New study below [1] [2].
I have some old posts where I claim that men at PCa diagnosis have lower T (as a group) than controls, & that those with the lowest T have a poorer prognosis. I need to expand on that.
The generally used T cutoff for hypogonadism these days seems to be 350 ng/dL. Age-related decline, which begins in our early 30's, can take us close to that, but there is also a birth year-related decline.
The 1948 birth year cohort to which I belong has better age-T numbers than the 1958 cohort, but worse than the 1938 cohort. Hypogonadism is not uncommon & is being seen at a younger age.
Morgentaler, in his saturation model, says that the body has enough T to bind to every androgen receptor [AR] that wants it, when T > 250 ng/dL, or so.
Men who are below that number, are actually in a form of ADT. So we have a paradox. Men below 350 ng/dL are at risk for more aggressive disease, while the subset below 250 ng/dL will have delayed detection - showing up as lower risk.
In the new study:
"... men in the group with the lowest levels of testosterone were significantly less likely to develop prostate cancer compared to all other men."
"Yet interestingly, when men in this group do get prostate cancer, they are 65% more likely to develop an aggressive form of the disease compared to all other men."
"For the men in the remaining nine groups, testosterone was not associated with prostate cancer risk."
"We analysed individual participant data from 20 prospective studies, with up to 6,933 prostate cancer cases and 12,088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group."
"Men in the lowest study-specific tenth of free testosterone had a lower risk of prostate cancer (OR=0.79 ...) compared with men in the 2nd-10th tenths."
There was "a decreased risk of low-grade prostate cancer (OR=0.76 ...) and an increased risk of high-grade disease (OR=1.65 ...) in men with very low levels of free testosterone."
I like that the study used deciles, rather than a smaller number of divisions, where the risks would have been diluted & perhaps not apparent.
I also like that they used free-T, which is the number that counts. As we age, T drops by 1-2% each year, but SHBG increases. Free-T is total T minus T bound to SHBG (or albumin). The age effect on free-T is much worse than the decline in total T would suggest.
Headlines in the UK Times: "Low testosterone reduces prostate cancer risk."
... which I'd say sends the wrong message, since the protection is for low-grade disease only: 24% less low-grade, but 65% more high-grade PCa.
Why would there be less low-grade disease? As T declines below 250 ng/dL, PSA declines too. Lower PSA = fewer biopsies = less inconsequential disease detected. It's a detection issue. We don't detect the lesser grade, & by the time PSA prompts a biopsy, the disease is more advanced.
With low T, basic arithmetic can be a challenge. How would men with low T respond to an offer of TRT (T supplementation) after being told that PCa risk would increase by x%, but aggressive PCa would decline by y%.
But perhaps there would be less aggressive disease if men who were heading to a dangerous free-T level could be identified early & treated?
-Patrick
