This plot shows the association of baseline testosterone levels with PCa aggressiveness. For example, if you have low aggressive PCA, your testosterone is likely to be Normal. But, if you have metastatic PCa, your testosterone is likely to be very Low.
This shows that having normal testosterone levels is protective against prostate cancer.
As opposed high or normal testosterone, my understanding is that men with low T have a higher incidence of developing prostate cancer. After it is present that is reversed. Huge unknowns around this. Does it matter what the GS is? Does it matter what the FSH, LH, PRL, E2 levels, etc. Don't think a comprehensive study has ever been attempted.
In addition every prostate cancer case is unique.
Makes approaches difficult.
Need for personalized medicine.
Here's a plot showing different Gleason scores and association with high/low testosterone levels . High Gleason scores are associated with low-T, as one might expect.
My doctors shoots for > 1000 ng/dL levels.
REF: spandidos-publications.com%...
Here's a schematic plot of Morgantaler's saturation model.
It shows two regimes. First is the "linear regime". For low testosterone < 250 ng/dL, there is a linear response to testosterone. Here, prostate cancer growth rates increase linearly with increasing testosterone. That's the basis for doing ADT, and why one strives to have a T-level close to zero.
But, in the "saturation regime" above 250 ng/dL, the curve flattens out (because the androgen receptors are saturated), meaning that any increase in testosterone above 250 has no additional increase in PCa growth rates. There are likely other mechanisms (not understand at present) that explain why higher levels of testosterone (e.g. 400 ng/dL) are protective against PCa.
Bob
Don't forget the heterogeneity of prostate cancer and its ability to create is own hormones including testosterone, DHT, estradiol, etc. intercellular which is not measurable. And can change over time.
A real challenge.
"Intra celllular"
I don't believe it is as simple as this. There are a plethora of highly educated, experienced MO and RO that don't subscribe to this theory. If it were indisputable by scientific evidence/trials, all MO would have their patient on T replacement therapy to boost their Testosterone levels.
Do you have links to any trials that have been done to prove the efficacy of high T = low G and is protective?
I think the takeaway from these plots is that hypogonadal men who naturally have very low testosterone levels (< 50-100 ng/dL) are at a much greater risk of developing PCa. No one understand why this is, though. For those men, supplementing with testostoren appears to be helpful in reducing the risk of getting PCa.
Actually, raising testosterone following radical prostectomy reduces the risk of a recurrance by ~54%. See: bjui-journals.onlinelibrary...
My neighbor is a highly respected retired urologist who has focused on this very subject (set up and ran a very successful clinic in the Detroit area). He maintains (my poor summary) that low testosterone leads to a "wackiness" in the body that leads to cancer development. He has written papers and done presentations on this in the US and elsewhere. He is currently setting up a clinical trial in the Philippines (his country of origin) to test out his theory.
For us he's been a God-send - he's been generous with his time and advice on our own journey.
Note - treating prostate cancer with testosterone is dicy - the % of men whose cancer responses well to that approach is low. One of our consulting MO's took part in the trial to test that out, and he knows first hand that it is not a good SOC solution. What we are talking about here is cancer prevention.
Yes, I agree.
High testosterone does help to prevent/reduce the incidence of new prostate cancer. Then, after you get cancer, reducing the testosterone to castrate level by ADT helps prevent further growth of the cancer.
It seems contradictory, but there are different mechanisms at work here. See my reply below about the Morgentaler Saturation Model, which explains at least some of this conundrum.
Low testosterone levels is associated with more aggressive PC? There goes the mainstream Official Truth that PC-sufferers should be on castration drugs.
It's a two-part answer.
I'm attaching a schematic version of the Morgentaler Saturation Model (Harvard) that shows Prostate Cancer Growth Rate versus testosterone level. For testosterone below 250 ng/dL, there is a linear response, wherein increasing testosterone causes increasing PCa growth. That's the basis of doing ADT, which is well understood and documented.
However, above 250 ng/dL, the PCa growth rate flattens out and becomes independent of testosterone levels. The explanation by Morgentaler is that the androgen receptors have become saturated above 250, and any increase in testosterone doesn't cause any increased rate of PCa growth.
I can't explain why the low levels of testosterone in my posting above is associated with metastatic cancer, and visa-versa. Clearly there are other, unknown, mechanisms at work here. But, the data is the data.
Note that there is an important distinction between (A) doing ADT to fight or reduce existing PCa by castrating men, versus the observation that (B) having a low baseline testosterone is initially associated with a greater incidence/diagnosis of PCa. They are two different things that must be considered individually, not together. But, I appreciate that it seems to be contradictory, at first look.
Doesn't mean anything but my testosterone was 400 when my Gleason 8 cancer was diagnosed.
I'm sorry about your cancer.
The Morgentaler saturation model predicts that there will be some prostate cancer growth even at testosterone levels above 250 ng/dL (see attached). So, having normal or high testosterone doesn't prevent the incidence of PCa.
But, having a higher testosterone is associated with a relatively lower risk of getting PCa. That's what the data shows. (I can't explain it, though...)
If there is a basis to make a decision on this one way or another it would be nice to clearly state that. As it is, it doesn't seem like the data makes any difference whatsoever. The data is the data but so what? I have low testosterone, I can get cancer; if I have normal testosterone, I can still get cancer.
Good perspective. Your statement is correct, but consider this plot...
Here's a companion plot from the same paper that shows the Odds Ratio of getting PCa versus baseline testosterone level. The odds of getting PCa increase by a huge amount for T-levels below 50-100 ng/dL. In other words, having a very low baseline testosterone is very bad for getting PCa. But, the odds ratio is relatively flat for T > 250 ng/dL (which matches the limit of 250 ng/dL in Morgentaler's Saturation Model). I don't think that's a coincidence!
We have to try and understand why this is true,
Bob
This is a really interesting topic. I think if your high risk e.g. family history of prostate cancer, checking if you are low testosterone is possibly as important as PSA (I'm not advocating not to check PSA but to add testosterone).
I have seen this mentioned anecdotally that low testosterone is a bad indicator at diagnosis, even though this flies in the face of taking ADT to reduce testosterone. We appear to still be a long way off in understanding Prostate cancer.
I agree 100%.
See my reply above about the Morgentaler Saturation Model, which partly explains this conundrum.
Remember the well-known observation that older men have higher incidence of prostate cancer, and naturally have lower levels of testosterone.
Baseline testosterone levels should be part of the NCCN risk guidelines, based on this data.
The mechanism that explains this, however, is unknown...as far as I know.
Bob
bummer didn’t work that way for me. At 65 I had testosterone level of 800 but had Gleason of 8 which was not cured by RP.
Testosterone levels !!
Is there seasonality to testosterone levels?
The human microbiome and its link in prostate cancer risk and pathogenesis
