title: Effect of tadalafil on male lower urinary tract symptoms: an integrated analysis of storage and voiding international prostate symptom subscores from four randomised controlled trials.
abstract: BACKGROUND
  The international prostate symptom score (IPSS) evaluates lower urinary tract symptoms (LUTS) in men with suspected benign prostatic hyperplasia (BPH); the total score does not differentiate between storage and voiding and is unevenly weighted (four questions [57%] on voiding, three questions [43%] on storage).
  
  
  OBJECTIVE
  To evaluate the relative contributions of storage and voiding IPSS subscores to total IPSS at baseline and in response to treatment with tadalafil.
  
  
  METHODS
  Integrated analysis of data from four placebo-controlled, 12-wk studies of tadalafil (5mg once daily) in 1499 men with LUTS/BPH.
  
  
  METHODS
  Relationships between total IPSS and the storage and voiding subscores were assessed using graphical exploration and linear regression modelling. Linear modelling was performed for the baseline and endpoint and for changes in subscores. The optimal storage subscore to total IPSS (S:T) ratio for IPSS improvement was identified using nonparametric regression and gradient-descent optimisation.
  
  
  CONCLUSIONS
  The contribution of storage and voiding subscores at baseline and endpoint was 38.8% and 61.2%, and 39.2% and 60.7%, respectively. This intuitive 40:60 storage-to-voiding ratio was similar at baseline and endpoint by treatment group and for changes in subscores, but spanned the entire range for individuals. Changes in total IPSS were greatest for a storage subscore percentage contribution to total IPSS of 42.7%. There was no statistical association between S:T ratio (≥ 40% vs < 40%) at baseline and response to tadalafil. The main limitation was the use of unvalidated storage and voiding IPSS subscores.
  
  
  CONCLUSIONS
  A constant S:T ratio of 4:10 was observed at baseline and endpoint. The greatest effect on total IPSS was noted for an S:T percentage contribution of 42.7%. Tadalafil efficacy was unaffected by the level of storage dysfunction at baseline.
  
  
  RESULTS
  This analysis shows that for men with BPH, improvements during treatment with tadalafil apply to both storage and voiding symptoms at a constant ratio. The extent of storage dysfunction before treatment did not affect the response to treatment.
authors.affiliation: Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield Hallam University, Sheffield, UK. Electronic address: c.r.chapple@sheffield.ac.uk.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chapple
authors.affiliation: Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Claus G
authors.initials: CG
authors.lastname: Roehrborn
authors.affiliation: Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McVary
authors.affiliation: Lilly UK, Basingstoke, UK.
authors.forename: Dapo
authors.initials: D
authors.lastname: Ilo
authors.affiliation: Lilly Deutschland, Bad Homburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Henneges
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Viktrup
mesh_terms: D002243:Carbolines / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011470:Prostatic Hyperplasia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D053448:Prostatism / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012720:Severity of Illness Index; D000068581:Tadalafil; D014554:Urination
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil
keywords: Benign prostatic hyperplasia; International prostate symptom score; Lower urinary tract symptoms; Storage; Tadalafil; Voiding