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Old 04-26-2012, 06:34 PM   #2
Tall Allen Tall Allen is offline
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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 low 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:


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:

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 not associated with the risk of PC.
Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies
J Natl Cancer Inst. 2008 Feb 6; 100(3): 170-83


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 no association between serum T levels and later PC development.
Serum T and SHBG concentrations and the risk of PC: a longitudinal study
Heikkila et al, Cancer 1999 Jul 15; 86(2):312-5


Another tissue study with 727 PC cases and 889 matched controls found PC risk was unrelated to serum T:
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


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 no association between T levels and PC incidence. (Researchers at UW-Seattle found this to be true of DHT as well).
Effect of TRT on prostate tissue in men with late-onset hypogonadism. Marks et al, JAMA July 6, 2011(306:1)

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:
“Serum T and the risk of PC” Parsons, et al (Johns Hopkins) Cancer Epedemiol Biomarkers Prev 2005 Sep; 14(9):2257-60
But this later analysis of the same data set found that serum T was associated with high risk disease only among men older than 70, but not among men under 70.
“Serum testosterone is associated with aggressive prostate cancer in older men”
Pierorazio, et al. (Johns Hopkins) BJU Int. 2010 Mar; 105 (6):824-9


There is no evidence that higher T levels causes PC. But can it aggravate known PC?

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, no cancer was found in more than half the f/u biopsies. 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.
“T therapy in men with untreated prostate cancer” Morgentaler et al. J Urol 2011 Apr; 185(4):1256-60


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.

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


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


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


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.
“T replacement in PC survivors with hypogonadal symptoms” Liebowitz, et al (USC) BJU Int. 2010 May; 105(10):1397-401

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:

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

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

- Allen

 
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