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61Frank 04-26-2012 03:10 PM

High PSA - negative biopsies - Low Testosterone - Connection ??
I have some interesting things going on - Sorry for the length of the post but I am trying to give as much information as possible.

PSA increased from 2.7 in 2007 to 6.1 in 2008 after regular Dr. physical exam.

Sent me to a Urologist - DRE showed enlarged prostate - Biopsy negative

PSA increased to 14.6 in 2009 - Second biopsy done - also negative

Sept. 2009 - had a Microwave procedure done to shrink prostate. Limited results.

Between 2009 and 2011 PSA checked almost every 4 to 6 months and has been ranging from 14 to 24 sometimes going up or down as much as 4 points between tests.

Additionally, over the time period 2009 to 2011 passed well over 100 uric acid bladder stones ranging from sand size to almost 1/4 inch in diameter.

Urologist had CAT scan done which showed nothing unusual except for prostate pushing into bladder with calcifications up to 1/2 inch in diameter.
Dr. felt these stones could be causing the fluctuating PSA readings.

I had these stones removed in Jan 2012. PSA was 22.1

PCA - 3 test performed also in Jan - Score was 11. Uro said that`s good.

Uro put me on antibiotic for 30 days and PSA is now 22.6. He also had a testosterone check done since I told him I had been feeling tired and the testosterone check came back as a 150 which he said is pretty low.

He said he would be reluctant to starting any treatment for the low testosterone without another biopsy which I am now scheduled to have performed next week.

I am really confused - I have read some places that low testosterone can cause PSA readings to increase. I have also heard that testosterone treatment can increase cancer cells.

Would appreciate anyone`s thoughts on my situation.

Thanks - Frank

Tall Allen 04-26-2012 07:34 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Congratulations on your low PCA3 score and your 2 negative biopsies. I think you would feel pretty confident that your rise in PSA, which is notoriously non-specific for cancer, is due to other causes, probably a combination of BPH and irritative reaction/prostatitis. Is there a reason you're not taking finasteride or dutasteride to shrink your prostate? They will also make your PSA go down so that any increase afterwards will be more specific to PC, after ruling out irritation from stones/prostatitis.

Your questions about testosterone comes up so often in my prostate cancer support group that I finally wrote a paper, complete with references, that you can hand to your urologist. To clear up the confusion about testosterone (T) and PC unequivocably I will state that there is no evidence to show that any amount of testosterone above castrate levels does anything to cause PC, to accelerate the growth of PC or to cause higher risk PC. Just the opposite -- naturally [U]low[/U] testosterone is associated with higher risk PC.

The way I handled my doctor was I emailed him the research studies (below) and asked to discuss it at our next appointment. He said he had no problem with Testosterone Replacement Therapy (TRT) after we are assured that my PSA has reached nadir (or, in the case after RP, undetectable levels). He said he wanted to start slow and monitor PSA as we go along.

I would also point out to your doctor the dangers of low T, and its effect on quality of life. I would ask your doctor what evidence is there that testosterone fuels PC in early-stage (Gleason 6) disease? If he remains recalcitrant, it's your right to get another opinion.

Here’s what I sent my oncologist:

[SIZE="4"][FONT="Arial"]Research has consistently failed to find an association between endogenous testosterone (T) levels and risk of PC development, and I think that most authorities would agree that T does not cause PC. This has been substantiated by many prospective controlled research studies. For example:[/FONT][/SIZE]

[SIZE="3"]In a very highly regarded and oft-quoted study, data from 18 worldwide prospective studies were pooled in this analysis of 3886 men with PC and 6438 controls. They found that serum concentrations of sex hormones were [U]not[/U] associated with the risk of PC.[/SIZE]
[SIZE="2"][I]Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies
J Natl Cancer Inst. 2008 Feb 6; 100(3): 170-83[/I][/SIZE]

[SIZE="3"]In this interesting research, they examined frozen serum samples of 166 men who were originally cancer free but were diagnosed with PC 24 years later and found [U]no[/U] association between serum T levels and later PC development.[/SIZE]
[SIZE="2"][I]Serum T and SHBG concentrations and the risk of PC: a longitudinal study
Heikkila et al, Cancer 1999 Jul 15; 86(2):312-5

[SIZE="3"]Another tissue study with 727 PC cases and 889 matched controls found PC risk was [U]unrelated[/U] to serum T:[/SIZE]
[SIZE="2"][I]Endogenous sex hormones and the risk of prostate cancer: a prospective study
Weiss et al. (Natl Cancer Inst, NIH) , Int J Cancer 2008 May 15;122(10):2345-50[/I][/SIZE]

[SIZE="3"]In a small randomized double-blind placebo controlled study, researchers at UCLA found that TRT raised T serum levels but had little effect on T prostatic tissue levels. They found [U]no[/U] association between T levels and PC incidence. (Researchers at UW-Seattle found this to be true of DHT as well).[/SIZE]
[SIZE="2"][I]Effect of TRT on prostate tissue in men with late-onset hypogonadism. Marks et al, JAMA July 6, 2011(306:1)[/I][/SIZE]

[SIZE="3"]The only studies I could find that showed a positive association were both based on a longitudinal analysis of the same data set, the Baltimore Longitudinal Study of Aging. This one showed an association between free T, but not total T and later development of PC:[/SIZE]
[SIZE="2"][I]“Serum T and the risk of PC” Parsons, et al (Johns Hopkins) Cancer Epedemiol Biomarkers Prev 2005 Sep; 14(9):2257-60[/I][/SIZE]
[SIZE="3"]But this later analysis of the same data set found that serum T was associated with high risk disease [I]only[/I] among men older than 70, but not among men under 70.[/SIZE]
[SIZE="2"][I]“Serum testosterone is associated with aggressive prostate cancer in older men”
Pierorazio, et al. (Johns Hopkins) BJU Int. 2010 Mar; 105 (6):824-9

[SIZE="4"][FONT="Arial"]There is no evidence that higher T levels causes PC. But can it aggravate known PC? [/FONT][/SIZE]

[SIZE="3"]There is one uncontrolled small study, by Morgentaler, in which T was given to men with known untreated PC. In this remarkable study, 13 men with known PC (12 with Gleason 6, 1 Gleason 7) were given T. On the average, there were two follow-up biopsies after a median of 2.5 years. Amazingly, [U]no cancer was found in more than half the f/u biopsies.[/U] Two men showed higher grade on initial f/u biopsy, but was not confirmed by a second f/u biopsy in one case or by RP in one case. No PC progression or distant disease was observed.[/SIZE]
[SIZE="2"][I]“T therapy in men with untreated prostate cancer” Morgentaler et al. J Urol 2011 Apr; 185(4):1256-60

[SIZE="4"][FONT="Arial"]But TRT to men, like me, who have been successfully treated for PC is another matter. The studies are small and uncontrolled, but they consistently demonstrate no lasting deleterious effect of TRT after treatment for PC. [/FONT][/SIZE]

[SIZE="3"]10 hypogonadal RP patients were given TRT. After a median of 19 months, [U]none[/U] had PSA recurrence.[/SIZE]
[SIZE="2"][I]TRT after primary treatment for PC
Agarwal et al, J Urol 2005 Feb; 173(2):533-6[/I][/SIZE]

[SIZE="3"]7 men received TRT post-RP with [U]no[/U] biochemical recurrence.[/SIZE]
[SIZE="2"][I]Androgen replacement after curative RP for PC in hypogonadal men
Kaufman et al J Urol 2004 Sep; 172(3):920-2[/I][/SIZE]

[SIZE="3"]31 men received TRT after prostate brachytherapy for a median of 4.5 years, and [U]none[/U] experienced a recurrence.[/SIZE]
[SIZE="2"][I]“T replacement for hypogonadism after treatment of early PC with brachytherapy”
Sarosdy, Cancer 2007 Feb 1; 109(3):536-41[/I][/SIZE]

[SIZE="3"]96 patients from 2000 to 2007 received TRT after initial treatment for PC. While most men in this series had increasing PSA levels during TRT, stopping TRT typically reversed it.[/SIZE]
[SIZE="2"][I]“T replacement in PC survivors with hypogonadal symptoms” Liebowitz, et al (USC) BJU Int. 2010 May; 105(10):1397-401[/I][/SIZE]

[SIZE="4"][FONT="Arial"]To definitively determine safety of TRT post-treatment would require a controlled study of 6000 men, by one estimation. This is not likely to ever happen. One has to also weigh the hypothetical risks of TRT on indolent undetected PC against the known risks of low T on bone density, lean muscle tissue, cardiovascular effects, insulin resistance, mental disturbances and sexual problems. There are non-prostatic risks to TRT as well, including erythrocytosis and hypercholesterolemia.

Whichever route one chooses, your doctor must frequently monitor PSA as well as the side effects of treatment or non-treatment. Here are a couple of good articles that gives many doctors’ recommendations for diagnosing, treating and monitoring hypogonadal men:[/FONT][/SIZE]
[SIZE="2"][I]Investigation, treatment and monitoring of late-onset hypogonadism in males. Wang et al (14 authors in the US and Europe) Eur J Endocrinol. 2008 Nov, 159(5):507-514[/I][/SIZE]

[SIZE="2"][I]Managing the Risks of Prostate Disease during TRT in older men: Recommendations for a standardized monitoring plan. Bhasin et al. (Doctors from UCLA, Johns Hopkins and Baylor) J of Andrology, May/June 2003; 24(3) 299[/I][/SIZE]

- Allen

61Frank 04-26-2012 08:39 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??

Thank you very much for your reply and all the information on Testosterone. I am going to print your reply and discuss with my Urologist.

I was kinda hoping my low T score of 150 was the cause of these high and very fluctuating PSA readings. I guess I don`t fully understand the connection if there is any between low T and PSA. By that I mean if some kinda hormonal thing was going on in my system over that past couple of years could that have caused my PSA to shoot up.... Or did my high PSA maybe cause my T level to drop ???

But on the other hand, all these Bladder stones I had (wherever they came from -) Dr. said my urine was stagnating in the bladder from not drinking enough during the day. Moved from Jersey to Florida shortly before this all started happening and had a job outdoors in the Florida heat and humidity and I rarely drank anything during the day - Not Good... (could those stones have raised my PSA ?? )

Anyways, I guess even though my PCA 3 score was pretty low at 11, I should probably go ahead with another biopsy next week ?? I don`t really care for them.

Thanks again for your time and response.


Tall Allen 04-26-2012 10:04 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Hi Frank,

I wanted to tell you what I could about your questions...
[QUOTE]By that I mean if some kinda hormonal thing was going on in my system over that past couple of years could that have caused my PSA to shoot up?[/QUOTE]
It seems clear that normal levels of testosterone are required to keep healthy prostates healthy. Prostate cells have a large number of androgen receptors on them. Testosterone and DHT, another androgen, activates them. PSA is released by "sick" prostate cells, so you may be right that you don't have enough testosterone to keep them healthy.

[QUOTE]Or did my high PSA maybe cause my T level to drop ???[/QUOTE]
I'm not aware of any kind of negative feedback between high PSA and T. Men with very high PSA due to prostate cancer, BPH or prostatitis don't suffer drops in T levels, other than the drops that are age related.

[QUOTE]I should probably go ahead with another biopsy next week ?? I don`t really care for them.[/QUOTE]

I can't imagine why on earth you would have yet another biopsy now. It's like your urologist refuses to take yes for an answer. :) Drilling holes in your prostate is not a good strategy, imho. It seems to me a better idea to:[LIST=1][*]rid yourself of the bladder stones.[*]take a course of Cipro to get rid of any possible prostate infection you may have, possibly from punching holes from your rectum into your prostate.[*]take Avodart or Proscar for 6 months to get rid of any BPH and establish a clean baseline PSA level[*]monitor PSA, % free PSA and PCA3 after that.[/LIST]
Then, after doing all that, if your PSA is still rising, it's a good idea to get any one of the following kinds of biopsies:[LIST=1][*]color doppler ultrasound or elastography guided biopsy[*]multiparametric MRI guided biopsy[*]saturation biopsy[/LIST]
In my opinion, it really isn't a good idea to keep punching random holes in your prostate. It creates scar tissue, can cause nerve damage that causes ED, and can cause serious prostate infections.

- Allen

61Frank 04-27-2012 04:32 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??

I am allergic to Cipro so he put me on Bactrim - after one week I started to itch terribly .( same thing use to happen to me with Cipro ) so he stopped the Bactrim and put me on Keflex 500 MG 4X a day for 30 days. After that PSA went from 22.4 to 22.6.

The Bladder stones are now gone. He removed the large ones and flushed my bladder out back in January.

I`ll see what he says about the Avodart or Proscar and monitoring things in 6 months.

Meanwhile he probably will not want to treat for the low T with a 22.6 PSA unless he does another biopsy - but I will have him review the info you sent me.

Thanks again - Frank

Tall Allen 04-27-2012 11:53 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Hi Frank--
I came across the following abstract today and thought of you. This group under Dr. Ash Tewari (probably the best prostate surgeon around, imho) found that men who had multiple preoperative biopsies are more likely to become impotent postoperatively than those who undergo surgery after a single biopsy. Only 57% of men who'd had multiple biopsies retained potency vs 80% of men who'd had only one biopsy. Biopsies have to look for perineural invasion, which entails punching holes through the neurovascular bundles. There seems to be a damaging consequence to doing this. Maybe show this to your urologist as well.

- Allen

61Frank 04-28-2012 08:57 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Hi Allen

Thank you for this info on dangers of increased chance for impotency if surgery is done after multiple biopsies. I have been having enough problem with my libido over the past couple of years as it is.

I am now wondering if my low testosterone level of 150 has been the cause of my prostate problems all along....... I have been reading up on this and am no expert but they say that low testosterone can increase levels of estrogen. Too much estrogen can cause various problems including BPH. It would seem to me logically that BPH prostate enlargement would cause an increase in PSA numbers. Does this sound logical ??

The bottom line is this......

I have had 2 previous biopsies and nothing was found.

CAT scan showed my prostate was protruding into my bladder.

I have passed over 100 bladder stones over the past 2 years.

I have just had some large stones removed from my bladder.

My PSA bounces around 3 or 4 points up and down every couple of months.

My PCA 3 test came back just this past January 2012 as a 11. They say this score is a good indication that a biopsy will come up negative.

And my testosterone level is a 150.


I am cancelling my scheduled biopsy for next week.

I am going to see another Urologist for a second opinion.

Then I`m going to see an endocronogist to see if anything is whacked out.

Best regards,

Tall Allen 04-28-2012 12:09 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Frank, I think your plan is great! Second opinions are [I]always[/I] a great idea.

Something I learned when seeking out a urologist is to find one who doesn't do prostatectomies for a living. Urosurgeons tend to see prostate cancer everywhere, even when there is no indication that it's there and other causes should be explored. Then they think that surgery is the only answer. Self-serving, eh? I went through three different urologists until I found one who really knew his stuff - he worked at a university hospital and devoted himself to teaching and research rather than surgery. I started noticing his name on a lot of interesting research studies and he was nearby at UCLA so I set up an appointment with him. He actually loves it when I email him these studies. He doesn't tell me how to treat stuff, he discusses options and their plusses and minuses and allows [I]me[/I] to decide.

Not too long ago, all doctors were expected to "play God" for their patients, because only they had access to information. Now, all that is changing with the democratization of information on the Internet. However, you have to be really careful about the sources of information you choose to listen to -- there's a lot of wacky stuff on the net -- especially from doctors who have their own websites. That's why I almost always give sources in peer-reviewed journals published on gov't websites; there is at least a minimum degree of quality needed to publish there.You seem like a man who likes to take control of his own destiny as much as possible, so finding a doctor who will actually work with you will, I think, make you a lot happier.

Good luck and let us know as things progress -- I think a lot of men here can learn from your experience.

- Allen

zippinger 05-08-2013 08:03 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??

I'm interested in the doctor you mention in your post above. Can you tell me who he is? I'd like to put my father in touch with him.


Tall Allen 05-08-2013 09:45 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
I don't think we are not allowed to give doctor recommendations on this board. You might be interested to read about his work on 5-alpha-reductase inhibitors, which can prevent the metabolism of T into DHT and relieve symptoms of BPH in men taking TRT:

- Allen

61Frank 07-03-2013 04:22 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
Hi Allen

I`m the guy that origionally started this post about a year ago and have some recent interesting developments I would like your opinion on. After having 2 biopsies done due to high PSA my uro. convinced me to get another one done a couple of months ago. My PSA was at a 28.8. So he did a 24 core biopsy instead of 12 cores as on the first 2 biopsies. The results again came back all negative. So he asked me if he could send the samples out to a place called Confirm MDX. They do some kind of DNA Methylation testing on the samples and check for 3 different things. On the report they are identified as GSTP1 Methylation. APC Methylation, and RASSF1 Methylation. So he just got the results back. Everything is negative except the following: The left lateral apex showed positive for the APC Methylation, the other 2 types of Methylation were negative. Also under Right Transition Zone, the Right Mid. showed positive for the GSTP1 Methylation and the APC Methylation and negative for the RASSF1 Methylation. All the other samples are negative. So now my urologist is asking me if I want to do another biopsy concentrating on the 2 areas which showed some positive DNA results. Just wondering if you have ever heard of this DNA testing. I don`t know what it all means but needless to say I am worried. My last PSA test came down from the 28.8 to 28.2. Would greatly appreciate any thoughts on this. Thank you.


Tall Allen 07-04-2013 11:21 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
The gene tests that got a lot of press lately were Prolaris and OncotypeDx.

DNA methylation is part of normal cell differentiation and also of carcinogenesis. I read that DNA methylation is associated with a breakdown of the androgen receptor, which wouldn't be surprising in your case given your history of low testosterone and the deleterious effect that has over time on the androgen receptor. There are drugs called 5-AZA inhibitors (Vidaza and Dacogen) that can reverse the DNA methylation.

I don't know that the information on such gene tests really tells one anything usable.

The questions I would have are:[LIST][*]Are there still some stones or blockage going on?[*]Is the prostate enlarged? Are you on Avodart or Proscar?[*]Did they culture any of the biopsy cores, looking for highly resistant bacteria? [*]Is the transition zone enlarged (common with BPH)?[*]Have you done any advanced imaging - multiparametric MRI or US?[/LIST]
As an aside, Johns Hopkins has a clinical trial now of supplementing testosterone during the off-cycle for men on ADT. Preliminary evidence is that it may slow down the progression of the cancer to a castration-resistant state.:

Henry 62 Surfer 04-10-2014 11:46 AM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
I'm at 285 testosterone, 60 free test, 4.8 PSA, with a 13,000 white count. I've had some low grade blatter cancer scrapped off, stopped the undetectable blood in urine and blood in my semin is demishing. Had 8 core samples in 2011 wete negative.

My question involves getting back on TRT after 5 years off. 600 feels a lot better than 285... I have testosterone on the way, needles and ready to go with 1cc once a week. Allen? What say you bro?


lexer 06-01-2014 09:11 PM

Re: High PSA - negative biopsies - Low Testosterone - Connection ??
How large is your prostate? How old are you?
Does proscar cause impotence ?
I am 48 and have a slightly enlarged prostate, 30 grams. I was thinking of taking proscar. My urine stream splits and sprays.

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