Testosterone treatment in hypogonadal men: prostate-specific antigen level and risk of prostate cancer

To assess prostate-specific antigen (PSA) levels in hypogonadal men after testosterone replacement by three different methods and attempt to determine any possible relationship between hypogonadism and prostate cancer in this study population.

A total of 90 consecutive men who had erectile dysfunction and were found to have hypogonadism were monitored with digital rectal examination (DRE) and measurement of PSA levels before and after testosterone replacement therapy. The patients were treated with one of three options: (1) testosterone enanthate by intramuscular injections, 200 or 300 mg every 2 or 3 weeks (N = 25); (2) testosterone nonscrotal patches, 5 mg daily (N = 16); or (3) clomiphene citrate, 50 mg orally three times a week, in patients with functional secondary hypogonadism (N = 49). Treatment was continued for 2 to 3 months, after which PSA levels were reassessed. Patients with suspicious results on DRE and increased PSA levels before or after treatment with testosterone underwent prostate biopsy. For statistical analysis, patients were categorized into two age-groups--40 to 60 years old and 61 to 80 years old.

With all methods of testosterone replacement, PSA levels increased in both age-groups. Endogenous testosterone elevation from clomiphene stimulation raised PSA levels the highest, and testosterone patches yielded the least PSA response. Ten men underwent biopsy of the prostate. In one patient, a nodule was found on DRE; the other nine men underwent biopsy because of suspicious PSA levels. Of these patients, two were found to have adenocarcinoma, and a third man who underwent rebiopsy was also found to have cancer. Therefore, 3 of the 90 patients (3.3%) had prostate cancer.

PSA levels increased in response to all types of testosterone replacement, regardless of whether the testosterone level was raised endogenously or exogenously. PSA levels are inappropriately low in hypogonadal men and may mask an underlying cancer. Determining PSA levels before and after testosterone treatment is recommended. Elevated PSA levels before or after testosterone therapy should prompt performance of a urologic evaluation for possible prostate biopsy.