Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging

Abstract

Study type: Prognosis (inception cohort).

Level of evidence: 1b.

Objective: To evaluate the relationship between testosterone levels and the development of high-risk prostate cancer, by prospectively examining serum androgen concentrations in a well-studied cohort, as the role of testosterone in prostate cancer progression is debated.

Patients and methods: The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of > or =20 ng/mL at diagnosis, or a Gleason score of > or =8. The hazard ratio (HR) of high-risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses.

Results: The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95% confidence interval, CI, 1.01-4.23; P = 0.047); the likelihood for men aged < or =65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35-2.6; P = 0.9). The risk rate per person-years increased from lowest to highest tercile of FTI for the oldest men (age >70 years) but this trend was not apparent among younger men.

Conclusion: Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone-replacement therapy.

Figures

FIG. 1

The FTI vs the rate of high-risk prostate cancer; results of proportional-hazards model that includes FTI, age and date of sample that was solved for three hypothetical 50-year-old men, each of whom were tracked with constant age-adjusted FTI levels, at the fifth, 50th and 95th percentiles, respectively. Differences in survival appear to be similar to age 65 years, so that by age 80 years the probability of developing high-risk prostate cancer for a man at the fifth percentile and the 50th percentile of FTI was estimated as 3.8% and 6.4%, respectively, compared to a rate of 13.6% for a man at the 95th percentile of FTI (P 0.001).