Introduction: Male lower urinary tract symptoms (LUTS) have been correlated with an increased risk of death, and it is unclear if this is a causal association. Our objective was to determine whether a reduction in LUTS is associated with a reduced risk of mortality. Methods: We conducted a secondary analysis of the pivotal Medical Treatment of Prostate Symptoms (MTOPS) randomised trial. Men age >50 years with moderate to severe LUTS on the AUASS were randomised to placebo, doxazosin, finasteride, or doxazosin and finasteride. Our primary exposure was the change in the AUASS from baseline. This was modelled as a time-varying covariate and recalculated for each of the biyearly protocolized visits. Our primary outcome was death, which was prospectively recorded during the study. We used an extended cox model and adjusted it for age and treatment assignment. We conducted a similarly adjusted sensitivity analysis among those who were assigned active treatment only. Means and standard deviations (SD) and hazard ratios (HR) with 95% confidence intervals are reported. Results: A total of 3046 men were randomised and had a baseline AUASS; 27 baseline variables were similar between the 705 men who did not have any LUTS improvement and the 2341 men who did have improvement. The mean age was 62.6 (SD7.3), and the mean baseline AUASS was 17.2 (SD6.1). During the mean observation period of 6.1 (SD1.2) years there were 117 (3.8%) deaths. For each 1-point improvement in the AUASS, the HR for death was 0.96 (0.94-0.99, p=0.01); a 5-point improvement in the AUASS resulted in a HR for death of 0.83 (95%CI 0.72-0.96). This relationship was similar among the 2309 men who received some form of active treatment (HR 0.95, 0.92-0.98, p<0.01), independent of treatment group. A comparable significant reduction in death was seen with improvements in the storage and voiding subscales individually. Conclusions: Improvement in male LUTS was associated with a reduced risk of death. Unmeasured confounding was partly mitigated by using clinical trial data, where randomisation determined the likelihood of LUTS improvement. Further study is warranted to determine if the male LUTS treatment paradigm should shift towards symptom treatment independent of bother. SOURCE OF Funding: None
