high levels of estrogen and consequently high levels of serotonin which correspond to increased aggression.
Despite the high doses of testosterone, this doctor is ahead of his peers.

This week I read about studies in monkeys that showed that e2 increased serotonin by inhibiting MAO-a and causing aggression. DHT, on the other hand, increases MAO-a and reduces serotonin and aggression.

He says in one of his interviews that only a few men he's seen needed a little more than e2, between 20 and 30pg. Even this number is very low by what most trt doctors advocate.

I got to have 150pg on trt and the doctor said it was normal, while I almost went crazy with such anxiety.

 

[Dave_Fit]

Yeah him saying that shows he is ahead of the pack for sure. Roid rage in bodybuilders who are typically doing 500-1000mg a week of various aromatizable steroids is definitely caused by a huge amount or conversion to estrogen > then increased serotonin activity. Unfortunately most bro’s don’t know this, some do, but most haven’t a clue. This same issue could easily rear its head with 200mg of T a week in a lot of men, so controlling e2 is a good idea. Still don’t think this is a path to longevity but it could be a path to a temporary improved quality of life, maybe even for a good number of years. Roulette if you ask me. There is definitely aggression activity caused by strong so called non aromatizing androgens as well, so there’s that.

 

[Gûs80]

Agree, constantly elevated androgens are likely not good long term for kidneys and heart, and 200 mg week if used for replacement would be more than double normal for all but possibly a few very rare exceptions, I'm sure a lot of guys may like the effect they get from 200 mg week, but it definitely should not be sold as some longevity dosage. Also at that level a decent amount would convert to e2 so at least Dr. Rand is attempting to control for that. You can put nitrous on virtually any car and it will definitely produce a lot more power. While this extra power can be very fun and may even last for a good while, the engine definitely won't last longer. Having said that. If a guy had low T and symptoms, It would probably be a good idea to look into ways to elevate T naturally, get rid of PUFA, increase SF intake, increase carbs, make sure your fat soluble vitamins are up to snuff, natural sources of sodium, calcium, selenium, boron, copper, zinc, as well as b-vitamins. If this fails, likely a lower dose at true replacement level would make more sense. I'm sure @haidut could get most guys a natural protocol that would get their numbers up into respectable territory.

I always thought like you, but lately I've been reviewing some points for not being able to improve my quality of life through natural means, diet and supplements considered safer.
I've tested several protocols over the past 13 years. I've had chronic insomnia since I was 15. I'm 41 and at 28 I got burnout and found out I had sleep apnea. Since then my life has been turned upside down. I spent 7 years testing alternative protocols, cpap, vitamins, diets and only got worse.
Until 5 years ago I decided to test trt and I can consider that things got even worse. During this period I entered and left TRT a few times, for having unbearable anxiety attacks. I developed lipomastia, it aromatized a lot, even with small doses like the approved use of Nebido. I tested different doses, from 50mg/week to 250mg/week. In none of those doses did I feel good. In all of them I gained weight. I only gained muscle mass by hiring a bodybuilding coach, who tested Stano. I think if I had used an aromatase inhibitor in that period it would have been amazing.
I am a great admirer of Dr Ray Peat and follow many of his concepts. Unfortunately, I came to the conclusion that the dietary guidelines, supplements, and medications he recommends didn't work as well as I expected, maybe because I've been sick for many years. I imagine if I had discovered it 10 years ago it would have had great results.

For the past few days I've been thinking about Dr Rand mcClain's protocol from another, somewhat Peatarian point of view: since he uses Aromatase Inhibitors and higher doses than we consider safe, it doesn't just greatly decrease the e2, but it also greatly increases the conversion of T to DHT. I guess maybe that's why he reports that only above these doses does his patients feel really good.

Maybe the result is as good as using Testosterone + Masteron (or Stano, DHT, etc).

 

[cupofcoffee]

Another interesting claim of his is that "roid rage" is caused by the lack of aromatase inhibition and the consequent increase in estrogen. As Peat always says: there is a clear link between high levels of estrogen and consequently high levels of serotonin which correspond to increased aggression.
Despite the high doses of testosterone, this doctor is ahead of his peers.

This week I read about studies in monkeys that showed that e2 increased serotonin by inhibiting MAO-a and causing aggression. DHT, on the other hand, increases MAO-a and reduces serotonin and aggression.

He says in one of his interviews that only a few men he's seen needed a little more than e2, between 20 and 30pg. Even this number is very low by what most trt doctors advocate.

I got to have 150pg on trt and the doctor said it was normal, while I almost went crazy with such anxiety.

If i recall correctly there Is a gene called the "Warrior gene" that reduces MAO-a activity and it's associated with aggression!

note that MAO also breaks down dopamine and noradrenaline so It could multifactorial, even if serotonin Is the main culprit

 

[Gûs80]

If i recall correctly there Is a gene called the "Warrior gene" that reduces MAO-a activity and it's associated with aggression!

note that MAO also breaks down dopamine and noradrenaline so It could multifactorial, even if serotonin Is the main culprit

Exactly, reading Dr Ben Lynch's book "Dirty Genes" recently, he cites two common alterations that increase or decrease the activity of MAO-a and COMT.

He demonstrates that people with Slow MAO-a/COMT have difficulties breaking down estrogen, serotonin and catecholamines, perhaps those who need AI the most.

Those with Fast MAO-a/COMT, on the other hand, degrade catecholamines, estrogen and serotonin very quickly, I imagine they are the ones who feel better with higher E2, in addition to being more predisposed to have depression due to low serotonin, if they decrease a lot e2 .

But he points out that even a Fast MAO-a/COMT person can become "Slow", depending on the amount of substances he is using. So even a person who metabolizes e2 very well, letting it float too high following large doses of Testosterone, could in theory have the tantrums even though they don't have the "Warrior Gene" (Slow MAO-a).

 

[Gûs80]

Yeah him saying that shows he is ahead of the pack for sure. Roid rage in bodybuilders who are typically doing 500-1000mg a week of various aromatizable steroids is definitely caused by a huge amount or conversion to estrogen > then increased serotonin activity. Unfortunately most bro’s don’t know this, some do, but most haven’t a clue. This same issue could easily rear its head with 200mg of T a week in a lot of men, so controlling e2 is a good idea. Still don’t think this is a path to longevity but it could be a path to a temporary improved quality of life, maybe even for a good number of years. Roulette if you ask me. There is definitely aggression activity caused by strong so called non aromatizing androgens as well, so there’s that.

As far as I've researched, the use of DHT derivatives alone is largely discouraged by bodybuilders. We know that DHT derivatives act as AI, but bodybuilders use very high doses of testosterone as the basis for their cycles.

So, would dht derivatives be able to inhibit e2 really effectively?

I don't think so, as in every athlete interview I've watched, they always say they let the e2 vary with the testo. Imagine someone with 4000ng of T, using high doses of Stano. Even so, your e2 would still be extremely high, even more in this ratio that Dr Rand considers high (20 to 30ng).

I think you're correct about longevity, apparently high doses of T can alter the heart. The deaths of Charles Poliquin and Dr Crisler have made me think a lot about this topic in recent years. (none of them were broadly supportive of AI use).

My paternal grandfather died at the age of 100. My father is 75 years old and is the only one of 7 siblings who has not developed diabetes, heart disease or cancer. He became a vegetarian 30 years ago... He eats large amounts of nuts daily as the main protein source besides beans. I already do very badly on this diet.

Being sick for many years changed my way of thinking about longevity. After all, longevity without health would be like suffering in hell, hahaha.

I confess that lately I've come to envy Poliquin and Dr Crisler, both died at about 60 years old, but they had an intense life and a lot of energy until the end, without being chronically ill for years. If there is reincarnation, I must have been a Viking, because death doesn't scare me, but life with limitations seems like a nightmare to me.

 

[Explorer]

My total T was 532ng/dl and E2 29pg/ml in 2021 August (I am 20) TSH 3.0 cortisol 600 at 9am after 6 hours of sleep in fasted state

 

[Gûs80]

My total T was 532ng/dl and E2 29pg/ml in 2021 August (I am 20) TSH 3.0 cortisol 600 at 9am after 6 hours of sleep in fasted state

Your Testo is good. You could benefit from lowering e2. But in your place I would focus on optimizing the thyroid first.

According to Peat the ideal tsh would be 1 or less. It can be corrected with low doses. I corrected with t4 25mcg + t3 5mcg (on fasting). And t3 5mcg at 5 pm.

 

[Donttreadonme]

Yeah him saying that shows he is ahead of the pack for sure. Roid rage in bodybuilders who are typically doing 500-1000mg a week of various aromatizable steroids is definitely caused by a huge amount or conversion to estrogen > then increased serotonin activity. Unfortunately most bro’s don’t know this, some do, but most haven’t a clue. This same issue could easily rear its head with 200mg of T a week in a lot of men, so controlling e2 is a good idea. Still don’t think this is a path to longevity but it could be a path to a temporary improved quality of life, maybe even for a good number of years. Roulette if you ask me. There is definitely aggression activity caused by strong so called non aromatizing androgens as well, so there’s that.

Estrogen isn't what causes roid rage. As someone involved in the lifestyle in the past it's the androgens. Most bodybuilders use anti e2.... I would say nearly100%. Roid rage also usually happens at the start of a cycle and then the brain adjusts

 

[Gûs80]

Estrogen isn't what causes roid rage. As someone involved in the lifestyle in the past it's the androgens. Most bodybuilders use anti e2.... I would say nearly100%. Roid rage also usually happens at the start of a cycle and then the brain adjusts

Hi, I'm not aware of their continued use. Bodybuilders use AI in PCT, during cycles the vast majority do not use it, only if they feel gyno symptoms. Last year I consulted with a bodybuilder and now I am with a bodybuilder doctor. Both are against the use of AI. Enter the bodybuilder videos and you'll see the vast majority saying not to use. On the forums the same thing.
What this doctor has been doing since the beginning of TRT is to use an AI EOD.

 

[Dave_Fit]

As far as I've researched, the use of DHT derivatives alone is largely discouraged by bodybuilders. We know that DHT derivatives act as AI, but bodybuilders use very high doses of testosterone as the basis for their cycles.

So, would dht derivatives be able to inhibit e2 really effectively?

I don't think so, as in every athlete interview I've watched, they always say they let the e2 vary with the testo. Imagine someone with 4000ng of T, using high doses of Stano. Even so, your e2 would still be extremely high, even more in this ratio that Dr Rand considers high (20 to 30ng).

I think you're correct about longevity, apparently high doses of T can alter the heart. The deaths of Charles Poliquin and Dr Crisler have made me think a lot about this topic in recent years. (none of them were broadly supportive of AI use).

My paternal grandfather died at the age of 100. My father is 75 years old and is the only one of 7 siblings who has not developed diabetes, heart disease or cancer. He became a vegetarian 30 years ago... He eats large amounts of nuts daily as the main protein source besides beans. I already do very badly on this diet.

Being sick for many years changed my way of thinking about longevity. After all, longevity without health would be like suffering in hell, hahaha.

I confess that lately I've come to envy Poliquin and Dr Crisler, both died at about 60 years old, but they had an intense life and a lot of energy until the end, without being chronically ill for years. If there is reincarnation, I must have been a Viking, because death doesn't scare me, but life with limitations seems like a nightmare to me.

 

[Dave_Fit]

Once your 54 with a 2 year old you likely won't envy people who died at 60 anymore no matter how full their life may have seemed. If you can get your T level to a point naturally where it's in the mid/high end of normal, 600 ish + -, you should be able to get fit and stay that way assuming your diet is right, and you have corrected insulin resistance issues, and your SHBG levels are not too high etc. Will you be freaky huge? Probably not. I have lifted weights for 30+ years rarely taken time off from lifting, there were a few 2-3 month periods but only a few in the last 30 years where I did not lift 3+ times a week. I don't care about being big or super strong anymore. I just want to be in shape and healthy. at 54 I have just tiny bit north of a 1000 lb total on squat, bench, and deadlift, combined. It's not a crazy total but respectable for someone who is 54. Are there guys who can do more, sure, but as a percentage of the population that number is very small.

 

[ecstatichamster]

I notice when I take DHT, my heart rate increases and the intensity of my heart increases. It's noticeable with 1mg of DHT. Sleep isn't as long, although quality is quite good.