We assessed self-reported health-related quality of life (HRQoL) and longitudinal changes in sex hormones among 86 prostate cancer (PCa) patients without distant metastases 5 years after radiotherapy (RT) combined with ongoing antiandrogen (AA) treatment. HRQoL outcomes were compared with scores from age-matched controls without a cancer diagnosis (NORM). Compared with NORM, patients scored statistically (Po0.05) and clinically (effect size X0.4) lower on sexual domains, and statistically (Po0.05) lower on physical function and vitality. Estimated free testosterone and measured serum estradiol had increased from baseline in most patients, but did not correlate with HRQoL outcomes 5 years after the start of treatment.