ABSTRACT
Multiple studies have evaluated the use of PDE5 inhibitors in penile rehabilitation following nerve-sparing prostatectomy. These studies have evaluated the use of various pharmacologic agents as well as various approaches to treatment (on-demand vs. rehabilitative). Most of these studies relied on self-reported outcomes to determine efficacy of the therapy which could allow response bias to affect their results. The aim of this study was to evaluate the effects of nightly sildenafil citrate therapy during penile rehabilitation, using nocturnal penile rigidity (RigiScan(™), Gotop Medical, Inc., St. Paul, MN, USA) in addition to the IIEF-EF. Patients with localized prostate cancer and normal erectile function prior to nsRP were randomized to take either nightly 50 mg sildenafil citrate or placebo starting the night following surgery. Both groups were allowed on-demand sildenafil citrate. Erectile function was evaluated at 2 weeks, 3, 6, 9 and 12 months post-operatively, with a final assessment made at 13 months, following a 1 month drug washout. At all time points, self-reported (IIEF-EF) and objective (RigiScan(™)) measures were obtained and evaluated. About 74 of 97 randomized patients completed the study. On completion, 40% of patients in each group had normal erectile function based on RigiScan(™) (p = 1.0). Additionally, no statistical differences were seen using the IIEF-EF domain (32.4% of placebo, 29% of treatment; p = 0.79). Multivariable analysis showed no significant differences in erectile function based on treatment intervention. Results did show that African-American men in this cohort were at higher risk for lower RigiScan(™) scores over time (OR: 0.48, p = 0.0399). This study demonstrates that nightly sildenafil citrate does not provide a therapeutic benefit for recovery of erectile function post-prostatectomy when compared to on-demand dosing using both self-reported as well as objective measures. Differences in objective recovery parameters based on patients' race/ethnicity warrant further investigation.
Subject(s)
Erectile Dysfunction/drug therapy , Penile Erection/drug effects , Phosphodiesterase 5 Inhibitors/therapeutic use , Prostatectomy/adverse effects , Sildenafil Citrate/administration & dosage , Sildenafil Citrate/therapeutic use , Double-Blind Method , Humans , Male , Phosphodiesterase 5 Inhibitors/administration & dosage , Placebos , Prospective Studies , Prostate/surgery , Prostatic Neoplasms/surgery , Recovery of FunctionABSTRACT
Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation with male virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectile mechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues.
Subject(s)
Erectile Dysfunction/drug therapy , Neurotransmitter Agents/therapeutic use , Penile Erection/drug effects , Phosphodiesterase 5 Inhibitors/therapeutic use , Animals , Drug Therapy, Combination , Erectile Dysfunction/diagnosis , Erectile Dysfunction/epidemiology , Erectile Dysfunction/physiopathology , Humans , Male , Neurotransmitter Agents/adverse effects , Phosphodiesterase 5 Inhibitors/adverse effects , Recovery of Function , Risk Factors , Signal Transduction/drug effects , Treatment OutcomeABSTRACT
The high prevalence of TMPRSS2-ERG rearrangements ( approximately 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.
