Low DHT increases risk of prostate cancer death

Decreased levels of DHT at the time of diagnosis result in increased
risk of dying from prostate cancer. See http://tinyurl.com/3myzz2

Ed Friedman

On April 9, Ed wrote:

> Decreased levels of DHT at the time of diagnosis result in increased
> risk of dying from prostate cancer. See http://tinyurl.com/3myzz2

That 2007 Swedish study concludes, based upon 17 PCa-related deaths out
of 41, in a study cohort of 65, "Although the prognostic value of DHT
levels at diagnosis remains unclear, these results provides (sic)
evidence of an association between low DHT and decreased survival in
prostate cancer patients."

(Well, there is an association between the cock's crow and sunrise, too.)

It is contradicted by every one of the many studies and essays I have
read, including this 2008 Mayo Clinic study:

Tindall DJ, et al., "The rationale for inhibiting 5alpha-reductase
isoenzymes in the *prevention* and treatment of prostate cancer."
(emphasis added)

It begins, "Androgens are essential for prostatic growth and development
but they also have a significant role in prostate disease pathogenesis.
Dihydrotestosterone, the primary prostatic androgen, is transformed from
testosterone by types 1 and 2 5alpha-reductase and, thus, a potential
therapeutic benefit could be achieved through the inhibition of
5alpha-reductase."

The operative sentence in the conclusion is, "The inhibition of
5alpha-reductase represents a valid target for prostate cancer risk
reduction and treatment strategies."

See Pub Med ID 18280514 at www.pubmed.gov Pub Med is a service of the
US National Library of Medicine.

Regards,

Steve J

Both pieces can fit together. In aggressive PCa, the tumor cells do
not need androgens (or at least not high levels). In low-risk
disease, an androgen supply is required. So it is not unreasonable to
find that low DHT levels signal advanced disease, and hence the risk
of death is increased. Here is a reference to an earlier study that
found a similar relationship between DHT and PCa aggressiveness...ron


J Urol. 2006 Oct;176(4):1387-91

Association between the dihydrotestosterone level in the prostate and
prostate cancer aggressiveness using the Gleason score.

Nishiyama T, Ikarashi T, Hashimoto Y, Suzuki K, Takahashi K.

Division of Urology, Department of Regenerative and Transplant
Medicine, Niigata University Graduate School of Medical and Dental
Sciences, Niigata, Japan.

PURPOSE: To our knowledge the association between dihydrotestosterone
in the prostate and prostate cancer aggressiveness has not yet been
elucidated. We analyzed dihydrotestosterone levels in the prostate and
Gleason score in patients diagnosed with clinically localized prostate
cancer.
MATERIALS AND METHODS: A total of 81 patients with suspected prostate
cancer underwent prostate biopsy. Serum samples were collected before
biopsy. Dihydrotestosterone levels in prostatic tissue and serum were
analyzed using liquid chromatography/electrospray ionization-mass
spectrometry after polar derivatization.
RESULTS: A total of 47 patients were diagnosed with stages T1 to
T3N0M0 prostate cancer and 34 were diagnosed with no malignancy. Of
the 47 patients 32 had a Gleason score of 6 or less and 15 had a score
of 7 to 10. Dihydrotestosterone in prostatic tissue in patients with
Gleason score 7 to 10 disease was significantly lower than in those
with Gleason score 6 or less disease (p = 0.025). Gleason score
correlated with the testosterone-to-serum dihydrotestosterone ratio
(rs = 0.329, p = 0.038).
CONCLUSIONS: Patients with Gleason score 7 to 10 prostate cancer have
low dihydrotestosterone in the prostate, although there were no
significant differences between patients with Gleason score 7 to 10 vs
6 or less prostate cancer with respect to serum androgens. Low
dihydrotestosterone in cases of aggressive prostate cancer is probably
sufficient to activate androgen receptor expression and propagate
tumor growth.
PMID: 16952639

On Apr 9, 3:14 pm, Steve Jordan <mycrofts...@cox.net> wrote:
> It is contradicted by every one of the many studies and essays I have
> read, including this 2008 Mayo Clinic study:
>
> Tindall DJ, et al., "The rationale for inhibiting 5alpha-reductase
> isoenzymes in the *prevention* and treatment of prostate cancer."
> (emphasis added)
>
> It begins, "Androgens are essential for prostatic growth and development
> but they also have a significant role in prostate disease pathogenesis.
> Dihydrotestosterone, the primary prostatic androgen, is transformed from
> testosterone by types 1 and 2 5alpha-reductase and, thus, a potential
> therapeutic benefit could be achieved through the inhibition of
> 5alpha-reductase."
>
> The operative sentence in the conclusion is, "The inhibition of
> 5alpha-reductase represents a valid target for prostate cancer risk
> reduction and treatment strategies."
>
> See Pub Med ID 18280514 atwww.pubmed.gov Pub Med is a service of the
> US National Library of Medicine.
>
> Regards,
>
> Steve J


Steve,

You are comparing apples and oranges here. The rationale for using a
5AR2 inhibitor is to increasee the imbalance between the agonism of
the membrane androgen receptor (mAR) and the intracellular androgen
(iAR), thus increasing the amount of pro-apoptic proteins produced (as
explained in my model - see http://www.tbiomed.com/content/4/1/28).
The disadvantage of this approach is its increase in the anti-
apoptotic Bcl-2 (which is why doing things that further increase
Bcl-2, such as taking phytoestrogens, can lead to very aggressive PC
as observed by Dr. Lebovitz). When you are not using drugs to create
an artificial imbalance in the agonism of mAR and iAR, then the more
agonism of iAR, the better. A 20 year study showed that the lower the
level of T, the more aggressive the PC was if that man developed PC
(the reference is in my paper). Basically, more agonism of iAR
translates into lower levels of Bcl-2 - the main reason you don't see
PC, even in autopsies, in teenagers.

Also, the statements made in that 2008 Mayo Clinic study demonstrate
the author's lack of understanding of PC. While he is correct that
androgens have an essential role in normal prostate cell growth and
development, he is wrong in saying that they have a significant role
in PC pathogenesis. There is simply no evidence to support that
statement (you don't have to believe me on this - check out the many
articles written about this by Dr. Morgentaler of Harvard).

In conclusion, in order to understand the role of mAR and iAR in PC,
you have to understand the power of balance. As I have stated in my
article, if you can create an imbalance between iAR and mAR agonism,
you increase the rate of apoptosis. Ideally, once they develop a drug
that specifically blocks just mAR, then total antagonism of mAR
coupled with total agonism of iAR may actually lead to a systemic cure
of PC. Even total agonism of mAR coupled with total antagonism of iAR
should be quite effective (which is why Dr. Lebovitz gets such
positive results with high T/ low DHT treatments).

Ed Friedman

On April 9, Ron replied to me:

> Both pieces can fit together.

(snip)

Not when, as I quoted above, "The inhibition of 5alpha-reductase
represents a valid target for prostate cancer risk reduction and
treatment strategies." And we know that inhibition of 5AR reduces if
not entirely stops the transformation of T into DHT. DHT, as I think we
can all agree, nourishes PCa cells.

Yes, some advanced PCa cells do not require T or DHT to flourish. So
what are we being told by the Swedish and the Japanese studies? That
lowering DHT by use of 5AR inhibitors will *cause* advanced PCa? That's
the implication as I see it, and it is not supported by the evidence.

On the other paw, we're told that a low amount of DHT at diagnosis is a
sign of advanced disease. How so? What is the causal relationship? They
don't tell us. Mainly because they don't know. All they are doing is
reporting what they observed; they do not try to explain it.

Just another of the multitude of conundrums in this business......

Regards,

Steve J

On April 9, ed Friedman replied to me:

> You are comparing apples and oranges here.

Au contraire, I am simply citing authorities that have a viewpoint that
differs from Ed's and the authors of the two previously-cited studies.

(snip interesting theory)

> Also, the statements made in that 2008 Mayo Clinic study demonstrate
> the author's lack of understanding of PC.

Whoa! It would be well, I think, to check the credentials of a medic
before claiming that he lacks understanding of the topic upon which he
writes. Dr. Tindall, the lead author, is a professor of
biochemistry/molecular biology and a professor of urology. He is engaged
in "....investigating the molecular mechanisms by which androgens
regulate gene expression in target tissues, particularly the
prostate...," according to his bio. His published, peer-reviewed, papers
on Pub Med total109.

Anyone who is interested can find his academic and professional bio at
http://www.mayoclinic.org/bio/10984372.html

I didn't take time to look up the co-author, Rittmaster.

> There is simply no evidence to support that
> statement (you don't have to believe me on this - check out the many
> articles written about this by Dr. Morgentaler of Harvard).

Please cite a source. Frex, Pub Med.

As for Ed's theory, maybe he's right, maybe he's wrong. I certainly
don't have a background that qualifies me to critique it. In what
peer-reviewed journal is the article published?

Regards,

Steve J

On Apr 9, 6:17 pm, Steve Jordan <mycrofts...@cox.net> wrote:
> On April 9, ed Friedman replied to me:
>
> > You are comparing apples and oranges here.
>
> Au contraire, I am simply citing authorities that have a viewpoint that
> differs from Ed's and the authors of the two previously-cited studies.

Steve,
Let me clarify what I mean about comparing apples and oranges.
Basically, when you lower DHT and couple it with high levels of T, you
get much different results than when you lower DHT and couple it with
low levels of T. Essentially, no good comes from both low T and low
DHT. To illustrate why you must take into account the level of T when
you talk about very low levels of DHT, consider what the effect would
be when T is below the castrate level. You certainly would agree that
effect is different than what occurs from just lowering DHT levels.

>
> > Also, the statements made in that 2008 Mayo Clinic study demonstrate
> > the author's lack of understanding of PC.
>
> Whoa! It would be well, I think, to check the credentials of a medic
> before claiming that he lacks understanding of the topic upon which he
> writes.
> Anyone who is interested can find his academic and professional bio athttp://www.mayoclinic.org/bio/10984372.html

Again, you misunderstand me. I mean no insult to any specific
doctor. However, anyone who puts forth a theory which is refuted by
experimental evidence, by definition does not have a correct theory
and therefore does not have a complete grasp of the subject. Needless
to say, this criticism applies to almost everyone who writes articles
about prostate cancer. Also, to criticize an experimental finding
just because it doesn't fit one's theory is anti-science. In biology
and medicine, properly done experiments are the benchmark that
determines what reality is, not theories or widely held beliefs that
are inconsistent with the properly done experimental findings.

> > There is simply no evidence to support that
> > statement (you don't have to believe me on this - check out the many
> > articles written about this by Dr. Morgentaler of Harvard).
>
> Please cite a source. Frex, Pub Med.

One of his papers can be viewed at: http://www.europeanurology.com/artic...787-1/fulltext

> As for Ed's theory, maybe he's right, maybe he's wrong. I certainly
> don't have a background that qualifies me to critique it. In what
> peer-reviewed journal is the article published?

I'm not sure which article you are referring to. I gave you the
reference in my first post of this thread to my most recent paper,
published in the peer-reviewed Journal of Theoretical Biology and
Medical Modelling. My latest paper, which hopefully will explain
things at a level most doctors will be able to understand, has been
submitted to the Lancet.

>
> Regards,
>
> Steve J

Again, you don't have to be an expert to evaluate a theory. When it
comes to something like prostate cancer, all you have to do is to find
a single experiment that is inconsistent with a model and by
definition that model is wrong. So far, I have not been able to
uncover any experimental finding which is not explained by my model,
nor has anyone else (or if they have, they haven't told me). I have
been contacted by patients who have asked pointed questions about my
model and challenged me to explain findings which I did not cover in
my paper. So far I have been able to answer all of their questions.
This means that if my model ultimately turns out to be correct, then
there are ordinary patients walking around today that understand
prostate cancer better than almost all of the big name prostate cancer
doctors.

Ed Friedman

On Wed, 9 Apr 2008 05:33:32 -0700 (PDT), ed@math.uchicago.edu wrote:

>Decreased levels of DHT at the time of diagnosis result in increased
>risk of dying from prostate cancer.

With apologies to you Ed, and Steve and Ron for interrupting the flow
of the thread. I have been totally unable to follow the cut and
thrust of what is a high level academic/technical argument. But I
would like to distill down to the one post I could understand - Ed's
orginal - above.

Assuming Ed, for the moment, your statement is correct.

The body also refers to high Gleason as increasing mortality
likelihood.

I was diagnosed Gleason 9. I am now T3c NI M0. Prostate and left
seminal vesicle primary sources ablated (HIFU) - but now lymph node
involvement. So my next step will be hormonal therapy. I am 81 in
November.

The study is valid. You're me. Would you go for HT? Theoretically?

With much thanks

MikeHi

Steve...see my comments within your text...ron

On Apr 9, 3:42*pm, Steve Jordan <mycrofts...@cox.net> wrote:
> On April 9, Ron replied to me:
>
> > Both pieces can fit together. *
>
> (snip)
>
> Not when, as I quoted above, "The inhibition of 5alpha-reductase
> represents a valid target for prostate cancer risk reduction and
> treatment strategies." *And we know that inhibition of 5AR reduces if
> not entirely stops the transformation of T into DHT. DHT, as I think we
> can all agree, nourishes PCa cells.

No. Again, generally speaking, aggressive disease does not have the
same androgen requirement to nourish the tumor cells as does less
aggressive, or earlier stage disease.

> Yes, some advanced PCa cells do not require T or DHT to flourish. So
> what are we being told by the Swedish and the Japanese studies? That
> lowering DHT by use of 5AR inhibitors will *cause* advanced PCa? That's
> the implication as I see it, and it is not supported by the evidence.

No. The implication is that low DHT at diagnosis is a warning sign of
advanced disease.

> On the other paw, we're told that a low amount of DHT at diagnosis is a
> sign of advanced disease. How so? What is the causal relationship? They
> don't tell us. Mainly because they don't know. All they are doing is
> reporting what they observed; they do not try to explain it.

Correct, that's often how science works. Initially, someone makes an
observation; later work will provide the causal relationship.
However, in the case at hand, it is known that the tumor cells in
aggressive disease are so dedifferentiated that they don't produce
PSA, they don't require T or DHT, etc. The entire tumor machinery is
redirected to grow blood vessels and survive on non-adrogenic
materials (or extremely low amounts of androgenic materials). There
is no need for T or DHT, so the cancerous cells redirect the
intracellular machinery away from using/producing these materials.
Hence there levels are low.

> Just another of the multitude of conundrums in this business......
>
> Regards,
>
> Steve J

On Apr 10, 5:30 am, Mik...@anon.co.uk wrote:
> On Wed, 9 Apr 2008 05:33:32 -0700 (PDT), e...@math.uchicago.edu wrote:
> >Decreased levels of DHT at the time of diagnosis result in increased
> >risk of dying from prostate cancer.
>
> With apologies to you Ed, and Steve and Ron for interrupting the flow
> of the thread. I have been totally unable to follow the cut and
> thrust of what is a high level academic/technical argument. But I
> would like to distill down to the one post I could understand - Ed's
> orginal - above.
>
> Assuming Ed, for the moment, your statement is correct.
>
> The body also refers to high Gleason as increasing mortality
> likelihood.
>
> I was diagnosed Gleason 9. I am now T3c NI M0. Prostate and left
> seminal vesicle primary sources ablated (HIFU) - but now lymph node
> involvement. So my next step will be hormonal therapy. I am 81 in
> November.
>
> The study is valid. You're me. Would you go for HT? Theoretically?
>
> With much thanks
>
> MikeHi

Mike,

I'm not an MD, but hypothetically, if I were in your situation, I
would opt for slowing down PSA velocity along with maximizing quality
of life. Basically, if you look at Dr. Leibowitz's case histories for
men treated with high T/low DHT, at http://www.compassionateoncology.org...orts_03_07.pdf,
then patient #5 opted for high T/ low DHT without doing HT first
(which is what I would opt for personally). Note that for this
patient, his PSA doubling time was greater than 15 years. I'm sure
that almost everyone in this group would be happy to have such a PSA
doubling time.

Of course, the problem is that at presently it is probably impossible
to find a doctor willing to treat you this way. Hopefully, this will
change after my next article gets published, but it will still take
time.

Ed Friedman

MikeHi writes:
>> On Wed, 9 Apr 2008 05:33:32 -0700 (PDT), e...@math.uchicago.edu wrote:
>> >Decreased levels of DHT at the time of diagnosis result in increased
>> >risk of dying from prostate cancer.

I wrote to Ed asking:
(snip)
>>
>> I was diagnosed Gleason 9. I am now T3c NI M0. Prostate and left
>> seminal vesicle primary sources ablated (HIFU) - but now lymph node
>> involvement. So my next step will be hormonal therapy. I am 81 in
>> November.
>>
>> The study is valid. You're me. Would you go for HT? Theoretically?

Ed has just replied to me as follows:
>
>I'm not an MD, but hypothetically, if I were in your situation, I
>would opt for slowing down PSA velocity

How, if no HighT treatment available? My PSA January 23 2008 6.0
(Aug 2007 -Jan 2008 PSADT 0.9yrs PSAV 4 ng/ml/yr).

>along with maximizing quality
>of life.

At my age, certain recurring aspects of QQL the study patients
celebrated, like libido, may unfortunately be kept from my eager grasp
by that humourless bloke preparing the scythe. My priorities are
rather more, not getting all sorts of new body problems. If it's
possible.

>Basically, if you look at Dr. Leibowitz's case histories for
>men treated with high T/low DHT, at http://www.compassionateoncology.org...orts_03_07.pdf,
>then patient #5 opted for high T/ low DHT without doing HT first
>(which is what I would opt for personally). Note that for this
>patient, his PSA doubling time was greater than 15 years. I'm sure
>that almost everyone in this group would be happy to have such a PSA
>doubling time.

The rapid rise in his testosterone levels over the years accompanied
by almost stable PSA for #5 looks remarkable to my lay eyes. But in
the UK, in my limited experience as a patient, no doctors look at
testosterone levels on their own. I certainly don't have a clue what
mine are. And there is no likelihood, as you note of high T treatment
being accepted anywhere 'real soon' :-) Looks like I might have to
mess around (stop start, see how it goes) with HT and all its question
marks- only way I can see at moment to buy time rather than let PSA
and stuff runaway.


>Of course, the problem is that at presently it is probably impossible
>to find a doctor willing to treat you this way. Hopefully, this will
>change after my next article gets published, but it will still take
>time.

Ed, I do not have the expertise to judge whether you're right or
wrong; you certainly have evidence. But I wish you the greatest
success on publication of your paper. I remember. many many years ago
as a very young man, before I became wise with a beard, being
instrumental in introducing very new technologies into the market
place. Some failed not because they didn't work (they are now
commonplace) but all the managers and experts at the time, the best
in the land, knew that abacuses and slide rules and messengers did.
You are doing something perhaps even more difficult - following up
leads first aired more than 50 years ago - which in modern science
terms are when the dinosaurs roamed. You like it tough. My very best
wishes, and thanks for your advice.

And my best wishes to all.
Mike Hi

On Apr 9, 11:26 pm, e...@math.uchicago.edu wrote:
> On Apr 9, 6:17 pm, Steve Jordan <mycrofts...@cox.net> wrote:
>
> > On April 9, ed Friedman replied to me:
>
> > > You are comparing apples and oranges here.
>
> > Au contraire, I am simply citing authorities that have a viewpoint that
> > differs from Ed's and the authors of the two previously-cited studies.
>
> Steve,
> Let me clarify what I mean about comparing apples and oranges.
> Basically, when you lower DHT and couple it with high levels of T, you
> get much different results than when you lower DHT and couple it with
> low levels of T. Essentially, no good comes from both low T and low
> DHT. To illustrate why you must take into account the level of T when
> you talk about very low levels of DHT, consider what the effect would
> be when T is below the castrate level. You certainly would agree that
> effect is different than what occurs from just lowering DHT levels.
>
>
>
> > > Also, the statements made in that 2008 Mayo Clinic study demonstrate
> > > the author's lack of understanding of PC.
>
> > Whoa! It would be well, I think, to check the credentials of a medic
> > before claiming that he lacks understanding of the topic upon which he
> > writes.
> > Anyone who is interested can find his academic and professional bio athttp://www.mayoclinic.org/bio/10984372.html
>
> Again, you misunderstand me. I mean no insult to any specific
> doctor. However, anyone who puts forth a theory which is refuted by
> experimental evidence, by definition does not have a correct theory
> and therefore does not have a complete grasp of the subject. Needless
> to say, this criticism applies to almost everyone who writes articles
> about prostate cancer. Also, to criticize an experimental finding
> just because it doesn't fit one's theory is anti-science. In biology
> and medicine, properly done experiments are the benchmark that
> determines what reality is, not theories or widely held beliefs that
> are inconsistent with the properly done experimental findings.
>
> > > There is simply no evidence to support that
> > > statement (you don't have to believe me on this - check out the many
> > > articles written about this by Dr. Morgentaler of Harvard).
>
> > Please cite a source. Frex, Pub Med.
>
> One of his papers can be viewed at:http://www.europeanurology.com/artic...787-1/fulltext
>
> > As for Ed's theory, maybe he's right, maybe he's wrong. I certainly
> > don't have a background that qualifies me to critique it. In what
> > peer-reviewed journal is the article published?
>
> I'm not sure which article you are referring to. I gave you the
> reference in my first post of this thread to my most recent paper,
> published in the peer-reviewed Journal of Theoretical Biology and
> Medical Modelling. My latest paper, which hopefully will explain
> things at a level most doctors will be able to understand, has been
> submitted to the Lancet.
>
>
>
> > Regards,
>
> > Steve J
>
> Again, you don't have to be an expert to evaluate a theory. When it
> comes to something like prostate cancer, all you have to do is to find
> a single experiment that is inconsistent with a model and by
> definition that model is wrong. So far, I have not been able to
> uncover any experimental finding which is not explained by my model,
> nor has anyone else (or if they have, they haven't told me). I have
> been contacted by patients who have asked pointed questions about my
> model and challenged me to explain findings which I did not cover in
> my paper. So far I have been able to answer all of their questions.
> This means that if my model ultimately turns out to be correct, then
> there are ordinary patients walking around today that understand
> prostate cancer better than almost all of the big name prostate cancer
> doctors.
>
> Ed Friedman

Just a shot in the dark - could low DHT levels result from the DHT
being excessively taken up by the cancer cells?

Lud

I'm no expert in any of this, but let me suggest another possible
explanation for a correlation between low DHT and aggressive
disease.

This suggestion is not meant as a theory explaining all phenomena
related to this, only as a possible factor that could, perhaps,
account for some correlation between the two.

Perhaps men with low testosterone and non-aggressive disease
don't show up on the radar screen. Perhaps they either don't get
cancer, or they usually get it so late in life, or at such low
levels, that their physical exams don't reveal anything.

On the other hand, if they DO have enough cancer to show up in
PSA and other tests, it's because the cancer they have is
unusually aggressive, and it grows in spite of the low levels of
testosterone.

Another way to state this theory is, given a population
containing a certain percentage of men with aggressive cancers
and a certain percentage with non-aggressive cancers, low T
levels will suppress more of the cancers in the low level disease
patients, leaving a higher proportion of such patients with
aggressive disease.

If that theory is right, the correlation between low T and high
aggressiveness is not a causal one. Low T doesn't cause
aggressive disease, rather it filters out some of the
non-aggressive disease. But the aggressiveness of cancers that
are detected among men with low T is higher.

If this explanation is right, and I have zero reason to believe
either that it is or it isn't, we could get evidence for or
against it by surveying a random sample of men of, say, a
particular age, and carefully evaluating them to find out 1)
their T level and 2) whether they have cancer - even small
amounts.

If my theory is right (again, I'm not proposing that it is), then
among ALL men, men with low T will have less overall cancer, and
no more aggressive cancer than men with high T. But among MEN
WITH CANCER, a higher percentage of men with low T will have
aggressive disease.

Does that sound plausible?

On Apr 9, 9:19 pm, e...@math.uchicago.edu wrote:

> ... Basically, more agonism of iAR
> translates into lower levels of Bcl-2 - the main
> reason you don't see PC, even in autopsies, in
> teenagers. ...

If cancer is brought about by an accumulation of
mutations in DNA then, for many cancers at least,
wouldn't you expect to find a strong correlation
between age and cancer?

Alan

On Apr 13, 10:15 pm, Alan Meyer <amey...@yahoo.com> wrote:
> If my theory is right (again, I'm not proposing that it is), then
> among ALL men, men with low T will have less overall cancer, and
> no more aggressive cancer than men with high T. But among MEN
> WITH CANCER, a higher percentage of men with low T will have
> aggressive disease.
>
> Does that sound plausible?

Actually, they have checked into this (Urology. 2006 Dec;68(6):
1263-7), and what they found was for men with low levels of T, the
lower the T the higher the percentage of them who were found to have
prostate cancer.

Ed Friedman

On Apr 13, 10:24 pm, Alan Meyer <amey...@yahoo.com> wrote:
> On Apr 9, 9:19 pm, e...@math.uchicago.edu wrote:
>
> > ... Basically, more agonism of iAR
> > translates into lower levels of Bcl-2 - the main
> > reason you don't see PC, even in autopsies, in
> > teenagers. ...
>
> If cancer is brought about by an accumulation of
> mutations in DNA then, for many cancers at least,
> wouldn't you expect to find a strong correlation
> between age and cancer?
>
> Alan

Alan,

An article by a group of Johns Hopkin doctors looked into the growth
rate of prostate cancer and calculated when the first prostate cancer
cell typically arises. They determined that the age when this happens
was in the 20's and 30's (http://clincancerres.aacrjournals.org/cgi/
content/abstract/1/5/473). By coincidence this also happens to be the
time when total bioavailable levels of T start to drop in men due to
the increase in SHBG.

Also, in order to get the mutations necessary for cancer to occur, it
helps to have uncontrolled cell growth, since the more inappropriate
cell divisions that occur in any tissue, the more likely that the
exact mutations that are needed to cause cancer will occur. In the
prostate, high local levels of estradiol are all that is needed to
start the uncontrolled growth of prostate cells, and this can happen
at any time following puberty.

Ed Friedman

ed@math.uchicago.edu wrote:
> On Apr 13, 10:15 pm, Alan Meyer <amey...@yahoo.com> wrote:
>> If my theory is right (again, I'm not proposing that it is), then
>> among ALL men, men with low T will have less overall cancer, and
>> no more aggressive cancer than men with high T. But among MEN
>> WITH CANCER, a higher percentage of men with low T will have
>> aggressive disease.
>>
>> Does that sound plausible?
>
> Actually, they have checked into this (Urology. 2006 Dec;68(6):
> 1263-7), and what they found was for men with low levels of T, the
> lower the T the higher the percentage of them who were found to have
> prostate cancer.
>
> Ed Friedman

My doc was saying that low T was the body's way of reacting to prostate
cancer. So, first you develop PCa, then your body lowers T, then your
Pca slows down.

I'm not a doctor, but I play one on the internet.

On Apr 14, 9:03 am, e...@math.uchicago.edu wrote:
> On Apr 13, 10:24 pm, Alan Meyer <amey...@yahoo.com> wrote:
>
> > On Apr 9, 9:19 pm, e...@math.uchicago.edu wrote:
>
> > > ... Basically, more agonism of iAR
> > > translates into lower levels of Bcl-2 - the main
> > > reason you don't see PC, even in autopsies, in
> > > teenagers. ...
>
> > If cancer is brought about by an accumulation of
> > mutations in DNA then, for many cancers at least,
> > wouldn't you expect to find a strong correlation
> > between age and cancer?
>
> > Alan
>
> Alan,
>
> An article by a group of Johns Hopkin doctors looked into the growth
> rate of prostate cancer and calculated when the first prostate cancer
> cell typically arises. They determined that the age when this happens
> was in the 20's and 30's (http://clincancerres.aacrjournals.org/cgi/
> content/abstract/1/5/473). By coincidence this also happens to be the
> time when total bioavailable levels of T start to drop in men due to
> the increase in SHBG.
>
> Also, in order to get the mutations necessary for cancer to occur, it
> helps to have uncontrolled cell growth, since the more inappropriate
> cell divisions that occur in any tissue, the more likely that the
> exact mutations that are needed to cause cancer will occur. In the
> prostate, high local levels of estradiol are all that is needed to
> start the uncontrolled growth of prostate cells, and this can happen
> at any time following puberty.
>
> Ed Friedman

Ed
What are the readings for DHT - it is many times more potent than T.
With low T and high SHBG, it is definitely possible to have very high
DHT levels. If the DHT levels are not studied then the paper is
incomplete and no conclusions can be established.

From my experience on high dose Casodex, I had T in the upper
reference range, SHBG was above reference range, my estradiol was
above the reference range and my DHT was way above the reference range
despite the 60% reduction by Proscar. In my case, I believe, the DHT
was the dominant reason for my PSA rise of my androgen dependent PCa.

Lud

On Apr 14, 1:23 pm, Lud <Ludwi...@gmail.com> wrote:
> On Apr 14, 9:03 am, e...@math.uchicago.edu wrote:
>
>
>
> > On Apr 13, 10:24 pm, Alan Meyer <amey...@yahoo.com> wrote:
>
> > > On Apr 9, 9:19 pm, e...@math.uchicago.edu wrote:
>
> > > > ... Basically, more agonism of iAR
> > > > translates into lower levels of Bcl-2 - the main
> > > > reason you don't see PC, even in autopsies, in
> > > > teenagers. ...
>
> > > If cancer is brought about by an accumulation of
> > > mutations in DNA then, for many cancers at least,
> > > wouldn't you expect to find a strong correlation
> > > between age and cancer?
>
> > > Alan
>
> > Alan,
>
> > An article by a group of Johns Hopkin doctors looked into the growth
> > rate of prostate cancer and calculated when the first prostate cancer
> > cell typically arises. They determined that the age when this happens
> > was in the 20's and 30's (http://clincancerres.aacrjournals.org/cgi/
> > content/abstract/1/5/473). By coincidence this also happens to be the
> > time when total bioavailable levels of T start to drop in men due to
> > the increase in SHBG.
>
> > Also, in order to get the mutations necessary for cancer to occur, it
> > helps to have uncontrolled cell growth, since the more inappropriate
> > cell divisions that occur in any tissue, the more likely that the
> > exact mutations that are needed to cause cancer will occur. In the
> > prostate, high local levels of estradiol are all that is needed to
> > start the uncontrolled growth of prostate cells, and this can happen
> > at any time following puberty.
>
> > Ed Friedman
>
> Ed
> What are the readings for DHT - it is many times more potent than T.
> With low T and high SHBG, it is definitely possible to have very high
> DHT levels. If the DHT levels are not studied then the paper is
> incomplete and no conclusions can be established.
>
> From my experience on high dose Casodex, I had T in the upper
> reference range, SHBG was above reference range, my estradiol was
> above the reference range and my DHT was way above the reference range
> despite the 60% reduction by Proscar. In my case, I believe, the DHT
> was the dominant reason for my PSA rise of my androgen dependent PCa.
>
> Lud

Lud,

The median level of DHT was 0.67 ng/l. The median level of DHT for
those who died of PC was 0.54 ng/l. The median level of DHT for those
who did not die of PC was 0.79 ng/l.

Ed Friedman

On April 14, Ed Freidman replied to Lud, in pertinent part:

> The median level of DHT was 0.67 ng/l. The median level of DHT for
> those who died of PC was 0.54 ng/l. The median level of DHT for those
> who did not die of PC was 0.79 ng/l.

Which means exactly nothing regarding the alleged "association" of
5-alpha reductase inhibitors with advanced PCa.

Somehow, I can't drill into certain heads the fact that "association"
(remember the cock & sunrise) does not prove, nor is it evidence of, a
causal relationship.

I can hardly balance my checking account, but by God I know how to
evaluate evidence.

Regards,

Steve J

On Apr 14, 6:42 pm, Steve Jordan <mycrofts...@cox.net> wrote:
> On April 14, Ed Freidman replied to Lud, in pertinent part:
>
> > The median level of DHT was 0.67 ng/l. The median level of DHT for
> > those who died of PC was 0.54 ng/l. The median level of DHT for those
> > who did not die of PC was 0.79 ng/l.
>
> Which means exactly nothing regarding the alleged "association" of
> 5-alpha reductase inhibitors with advanced PCa.
>
> Somehow, I can't drill into certain heads the fact that "association"
> (remember the cock & sunrise) does not prove, nor is it evidence of, a
> causal relationship.
>
> I can hardly balance my checking account, but by God I know how to
> evaluate evidence.
>
> Regards,
>
> Steve J

Steve,

I was saying nothing about any "association" of 5AR inhibitors and
advanced PCa. The DHT levels were what were observed at diagnosis for
PCa. Those men with lower DHT levels at that time were more likely to
die within the next 15 years. Either this is just a coincidence or
more aggressive PCa lowers DHT or low DHT causes more aggressive PCa.
I believe that the last choice is the most likely, simply because (as
I explained in my model) lower DHT results in higher levels of Bcl-2,
which by definition (all else being equal) makes any PCa more
aggressive. If you have reasonable explanations for how this could be
an unrelated coincidence or how faster growing PCa can lower the
entire body's DHT level, then you are free to put them forth.
Although no mention was made in the paper, I strongly suspect that
those men with lower DHT also had lower levels of free T.

Ed Friedman