Autonomic nervous system overactivity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia

Purpose: The relationship of lower urinary tract symptoms (LUTS) to objective measures of benign prostatic hyperplasia (BPH), such as prostatic size and urodynamic parameters, has proved difficult to evaluate. Studies in animal models of BPH suggest that autonomic nervous system (ANS) activity is an important determinant of prostatic growth. We investigated the relationship of ANS activity to LUTS as well as to objective measures of BPH in men with BPH. Materials and Methods: This study was done in 3,047 men with LUTS secondary to BPH during screening for enrolment at 1 center in a large, multicenter, double-blind, placebo controlled trial designed to assess the long-term effects of medical therapy on BPH progression. A total of 38 men with an American Urological Association (AUA) symptom score of 8 or greater and a maximum urinary flow rate of 4 to less than 15 ml per second had ANS activity assessed based on heart rate, blood pressure, the response to circulatory stress via tilt table, and plasma and urinary catecholamine. These ANS related variables were compared with subjective measures of LUTS (AUA symptom score, quality of life score and BPH impact index), overall health measures (RAND 36-Item Health Survey) and objective clinical measures of BPH (prostate size, post-void residual volume and maximum urinary flow rate). Pearson correlation coefficients were calculated for each ANS variable vs each LUTS and BPH variable. These correlations were further assessed using stepwise multiple regression analysis to determine which BPH and LUTS variables were independently related to the ANS variable. Relationships that were identified as significant then underwent final multiple regression analysis together with control variables to exclude known extraneous and confounding influences on ANS activity. Results: After adjusting for extrinsic influences on ANS activity AUA symptom score (p < 0.01), BPH impact index score (p < 0.001) and quality of life score (p < 0.05) were independently associated with the change in systolic and diastolic blood pressure 1 and 5 minutes after tilt. Additionally, prostate transition zone volume (p < 0.001) and the RAND 36-Item Health Survey mental subscale score (p < 0.001) were independently associated with the plasma norepinephrine response to tilt. Conclusions: ANS hyperactivity is significantly associated with the most commonly used measures of LUTS, namely AUA symptom score and BPH impact index score. Also, the magnitude of the serum norepinephrine increase after tilt predicts prostate size. These relationships persist after controlling for extrinsic influences on ANS activity. The current findings may have important implications concerning the pathophysiological mechanisms underlying or influencing LUTS as well as its optimal treatment in men with BPH.