Sex hormone balance and PSA-derived biomarkers in cancer-free African migrant men in Italy: Implications for prostate cancer early detection

Background: Men of African ancestry experience a disproportionate burden of prostate cancer (PCa), with higher incidence and mortality than men of European ancestry. Although social determinants of health, barriers to care, and delayed diagnosis are key contributors to these disparities, ancestry- and context-related differences in sex hormone milieu and PCa-associated laboratory biomarkers remain insufficiently characterized. We investigated sex hormone profiles, PSA molecular forms, and derived hormone-to-biomarker ratios in cancer-free African migrant men living in Italy compared with White controls. Methods: This single-center prospective observational study included 87 cancer-free men: 40 Black men of African origin and 47 White controls. Serum total prostate-specific antigen (PSA), testosterone, estradiol, and the testosterone-to-estradiol ratio were compared between groups. Free PSA, [-2]proPSA, and the Prostate Health Index (PHI) were assessed in the subset of participants with available PSA molecular form measurements. Exploratory hormone-to-biomarker ratios were calculated by relating testosterone, estradiol, and the testosterone-to-estradiol ratio to total PSA, free PSA, [-2]proPSA, and PHI. Results: Total PSA levels did not significantly differ between Black men of African origin and White controls (median 1.22 vs. 1.10 ng/mL; P = 0.407). Testosterone concentrations were also comparable between groups (median 468.48 vs. 412.88 ng/dL; P = 0.362). Conversely, estradiol concentrations were significantly higher in Black men of African origin (median 32.29 vs. 21.53 pg/mL; P < 0.001; q < 0.001), while the testosterone-to-estradiol ratio was significantly lower (median 12.85 vs. 20.20; P < 0.001; q < 0.001). PHI and [-2]proPSA were significantly lower in Black men of African origin than in White controls (PHI: median 27.06 vs. 52.72, P = 0.004, q = 0.012; [-2]proPSA: median 8.90 vs. 23.80 pg/mL, P = 0.008, q = 0.021). Estradiol-to-PSA molecular-form ratios were consistently higher in Black men of African origin, particularly estradiol/free PSA, estradiol/[-2]proPSA, and estradiol/PHI, whereas the (testosterone-to-estradiol ratio)/total PSA was lower. Conclusions: Cancer-free African migrant men living in Italy showed a distinct biochemical phenotype characterized by higher estradiol levels and a lower testosterone-to-estradiol ratio, despite comparable total PSA and testosterone levels. The concomitantly lower PHI and [-2]proPSA values, together with higher estradiol-to-PSA-derived biomarker ratios, suggest that sex hormone balance may influence the context-aware interpretation of PCa biomarkers in this population.