Benign Prostatic Hyperplasia (BPH) is driven by changes in the proliferation and contractility of stromal cells within the human prostate. Pharmacotherapies targeting smooth muscle tone are first line therapies in the treatment of BPH, but commonly fail and the subset of responsive patients is unknown. To understand the mechanism underlying responsiveness to pharmacotherapy, we developed a novel model of prostate contractility, focussing on myogenic tone. Individual patient responses were stratified to two commonly used classes of pharmacotherapy, α1-antagonists (Tamsulosin) and PDE-5 inhibitors (Sildenafil).
Non-malignant human prostate tissue was collected from the Transition Zone (TZ) of men undergoing radical prostatectomy. Tension recordings were obtained from samples for a baseline period, and then exposed to Tamsulosin (0.1nM) or Sildenafil (10µM). A multi-variate regression analysis was constructed against retrospectively accessed patient clinical details, and patient responsiveness to pharmacotherapies, as measured by the basal tension (mN), amplitude (N/g) and frequency (min-1) of contractions.
Myogenic tone was present in TZ specimens, with the frequency of contractions significantly (p < 0.05) greater in specimens from men with clinically diagnosed BPH, when compared to both age and prostate-volume matched controls. Tamsulosin and Sildenafil both significantly attenuated myogenic tone, with a notable inter-patient variability in responsiveness. When correlated to patient parameters, responsiveness to Tamsulosin was positively correlated with age (R2 =0.36, p < 0.01) and prostate volume (R2 =0.41, p < 0.05). Responsiveness to Sildenafil was negatively correlated with age (R2 =0.45, p < 0.05).
Our results demonstrate that myogenic tone is present within the human prostate, and significantly upregulated in patients with BPH. Tamsulosin was more effective in older men or those with larger prostates, while Sildenafil was more effective in older men. Consequently, myogenic tone is of interest identifying responders to BPH pharmacotherapies, where patient parameters can be used to provide the best personalized, evidence-based treatment.