Endogenous testosterone as a predictor of prostate growing disorders in the aging male

Porcaro, Antonio Benito; Amigoni, Nelia; Tafuri, Alessandro; Rizzetto, Riccardo; Shakir, Aliasger; Tiso, Leone; Cerrato, Clara; Lacola, Vincenzo; Antoniolli, Stefano Zecchini; Gozzo, Alessandra; Odorizzi, Katia; Brunelli, Matteo; Migliorini, Filippo; Artibani, Walter; Cerruto, Maria Angela; Siracusano, Salvatore; Antonelli, Alessandro

doi:10.1007/s11255-020-02747-w

Cited by 15 publications

(20 citation statements)

References 28 publications

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“…Our study showed that patients presenting with either lower ET or PSA levels, when related to respective densities, were more likely to have unfavorable disease in the surgical specimen. These results can be explained by considering dynamics relating ET, PSA and PV variations, which occur in the aging male, as well [ 6 ]. Age and BMI are the main physical factors impacting on hormonal dynamics with the former associating with lower free testosterone levels and the latter with either lower free or total testosterone levels, as well [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Endogenous testosterone (ET) is an important factor for evaluating prostate growing disorders including either benign prostatic hyperplasia (BPH) or PCa, which may also coexist [ 1 ]. Our group greatly focused its attention of the role of ET in PCa, finding that it could be associated with several unfavorable prognostic factors [ 6 – 8 ]. In low-risk PCa, we have recently shown that ET density (ETD), defined as the ratio of ET and prostate volume (PV), was an independent predictor of the risk of high tumor load (TL), which associated with unfavorable disease in the surgical specimen [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Endogenous testosterone density predicts unfavorable disease at final pathology in intermediate risk prostate cancer

et al. 2021

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Objective To test the hypothesis that endogenous testosterone (ET) density could be associated with tumor load (TL) in patients with intermediate risk (IR) prostate cancer (PCa). Materials and methods Endogenous testosterone density (ETD, ratio between ET and prostate volume [PV]), biopsy positive cores density (BPCD, the ratio between the number of positive cores and PV) and prostate-specific antigen density (PSAD, ratio between total PSA and PV) were retrospectively evaluated on a prospectively collected data on 430 patients with IR PCa submitted to radical prostatectomy (RP). Tumor load (TL) was measured as the percentage of prostatic volume occupied by cancer at final pathology. Unfavorable disease (UD) was defined as tumor upgrading (ISUP grading group 4, 5) and/or upstaging (pT3a or 3b) in prostate specimens. Associations were assessed by the logistic regression and linear regression models. Results Overall, UD, which was detected in 122 out of 430 IR patients (28.4%), was predicted by BPCD (odd ratio, OR = 1.356; 95% CI 1.048–1.754; p = 0.020) with a sensitivity 98.4% and overall accuracy 71.9%. On multivariate analysis, BPCD was independently predicted by PSAD (regression coefficient, b = 1.549; 95% CI 0.936–2.162; p < 0.0001), ETD (b = 0.032; 95% CI 0.023–0.040; p < 0.0001) and TL (b = 0.009; 95% CI 0.005–0.014; p < 0.0001). As BPCD increased, ETD and ET levels increased accordingly, but patients with BPCD > 1.0%/mL had significantly lower ET levels. Conclusions As ETD increased, BPCD and TL increased, accordingly; furthermore, patients with lower ET levels were more likely to have occult UD. The influence of tumor load, and unfavorable disease on ET and ETD needs to be addressed by further studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endogenous testosterone density predicts unfavorable disease at final pathology in intermediate risk prostate cancer

et al. 2021

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“…As a result, prostate epithelial cells need appropriate levels of ET to evolve up to well-differentiated androgen-dependent cells [35]. So far, prostate malignant disorders when associated with low intraprostatic ET levels for enlarged prostates, epithelial cells undergo cancer induction because intraglandular diffusion of testosterone is insufficient to provide differentiation up to androgen-dependent cells [5,9,35]. The dynamics of ET Fig.…”

Section: Discussionmentioning

confidence: 99%

“…5 Prostate-specific antigen (PSA) density (PSAD), as the ratio of PSA on prostate volume [ng/(dL mL)] versus density of biopsy positive cores (BPCD; %/mL). As BPCD increased, PSAD raised up; however, upgraded patients showed significantly higher mean PSAD levels levels as well as of their prostate densities may associate with metabolic disorders and increasing BMI so that all these changes impact by promoting cancer induction and progression in an environment where epithelial cells are poorly differentiated for not being exposed to appropriate levels of testosterone; furthermore, lower PSA amounts are produced by the specific cells [5,9,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…Prostate-specific antigen (PSA), prostate volume (PV) and PSA density (PSAD), which is the ratio of circulating PSA to PV are also important factors for evaluating prostate diseases [1,5]. Since ET is decreasing during aging, it has been indicated as a potential risk factor for PCa together with other metabolic features such as diet, obesity, and metabolic syndrome [1,2,5]. Because of the close hormonal dependency of the prostate gland on ET levels, it has been suggested that ET levels may associate with different levels of PCa aggressivity; however, the issue remains controversial for controlled studies are missing [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Endogenous testosterone density as ratio of endogenous testosterone levels on prostate volume predicts tumor upgrading in low-risk prostate cancer

et al. 2021

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Objectives To evaluate preoperative endogenous testosterone (ET) density (ETD), defined as the ratio of ET on prostate volume, and tumor upgrading risk in low-risk prostate cancer (PCa). Materials and methods From November 2014 to December 2019, 172 low-risk patients had ET (nmol/L) measured. ETD, prostate-specific antigen density (PSAD) and the ratio of percentage of biopsy positive cores (BPC) to prostate volume (PV), defined as BPC density (BPCD), were evaluated. Associations with tumor upgrading in the surgical specimen were assessed by statistical methods. Results Overall, 121 patients (70.3%) had tumor upgrading, which was predicted by BPCD (odds ratio, OR = 4.640; 95% CI 1.903–11.316; p = 0.001; overall accuracy: 70.3%). On multivariate analysis, tumor upgrading and clinical density factors related to each other for BPCD being predicted by ETD (regression coefficient, b = 0.032; 95% CI 0.021–0.043; p < 0.0001), PSAD (b = 1.962; 95% CI 1.067–2.586; p < 0.0001) and tumor upgrading (b = 0.259; 95% CI 0.112–0.406; p = 0.001). According to the model, as BPCD increased, ETD and PSAD increased, but the increase was higher for upgraded cases who showed either higher tumor load but significantly lower mean levels of either ET or PSA. Conclusions As ETD increased, higher tumor loads were assessed; however, in upgraded patients, lower ET was also detected. ETD might stratify low-risk disease for tumor upgrading features.

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Are higher pre‐diagnosis follicle stimulating hormone levels associated with long‐term prostate cancer risk?

et al. 2022

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Background: Follicle stimulating hormone (FSH) is a pituitary hormone that helps regulate testosterone homeostasis. Although it is generally accepted that FSH levels increase with LHRH-agonist therapy for prostate cancer (PC), the specific impact of FSH levels on risk of PC diagnosis is largely unknown. The objective of this study was to perform a population-level analysis to assess the association between FSH levels and PC diagnosis. Methods: All men (n = 386,018) who had a pre-PC diagnosis FSH level and complete data were identified within the Veterans Affairs Health System between 1999 and 2018. The association between FSH level and time from FSH test to PC diagnosis was tested using stratified Cox proportional hazards models. Multivariable models were adjusted for age, year, race, body mass index, and Charlson comorbidity index. Due to nonproportional hazards over time, time to PC was modeled separately: ≤4 years after an FSH test and >4 years following an FSH test. Results: Median age at first FSH level was 64 years (interquartile range [IQR]: 54-72), median year of FSH was 2010 (IQR: 2005-2014), and 70% of the cohort was white. Median follow-up was 76 months (IQR: 38-126) during which 17,519 men (4.5%) were diagnosed with PC. On multivariable analysis, in the first 4 years after FSH test, there was no association between FSH and time to PC diagnosis.Starting from 4 years after FSH test, on multivariable analysis, a higher FSH level was associated with lower risk of PC with continuous modeling, but found no association with log continuous and categorical modeling. Conclusions:In this population-level study among male veterans receiving an FSH test for an unknown clinical indication, associations between FSH levels and PC risk were inconsistent and likely driven by selection bias and confounding variables.Future studies should consider different study designs.

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Endogenous testosterone as a predictor of prostate growing disorders in the aging male

Cited by 15 publications

References 28 publications

Endogenous testosterone density predicts unfavorable disease at final pathology in intermediate risk prostate cancer

Endogenous testosterone density predicts unfavorable disease at final pathology in intermediate risk prostate cancer

Endogenous testosterone density as ratio of endogenous testosterone levels on prostate volume predicts tumor upgrading in low-risk prostate cancer

Are higher pre‐diagnosis follicle stimulating hormone levels associated with long‐term prostate cancer risk?

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