The illusion of prostate-specific antigen decline in patients with metabolic syndrome and insulin resistance.

UNLABELLED: What's known on the subject? and What does the study add? Studies have shown that PSA is negatively associated with obesity as a result of hemodilution or metabolic effect. Hemodilution could be the main reason for low PSA levels in obese men. However, the intrinsic metabolic effects such as insulin resistance (IR) or metabolic syndrome (MS) on PSA level have not been clearly evaluated although obesity is closely tied to MS and IR. We regarded MS and IR as the pathophysiological cornerstone of metabolic disorder in obesity and analyzed the relationships among MS, IR, and PSA levels, and plasma volume by using the concept of PSA mass, the total circulating PSA protein. PSA mass did not change depending on the severity of the obesity, MS or IR. Even the group with both MS and IR, which could be the most metabolically disturbed in this study, did not have different PSA mass, comparing with the group without any MS or IR. Thus, the decline in PSA level in men with MS or IR can be also explained by increased plasma volume other than any intrinsic metabolic effects. OBJECTIVE: • To investigate the detailed mechanism of prostate-specific antigen (PSA) decline in metabolic syndrome (MS) and insulin resistance (IR), which lowers the predictive value of the PSA test, we examined the effect of haemodilution and the possibility of an intrinsic metabolic effect. PATIENTS AND METHODS: • We analysed 28,315 men who underwent routine check-ups. We compared the age-adjusted mean PSA levels in subjects with and without MS before and after adjusting or stratifying the plasma volume. We analysed changes in PSA level, plasma volume and PSA mass according to obesity grade, number of MS components, IR severity and diagnosis of MS, IR or both using an analysis of covariance. RESULTS: • The PSA levels were lower in the group with MS than in the group without MS (P= 0.001), but this difference disappeared after adjusting or stratifying the plasma volume (P > 0.05 for all). The PSA levels decreased, plasma volume increased, and PSA mass did not change as the number of MS components increased (P= 0.002, P < 0.001, P= 0.55, respectively) or the IR severity increased (P= 0.001, P < 0.001, P= 0.34, respectively). • Similarly, PSA levels were lower, plasma volumes were higher and PSA masses were the same in subjects with MS (P= 0.002, P < 0.001, P= 0.10, respectively), IR (P= 0.018, P < 0.001, P= 0.94, respectively), or both (P= 0.003, P < 0.001, P= 0.86, respectively) than in subjects without those conditions. CONCLUSION: • The PSA decline in MS and IR may result simply from a haemodilution effect and be unrelated to intrinsic metabolic disturbances. For this reason, PSA levels could be underestimated in patients with MS or IR because of haemodilution.