INVITATION to join -=- http://health.groups..com/group/21CUPC/ -=- androgen challenge -vs- baseline testosterone -=- ws -=- Lupron newbie

[Guest guest]

Dear Group,

 

Below is an example of the kind of discussion I would like to nurture at the new

group I am running. You can join it at:

 

http://health.21CUPC/

 

If anyone wishes to take part, or simply listen and learn, please feel free. The

group will be based on what I have written in a manuscript I call: " A 21st

Century Understanding of Prostate Cancer " which is available at this web site:

 

http://www.prostateman.org/

 

Anyone with a history of reviewing papers may obtain a copy free of charge. I do

however insist on some 'feedback' after you have read it ;-)

 

Kind regards,

 

Sammy.

 

http://health.21CUPC/

 

 

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

 

 

Donna said:

 

> I hope that you had a baseline testosterone test done as well so that you know

what your normal level was when you started.

 

 

Sammy:

 

I agree with this baseline testosterone testing but I am unsure why Donna

mentions it in this context.

 

In my searching of P2P archives I have never found a reference to " baseline

testosterone " or " baseline androgen " So is this a new development for you Donna

? Do your colleagues agree with this procedure, and what are your reasons? I

would be very grateful to learn more about this apparent change in your

direction.

 

In my view, MERELY testing baseline androgens in the context of using those

levels (either testosterone or DHT) as the target levels post HB treatment is

absolute folly and will lead to disease recurrence in double quick time. The

level that you will be targeting post HB is the very level that was sustaining

the cancer before it was brought under control. Are you now going to subject the

patient to the same hormonal milieu which drove his cancer in the first place?

 

The first problem arises out of the fact that men Dx'd PC almost invariably have

a low androgen status. For these men, baseline testosterone testing will give a

good prognostic predictor of success with HB since the longer a person has been

hypogonadic prior to Dx, the less likely he will respond to HB and the more

likely will he become HRPC. This is documented in my paper at

http://wwww.prostateman.org/

 

 

The second problem arises because baseline testosterone values at Dx will

reflect a lower than normal androgen level for that individual, up to that point

in his life. [ The LEF article on Male Hormone Modulation Therapy points out

quite clearly that what some labs consider 'normal androgen levels'

(testosterone and dihydrotestosterone) are often way below normal for a 30 year

old. Since normal 30 year old men do not get prostate cancer, that is the target

level we should aim for when coming OFF HB.] To continue .. this baseline

testosterone value can be used as a pointer to the next step in treatment - but

only a pointer, NEVER a target.

 

I have already mentioned the prognostic value of low testosterone at the point

of DX in context of HB treatment. If we now take (instead of a single baseline)

testosterone value as a series of values pre-treatment along with PSA then we

get a picture of what the disease is doing. If a low testosterone / rising PSA

is evident and if it possible to raise that level of testosterone to above

normal male levels and observe the changes in PSA and symptoms we may find in

many cases that the disease resolves itself.

 

This is the whole point of Part 4 and 5 in the manuscript you have before you

Donna. Cross cultural comparisons show that when different medical systems (e.g.

TCM) treat this disease as a form of deficiency, addressing it with tonifying

means, then prostate cancer never reaches the stage it does in western medicine.

 

If the disease does not resolve itself with this 'androgen challenge' then

timely treatment with abarelix (24 hours to castrate status) will ensure no long

term damage is done. Indeed, the androgen challenge can be repeated with renewed

intent after six months of castration therapy which is long enough to have

knocked out most prostate tumour cells.

 

I have to say something about 'PSA slavery' - my doubts about the relevance of

getting a man's PSA to 'undetectable' as so many recommend. There is no need to

go to such extreme lengths because androgen challenge on a small remaining group

of active PC cells after 6 months treatment with HB will have much greater

success than on a larger tumour mass - of which not all may be exposed to the

cell kill effect produced my normal healthy levels of androgen (testosterone AND

dihydrotestosterone).

 

The full text of both these papers is available:

 

1: Endocrinology. 2002 Jul;143(7):2708-14.

 

Mechanism of androgen action on cell proliferation: AS3 protein as a mediator of

proliferative arrest in the rat prostate.

 

Maffini MV, Geck P, Powell CE, Sonnenschein C, Soto AM.

 

Department of Anatomy and Cellular Biology, Tufts University School of Medicine,

Boston, Massachusetts 02111-1800, USA.

 

Androgens control the proliferation of their target cells first by increasing

cell proliferation and later by inhibiting the proliferation of those same

cells. Recently, we reported that the AS3 protein mediates the androgen-induced

quiescence in androgen-target human cell lines. Our aims were to investigate the

expression of the AS3 protein in the rat prostate in situ and in human cells in

culture. Adult rats were separated into four groups (intact, castrated,

castrated plus 3-d testosterone propionate replacement, and castrated plus 7-d

testosterone propionate replacement). S9 cells expressing a

tetracycline-regulated sense AS3 were also used. AS3 was expressed in the nuclei

of over 90% of the epithelial cells and about 40% of the smooth muscle cells of

the intact rat prostate. AS3 was not expressed in castrated rats or during the

proliferative phase of androgen-induced regeneration. It was expressed in intact

and castrated animals when the prostate has reached adult organ size. The AS3

protein was not expressed in cells that incorporate bromodeoxyuridine. These

data suggest that AS3 is a mediator of the proliferative arrest in the normal

rat prostate in situ and human prostate cell lines and that its expression is

androgen-induced.

 

PMID: 12072405 [PubMed - indexed for MEDLINE]

 

 

 

2: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10185-90.

 

Androgen-induced proliferative quiescence in prostate cancer cells: the role of

AS3 as its mediator.

 

Geck P, Maffini MV, Szelei J, Sonnenschein C, Soto AM.

 

Department of Anatomy and Cell Biology, Tufts University School of Medicine, 136

Harrison Avenue, Boston, MA 02111, USA.

 

In the prostate gland of adult mammals, most epithelial cells are in a state of

proliferative quiescence. Androgens regulate this effect by inducing cell cycle

arrest in the G(0)/G(1) phase. Potential mediators of this androgen-induced

proliferative shutoff were identified by means of subtracted cDNA libraries. The

expression pattern of one of these sequences, AS3, strongly correlated with the

expression of the androgen-induced proliferative shutoff both temporally and

dosewise. The AS3 gene is located on chromosome 13 q12.3, in close proximity to

the BRCA2 gene. The loss of chromosomal regions where AS3 alleles are located

correlates with various human cancers, including prostate. The biological effect

of AS3 was tested in two stable cell lines, one expressing sense and another

expressing antisense AS3 constructs, both under tetracycline regulation. S9

cells were obtained by retroviral infection with virions containing a

tetracycline-regulated sense AS3 construct. In these cells, sense AS3 was

negatively regulated by tetracycline. Tetracycline withdrawal increased the

expression of AS3 mRNA and protein. The expression of tetracycline-regulated AS3

resulted in inhibition of cell proliferation. A4 cells were obtained by

retroviral infection with virions containing a tetracycline-regulated antisense

AS3 construct. Vector-driven expression of antisense-AS3 blocked the induction

of androgen-induced endogenous AS3 mRNA and blocked the inhibitory effect of

androgens on cell proliferation. Tetracycline-regulated expression of the empty

vector control had no effect on cell proliferation. These experiments strongly

suggest that AS3 is a mediator of the androgen-induced proliferative shutoff.

 

PMID: 10963680 [PubMed - indexed for MEDLINE]

 

 

-

 

 

 

I would hope that your doctor pre-treated you with an anti-androgen prior to

the administration of the Lupron, but it seems not since you didn't mention

that. Your testosterone level will therefore actually increase for a short

time before falling, hopefully to castrate levels. Also, in the event that

you exhibit any sort of allergic reaction, I would have preferred the first

administration of the medication to be a one month depot. I hope that you

had a baseline testosterone test done as well so that you know what your

normal level was when you started.

 

The androgen deprivation syndrome is covered in the Primer. Typical

symptoms include impotence, loss of libido, mood swings, hot flashes, night

sweats, weight gain, loss of muscle tone and muscle mass and other less

common side effects.

 

One thing you absolutely have to watch on androgen deprivation therapy is

your bone integrity. It would be wise to have a qCT scan (a better

diagnostic test than the standard DEXA scan) and to start on a

bisphosphonate if your bone integrity is or becomes compromised. Oral

medications like fosamax and actonel can be used. Better yet, the infused

drugs Zometa (preferred) and Aredia can be used to effectively reverse the

bone loss associated with androgen deprivation therapy.

 

To see what else your doctor might have overlooked in educating you about

the treatment you have already begun, you might want to read the section on

androgen deprivation therapy in the Primer. I guarantee you a better

understanding of what you will be dealing with.

 

Donna.

 

 

 

 

 

Hi Group

Just had my first dose of Lupron and thought I would join the group to

find out what to expect that my Doc didn't want to mention. Brief

history: I am 63, had a rad prost. in 92, had a rising psa in 93,

had radiation in 93, then a rising psa in 98 (very low but doubling

every four months), psa got to 2 in 00, then fell back to 1 over the

next three years, then started up a year ago and went from 1.8 to 4.2

from May to Aug. Had my first 3 mo dose of Lupron yesterday and will

have another in Dec then cycle off and on.

Would appreciate any comments on what to expect in way of side effects.

Thanks