Understanding the effects of sildenafil treatment on erection maintenance and erection hardness.
BACKGROUND
Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance. Although intuitively related, the link between erection hardness and erection maintenance has not been formally established and quantified.


OBJECTIVE
To understand the components of erection maintenance through statistical modeling.


METHODS
Data from a double-blind placebo-controlled trial of fixed-dose sildenafil (100 or 50 mg, 8 weeks) with open-label extension of flexible-dose sildenafil (100 and 50 mg, 4 weeks) were analyzed. Erection maintenance was assessed with item 4 (how often erection was maintained) or item 5 (difficulty in maintaining erection) of the International Index of Erectile Function (IIEF). Erection hardness was assessed with the Erection Hardness Score.


METHODS
Longitudinal modeling estimated mean treatment differences averaged over the double-blind phase for sildenafil 100 mg vs. placebo and 50 mg vs. placebo. Statistical mediation analysis was applied to partition the effect of sildenafil (pooled into one treatment group) on erection maintenance directly and indirectly through erection hardness.


RESULTS
Longitudinal mean differences for sildenafil 100 and 50 mg vs. placebo were high (P < 0.0001 for each), with large standardized effect sizes (>0.8). Mediation modeling showed that sildenafil treatment affected maintenance directly as well as indirectly via erection hardness, when measured by IIEF item 4 (direct effect, 44.6%; indirect effect, 55.4%) or IIEF item 5 (direct effect, 56.9%; indirect effect, 43.1%).


CONCLUSIONS
Sildenafil treatment significantly improved erection maintenance, a physiologic requirement for satisfactory sexual performance. According to our model, only approximately half of the effect of sildenafil on erection maintenance was estimated to be driven through direct effects. Rather, the effect of sildenafil on erection maintenance seems to be substantially driven by erection hardness. Therefore, achievement of optimal initial erection hardness appears to be an important treatment goal for enhancing erection maintenance and achieving successful ED treatment.
Claes
Hubert I M
HIM
Department of Urology, University Clinics Gasthuisberg, Leuven, Belgium. Electronic address: hubert.claes@scarlet.be.
Goldstein
Irwin
I
Alvarado Hospital, Sexual Medicine and Department of Surgery, San Diego, CA, USA.
Althof
Stanley E
SE
Case Western Reserve University Medical School, Cleveland, OH, USA.
Berner
Michael M
MM
University Hospital Medical Center, Freiburg, Germany.
Cappelleri
Joseph C
JC
Pfizer Inc, Global Research & Development, New London, CT, USA.
Bushmakin
Andrew G
AG
Pfizer Inc, Global Research & Development, New London, CT, USA.
Symonds
Tara
T
Pfizer Ltd Outcomes Research, Sandwich, UK.
Schnetzler
Gabriel
G
Pfizer, International Operations, Paris, France.
D000328:Adult; D000368:Aged; D003431:Cross-Cultural Comparison; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D055815:Young Adult
D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate