Diabetes mellitus has been linked to lower serum prostate-specific antigen (PSA) levels, potentially influencing prostate cancer screening accuracy. While some studies have suggested that type 2 diabetes is associated with a reduced risk of prostate cancer, diabetic patients experience higher prostate cancer mortality and more advanced disease at diagnosis. The mechanisms underlying these associations remain unclear. This systematic review investigates the effect of diabetes and its treatments on serum PSA levels in asymptomatic men without prostate cancer.

A systematic search of PubMed was conducted using predefined criteria. Studies published after 1988, assessing PSA levels in diabetic and non-diabetic men over 18 years old, were included. Meta-analysis was performed using a random-effects model to estimate the mean difference in PSA levels. Study quality was assessed using the Newcastle-Ottawa Scale, and publication bias was evaluated via funnel plots.

A total of 778 studies were screened, with 13 studies included in final analysis. The pooled analysis showed lower PSA level in diabetic men compared to non-diabetics (standardized mean difference: -0.51; 95% CI: -0.95 to -0.21). High study heterogeneity (I² = 99%) was observed. Hormonal alterations, chronic inflammation, and metabolic changes were proposed as potential mechanisms. Differences in study design, population characteristics, and PSA measurement methods contributed to variability.

Diabetes is associated with lower PSA levels, which may affect prostate cancer detection. Adjustments to PSA screening thresholds in diabetic men should be considered. Further research is needed to explore the impact of diabetes management on PSA levels and prostate cancer outcomes.