Prostate-Specific Antigen Levels During Testosterone Treatment of Hypogonadal Older Men: Data from a Controlled Trial

Context Prostate-specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated. Design Double-blinded, placebo-controlled trial. Setting Twelve US academic medical centers. Participants Seven hundred ninety hypogonadal men ≥65 years of age with average testosterone levels ≤275 ng/dL. Men at high risk for prostate cancer were excluded. Interventions Testosterone or placebo gel for 12 months. Main Outcomes Percentile changes in PSA during testosterone treatment of 12 months. Results Testosterone treatment that increased testosterone levels from 232 ± 63 ng/dL to midnormal was associated with a small but substantially greater increase (P < 0.001) in PSA levels than placebo treatment. Serum PSA levels increased from 1.14 ± 0.86 ng/mL (mean ± SD) at baseline by 0.47 ± 1.1 ng/mL at 12 months in the testosterone group and from 1.25 ± 0.86 ng/mL by 0.06 ± 0.72 ng/mL in the placebo group. Five percent of men treated with testosterone had an increase ≥1.7 ng/mL and 2.5% of men had an increase of ≥3.4 ng/mL. A confirmed absolute PSA >4.0 ng/mL at 12 months was observed in 1.9% of men in the testosterone group and 0.3% in the placebo group. Four men were diagnosed with prostate cancer; two were Gleason 8. Conclusions When hypogonadal older men with normal baseline PSA are treated with testosterone, 5% had an increase in PSA ≥1.7 ng/mL, and 2.5% had an increase ≥3.4 ng/mL.