"One of ours"

[Sam]

Below is a copy of a recent post on another public domain site. I cannot reply directly so here is my comment on p-d-t@google.

Leo was indeed "one of ours" and keen to know about & try types of treatment that would permit his androgen levels to rise to a point where he could function as a normal guy. [Aside: with a PSA of 0.2 he had no other reason than to than to get his tetsosterone working for him].

Leo went to see Morgentaler, because he believed Morgentaler was an expert in the area of treating hypogonadic men who had experienced a history of PC. It seemed feasable that Morgentaler would offer a degree of safety that internet correspondence with others (the likes of us for example) could not offer. After that we heard _not a lot_ from Leo until the bad news came trickling in.

It appears that Morgentaler was not monitoring bloods regularly or spending enough time with individual high risk patients. Morgentaler expected his "saturation model" to behave fully predictably and automatically reduce PSA after the saturation point.

This somewhat cavalier attitude failed to instill a sense of caution and need for double - checking of results. It had disastrous repercussions.

When Leo's symptoms failed to go away, and when his PSA velocity failed to brake after the predicted saturation point Morgentaler seemed to let him go. I am not in possession of the full story since Leo seemed reluctant to keep us posted until long after the event, making corresponding with him very frustrating.   

So Patrick & all Leo tried estrogen and LHRH-a ? is that correct ?

I always have emphasised the need to monitor every fortnight when PSA  velocity is rising strongly in that ill-famed pre-saturation region. Described in my book ISBN 9780954993511: If during this time PSA keeps rising then you need to remove the stimulus. I have no idea what Morgentaler was giving Leo or how effective it was after deciding not to keep chasing the elusive saturation point.

I deeply regret not being in touch with Leo on a weekly basis through those times. As patients up against a myriad of conflicting and not so patient oriented forces, we are the only reference point in our illness. I hope to see the value of Internet groups hold and not go under as they offer a new way of presenting evidence based data that free from the distortions we so often find in medically / pharmaceutically funded research.

Sam.


>> To put Leo's numbers in perspective, his RP failed in 2002 as did salvage radiation in 2003.  His PSA was 2.2 in 2004, when he began using Q+.  By 2008, people were reporting ineffective lots, so he decided to try Morgentaler.

The PSA=0.2 result is the last while on Q+, & we have no idea what it would have been 8 months later, if he had discontinued Q+ & skipped TRT.

It seems that his T went from 25 to 300 in one month, while his PSA jumped to 28.  Morgentaler's Saturation Model would have predicted that his PSADT at that point would have leveled off.  i.e. extra T would not make the cancer more aggressive than it already was after one month.

After 8 months, his T had only reached 750 - he was aiming for 1,000.  He reported an E2 of 37, which is high.

It looks as though he had two TRT sessions, with Q+ in between (?).

Ultimately, he wished he had backed away when the PSA hit 50 & T had not reached 1,000.

The one person who might be able to give a coherent possible explanation is Morgentaler, but he is unlikely to do so.  He really ought to, though, since Leo's case undermines the saturation model.

The curious thing in that, while his PSA rose on TRT, it continued to do so when he was given Lupron & E2 patches.  i.e. he had become resistant to treatments that he had never received.

Puzzling & disturbing.

-Patrick

 

Dx04 @ 56 (DRE nodule 2002) |bPSA 3.3 (0.8 when nodule found)| GS=4+3, RP - no LN, no SV, but PSA nadir-0.3. DT=3 months Salvage RT 2005. Again, nadir=0.3. No HB. Arimidex. AndroDerm.

---

From: tinycamera1 <DavidCohen99@...>
To: natural_prost...@yahoogroups.com
Sent: Sunday, November 18, 2012 12:23 PM
Subject: [NTPC Yahoo Group] Re: [NTPC Yahoo Group Leo and TRT

 

To David and Dominick:

I just spoke to Leo Frawley's wife (Leo used Frawlele on this forum), and it's been over a year since Leo's death. His PSA was 0.2 before he did TRT, and she directly blames it for his death, and especially the doctor that did it.

She was considering posting here. We'll see.

David

[Patrick OShea]

Sam,

Yes, it is difficult to piece together the chronology of Leo's experience with Morgentaler.  But the following, in his Feb 7, 2011 words, indicate the outcome.  He died Sep 7, 2011  -  7 months later..

"Once my PSA hit 89 ng/dl I was sent in for bone and Ct scans. Findings pointed to progression to the bone and lymph system. I'm am currently under the care of an Oncologist but my PSA has continued to rise even with the use of Lupron and estradiol patches."

Leo was a stoic, & too much of a nice man to complain about his treatment under Morgentaler.  Being an engineer, I can't imagine him going through the M experiment without keeping good records, but he was disinclined to report back until his became a cautionary tale.

He was using 4 pumps of AndroGel daily:

http://www.androgel.com/using-androgel.aspx

Prior to using T, the only hormone therapy he had used (as far as I can tell) was Q+ (now presumed to be DES).  The Q+ was still working for him, but newer batches of Q+ were not working for anyone, so he knew that he needed to find a different approach before his supply ran out.

The questions I have are:

i)  Is it reasonable to believe that his time on TRT affected his ability to respond to Lupron?  Perhaps he would have had the same problem in going directly from Q+ to Lupron?

ii)  DES has been used in CRPC cases - perhaps he would have responded to DES?

-Patrick

--
--
Prostate cancer is an exceptionally heterogenous disease. What is good for one man may not be so kind on the next. Be sure to research and test any new supplement or treatment before adopting it - and in any case run it past a medically qualified person for a second opinion.
 
 
 

[EdF]

Dr. Morgentaler is correct in his assumption that T does not stimulate PCa growth, but he is wrong in thinking that it is safe to give T to men with PCa. The problem is that T gets converted to E2, quite likely to a level in the prostate that would be ~10 times greater than the serum level. E2 is what cause PCa initially and it stimulates PCa growth. E.g., in LNCaP, E2 not only stimulates growth but this stimulation is unaffected by the administration of bicalutamide (Castagnetta et al., 1995, "Growth of LNCaP Human Prostate Cancer Cells is Stimulated by Estradiol via its own Receptor", Endocrinology, 136:2309-2319.

If you think about it logically, E2 (and not T) must be the villain in PCa. If T were the culprit, then there should be an increasing number of copies of intracellular androgen receptor as PCa evolves, which is not the case (only in low DHT or ADT situations, then intracellular androgen receptor increases in number). However, ER-alpha goes from almost undetectable in normal prostate epithelial cells to being present 94% of the time in CRPC. In fact, ER-beta also decreases as PCa evolves, since ER-alpha stimulates cell division and increases the anti-apoptotic protein Bcl-2, whereas ER-beta decreases Bcl-2.

My own opinion is that whenever T is administered, it must be accompanied by an aromatase inhibitor. Also, enough estriol should be administered to interfere with the action of estradiol and estrone to bind to ER-alpha.

Ed Friedman

[Patrick OShea]

Ed,

Everything I have read on this subject in the past +8 years leads to the same conclusion.

A big debate concerning aging men, where hypogonadism & PCa become increasingly common, is whether TRT is safe.  Studies seem to show that TRT does not unmask occult PCa.  However, there is a window of vulnerability while T climbs through the hypogonadal range.  E2 could well be dominant for an extended period.

Some men with undiagnosed PCa might have diagnosis delayed if T quickly rises to a safe level, whereas others have increased risk if T remains in the doldrums.

But it is incomprehensible to me that doctors fail to look at the complete hormone picture.  Elevated E2 is a mortality risk factor.

LEF:  http://www.lef.org/magazine/mag2010/may2010_Why-Estrogen-Balance-is-Critical-to-Aging-Men_01.htm?source=search&key=estradiol

My feeling is that E2 should virtually be suppressed while T is being restored.  Furthermore, the aim should be a speedy restoration - & doctors should not be satisfied with a T of 350 ng/dL.  The observed "normal" range is so wide, common sense would suggest that they aim for the upper tertile, say.  Or the normal range for a 20 year old.

Once T is at a healthy youthful level, E2 would be permitted to drift upward, but not beyond the 20-30 pg/mL range recommended by LEF.  When PCa is present, 12-20 might be a safer range.  Below 12 risks weakened bones from what I read.

Incidentally, Myers has discounted a role for E2 in progression.  That's OK, he has shifted his position on a number of issues over the years.  I admire an open mind.  What I dislike about his mindset is that he will use studies to justify a new view, but will not use such a rigorous approach when holding to the status quo.

-Patrick

 

Dx04 @ 56 (DRE nodule 2002) |bPSA 3.3 (0.8 when nodule found)| GS=4+3, RP - no LN, no SV, but PSA nadir-0.3. DT=3 months Salvage RT 2005. Again, nadir=0.3. No HB. Arimidex. AndroDerm.

---

From: EdF <e...@math.uchicago.edu>
To: prostatic-dise...@googlegroups.com
Sent: Monday, November 19, 2012 2:06 PM
Subject: [PDT:1246] Re: "One of ours"

[EdF]

Patrick,

It is interesting to note that Dr. Morgentaler also discounts the role of E2 in PCa progression. In fact, I wrote a letter to the editor to the Journal of Urology to point out his folly in this regard. He replied by citing an article that showed no correlation between serum E2 and PCa as "proof" that I was wrong. When he wrote that, I already knew that there was a strong correlation between E1 and PCa (http://www.ncbi.nlm.nih.gov/pubmed/20451981). However, there is no way to write a response to a response to a letter to the editor, so I never got to make my point. Fortunately, this will be covered in my upcoming book in which I point out that since E1 cannot cause PCa or BCa (E2 does), then PCa must be the cause of the high E1. This makes sense since there is a selective growth advantage for PCa to have more activity of ER-alpha (which is what E1 does). Since E1, like E2, can only arise from the action of aromatase, this is even more evidence of the necessity of using aromatase inhibitors in the treatment of PCa. If E3 is used to maximize ER-beta activity, then some of it will be converted to E2. If TRT, aromatase inhibitor (none of which are 100% effective yet), and E3 is used, then E2 levels should be high enough to maintain minimum health. If not, E2 can be added instead of lowering the amount of aromatase inhibitor. What matters is keeping local levels of E2 as low as possible within the PCa, and aromatase inhibitors are the only way to accomplish that.

Ed Friedman

[Patrick OShea]

Ed,

You touch on a point that is almost always overlooked - serum tests are unreliable windows into local PCa conditions.

I have mostly avoided drugs.  The 3 I do take are not because I need them for general health:  Arimidex, Metformin & Simvastatin.

I have no problems with my cholesterol numbers, but PCa/cholesterol studies show that there is a greater uptake & synthesis of cholesterol in PCa cells, & that high levels do not bode well.  I will stay on Simvastatin no matter how low serum cholesterol goes.

Aromatase is often overexpressed in PCa.  Most doctors would probably think one crazy for using a powerful aromatase inhibitor & a low-dose E2 patch.  Makes sense to me.  LOL

-Patrick 

 

Dx04 @ 56 (DRE nodule 2002) |bPSA 3.3 (0.8 when nodule found)| GS=4+3, RP - no LN, no SV, but PSA nadir-0.3. DT=3 months Salvage RT 2005. Again, nadir=0.3. No HB. Arimidex. AndroDerm.

From: EdF <e...@math.uchicago.edu>
To: prostatic-dise...@googlegroups.com

Sent: Monday, November 19, 2012 5:42 PM
Subject: [PDT:1248] Re: "One of ours"

Patrick,

It is interesting to note that Dr. Morgentaler also discounts the role of E2 in PCa progression. In fact, I wrote a letter to the editor to the Journal of Urology to point out his folly in this regard. He replied by citing an article that showed no correlation between serum E2 and PCa as "proof" that I was wrong. When he wrote that, I already knew that there was a strong correlation between E1 and PCa (http://www.ncbi.nlm.nih.gov/pubmed/20451981). However, there is no way to write a response to a response to a letter to the editor, so I never got to make my point. Fortunately, this will be covered in my upcoming book in which I point out that since E1 cannot cause PCa or BCa (E2 does), then PCa must be the cause of the high E1. This makes sense since there is a selective growth advantage for PCa to have more activity of ER-alpha (which is what E1 does). Since E1, like E2, can only arise from the action of aromatase, this is even more evidence of the necessity of using aromatase inhibitors in the treatment of PCa. If E3 is used to maximize ER-beta activity, then some of it will be converted to E2. If TRT, aromatase inhibitor (none of which are 100% effective yet), and E3 is used, then E2 levels should be high enough to maintain minimum health. If not, E2 can be added instead of lowering the amount of aromatase inhibitor. What matters is keeping local levels of E2 as low as possible within the PCa, and aromatase inhibitors are the only way to accomplish that.

Ed Friedman

[Henry Campbell]

Ed I hope you'r right !!

I have been on high T for over 8 years. Based on some of your comments I am now taking Arimidex and Finasteride. On your comment "My own opinion is that whenever T is administered, it must be accompanied by an aromatase inhibitor. Also, enough estriol should be administered to interfere with the action of estradiol and estrone to bind to ER-alpha."  could you expand on estriol and estrone ? I take 1/4mg of Arimidex every three days and 5mg Finasteride per day.  

Hope you hve  good Thanksgiving and don't over do the turky'

Henry

//////////////////

[EdF]

On Monday, November 19, 2012 7:08:34 PM UTC-6, Henry_soup wrote:

Ed I hope you'r right !!

I have been on high T for over 8 years. Based on some of your comments I am now taking Arimidex and Finasteride. On your comment "My own opinion is that whenever T is administered, it must be accompanied by an aromatase inhibitor. Also, enough estriol should be administered to interfere with the action of estradiol and estrone to bind to ER-alpha."  could you expand on estriol and estrone ? I take 1/4mg of Arimidex every three days and 5mg Finasteride per day.  

Hope you hve  good Thanksgiving and don't over do the turky'

Henry,

If you are not experiencing any rise of your PSA after 8 years on your treatment protocol, then you should keep doing it. If it ain't broke, don'[t fix it:)

However, to answer your question about the estrogens, estrone binds 5 times more strongly to ER-alpha than to ER-beta; estriol binds 3.5 times more strongly to ER-beta than to ER-alpha. Estradiol binds with equal strength to both ER-alpha and ER-beta. As PCa evolves, you end up with more and more ER-alpha and less and less ER-beta. Also, you have more estrone and lots of estradiol (high local aromatase activity). Estriol works by interfering with the binding of estradiol to ER-alpha. Bascially, a hormone binds to a hormone receptor in the cytoplasm, then that complex migrates to the nucleus and binds to the appropriate receptor on the DNA and causes specific proteins to be upregulated or downregulated. When a hormone with low binding affinity binds to a hormone receptor, it is likely to fall off before it can reach the receptor on the DNA. Therefore, estriol would decrease the effectiveness of estradiol and estrone to activate ER-alpha. However, if there is too much estriol, then as soon as it dissociates from the hormone receptor, another molecule would be present to take its place. So the goal is to have enough estriol to barely saturate ER-beta but nowhere near enough to saturate ER-alpha. No research has been done to determine what the optimal amount of estriol might be, so at this point it is a pure guess. My own guess is to have slightly more estriol than the combined total of estradiol plus estrone, but this is almost certainly not the optimal amount of estriol to use.

One other point is that I believe that saliva testing is the best way to determine your levels of estradiol, estrone, and estriol. Also, the only way to lower your levels of estradiol and estrone is through aromatase inhibitors.

Ed Friedman

[Sam]

Ed & All -- Just picking up on this. How about a non-aromstizable for of T such a Pro-Viron a derivative of DHT?

And what about saliva testing? Where can we get this done across international borders ?

Thanks -- Sam.

[Sam]

Interesting discussion. Can't say I daisgree with much. If only the
professors would trythese ideas out instead of running along the track
made 70 years ago

Pat asked:

The questions I have are:

i) Is it reasonable to believe that his time on TRT affected his

ability to respond to Lupron? SAM> I think T upregulates AR, so
its(T) removal and insertion of LHRH-a should enhance the 'castration
response' [ By this I mean the undermining of malignant cells by
poisoning them ... of calreticulin - heightening the toxic milieu in
which the PC cells found themselves. ] Isn'tthis why IHT works in
general better than uninterrupted ADT by resetting the sensitivity
switch & promoting another round of apoptosis ?

PAT> Perhaps he would have had the same problem in going directly from
Q+ to Lupron? SAM> Q wll have a different effect on AR so I am not
sure here. Maybe not such a proufound effect on PC cell kill.

PAT> ii) DES has been used in CRPC cases - perhaps he would have
responded to DES? Perhaps so. DES has peculiar properties. It kills PC
but it drives BC growth through ERalpha. Both estradiol and DES
increase the risk of male BC.

Sam.

[EdF]

On Wednesday, November 28, 2012 6:30:23 PM UTC-6, Sam wrote:

Ed & All -- Just picking up on this. How about a non-aromstizable for of T such a Pro-Viron a derivative of DHT?

And what about saliva testing? Where can we get this done across international borders ?

Thanks -- Sam.

Sam,

The following info is from a saliva testing company called ZRT (www.zrtlab.com). " ZRT does not typically cover the cost of samples being returned from outside of the US. International testers will need to purchase return shipping at their own expense.  These samples are not bio-hazardous so as long as they are packaged according to the Collection Instructions, there should not be any restrictions imposed by customs.

I am not familiar with the pros and cos of Pro-Viron, but on principle I am opposed to modified hormones such as methyl-testosterone or methyl-dihydrotestosterone(Pro-Viron).

Ed Friedman

[EdF]

On Wednesday, November 28, 2012 7:11:24 PM UTC-6, Georgia Sam wrote:

Interesting discussion. Can't  say I daisgree with much. If only the
professors would trythese ideas out instead of running along the track
made 70 years ago

Pat asked:
The questions I have are:

i)  Is it reasonable to believe that his time on TRT affected his
ability to respond to Lupron?  SAM> I  think  T upregulates AR, so
its(T)  removal and insertion of LHRH-a should enhance the 'castration
response' [ By this I mean the undermining of malignant cells by
poisoning them ... of calreticulin - heightening the toxic milieu in
which the PC cells found themselves. ]  Isn'tthis why IHT works in
general better than uninterrupted ADT by resetting the sensitivity
switch & promoting another round of apoptosis ?

Sam,

Actually, the amount of iAR goes up during ADT (PCa is desperately trying to make more calreticulin) and goes down during TRT (too much binding to iAR would increase AS3 production and stop cell division). Alternating between the two is what the researchers from Johns Hopkins did in their BAT paper - going 2 weeks with superphysiological levels of T alternating with 2 weeks of close to castrate levels of T. I'm hoping they come out with a full paper on their results, but as mentioned before, the only info they have revealed so far is that 2 of 4 men with CRPC had PSA drops of over 50% using this protoc

Ed Friedman