EAU19 Barcelona – 15-19 March 2019 - Low Free Testosterone is an Independent Risk Factor for High Grade PCa

[pjoshea13]

Total testosterone [T] is often used as a surrogate for T status. Free T would be more accurate. About 2% of T is 'free' - i.e. not bound to protein. Blood tests that report total & free T often estimate free T. About half of circulating T is bound to SHBG (sex hormone binding globulin) & is considered to be bio-unavailable. The rest is lightly-bound to albumin. The calculation uses measured SHBG but makes an assumption about albumin.

An interesting thing about SHBG is that numbers tend to go down as T rises, thereby increasing the freeT%.

As we get older, our total T tends to drop & estradiol [E2] tends to rise. When E2 is elevated, the body targets total T, since we make E2 from T. T production is inhibited and SHBG production goes up. i.e. less T is made & more T is bound to SHBG.

Albumin-bound T is considered to be weakly bound & therefore bioavailable, but free T is the immediately active form. Albumin is an inflammation marker and has been linked to survival. The LabCorp reference range is 3.6-4.8 g/dL, but one should aim for 4.5 or higher. Below 4.0, one should be seriously addressing inflammation, regardless of PSA, etc. For some reason, variation in albumin levels is not considered to be important when estimating free T.

"The study team that patients with free testosterone (FT) level in the lowest quartile (<4.42 nd/dL) had the highest proportion (15.6%) of very high risk (i.e. Gleason grade group 5) prostate cancer." i.e. GS = 4+5, 5+4 & 5+5 cases.

-Patrick

urotoday.com/conference-hig...

"Barcelona, Spain (UroToday.com) The relationship between testosterone and prostate cancer is controversial, with much remaining to be learned. While there is some contention regarding exacerbation of prostate cancer in men with higher testosterone, current systematic reviews show no such relationship.

Maxwell Towe, a clinical research fellow in the Department of Urology at UC Irvine Health, presented his findings on the relationship between total and free testosterone and its correlation with grade and stage of prostate cancer. His findings were further echoed by a German group presenting their data in the same session.

Overall, Towe’s study included 830 consecutive patients presenting to a single surgeon’s practice for management of local prostate cancer. Correlation between total and free testosterone were compared with clinicodemographic of age, preoperative PSA, prostate volume, pathologic grade, and pathologic stage. The study team that patients with free testosterone (FT) level in the lowest quartile (<4.42 nd/dL) had the highest proportion (15.6%) of very high risk (i.e. Gleason grade group 5) prostate cancer. Compared to those with high free testosterone, this was a statistically significant difference.

In multivariate analysis, lower free testosterone was an independent risk factor of very high-risk prostate cancer. This was found after controlling for previous indicators of prostate cancer aggressiveness: preoperative PSA, body mass index, and age. Even further, adding free testosterone into a nomogram for prostate cancer aggressiveness increased sensitivity and specificity significantly.

Overall, Towe stresses the importance of assessment of testosterone (and more importantly, of free testosterone) not only in prostate cancer patients but in older men in general. He cites previous work showing decreasing free testosterone with increased age. Future studies on testosterone replacement therapy and prostate cancer are encouraged, as these findings have significant and widespread benefit.

Presented by Maxwell Towe, Prostate Cancer and Men's Health Fellow, University of California, Irvine, Department of Urology, Orange, United States

Written by: Linda My Huynh, Senior Clinical Research Coordinator, Department of Urology, University of California-Irvine, at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019."

[bdriggers]

pjoshea13, a few post back you started the post with ( I’m paraphrasing) “ when my surgery immediately failed” I think you were offered ADT. But the next sentence is wat caught my eye. You said 15 years later, you felt like ADT was in your future. This reply is not about ADT. Would you share what you did that has worked for 15 years? Is there somewhere on healthunlocked that you have posted that?

I am so interested, can you shed some light?

[pjoshea13 in reply to bdriggers]

Well, in 2004 I was reading how the recently discovered beta estrogen receptor [ERbeta] was down-regulated in PCa, while 'traditional' ER, renamed ERalpha, took its place. ERalpha is otherwise confined to the stroma. At the same time, I was finding no evidence that testosterone caused or accelerated PCa that had not been treated with ADT.

At that time, one could buy androstenedione without a prescription (insanely, possession became a felony in January 2005.) Andro can convert to T. My PSA was rising after a failed RP & salvage radiation. Many would have started Lupron - I started on andro, but I paired it with chrysin, to stop T from converting to estradiol [E2].

Naturally, I was wary, so I tested PSA monthy. To my surprise I had 6 identical PSA readings.

I had found a sympathetic integrative medicine doc. My plan was to get him to prescribe T when the andro ran out. He thought I should switch from chrysin to Arimidex, which I did. He also thought I was deficient in B12 (high homocysteine & no cobalt in my hair), so he had me injecting B12. A huge mistake.

Eventually, my PSA doubling time [PSADT] settled down to >24 months. But after a few years, PSADT began to shorten. I figured that DHT was no longer my friend, so I started using Avodart. & then, reluctantly, I began 3-month knockdowns of PSA followed by 3 months of T.

Did that for some years but recently switched to a BAT timeframe. Figured that a more rapid cycle was better. Wish I had thought of it.

I don't know how long I can do this. My PSADT was ~3 months 15 years ago. It would be that now if I stopped what I am doing. Surviving to 71 was unexpected. Seems greedy to want another 5 years.

If I were diagnosed today, I wouldn't be doing my own thing. I would be bogged down trying to decide on combinations & sequencing of drugs. Back then there was essentially Lupron followed by lackluster Taxotere. Scared the hell out of me; empowered me.

-Patrick

[bdriggers in reply to pjoshea13]

Thank you!

[Hidden in reply to pjoshea13]

I'm unlikely to find a doctor who would write a prescription for T supplementation. I am age 69 and have been treated for prostate cancer. I am wondering about the use of DHEA. Some extol its benefits while others say beware.

livestrong.com/article/2046...

This paper would seem to suggest that my wife take it instead of me:

ncbi.nlm.nih.gov/pmc/articl...

[pjoshea13 in reply to Hidden]

One of the mysteries of life is the the decline of DHEA after age ~20 (Wikipedia). Restoring youthful hormone levels has its attraction. Some worry about the biological fate of supplemental DHEA. This shows the paths that may be followed:

en.wikipedia.org/wiki/Dehyd...

What is strange to me is that when I supplement with T my DHEA-S shoots up to normal high (near the top of the LabCorp range) when T is ~1,000 ng/dL..

There is no reason to believe that DHEA will send estradiol through the roof, but it's worth getting a hormone panel tested when tinkering with them.

-Patrick

[LeeLiam]

Patrick,

When you say "The LabCorp reference range is 3.6-4.8 g/dL" did you mean for Free T? And did you mean ng/dL?

On my last blood test, my Free T was 6.9 with a range of 6.6-18.1 pg/mL.

[pjoshea13 in reply to LeeLiam]

I was referring to albumin. -P.

[Spaceman210]

A year ago my T was 991. Just got this from UCI:

Your Testosterone level is 581

SHBG: 124

Calculated Free testosterone 4.45

"The findings of Dr. Ahlering’s clinical study demonstrated that non-metastatic hypo gonadal men treated with TRT had a 50% reduction in PSA recurrence."

In the past year I have been on metformin and see where this could have caused a T drop. Does this mean I should get off of metformin due to the low T risk cited in the study and switch to berberine which supposedly does not have this effect? I have a low level recurrence at present which is not showing a trend but bouncing around 0.1.

[pjoshea13 in reply to Spaceman210]

Hi Spaceman,

I wasn't aware that Metformin might have an effect on testosterone [T], except by improving symptoms of the metabolic syndrome [MetS] & raising T, but this paper [1] discusses the possibility of a rise or a fall:

"metformin ... improves fertility of adult men with metabolic syndrome through increased testosterone production"

"In males, Tartarin et al. demonstrated that exposure of mice and human fetal testes to metformin decreases testosterone production. In vivo, administration of metformin resulted in a decrease in testosterone secretion"

Do you have a better reference for potential adverse effects on T?

Presumably, with a T of 991 a year ago, you were not suffering from MetS?

I don't know your age, but I'm guessing that most here are a couple of decades or more past the point when T was last at 991 ng/dL.

581 is still a pretty good number, but I understand your concern.

I can't speak to the lack of a T effect of berberine. Do you have a reference?

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[Spaceman210 in reply to pjoshea13]

Hi Patrick, on T I saw this with a Google search: ncbi.nlm.nih.gov/pubmed/117....

On berberine, only unsupported allegations: faim.org/avoid-the-metformi....

examine.com/supplements/ber...

However thanks to your question, I just saw this discussing significant concerns:

diabetesupdate.blogspot.com...

I'm 66, no mets detected.

Thanks,

Jeff