11-Ketotestosterone main driver of malign prostate cancer

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
I see only unproven assumptions: DHT universally beneficial in PC

Not sure if you are trolling, but here are some published, peer-reviewed, "unproven assumptions" below. The last link is especially telling as it shows that DHT was therapeutic, while estrogen made the prostate cancer grow.

Also, do you mind showing me where in the studies you posted they describe 11KT and 11KDHT as the "main driver" of malignant prostate cancer??

I am trying to get my own DHT study with prostate cancer (LNCaP mouse model) finalized and published. My preliminary results closely match the results of the last link above - i.e. DHT, in a HED of about 0.15mg/kg daily (oral administration, dissolved in tocopherols/oil) was basically curative.
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
@haidut

I‘m definitely not trolling. I read most of these studies and the threads you made about them over the month and years.

I already addressed the merits and truths of your addressing PC and androgens role in treatment, progression, etiology.

I don’t agree though that every form and stage of the different forms of PC will benefit from androgen/DHT treatment.

This about your cell line:
In vivo, Male mice develop tumors earlier and at a greater frequency than do females and hormonal manipulations show that the frequency of tumor development correlates with serum androgen levels.[1] The rate of the tumor growth, however, is independent of the gender or hormonal status of the host.[1]

That’s not castration resistant cancer. CRPC growth -rate is dependent on androgen status.
Regards to LNCaP his is where I absolutely agree with you and acknowledge the value of the work you do. These types of tumors develop for specific reasons and DHT exerts protective effects. That’s an evolved mechanism of DHT, it in some way substituted for other anti-cancer mechanisms. That’s why males develops these tumors earlier and more frequent. But not all. Those who don’t don’t need to Fall back on That mechanism. Their prostate doesn’t display hyperplasia either.
In Women the DHT-associated Tumor-Protection does not seem to exist. Something similar does, maybe revolving around Progesterone.
The thing is that there are cancerous stages where DHT isn’t longer effective in preventing deadly progress. Things get so deranged that androgens promote the deadly Growth of the Tumor.
The first Publikation I posted addresses that. Ablate DHT and Test - 11-oxydht still promotes growth.
Maybe that is still a part of a now disfunctional coping attempt. It doesn’t matter. It’s making the tumor grow.
 
Last edited:

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
@haidut

I‘m definitely not trolling. I read most of these studies and the threads you made about them over the month and years.

I already addressed the merits and truths of your addressing PC and androgens role in treatment, progression, etiology.

I don’t agree though that every form and stage of the different forms of PC will benefit from androgen/DHT treatment.

This about your cell line:
In vivo, Male mice develop tumors earlier and at a greater frequency than do females and hormonal manipulations show that the frequency of tumor development correlates with serum androgen levels.[1] The rate of the tumor growth, however, is independent of the gender or hormonal status of the host.[1]

That’s not castration resistant cancer. CRPC growth -rate is dependent on androgen status.
Regards to LNCaP his is where I absolutely agree with you and acknowledge the value of the work you do. These types of tumors develop for specific reasons and DHT exerts protective effects. That’s an evolved mechanism of DHT, it in some way substituted for other anti-cancer mechanisms. That’s why males develops these tumors earlier and more frequent. But not all. Those who don’t don’t need to Fall back on That mechanism. Their prostate doesn’t display hyperplasia either.
In Women the DHT-associated Tumor-Protection does not seem to exist. Something similar does, maybe revolving around Progesterone.
The thing is that there are cancerous stages where DHT isn’t longer effective in preventing deadly progress. Things get so deranged that androgens promote the deadly Growth of the Tumor.
The first Publikation I posted addresses that. Ablate DHT and Test - 11-oxydht still promotes growth.
Maybe that is still a part of a now disfunctional coping attempt. It doesn’t matter. It’s making the tumor grow.

I am doing actually two studies - one with LNCaP and one with PC-3. The second one is castration-resistant line, so if DHT is shown to work there too then I think it would be a good indication that DHT is therapeutic for this type of most types of prostate cancer.
Btw, both LNCaP and PC-3 are human cancer lines, they are just transplanted in rodents as host organisms. So, there is very good translation of effects from these models to humans, because you are in effect treating human cancers. So, in one such model (last link above) of androgen-sensitive human prostate cancer (LNCaP) we have evidence that DHT is highly therapeutic while estrogen promotes growth. Those are in-vivo results, so to me that takes precedence over the in-vitro LNCaP results. Btw, there are thousands of in-vitro studies with LNCaP showing DHT promotes growth of that cancer, yet in-vivo we get the opposite effects. Also, we now have evidence from (small) human trials that testosterone injection into the prostate obliterates castration-resistant, terminal, prostate cancer (very similar to the PC-3 human line used in rodent models). So, the in-vivo evidence so far points to androgens being therapeutic for both androgen-sensitive and androgen-insensitive (castration-resistant) human prostate cancer.
I do agree though that more studies are needed with the 11-oxy androgens to see if they have any unique effects on cancer growth that regular androgens like T and DHT do not.
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Also, we now have evidence from (small) human trials that testosterone injection into the prostate obliterates castration-resistant, terminal, prostate cancer (very similar to the PC-3 human line used in rodent models
Gets Test reduced to DHT there, is that known? I speculate that lack of functional androgen Steroid homeostasis is one of the onset factors to begin with. Too few Test, too much DHT relatively and too few Test absolutely. But I cannot substantiate that well. Could Test injection directly maybe have overcome that?

one with PC-3. The second one is castration-resistant line, so if DHT is shown to work there too then I think it would be a good indication that DHT is therapeutic for this type of most types of prostate cancer.

Absolutely. That‘d be big news.

What is also intriguing are the studies with prolactin inhibitors and their success in treating some PCs. Many of the decades old wrong pro-estro /bad-Androgen Dogmas will fall eventually, thanks to your work also.
But with androgens too there are nuances we need to observe and consider
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
Gets Test reduced to DHT there, is that known? I speculate that lack of functional androgen Steroid homeostasis is one of the onset factors to begin with. Too few Test, too much DHT relatively and too few Test absolutely. But I cannot substantiate that well. Could Test injection directly maybe have overcome that?

Those men had undetectable levels of DHT (actually low levels of ALL androgens) due to prior castration therapy. In fact, the second human study with T for prostate cancer only used men who were still taking a castration drug (leuprolide), which guarantees that they had very low androgen levels. So, it was definitely not a situation of high DHT, but low T. The injections of T at the very least raised T levels. However, since the injections were done directly into the prostate, this results in very high conversion of T into DHT since the prostate is one of the organs with higher expression of 5-AR enzyme. This is actually the reason drugs like finasteride were invented - i.e. to lower DHT levels specifically in the prostate, and later the medical establishment realized they can also market the drug for baldness since skin also has high 5-AR expression.

Anyways, as you mentioned, the fact that anti-prolactin drugs (which have potent anti-estrogenic effects) are also used therapeutically for prostate (and breast) cancer implicate estrogen a lot more than androgens, but only more studies will show where the truth lies. Unfortunately, aside from crazy people like me virtually nobody else working in the biochemical field is willing to rock the boat and do in-vivo studies with DHT or other androgens. Challenging the "androgen hypothesis" is frowned upon by scientific journals and as you can see there are maybe no more than 10 studies over a span of 50+ years that raise any doubt/questions about the role of androgens in this condition. Hopefully, we can change that status quo soon.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
For those who are interested , the main metabolite of 11oxo (and thus11ketoT )seems to be an androsterone derivative. There's not much out there known so I think every piece of the puzzle counts.

"Oral administration of
androst-4-ene-3,11,17-trione resulted in several reduced metabolites with 11β-
hydroxyandrosterone
as main product. "

 
Last edited:

tankasnowgod

Member
Joined
Jan 25, 2014
Messages
8,131
It doesn’t „cause“ cancer. But in the most aggressive stages of prostate cancer (regardless of cause) it doesn’t cure or hold progression anymore. It speeds up growth of the tumor.

It sure would be nice is there were literally any evidence that this happens in any living organism.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
T and 11ketoT, and DHT and 11ketoDHT have literally the exact same androgenicity.

1609545957834.png
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
A word on half life. Here we got 2 different experiments for the determination of the half life.

1. Experiment : T= ca. 3 h ; 11ketoT= ca. 20 h
2. Experiment: T= ca. 7-8h; 11ketoT = ca 75h

So it seems 11ketoT has a half life that is about 10x greater then the one of regular T and lies somewhere between 20-75h as a rough estimate. So if that's true there's definitely no need to dose every day . Every second or third fay might be enough.
@ddjd

1609547298654.png
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
It sure would be nice is there were literally any evidence that this happens in any living organism.

There is as much evidence as state of the Art can deliver. If you’re first convince when you see live footage from inside a living organism where a Androgen molecule sets in motion growth cascade then you’re free to operate on sceptics.

Same then applies for estrogens mind
 

tankasnowgod

Member
Joined
Jan 25, 2014
Messages
8,131
If you’re first convince when you see live footage from inside a living organism where a Androgen molecule sets in motion growth cascade then you’re free to operate on sceptics.

How did any researcher ever get live footage of a living animal's Prostate as cancer was developing?

Anyway, that's unnecessary. Just get some animals with prostate cancer, and give them additional DHT to get it to speed up growth of the tumor. Haidut's experiment shows the exact opposite, that it stops and reverses the growth of the tumor.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
 

Cameron

Member
Joined
Jul 14, 2018
Messages
912
Location
Tennessee
For those who are interested , the main metabolite of 11oxo (and thus11ketoT )seems to be an androsterone derivative. There's not much out there known so I think every piece of the puzzle counts.

"Oral administration of
androst-4-ene-3,11,17-trione resulted in several reduced metabolites with 11β-
hydroxyandrosterone
as main product. "

Wow I wonder if androsterone (or just a derivative) may have an affinity to convert to the keto androgens this whole time. That would be quite a funny coincidence! 11 Keto - androgens are practically undetectable in humans although they play a large role in mammals. At least in mammals that don’t use 5 ar reduced androgens exogenously
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Wow I wonder if androsterone (or just a derivative) may have an affinity to convert to the keto androgens this whole time. That would be quite a funny coincidence! 11 Keto - androgens are practically undetectable in humans although they play a large role in mammals. At least in mammals that don’t use 5 ar reduced androgens exogenously
That question could be answered by a competent biochemist. If it’s even possible that androsterone could become oxygenated etc that way. I can’t.

Anyway, In the meantime I got more convinced by my cancer hypothesis. That DHT can sorta act in place of cortisol as a recent study shared here by Haidut showed is a big substantiation of that.
 

Dr. B

Member
Joined
Mar 16, 2021
Messages
4,322
That question could be answered by a competent biochemist. If it’s even possible that androsterone could become oxygenated etc that way. I can’t.

Anyway, In the meantime I got more convinced by my cancer hypothesis. That DHT can sorta act in place of cortisol as a recent study shared here by Haidut showed is a big substantiation of that.
dht can have effects like cortisol?
 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
It shares its anti inflammatory effects.

It substitutes for functional cortisol action and sensitivity. It’s a protection and compensation mechanism against deranged inflammation and cortisol damages. But the flip side is, that very mechanisms Leads to senescence. Hairloss. And other undesirable states. It prevents cancer though up to a point.
 

Makrosky

Member
Joined
Oct 5, 2014
Messages
3,982
haidut. I seem to have missed on your current activities for the last 2 or 3 years. Are you doing experiments?? Where and how? Would love to hear from you a bit more.

Also I read recently that you are preparing a lab analysis business? Impressive. Where are you posting all these news man? They are scatttered all round the forum.

Not sure if you are trolling, but here are some published, peer-reviewed, "unproven assumptions" below. The last link is especially telling as it shows that DHT was therapeutic, while estrogen made the prostate cancer grow.

Also, do you mind showing me where in the studies you posted they describe 11KT and 11KDHT as the "main driver" of malignant prostate cancer??

I am trying to get my own DHT study with prostate cancer (LNCaP mouse model) finalized and published. My preliminary results closely match the results of the last link above - i.e. DHT, in a HED of about 0.15mg/kg daily (oral administration, dissolved in tocopherols/oil) was basically curative.
 

Similar threads

Back
Top Bottom