Changes in molecular forms of prostate-specific antigen during treatment with finasteride

Objective To study the influence of finasteride treatment on the molecular forms of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). Patients and methods Total PSA, free PSA and PSA complexed to alpha(1)-antichymotrypsin (PSA-alpha(1)ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in-house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). Results The baseline values were not significantly different between the groups, with mean (SD) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA-alpha(1)ACT levels in plasma and serum (P < 0.001). However, complexed-to-total (c/t) and free-to-total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow-up. Conclusion The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA-alpha(1)ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.