madman
Super Moderator
* Our study found that men receiving TRT had significantly lower 4Kscores and PSA levels despite equivalent age and prostate volumes along with similar rates of clinically significant prostate cancer. These findings suggest that 4Kscore may be less affected by exogenous testosterone than PSA, supporting its potential utility as a more reliable screening tool for prostate cancer in hypogonadal men on TRT.
Figure 1:
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The Impact of Testosterone Replacement Therapy on 4KSCORE and PSA: A Matched Cohort Analysis (2025)
Guerard, T1; Nativ, O1; Angulo Llanos , L1; Ryan, J1; Porto, J1; Cortizas, E1; Parekh, D1; Kava, B1; Masterson, T1; Punnen, S1
1 - University of Miami
Introduction
Testosterone replacement therapy (TRT) is commonly prescribed in hypogonadal men, but its effect on prostate cancer biomarkers remains unclear. While PSA is known to fluctuate with the use of exogenous testosterone, the impact of TRT on the 4Kscore, a validated blood-based risk assessment test for clinically significant prostate cancer (Grade Group ≥2), has not been studied. We aimed to evaluate whether 4Kscore performance in men receiving TRT compared to matched non-users.
Objective
To evaluate whether testosterone replacement therapy (TRT) influences 4Kscore results in men undergoing prostate cancer screening. Specifically, we aimed to determine if 4Kscore is less susceptible than PSA to elevation from exogenous testosterone, and whether its performance remains consistent across different routes of administration.
Methods
We retrospectively identified 137 men receiving TRT prior to 4Kscore testing and matched them 1:1 to 137 non-users by age (±5 years), race, and prostate volume (±10 cc). PSA, PSA density, 4Kscore, MRI PIRADS scores, and biopsy outcomes were compared between groups. Median total and free testosterone levels in the TRT group were reported for context. Subgroup analysis was conducted on the type of administration including: intramuscular (IM), transdermal gel, and subdermal pellet.
Results
Despite receiving TRT (median total testosterone: 454 ng/dL; median free testosterone: 30 ng/dL), men on TRT had significantly lower PSA (5.1 vs. 6.7 ng/mL, p < 0.001), PSA density (0.10 vs. 0.13 ng/mL/cc, p = 0.0054), and 4Kscore (13% vs. 17%, p = 0.0013) compared to controls. PIRADS 4–5 lesions were more frequent in non-TRT men (47% vs. 26%). GG2+ cancer rates were similar (15 vs. 16), though fewer biopsies were performed in the TRT group (47% vs. 98%). Among TRT users, IM injection yielded the highest median 4Kscore of 13 (8, 24), however there was no significant difference in 4Kscore based on testosterone formulation (IM, gel, or pellet; p = 0.29), suggesting 4Kscore performance is consistent across routes of administration.
Conclusions
Our study found that men receiving TRT had significantly lower 4Kscores and PSA levels despite equivalent age and prostate volumes along with similar rates of clinically significant prostate cancer. These findings suggest that 4Kscore may be less affected by exogenous testosterone than PSA, supporting its potential utility as a more reliable screening tool for prostate cancer in hypogonadal men on TRT. Prospective studies are needed to validate these findings and further assess the clinical implications of 4Kscore use in this growing population.
Figure 1:
==========
The Impact of Testosterone Replacement Therapy on 4KSCORE and PSA: A Matched Cohort Analysis (2025)
Guerard, T1; Nativ, O1; Angulo Llanos , L1; Ryan, J1; Porto, J1; Cortizas, E1; Parekh, D1; Kava, B1; Masterson, T1; Punnen, S1
1 - University of Miami
Introduction
Testosterone replacement therapy (TRT) is commonly prescribed in hypogonadal men, but its effect on prostate cancer biomarkers remains unclear. While PSA is known to fluctuate with the use of exogenous testosterone, the impact of TRT on the 4Kscore, a validated blood-based risk assessment test for clinically significant prostate cancer (Grade Group ≥2), has not been studied. We aimed to evaluate whether 4Kscore performance in men receiving TRT compared to matched non-users.
Objective
To evaluate whether testosterone replacement therapy (TRT) influences 4Kscore results in men undergoing prostate cancer screening. Specifically, we aimed to determine if 4Kscore is less susceptible than PSA to elevation from exogenous testosterone, and whether its performance remains consistent across different routes of administration.
Methods
We retrospectively identified 137 men receiving TRT prior to 4Kscore testing and matched them 1:1 to 137 non-users by age (±5 years), race, and prostate volume (±10 cc). PSA, PSA density, 4Kscore, MRI PIRADS scores, and biopsy outcomes were compared between groups. Median total and free testosterone levels in the TRT group were reported for context. Subgroup analysis was conducted on the type of administration including: intramuscular (IM), transdermal gel, and subdermal pellet.
Results
Despite receiving TRT (median total testosterone: 454 ng/dL; median free testosterone: 30 ng/dL), men on TRT had significantly lower PSA (5.1 vs. 6.7 ng/mL, p < 0.001), PSA density (0.10 vs. 0.13 ng/mL/cc, p = 0.0054), and 4Kscore (13% vs. 17%, p = 0.0013) compared to controls. PIRADS 4–5 lesions were more frequent in non-TRT men (47% vs. 26%). GG2+ cancer rates were similar (15 vs. 16), though fewer biopsies were performed in the TRT group (47% vs. 98%). Among TRT users, IM injection yielded the highest median 4Kscore of 13 (8, 24), however there was no significant difference in 4Kscore based on testosterone formulation (IM, gel, or pellet; p = 0.29), suggesting 4Kscore performance is consistent across routes of administration.
Conclusions
Our study found that men receiving TRT had significantly lower 4Kscores and PSA levels despite equivalent age and prostate volumes along with similar rates of clinically significant prostate cancer. These findings suggest that 4Kscore may be less affected by exogenous testosterone than PSA, supporting its potential utility as a more reliable screening tool for prostate cancer in hypogonadal men on TRT. Prospective studies are needed to validate these findings and further assess the clinical implications of 4Kscore use in this growing population.
