DHT Prevents Prostate Cancer And May Even Treat It

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haidut

haidut

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Anything after the pilot study. Are more being scheduled?

I emailed the JHU guy and he said he cannot comment on future planned studies until they are registered on ClinicalTrials.gov, which made it sound like there were indeed more in the works.
 

LeeLemonoil

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Testosterone metabolites inhibit proliferation of castration- and therapy-resistant prostate cancer. - PubMed - NCBI

Testosterone metabolites inhibit proliferation of castration- and therapy-resistant prostate cancer.

Bremmer F1, Jarry H2, Unterkircher V1, Kaulfuss S3, Burfeind P3, Radzun HJ1, Ströbel P1, Thelen P4.
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Abstract

Novel treatments for castration-resistant prostate cancer (CRPC) such as abiraterone acetate (AA) or enzalutamide effectively target the androgen pathway to arrest aberrant signalling and cell proliferation. Testosterone is able to inhibit tumour cell growth in CRPC. Estrogen receptor-beta (ERβ) binds the testosterone-metabolites 3β-androstanediol and 3α-androstanediol in parallel to the canonical estradiol. In the prostate it is widely accepted that ERβ regulates estrogen signalling, mediating anti-proliferative effects. We used the prostate cancer cell lines LNCaP, PC-3, VCaP, and the non-neoplastic BPH-1. VCaP cells were treated with 1 nmol/L testosterone over 20 passages, yielding the cell line VCaPrev, sensitive to hormone therapies. In contrast, LNCaP cells were grown for more than 100 passages yielding a high passage therapy resistant cell line (hiPLNCaP). VCaP and hiPLNCaP cell lines were treated with 5 μmol/L AA for more than 20 passages, respectively, generating the AA-tolerant-subtypes VCaPAA and hiPLNCaPAA. Cell lines were treated with testosterone, dihydrotestosterone (DHT), R1881, and the androgen-metabolites 3β-androstanediol and 3α-androstanediol. 3β-androstanediol or 3α-androstanediol significantly reduced proliferation in all cell lines except the BPH-1 and androgen receptor-negative PC-3 and markedly downregulated AR and estrogen receptor alpha (ERα). Whereas ERβ expression was increased in all cell lines except BPH-1 or PC-3. In summary, 3β-adiol or 3α-adiol, as well as DHT and R1881, significantly reduced tumour cell growth in CRPC cells. Thus, these compounds represent novel potential therapeutic approaches to overcome drug-resistance in CRPC, especially with regard to AR-V7 function in therapy resistance. Furthermore, these data confirm the tumour suppressor properties of ERβ in CRPC.
 

LeeLemonoil

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Desn't mean it's a bad thing. If Androgen-receptors are overexpressed, as in advanced prostate cancer cells, downregulatin them is part of a normalizing cell-environment. 3ß-diol and 3a-diol are both DHT and Androsterone .etbaolites. 3ß-diol especially is an interesting substance - highly beneficial in the entire organism. It highly binds ERß and by that antagonizes E2
 

Wagner83

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I meant it can still be interesting in the sense that we're always told dht and the likes when supplemented will increase ARs. I don't know if others on here think AR are overexpressed in prostate cancer.
Btw not sure ray gives any particular importance to receptors, speak ing about anti serotonin chemicals upregulating serotonin receptors he said "I think their place is heavily ideologized, i.e., tending to deflect from thorough investigation of the situation"
 
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I meant it can still be interesting in the sense that we're always told dht and the likes when supplemented will increase ARs. I don't know if others on here think AR are overexpressed in prostate cancer.
Btw not sure ray gives any particular importance to receptors, speak ing about anti serotonin chemicals upregulating serotonin receptors he said "I think their place is heavily ideologized, i.e., tending to deflect from thorough investigation of the situation"

The estrogenic metabolites 3a-diol and 3b-diol decreased AR expression, but the androgens R1881 and DHT increased AR expression.
"...Pre-therapy androgen-sensitive VCaPrev moderately express AR in the presence of sufficient, but sub-physiological (1 nM, 0.3 ng/ml) testosterone. But also from this low expression level, 3α-adiol or 3β-adiol treatments led to a considerable reduction in AR expression, whereas the androgen R1881 increased AR expression. "

So, in line with previous discussions on the forum about androgens increasing AR expression. More importantly, both DHT and R1881 inhibited cancer growth. Unlike DHT, the steroid R1881 cannot be metabolized into any *diols, so its inhibitory effects on cancer are strictly due to its androgenic and anti-estrogenic effects. I think that pretty much confirms medicine's nightmare that high estrogen and low androgens drive prostate cancer. So, all of the estrogenic and anti-androgenic therapies pretty much ensure death.
"...In summary, 3β-adiol or 3α-adiol, as well as DHT and R1881, significantly reduced tumour cell growth in CRPC cells. Thus, these compounds represent novel potential therapeutic approaches to overcome drug-resistance in CRPC, especially with regard to AR-V7 function in therapy resistance. Furthermore, these data confirm the tumour suppressor properties of ERβ in CRPC."
 

LeeLemonoil

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I agree with Haidut, the decades long treatment and expplainations of prostate cancer was blatant malpractice. I still would like to stress 3ß-diol here. Even if the study is in favour of the AR-expression increasing stronger androgens DHT and the synthetic one, in a healthy non cancerous orgnism DHT gets metbaolized back and forth to 3a- and 3ß-diol respecively. They are androgens with high affinity to ERß, 3ß-diol especially, and thus contribute significantly to androgens protective effects by acting where in estrogen dominant, pathological states Estrogens would act.
A different thing is a highly advance cancer as discussed in the study, here 3a and 3ß-diol seem to act a bit different to DHT or the synthetic, though all compounds reduce tumor growth
 
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I agree with Haidut, the decades long treatment and expplainations of prostate cancer was blatant malpractice. I still would like to stress 3ß-diol here. Even if the study is in favour of the AR-expression increasing stronger androgens DHT and the synthetic one, in a healthy non cancerous orgnism DHT gets metbaolized back and forth to 3a- and 3ß-diol respecively. They are androgens with high affinity to ERß, 3ß-diol especially, and thus contribute significantly to androgens protective effects by acting where in estrogen dominant, pathological states Estrogens would act.
A different thing is a highly advance cancer as discussed in the study, here 3a and 3ß-diol seem to act a bit different to DHT or the synthetic, though all compounds reduce tumor growth

True, and as I mentioned in another post, all 5-AR derived steroids should be taken into account when calculating body reserves because most of then are interconvertible with each other. At least DHT, 5a-diol, 5a-dione, and androsterone are, so each one of these 4 is in effect a prohoromone - i.e. serve as precursor for the other 3. In addition, 5a-DHP and allopregnanolone also should be counted because they both convert to androsterone and thus add to the pool.
But to your point - I agree that the *diols are beneficial and many of those benefits come from displacing estrogen from ER. Also, by acting on ER-b they also lead to lower synthesis of estrogen because the organism uses the ER as a sensor how much estrogen to synthesize. So, the effects of *diols on estrogen are akin to the so-called "silent antagonists".
 

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So, in line with previous discussions on the forum about androgens increasing AR expression. [...]

Why would the effects in human not have to take into account the metabolites and how dht/androsterone is dealt with by the body? In vitro result should be very different in that case.
 
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Why would the effects in human not have to take into account the metabolites and how dht/androsterone is dealt with by the body? In vitro result should be very different in that case.

They would have to take it into account, but human studies have shown that men with higher DHT levels or treated with DHT have higher AR expression. So, I guess even though DHT metabolizes into the *diols it seems to have higher affinity (EC50 1nM /L for DHT compared to EC50 of about 1 uM/L for the *diols) for the AR than the *diols and its effects prevail (if DHT levels are high enough).
 

LeeLemonoil

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Thanks @Wagner83

I think what Haidut recently wrote is true:
The pharma-establishment is in a threatening situation: sales are tanking and more and more people due to available information are aware that we are and were sold factually wrong narratives and scientific psradigmas.
No they finally yield to the need to actually research and develop what really can heal: e.g. metabolic, mitochondrial, hormonal health,
But they will still want to keep their hands on it for the profits: so „adjuvant“ treatments will surely rise and hithertho free substances will be seized by the fda to be retailed later at hefty premiums
 

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@haidut
And anyone else interested, of course.
Posting this in the first DHT thread that came up. This study shows that administration of DHT to female guinea pigs for 60 days @1mg/kg (although it was dissolved in peanut oil) increased DHEA-S levels (pretty substantially) as well as DHEA and even more interestingly had a trophic effect on the zona reticularis of the adrenal gland. If i’m not mistaken, this is the layer of the gland that functions in the production of DHEA. Moreover, pregnenolone was elevated, and of course the DHT was elevated yet estradiol wasnt elevated. In fact the 60 day animals became acyclic, perhaps due to an overall decrease in estrogen from DHT’s antagonism to aromatase? Its crazy that bio-identical DHT is banned in the US.

Effects of dihydrotestosterone treatment on adrenal gland function and morphology in adult female guinea-pigs. - PubMed - NCBI
 
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I for one got massive shedding from Proviron, Anadrol. Typically anyone with some drug-induced hair shedding would freak out and not wait it out for months and see what grows back, right?

So here's a simpleton theory: could DHT-based steroids promote hair regrowth like Minoxidil does? DHT induces vasodilatation, as per the studies on rats' weiners. And since at the same time, steroid users abuse Testosterone, maybe they don't understand how aromatization leads to e1 and prolactin accumulation over time (whilst Nandrolone-only lowers prolactin) = such a picture is a disaster at the hair, prostate, skin isn't it

My buddy got impressive skin improvements, high sex drive, thickest hair ever and visibly shrunk nips on low dose TRESTOLONE plus MASTERON. Talk about potent androgens! Now Trestolone does aromatize but pretty much only yields methyl-estradiol, not estrone or estriol. I think Estradiol is a neutral/positive estrogen as long as it is in range, going by activities on ERa and ERb receptors. Hair loss people get superb hair regrowth from (topical) estradiol.

Are AIs misguided? If we're using aromatase inhibitors, how are we sure that one of the consequences of low e2 isn't higher e1? Could we be getting more androstenedione > estrone as a compensatory mechanism? Supplementing DHEA could also be interesting as its metabolites largely act on the ERb, not the ERa. And we know how prolactin and cortisol tend to lower DHEA.

Its crazy that bio-identical DHT is banned in the US.

How surprising... Conspiracy theories are my favorites, and this isn't a sarcasm
 
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LeeLemonoil

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I don't think E2 is neutral - of course there is homeostasis where too low E2 is not ideal, but I would sill consider it a stress-hormone benign only in contextual situations.

3a- and 3ß-androstanediol are direct DHT metabolites that act on ERa and ERb instead of on the AR. MAybe these are involved in hiar-regrow effects assoicated with DHT or synthetics based on it.

ß-Ecdysterone acts on the ERb and is shown to act similar to Estradiol in wound healing and skin-care effects and in bone and cartilage protection but I would consider it much more benign than E2.
 
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you're right I edited. E2 is better kept in range, very possibly the lower half is optimal. The issue with exogenous Testosterone excess is the myriad of systemic adaptations since the body "knows" how to "deal" with T. Among which estrogens, prolactin, poor DHT metabolism. I believe that in TRT, less can be way more.

It also looks like DHT is probably beneficial thanks to its metabolites. What if someone doesn't have a good DHT metabolism because of insufficient enzymes? It is discussed here:

Anticancer Testosterone Metabolite 3β-Adiol (July 2012) Townsend Letter for Doctors & Patients
 
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@haidut
And anyone else interested, of course.
Posting this in the first DHT thread that came up. This study shows that administration of DHT to female guinea pigs for 60 days @1mg/kg (although it was dissolved in peanut oil) increased DHEA-S levels (pretty substantially) as well as DHEA and even more interestingly had a trophic effect on the zona reticularis of the adrenal gland. If i’m not mistaken, this is the layer of the gland that functions in the production of DHEA. Moreover, pregnenolone was elevated, and of course the DHT was elevated yet estradiol wasnt elevated. In fact the 60 day animals became acyclic, perhaps due to an overall decrease in estrogen from DHT’s antagonism to aromatase? Its crazy that bio-identical DHT is banned in the US.

Effects of dihydrotestosterone treatment on adrenal gland function and morphology in adult female guinea-pigs. - PubMed - NCBI

Thanks, it matches the old study with women taking high dose androsterone ( @Wagner83 ). It elevated DHEA in them too. The effects are probably due to reduced estrogen levels, as estrogen is what suppressed DHEA/T/pregnenolone synthesis very potently. Cortisol does too and since DHT suppresses cortisol, it allowed the adrenal layer generating DHEA/pregnenolone to recover.
Even A Slight Increase In Estrogen Strongly Decreases DHEA Levels
 

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