Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory

PurposeWe measured prostate specific antigen after 12 months of testosterone replacement therapy in hypogonadal men.Materials and MethodsData were collected from the TRiUS (Testim® Registry in the United States), an observational registry of hypogonadal men on testosterone replacement therapy (849). Participants were Testim naïve, had no prostate cancer and received 5 to 10 gm Testim 1% (testosterone gel) daily.ResultsA total of 451 patients with prostate specific antigen and total testosterone values were divided into group A (197 with total testosterone less than 250 ng/dl) and group B (254 with total testosterone 250 ng/dl or greater). The groups differed significantly in free testosterone and sex hormone-binding globulin, but not in age or prostate specific antigen. In group A but not group B prostate specific antigen correlated significantly with total testosterone (r = 0.20, p = 0.005), free testosterone (r = 0.22, p = 0.03) and sex hormone-binding globulin (r = 0.59, p = 0.002) at baseline. After 12 months of testosterone replacement therapy, increase in total testosterone (mean ± SD) was statistically significant in group A (+326 ± 295 ng/dl, p <0.001; final total testosterone 516 ± 28 ng/dl) and group B (+154 ± 217 ng/dl, p <0.001; final total testosterone 513 ± 20 ng/dl). After 12 months of testosterone replacement therapy, increase in prostate specific antigen was statistically significant in group A (+0.19 ± 0.61 ng/ml, p = 0.02; final prostate specific antigen 1.26 ± 0.96 ng/ml) but not in group B (+0.28 ± 1.18 ng/ml, p = 0.06; final prostate specific antigen 1.55 ± 1.72 ng/ml). The average percent prostate specific antigen increase from baseline was higher in group A (21.9%) than in group B (14.1%). Overall the greatest prostate specific antigen was observed after 1 month of treatment and decreased thereafter.ConclusionsPatients with baseline total testosterone less than 250 ng/dl were more likely to have an increased prostate specific antigen after testosterone replacement therapy than those with baseline total testosterone 250 ng/dl or greater, supporting the prostate saturation hypothesis. Clinicians should be aware that severely hypogonadal patients may experience increased prostate specific antigen after testosterone replacement therapy.