Does "high" Testosterone predict more serious PCa?

[pjoshea13]

New Italian study below [1].

Here is the conclusion:

"Elevated preoperative {total testosterone} levels are associated with the risk of aggressive PCA in the surgical specimen."

From the full text:

{total testosterone} (ng/dl); median ({interquartile range})

410 (320.5–512)

Non-aggressive PCA 385.6 (304–501)

Aggressive PCA 432 (340.6–519)

Bear in mind that 350 ng/dL is the cut-off for hypogonadism.

(The LabCorp T range is 264-916 ng/dL, but the range varies by lab.

"In general, the normal range in males is about 270-1070 ng/dL with an average level of 679 ng/dL." [2])

Looking at the interquartile ranges, the aggressive group (340.6-519) is 178.4 wide & overlaps the nonaggressive group (340.6-501) by 160.6 - i.e. a 90% overlap.

It seems to me to be an exaggeration to refer to the aggressive group as having "elevated" T when some in that group were hypogonadal & when the interquartile range ended 500 points below what I would consider to be high (but not 'elevated').

It would be interesting to rework the analysis, excluding men with T in the castrate or semi-castrate range. i.e. those benefiting from natural ADT.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/326...

Ther Adv Urol

. 2020 Jun 24;12:1756287220929481. doi: 10.1177/1756287220929481. eCollection Jan-Dec 2020.

Basal Total Testosterone Serum Levels Predict Biopsy and Pathological ISUP Grade Group in a Large Cohort of Caucasian Prostate Cancer Patients Who Underwent Radical Prostatectomy

Alessandro Tafuri 1 , Marco Sebben 1 , Riccardo Rizzetto 1 , Nelia Amigoni 1 , Aliasger Shakir 2 , Tania Processali 1 , Marco Pirozzi 1 , Alessandra Gozzo 1 , Katia Odorizzi 1 , Mario De Michele 1 , Sebastian Gallina 1 , Alberto Bianchi 1 , Paola Irene Ornaghi 1 , Matteo Brunelli 3 , Filippo Migliorini 1 , Maria Angela Cerruto 1 , Salvatore Siracusano 1 , Walter Artibani 1 , Alessandro Antonelli 1 , Antonio B Porcaro 4

Affiliations collapse

Affiliations

1 Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

2 USC Institute of Urology, Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA, USA.

3 Department of Pathology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

4 Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale Civile Maggiore, Polo Chirurgico Confortini, Piazzale Stefani 1, 37126, Verona, Italy.

PMID: 32636934 PMCID: PMC7318822 DOI: 10.1177/1756287220929481

Abstract

Aims: The study aimed to evaluate associations of preoperative total testosterone (TT) with the risk of aggressive prostate cancer (PCA).

Materials & methods: From 2014 to 2018, basal TT levels were measured in 726 consecutive PCA patients. Patients were classified according to the International Society of Urologic Pathology (ISUP) system. Aggressive PCA was defined by the detection of ISUP > 2 in the surgical specimen. The logistic regression model evaluated the association of TT and other clinical factors with aggressive PCA.

Results: On univariate analysis, there was a significant association of basal TT with the risk of aggressive PCA as well as age, prostate-specific antigen (PSA), percentage of biopsy positive cores (BPC), tumor clinical stage (cT), and biopsy ISUP grade groups. On multivariate analysis, two models were considered. The first (model I) excluded biopsy ISUP grading groups and the second (model II) included biopsy ISUP grade groups. Multivariate model I, revealed TT as well as all other variables, was an independent predictor of the risk of aggressive disease [odds ratio (OR) = 1.585; 95% confidence interval (CI): 1.113-2.256; p = 0.011]. Elevated basal PSA greater than 20 µg/dl was associated with the risk of aggressive PCA. Multivariate model II revealed that basal TT levels maintain a positive association between aggressive PCA, whereas age, BPC, and clinical stage cT3 lost significance. In the final adjusted model, the level of risk of TT did not change from univariate analysis (OR = 1.525; 95% CI: 1.035-2.245; p = 0.011).

Conclusion: Elevated preoperative TT levels are associated with the risk of aggressive PCA in the surgical specimen. TT may identify patients who are at risk of aggressive PCA in the low and intermediate European Association of Urology (EAU) risk classes.

[2] medicinenet.com/high_and_lo...

[Hidden]

An example of needing to read the study instead of just ingesting the conclusion.

500 ng/dl TT high? I consider high normal to be 1000-1300 (This doesn't account for the decreasing TT levels over the past 50 years. And I'm not going to account for them.)

Before I did 6 months of estrogen based ADT my natural TT was 1200. I wasn't on anything. My SHBG was 295 ng/dl so my free and bioavailable were actually low.

Now I inject 400mg cypionate a week and my TT is 2169. Not sure why but my SHBG has been dropping steadily and is now 135.

[pjoshea13 in reply to Hidden]

That is the curious thing about SHBG - levels fall as T rise. Both of which improve free-T numbers.

{When E2 is elevated, the body reacts by reducing T production (male E2 is made from T, mostly). But the body also increases SHBG, to tie up circulating T & reduce free-T.}

-Patrick

[pwallace in reply to pjoshea13]

i just posted about this on a sep thread- my husband’s SHBG has been decreasing for years & it’s not tied to his T levels at all (they were low for a bit and then he supplemented & then stopped supplementing) & all the while SHBG was on its own steady decline. any theories patrick?

[pjoshea13 in reply to pwallace]

Well, as I mentioned above, SHBG rises when estradiol rises. Perhaps his estradiol was dropping? Other than that ...?

-Patrick

[GeorgesCalvez]

Not being unkind to the authors but it is a 20 author paper that does not have a lot of data or say very much.

What did they all do?

My guess is that it is a career boosting omnibus, stick it on the CV, hope that the interviewer looks at the more significant stuff, if there is any.

Big papers that matter do tend to have only a few authors.