TY - JOUR
T1 - Phosphodiesterase Type 5 Inhibitors in Postprostatectomy Erectile Dysfunction
T2 - A Critical Analysis of the Basic Science Rationale and Clinical Application
AU - Hatzimouratidis, Konstantinos
AU - Burnett, Arthur L.
AU - Hatzichristou, Dimitrios
AU - McCullough, Andrew R.
AU - Montorsi, Francesco
AU - Mulhall, John P.
N1 - Funding Information:
Data from limited clinical studies show that PDE5-Is are efficacious in the treatment of post-RP ED. While experimental evidence suggests that PDE5-Is can prevent smooth-muscle apoptosis and fibrosis related to ED after RP in the animal model, these findings have not yet been replicated in humans. Therefore, their use in penile rehabilitation programs remains controversial. More prospective, randomized, placebo-controlled studies are needed to firmly establish efficacy of PDE5-Is in rehabilitation programs. Much like breast reconstruction after mastectomy for breast cancer, the treatment of ED after RP has a tremendously positive impact on quality of life for the patient and his partner. We should properly counsel patients preoperatively and offer medical treatment based on the currently available data. Ultimately, the patient will decide to seek and accept treatment, but optimally both he and his partner should be involved in the decision-making process. Author contributions : Konstantinos Hatzimouratidis had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design : Montorsi, Hatzichristou, Hatzimouratidis. Acquisition of data : Hatzimouratidis. Analysis and interpretation of data : Hatzimouratidis. Drafting of the manuscript : Hatzimouratidis. Critical revision of the manuscript for important intellectual content : Montorsi, Hatzichristou, Mulhall, Burnett, McCullough. Statistical analysis : None. Obtaining funding : None. Administrative, technical, or material support : Hatzimouratidis. Supervision : Montorsi, Hatzichristou, Mulhall, Burnett, McCullough. Other (specify): None. Financial disclosures : I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Francesco Montorsi, Dimitrios Hatzichristou, John Mulhall, Arthur Burnett, and Andrew McCullough are consultants/investigators of Bayer-GlaxoSmithKline, Lilly-ICOS, and Pfizer. Funding/Support and role of the sponsor : None.
PY - 2009/2
Y1 - 2009/2
N2 - Context: Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs. Objective: To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED. Evidence acquisition: A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed. Evidence synthesis: Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine. Conclusions: PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.
AB - Context: Erectile dysfunction (ED) after radical prostatectomy (RP) has a significant negative impact on a patient's health-related quality of life. Phosphodiesterase type 5 inhibitors (PDE5-Is) have recently been utilized not only as a treatment of ED in this population but also as a preventive strategy in penile rehabilitation programs. Objective: To elucidate the pathophysiologic mechanisms of post-RP ED, to assess the need for rehabilitation following surgery, and to analyze the basic scientific evidence and clinical applications of PDE5-Is for the prevention and treatment of ED. Evidence acquisition: A systematic review of the literature using Medline, Cancerlit, and the Cochrane Library was conducted for the period between January 1997 and June 2008 using the keywords erectile dysfunction, radical prostatectomy, and phosphodiesterase inhibitors. Efficacy and safety of PDE5-Is in the randomized, placebo-controlled trials are evaluated in this review, and the limitations of the remaining studies are also discussed. Evidence synthesis: Post-RP ED has many factors. Cavernosal nerve injury induces pro-apoptotic factors (ie, loss of smooth muscle) and pro-fibrotic factors (ie, an increase in collagen) within the corpora cavernosa. Cavernosal changes may also be attributed to poor oxygenation due to hemodynamic changes. Experimental data support the concept of cavernosal damage and suggest a protective role for daily dosage of a PDE5-I; however, similar data have not yet been replicated in humans. Penile rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their use or the best treatment strategy. PDE5-Is are efficacious and safe in young patients with normal preoperative erectile function who have undergone bilateral nerve-sparing radical prostatectomy. On-demand use of a PDE5-I may be at least as efficacious as daily use. PDE5-I use in penile rehabilitation programs is not supported by rigorous level 1 evidence-based medicine. Conclusions: PDE5-Is are an efficacious and safe treatment for post-RP ED in properly selected patients. The experimental results on the protective role of daily dosages of PDE5-Is, while robust, have not been replicated in humans. With current human data, the role of a PDE5-I alone as a rehabilitation strategy is unclear and deserves further investigation.
KW - Erectile dysfunction
KW - Penile rehabilitation
KW - Phosphodiesterase type 5 inhibitors
KW - Radical prostatectomy
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U2 - 10.1016/j.eururo.2008.10.028
DO - 10.1016/j.eururo.2008.10.028
M3 - Review article
C2 - 18986755
AN - SCOPUS:57649184019
SN - 0302-2838
VL - 55
SP - 334
EP - 347
JO - European Urology
JF - European Urology
IS - 2
ER -