Hormone Refractory Question...

Good question is it complicated to some degree I can refer you to Journal of Urology Article and you can learn about it alot more. PCa cells have receptors on the cells, oddly enough regardless of 'T' level you have, these cells take in (accept) the DES (estrogenic drugs of various types) and can cause direct apoptosis (direct kill)..says so in Journal Article. Does it kill them all???, that is actually either a no answer or unknown to some degree, in select patients maybe (there exists an old Journal Article-relating to anectdotal cure-but is not in the psa era so maybe it wasn't definable, sure looked good anyway). There are cases of patients using such drugs (mostly blasts from the past), that lived so long they died from other ailments not PCa related (one by a poster on this forum-a grandfather). This was used for decades as front line treatment not just hrpca patients and worked well other than the overdosing with 5-mg and no aspirin or blood thinners...those caused the negatives...other wise was very useful and still is, 1-mg found safe per Journal Article. Note unlike LHRH or casodex....No hot flashes, no sweating, they say no bone density loss or memory loss...it has much different mechanisms at work. On bones it talks about osteoclasts and osteoblasts...read in article to comprehend, it is much different and  doesn't ruin your bones. (gee no doc mentioned these things or the drug probably). I found that 1/2 mg likely will work too. Technically I don't see why one couldn't use this drug at any level of PCa,  doesn't have to be 2nd line or towards final line, although docs using such put this as 2nd line therapies. So where are the abstracts in low or med. risk patients??? (no money zone???)

Unlike LHRH this can work on cells that become resistant to Lupron etc and casodex, whereby you have a rising psa level and likely your 'T' was increasing and was the cause for the psa level increases, monitored of course. There is a rare exception (like usual) in PCa whereby very aggressive types give off no psa, low number doesn' always mean safe, onco-docs monitor various markers and other tests to determine what is going on in such patients. Estrogenics could still be useful even in those highly aggressive situations, I have witnessed such in a couple patients, the bad news is the duration could be alot shorter or even lousy. Some of those rare very aggressive or variant PCa's don't respond well to about anything, but they are very rare...and very worrisome. Tried to answer  this stuff not sure it is clear. Someone else may have something to say on it, besides bashing it based upon non-useage and not reading the Journal Article.

ttp://ffyates.com/prostate/des.pdf     (Journal of Urology, Nov. 2003)

(only the messenger, if you don't like the message, find other targets )

Zufus:

Something I always wondered about in HRPCA:

Do the cancer cells start out getting killed by the HT and then mutate and become resistant? Or are there a very small number of cells that are HRPCA from the start. In this scenario, as the other cancer cells die, these cells keep multiplying and eventually are the noticeable ones.

Mel

Thanks John, looks like a great answer and decently said, you have been really busy on PCa analysis in totality on all fronts. You have put more time into studying up than me and probably a lot of people and it shows, kudos in your direction.

Tarhoosier- good reply also, thanks for adding

Mel- Johns reply is what I have heard also for your questions

Our best appearing hope is at the cellular level to either repair the DNA that caused the normal cells to change to PCa, or effect the DNA in PCa by mechanisms like dendretic cell action, or some kind of genetic engineering concepts. This kind of stuff is being worked on right now and the market is axious for it. Logically this would be way better than all the drugs being used right now. Could become the break through.

This is right from the CDC own web site on DES:

http://www.cdc.gov/des/hcp/nurses/history.html

Another way to present this is to know that at diagnosis every man has some PCa cells that have the POTENTIAL to divide in a low testosterone environment. Maybe that function exists or maybe the dna has mutated such that this function will arise in the future, while in other cells it will not. There is a term "genetic drift" which implies that some cells are without the function currently but in the future will develop this nasty feature. Some say that low testosterone environment causes this function, others say it reveals this function, while others say it allows it to develop at a later time.
Gleason score is relevant here also. Higher G means it is more likely that dna changes have created this adaptation. Men with G 3 and 2 can go on hormone therapy for long periods, decades, without this adaptation appearing.

Just wondering why folks go with DES vs. estrogen (or estradiol?) transdermal patches? I've read that some side effects might be lessened with the patch. Do they both do the same thing? I'm not trying to argue for/against DES, just trying to understand if there's an advantage to using DES in this situation?