Evidence for the integration of total and free testosterone levels in the management of prostate cancer

Abstract

L.M.H. made equally significant contributions to the present study. ObjectiveTo comprehensively assess total and calculated free testosterone levels in a consecutive group of patients with prostate cancer (PCa) and any potential impact on disease aggressiveness and recurrence outcomes. Participants and MethodsThe study included a single-centre prospective cohort of 882 patients presenting for radical prostatectomy from 2009 to 2018. Data on total testosterone (TT), sex hormone-binding globulin (SHBG), and calculated free testosterone (cFT) were prospectively collected. Stepwise logistic regression models were used to assess correlations of TT and cFT with pathological Gleason Grade Group (GGG), extraprostatic extension (EPE), seminal vesicle invasion (SVI) and biochemical recurrence (BCR). ResultsTotal testosterone remained nearly constant across decades (40s-80s): 0.09 decrease/year (R = 0.02), while SHBG increased 0.87/year (R = 0.32) and cFT decreased 0.08/year (R = À0.02). Low cFT of <5.5 independently predicted: very-high-risk GGG (odds ratio [OR] 0.435, 95% confidence interval [CI] 0.846-0.994; P = 0.036), EPE (OR 0.557, 95% CI 0.810-0.987; P = 0.011), SVI (OR 0.396, 95% CI 0.798-1.038; P = 0.059), and BCR within 1 year after robot-assisted radical prostatectomy (OR 0.638, 95% CI 0.971-3.512, P = 0.046). TT was not a predictor. ConclusionIn contrast to popular belief, testosterone remained stable in men aged 40-80 years, whereas free testosterone decreased by 2-3%/year. Low cFT was an independent predictor of very-high-risk PCa and BCR.

Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis

“…Although SLE may reduce PC risk by curtailing the sex hormone pathway (Watts et al 2018 ), lower testosterone levels in PC tend to be accompanied by higher aggressive malignancy and a poor prognosis with androgen deprivation therapy (ADT) (Patel 2021 ; Lane et al 2008 ; Huynh et al 2021 ). Castration levels of testosterone (Oefelein et al 2000 ) below the saturation point (< 0.7 nM) can cause altered differentiation and enhanced metastatic potential in PC cells (Ishiwata et al 2011 ; Jennbacken et al 2010 ; Wei et al 2007 ).…”

Androgens, aging, and prostate health

“…Intriguingly, in some of the above-mentioned studies, lower testosterone was associated with more frequent aggressive high-risk disease [59,79], and predicted poorer survival on ADT [63]. These associations do not fully fit into the saturation model, since even at these somewhat lower testosterone levels, the AR should be fully saturated and activated.…”