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Important Note: The following information
is provided for your education. It should not be relied upon for
personal diagnosis or treatment. If you believe that a
particular therapy applies to you or someone you care about, be
sure to consult a doctor before trying it.
Erectile Dysfunction Research:
2002-2006
J Sex Med. 2006 Nov 1; [Epub ahead of print]
Sexual Function and Obstructive Sleep Apnea-Hypopnea: A
Randomized Clinical Trial Evaluating the Effects of Oral-Appliance and
Continuous Positive Airway Pressure Therapy.
Hoekema A, Stel AL, Stegenga B, van der Hoeven JH, Wijkstra PJ, van Driel
MF, de Bont LG.
Department of Oral and Maxillofacial Surgery, University Medical Center
Groningen, University of Groningen, Groningen, The Netherlands.
Introduction. The obstructive sleep apnea-hypopnea syndrome (OSAHS) is
associated with sexual dysfunction. Although successful treatment with
continuous positive airway pressure (CPAP) has been demonstrated to improve
sexual function, the effects of oral-appliance therapy are unknown. Aim. The
aims of this study were to determine to what extent untreated male OSAHS
patients experience sexual dysfunctions compared with control subjects, and
second, to evaluate the effects of oral-appliance and CPAP therapy on sexual
functioning. Methods. Sexual functioning was determined in 48 OSAHS patients
with the Golombok Rust inventory of sexual satisfaction (GRISS) and a
testosterone measurement. GRISS outcomes were compared with 48 age-matched male
controls without any sexual problems. Patients were randomized for either
oral-appliance or CPAP therapy. After 2-3 months of treatment, the GRISS and
testosterone measurements were repeated. Main Outcome Measure. The outcomes on
the GRISS were used as the main outcome measure. Results. Compared with
controls, OSAHS patients had significantly more erectile dysfunction (mean +/-
standard deviation; OSAHS 8.7 +/- 3.8 vs. controls 6.8 +/- 2.6) and sexual
dissatisfaction (mean +/- standard deviation; OSAHS 9.7 +/- 4.2 vs. controls 8.1
+/- 2.6) as indicated by the GRISS. No significant changes in the GRISS or
testosterone levels were observed in the 20 and 27 patients completing the
follow-up review for oral-appliance and CPAP therapy. A correlation was
demonstrated between the extent of erectile dysfunction at baseline and
improvements in erectile function following treatment (r = -0.547, P = 0.000).
Conclusions. This study confirms that male OSAHS patients show more sexual
dysfunctions compared with age-matched control subjects. Although significant
improvements in sexual functioning in neither the oral-appliance nor CPAP-treated
group could be established, our findings suggest that untreated OSAHS patients
with pronounced erectile dysfunction experience some improvement following
treatment.
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Curr Med Res Opin. 2006 Nov;22(11):2111-20.
Sildenafil citrate for erectile dysfunction in men with diabetes
and cardiovascular risk factors: a retrospective analysis of pooled data from
placebo-controlled trials.
Blonde L.
Ochsner Clinic Foundation, New Orleans, LA 70121, USA. lblonde@ochsner.org
OBJECTIVE: Cardiovascular (CV) risk factors are associated with an increased
risk of erectile dysfunction (ED). In men with diabetes mellitus (DM), pooled
from clinical trials of sildenafil treatment for ED, this retrospective analysis
determined efficacy and safety, overall and in subgroups with additional CV risk
(i.e., hypertension, dyslipidemia, and smoking). RESEARCH DESIGN AND METHODS:
From the manufacturer's database of worldwide research, 12-week data from men
with DM were pooled from randomized, double-blind, placebo-controlled trials of
flexible-dose sildenafil (25, 50, or 100 mg, PRN) for ED. MAIN OUTCOME MEASURES:
Question 3 (achieving an erection), question 4 (maintaining an erection), and
the Erectile Function domain of the International Index of Erectile Function;
percentage of successful intercourse attempts according to patient event logs;
and response to a global efficacy question (GEQ). Differences between groups
were determined using logistic regression (percentage of responders according to
GEQ) and analysis of covariance (all other outcomes). RESULTS: Inclusion
criteria were met by 11 trials and by 974 men with DM and ED who were randomized
to placebo (n = 482) and sildenafil (n = 492) within the selected trials. For
all outcomes, overall and regardless of additional CV risk, the benefit was
greater for sildenafil versus placebo (p < or = 0.0001), including 3-fold more
men responding that sildenafil treatment improved their erections (62% vs. 18%)
and a more than doubling of the mean +/- standard error percentage of successful
sexual intercourse attempts (52.6 +/- 5.0 vs. 22.4 +/- 5.1). Adverse events were
mild to moderate and included (sildenafil vs. placebo) headache (5% vs. 2%),
flushing (7% vs. 2%), and dyspepsia (4% vs. 0%), which is consistent with the
profile in the general population of men treated with sildenafil for ED.
CONCLUSION: This retrospective analysis of pooled data showed that sildenafil
was well tolerated and improved erectile function and intercourse success in men
with ED and DM, regardless of additional CV risk factors.
-----
Int J Clin Pract. 2006 Nov;60(11):1378-85.
First-dose success with vardenafil in men with erectile
dysfunction and associated comorbidities: RELY-I.
Valiquette L, Montorsi F, Auerbach S; FOR THE VARDENAFIL STUDY GROUP.
Department of Urology, Hopital St-Luc du CHUM, Montreal, Quebec, Canada.
First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be
adversely affected in patients with comorbidities. This article reports
first-dose success rates for vardenafil 10 mg in men with erectile dysfunction
(ED) and associated comorbidities who participated in the challenge phase of the
Reliability - Vardenafil for Erectile Dysfunction I study. This study involved
an open-label, single-dose, 1-week challenge period where patients who achieved
SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for
12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and
SEP-3 (maintenance of erection to completion of intercourse) were stratified
according to comorbidities. Safety was assessed using adverse events (AEs). Of
600 men who received a single 10 mg dose of vardenafil, 32% had hypertension,
16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall
effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients
with and without specific comorbidities. Initial overall success rates for SEP-2
and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose
SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n =
191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men
with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including
the most frequently reported flushing (3.5%), were mild to moderate in
intensity. Vardenafil 10 mg is generally well tolerated and efficacious,
providing first-dose success with a consistently high rate of reliability of
penetration and maintenance of erection in men with ED and associated
comorbidities.
-----
J Long Term Eff Med Implants. 2006;16(3):235-47.
Technical advances in penile prostheses.
Lazarou S, Reyes-Vallejo L, Morgentaler A.
Harvard Medical School, Beth Israel Deaconess Medical Center, Division of
Urology, Boston, MA, USA.
Despite the introduction of oral phosphodiesterase inhibitors, penile prostheses
continue to be an important form of treatment for erectile dysfunction (ED).
Penile prostheses are associated with high satisfaction rates due to their ease
of use, reliability, and ability to provide excellent rigidity. Advances over
the last decade include steps to reduce mechanical failures and surface coatings
to prevent prosthetic infections. These advances make the penile prosthesis an
excellent option for the treatment of ED, particularly for men who fail oral
therapy.
-----
Curr Urol Rep. 2006 Nov;7(6):490-6.
Erectile dysfunction and cardiac disease: recommendations of the
Second Princeton Conference.
Rosen RC, Jackson G, Kostis JB.
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical
School, 671 Hoes Lane, Piscataway, NJ 08854, USA. rosen@umdnj.edu
Erectile dysfunction (ED) has been linked increasingly to cardiovascular risk
factors and comorbidities. Considering the potential risk associated with sexual
activity, guidelines were developed (Princeton I) for assessment and management
of patients with varying degrees of cardiac risk. These guidelines were recently
updated (Princeton II) based on new data concerning the link between ED and
cardiovascular disease and the availability of additional phosphodiesterase type
5 inhibitors (vardenafil, tadalafil). Despite the need for careful risk
assessment in all cases, sexual activity remains safe for the large majority of
patients. However, all patients presenting with complaints of ED should be
carefully assessed for the presence of cardiovascular risk factors (eg, obesity,
hypertension, hyperlipidemia). Risk-factor modification, including lifestyle
interventions (eg, exercise, weight loss) is strongly encouraged. Guidelines are
presented for the management of acute coronary syndromes in patients taking
phosphodiesterase type 5 inhibitors, including alternatives to the use of
nitrates for these patients. Other drug interactions and the cardiovascular
safety of testosterone replacement therapy are considered.
-----
Curr Urol Rep. 2006 Nov;7(6):485-9.
Current use of penile implants in erectile dysfunction.
Mulcahy JJ, Wilson SK.
johnmulc@gmail.com
Penile implants became popular with the introduction of effective models more
than 30 years ago. Today they play a secondary but definitive role in the
treatment of erectile dysfunction at times when more conservative therapies have
failed. Improvements in reducing the incidence of infection, treating infection
with antiseptic washes, enhancing device longevity, and instituting new
techniques to manage complicated implantation procedures have made them more
acceptable to patients. Although penile implants are the least often chosen and
most invasive treatment for erectile dysfunction, they have the highest
satisfaction rate--in the range of 80% to 90%--among both patients and partners.
-----
Curr Pharm Des. 2006;12(27):3467-84.
Phosphodiesterase 5 inhibitors in the treatment of erectile
dysfunction.
Aversa A, Bruzziches R, Pili M, Spera G.
Department of Medical Pathophysiology, University La Sapienza 00161 Rome Italy.
antonio.aversa@uniroma1.it
Erectile dysfunction (ED) has multifactor pathogenesis, with neurological,
vascular, endocrinological and psychogenic components described. However, about
50-85% of ED population report the presence of one or more comorbidities i.e.
hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair
endothelial function and, erection is a basically vascular event that
necessitates an intact endothelium to occur. Hence, ED may be mostly considered
as the clinical manifestation of a disease affecting penile circulation as a
part of a generalized vascular disorder due to atherosclerosis. Orally active
drugs, i.e. phosphodiesterase type-5 inhibitors (PDE5-i), are a group of
on-demand drugs licensed for ED treatment and appear to offer advantages over
past therapies in terms of ease of administration and cost, and they are now
widely advocated as first-line therapy. The recent discovery that chronic not
on-demand administration of these drugs may improve erectile and endothelial
response in men previously unresponding to on-demand regimes, opens a new
scenario in the treatment of men with ED and comorbidities. Finally, the recent
approval of PDE5-i sildenafil for the treatment of pulmonary arterial
hypertension represents the new challenge for these class of drugs. Aim of this
article will be to provide an update on the pathophysiology of ED and how to use
of different available PDE5-i in approaching sexual dysfunctional men, pointing
out on their characteristic of efficacy and safety and different indications in
special sub-populations.
-----
J Gen Intern Med. 2006 Jul 7; [Epub ahead of print]
Self-Esteem, Confidence, and Relationships in Men Treated with
Sildenafil Citrate for Erectile Dysfunction: Results of Two Double-blind,
Placebo-controlled Trials.
Althof SE, O' Leary MP, Cappelleri JC, Glina S, King R, Tseng LJ, Bowler JL; on
behalf of the US and International SEAR study group.
Case Western Reserve University, Cleveland, OH, USA.
Men with erectile dysfunction (ED) often have low self-esteem, confidence, and
sexual relationship satisfaction. We evaluated the impact of sildenafil citrate
and its generalizability across cultures on self-esteem, confidence, and sexual
relationship satisfaction in men with ED using the Self-Esteem And Relationship
(SEAR) questionnaire. Pooled analysis of 2 double-blind, placebo-controlled,
flexible-dose trials of sildenafil with identical protocols: 1 was conducted in
the United States and the other in Mexico, Brazil, Australia, and Japan. Men
>/=18 years old with ED. The impact of treatment on psychosocial factors
associated with ED was determined by patient responses to the SEAR
questionnaire. Erectile function was determined using the International Index of
Erectile Function (IIEF) and a global efficacy question. Successful sexual
intercourse attempts were derived from event logs of sexual activity. Treatment
effect sizes were calculated for all study outcomes. Compared with patients who
received placebo (n=274), patients who received sildenafil (n=279) reported
significantly greater improvements (P<.0001) in self-esteem, confidence, sexual
relationship satisfaction, and in all sexual function domains of the IIEF.
Treatment effect sizes were large (range, 0.7 to 1.2) for all SEAR components,
and improvement in psychosocial measures showed moderate to high correlations
(range, 0.50 to 0.83, P<.0001) with improvement in erectile function, percentage
of successful intercourse attempts, and global efficacy. In men with ED from 5
different nations, sildenafil produced substantial improvements in self-esteem,
confidence, and sexual relationship satisfaction. Improvements in these
psychosocial factors were observed crossculturally and correlated significantly
and tangibly with improvements in erectile function.
-----
Urology. 2006 Jul;68(1):166-71.
Use of medications or devices for erectile dysfunction among
long-term prostate cancer treatment survivors: potential influence of sexual
motivation and/or indifference.
Miller DC, Wei JT, Dunn RL, Montie JE, Pimentel H, Sandler HM, McLaughlin
PW, Sanda MG.
Michigan Urology Center, University of Michigan Medical Center, Ann Arbor,
Michigan, USA. msanda@bidmc.harvard.edu
OBJECTIVES: To evaluate the potential association between sexual motivation and
patterns of erectile dysfunction (ED) therapy among a large cohort of localized
prostate cancer treatment survivors. METHODS: The use of medications and devices
to improve erections and sexual health-related quality of life (HRQOL) were
evaluated using a mailed Expanded Prostate Cancer Index Composite survey
administered to 896 men 4 to 8 years after brachytherapy, three-dimensional
conformal external beam radiotherapy (3D-CRT), or radical prostatectomy and 112
control men. The responding participants (73% of those surveyed) were classified
by prostate cancer treatment, sexual motivation, and ED therapy use. Bivariate
and multivariate analyses were used to identify the factors associated with ED
therapy use and sexual HRQOL outcome. RESULTS: The quality of erections
unassisted by medications or devices was not different among the treatment
groups. Prostate cancer survivors used medications or devices for ED more
commonly than did the control men (30% versus 13%; P <0.01). One half of the
prostate cancer survivors with ED reported indifference regarding their ED
(small to no sexual bother despite absent or poor unassisted erections).
Conversely, among men who were bothered by poor erections, 48% of the
brachytherapy, 61% of the 3D-CRT, and 23% of radical prostatectomy subjects had
never tried commonly available medications or devices to improve their erections
(P <0.01). The current use of at least one erection aid was an independent
determinant of more favorable sexual HRQOL (P <0.01). CONCLUSIONS: Many men who
are bothered by posttreatment ED reported never having tried medications or
devices to improve their erections. The lack of ED therapy was more prevalent
among patients with erectile concerns after brachytherapy or 3D-CRT than after
radical prostatectomy, suggesting possible opportunities for improving sexual
HRQOL among long-term survivors.
-----
J Sex Med. 2006 Jul;3(4):743-8.
Determinants of patient satisfaction following penile prosthesis
surgery.
Akin-Olugbade O, Parker M, Guhring P, Mulhall J.
Department of Urology, Weill Medical College of Cornell University, New York, NY
10021, USA. yemiakin@yahoo.com
PURPOSE: Penile prosthetic surgery is associated with satisfaction rates >90%
for the general penile implant population. It is suggested that satisfaction
rates may be lower in certain populations. This study was undertaken to define
potential predictors of satisfaction. METHODS: Patients undergoing penile
prosthesis surgery completed the International Index of Erectile Function (IIEF)
prior to surgery, and the IIEF and Erectile Dysfunction Inventory of Treatment
Satisfaction (EDITS) questionnaires at least 6 months postoperatively
accompanied by a Global Satisfaction Question (GSQ). RESULTS: A total of 114
patients constituted the study population. Subgroups evaluated included patients
with Peyronie's disease (PD), body mass index (BMI) > 30 kg/m2, radical
prostatectomy (RP), and patient age > 70 years. The mean patient age and
duration of ED were 59 +/- 14 and 3.2 +/- 1.9 years, respectively. All groups
demonstrated statistically significant differences between pre- and
postoperative scores for the IIEF and EDITS. Patients with PD, a history of RP,
and BMI > 30 kg/m2 had significantly lower scores on the GSQ, IIEF satisfaction
domain, and EDITS compared with the general implant population. Only PD impacted
negatively on the postoperative IIEF erectile function domain score. On the
multivariate analysis, factors associated with >or=5-point difference in the
IIEF satisfaction domain score compared with the general implant population were
PD (RR = 4.2), RP (RR = 2.2), and BMI > 30 (RR = 1.8). CONCLUSIONS: These data
suggest that men diagnosed with PD, BMI > 30, or previous RP undergoing penile
prosthesis surgery have lower satisfaction rates than the general penile implant
population.
-----
J Sex Med. 2006 Jul;3(4):668-75.
Efficacy of tadalafil in men with erectile dysfunction naive to
phosphodiesterase 5 inhibitor therapy compared with prior responders to
sildenafil citrate.
Broderick GA, Donatucci CF, Hatzichristou D, Torres LO, Valiquette L, Zhao Y,
Loughney K, Sides GD, Ahuja S.
Department of Urology, Mayo Clinic, Jacksonville, FL 32224, USA.
broderick.gregory@mayo.edu
INTRODUCTION: Tadalafil, an inhibitor of phosphodiesterase 5 (PDE5), is
indicated for treatment of erectile dysfunction. Most tadalafil clinical trials
excluded patients with unsuccessful prior treatment with sildenafil citrate (sildenafil).
AIM: This retrospective analysis of pooled data from 14 tadalafil clinical
trials examines the effect of this exclusion by comparing efficacy results in
1,349 patients without prior sildenafil use (naive, presumably a mixture of
potential responders and nonresponders) with efficacy results in 1,440 patients
previously responsive to sildenafil (prior responders). MAIN OUTCOME MEASURES:
Efficacy measures included the International Index of Erectile Function (IIEF)
erectile function (EF) domain, overall satisfaction (OS), and intercourse
satisfaction (IS) domain scores; Sexual Encounter Profile (SEP) diary questions
2 through 5 (SEP2 [successful penetration], SEP3 [successful intercourse], SEP4
(satisfaction with hardness of erection), and SEP5 [overall satisfaction with
the sexual experience]); and a Global Assessment Question (GAQ1) (13/14 trials)
about erection improvement. Efficacy was compared using analysis of covariance (IIEF
and SEP) and logistic regression (GAQ1) models. METHODS: After a 4-week,
treatment-free, run-in period, patients in 14 double-blind, placebo-controlled,
parallel-group trials were treated with tadalafil 10 mg, tadalafil 20 mg, or
placebo for 12 weeks (dosed as needed before sexual activity, no more than once
daily). RESULTS: Tadalafil improved erectile function compared with placebo (P <
0.001) in naive patients and sildenafil prior responders for all efficacy
measures. For most efficacy outcomes, responses in the naive group (probable mix
of responders and nonresponders) were not statistically different from responses
in the prior-responder group (P >or= 0.10). CONCLUSIONS: The similar responses
of these two patient groups observed in this post hoc analysis suggest, but do
not confirm, that exclusion of sildenafil nonresponders in previously reported
tadalafil clinical trials may not have substantially affected efficacy outcomes.
Tadalafil improved erectile function in patients naive to PDE5 inhibitor therapy
and in patients who previously responded to sildenafil therapy.
-----
J Sex Med. 2006 Jul;3(4):662-7.
Assessment of the impact of sildenafil citrate on lower urinary
tract symptoms in men with erectile dysfunction.
Mulhall JP, Guhring P, Parker M, Hopps C.
Department of Urology, Weill Medical College of Cornell University, New York, NY
10021, USA. jpm2005@med.cornell.edu
INTRODUCTION: Sildenafil citrate is an effective and well-tolerated oral
erectogenic medication. Through phosphodiesterase type 5 (PDE5) inhibition, it
induces relaxation in penile smooth muscle, resulting in erection. Due to its
mild affinity for other PDE enzymes, it may cause smooth muscle relaxation in a
number of other organs. Recent data suggest an association between erectile
dysfunction (ED) and lower urinary tract symptoms (LUTS). Anecdotally some
patients cite improvement in LUTS while using sildenafil. AIM: This study was
conducted to assess the impact of Viagra on LUTS, using the International
Prostate Symptom Score (IPSS) questionnaire. MAIN OUTCOME MEASURE: International
Index of Erectile Function (IIEF) and IPSS inventories. METHODS: Men presenting
to a sexual dysfunction clinic who were candidates and opted for treatment with
sildenafil completed the IIEF and IPSS. Men with the IPSS scores greater than 10
were enrolled and completed the IPSS and IIEF questionnaires at least 3 months
after the commencement of sildenafil. Comparisons were made between pre- and
posttreatment scores in the IPSS and erectile function (EF) domain of the IIEF.
RESULTS: Forty-eight men were enrolled, with a mean age of 62 +/- 11 years. The
mean improvement in the EF domain score was 7 points (P = 0.01). The mean
improvement in the IPSS score was 4.6 points (P = 0.013) and in quality of life
(QOL) score was 1.4 points (P = 0.025). In total, 60% of men improved their IPSS
score, and 35% had at least a 4-point improvement in their score. The mean
number of uses of sildenafil per week was 2.0 +/- 0.6. No significant
correlation was seen between the degree of the IPSS improvement and baseline
IPSS, baseline EF domain score, or magnitude of improvement in EF domain score.
CONCLUSIONS: These data indicate a positive impact of Viagra on men with mild to
moderate LUTS. It is presumed, although unproven, that the medication's effect
is mediated through bladder neck/prostatic smooth muscle relaxation.
-----
J Sex Med. 2006 Jul;3(4):650-61.
Psychosocial outcomes and drug attributes affecting treatment
choice in men receiving sildenafil citrate and tadalafil for the treatment of
erectile dysfunction: results of a multicenter, randomized, open-label,
crossover study.
Dean J, Hackett GI, Gentile V, Pirozzi-Farina F, Rosen RC, Zhao Y, Warner MR,
Beardsworth A.
The Prostate Center, London, UK. john@dean.eu.com
INTRODUCTION: Although sildenafil citrate (sildenafil) and tadalafil are
efficacious and well-tolerated treatments for erectile dysfunction (ED),
preference studies have shown that patients may favor one medication over the
other. AIM: To determine whether psychosocial outcomes differed when men with ED
received tadalafil compared with sildenafil. MAIN OUTCOME MEASURES: Measures
included a treatment preference question, Psychological and Interpersonal
Relationship Scales (PAIRS), and Drug Attribute Questionnaire. METHODS:
Randomized, open-label, crossover study. After a 4-week baseline, men with ED (N
= 367; mean age = 54 years; naive to type 5 phosphodiesterase inhibitor therapy)
were randomized: tadalafil for 12 weeks then sildenafil for 12 weeks or vice
versa (8-week dose optimization/4-week assessment phases). During dose
optimization, patients started with 10 mg tadalafil, or 25 or 50 mg sildenafil
and could titrate to their optimal dose (10 or 20 mg tadalafil; 25, 50, or 100
mg sildenafil). Medications were taken as needed. Patients completing both
12-week periods chose which medication to continue during an 8-week extension.
RESULTS: Of 291 men completing both treatment periods, 71% (N = 206) chose
tadalafil and 29% (N = 85) chose sildenafil (P < 0.001) for the 8-week
extension. When taking tadalafil compared with sildenafil men had higher mean
endpoint scores on PAIRS Sexual Self-Confidence (tadalafil = 2.91 vs. sildenafil
= 2.75; P < 0.001) and Spontaneity (tadalafil = 3.32 vs. sildenafil = 3.17; P <
0.001) Domains and a lower mean endpoint score on Time Concerns Domain (tadalafil
= 2.2 vs. sildenafil = 2.59; P < 0.001). The two most frequently chosen drug
attributes to explain treatment preference were ability to get an erection long
after taking the medication and firmness of erections. Tadalafil and sildenafil
were well tolerated with 12 (3.3%) patients discontinuing for an adverse event.
CONCLUSIONS: As measured with PAIRS, men with ED had higher sexual
self-confidence and spontaneity and less time concerns related to sexual
encounters when treated with tadalafil compared with sildenafil. These
psychosocial outcomes may help explain why more men (71%) preferred tadalafil
for the treatment of ED in this clinical trial.
-----
Eur Urol. 2006 Jun 27; [Epub ahead of print]
Sexual Function Before and After Radical Retropubic
Prostatectomy: A Systematic Review of Prognostic Indicators for a Successful
Outcome.
Dubbelman YD, Dohle GR, Schroder FH.
Erasmus University Medical Center, Rotterdam, The Netherlands.
OBJECTIVES: Erectile dysfunction is common after surgery for prostate cancer.
Potency rates after radical retropubic prostatectomy (RRP) vary widely among
different studies. Since the introduction of the nerve-sparing technique potency
rates have increased. Erectile function recovery rates for selected groups of
patients are high. However, studies from community practices have shown less
favourable outcomes after RP. METHODS: We have performed a systematic review of
the literature concerning sexual function after RRP and focused on prognostic
indicators for a successful sexual outcome. RESULTS: Most important prognostic
factors for the return of potency after RRP are preservation of the
neurovascular bundles, age of the patient and sexual function before the
operation. Neurogenic and vasculogenic factors seem to play an important role in
the aetiology of the erectile dysfunction after surgery. The role of preserving
the accessory pudendal artery is not certain, although some investigators found
significant hemodynamic changes after sacrificing the accessory pudendal artery.
Colour Doppler ultrasound studies in combination with intracavernous injection
of vasoactive drugs or after PDE-5 inhibitors administration has shown to be a
reliable test for vascular factors. CONCLUSIONS: After bilateral nerve-sparing
RRP sexual potency is preserved in 31-86% of sexually active men with
organ-confined disease. The aetiology of impotence following RRP is
multifactorial, but neurogenic factors seem to play a major role. Vascular
factors may be of importance in selective cases. Colour Doppler ultrasound
appears to be the most reliable, non-invasive diagnostic test for erectile
dysfunction after RRP in patients who do not respond to pharmacotherapy.
-----
BJU Int. 2006 Apr;97 Suppl 2:39-43.
Combination of phosphodiesterase-5 inhibitors and alpha-blockers
in patients with benign prostatic hyperplasia: treatments of lower urinary tract
symptoms, erectile dysfunction, or both?
Carson CC.
University of North Carolina, Chapel Hill, North Carolina, USA.
As the prevalence of both erectile dysfunction (ED) and lower urinary tract
symptoms (LUTS) increases with age, physicians could be in the position to
manage these two conditions simultaneously. Moreover, medical therapies for
either one of these conditions can affect the other and this should be carefully
considered when making treatment decisions. Pharmacotherapy for benign prostatic
hyperplasia (BPH)/LUTS can cause side- effects affecting sexual function. Hence,
5alpha-reductase inhibitors such as finasteride and dutasteride are associated
with a greater risk of ED, ejaculatory disorders (EjD) and decreased libido than
is placebo. Among alpha(1)-adrenergic blockers, tamsulosin is associated with an
increased risk of EjD. However, some alpha(1)-adrenergic blockers can also have
a positive impact on erection. This is the case for alfuzosin, which has been
shown to enhance erectile function in experimental models, probably by reducing
the sympathetic tone and thus relaxing corpus cavernosum smooth muscle cells.
Phosphodiesterase 5 (PDE-5) inhibitors are commonly used to treat ED. There is
increasing evidence that they might also have a beneficial effect on LUTS,
probably through the nitric-oxide pathway. Nitric oxide is an important mediator
of the relaxation of isolated bladder and urethral smooth muscle, and could
modulate prostatic smooth muscle tone. alpha(1)-adrenergic blockers and PDE-5
inhibitors can therefore have a positive impact on both ED and LUTS. Although
placebo-controlled studies are needed to confirm the impact of these drugs,
alone or combined, on both ED and LUTS, this reinforces the need for a common
approach to managing these two highly prevalent and bothersome conditions.
-----
Asian J Androl. 2006 Mar;8(2):219-24.
Long-term treatment with intracavernosal injections in diabetic
men with erectile dysfunction.
Perimenis P, Konstantinopoulos A, Perimeni PP, Gyftopoulos K, Kartsanis G,
Liatsikos E, Athanasopoulos A.
Department of Urology, University Hospital of Patras, 26500 Rio, Patras, Greece.
Tel: +30-61-999-397, Fax: +30-61-993-981 E-mail: petperim@upatras.gr.
Aim: To assess the behavior of patients with diabetes mellitus (DM) and erectile
dysfunction (ED) during 10 consecutive years of treatment with self-injection of
vasoactive drugs. Methods: Thirty-eight diabetic men, including 12 with type I
and 26 with type II diabetes, were followed up regularly for 10 years after they
began self-injecting for severe ED. Real time rigidity assessment was used for
the objective determination of the initial dosage and then doses were regulated
in order to introduce an erection suitable for penetration and maintenance of
erection for approximately 30 min. Patients were followed up every two months,
and doses were increased only when the treatment response was not satisfactory.
Results: The number of injections used per year by the patients was reduced each
year (mean numbers: 50 in the first year and 22.5 in the 10th) and treatment
shifted towards stronger therapeutic modalities (mixtures of vasoactive drugs
instead of prostaglandin E1 alone). Type I diabetic men were standardized to a
level of treatment as early as 5 years after the initiation of treatment. That
level was finally reached by type II patients after another 4-5 years.
Conclusion: Treatment with self-injections of vasoactive drugs in diabetic men
with severe ED is a safe and effective alternative in the long term. Diabetic
men of both types show the same preferences in quality and quantity of treatment
after 10 years. The key point for maintenance in treatment is the adjustment of
the therapeutic method and dosage to optimal levels for satisfactory erections.
-----
Asian J Androl. 2006 Mar;8(2):177-82.
Beneficial effects of switching from beta-blockers to nebivolol
on the erectile function of hypertensive patients.
Doumas M, Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, Tsiodras
S, Dimitriou D, Giamarellou H.
First Department of Internal Medicine, Academic Hospital of Alexandroupolis,
68100 Alexandroupolis, Greece. Tel: +30-694-700-6001, Fax: +30-255-103-0450
E-mail: michalisdoumas@yahoo.co.uk.
Aim: To investigate the effect of substituting beta-blockers with nebivolol on
the erectile function of patients suffering from essential hypertension.
Methods: Forty-four young and middle-aged men (31-65 years) with essential
hypertension visited our outpatient clinic and took beta-blocker treatment (atenolol,
metoprolol or bisoprolol) for more than 6 months. All the patients completed a
questionnaire regarding erectile function (International Index for Erectile
Function). Patients were then switched to an equipotent dose of nebivolol for 3
months and, at the end of this time period, filled out the same questionnaire.
Results: Twenty-nine out of the 44 (65.9%) patients who took b-blockers (atenolol,
metoprolol or bisoprolol) had exhibited erectile dysfunction (ED). Their
systolic and diastolic blood pressure did not change significantly with the
treatment switch. In 20 out of these 29 (69%) patients, a significant
improvement in the erectile function score was exhibited after 3 months of
nebivolol administration, and in 11 of these 20 patients, erectile function was
normalized. Conclusion: Nebivolol seems to have a beneficial effect on ED
(possibly due to increased nitric oxide availability); however, further
prospective, randomized, placebo-controlled studies are needed to confirm the
beneficial effects of nebivolol.
-----
J Sex Med. 2006 Mar;3(2):361-6.
Management of honeymoon impotence.
Shamloul R.
Department of Andrology, Sexology and STDs, Cairo University, Cairo, Egypt; and
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan,
Canada.
Introduction. Honeymoon impotence can be defined as the failure to be
successfully involved in sexual intercourse at the beginning of marriage,
particularly in the first few nights. While its exact causes are not yet
elucidated, many studies recognize this problem as related to performance
anxiety. Aim. The aim of this study was to report the outcome of management of
patients with honeymoon impotence. Methods and Main Outcome Measures. This study
included 100 consecutive patients presenting to our department complaining of
failed sexual intercourse since the beginning of their marriage. History taking,
completion of the abridged form of the International Index of Erectile Function
(IIEF-5) questionnaire, and combined intracavernous injection and stimulation
and nocturnal penile tumescence monitoring were performed. Penile duplex was
performed to elucidate vascular insufficiency. All psychogenic patients with
erectile dysfunction (ED) were treated with sildenafil and sex therapy. All
organic ED patients were treated either with sildenafil alone or combined
therapy with either intracavernous prostaglandin E1 or vacuum constriction
device. Results. Seventy-four patients had psychogenic ED and 26 patients had
vasculogenic ED. All psychogenic ED patients were treated successfully with
sildenafil and sex therapy. Twenty-two patients with vasculogenic ED were
treated successfully with sildenafil or combined therapy, while four patients
needed venous surgery. Minimal side effects of all treatment modalities occurred
throughout the study. Conclusions. Management of honeymoon impotence requires
profound diagnosis of its causative factors. Treating physicians in areas with
high prevalence of this condition should be ready to manage this problem with
vigilant systematic overture. A combined approach of sildenafil and sex therapy
proved highly effective in treatment of honeymoon impotence of psychogenic
origin; however, controlled studies are needed. Other patients showing
functional erectile abnormalities should be treated accordingly.
-----
J Sex Med. 2006 Mar;3(2):274-82.
Comparison between sildenafil-treated subjects with erectile
dysfunction and control subjects on the self-esteem and relationship
questionnaire.
Cappelleri JC, Bell SS, Althof SE, Siegel RL, Stecher VJ.
Pfizer Inc, Global Research & Development, Groton, CT, USA.
Introduction. Erectile dysfunction (ED) can negatively impact psychosocial
measures of a patient's sexual life. Aim. To evaluate self-esteem, confidence,
and relationships in men with ED, before and after treatment with sildenafil
citrate (Viagra((R))), with reference to controls without ED. Methods.
Sildenafil-naive patients with ED were enrolled in a 10-week, open-label,
flexible-dose (25 mg, 50 mg, or 100 mg) trial of sildenafil. In a separate
study, men without ED who did not take sildenafil also completed the Self-Esteem
And Relationship (SEAR) questionnaire. In addition to traditional statistical
testing, equivalency testing was applied to compare the ED group, before and
after treatment, with the control group and to examine whether the ED group
improved to normative ranges on the SEAR questionnaire after treatment (within
half a standard deviation of the normative or control group mean). Main Outcome
Measures. Baseline and end-of-treatment responses on psychosocial aspects of ED
were measured with the validated SEAR. Results. Mean SEAR scores between
subjects with ED (N = 93, mean age 55.0 years) at baseline and control subjects
without ED (N = 94, mean age 52.5 years) were statistically different from zero
and not statistically equivalent. Conversely, mean SEAR scores between ED
subjects after treatment and control subjects were statistically equivalent and
not statistically different from zero. Conclusions. The results indicate that
sildenafil is associated with normalization of relationships, confidence, and
self-esteem in men with ED.
-----
J Sex Med. 2006 Mar;3(2):267-73.
Sexual counseling improved erectile rehabilitation after
non-nerve-sparing radical retropubic prostatectomy or cystectomy-results of a
randomized prospective study.
Titta M, Tavolini IM, Moro FD, Cisternino A, Bassi P.
Department of Urology, University of Padova, Padova, Italy.
Aim. The efficacy of prostaglandin E1 (PGE1)-intracavernous injection (ICI)
therapy for erectile dysfunction (ED) after non-nerve-sparing (NNS) radical
pelvic surgery depends on patient compliance. The purpose of this study was to
verify the utility of sexual counseling in ICI in terms of treatment efficacy,
compliance, and dropout rate. Methods. In this prospective randomized study, 57
patients with ED after NNS radical prostatectomy or cystectomy were divided: 29
patients (group SC+) were treated with sexual counseling and PGE1-ICI therapy;
the others 28 (group SC-) were treated with only ICI. At the start of the study
all patients were administered the International Index of Erectile Function (IIEF)
questionnaire and ICI training test; follow-up (at 3, 6, 9, 12, 18 months) was
achieved by home Sildenafil test and ambulatory IIEF test; sexual counseling was
provided only to group SC+. Results. The mean IIEF score at the end of study was
26.5 (SC+) vs. 24.3 (SC-) (P < 0.05); eight patients (SC+, 27.5%) became
responders to home Sildenafil vs. five (SC-, 17.8%) (P < 0.05); no dropout cases
occurred (SC+) vs. eight (SC-, 28.5%) (P < 0.05). Moreover, we recorded best
IIEF scores in group SC+ in sexual satisfaction (P < 0.05), sexual desire (P <
0.05), orgasmic function, and general satisfaction. Mean PGE1 doses were better
in group SC+ (P < 0.05). ICI-oriented sexual counseling was utilized to motivate
couples, to improve sexual intercourses, to correct mistakes in ICI
administration. At the end of follow-up 21 patients (SC+) declared themselves
satisfied vs. 12 (SC-). Conclusions. ICI-oriented sexual counseling in ICI
increased the efficacy of treatment, the compliance, and Sildenafil responders
rate, decreased the dropout rate.
-----
J Urol. 2006 Mar;175(3 Pt 1):1058-62.
Self-esteem, confidence and relationship satisfaction of men with
erectile dysfunction treated with sildenafil citrate: a multicenter, randomized,
parallel group, double-blind, placebo controlled study in the United States.
O'Leary MP, Althof SE, Cappelleri JC, Crowley A, Sherman N, Duttagupta S; The
United States Self-Esteem and Relationship Questionnaire Study Group.
Department of Surgery, Harvard Medical School, and Division of Urology, Brigham
and Women's Hospital, Boston, Massachusetts 02115-6105, USA. moleary1@bics.bwh.harvard.edu
PURPOSE: We assessed the change in confidence, relationships and self-esteem,
and its correlation with erectile function in men with ED treated with
sildenafil citrate in the first United States based, double-blind, placebo
controlled, randomized trial assessed by the validated SEAR. MATERIALS AND
METHODS: This 12-week flexible dose (25, 50 or 100 mg) trial determined change
scores from baseline to end of treatment for the 5 SEAR components (Sexual
Relationship domain, Confidence domain, Self-Esteem subscale [prespecified as
the primary end point], Overall Relationship subscale and Overall score), and
their correlations with the IIEF and event log data, as well as correlations
between SEAR components and a general efficacy question at the end of treatment.
RESULTS: Compared with the placebo group (125 patients, mean age +/- SD 55 +/-
13 years, mean years ED 3.8 +/- 4.2), the sildenafil group (128 patients, mean
age +/- SD 56 +/- 12, mean years ED 4.6 +/- 4.3) had significantly greater
improvements in all 5 SEAR components (p < 0.0001) and all sexual function
measures. SEAR component scores showed significant correlations with IIEF
Erectile Function domain scores (r range 0.34 to 0.69, p < 0.0001), other IIEF
domain scores (p < 0.0001), percentage of successful intercourse attempts (p <
0.0001) and frequency of erection that allowed satisfactory intercourse (p <
0.0001). CONCLUSIONS: In this study of men with ED, sildenafil produced
substantial improvements in self-esteem, confidence and relationship
satisfaction as measured by SEAR scores, which showed moderate to high positive
correlations with IIEF scores.
-----
J Urol. 2006 Mar;175(3 Pt 1):1041-4; discussion 1044.
Penile prosthetic surgery in neurologically impaired patients:
long-term followup.
Zermann DH, Kutzenberger J, Sauerwein D, Schubert J, Loeffler U.
Department of Urology, University Hospital, Friedrich-Schiller-University Jena,
Jena, Germany. dhzer@arcor.de
PURPOSE: Penile prosthetics are a viable option for erectile dysfunction in
neurologically impaired patients. Penile implants can also be used to facilitate
the management of urinary drainage when penile retraction has made this
difficult. MATERIALS AND METHODS: Between 1980 and 1996, 245 neurologically
impaired patients with a mean age of 40.8 years (range 16 to 75), including 188
with paraplegia, 57 with quadriplegia and 197 with spinal cord injuries, were
treated for erectile dysfunction and/or urinary incontinence with penile
prosthesis implantation. The mean history of paralysis was 11.2 years (range 1
to 52). After neuro-urological evaluation all patients included in this study
were considered candidates for penile prosthesis implantation. A followup
program for treatment success, patient satisfaction, problems and complications
was subsequently initiated. RESULTS: During 17 years a total of 293 surgical
procedures in 245 patients were done with the implantation of 147 semirigid
(Jonas), 113 self-contained inflatable (Dynaflex) and 33 inflatable 3-piece (AMS
700) prostheses. There were 3 patient groups based on the indication for penile
prosthetic surgery, namely group 1-134 patients with urinary management only,
group 2-60 with erectile dysfunction only, and group 3-51 with urinary
management and erectile dysfunction. At a mean followup of 7.2 years (maximum
17) 195 patients were reevaluated in clinic. In 122 patients (90.3%) urinary
management problems were resolved. Erectile dysfunction treatment was successful
in 76 patients (82.6%). There were 43 revisions for technical reasons and
infections. The infection rate was 5% (12 patients). The perforation rate was
different for different implant devices, that is 18.1% (15 of 83 cases) for
semirigid devices, 2.4% (2 of 84) for self-contained inflatable devices and 0%
(0 of 28) for inflatable 3-piece devices. CONCLUSIONS: The implantation of a
penile prosthesis is a safe procedure for erectile dysfunction and/or urinary
incontinence in neurologically impaired patients. Based on technical advances
the complication rates significantly decreased during the years. The
implantation of an inflatable 3-piece penile prosthesis in a neurologically
impaired patient is a safe and viable procedure. Indications include the
management of erectile dysfunction and problematic urinary collection.
-----
J Urol. 2006 Mar;175(3 Pt 2):S25-31.
Erectile dysfunction.
Burnett AL.
Johns Hopkins University, Baltimore, Maryland 21287, USA. aburnett@jhmi.edu
PURPOSE: An overview of the latest concepts advanced with regard to the
epidemiology, pathophysiology, and management of male ED is provided. MATERIALS
AND METHODS: Published literature and current paradigms promoted by consensus
bodies in the field with regard to the management of ED were reviewed. RESULTS:
ED is a neurovascular phenomenon modulated by hormonal, local biochemical, and
biomechanical/structural factors of the penis. Once viewed primarily as a
psychological issue, ED is now understood to represent predominantly organic
etiologies. It has a significant association with cardiovascular disease and
could serve as a harbinger of subsequent cardiovascular events. Goal directed
assessment and management implies a focus on patient (and partner) preferences
regarding various treatment options. These options range from oral
pharmacological agents to surgery and may be pursued according to a stepwise
management approach. Psychosocial interventions also may serve as useful
therapeutic adjuncts. CONCLUSIONS: ED is a highly manageable disorder in most
patients. The patient and his partner have integral roles in the decision making
process, since preferences regarding the importance of sexual activity, and the
risks and benefits of treatment will vary greatly among individuals.
-----
Int J Impot Res. 2006 Feb 16; [Epub ahead of print]
Early combination therapy: intracavernosal injections and
sildenafil following radical prostatectomy increases sexual activity and the
return of natural erections.
Nandipati K, Raina R, Agarwal A, Zippe CD.
1Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Early pharmacological prophylaxis has been reported to increase the return of
spontaneous erections following radical prostatectomy (RP). In this study, we
evaluated the role of intracavernosal alprostadil (PGE1) combined with
sildenafil in stimulating early recovery of spontaneous erections following RP.
In this prospective study, we included 22 patients who underwent bilateral
nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at
the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 mug (1-8)
and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are
followed up at regular intervals (3, 6, 9 and 12 months) with abridged version
of the International Index for Erectile Function-5 questionnaire. Patient
compliance, return of sexual activity and return of natural erection, adverse
effects and reasons for discontinuation were recorded. Penile doppler studies
were performed during followup visits to assess the vascular status. After a
mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of
spontaneous partial erections. Of the 18 PGE1 users, six continued 4 mug PGE1,
four increased the dose to 8 mug, six decreased the dose to 2 mug and two
patients further reduced the dose to 1 mug. Of four low-dose Trimix users, three
increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21
were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%)
with combination therapy (injections (PGE1) and sildenafil). Penile doppler
studies revealed arterial insufficiency in 77% (17/22) patients and venous
insufficiency in one patient. Early intracavernosal injections following RP
facilitated early sexual intercourse, patient satisfaction and potentially
earlier return of natural erections. Early combination therapy with sildenafil
allowed a lower dose of intracavernous injections, minimizing the penile
discomfort.International Journal of Impotence Research advance online
publication 16 February 2006; doi:10.1038/sj.ijir.3901448.
-----
BJU Int. 2005 Dec;96(9):1323-32.
An open-label, multicentre, randomized, crossover study comparing
sildenafil citrate and tadalafil for treating erectile dysfunction in men naive
to phosphodiesterase 5 inhibitor therapy.
Eardley I, Mirone V, Montorsi F, Ralph D, Kell P, Warner MR, Zhao Y, Beardsworth
A.
St. James University Hospital, Pyrah Department of Urology, Leeds, UK.
Associate Editor Michael G. Wylie Editorial Board Ian Eardley, UK Jean Fourcroy,
USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar,
UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands
OBJECTIVES To compare treatment preference, efficacy, and tolerability of
sildenafil citrate (sildenafil) and tadalafil for treating erectile dysfunction
(ED) in men naive to phosphodiesterase 5 (PDE5) inhibitor therapy. PATIENTS AND
METHODS This was an open-label, crossover study of sildenafil and tadalafil
(taken as needed). After a 4-week baseline assessment, 367 men with ED (mean age
54 years) were randomized to receive sildenafil for 12 weeks followed by
tadalafil for 12 weeks or vice versa (8-week dose optimization and 4-week
assessment phases). During dose optimization, patients started taking 25- or
50-mg sildenafil or 10-mg tadalafil and could titrate to find their optimum dose
(25-, 50- or 100-mg sildenafil; 10- or 20-mg tadalafil). After completing both
12-week periods, patients chose which treatment to continue during an 8-week
extension. Efficacy was measured with the International Index of Erectile
Function (IIEF) and Sexual Encounter Profile (SEP) diary. RESULTS Of the 291 men
who completed both treatments, 85 (29%) chose sildenafil and 206 (71%) chose
tadalafil (P < 0.001) for the 8-week extension. The IIEF erectile function
domain scores were 14.2 at baseline, 23.9 at endpoint on sildenafil, and 24.3 at
endpoint on tadalafil (P = 0.08, sildenafil vs tadalafil). The mean per patient
percentage success scores for SEP2 (penetration) were: baseline (46%),
sildenafil (post-baseline 82%) and tadalafil (post-baseline 85%; P = 0.06,
sildenafil vs tadalafil), and for SEP3 (successful intercourse) were: baseline
(19%), sildenafil (post-baseline 72%), and tadalafil (post-baseline 77%; P =
0.003, sildenafil vs tadalafil). The only treatment-emergent adverse events that
were reported by >5% of men were headache and flushing. CONCLUSIONS In men with
ED who were naive to PDE5 inhibitor therapy, sildenafil and tadalafil were both
effective and well tolerated. After treatment with sildenafil and tadalafil, 29%
of men chose sildenafil and 71% chose tadalafil for ED therapy during an 8-week
extension.
-----
J Androl. 2005 Nov-Dec;26(6):757-60.
Combination therapy: medicated urethral system for erection
enhances sexual satisfaction in sildenafil citrate failure following
nerve-sparing radical prostatectomy.
Raina R, Nandipati KC, Agarwal A, Mansour D, Kaelber DC, Zippe CD.
Department of Internal Medicine and Pediatrics, 2500 Metrohealth Drive, CASE
School of Medicine, Cleveland, OH 44105. rraina@metrohealth.org.
The objective of our study was to assess the effectiveness of combining
medicated urethral system for erection (MUSE) with sildenafil citrate in men
unsatisfied with the sildenafil alone. Baseline and follow-up data from 23
patients (mean age, 62.5 +/- 5.23 years) unsatisfied with the use of the
sildenafil citrate alone for the treatment of erectile dysfunction following
nerve-sparing radical prostatectomy (mean use, 4 attempts/100-mg dose) was
obtained. All patients started oral sildenafil citrate more than 6 months after
radical prostatectomy. Combination therapy was initiated using 100 mg sildenafil
citrate orally 1 hour prior to intercourse. Patients used combination therapy
for a minimum of 4 attempts prior to assessment with the Sexual Health Inventory
of Men (International Index for Erectile Function-5) and visual analog scale to
gauge rigidity (0-100). The effect of therapy on the total International Index
for Erectile Function (IIEF) score and penile rigidity score was assessed. Of
the 23 patients, 4 (17%) had no improvement with the addition of medicated
urethral system for erection and discontinued the drug, while 19 (83%) reported
improvement with the penile rigidity and sexual satisfaction. The IIEF scores of
these 19 patients showed significant improvements in each sexual domain, and the
patients reported that erection was sufficient for vaginal penetration 80% of
the time. Rigidity scores on a scale of 0-100 with sildenafil alone averaged 38%
(23-53) for men and 46% (26-67) for their partners. With the addition of MUSE,
scores increased to 76% for men and 62% for their partners. We conclude that the
addition of MUSE to sildenafil improved sexual satisfaction and penile rigidity
in patients unsatisfied with sildenafil alone.
-----
Urol Oncol. 2005 Nov-Dec;23(6):465.
The effect on erectile function of (103)palladium implantation
for localized prostate cancer.
Smith JA. Ponholzer A, Oismuller R, Somay C, Buchler F, Maier U,
Hawliczek R, Rauchenwald M, Madersbacher S,
Department of Urology and Andrology, Ludwig Boltzmann Institute for Urological
Oncology, Vienna, Austria.
OBJECTIVE: To determine in a prospective study the effect on erectile function
of (103)Pd brachytherapy for localized prostate cancer, using a validated
questionnaire. PATIENTS AND METHODS: Between July 1999 and April 2003, 113 men
with localized prostate cancer were treated by permanent implantation of (103)Pd
seeds, of whom 78 with a follow-up of 30 months were included in this study. No
patient received supplemental external beam radiation therapy. At baseline and
3-month intervals, erectile function (EF) was assessed by the EF domain score of
the International Index of Erectile Function-15 (IIEF-15); 77% received (neo)adjuvant
antiandrogen therapy for up to 3 months. RESULTS: At baseline, 27 (35%) patients
had no erectile dysfunction (ED; EF domain score 26-30), 24 (31%) had
mild/moderate ED (score 11-25) and 27 (35%) severe ED (score 6-10). The mean EF
domain score decreased from 17 to 12 (P < 0.001) after 30 months. Overall, 52
men (67%, including those with severe ED at baseline) remained in the same ED
category at 30 months after therapy as before, 12 (15%) deteriorated by one
category, 14 (18%) by two or more, and no patient improved. Of the 27 patients
fully potent (score 26-30) at baseline, 37% remained so after 30 months, 19%
developed mild and the remaining 44% moderate/severe ED. In a multivariate
analysis, neither age nor preoperative prostate-specific antigen level, prostate
volume, D90, hormonal treatment, diabetes, smoking or hypertension were
predictive of preserving potency (P > 0.05). CONCLUSIONS: There was a high
prevalence of pre-existing ED in these men; 57% of men fully potent or with mild
ED at baseline remained so 30 months after brachytherapy.
-----
Am J Ther. 2005 Nov-Dec;12(6):605-11.
Evaluation of erectile dysfunction therapy in patients previously nonadherent to
long-term medications: a retrospective analysis of prescription claims.
McLaughlin T, Harnett J, Burhani S, Scott B.
NDCHealth, Phoenix, AZ 85016, USA. McLaughlin@ndchealth.com
Erectile dysfunction (ED) can lead to treatment noncompliance in patients taking
medications for chronic health conditions. Using the Intelligent Health
Repository, NDCHealth's longitudinal, United States health care claims database,
we examined the impact of treating ED on adherence to long-term therapies in
previously nonadherent patients. Male patients >or=18 years of age were
identified who received antidepressant (AD), antihypertensive (AH), oral
hypoglycemic (OHG), or lipid-lowering (LL) agents and initiated therapy with
sildenafil citrate (Viagra) between January and June 2003. Treatment adherence
was determined using medication possession ratios (MPRs) for the 12 months
before and after the first prescription of sildenafil. Prior to initiation of
therapy for ED with sildenafil, 64% of patients with comorbid medications were
not adherent (MPR <0.8). Among these patients, 728 (27%) received AD, 2112 (78%)
received AH, 984 (18%) received OHG, and 1078 (40%) received LL agents, with 66%
of patients receiving multiple therapeutic classes. During the 12-month period
after the first sildenafil prescription, patients had a significant increase in
medication adherence compared with the 12 months before the first prescription
of sildenafil (P < 0.0001). The percentage of patients who became adherent (MPR
>or=0.8) with medications after sildenafil treatment was from 22% to 36%. With
the exception of the LL group, there was a significant relationship between
>or=3 sildenafil prescriptions and change in MPR (P < 0.05). Patients aged
>or=65 years had similar improvement in MPR as patients <or=65 years. Treatment
of ED with sildenafil improved adherence in patients taking common long-term
medications who were previously nonadherent.
--
Int J Impot Res. 2005 Nov 10; [Epub ahead of print]
Gene transfer for the therapy of erectile dysfunction: progress in the 21st
century.
Melman A.
1Department of Urology, Montefiore Medical Center/Albert Einstein College of
Medicine, Bronx, NY, USA.
Gene transfer represents the next potential era of advancement in medicine for
the prevention of the effects of aging or for treatment of genetic or acquired
disease. For gene transfer to be a practical successor to today's oral and
minimally invasive therapies, the product must have a high safety profile and a
long duration of effectiveness to correct the need for on-demand administration.
Several types of vectors have been used in preclinicals studies, but because of
widely publicized adverse events, progress using viral vectors in humans has
been limited. There is a current phase I human trial using naked DNA as the
vector with the maxi-K gene to modify cellular contractility. Preliminary
results in the safety trial thus far have shown no treatment-related adverse
events, no transfer to the semen, and the possibility of efficacy in one
participant.International Journal of Impotence Research advance online
publication, 10 November 2005; doi:10.1038/sj.ijir.3901412.
--
Curr Med Res Opin. 2005 Nov;21(11):1701-9.
The efficacy of tadalafil in improving sexual satisfaction and overall
satisfaction in men with mild, moderate, and severe erectile dysfunction: a
retrospective pooled analysis of data from randomized, placebo-controlled
clinical trials.
Rosen RC, Shabsigh R, Kuritzky L, Wang WC, Sides GD.
Department of Psychiatry, University of Medicine and Dentistry of New Jersey,
Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
BACKGROUND: Satisfaction with the sexual experience is considered important when
evaluating the impact of treatments for erectile dysfunction (ED), yet
satisfaction has been infrequently assessed in clinical trials. OBJECTIVE: To
evaluate satisfaction with, and enjoyment of, the sexual experience in men with
ED enrolled in 11 placebo-controlled clinical trials of tadalafil. STUDY DESIGN
AND METHODS: Retrospective pooled analysis of data from 11 randomized, double
blind, placebo-controlled clinical trials of tadalafil. Men with mild (N = 838),
moderate (N = 558), or severe (N = 703) ED who were randomized to tadalafil 10
mg or 20 mg or placebo taken as needed for 12 weeks were included in this
analysis. Efficacy measures included the International Index of Erectile
Function (IIEF). Reported herein are the scores on the IIEF overall satisfaction
domain and individual IIEF questions (IIEF-Q7, satisfaction with intercourse;
and IIEF-Q8, enjoyment of intercourse). RESULTS: At least moderate satisfaction
(IIEF overall satisfaction domain) was reported by 55% and 72% of patients with
mild ED taking tadalafil 10 mg and 20 mg, respectively, compared with 33% taking
placebo (p < 0.002); 60% and 65% vs. 19% of patients with moderate ED (p <
0.001); and 32% and 49% vs. 9% with severe ED (p < 0.001). Satisfactory
intercourse during most attempts or almost always/always (IIEF-Q7) was reported
by 59% and 79% of patients with mild ED taking tadalafil 10 mg and 20 mg vs. 32%
taking placebo (p < 0.001); 52% and 65% vs. 18% with moderate ED (p < 0.001);
and 28% and 49% vs. 5% with severe ED (p < 0.001). Highly or very highly
enjoyable intercourse (IIEF-Q8) was reported by 45% and 63% of patients with
mild ED taking tadalafil 10 mg and 20 mg vs. 21% taking placebo (p < 0.001); 43%
and 56% vs. 16% with moderate ED (p < 0.001); and 19% and 44% vs. 5% with severe
ED (p < 0.001). CONCLUSIONS: Compared with placebo, tadalafil 10 mg and 20 mg
improved overall satisfaction with the sexual experience, intercourse
satisfaction, and intercourse enjoyment in men with mild, moderate, and severe
ED.
--
World J Urol. 2005 Nov 5;:1-8 [Epub ahead of print]
Treating erectile dysfunction by endothelial rehabilitation with
phosphodiesterase 5 inhibitors.
Sommer F, Schulze W.
Department of Men's Health and Clinic of Urology, University Hospital Hamburg-Eppendorf,
P.O. Box 202101, 20214, Hamburg, Germany, Frank.Sommer@men-and-health.info.
A large body of evidence has accumulated demonstrating that a common pathway in
conditions such as hypertension, atherosclerosis, hypercholesterolemia, diabetes
mellitus, and erectile dysfunction (ED) is endothelial dysfunction. Although a
complete pharmacological cure for ED is currently unavailable, the
phosphodiesterase 5 (PDE5) inhibitors sildenafil, vardenafil, and tadalafil are
efficacious oral therapy for ED. Results from recent studies suggest that
regular treatment with a PDE5 inhibitor may lead to enhanced erectile function (EF)
beyond that observed with on-demand usage, possibly through improvement of
endothelial function. Such an effect may be viewed as rehabilitation of damaged
erectile tissue. The present review focuses on several recent studies which
provide evidence for the beneficial effect of regular PDE5 inhibitor
administration on the improvement of EF by rehabilitation of vascular
endothelium.
--
World J Urol. 2005 Nov 5;:1-11 [Epub ahead of print]
Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction.
Briganti A, Salonia A, Deho' F, Zanni G, Barbieri L, Rigatti P, Montorsi F.
Department of Urology, Universita Vita-Salute San Raffaele, Milan, Italy.
Erectile dysfunction (ED) affects the sexual lives of millions of men. The
first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5
(PDE-5) inhibitors, of which three are available. Sildenafil is the most widely
prescribed oral agent for ED and has a very satisfactory efficacy-safety profile
in all patient categories. Tadalafil and vardenafil were introduced in the
European Union and in the United States in 2003 and 2004, respectively. The
three PDE-5 inhibitors share many pharmacological and clinical characteristics,
and each has unique features. This review, which is based on the contemporary
literature on PDE-5 inhibitors, describes the chemical, pharmacological, and
clinical features of sildenafil, vardenafil, and tadalafil. The first section
reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology.
The second section summarizes data regarding efficacy and safety of the three
drugs in treating ED in the general population as well as in selected patient
categories.
--
Br J Nurs. 2005 Oct 27-Nov 9;14(19):1014-8, 1020-1.
Restoring pelvic floor function in men: review of RCTs.
Dorey G.
The Somerset Nuffield Hospital, Taunton.
The male pelvic floor muscles support the abdominal contents, are active during
breathing, maintain urinary and faecal continence, increase local blood supply
and are active during sexual intercourse. It was hypothesized that weak pelvic
floor muscles would compromise these functions in men and lead to urinary and
faecal incontinence and sexual dysfunction and that pelvic floor muscle
strengthening would restore normal function. After a literature search of
randomized controlled trials was undertaken, it was found that weak pelvic floor
muscles compromised normal pelvic floor function and led to urinary incontinence
and erectile dysfunction. Strengthening the pelvic floor muscles was shown to
significantly improve post-prostatectomy urinary continence, post-micturition
dribble and erectile function. It would be prudent for all men to exercise their
pelvic floor muscles to maintain normal pelvic floor function.
--
Int J Impot Res. 2005 Oct 20; [Epub ahead of print]
Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative
meta-analysis of fixed-dose regimen randomized controlled trials administering
the International Index of Erectile Function in broad-spectrum populations.
Berner MM, Kriston L, Harms A.
1Department of Psychiatry and Psychotherapy, University Medical Center, Freiburg,
Germany.
This meta-analytic study aims to estimate the likely improvements of erectile
dysfunction (ED) measured by the International Index of Erectile Function (IIEF)
at the highest fixed dosages of the three available PDE-5-inhibitors: sildenafil,
tadalafil, and vardenafil. MEDLINE and the Cochrane Library were searched
electronically for efficacy trials of PDE-5-inhibitors for treating ED. In
addition drug manufacturers were contacted to provide unpublished or unrecorded
congress proceedings. Randomized, double-blind, placebo-controlled,
parallel-group, maximum fixed-dose, broad-spectrum efficacy trials using IIEF
were included in the analysis. Data were independently extracted by two
reviewers. The results were pooled using weighted mean differences. A formal
indirect comparison (including Bonferroni-correction) was conducted to estimate
the differences between agents. A total of 14 trials were included in the
meta-analysis (three with 100 mg sildenafil, eight with 20-25 mg tadalafil, and
three with 20 mg vardenafil). All trials were of good methodological quality.
Overall heterogeneity was moderate: I(2)=33.2%, chi(2)=19.47, P=0.11. The funnel
plot suggested moderate likelihood of publication bias. Pooled results of IIEF-improvement
were for sildenafil 9.65 (95% CI: 8.50, 10.79) points, tadalafil 8.52 (7.61,
9.42) points, and vardenafil 7.50 (6.50, 8.50) points, respectively. Sildenafil
proved to be significantly more effective than vardenafil (d=2.15, P=0.006),
other pairwise comparisons showed no difference in efficacy. All
PDE-5-inhibitors are highly effective in the treatment of ED. At maximum dosage
they improve erectile function 7-10 points on the IIEF compared to
placebo-treatment. There is evidence that sildenafil might be more efficacious
than vardenafil, although this is to be interpreted with caution. To prove
higher efficacy truly independent comparative trials are needed.International
Journal of Impotence Research advance online publication, 20 October 2005;
doi:10.1038/sj.ijir.3901395.
BJU Int. 2005 Oct;96(6):857-63.
Time from dosing to sexual intercourse attempts in men taking
tadalafil in clinical trials.
Shabsigh R, Burnett AL, Eardley I, Sharlip ID, Ellsworth PI, Garcia CS,
Natanegara F, Ahuja S.
Department of Urology, Columbia University, New York, NY, USA.
Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy,
USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar,
UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands
OBJECTIVE To determine whether patients with erectile dysfunction (ED) and
treated with tadalafil use the 36-h duration of effect of the drug, and to
discern if the timing of intercourse attempts is influenced by patient age,
baseline severity of ED, or previous experience with sildenafil citrate.
PATIENTS AND METHODS In 11 multicentre, double-blind, placebo-controlled
studies, 2102 patients with ED were randomized to a maximum of one dose per day
of tadalafil 10 or 20 mg (1464 men), or placebo (638 men) with no time
restrictions before attempting sexual activity after the dose. A post hoc
analysis was used to determine the proportion of men with ED who attempted
sexual intercourse during various intervals (>0 to </= 1, >1 to </= 4, and >4 to
</= 36, including >12 to </= 36 h) after dosing with tadalafil or placebo over a
12-week period. Patients were stratified by age, baseline severity of ED, and
previous history of sildenafil use. RESULTS Of patients in different age groups
and various ED severity, >/= 79% and >/= 53% chose to attempt sexual intercourse
at least once during the 12-week treatment period at 4-36 and 12-36 h,
respectively, after taking tadalafil. Regardless of previous experience with
sildenafil, about a third of patients using tadalafil attempted intercourse a
mean of at least once per week at 4-36 h after the dose over 12 weeks.
Furthermore, 58% of patients attempted intercourse at least once during two
intervals (>1 to </= 4 h and >12 to </= 36 h) after separate doses of tadalafil.
CONCLUSION Regardless of age, ED severity, or previous experience with
sildenafil, most patients attempted sexual intercourse at least once at 12-36 h
after one dose of tadalafil over a 12-week treatment period. Furthermore, by
engaging in sexual intercourse at both earlier and later intervals after
separate doses, most patients on treatment did not adhere to a fixed schedule of
intimacy and thus took advantage of the 36-h duration.
-----
J Urol. 2005 Oct;174(4 Pt 1):1395-8.
Quality of life following simultaneous placement of penile
prosthesis with radical prostatectomy.
Ramsawh HJ, Morgentaler A, Covino N, Barlow DH, Dewolf WC.
>From the Department of Psychology, Boston University (HJR, DHB), and the
Divisions of Psychology (NC) and Urology (AM, WCD), Beth Israel Deaconess
Medical Center, Harvard Medical School, Boston, Massachusetts.
PURPOSE:: The present study examined erectile functioning, frequency of sexual
contact, psychological functioning, partner/marital satisfaction and overall
quality of life (QOL) after immediate sexual rehabilitation for prostate cancer
via simultaneous placement of a penile prosthesis at radical retropubic
prostatectomy (RP). MATERIALS AND METHODS:: Questionnaire packets were sent to
and received from 51 men who had undergone simultaneous implantation of a penile
prosthesis at the time of RP (PP+) and from a comparison group of 47 men who
undergone RP alone (PP-) matched by age and year of surgery. Questionnaires
included the Erectile Dysfunction Inventory of Treatment Satisfaction, the
Depression Anxiety Stress Scales, the Dyadic Adjustment Scale and a prostate
specific European Organization for the Research and Treatment of Cancer (EORTC)
QOL questionnaire. Further comparisons were performed for a PP- subgroup
consisting of 15 patients who had undergone nerve sparing RP. RESULTS:: Higher
Erectile Dysfunction Inventory of Treatment Satisfaction, EORTC Sexual
Functioning, EORTC Total scores and more frequent sexual contact were reported
by the PP+ group compared with the PP- group. The PP+ group also had better
outcomes that approached but did not reach statistical significance compared
with the nerve sparing subgroup with regard to Depression Anxiety Stress Scales
and EORTC Emotional Functioning scores. CONCLUSIONS:: Men who chose simultaneous
placement of a penile prosthesis with RP reported greater overall QOL, erectile
function and more frequent sexual contact than a comparison group of men who
underwent RP alone. Placement of penile prosthesis at the time of RP may be a
desirable option for men with prostate cancer in whom a nerve sparing procedure
may not be ideal. These results underscore the importance of sexual function for
men undergoing prostate cancer treatment.
-----
J Urol. 2005 Oct;174(4, Part 1 of 2):1356-1359.
Effect of Tadalafil on sexual timing behavior patterns in men
with erectile dysfunction: integrated analysis of randomized, placebo controlled
trials.
Hatzichristou D, Vardi Y, Papp G, Pushkar D, Basson BR, Kopernicky V.
>From the Second Department of Urology, "Papageorgiou" General Hospital and
Director, Center for Sexual and Reproductive Health, Aristotle University of
Thessaloniki (DH), Thessaloniki, Greece, Department of Neuro-Urology, Rambam
Medical Center (YV), Haifa, Israel, Department of Urology, Semmelweis University
Medical School (GP), Budapest, Hungary, Department of Urology, Moscow State
Medical University (DP), Moscow, Russia, and Eli Lilly and Co. (BRB, VK),
Vienna, Austria.
PURPOSE:: Tadalafil, a new phosphodiesterase type 5 inhibitor, has an extended
period of responsiveness compared with other agents in this class. The distinct
pharmacological profile of tadalafil may allow more flexibility for men to
establish individual sexual timing behavior patterns. We determined if patients
took advantage of the pharmacological profile of tadalafil by assessing the
frequency, timing and success of intercourse attempts in men with erectile
dysfunction. MATERIALS AND METHODS:: Data on Eastern European countries were
combined from 2 identically designed, randomized, double-blind, placebo
controlled, parallel group studies. Patients self-administered 20 mg tadalafil
(406) or placebo (108) as needed for 12 weeks. RESULTS:: Of the men 63% made at
least a quarter of their attempts and 42% made at least half of their attempts
more than 4 hours after dose. At least 1 attempt was made after 8, 12 or 24
hours after dose by 87%, 75% and 52% of the men, respectively. Throughout a
36-hour post-dose period tadalafil was associated with significantly higher
intercourse success rates than placebo (p <0.001) with 61% to 69% of tadalafil
treated patients reporting success rates of greater than 75% compared with 19%
to 30% of those on placebo (p <0.001). Tadalafil was well tolerated.
CONCLUSIONS:: In this study various use patterns of the tadalafil period of
effectiveness were apparent, reflecting differences in the sexual timing
behavior of patients. Tadalafil may provide men with erectile dysfunction more
flexibility in deciding when to attempt intercourse in accordance with their
sexual habits and attitudes.
-----
J Androl. 2005 Sep-Oct;26(5):604-9.
Vardenafil in patients with erectile dysfunction: achieving
treatment optimization.
Hellstrom WJ, Elhilali M, Homering M, Taylor T, Gittleman M.
Tulane University Medical Center, Department of Urology, 1430 Tulane Avenue, New
Orleans, LA 70112. whellst@tulane.edu.
This post hoc analysis of data from a multicenter, randomized, double-blind
study determined how many attempts were needed to record at least 1 successful
penetration and maintenance of erection long enough for successful intercourse
in a broad population of men with erectile dysfunction taking vardenafil at 5,
10, or 20 mg or placebo. The cumulative probability of achieving successful
penetration and of maintaining an erection increased with the number of attempts
for all 3 vardenafil groups. For the first attempt, the probability of achieving
successful penetration was higher in all 3 vardenafil groups compared with
placebo; 67% in the 5-mg vardenafil group, 77% in the 10-mg vardenafil group,
and 74% in the 20-mg vardenafil group compared with 46% for placebo. By the
third attempt, the probability of at least 1 success was 82% for 5, 88% for 10,
and 85% for 20 mg vardenafil compared with 68% for placebo. The probability of
maintaining an erection long enough to complete intercourse at the first attempt
was 51% for 5, 69% for 10, and 61% for 20 mg vardenafil compared with 28% for
the placebo group. By the third attempt, the probability of maintaining an
erection was 66% for 5, 81% for 10, and 77% for 20 mg vardenafil in contrast to
53% for placebo. The results of this analysis indicate that patients without
initial treatment success should continue treatment or increase the dose because
the cumulative probability of success increases with additional attempts with
vardenafil, with a plateau at about the fourth dose.
-----
Urologe A. 2005 Sep 9; [Epub ahead of print]
[Therapy for organic erectile dysfunction.]
[Article in German]
Becker AJ, Mayer M, Stief CG.
Urologische Klinik und Poliklinik, LMU, Munchen.
Erectile dysfunction is a common disease of men. It is associated with various
comorbidities and has a prevalence of about 50% in the 7th decade. Erectile
dysfunction often affects the quality of life of the patient and his partner,
and it is very important to offer adequate therapy that respects the individual
circumstances of each patient.The mandatory diagnostic work-up includes a
medical and psychosexual history, a physical examination and routine laboratory
tests. Besides psychotherapy, oral pharmacotherapy with oral PDE-5 inhibitors (sildenafil,
tadalafil, vardenafil) is the most effective therapy for erectile dysfunction
and is superior to centrally acting drugs (yohimbine). In cases of failure or
contraindication of oral pharmacotherapy, local pharmacotherapy is the
second-line therapy.The third-line options are vacuum erectile devices and
penile implants, and these have a high patient satisfaction. New therapeutic
strategies such as anti-serotoninergic substrates and growth hormone offer a
promising future for the therapy of erectile dysfunction but remain to be
evaluated.
-----
Compr Ther. 2005 Fall;31(3):194-208.
Noninvasive management of lower urinary tract symptoms and sexual
dysfunction associated with benign prostatic hyperplasia in the primary care
setting.
Kuritzky L.
Department of Community Health and Family Medicine, University of Florida,
Gainesville, FL.
Most men who live to middle age and beyond will ultimately develop lower urinary
tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), and many
will also experience sexual dysfunction. Clinical studies indicate that most
patients will experience improvement in BPH-related LUTS with alpha-adrenergic
blockade or 5alpha-reductase inhibition. Recent studies suggest that
alpha-blockers and 5alpha-reductase inhibitors may help to slow the progression
of LUTS; 5alpha-reductase inhibitors reduce the need for surgery and
complications, such as acute urinary retention. Third-generation alpha-blockers
(alfuzosin, tamsulosin) are infrequently associated with cardiovascular side
effects, in contrast to their predecessors (doxazosin, terazosin, prazosin).
This may provide an advantage for consideration as firstline therapy.
alpha-Blocker therapy may also improve sexual functioning, with the exception of
ejaculation disorders, predominantly associated with subtypeselective
alpha-blockers. By contrast, 5alpha-reductase inhibition is not recommended for
men without demonstrable prostatic enlargement, may be associated with a long
delay between treatment initiation and LUTS improvement, and is clearly
associated with sexual side effects, including decreased libido, ejaculatory
dysfunction, and erectile dysfunction. When choosing appropriate
pharmacotherapy, the clinician should consider not only the expeditious relief
of the presenting symptoms but also the patient's quality of life, including
sexual function and potential long-term outcomes, such as acute urinary
retention and the need for surgical intervention.
-----
BJU Int. 2005 Sep;96(4):595-7.
Pelvic floor exercises for erectile dysfunction.
Dorey G, Speakman MJ, Feneley RC, Swinkels A, Dunn CD.
The Somerset Nuffield Hospital, Taunton, UK. grace.dorey@virgin.net
OBJECTIVE: To examine the role of pelvic floor exercises as a way of restoring
erectile function in men with erectile dysfunction. PATIENTS AND METHODS: In
all, 55 men aged > 20 years who had experienced erectile dysfunction for > or =
6 months were recruited for a randomized controlled study with a cross-over arm.
The men were treated with either pelvic floor muscle exercises (taught by a
physiotherapist) with biofeedback and lifestyle changes (intervention group) or
they were advised on lifestyle changes only (control group). Control patients
who did not respond after 3 months were treated with the intervention. All men
were given home exercises for a further 3 months. Outcomes were measured using
the International Index of Erectile Function (IIEF), anal pressure measurements
and independent (blinded) assessments. RESULTS: After 3 months, the erectile
function of men in the intervention group was significantly better than in the
control group (P < 0.001). Control patients who were given the intervention also
significantly improved 3 months later (P < 0.001). After 6 months, blind
assessment showed that 40% of men had regained normal erectile function, 35.5%
improved but 24.5% failed to improve. CONCLUSION: This study suggests that
pelvic floor exercises should be considered as a first-line approach for men
seeking long-term resolution of their erectile dysfunction.
-----
Int J Impot Res. 2005 Aug 18; [Epub ahead of print]
Early use of vacuum constriction device following radical
prostatectomy facilitates early sexual activity and potentially earlier return
of erectile function.
Raina R, Agarwal A, Ausmundson S, Lakin M, Nandipati KC, Montague DK, Mansour D,
Zippe CD.
[1] 1Center for Advanced Research in Human Reproduction, Infertility and Sexual
Function, Glickman Urological Institute, The Cleveland Clinic Foundation,
Cleveland, OH, USA [2] 2Department of Internal Medicine and Pediatrics, Case
Western Reserve University (MHMC), Cleveland, OH, USA.
To assess the efficacy of vacuum constriction devices (VCD) following radical
prostatectomy (RP) and determine whether early use of VCD facilitates early
sexual activity and potentially earlier return of erectile function. This
prospective study consisted of 109 patients who underwent nerve-sparing (NS) or
non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed
erectile dysfunction following surgery. The patients were randomized to VCD use
daily for 9 months (Group 1, N=74) or observation without any erectogenic
treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the
Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of
Erectile Function (IIEF-5)), which were stratified by the NS status. Patient
outcome regarding compliance, change in penile length, return of natural
erection, and ability for vaginal intercourse were also assessed. The mean
patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD
began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully
used their VCD with a constriction ring for vaginal intercourse at a frequency
of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all,
19 of these 60 patients (32%) reported return of natural erections at 9 months,
with 10/60 (17%) having erections sufficient for vaginal intercourse. The
abridged IIEF-5 score significantly increased after VCD use in both the NS and
NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In
Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum
follow-up of 9 months after surgery. However, only four of these patients (29%)
had erections sufficient for successful vaginal intercourse and rest of patients
(71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a
decrease in penile length and circumference at 9 months (range, 4-8 months)
compared to 12/14 (85%) among the nonresponders. However, in control group 22/35
reported decrease in penile length and circumference. Early use of VCD following
RP facilitates early sexual intercourse, early patient/spousal sexual
satisfaction, and potentially an earlier return of natural erections sufficient
for vaginal penetration.International Journal of Impotence Research advance
online publication, 18 August 2005; doi:10.1038/sj.ijir.3901380.
-----
Prog Urol. 2005 Jun;15(3):447-55; discussion 455-6.
[Erectile dysfunction in renal failure patients and renal
transplant recipients]
[Article in French]
Kleinclauss F, Kleinclauss C, Bittard H.
Service d'Urologie, Hopital Saint Jacques, Besancon, France. fkleinclauss@chu-besancon.fr
The frequency of erectile dysfunction can be increased in certain populations,
such as patients with renal failure in whom the incidence of erectile
dysfunction is estimated to be between 50% to 70% depending on the stage of
renal failure. In this population, even more than in the general population,
erectile dysfunction appears to be due to multiple aetiologies, combining
organic and psychological disorders. Although renal transplantation is the
treatment of choice for end-stage renal failure, it appears to have very
variable effects on erectile dysfunction, as it may improve erectile dysfunction
in the same way as global quality of life. However, some authors have
demonstrated the aggravating role of renal transplantation on quality of
erection, or even de novo appearance of erectile dysfunction. Progress in the
fields of dialysis and renal transplantation have considerably improved the
quality of life of patients with chronic renal failure. However, this
improvement of quality of life does not always concern the patient's sex life.
The main causes of erectile dysfunction in haemodialysed patients are endocrine
disorders, uraemic neuropathy, tissue lesions related to chronic renal failure,
and drugs. These factors of erectile dysfunction are partially corrected by
transplantation, but other factors can subsequently be involved, such as drugs
or vascular causes. The objective of this study is therefore to conduct a review
of the literature on erectile dysfunction (epidemiology, pathophysiology,
treatment) in patients with end-stage renal failure (dialysis) and after renal
transplantation.
-----
Drugs. 2005;65(12):1621-50.
A comparative review of the options for treatment of erectile
dysfunction: which treatment for which patient?
Hatzimouratidis K, Hatzichristou DG.
Center for Sexual and Reproductive Health, Aristotle University of Thessaloniki,
Thessaloniki, Greece. hatzichr@med.auth.gr
The field of erectile dysfunction (ED) has been revolutionised over the last two
decades. Several treatment options are available today, most of which are
associated with high efficacy rates and favourable safety profiles. A MEDLINE
search was undertaken in order to evaluate all currently available data on
treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil,
tadalafil, vardenafil) are currently the first-choice of most physicians and
patients for the treatment of ED. PDE5 inhibitors have differences in their
pharmacological profiles, the most obvious being the long duration of action of
tadalafil, but there are no data supporting superiority for any one of them in
terms of efficacy or safety. Sublingual apomorphine has limited efficacy
compared with the PDE5 inhibitors, and its use is limited to patients with mild
ED. Treatment failures with oral drugs may be due to medication, clinician and
patient issues. The physician needs to address all of these issues in order to
identify true treatment failures. Patients who are truly unresponsive to oral
drugs may be offered other treatment options.Intracavernous injections of
alprostadil alone, or in combination with other vasoactive agents (papaverine
and phentolamine), remain an excellent treatment option, with proven efficacy
and safety over time. Topical pharmacotherapy is appealing in nature, but
currently available formulations have limited efficacy. Vacuum constriction
devices may be offered mainly to elderly patients with occasional intercourse
attempts, as younger patients show limited preference because of the unnatural
erection that is associated with this treatment modality. Penile prostheses are
generally the last treatment option offered, because of invasiveness, cost and
non-reversibility; however, they are associated with high satisfaction rates in
properly selected patients.All treatment options are associated with particular
strengths and weaknesses. A patient-centred approach based on patient needs and
expectations is necessary for the management of ED. The clinician must educate
the patient and provide a supportive environment for shared decision making. The
management strategy must be supplemented by careful follow-up in order to
identify changes in patient health and relationship/emotional status that may
necessitate treatment optimisation.
-----
Ann Pharmacother. 2005 Jun 7; [Epub ahead of print]
Phosphodiesterase 5 Inhibitors for Erectile Dysfunction (CE)
(July/August).
Setter SM, Iltz JL, Fincham JE, Campbell RK, Baker DE.
Department of Pharmacotherapy, College of Pharmacy, Washington State
University/Elder Services, Spokane, WA.
OBJECTIVE: To review the pharmacologic and clinical trial data of the Food and
Drug Administration-approved phosphodiesterase 5 (PDE5) inhibitors for the
treatment of erectile dysfunction (ED). DATA SOURCES: Primary research and
review articles were identified through a search of ScienceDirect, PubMed/MEDLINE,
and International Pharmaceutical Abstracts (1990-August 2004). The following
search terms were used in the Medicine Dentistry and Pharmacology, Toxicology,
and Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5
inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil,
prostatectomy, and diabetes. Web of Science (1990-August 2004) was used to
search for additional abstracts using the same search terms as above. The
package inserts for sildenafil, vardenafil, and tadalafil were also consulted.
STUDY SELECTION AND DATA EXTRACTION: All identified research, review articles,
and abstracts were assessed for relevance, and all relevant information was
included. Priority was given to the primary medical literature and clinical
trial reports. DATA SYNTHESIS: ED is a common disorder in males with increased
prevalence associated with age and presence of cardiovascular disease,
prostatectomy, or diabetes mellitus. Sildenafil, vardenafil, and tadalafil are
selective PDE5 inhibitors currently available for treatment of ED. Their
pharmacology and pharmacokinetics vary slightly, but with potentially important
clinical differences in duration of activity; all have similar clinical efficacy
and adverse effect profiles in patients with ED of various causes. CONCLUSIONS:
Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for
the treatment of ED. ((CE)) This article is approved for continuing education
credit ACPE UNIVERSAL PROGRAM NUMBER: 407-000-05-xxx-H01.
-----
J Urol. 2005 Jun;173(6):2067-71.
Vardenafil improved patient satisfaction with erectile hardness,
orgasmic function and sexual experience in men with erectile dysfunction
following nerve sparing radical prostatectomy.
Nehra A, Grantmyre J, Nadel A, Thibonnier M, Brock G.
Department of Urology, Mayo Clinic, Rochester, Minnesota, USA. nehra.ajay@mayo.edu
PURPOSE: Nerve sparing radical retropubic prostatectomy (NS-RRP) results in
erectile dysfunction in a significant number of patients. Vardenafil, a potent
and selective phosphodiesterase type 5 inhibitor, is generally safe. It improves
International Index of Erectile Function erectile function domain scores, and
penetration and erection maintenance success rates in patients who have
undergone NS-RRP. We report additional parameters important to patient
perceptions regarding erection quality and satisfaction with sexual experience
following NS-RRP. MATERIALS AND METHODS: A total of 440 men at 58 centers
throughout the United States and Canada participated in this randomized, placebo
controlled, double-blind trial with 3 phases, namely baseline (4-week untreated
period), treatment (12 weeks) and followup (7 days). Participants received
placebo (145), 10 mg vardenafil (146) or 20 mg vardenafil (149) at home on
demand but no more than once per calendar day. Efficacy and satisfaction with
erection quality and sexual experience were determined during the trial.
RESULTS: The 10 and 20 mg vardenafil doses were significantly superior to
placebo for the International Index of Erectile Function domains for intercourse
satisfaction, orgasmic function and overall satisfaction with sexual experience
(vs placebo p <0.0009). Significant improvement in the satisfaction rate with
erection hardness were demonstrated for each vardenafil dose compared with
placebo (p <0.0001). Vardenafil was generally well tolerated. Common adverse
events were headache, vasodilatation and rhinitis. CONCLUSIONS: In this
difficult to treat population of men with erectile dysfunction subsequent to NS-RRP
on demand treatment with vardenafil during a 3-month period significantly
improved key aspects of the sexual experience important to patient quality of
life.
-----
Int J Clin Pract. 2005 Jun;59(6):680-91.
Past, present, and future: a 7-year update of Viagra (sildenafil
citrate).
Jackson G, Gillies H, Osterloh I.
Guys and St.Thomas Hospital Trust, London, UK.
Summary More than 30 million men are estimated to have erectile dysfunction (ED)
in the United States (Feldman et al. J Urol 1994;151: 54-61). Worldwide, ED is
estimated to affect more than 150 million men, and that number is expected to
exceed 300 million men by the year 2025 (Aytac et al. BJU Int 1999;84: 50-6).
The prevalence of ED ranges from 7% in men aged 18-29 years (Laumann et al. JAMA
1999;281: 537-44) to 85% in men aged 76-85 years. In addition, a recent report
showed that 68% of patients with ED aged 18 years and older have at least one
comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression (Seftel
et al. J Urol 2004;171: 2341-5), and research suggests that ED may be an early
indicator of systemic vascular disease (Kaiser et al. J Am Coll Cardiol 2004;43:
179-84). Viagra((R)) (sildenafil citrate), the first-in-class phosphodiesterase
type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED (Boolell
et al. Br J Urol 1996;78: 257-61; Boolell et al. Int J Impot Res 1996;8: 47-52).
In the 7 years since its market launch, more than 750,000 physicians have
prescribed sildenafil to more than 23 million men, helping establish an
excellent safety and efficacy record. Clinical studies have demonstrated that
sildenafil successfully treats ED of varied organic, psychogenic or mixed
aetiology, and is effective in men with ED and comorbidities such as
hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a
breakthrough medication that addressed a previously unfulfilled medical need.
The impact of sildenafil has stimulated academic, clinical and industrial
research to better understand the nature of sexual function and develop better
treatment and management for sexual dysfunctions such as ED. With the advent of
other erectogenic therapies for the treatment of ED, this 7-year update will
focus on the unique history and development of sildenafil, its current use and
applications and its future directions and indications. Special emphasis is
placed on the impact of sildenafil on our understanding of sexual health and on
the extensive safety and efficacy data that have been amassed from numerous
clinical trials.
-----
J Int Med Res. 2005 May-Jun;33(3):337-48.
The real-life safety and efficacy of vardenafil: an international
post-marketing surveillance study--results from 29 358 German patients.
van Ahlen H, Zumbe J, Stauch K, Landen H.
Klinikum Osnabruck, Osnabruck, Germany.
We assessed the safety, efficacy and patient acceptability of vardenafil (Levitra,
Bayer HealthCare, Leverkusen, Germany) under real-life conditions in patients
with erectile dysfunction (ED) in a multinational post-marketing surveillance
study. An initial and up to two follow-up visits were documented for 29 358
German ED patients receiving vardenafil. Patients were interviewed about overall
treatment success, and individual sexual attempts were evaluated in a patient
questionnaire. Overall erectile improvement was reported by 93.9% of physicians,
and similar improvement rates were reported for both 10 mg and 20 mg vardenafil
dosages. Most patients experienced improved erections after the first (73.6%) or
second (88.5%) tablet. Sexual attempts were successful with respect to partner
penetration in 94.9% of patients and with respect to maintenance of erection
during intercourse in 87.7% of patients. Adverse drug reactions were very rare
(1.3% of patients). Vardenafil was highly effective, reliable and well tolerated
in ED patients treated under real-life conditions.
-----
J Androl. 2005 May-Jun;26(3):310-8.
Tadalafil improved erectile function at twenty-four and
thirty-six hours after dosing in men with erectile dysfunction: US trial.
Young JM, Feldman RA, Auerbach SM, Kaufman JM, Garcia CS, Shen W, Murphy AM,
Beasley CM Jr, Hague JA, Ahuja S.
South Orange County Medical Research Center, 24301 Paseo de Valencia, Suite 100;
Laguna Woods, CA 92653, USA. jyoung20@cox.net
In a previous study assessing tadalafil for the treatment of erectile
dysfunction (ED), tadalafil 20 mg was shown to improve erectile function for up
to 36 hours vs placebo. This study sought to demonstrate the effectiveness of
both 10- and 20-mg tadalafil vs placebo at 2 prespecified assigned times of 24
and 36 hours postdosing. This double-blind, placebo-controlled, parallel-group
study randomized 483 men with ED into 6 groups according to a combination of
treatment (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours)
for intercourse attempts. Patients were stratified by baseline ED severity based
on Erectile Function Domain scores. The study had 4 phases: a 4-week run-in (no
ED medication taken); a 2- to 4-week equilibration (dosing as needed); a 4- to
6-week assessment; and a 6-month open-label extension. During the assessment
phase, men took a total of 4 doses of study medication, each dose separated by
more than or equal to 7 days. Efficacy was measured as the mean per-patient
percentage of successful intercourse attempts (Sexual Encounter Profile Diary
Question 3: SEP3) during the assessment phase. Men taking either 10- or 20-mg
tadalafil had a significant increase in SEP3 from baseline scores vs placebo at
both 24 hours (P = .038 and <.001 for 10 and 20 mg, respectively) and 36 hours
(P < .001 for both doses) postdose. The mean per-patient percentages of
successful intercourse attempts for the 24-hour time point were 41.8%, 55.8%,
and 67.3% for placebo and tadalafil 10 and 20 mg, respectively; for the 36-hour
time point, the mean per-patient percentages were 32.8%, 56.2%, and 61.9% for
placebo and tadalafil 10 and 20 mg, respectively. The most common
treatment-emergent adverse events were headache, back pain, dyspepsia, and
nasopharyngitis. Both 10- and 20-mg tadalafil improved erectile function for up
to 36 hours postdosing in men with ED of varied severity.
-----
Expert Opin Drug Saf. 2005 May;4(3):531-40.
Pharmacotherapy of erectile dysfunction: focus on cardiovascular
safety.
Reffelmann T, Kloner RA.
The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular
Medicine, Keck School of Medicine, University of Southern California, 1225
Wilshire Boulevard, Los Angeles, CA 90017-2395, USA.
Therapy of erectile dysfunction has been revolutionised in recent years, as
specific pharmacological inhibitors of phosphodiesterase 5 (PDE5), such as
sildenafil, tadalafil, or vardenafil, were shown to be highly effective in the
treatment of erectile dysfunction. They dilate arterial smooth muscle cells of
the corpora cavernosa, which express PDE5 abundantly, by inhibiting the
breakdown of 3'5'-cyclic guanosine monophosphate. Despite theoretical concerns
of a reduced myocardial tolerance to ischaemia or promoting cardiac arrhythmias,
randomised trials and retrospective analyses do not support an increased cardiac
risk with oral treatment. Therapeutic doses of PDE 5 inhibitors exhibit slight
blood pressure lowering effects, and do not appear to compromise coronary blood
flow in coronary artery disease. However, the combination of PDE5 inhibitors
with any nitric oxide donor is absolutely contraindicated because of potentially
life-threatening hypotension. Before prescribing medication for erectile
dysfunction, any patient with cardiovascular disease should be evaluated for a
potential risk of a cardiovascular event during sexual activity according to the
Princeton Consensus Panel. When a stable cardiac condition can be achieved (low
risk group), oral treatment for erectile dysfunction may be appropriate.
-----
Int J Impot Res. 2005 May 12; [Epub ahead of print]
Evaluation of a progressive treatment program for erectile
dysfunction in patients with diabetes mellitus.
Israilov S, Shmuely J, Niv E, Engelstein D, Livne P, Boniel J.
1Institute of Urology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa,
Israel.
The aim was to evaluate the effectiveness of a progressive program, starting
with simple methods and, when not effective, moving to more complex methods, to
treat erectile dysfunction (ED) in patients with diabetes mellitus. A total of
284 diabetic patients with ED entered into a 6-phase program starting with
sildenafil citrate (Viagra). Those with contraindications, side effects, or
negative response (erection insufficient for vaginal penetration) were switched
to the vacuum erection device (VED), and then progressively (for failures) to
intracavernous injection (ICI), sildenafil citrate+ICI, ICI+VED, and penile
prosthesis. Patients were followed for 2 y. Of the 284 patients 276 patients
were eligible for sildenafil citrate and 147 (53.3%) responded positively, but
25 (9.1%) patients stopped it soon due to adverse effects. Of 162 patients (129
nonresponders, eight noneligible for the sildenafil and 25 patients who dropped
out due to adverse effects), treated with VED, 114 (70.4%) responded well,
however, only 19 (11.7%) patients agreed to continue its use. Of the remaining
143 patients (nonresponders, noneligible for the previously mentioned treatments
and patients who dropped out due to adverse effects), 103/143 (72%) responded to
ICI, 27/40 (67.5%) to sildenafil+ICI, and 9/13 (69.2%) to ICI+VED. Four patients
received a penile implant. At the 2 y follow-up, 81 of 284 patients who entered
the study (28.5%) were still responding to sildenafil, seven (2.5%) to VED, 113
(39.8%) to ICI, 24 (8.5%) to sildenafil+ICI, two (0.7%) to ICI+VED; 15 (5.3%)
had a penile implant. In all 17 (6%) patients reported spontaneous erections, 11
(3.9%) stopped the treatment due to family reasons and 14 (4.9%) failed the
treatment. In conclusion, the progressive treatment program for ED seems to be
very effective for diabetic patients, yielded a complete response for short-term
and 91.2% rate of success at the end of 2 y follow-up.International Journal of
Impotence Research advance online publication, 12 May 2005;
doi:10.1038/sj.ijir.3901337.
-----
Int J Impot Res. 2005 May 12; [Epub ahead of print]
Recovery of erection after pelvic urologic surgery: our
experience.
Gallo L, Perdona S, Autorino R, Celentano E, Menna L, Di Lorenzo G, Gallo
A.
1Division of Urology, National Cancer Institute, 'Fondazione Pascale', Naples,
Italy.
The incidence of erectile dysfunction (ED) in patients undergoing pelvic
urologic surgery, the efficacy and tolerability of vardenafil-based
rehabilitative treatment as first option in these patients, the role of
spontaneous erection (SE) as a possible positive predictive factor to erection
recovery after such treatment, and the role of second-line therapies in those
nonresponders are evaluated. All the patients undergoing pelvic urologic surgery
at our Institution between November 2002 and December 2003 were considered.
Preoperative erectile function (EF) was evaluated by using the abridged
five-item version of the International Index of Erectile Function (IIEF5)
questionnaire. Study population was divided into separate groups considering
grade of preoperative EF, nerve sparing (NS) surgery and type of procedure
(radical prostatectomy, radical cystectomy (RC) or nerve and seminal sparing
cystectomy). In total, 86 patients were evaluated. After 6 months, an increase
in mean IIEF5 score of 12.9 points was found in those who had undergone a
bilateral NSRP after vardenafil therapy, of 8.0 points in those who had
undergone unilateral NSRP, of 11.3 in those who had undergone NSRC and of 11.5
in nerve and seminal sparing cistectomies. A better vardenafil response was
found in patients with SE+(P<0.001). Among those vardenafil notresponders, 13
were treated by using intracavernous injections, one by vacuum device and three
with penile prosthesis implant. In conclusion, in our experience, vardenafil
showed to be well tolerated and effective for recovery of EF in patients
undergoing pelvic urologic surgery. This drug was particularly effective for
those with a normal preoperative EF undergoing an NS procedure. Of course, it
should be recognized that the absence of a control group in the study represents
an important limitation. However, based on the data from the literature, there
is a strong belief that such an approach will lead to an earlier recovery of EF
than without rehabilitative treatment.International Journal of Impotence
Research advance online publication, 12 May 2005; doi:10.1038/sj.ijir.3901338.
-----
Drugs Aging. 2005;22(4):323-38.
Safety and tolerability of oral erectile dysfunction treatments
in the elderly.
Salonia A, Briganti A, Montorsi P, Maga T, Deho F, Zanni G, Mazzoccoli B, Suardi
N, Rigatti P, Montorsi F.
Department of Urology, Universita Vita-Salute San Raffaele, Milan, Italy.
Erectile dysfunction (ED) is a common medical condition that affects the sexual
life of millions of men worldwide. It is generally accepted that sexual function
tends to decline with aging, which is often associated with a higher prevalence
of sexual problems, including ED and loss of libido. As the mean age of men
seeking medical help for sexual dysfunction continues to increase, it is
important to assess the safety and tolerability of currently available medical
treatments in elderly men, who often share other co-morbidities that should be
carefully evaluated when any type of ED therapy is considered. With this aim in
mind, a MEDLINE search was conducted from 1 January 1998 to 31 May 2004 to
identify studies assessing the efficacy, safety and tolerability of treatments
for ED in the elderly. Particular care was taken to assess the cardiovascular
safety of oral drugs for ED in this subset of patients, who often have multiple
cardiovascular risk factors which contribute to a complicated clinical scenario.
The most important conclusion of the paper is that the high efficacy,
reliability, safety and tolerability of oral ED treatments makes them
appropriate first-line therapies for elderly patients with ED.
-----
J Manag Care Pharm. 2005 Mar;11(2):151-71.
Clinical monograph for drug formulary review: erectile
dysfunction agents.
Campbell HE.
WellPoint Pharmacy Management, P.O. Box 9, Cherry Valley, NY, 13320, USA.
Helen.campbell@wellpoint.com.
BACKGROUND: Significant advances in the pharmacologic treatment of erectile
dysfunction (ERD) have occurred in recent years, most notably the introduction
of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5)
inhibitor, in 1998. Sildenafil quickly gained acceptance by the medical
community and the public because of its broad efficacy for different types of
ERD and its ease of use. Two PDE5 inhibitors, vardenafil and tadalafil, have
since joined sildenafil to compete in the ERD market. A review was conducted by
the Drug Information Service of a pharmacy benefits manager (PBM) to determine
the relative merits and place in therapy of commonly used ERD drugs as part of
drug formulary management process and decision making by the Pharmacy &
Therapeutics (P&T) committee. OBJECTIVE: To provide readers with a comprehensive
clinical monograph on ERD drugs written from a managed care perspective.
METHODS: The PBM clinical monograph is designed to provide health plans with an
evidence-based review of drugs, therapeutic classes, and disease states with a
managed care focus. For each therapeutic class or disease review, an extensive
and thorough literature search of MEDLINE is conducted for efficacy, safety,
effectiveness, and humanistic and economic data. Drug/disease-state databases (UptoDate
online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key
Internet sites, medical/pharmacy-related news sites, clinical guidelines, and
AMCP dossiers are also reviewed. Formulary drug monographs prepared by the Drug
Information Service of the PBM include a critical analysis and summary of
disease-oriented and patient-oriented clinical outcomes, effectiveness, and
humanistic data. Additional data considered and included in the formulary review
process are clinical attributes, patent expirations/generic competition,
off-label or pending indications, and pharmacoeconomic data. RESULTS: Despite
the lack of head-to-head comparative studies, all 3 PDE5 inhibitors appear to
have equivalent efficacy in the treatment of general ERD and ERD associated with
diabetes and postprostatectomy. Sildenafil has additional efficacy data in the
management of ERD associated with spinal cord injury and antidepressant
medications. Tadalafil has the longest duration of action (up to 36 hours); this
feature can be both beneficial (greater sexual spontaneity) or possibly
detrimental (greater exposure to drug, delayed adverse events). All 3 PDE5
inhibitors appear to be generally well tolerated and have similar
contraindications and warnings. However, vardenafil is the only PDE5 inhibitor
with a cardiac conduction precaution. Alprostadil products are recommended in
current ERD guidelines as second-line therapy for those who have not responded
or cannot take the oral PDE5 inhibitors. Overall, higher clinical efficacy rates
are achieved with intracavernous than with transurethral administration.
CONCLUSION: A large amount of clinical efficacy and safety data has been
published since the market launch of sildenafil in 1998. Sildenafil has the
greatest body of efficacy and safety evidence. No comparative studies have been
conducted with any of the PDE5 inhibitors. Differences in study populations,
primary end points, and measurement tools make comparisons difficult. However,
all PDE5 inhibitors appear to be roughly equivalent in efficacy, with minor
differences in adverse event profiles. Until more comparative data are
available, economic considerations will be a significant factor in choosing ERD
products for formulary inclusion.
-----
Scand J Urol Nephrol. 2005;39(1):69-72.
Clinical experience with the mentor alpha-1 inflatable penile
prosthesis: Report on 65 patients.
Jensen JB, Larsen EH, Kirkeby HJ, Jensen KM.
Departments of Urology, Skejby Sygehus Aarhus University Hospital Aarhus
Denmark.
Objective To evaluate the complications and prosthesis survival associated with
implantation of the Mentor Alpha-1 inflatable penile prosthesis (IPP) for the
treatment of erectile dysfunction (ED). Material and Methods Between August 1995
and March 2003, 65 patients underwent implantation of a Mentor Alpha-1 IPP at
the Urological Departments of Skejby or Aalborg University Hospitals. Patient
data were obtained retrospectively from medical files. Results The follow-up
period ranged from 1 to 96 months (median 48.5 months). Twenty-one patients
(32%) experienced complications that required revision. The majority of
complications consisted of mechanical problems, but infection was also a large
contributor to the complication rate. Seven patients (11%) had the prosthesis
permanently removed due to infection. Kaplan-Meier estimates of the 5-year
prosthesis survival rates with and without successful revisions due to
complications were 88% and 63%, respectively. Conclusions The Mentor Alpha-1 IPP
is an efficient treatment for ED in situations where less invasive therapy has
failed. The risk of infection or mechanical failure must not be ignored.
Patients should be informed of this risk before agreeing to implantation
surgery.
-----
Scand J Urol Nephrol. 2005;39(1):66-68.
Patient and partner satisfaction with the mentor alpha-1
inflatable penile prosthesis.
Jensen JB, Madsen S, Larsen EH, Jensen KM, Kirkeby HJ.
Departments of Urology, Skejby Sygehus Aarhus University Hospital Aarhus
Denmark.
Objective To evaluate the satisfaction level of patients and partners after
implantation of a Mentor Alpha-1 inflatable penile prosthesis (IPP) for the
treatment of erectile dysfunction (ED). Material and methods A questionnaire was
sent to 46 patients who had been operated on for ED with implantation of a
Mentor Alpha-1 IPP. The investigation was designed to evaluate patient and
partner satisfaction. Results Eighty-five percent of the questionnaires were
returned. Sexual desire had not changed but the quality of sexual activity had
significantly improved. Acceptance by the partner was good. Overall satisfaction
among both patients and partners was high. In total, 95% of patients said that
they would recommend the procedure to other patients in the same situation.
Conclusions Patient and partner satisfaction with the Mentor Alpha-1 IPP was
high, with the exception of the minority of patients who experienced
unacceptable complications. Infection and mechanical failure are important risks
which patients should be informed of before agreeing to implantation surgery.
-----
Int J Impot Res. 2005 Feb 24; [Epub ahead of print]
Erectile dysfunction in patients with coronary artery disease.
Kloner R, Padma-Nathan H.
1Heart Institute, Good Samaritan Hospital (USC), Los Angeles, CA, USA.
Recent studies suggest that erectile dysfunction (ED) may be an early marker of
endothelial dysfunction and coronary artery disease (CAD). Conversely, patients
with CAD commonly have ED. The phosphodiesterase 5 (PDE5) inhibitors are very
effective for the treatment of ED in patients with CAD. Numerous studies show
that this class of drugs is in general safe in patients with stable CAD and
these agents do not exacerbate ischemia in men with CAD undergoing exercise
stress testing. Analysis of placebo-controlled trials did not show an increase
in cardiovascular events among men receiving PDE5 inhibitors, and post-marketing
surveillance studies with sildenafil did not observe an increase in
cardiovascular events compared to expected age-matched rates. Organic nitrates
remain a contraindication for PDE5 inhibitors and alpha blockers have
precautions/contraindications depending upon specific drugs. The Princeton
Consensus Guidelines (soon to be updated) suggest a logical approach to the
patient with CAD seeking therapy for sexual dysfunction.International Journal of
Impotence Research advance online publication, 24 February 2005;
doi:10.1038/sj.ijir.3901309.
-----
Urology. 2005 Feb;65(2):353-9.
Efficacy, safety, and treatment satisfaction of tadalafil versus
placebo in patients with erectile dysfunction evaluated at tertiary-care
academic centers.
Carson C, Shabsigh R, Segal S, Murphy A, Fredlund P, Kuepfer C; Trial Evaluating
the Activity of Tadalafil for Erectile Dysfunction-United States (TREATED-US)
Study Group.
Division of Urology, University of North Carolina, Chapel Hill, North Carolina
27599-7235, USA.
OBJECTIVES: To determine the efficacy, safety, and treatment satisfaction of
tadalafil 20 mg for erectile dysfunction (ED) in patients evaluated at
tertiary-care academic centers. METHODS: In this randomized, double-blind,
placebo-controlled trial, patients were randomly allocated to receive fixed-dose
tadalafil 20 mg (n = 146) or placebo (n = 49) for 12 weeks. Efficacy was
assessed by the International Index of Erectile Function (IIEF), Sexual
Encounter Profile (SEP), and Global Assessment Question (GAQ); patient and
partner treatment satisfaction by the Erectile Dysfunction Inventory of
Treatment Satisfaction (EDITS) and SEP; and safety by adverse events, laboratory
values, and vital signs. RESULTS: Mean baseline IIEF erectile function (EF)
domain was 12.98. Fifty-one percent of enrolled patients had severe baseline ED,
and 82% had organic ED. Pre-existing, ED-associated comorbid conditions were
common. When compared with patients treated with placebo, those receiving
tadalafil reported significant improvement from baseline in the IIEF EF domain
(P <0.001), successful penetration attempts (SEP question 2; P <0.001),
successful intercourse (SEP question 3; P <0.001), and all secondary efficacy
outcomes (P <0.001). Patients and their sexual partners were also significantly
more satisfied with tadalafil treatment (P <0.001), including overall
satisfaction (P <0.001) and length of time the treatment worked (P <0.001). Mild
or moderate headache, dyspepsia, and myalgia were the most frequent
treatment-emergent adverse events reported. CONCLUSIONS: Tadalafil significantly
improved erectile function and patient and partner satisfaction and was well
tolerated. These results were observed in a tertiary-care, academic center
population with a high incidence of severe, organic ED, and comorbid medical
conditions, factors known to compromise erectile function and treatment outcome.
-----
J Urol. 2005 Feb;173(2):530-2.
Does sildenafil combined with testosterone gel improve erectile
dysfunction in hypogonadal men in whom testosterone supplement therapy alone
failed?
Greenstein A, Mabjeesh NJ, Sofer M, Kaver I, Matzkin H, Chen J.
Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of
Medicine, Tel-Aviv University, Tel Aviv, Israel. surge04@post.tau.ac.il
PURPOSE: We evaluated the efficacy of testosterone gel (T-gel) alone and in
combination with sildenafil in hypogonadal patients with erectile dysfunction
(ED). MATERIALS AND METHODS: A total of 49 hypogonadal men (mean age 60.7 years)
with ED participated for a mean of 20.2 months. Blood was tested for total and
bioavailable testosterone, and prostate specific antigen. Sexual function was
assessed using the International Index of Erectile Function questionnaire and a
global assessment question (GAQ). Men received 1% 5 gm T-gel for 6 months, and
100 mg sildenafil was added to those with a "no" response to the GAQ after 3
months on testosterone supplement. RESULTS: A total of 31 patients reported
significant improvement in the sexual desire domain (from a mean +/- SD of 4.2
+/- 0.8 to 8.6 +/- 0.4) and erectile function (EF) domain (from 13.6 +/- 1.9 to
27 +/- 0.8) following treatment with testosterone supplement alone. One patient
was excluded from study after urinary retention developed and 9 reported
irritation at the gel application site. In spite of normalization of total and
bioavailable testosterone values, and significant improvement of sexual desire
domain scores, the EF of 17 men remained less than 26 or they responded "no" to
the GAQ. These men received combined T-gel and sildenafil, after which all
graded EF greater than 26 and responded positively to the GAQ. CONCLUSIONS:
Combined treatment with sildenafil and T-gel has a beneficial effect on ED in
hypogonadal patients in whom treatment with testosterone supplement alone
failed.
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Expert Opin Pharmacother. 2005 Jan;6(1):75-84.
Comparison of clinical trials with sildenafil, vardenafil and
tadalafil in erectile dysfunction.
Doggrell SA.
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New
Zealand. s_doggrell@yahoo.com.
Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70years of
age. In the first major trial of sildenafil in ED, at 24weeks, improved
erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg,
respectively. Subsequently, sildenafil has been reported to be effective in men
with ED associated with diabetes and prostate cancer, and in psychogenic ED.
Sildenafil is safe in men with coronary artery disease, provided it is not used
with the nitrates (a contraindication). The most commonly reported adverse
effects with sildenafil are headache, flushing and dyspepsia. Vardena-fil is
more potent and more selective than sildenafil at inhibiting
phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the
treatment of ED. The only advantage that vardenafil has over sildenafil is that
it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side
effect which sometimes occurs with sildenafil. Tadalafil has a longer duration
of action than sildenafil and vardenafil. Tadalafil is similarly effective as
sildena-fil in the treatment of ED. In comparison studies, tadalafil is
preferred to sildenafil (50/100mg) by men with ED, possibly because of its
longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may
displace sild-enafil as the drug of choice among men with ED.
-----
Int J Impot Res. 2005 Jan 27; [Epub ahead of print]
Sildenafil in the treatment of erectile dysfunction in men with
diabetes: demand, efficacy and patient satisfaction.
Behrend L, Vibe-Petersen J, Perrild H.
Internal Medical Clinic I, University Hospital, Copenhagen NV, Denmark.
The objective of this study is to describe the eligibility, consumption,
efficacy and patient satisfaction when treating men with diabetes with
Sildenafil. The study is a prospective, self-reported, flexible-dose study. In
total, 45 patients with diabetes (type 1 or 2), complaining of erectile
dysfunction, were treated with Sildenafil over a 12-week period. Efficacy was
assessed using a patientlog, a general satisfaction questionnaire and the
International Index of Erectile Function (IIEF). Of 326 men, 192 reported
erectile dysfunction, 79 did not fulfil the criteria for Sildenafil treatment
and 49 declined to participate. In the group of 33 (age 45-75 y, mean+/-s.d.:
58.1+/-7.2) completing the study, erectile function was significantly improved
(P<0.0001). A total of 12 patients (36.4%) experienced no treatment effect at
all. Eligibility and desire for treatment was low. Sildenafil is far from being
a 'cure all' in the treatment of ED in diabetes.International Journal of
Impotence Research advance online publication, 27 January 2005;
doi:10.1038/sj.ijir.3901302.
-----
Am J Cardiol. 2005 Jan 1;95(1):36-42.
Efficacy and safety of sildenafil citrate in men with erectile
dysfunction and chronic heart failure.
Katz SD, Parker JD, Glasser DB, Bank AJ, Sherman N, Wang H, Sweeney M.
Department of Internal Cardiovascular Medicine, Yale University School of
Medicine, New Haven, Connecticut.
Chronic heart failure (CHF) is an increasingly common cardiovascular disorder.
Many patients who have CHF report moderate to marked decreases in the frequency
of sexual activity, and up to 75% of patients report erectile dysfunction (ED).
There are few controlled clinical data on the efficacy and safety of sildenafil
citrate in men who have ED and CHF; thus, we evaluated these parameters in
patients who had stable CHF. This was a double-blind, placebo-controlled,
flexible-dose study. Men who had ED and stable CHF were randomized to receive
sildenafil or placebo for 12 weeks. Primary outcomes were questions 3 and 4 of
the International Index of Erectile Function. Secondary outcomes included the 5
functional domains of the International Index of Erectile Function, 2 global
efficacy assessment questions, intercourse success rate, the Erectile
Dysfunction Inventory of Treatment Satisfaction, and the Life Satisfaction
Checklist. By week 12, patients who received sildenafil (n = 60) showed
significant improvements on questions 3 and 4 compared with patients who
received placebo (n = 72; p <0.002). Larger percentages of patients who received
sildenafil reported improved erections (74%) and improved intercourse (68%)
compared with patients who received placebo (18% and 16%, respectively).
Intercourse success rates were 53% among patients who received sildenafil and
20% among those who received placebo. Patients who received sildenafil were
highly satisfied with treatment and their sexual life compared with patients who
received placebo. Sixty percent of patients who received sildenafil and 48% of
patients who received placebo developed adverse events, including transient
headache, facial flushing, respiratory tract infection, and asthenia. The
incidence of events related to cardiovascular effects was low. Sildenafil is an
effective and well-tolerated management of ED in men who have mild to moderate
CHF.
-----
BJU Int. 2004 Dec;94(9):1301-9.
Erectile response with vardenafil in sildenafil nonresponders: a
multicentre, double-blind, 12-week, flexible-dose, placebo-controlled erectile
dysfunction clinical trial.
Carson CC, Hatzichristou DG, Carrier S, Lording D, Lyngdorf P, Aliotta P,
Auerbach S, Murdock M, Wilkins HJ, McBride TA, Colopy MW.
University of North Carolina, Chapel Hill, NC, USA.
Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy,
USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar,
UK Alvaro Morales, Canada Michael Perelman, USA OBJECTIVE To evaluate the
efficacy of vardenafil in patients previously unresponsive to sildenafil.
PATIENTS AND METHODS A multicentre, double-blind, 12-week, flexible-dose,
placebo-controlled trial was conducted, involving 463 men aged >/= 18 years with
moderate-to-severe erectile dysfunction (ED) and who were unresponsive to
sildenafil (by history). After a 4-week treatment-free run-in, patients received
placebo or vardenafil 10 mg with the option to maintain current dose or to
titrate by one dose level (5, 10 or 20 mg) based on efficacy and tolerability at
4 and 8 weeks. Outcome measures were the erectile function (EF) domain score of
the International Index of Erectile Function, two Sexual Encounter Profile diary
questions (vaginal penetration and maintenance of erection until successful
completion of intercourse), and the Global Assessment Question (GAQ). RESULTS
There was significantly better EF with vardenafil than with placebo throughout
the study. The least-square mean EF domain scores increased from 9.3 at baseline
to 17.6 at the 'last' observation carried forward (LOCF) analysis with
vardenafil (P < 0.001). Overall least-square mean per-patient success rates more
than doubled for penetration (30.3% to 62.3%) and quadrupled for successful
intercourse (10.5% to 46.1%) with vardenafil. Improved erections (positive
response to the GAQ) were reported by 61.8% of patients receiving vardenafil and
14.7% of those receiving placebo at LOCF (P < 0.001). Normal EF (domain score
>/= 26) was achieved by 30% of patients receiving vardenafil and 6% receiving
placebo at LOCF (P < 0.001). Adverse events were infrequent and representative
of the phosphodiesterase-5 inhibitor profile. CONCLUSION Vardenafil is an
effective and generally safe treatment for ED, even in men unresponsive to
sildenafil (by history).
-----
Am J Hypertens. 2004 Dec;17(12 Pt 1):1135-42.
Sildenafil citrate for erectile dysfunction in men receiving
multiple antihypertensive agents A randomized controlled trial.
Pickering TG, Shepherd AM, Puddey I, Glasser DB, Orazem J, Sherman N, Mancia G.
Columbia University Medical College, New York, New York.
BACKGROUND: Erectile dysfunction (ED) is common among men taking
antihypertensive drugs to control blood pressure. We evaluated the safety and
efficacy of sildenafil citrate for treating ED in men taking multiple
antihypertensive medications in a randomized, double-blind, placebo-controlled
trial. METHODS: A total of 568 men (>/=18 years) with ED and hypertension who
were taking two or more antihypertensives were randomized to sildenafil (n =
281) or matching placebo (n = 287) for a 6-week double-blind trial followed by a
6-week open-label phase during which all patients received sildenafil. Primary
efficacy variables were questions (Q) 3 and 4 (frequency of erections and
penetration) of the International Index of Erectile Function (IIEF), and
secondary efficacy variables were two global efficacy assessment (GEA) questions
regarding improvement in erections and intercourse. RESULTS: A total of 562 men
(mean age, 59 years) took >/=1 dose of study drug. At week 6, mean scores on
both Q3 and Q4 improved significantly among sildenafil-treated compared with
placebo-treated patients. In regard to Q3 and Q4 there were no differences
between patients taking two and those taking three or more antihypertensive
agents. In all, 71% and 69% of sildenafil-treated patients reported improved
erections (GEA1) and intercourse (GEA2) compared with 18% and 20% of
placebo-treated patients, respectively. By week 12, >80% of all patients
(regardless of initial treatment group) had improved erections and intercourse.
During double-blind treatment, 40% of sildenafil-treated and 25% of
placebo-treated patients experienced adverse events; fewer than 2% in each group
discontinued because of adverse events. CONCLUSIONS: Sildenafil was an effective
and well tolerated treatment for ED in men receiving multiple antihypertensives.
The results suggest that there were no additional safety risks associated with
the use of sildenafil in these patients.
-----
Urology. 2004 Dec;64(6):1187-95.
Vardenafil provides reliable efficacy over time in men with
erectile dysfunction.
Montorsi F, Hellstrom WJ, Valiquette L, Bastuba M, Collins O, Taylor T,
Thibonnier M, Homering M, Eardley I; North American and European Vardenafil
Groups.
Instituto San Raffaele, Milan, Italy.
OBJECTIVES: To evaluate the reliability of vardenafil efficacy and tolerability
within 12 weeks in a broad population of men with erectile dysfunction (ED).
METHODS: In a retrospective analysis of two pivotal, Phase III, randomized,
double-blind, placebo-controlled trials conducted in 107 centers, 1650 men aged
18 years or older with ED received vardenafil 5 mg, 10 mg, or 20 mg on demand
for 12 to 26 weeks. Outcome measures included the first-time and subsequent
overall success rate until week 12 for diary entries regarding vaginal
penetration (Sexual Encounter Profile [SEP]-2), erection maintenance (SEP-3),
satisfaction with erection hardness, and overall satisfaction with the sexual
experience. Mean efficacy was calculated for each patient during 12 weeks and
then averaged for all patients within each treatment group. RESULTS: At
baseline, the intention-to-treat population had moderate ED (International Index
of Erectile Function-Erectile Function domain score of 13). For SEP-2
(penetration), the first-attempt and subsequent success rate was 44% and 74% for
placebo, 71% and 81% for vardenafil 5 mg, 76% and 86% for vardenafil 10 mg, and
76% and 91% for vardenafil 20 mg, respectively. For SEP-3 (maintenance),
first-attempt and subsequent success rate was 25% and 56% for placebo, 51% and
76% for vardenafil 5 mg, 65% and 76% for vardenafil 10 mg, and 59% and 84% for
vardenafil 20 mg, respectively. For overall satisfaction with the sexual
experience, the first-attempt and subsequent success rate was 19% and 48% for
placebo, 48% and 68% for vardenafil 5 mg, 57% and 72% for vardenafil 10 mg, and
56% and 79% for vardenafil 20 mg, respectively. The reliability of vardenafil
was similar or slightly greater in sildenafil-naive subjects compared with prior
sildenafil responders. The most common adverse events were mild-to-moderate
headache, flushing, and rhinitis. CONCLUSIONS: Vardenafil provides reliable
efficacy for key erectile function parameters important to patients when
continuing oral treatment for ED.
-----
Curr Urol Rep. 2004 Dec;5(6):460-6.
Penile prosthesis coating and the reduction of postoperative
infection.
Abouassaly R, Montague DK.
Glickman Urological Institute, A/100, Cleveland Clinic Foundation, 9500 Euclid
Avenue, Cleveland, OH 44195, USA.
Despite the recent development of effective oral agents for the treatment of
erectile dysfunction, penile prosthesis implantation remains an effective and
acceptable treatment for the significant number of men who fail to respond to
nonsurgical therapy. The most serious complication that can affect the use of
most prosthetic devices is infection. In penile prostheses, this can be
devastating and frequently results in removal of the device despite aggressive
antibiotic therapy. In recent years, new strategies have been developed in an
attempt to minimize this risk. This review focuses on one such method, namely
the use of an antibiotic coating on the device. It reviews recent published data
regarding the effectiveness of such devices at decreasing infection rates.
-----
J Urol. 2004 Dec;172(6 Pt 1):2347-9.
Prospective, randomized, crossover comparison of sublingual
apomorphine (3 mg) with oral sildenafil (50 mg) for male erectile dysfunction.
Pavone C, Curto F, Anello G, Serretta V, Almasio PL, Pavone-Macaluso M.
>From the Department of Urology and Institute of Internal Medicine (PLA),
University of Palermo, Palermo, Italy.
PURPOSE:: We established the efficacy and safety of sublingual apomorphine
compared with oral sildenafil in comparable groups of patients with erectile
dysfunction (ED). MATERIALS AND METHODS:: This prospective, randomized,
crossover study included 77 heterosexual men with ED of various etiologies and
severities. A total of 62 men were randomized but only 34 were evaluable for
efficacy and tolerability. The study started with a run-in period of 2 to 4
weeks. The first 4 weeks of treatment were followed by a washout period of 4
weeks, after which patients changed to the alternate treatment for an additional
4-week period. The sequence of the 2 treatments was established by a
randomization list in blocks in closed packets. The primary efficacy end point
was the percent of attempts resulting in erection firm enough for intercourse.
Additional variables were the percent of attempts resulting in intercourse and
improvement in ED, as evaluated by the erectile function domain score of the
International Index of Erectile Function questionnaire. RESULTS:: Sildenafil was
significantly more effective than apomorphine in regard to the percent of
attempts resulting in erection firm enough for intercourse (85% vs 44%, p
<0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well
as erectile function evaluated by the erectile function domain score of the
International Index of Erectile Function (p <0.001). The incidence of adverse
events was not significantly different for the 2 drugs. Although the number of
patients was small, this study had strong statistical power due to the striking
difference in results. CONCLUSIONS:: Sildenafil was significantly more effective
than apomorphine for ED. No statistical difference in adverse events was noted.
-----
Zhonghua Nan Ke Xue. 2004 Nov;10(11):876-9.
[Efficacy and safety of vardenafil in men with erectile
dysfunction and depression]
[Article in Chinese]
Hu L.
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei
430071, China. huliquan0202@sina.com
Erectile dysfunction (ED) usually exists in combination with depression in men.
The comorbidity of the two diseases may bring more troubles to patients, so it
is important to find an effective treatment. Recently, DRIVER (Depression
Related Improvement with Vardenafil for Erectile Response) trials showed that,
phosphodiesterase 5 (PDE 5) inhibitor vardenafil could improve not only erectile
function but also depressive symptoms and quality of life in men with ED and
depression. Vardenafil was generally safe and well tolerated.
-----
Curr Opin Urol. 2004 Nov;14(6):375-80.
Current role of penile implants for erectile dysfunction.
Moncada I, Martinez-Salamanca JI, Allona A, Hernandez C.
aGregorio Maranon General Hospital, and bRuber International Hospital, Madrid,
Spain.
PURPOSE OF REVIEW: The purpose of this review is to appraise new developments
and publications in the field of penile prosthetic surgery. Urologists dealing
with erectile dysfunction need to recognize the value of penile prosthetic
surgery as a very efficacious treatment for this common condition. This type of
surgery is needed in a considerable proportion of patients with erectile
dysfunction so this review is timely and relevant. RECENT FINDINGS: The main
themes in the literature covered include risk factors for infection of penile
prostheses, its prevention with the use of hydrophilic and antibiotic-coated
prostheses, particularly in re-operations, and its management with the new
rescue procedures. Surgical tips for prosthetic surgery are also reviewed as
well as clinical outcomes and factors influencing them. SUMMARY: Of all the
invasive treatments currently available, placement of a penile prosthesis is one
of the most successful, giving high levels of satisfaction. With the aid of new
technical advances, the risk of infection - the most feared complication - can
be minimized so prosthetic surgery may play a major role in the treatment of
erectile dysfunction.
-----
BJU Int. 2004 Oct;94(6):871-7.
Efficacy and safety of tadalafil in a Western European population
of men with erectile dysfunction.
Eardley I, Gentile V, Austoni E, Hackett G, Lembo D, Wang C, Beardsworth A.
Department of Urology, St James University Hospital, Leeds, West Yorkshire, UK.
Section Editor Michael G. Wyllie Panel of Advisors Ian Eardley, UK Jean Fourcroy,
USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar,
UK Alvaro Morales, Canada Michael Perelman, USA OBJECTIVE To evaluate, in a
randomized, double-blind, placebo-controlled, multicentre trial, the safety and
efficacy of on-demand tadalafil (an oral phosphodiesterase type-5 inhibitor
approved in many countries for treating erectile dysfunction, ED) in a Western
European population of men with mild-to-severe ED. PATIENTS AND METHODS Patients
were randomized according to baseline severity of ED in a ratio of 3 : 1 to
receive either tadalafil 20 mg or placebo for 12 weeks. Primary efficacy
endpoints were mean changes from baseline to endpoint (12 weeks) in the erectile
function (EF) domain of the International Index of Erectile Function (IIEF) and
percentages of 'Yes' responses to Sexual Encounter Profile (SEP) diary Question
2 ('Were you able to insert your penis into your partner's vagina?') and
Question 3 ('Did your erection last long enough for you to have successful
intercourse?'). Secondary endpoints included mean changes from baseline to
endpoint in IIEF Intercourse Satisfaction and Overall Satisfaction domains,
selected questions of the IIEF, and the percentage of 'Yes' responses to Global
Assessment Questions (GAQ) at the last visit. Other analyses included the
percentage of patients in each treatment group at endpoint with IIEF EF domain
scores in the normal range (>26), the frequency of intercourse attempts and mean
per-patient intercourse success rate at various times after dosing. RESULTS The
mean age of the patients was 53 years and 80% had a history of ED of >/= 1 year.
The mean baseline EF domain score was 13.5, with 40.5% of patients in the severe
category. Tadalafil improved mean EF domain scores by 11.1, vs 0.4 for placebo
(P < 0.001). In addition, 73.9% of sexual intercourse attempts were successful
(SEP-Q3) in tadalafil-treated patients, compared with 29.9% in placebo-treated
patients during the period after baseline (P < 0.001). Tadalafil significantly
improved the mean IIEF intercourse satisfaction (5.1, tadalafil; 1.1, placebo)
and overall satisfaction domain scores (3.9, tadalafil; 0.5, placebo), P <
0.001. GAQs used to assess the overall effect of the treatment indicated that
tadalafil was superior to placebo (P < 0.001) in improving erections (82.1%,
tadalafil; 23.1%, placebo) and sexual activity (78.6% and 17.3%). The most
common treatment-emergent adverse events more frequent (>2%) with tadalafil than
placebo were headache, dyspepsia, flushing, back pain, pain in limb and myalgia.
These adverse events were mostly mild to moderate. CONCLUSIONS Tadalafil
improved erectile function and was well tolerated when taken by men from Western
Europe with mild-to-severe ED.
-----
Psychosom Med. 2004 Sep-Oct;66(5):664-71.
Erectile dysfunction: evaluation and new treatment options.
Carson CC.
Division of Urology, School of Medicine, University of North Carolina at Chapel
Hill, 427 Burnet-Womack Building, Campus Box 7235, Chapel Hill, NC 27599-7235,
USA. Carson@med.unc.edu
OBJECTIVE: Erectile dysfunction (ED) is a common condition of aging men. Indeed
as many as 50% of men over age 40 will suffer some degree of ED. This erectile
dysfunction has substantial impact on interaction with their partners, families,
and employment. ED may be a harbinger of more serious vascular events and is
commonly associated with depression. METHODS: Evaluation of ED begins with a
careful history, asking the patient about his sexual function during clinical
visits. Once identified, ED must be carefully considered with full history,
careful physical examination, and laboratory studies to include markers of
vascular risk factors, diabetes, and hypogonadism. RESULTS: The treatment of ED
was revolutionized by the introduction of phosphodiesterase type 5 (PDE5)
inhibitors in 1998. Currently, 3 PDE5 inhibitors are available internationally
with excellent expected results and somewhat unique profiles. Although these
agents are safe in all patients who do not have severe cardiac disease or who
are taking nitrate medications, they require some patient instruction and
counseling to optimize results. In that small group of patients who do not
respond to these oral medications, additional alternatives are available for
patients motivated to pursue treatment of their ED.CONCLUSION: Currently
available safe and effective alternatives for the treatment of ED can improve
the lives of patients and partners and increase their quality of life.
-----
Curr Med Res Opin. 2004 Sep;20(9):1377-84.
Preliminary observations on the use of propionyl-L-carnitine in
combination with sildenafil in patients with erectile dysfunction and diabetes.
Gentile V, Vicini P, Prigiotti G, Koverech A, Di Silverio F.
Department of Urology 'U Bracci', University 'La Sapienza', Rome, Italy.
PURPOSE: To investigate the efficacy and tolerability of oral
propionyl-L-carnitine (PLC) plus sildenafil in men with erectile dysfunction
(ED) and diabetes unresponsive to sildenafil monotherapy. MATERIALS AND METHODS:
Patients with medically documented ED of organic or mixed aetiology and diabetes
(type 1 and 2) were randomised to receive oral PLC (2 g/day) plus sildenafil (50
mg twice weekly) (20 patients, Group 1) or sildenafil alone (20 patients, Group
2), in a double-blind, fixed-dose study. All patients had been previously
treated unsuccessfully with a minimum of eight administrations of sildenafil.
Efficacy was evaluated using the International Index of Erectile Function (IIEF)
questionnaire: total score, subscores for questions 3 (Q3; achieving an
erection) and 4 (Q4; maintaining an erection) and global efficacy question (GEQ:
'Has treatment improved your erections?'). Patients Event Logs were also used.
RESULTS: After 24 weeks of treatment, mean scores for IIEF Q3 and Q4 had
improved significantly in patients of Group 1 (4.25 +/- 0.63 and 3.95 +/- 1.0)
compared with Group 2 (2.9 +/- 0.71 and 2.7 +/- 0.96) (p < 0.01). Moreover, the
percentage of patients with improved erections (GEQ 68% vs. 23%) and successful
intercourse attempts (76% vs. 34%) was significantly increased in Group 1
compared with Group 2 (p < 0.01). Fourteen (70%) patients in Group 1 and four
(20%) in Group 2 reported an increase in mean IIEF EF domain score of >/= 4 (p <
0.01). Treatments were well tolerated and no patient discontinued study
medication. Two patients in Group 1 reported mild gastric pain.CONCLUSIONS:
Salvage therapy with PLC plus sildenafil was more effective than sildenafil in
the treatment of ED in patients with diabetes refractory to sildenafil
monotherapy.
-----
Clin Endocrinol (Oxf). 2004 Sep;61(3):382-6.
Type V phosphodiesterase inhibitor treatments for erectile
dysfunction increase testosterone levels.
Carosa E, Martini P, Brandetti F, Di Stasi SM, Lombardo F, Lenzi A, Jannini EA.
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
OBJECTIVE: Lack of sexual activity due to erectile dysfunction (ED) decreases
testosterone (T) levels through a central effect on the hypothalamic-pituitary
axis. In this paper we studied the effect of different type V phosphodiesterase
(PDE5) inhibitor treatments for ED on the reversibility of this endocrine
pattern. DESIGN: Open-label, retrospective study. PATIENTS: Seventy-four
consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and
tadalafil (Tad) 20 mg. MEASUREMENTS: The success in sexual intercourse was
recorded and total (tT) and free testosterone (fT) levels were studied before
and after 3 months of treatment. RESULTS: Basal level of tT and fT were at the
bottom of the normal range and LH levels were at the top of the high normal
range. After treatments, this endocrine pattern was reversed in both groups.
However, the T increase in Sild-treated patients was significantly lower than in
those treated with Tad (4.7 +/- 2.7 vs. 5.1 +/- 0.9, P < 0.001). fT levels
followed a directly proportional pattern, while the inverse was found when LH
production was studied. The intercourse rate reflected this effect: in fact, the
Sild group showed a 4.9 +/- 2.9/month full sexual intercourse rate while in the
Tad group a significantly higher rate of sexual intercourse was found (6.9 +/-
4.6/month, P = 0.04). However, drug consumption was comparable between the
groups (Sild 4.9 +/- 2.9 vs. Tad 4.4 +/- 2.8 pills/month, P = 0.72).
CONCLUSIONS: As it is unlikely that the two drugs have a different direct effect
on the pituitary-testis axis, this effect is probably due to the higher
frequency of full sexual intercourse in the Tad-treated group, because of the
drug's longer half-life.
-----
J Urol. 2004 Sep;172(3):1036-41.
Tadalafil in the treatment of erectile dysfunction following
bilateral nerve sparing radical retropubic prostatectomy: a randomized,
double-blind, placebo controlled trial.
Montorsi F, Nathan HP, McCullough A, Brock GB, Broderick G, Ahuja S, Whitaker S,
Hoover A, Novack D, Murphy A, Varanese L.
Department of Urology, Universita Vita Salute San Raffaele, Via Olgettina 60,
20132 Milan, Italy. montorsi.francesco@hsr.it
PURPOSE: We evaluated the efficacy and safety of tadalafil 20 mg, taken on
demand, in men with erectile dysfunction following bilateral nerve sparing
radical retropubic prostatectomy (BNSRRP). MATERIALS AND METHODS: This
randomized, double-blind, placebo controlled multicenter study consisted of a
4-week treatment-free run-in period (baseline) followed by 12 weeks of
treatment. A total of 303 men (mean age 60 years) with preoperative normal
erectile function who had undergone a BNSRRP 12 to 48 months before study were
randomized (2:1) to tadalafil (201) or placebo (102). The 3 co-primary end
points were changes from baseline in the International Index of Erectile
Function erectile function domain score, and the percentage of positive
responses to Sexual Encounter Profile questions 2 (successful penetration) and 3
(successful intercourse). The Global Assessment Question and the Erectile
Dysfunction Inventory of Treatment Satisfaction questionnaire were secondary end
points. We defined a priori a subgroup of 201 patients reporting evidence of
postoperative tumescence, defined as 50% or greater "yes" responses to Sexual
Encounter Profile question 1 (ability to achieve at least some erection) during
baseline intercourse attempts and stratified randomization based on this
criterion. RESULTS: Patients receiving tadalafil reported greater improvement on
all primary and secondary end points (p <0.001) compared to placebo. For all
randomized patients and for the subgroup with evidence of postoperative
tumescence, the mean International Index of Erectile Function erectile function
domain score increased for patients receiving tadalafil (mean +/- SEM 5.3 +/-
0.5 and 5.9 +/- 0.7, respectively, p <0.001 vs placebo for both). For all
randomized patients who received tadalafil, the mean percentage of successful
penetration attempts was 54% and the mean percentage of successful intercourse
attempts was 41%. For the subgroup with evidence of postoperative tumescence
these values were 69% and 52%, respectively. Of all patients randomized to
tadalafil 62% and of the subgroup patients randomized to tadalafil 71% reported
improved erections. Patients receiving tadalafil reported greater treatment
satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction
than those receiving placebo. Headache (21%), dyspepsia (13%) and myalgia (7%)
were the most commonly reported adverse events. CONCLUSIONS: Tadalafil 20 mg,
taken on-demand, was an efficacious and well tolerated treatment for erectile
dysfunction following BNSRRP.
-----
Annu Rev Med. 2004 Aug 20 [Epub ahead of print]
Andropause: Is Androgen Replacement Therapy Indicated for the
Aging Male?
Hijazi RA, Cunningham GR.
Department of Medicine, Baylor College of Medicine and VA Medical Center,
Houston, Texas rhijazi@bcm.tmc.edu, Departments of Medicine and Molecular and
Cellular Biology, Baylor College of Medicine and VA Medical Center, Houston,
Texas glennc@bcm.tmc.edu
The number of men in the United States 65 years of age is projected to increase
from 14,452,000 in 2000 to 31,343,000 in 2030. Approximately 30% of men 6070
years of age and 70% of men 7080 years of age have low bioavailable or free
testosterone levels. Symptoms and findings of testosterone deficiency are
similar to those associated with aging. They include loss of energy, depressed
mood, decreased libido, erectile dysfunction, decreased muscle mass and
strength, increased fat mass, frailty, osteopenia, and osteoporosis. Several
small clinical trials indicate that testosterone replacement therapy can improve
many of these findings; however, the studies have not been powered to assess
potential risks, such as the need for invasive treatment of benign prostatic
hyperplasia, development of a clinical prostate cancer, or cardiovascular
events. Thus, the benefit/risk ratio of testosterone replacement therapy in
aging men is not known. Expected online publication date for the Annual Review
of Medicine Volume 56 is January 7, 2005. Please see http://www.annualreviews.org/catalog/pub_dates.asp
for revised estimates.
-----
Int J Clin Pract. 2004 Aug;58(8):801-6.
Vardenafil: a new oral treatment for erectile dysfunction.
Eardley I.
St James University Hospital, Leeds, UK. ian.eardley@btinternet.com
Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men
with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in
the USA in late 2003. It is a potent and selective inhibitor of the enzyme
phosphodiesterase type 5, and in the presence of an erectile stimulus
potentiates the intracellular actions of cyclic guanylate monophosphate. Several
large, placebo-controlled trials have demonstrated efficacy both in the broad
population of men with ED and in men with more difficult to treat ED. It is well
tolerated with a side effect profile typical of this class of drugs. It has a
rapid onset of action and has demonstrable efficacy for men using the medication
for up to 2 years.
-----
Arch Androl. 2004 Jul-Aug;50(4):255-60.
Clinical efficacy and safety of sildenafil in elderly patients
with erectile dysfunction.
Fujisawa M, Sawada K.
Department of Urology, Kawasaki Medical School, Kurashiki, Japan. masato@med.Kawasaki-m.ac.jp
Erectile dysfunction (ED) is a common medical disorder affecting elderly men.
Sildenafil citrate has been shown to be an effective and well-tolerated oral
agent for treating ED in the general population of adult men with ED of
broad-spectrum etiology. Elderly men are more likely to have concomitant medical
problems than the general population of men with ED. In this study, we examined
the efficacy and safety of sildenafil administration in elderly patients with
ED. Forty-four elderly men with ED (> or = 60 years old) of broad-spectrum
etiology were treated with 25 mg or 50 mg doses of sildenafil citrate. Age
ranged from 60 to 78 years (65 +/- 4.5; means +/- S.D.). Mean follow-up period
was 12.3 +/- 6.5 months, with a range of 1 to 25 months. Primary efficacy
assessments were performed using the International Index of Erectile Function 5
(IIEF5) before their first dose of sildenafil and after at least 4 weeks of
therapy. Serum testosterone was measured before treatment. The mean IIEF5 among
all patients increased from 8.5 +/- 3.9 to 20 +/- 4.2 after sildenafil use (P <
0.0001). In patients younger than 70 years, the IIEF5 score increased from 9.5
+/- 5.0 to 17 +/- 4.3 while in patients 70 years and older, the score increased
from 8.2 +/- 3.6 to 21 +/- 3.9, a near normalization. The rate of improvement in
younger men was higher than in older men. Serum testosterone before treatment
was similar in the two groups. The most commonly experienced adverse events were
flushing and dyspepsia, which occurred in 6.8% and 2.3%, respectively. No
patients discontinued sildenafil treatment due to adverse events. In conclusion,
oral sildenafil is efficacious and well tolerated by elderly men with ED, even
among those older than 70 years.
-----
Nervenarzt. 2004 Jun;75(6):595-605; quiz 606-7.
[Erectile function disorders. Epidemiology, physiology, etiology,
diagnosis and therapy]
[Article in German]
Derouet H, Osterhage J, Sittinger H.
Urologische Universitatsklinik, Homburg/Saar. DRDEROUET@aol.com
Erectile dysfunction is a common, age-dependent functional disturbance of men
associated to various comorbidities. Interdisciplinary cooperation with
neurologists in ca-ses of a suspected neurological aetiology and with
psychiatrists in cases with normalorganic diagnostic findings is necessary.
Hormone replacement and psychotherapy can cure certain patients. Oral
pharmacotherapy is the most effective therapy for erectile dysfunction with the
highest patient preference. Oral PDE-5-inhibitors(sildenafil, tadalafil,
vardenafil) are superior in effectiveness to centrally acting drugs (apomorphin,
yohimbine). Local pharmacotherapy (MUSE, ICI) is a second line therapy in cases
of failure or contraindications for oral pharmacotherapy. Vacuum therapy and
operative procedures(penile implants) complete the therapeutic options of
erectile dysfunction.
-----
Zhonghua Nan Ke Xue. 2004 Jun;10(6):455-7.
[Sildenafil citrate for erectile dysfunction in male kidney
transplant recipients]
[Article in Chinese]
Liu F, Zhang G, Ji X, Huang C, Wang P, Fan M.
Renal Disease Research Center, Department of Urinary Surgery, XinQiao Hospital,
Third Military Medical University, Chongqing 400037, China. liufwh@hotmail.com
OBJECTIVE: To evaluate the efficacy and safety of sildenafil citrate in man
kidney transplant recipients with erectile dysfunction. METHODS: One hundred and
seventy married males, aged 26 approximately 50 years, who had received kidney
transplantations at least half a year before and whose serum creatinine was
under 133 umol/l, were selected randomly in the study. Their sexual function was
investigated according to the International Index of Erectile Function-5
(IIEF-5), and those with erectile dysfunction (ED) were treated with oral
sildenafil citrate for 6 months. The efficacy was assessed by IIEF-5. RESULTS:
Fifty-three men with ED received oral sildenafil citrate for 6 months. At the
end of the treatment, each index in IIEF-5 increased significantly. There were
no interactions between sildenafil and cyclosporine and there was no significant
adverse effect of sildenafil on the graft function. CONCLUSION: Sildenafil is an
effective and safe agent for the treatment of ED in kidney transplant
recipients.
-----
Clin Cardiol. 2004 Apr;27(4 Suppl 1):I3-7.
Role of the cardiologist: clinical aspects of
managing erectile dysfunction.
Hutter AM Jr.
Department of Cardiology, Harvard Medical School, Massachusetts
General Hospital, Boston, Massachusetts 02114, USA. ahutter@partners.org
Erectile dysfunction (ED) is often a marker for serious underlying
cardiovascular disease (CVD), and cardiologists are increasingly
involved in the care of men with ED. It is important to ask specifically
about ED when evaluating men with CVD, since they may be embarrassed
to volunteer this information. During the clinical workup, it
is also important to check for contributing factors to ED such
as diabetes, depression, stress, alcohol abuse, and cardiovascular
risk factors. Patients should be advised that many treatment options
are available for ED, including the phosphodiesterase type 5 (PDE5)
inhibitors. The PDE5 inhibitors are safe and effective in most
patients with CVD, including those taking multiple antihypertensive
drugs. Furthermore, they have no deleterious effect on exercise
capacity, heart rate, or extent of exercise-induced ischemia.
In the future, the PDE5 inhibitors may have a role in reducing
pulmonary hypertension in persons with primary pulmonary arterial
hypertension (PAH) or congestive heart failure. The one major
precaution for men taking PDE5 inhibitors is to avoid concomitant
administration of therapeutic and recreational nitrate preparations.
Patients with chest pain suggestive of a heart attack need to
inform emergency room (ER) personnel if they are taking a PDE5
inhibitor. Similarly, before giving nitrates, ER personnel need
to ask patients if they have used PDE5 inhibitors. Nitrates should
not be given for at least 24 h after a patient uses sildenafil
or vardenafil and at least 48 h after a patient uses tadalafil.
-----
CMAJ. 2004 Apr 27;170(9):1429-37.
Erectile dysfunction: management update.
Fazio L, Brock G.
Division of Urology, Faculty of Medicine and Dentistry, University
of Western Ontario, London, Ont.
DRAMATIC ADVANCES IN THE MANAGEMENT of erectile dysfunction
have occurred over the past decade. Oral therapy with vasoactive
agents has emerged as first-line treatment and has transformed
both the manner in which the public views erectile dysfunction
and the way health care providers deliver care. Whereas an extensive
investigation was previously common in the management of erectile
dysfunction, recent treatment guidelines promote a more minimalist,
goal-oriented approach. In this article, we review the physiology
of erection, and the pathophysiology, diagnosis and clinical management
of erectile dysfunction. We also present the existing evidence
for the efficacy of 3 phosphodiesterase inhibitors, the most widely
used class of agents for erectile dysfunction.
-----
Cochrane Database Syst Rev. 2004;2:CD001784.
Prostaglandin E1 for treatment of erectile dysfunction.
Urciuoli R, Cantisani T, CarliniI M, Giuglietti M, Botti
F.
Neurofisiopatologia, Azienda Ospedaliera di Perugia, S. Andrea
Delle Fratte, San Sisto, Perugia, ITALY, 06156.
BACKGROUND: Erectile dysfunction (ED), the inability to achieve
or maintain an erection sufficient for satisfactory sexual activity,
is one of the most common sexual dysfunctions in men. ED may have
a dramatic impact on the quality of life of many men and their
partners. OBJECTIVES: The aim of this systematic review was to
evaluate and summarise the effectiveness and safety of PGE1 in
the treatment of erectile dysfunction. SEARCH STRATEGY: We searched
the Cochrane MS Group Trials Register (June 2003), the Cochrane
Central Register of Controlled Trials (issue 2, 2003), MEDLINE
(January 1966 - June 2003), EMBASE (January 1988 - June 2003)
and reference lists of articles. We also undertook handsearching
and contacting trialists and pharmaceutical companies. SELECTION
CRITERIA: All unconfounded, double blind, randomised controlled
trials comparing PGE1 and placebo treatment in participants with
ED of different aetiology were considered. Primary outcomes were:
(a) patient and partner satisfaction measured by means of a self-assessment;
(b) quality of life and (c) safety assessment. Both parallel group
and cross-over design trials were considered for inclusion. DATA
COLLECTION AND ANALYSIS: All the reviewers independently selected
articles for inclusion, assessed the trials' quality and extracted
the data. Study authors were contacted for additional information.
MAIN RESULTS: Four trials involving 1.873 people, heterogeneous
with respect to aetiology of ED, were included. Study design was
two cross-over and two parallel group trials. Only the latter
provided adequate data for meta-analyses. PGE1 was effective during
follow-up in the "at least one successful intercourse"
outcome (Peto Odds Ratio, OR 7.22, 95% CI. 5.68-9.18) and "number
of successful intercourse/number of PGE1 administrations"
(Peto Odds Ratio, OR 6.46, 95% CI. 5.95-7.01). One cross-over
study reported "at least one successful intercourse"
in 63.6% of participants with at least one dose of PGE1 (P <
0.01 for each active dose versus placebo). In the other cross-over
study, only one of three treatment groups conducted a self-evaluation
(55.5%: "good" or "excellent" response). Adverse
effects were most frequent in the treated groups and occurred
more often and intensely as doses increased. Penile pain (Peto
OR 7.39, 95% CI. 5.40-10.12) and minor urethral trauma (Peto OR
3.79, 95% CI. 1.88-7.65) were predominant. REVIEWERS' CONCLUSIONS:
PGE1 was beneficial for many participants with ED of different
aetiology. Adverse effects were proportional to dosage, albeit
never serious. The use of PGE1 in ED could have been better interpreted
if its effectiveness were compared by aetiology and with different
forms of administrations, a longer follow-up were considered and
more emphasis given to patient/partner relationships and quality
of life.
-----
Int J Clin Pract. 2004 Mar;58(3):230-9.
Sustained efficacy and tolerability with vardenafil
over 2 years of treatment in men with
erectile dysfunction.
Stief C, Porst H, Saenz De Tejada I, Ulbrich E, Beneke
M; Vardenafil Study Group.
Department of Urology, Medizinische Hochschule, Hannover, Germany.
stief.christian@mh-hannover.de
This randomised, double-blind study assessed the long-term
efficacy and tolerability of vardenafil 10 and 20 mg in men with
erectile dysfunction (ED). A total of 566 men who completed an
initial 12-month treatment period entered a 12-month extension.
In these men, both doses of vardenafil produced improvement in
scores for the 'erectile function' Domain of the International
Index of Erectile Function, evident from week 4 and maintained
through 2 years. Sexual Encounter Profile diary responses indicated
that following treatment, penetration was achieved on 92-94% of
attempts and erections that lasted long enough for successful
intercourse were achieved on 87-89% of attempts. In response to
the General Assessment Question, 90-92% of patients reported improved
erections with vardenafil. Most treatment-emergent events were
mild and transient with no cardiovascular safety concerns. These
results support the long-term efficacy, reliability and tolerability
of vardenafil 10 and 20 mg in men with ED.
-----
Expert Opin Pharmacother. 2004 Mar;5(3):623-32.
Topical alprostadil cream for the treatment of
erectile dysfunction.
Becher E.
University of Buenos Aires.
Erectile dysfunction (ED) has serious negative consequences
on both sexual experience and emotional well being and affects
a broad range of age groups. The prevalence of ED is associated
with increasing age and has been reported to be as high as 70%.
Although the disorder is common and underdiagnosed, its treatment
can significantly improve patients' quality of life. Systemic
treatment with oral phosphodiesterase type-5 (PDE-5) inhibitors
is the current standard of care for patients with ED. Some patients,
however, have absolute contraindications for PDE-5 inhibitors.
In addition, these agents can be associated with adverse effects.
Furthermore, because PDE-5 inhibitors are not as effective in
patients who have undergone radical prostatectomy or who have
severe vascular disease, a substantial unmet medical need exists
among patients who have ED as a result of these conditions. Consequently,
PDE-5 inhibitor therapy is associated with a high rate of discontinuation,
as are intracavernosal or transurethral therapies, which are inconvenient
and invasive. Several studies, including four double-blind, placebo-controlled,
Phase II trials, show that alprostadil topical cream is efficacious
and well-tolerated in ED in patients with mild-to-severe symptoms,
in those undergoing treatment for cardiovascular diseases and
diabetes and in otherwise healthy ED patients. Thus, alprostadil
topical cream is a potential first-choice alternative for ED in
patients who do not respond or who cannot tolerate or do not accept
PDE-5 inhibitor therapy.
-----
Int J Urol. 2004 Mar;11(3):159-163.
Role of sildenafil citrate in treatment of erectile
dysfunction after radical retropubic prostatectomy.
Ogura K, Ichioka K, Terada N, Yoshimura K, Terai A, Arai
Y.
Departments of Urology,Otsu Red Cross Hospital Kurashiki Central
Hospital Tohoku University School of Medicine, Japan.
BACKGROUND: Sildenafil citrate was introduced as a treatment
for erectile dysfunction in April 1998 in the United States and
has been available since March 1999 in Japan. In this article,
we assess the efficacy of sildenafil in the treatment of erectile
dysfunction in Japanese men after radical retropubic prostatectomy
for localized prostate cancer. METHODS: Of 106 men who underwent
radical retropubic prostatectomy between January 1994 and March
2000, 43 were prescribed sildenafil at their request after radical
retropubic prostatectomy. Medication was initiated at 25 mg, and
if this was ineffective, the dose was increased to 50 mg. Of the
patients, 18 underwent bilateral and 21 unilateral nerve sparing
(NS) procedures, while in 4 patients, a non-NS procedure was performed.
These patients were interviewed using a questionnaire about their
response to sildenafil and using the 5-item International Index
of Erectile Function (IIEF-5) questionnaire. RESULTS: Thirty-three
of the 43 patients were eligible for evaluation of the efficacy
of sildenafil and 27 completed the IIEF-5 questionnaires. Sildenafil
at 50 mg had a better effect on sexual function than 25 mg in
most Japanese patients. Of the 16 patients who underwent bilateral
NS procedures, 10 (62.5%) had improved ability for intercourse
and 3 (18.8%) had improved erections. Of the 13 patients who underwent
unilateral NS procedures, 7 (53.8%) had improved ability for intercourse
and 4 (30.8%) had improved erections. None of the 4 patients who
underwent non-NS procedures had a positive response. Of 24 patients
with positive response to sildenafil, 3 (12.5%) did not have to
take sildenafil after receiving it because they did not require
it for intercourse. Mean IIEF-5 score increased from 4.3 to 11.4
(P < 0.0001). Patient age, time since surgery, PSA and pathological
stage did not have statistically significant effects on outcome.
The most commonly cited adverse effect was headache (21%). CONCLUSION:
Sildenafil is equally effective for erectile dysfunction in Japanese
patients who have undergone bilateral and unilateral NS procedures,
and aids recovery of natural erectile function after radical retropubic
prostatectomy. However, non-NS procedure patients had no response
to sildenafil. This study suggested that sildenafil is well tolerated
and should be initially used for treatment of Japanese men with
erectile dysfunction after radical retropubic prostatectomy.
-----
Altern Med Rev. 2004 Mar;9(1):4-16.
Nutrients and botanicals for erectile dysfunction:
examining the evidence.
McKay D.
Technical Advisor, Thorne Research, Inc; Senior Editor, Alternative
Medicine Review; private practice, Sandpoint, ID. Correspondence
address: Thorne Research, PO Box 25, Dover, ID 83825. E-mail:
duffy@thorne.com
Erectile dysfunction affects 50 percent of men ages 40-70 in
the United States and is considered an important public health
problem by the National Institutes of Health. Consumers are exposed
to a plethora of natural products claiming to restore erection
and sexual vitality. A review of the available empirical evidence
reveals most naturally occurring compounds lack adequate clinical
trials to support efficacy. However, arginine, yohimbine, Panax
ginseng, Maca, and Ginkgo biloba all have some degree of evidence
they may be helpful for erectile dysfunction. Improvements in
penile endothelial L-arginine-nitric oxide activity appear to
be a unifying explanation for the actions of these naturally occurring
agents.
-----
Int J Impot Res. 2004 Jan;16(1):64-8.
Rechallenge prior sildenafil nonresponders.
Jiann BP, Yu CC, Su CC, Huang JK.
1Department of Surgery, Division of Urology, Kaohsiung Veterans
General Hospital, Kaohsiung, Taiwan.
To assess inappropriate use as a cause of sildenafil (Viagra
trade mark ) failure and the feasibility of successfully rechallenging
nonresponding patients, a total of 60 consecutive erectile dysfunction
(ED) patients who first presented to our hospital and claimed
poor response to sildenafil were enrolled into the study. The
International Index of Erectile Function-5 (IIEF-5) was used to
evaluate their baseline ED status and a self-administered sildenafil-use
questionnaire composed of nine questions (SUQ-9) to assess how
they had used sildenafil. A total of 44 subjects consent to rechallenge
with sildenafil and were given thorough instruction based on individual
answers to SUQ-9 and four doses of sildenafil 100 mg. After a
4-week follow-up, end point efficacy of rechallenge was evaluated
using the IIEF-5 and the global assessment question (GAQ), 'After
the treatment, did you have successful sexual intercourse?' Of
the 60 subjects, 44 (77.3%) had one or more areas of major suboptimal
use of sildenafil: 18 (30.0%) did not know that sexual stimulation
was necessary for sildenafil to work, 36 (60.0%) attempted to
use sildenafil less than four times, and 27 (45.0%) took a maximal
dose less than 100 mg. Of the 44 patients undergoing sildenafil
rechallenge, 34 (77.3%) completed the follow-up, while seven (15.9%)
received only GAQ assessment by telephone interview and three
(6.8%) were lost to follow-up. The total follow-up rate was 93.2%
(41/44). Based on answers to the GAQ, the response rate to rechallenge
was 58.5% (24/41). The mean improvement in the IIEF-5 score was
8.4+/-5.5 in responders (P <0.05). With individualized thorough
instruction based on answers to SUQ-9 and scheduled follow-up,
a high success rate was achieved by rechallenge with sildenafil
in prior failures. The efficacy of sildenafil could be improved
to a great extent by adequate education of patients and continuing
medical education given to primary-care physicians.International
Journal of Impotence Research (2004) 16, 64-68. doi:10.1038/sj.ijir.3901143
-----
Int J Impot Res. 2004 Jan;16(1):8-12.
Sildenafil citrate vs intracavernous alprostadil
for patients with arteriogenic erectile dysfunction: a randomised
placebo controlled study.
Mancini M, Raina R, Agarwal A, Nerva F, Colpi GM.
1Andrology Unit, San Paolo Hospital, Milan, Italy.
We compared the effectiveness of sildenafil citrate and alprostadil
in improving arterial penile inflow (peak systolic velocity (PSV))
and penile rigidity in 55 patients with erectile dysfunction caused
by atherosclerosis. A total of 35 patients with pure vasculogenic
impotency were randomly assigned to alprostadil (Av group; n=11),
sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20
patients with nonvasculogenic impotency were randomly assigned
to alprostadil (A group; n=10) or Sildenafil (S group; n=10):
Av and A used alprostadil injection (capable of giving a full
erection) once a week for 1 month, Sv and S took daily oral sildenafil
(25 mg) for 1 month, and P took daily oral placebo for one month.
The PSV was measured with Duplex sonography and penile rigidity
was assessed using the IIEF-15 questionnaire, both of which were
administered before and after treatment. Although both treatments
improved penile rigidity, they increased PSV only in the Av and
Sv groups. Our results suggest that alprostadil and oral therapy
should be the starting therapy in men with vasculogenic impotency,
whereas alprostadil should be avoided as the first-line approach
in men with nonvasculogenic impotency.International Journal of
Impotence Research (2004) 16, 8-12. doi:10.1038/sj.ijir.3901123
-----
Drugs Aging. 2004;21(2):135-40.
Spotlight on vardenafil in erectile dysfunction.
Keating GM, Scott LJ.
Adis International Limited, Auckland, New Zealand.
Vardenafil (Levitra((R))) is a potent and highly selective
oral phosphodiesterase type 5 (PDE5) inhibitor.Vardenafil improved
erectile function in men with mild to severe erectile dysfunction
(ED) of varying aetiology in two randomised, double-blind, multicentre,
fixed-dose studies of 12 or 26 weeks' duration. Men receiving
vardenafil 10 or 20mg had significantly greater improvements in
International Index of Erectile Function (IIEF) questionnaire
erectile function domain scores than placebo recipients. Moreover,
improvements in penetration and maintenance of erection (assessed
using IIEF or Sexual Encounter Profile [SEP] questions) were significantly
greater with vardenafil 5-20mg than with placebo. Improvements
in IIEF intercourse satisfaction and orgasmic function domain
scores were significantly greater with vardenafil 10 or 20mg than
with placebo and the proportion of patients with a positive response
to a Global Assessment Question (GAQ) concerning improvement in
erections after 12 or 26 weeks' therapy was significantly higher
with vardenafil 5-20mg than with placebo.Vardenafil improved erectile
function in men with ED associated with diabetes mellitus or ED
following unilateral or bilateral nerve-sparing radical retropubic
prostatectomy in two randomised, double-blind, multicentre, fixed-dose,
3-month studies. In both studies, improvements from baseline in
the erectile function domain score of the IIEF and in positive
responses to SEP questions were significantly greater with vardenafil
10 or 20mg than with placebo. In addition, a significantly higher
proportion of vardenafil 10 or 20mg recipients than placebo recipients
had positive GAQ responses.Vardenafil was generally well tolerated
in men with ED; treatment-emergent adverse events were of mild
to moderate intensity and transient in nature. The most commonly
reported adverse events (typical of those seen with PDE5 inhibitors)
in vardenafil 5-20mg recipients included headache, flushing, rhinitis,
dyspepsia and sinusitis. There were no reports of abnormal colour
vision in men with ED taking vardenafil at clinically recommended
doses (5-20mg).CONCLUSION: Vardenafil is a potent and highly selective
oral PDE5 inhibitor. It is effective and generally well tolerated
in men with mild to severe ED of varying aetiology, as well as
in men with ED associated with diabetes mellitus or ED after radical
prostatectomy. Vardenafil should be considered a first-line treatment
option in men with ED who are suitable candidates for oral PDE5
inhibitor therapy.
-----
Ann Pharmacother. 2004 Jan;38(1):77-85.
Vardenafil treatment for erectile dysfunction.
Crowe SM, Streetman DS.
Department of Pharmacy Services, University of Michigan Health
System, University of Michigan, Ann Arbor, MI, USA.
OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical
trial data, and adverse effects of vardenafil in the treatment
of erectile dysfunction (ED). DATA SOURCES: Literature searches
were performed using the MEDLINE database (referenced citations
through December 2002), and the references of all identified articles
were scanned for additional publications of interest. Unpublished
information provided by the manufacturer and proceedings of professional
meetings were also evaluated. STUDY SELECTION AND DATA EXTRACTION:
All available studies were utilized to obtain information regarding
pharmacology. Only human studies were used to gather pharmacokinetic,
drug interaction, efficacy, and safety data. DATA SYNTHESIS: Vardenafil
is a potent and selective inhibitor of the phosphodiesterase 5
(PDE5) enzyme that has been shown to improve erectile function
in several populations of men with ED. Vardenafil has a rapid
onset of action, is hepatically metabolized, and has a half-life
of 4-6 hours. Clinical trials in otherwise healthy men with ED,
men with ED and diabetes, and men with ED and a history of prostatectomy
have demonstrated vardenafil's efficacy. Adverse effects appear
to be relatively mild in intensity and dose dependent, with 22-61%
of subjects reporting adverse effects. CONCLUSIONS: Vardenafil
is a safe and effective oral agent for the treatment of ED. Its
greater potency and PDE5 selectivity compared with sildenafil
appear to confer a lower risk of vision-related adverse effects,
but other clinical consequences of these differences are currently
unclear.
-----
Int J Impot Res. 2003 Dec;15(6):444-9.
Treatment satisfaction in patients with erectile
dysfunction switching from prostaglandin E(1) intracavernosal
injection therapy to oral sildenafil citrate.
Montorsi F, Althof SE, Sweeney M, Menchini-Fabris F, Sasso
F, Giuliano F.
1Department of Urology, Universita' Vita Salute San Raffaele,
Milan, Italy.
Treatment satisfaction, subanalysed by demographic variables,
was evaluated in patients switching from successful intracavernosal
prostaglandin E(1) (PGE(1)) therapy to oral sildenafil citrate.
The validated Erectile Dysfunction Inventory of Treatment Satisfaction
questionnaire was administered at the end of PGE(1) therapy and
after 12 weeks of sildenafil treatment in a multicentre, open-label
study. Men with erectile dysfunction (n=176) who were switched
from stable PGE(1) therapy to sildenafil (25-100 mg) were equally
satisfied with onset of action, duration of action, and confidence
in ability to engage in sexual activity, but expressed greater
overall treatment satisfaction with sildenafil (P<0.01), better
ease of use (P<0.001), naturalness of erectile process (P<0.001),
and intention to continue treatment (P<0.001). Partners (n=32)
were overall more satisfied with sildenafil (P<0.05), and their
responses correlated with patient satisfaction (r=0.68). Compared
with PGE(1) injection, these data suggest that patients may be
less likely to discontinue taking sildenafil treatment for their
erectile dysfunction.International Journal of Impotence Research
(2003) 15, 444-449. doi:10.1038/sj.ijir.3901049
-----
Curr Urol Rep. 2003 Dec;4(6):488-96
Sildenafil: a 4-year update in the treatment of
20 million erectile dysfunction patients.
Carson III CC.
Division of Urology, School of Medicine, University of North Carolina
at Chapel Hill, 427 Burnet-Womack Bldg, Campus Box 7235, Chapel
Hill, NC 27599-7235, USA. Carson@med.unc.edu
Sildenafil citrate, the first internationally approved and
widely used oral agent for the treatment of erectile dysfunction
(ED), has revolutionized the treatment of ED throughout the past
5 years. This phosphodiesterase type-5 (PDE-5) inhibitor is selective
for corpus cavernosum smooth muscle tissue and produces excellent
erectile function. Its efficacy and safety over a wide variety
of etiologies of ED and severities of ED demonstrates its usefulness
in the clinical treatment of these patients. More than 20 million
men have been treated worldwide with sildenafil with excellent
results. ED caused by difficult-to-treat etiologies such as radical
prostatectomy, severe diabetes, and spinal cord injury have demonstrated
efficacy. Although sildenafil citrate, like all PDE-5 inhibitors,
is contraindicated in patients taking nitrate medications for
cardiac disease, it is effective and safe for those cardiovascular
patients who are not taking nitrate medications. The incidence
of adverse cardiovascular events in patients taking sildenafil
does not differ from those of the general population. Investigations
into the pharmacologic effect of sildenafil on coronary myocardial
tissue further supports the safety of this medication. Sildenafil
has been safe and effective in patients taking various medications
including multiple antihypertensive drugs, selective serotonin
reuptake inhibitors, cardiac, and diabetic medications.
-----
Curr Urol Rep. 2003 Dec;4(6):479-87.
Vardenafil: a new approach to the treatment of
erectile dysfunction.
Hellstrom WJ.
Department of Urology, Section of Andrology, Tulane University
Medical Center, 1430 Tulane Avenue, SL-42, New Orleans, LA 70112,
USA. whellst@tulane.edu
Vardenafil is a phosphodiesterase type-5 (PDE-5) inhibitor
developed as an oral therapy for erectile dysfunction (ED). Multiple
phase 3 clinical trials have been completed and vardenafil is
expected to launch worldwide in 2003. Two pivotal, randomized,
double-blind, multicenter studies have evaluated the use of vardenafil
in men with ED. Vardenafil improved the rate of achieving and
maintaining an erection during sexual intercourse. Improvement
also was noted in other aspects of sexual function, including
confidence, orgasmic function, and overall satisfaction. Vardenafil
produces clinically and statistically significant improvements
in erectile function regardless of age, baseline severity, and
etiology and is efficacious for the treatment of ED in diabetic
and postprostatectomy patients. Vardenafil has a rapid onset of
action and completion of successful sexual intercourse is possible
for some patients 16 minutes after its administration. Twenty
milligrams of vardenafil has sustained long-term efficacy by providing
up to 92% of patients with improved erections during more than
2 years of treatment. Vardenafil is well tolerated, with an adverse
event profile typical of the class of PDE-5 inhibitors. The most
common adverse events were headache, flushing, rhinitis, and dyspepsia,
which were mild or moderate and generally decreased with continued
treatment. Vardenafil may be associated with transient reductions
in blood pressure and commensurate increases in heart rate, with
the overall incidence of cardiovascular-related adverse events
similar to that of placebo.
-----
Curr Urol Rep. 2003 Dec;4(6):472-8.
Tadalafil in the treatment of erectile dysfunction.
Bella AJ, Brock GB.
The Department of Surgery, Division of Urology, St. Joseph's Health
Center, The University of Western Ontario, London, Ontario, Canada.
gebrock@sympatico.ca
Oral phosphodiesterase-5 inhibitors have emerged as the preferred
first-line treatment for erectile dysfunction worldwide because
of patient convenience, efficacy, and safety. Clinical trials
have shown that tadalafil significantly enhances erectile function
across a wide range of etiologies and provides a prolonged period
of effectiveness independent of food or alcohol. In this review,
the pharmacokinetic and pharmacodynamic characteristics, efficacy,
and safety of tadalafil are discussed.
-----
Am J Cardiol. 2003 Nov 6;92(9A):37M-46M.
Cardiovascular effects of tadalafil.
Kloner RA, Mitchell M, Emmick JT.
Division of Cardiovascular Medicine, Keck School of Medicine of
the University of Southern California, Los Angeles, California,
USA. rkloner@goodsam.org
To determine the effects of tadalafil on the cardiovascular
system, safety assessments were performed on a database of >4000
subjects who received tadalafil in >60 clinical pharmacology,
phase 2, phase 3, and open-label studies. In healthy subjects,
tadalafil resulted in small changes in blood pressure, which are
not believed to be clinically relevant. Daily administration of
tadalafil 20 mg for 26 weeks in healthy male subjects or patients
with mild erectile dysfunction resulted in blood pressure changes
similar to those observed after placebo administration. In patients
with coronary artery disease (CAD), tadalafil administration before
nitrate administration resulted in small decreases in blood pressure.
The resulting mean maximal change in standing systolic blood pressure
(SBP) after coadministration of sublingual nitroglycerin in patients
with chronic stable angina was -36 mm Hg for tadalafil 5 mg, -31
mm Hg for tadalafil 10 mg, and -28 mm Hg for placebo. In addition,
a larger number of men had a standing SBP <85 mm Hg after coadministration
of sublingual nitroglycerin and tadalafil 5 mg (p <0.001 vs
placebo) or tadalafil 10 mg (p <0.01 vs placebo) compared with
coadministration with placebo. In patients with chronic stable
angina taking doses of isosorbide mononitrate on a long-term basis,
the mean maximal change in standing SBP was -23 mm Hg for placebo,
-23 mm Hg for tadalafil 5 mg, and -26 mm Hg for tadalafil 10 mg.
In a study of older subjects (>or=55 years of age) with no
overt evidence of CAD, the resulting mean maximal change in standing
SBP after coadministration of sublingual nitroglycerin was -25
mm Hg for tadalafil 10 mg, -29 mm Hg for sildenafil 50 mg, and
-25 mm Hg for placebo. Cardiac mortality rates in tadalafil studies
are consistent with the expected rate in this male population.
Across all studies, the incidence rate of myocardial infarction
was low in tadalafil-treated patients (0.43 per 100 patient-years)
compared with patients who received placebo (0.6 per 100 patient-years),
and the incidence rate was comparable to that observed in the
age-standardized male population (0.60 per 100 patient-years).
The incidence rate of presumed thrombotic strokes in tadalafil
studies (0.27 per 100 patient-years) is comparable to the expected
rate in this patient population. The data presented herein suggest
that tadalafil can be safely used by healthy subjects and by patients
with cardiovascular diseases. As with sildenafil, the use of tadalafil
is contraindicated in patients receiving nitrate therapy because
of the potential for significant hypotensive effects.
-----
Skinmed. 2003 Nov-Dec;2(6):350-6.
Erectile dysfunctions.
Sehgal VN, Srivastava G.
The Dermato-Venereology (Skin/VD) Centre, Sehgal Nursing Home,
Panchwati, Azadpur, Delhi, India drsehgal@ndf.vsnl.net.in
Erectile dysfunction is one of the prime challenges confronting
the treating physician. Its prevalence is directly proportional
to aging. It is imperative to comprehend the intricate mechanism
of erection in order to individualize the approach to management.
Thus, it is appropriate to evaluate the etiology of erectile dysfunction.
Normal aging, as well as psychogenic, vascular, neurogenic, and
endocrinologic causes and/or those due to structural abnormalities
of the penis should be considered when evaluating details to determine
its probable cause. An increasing use of drugs, a legacy of civilization,
has considerably compounded the problem. Therapy for erectile
dysfunction, apart from psychosexual counseling, includes medical
treatment by alpha adrenoceptor antagonists, dopamine agonists,
phosphodiesterase type 5 inhibitors, sublingual apomorphine hydrochloride,
or hormone therapy. Transdermal or transurethral corporeal drug
delivery are other possible treatment modalities. Vacuum devices
and surgical approaches are considered relevant only in refractory
cases.
-----
Drugs. 2003;63(23):2673-703.
Vardenafil: a review of its use in erectile dysfunction.
Keating GM, Scott LJ.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Vardenafil (Levitra) is a potent and highly selective oral
phosphodiesterase type 5 (PDE5) inhibitor. Vardenafil improved
erectile function in men with mild to severe erectile dysfunction
(ED) of varying aetiology in two randomised, double-blind, multicentre,
fixed-dose studies of 12 or 26 weeks' duration. Men receiving
vardenafil 10 or 20 mg had significantly greater improvements
in International Index of Erectile Function (IIEF) questionnaire
erectile function domain scores than placebo recipients. Moreover,
improvements in penetration and maintenance of erection (assessed
using IIEF or Sexual Encounter Profile [SEP] questions) were significantly
greater with vardenafil 5-20 mg than with placebo. Improvements
in IIEF intercourse satisfaction and orgasmic function domain
scores were significantly greater with vardenafil 10 or 20 mg
than with placebo and the proportion of patients with a positive
response to a Global Assessment Question (GAQ) concerning improvement
in erections after 12 or 26 weeks' therapy was significantly higher
with vardenafil 5-20 mg than with placebo. Vardenafil improved
erectile function in men with ED associated with diabetes mellitus
or ED following unilateral or bilateral nerve-sparing radical
retropubic prostatectomy in two randomised, double-blind, multicentre,
fixed-dose, 3-month studies. In both studies, improvements from
baseline in the erectile function domain score of the IIEF and
in positive responses to SEP questions were significantly greater
with vardenafil 10 or 20 mg than with placebo. In addition, a
significantly higher proportion of vardenafil 10 or 20 mg recipients
than placebo recipients had positive GAQ responses. Vardenafil
was generally well tolerated in men with ED; treatment-emergent
adverse events were of mild to moderate intensity and transient
in nature. The most commonly reported adverse events (typical
of those seen with PDE5 inhibitors) in vardenafil 5-20 mg recipients
included headache, flushing, rhinitis, dyspepsia and sinusitis.
There were no reports of abnormal colour vision in men with ED
taking vardenafil at clinically recommended doses (5-20 mg). CONCLUSION:
Vardenafil is a potent and highly selective oral PDE5 inhibitor.
It is effective and generally well tolerated in men with mild
to severe ED of varying aetiology, as well as in men with ED associated
with diabetes mellitus or ED after radical prostatectomy. Vardenafil
should be considered a first-line treatment option in men with
ED who are suitable candidates for oral PDE5 inhibitor therapy.
-----
Urology. 2003 Nov;62(5):922-7.
Efficacy and safety of daily intake of apomorphine
SL in men affected by erectile dysfunction and mild hyperprolactinemia:
a prospective, open-label, pilot study.
Caruso S, Intelisano G, Farina M, DiMari L, Agnello C,
Giammusso B.
Department of Microbiological and Gynecological Sciences, University
of Catania School of Medicine, Ospedale S. Bambino, Catania, Italy.
OBJECTIVES: To evaluate the efficacy of the "daily"
use of apomorphine SL compared with the "on demand"
administration of the drug in patients with mild to moderate erectile
dysfunction (ED) and mild hyperprolactinemia who were nonresponders
to apomorphine administered "on demand." METHODS: In
this open-label prospective study, 34 patients with mild-to-moderate
ED and mild hyperprolactinemia were screened. The subjects answered
the International Index of Erectile Function (IIEF) questionnaire
and underwent follicle-stimulating hormone, luteinizing hormone,
testosterone, free testosterone, and prolactin plasma testing,
and Doppler sonography at the 2-week screening period to define
the ED severity and etiology, at the end of a 4-week "as
required" dose-escalation regimen of 2 mg/3 mg apomorphine
SL, and at the end of a 4-week period of daily administration
of the drug to assess the efficacy of each treatment modality.
RESULTS: Twenty patients (age range 27 to 46 years) were included
in the study. Eighteen subjects completed the 4-week "as
required" drug intake period, and three (16.7%) benefited
from this modality of treatment (P <0.05). Fifteen nonresponder
patients participated in the 4-week daily apomorphine SL use,
and 13 (86%) reported satisfaction with the treatment (P <0.05).
The 3-mg daily administration was more effective than the 2-mg
daily administration for erectile function (P <0.02) but not
for other sexual domains scored with IIEF. Adverse events were
of mild or moderate severity, either during the "as required"
drug intake (4 patients) or during daily use (3 subjects) and
were mainly nausea, dizziness, or headache. CONCLUSIONS: Data
from the clinical evaluation of symptomatic apomorphine SL use
have always shown a poor success rate, probably because it is
used "as sildenafil." Using apomorphine SL as a treatment
of ED, we observed a significant improvement in both subjective
and objective aspects scored with the IIEF. The increase of prolactin
could influence the erective mechanisms, and it cannot be excluded
that a subgroup of men with ED may have an impairment of central
dopaminergic function. Moreover, additional studies need to define
the daily use of apomorphine SL in large subgroups of men on the
basis of ED etiology and severity.
-----
Hosp Med. 2003 Oct;64(10):589-92.
Cialis (tadalafil): a new treatment for erectile
dysfunction.
Minhas S, Kalsi JS, Ralph DJ.
Institute of Urology and Nephrology, University College London,
London W1P 7NN.
Oral phosphodiesterase inhibitors have become the mainstay
of treatment for erectile dysfunction. A novel and potent phosphodiesterase
inhibitor, tadalafil, known as Cialis, has been introduced in
the UK as an alternative to the other currently available phosphodiesterase
inhibitors for the treatment of erectile dysfunction.
-----
Int J Impot Res. 2003 Oct;15 Suppl 5:S139-46.
Diagnosis, treatment and prevention of penile
prosthesis infection.
Carson CC.
Division of Urology, University of North Carolina School of Medicine,
Chapel Hill, North Carolina, USA.
The implantation of inflatable penile prostheses for the treatment
of erectile dysfunction continues to be widely practiced in the
United States and internationally. As third-line therapy for erectile
dysfunction, the numbers of implants continue to rise as the population
of men treated for erectile dysfunction increases. Complications
of penile prosthesis implantation continued to decline as mechanical
malfunctions have decreased as a result of re-engineering inflatable
penile prostheses. Inflatable penile prostheses from both available
vendors continue to be reliable, effective methods for restoring
erectile function with high satisfaction rates. The most troublesome
complication of these prostheses, however, is not mechanical but
rather that of prosthesis infection. Prosthesis infections may
result in further surgery, loss of penile tissue, and even the
inability to replace penile prosthesis. While standard sterile
technique perioperative antibiotics and careful surgical procedures
continue to be the cornerstone of penile prosthesis infection
avoidance, newer designs of penile prostheses for antibiotic coating
have resulted in an improvement in the prevalence and incidents
of penile prosthesis infection. For those patients in whom penile
prostheses become infected despite adequate prophylaxis, newer
techniques of salvage have demonstrated increasing success. Once
and still the most dreaded complication of penile prosthesis implantation,
prothesis infections can now be avoided by perioperative preparation
and antibiotics as well as antibiotic-coated penile prostheses.
Treatment of penile prosthesis infections once associated with
severe loss of function can often be successful with modern salvage
techniques. Implanting urologists must be familiar prophylaxis,
avoidance, and treatment of penile prosthesis infections.
-----
Int J Impot Res. 2003 Oct;15 Suppl 5:S33-40.
Frontiers in gene therapy for erectile dysfunction.
Christ GJ.
Department of Urology, Albert Einstein College of Medicine, Bronx,
New York 10461, USA.christ@aecom.yu.edu
Complete sequencing of the human genome has made possible a
new age of molecular medicine. The utilization of sophisticated
genomic technologies has important implications to the understanding,
diagnosis and treatment of erectile dysfunction. This report will
review one aspect of the impact of the genomic revolution on urology,
to wit, the preclinical evidence emerging from several laboratories
indicating that gene therapy for erectile dysfunction may well
provide the first safe and effective application of gene therapy
to the treatment of human smooth muscle disease. The molecular
targets explored thus far have concentrated largely on manipulating
various aspects of the nitric oxide/guanylate cyclase/cGMP system,
although genetic modulation of growth factors, calcium sensitization
mechanisms and potassium channel expression have also been explored.
Cell-based gene therapy techniques are also being explored. The
apparent preclinical success of virtually all of these gene-based
strategies reflects the multifactorial nature of erectile disease
as well as the numerous regulatory mechanisms available for restoring
erectile capacity. While technical hurdles remain with respect
to the choice of delivery vectors, molecular target validation
and duration of efficacy, 'proof-of-concept' has clearly been
documented. The ultimate goal of gene therapy is to provide a
safe, effective and specific means for altering intracavernous
pressure 'on demand', while simultaneously eliminating the necessity
for other forms of therapy, and moreover, without altering resting
penile function, or the physiology of other organ systems. It
is in these arenas that the groundbreaking potential of gene transfer
technology to the treatment of erectile dysfunction will be fully
tested. In fact, the potential benefits of the application of
gene transfer techniques to this important medical problem is
just now beginning to be appreciated/recognized.
-----
Int J Impot Res. 2003 Oct;15 Suppl 5:S13-9.
Phosphodiesterase type 5 inhibitors: a biochemical
and clinical correlation survey.
Kim NN.
Department of Urology, Institute for Sexual Medicine, Boston University
School of Medicine, Boston, Massachusetts 02118, USA. nnkim@bu.edu
Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing
enzyme in penile corpus cavernosum and is an important regulator
of nitric oxide-mediated smooth muscle relaxation. The critical
role of PDE 5 in penile erection and the recent availability of
specific and potent inhibitors of PDE 5 have enabled the development
of effective oral treatment strategies that have been widely accepted
by both health-care professionals and the lay public. This article
examines the correlation between the available biochemical and
clinical data for the PDE 5 inhibitors sildenafil (Viagra), tadalafil
(Cialis) and vardenafil (Levitra).
-----
J Urol. 2003 Oct;170(4 Pt 1):1284-6.
The place of surgery for vascular impotence in
the third millennium.
Wespes E, Wildschutz T, Roumeguere T, Schulman CC.
Department of Urology, C.H.U. de Charleroi, Belgium. dr.wespes@skynet.be
PURPOSE: With the arrival of new oral therapies the question
arises about the role of surgery in patients with vascular impotence.
We compared the sexual satisfaction rate in patients with arterial
and/or venous impotence treated with 4 surgical techniques with
long-term followup. MATERIALS AND METHODS: Surgery was performed
in 130 patients with vascular erectile dysfunction by 1 surgeon.
Two young patients (2%) with traumatic arterial lesions underwent
penile revascularization (group 1), while 128 with arterial and/or
venous impotence were also treated with surgery, including 11
of 130 (8%) with deep dorsal penile vein resection (group 2),
39 (30%) with arterialization of the deep dorsal penile vein (group
3) and 78 (60%) with penile implants (group 4). Sexual satisfaction,
defined as the possibility of satisfactory sexual intercourse
without any additional treatment or pain, was evaluated by patient
interview. RESULTS: Of the 130 patients 111 (85%) participated
in the sexual life events interview, including 2 of 2 (100%) in
group 1, 7 of 11 (63.6%) in group 2, 33 of 39 (85%) in group 3
and 69 of 78 (88%) in group 4. Mean followup was 50, 48, 46 and
54 months for groups 1 to 4, respectively. The sexual satisfaction
rate was 2 of 2 (100%) for penile revascularization, 1 of 7 (14%)
for venous resection, 4 of 33 (12%) for arterialization and 64
of 69 (93%) for penile implantation. Complications occurred in
9.5%, 12.5% and 20.5% of the patients in groups 2 to 4, respectively.
CONCLUSIONS: Except for young patients with traumatic arterial
lesions this study demonstrated the poor sexual satisfaction rate
in impotent patients treated with the vasculogenic approach and
the high rate of satisfaction in those treated with penile implants.
Better selection criteria must be applied for vascular surgical
treatment for impotence.
-----
J Urol. 2003 Oct;170(4 Pt 1):1278-83.
Safety and efficacy of vardenafil for the treatment
of men with erectile dysfunction after radical retropubic prostatectomy.
Brock G, Nehra A, Lipshultz LI, Karlin GS, Gleave M, Seger
M, Padma-Nathan H.
St. Joseph's Medical Center, Lawson Research Institute, London,
Ontario, Canada. gebrock@sympatico.ca
PURPOSE: More than one-third of men may experience erectile
dysfunction (ED) after nerve sparing radical retropubic prostatectomy.
The efficacy and safety of vardenafil, a potent, selective, phosphodiesterase
5 inhibitor, was assessed for the treatment of ED after radical
prostatectomy. MATERIALS AND METHODS: In this double-blind study
440 men with ED after nerve sparing radical prostatectomy were
randomized to take placebo, or 10 or 20 mg vardenafil. Efficacy
was measured after 12 weeks using the erectile function domain
of the International Index of Erectile Function, diary questions
measuring vaginal penetration and intercourse success rates, and
a global assessment question (GAQ) on erection. RESULTS: Of the
intent to treat population 70% had severe ED (erectile function
less than 11) at baseline. After 12 weeks both vardenafil doses
were significantly superior to placebo (p <0.0001) for all
efficacy variables. Improved erections (based on GAQ) were reported
by 65.2% and 59.4% of patients on 20 and 10 mg vardenafil, respectively,
and by only 12.5% of patients on placebo (p <0.0001). Among
men with bilateral neurovascular bundle sparing, positive GAQ
responses were reported by 71.1% and 59.7% of patients on 20 and
10 mg vardenafil, respectively, versus 11.5% of those on placebo
(p <0.0001). The average intercourse success rate per patient
receiving 20 mg vardenafil was 74% in men with mild to moderate
ED and 28% in men with severe ED, compared to 49% and 4% for placebo,
respectively. Few adverse events were observed. They were generally
mild to moderate headache, flushing and rhinitis. CONCLUSIONS:
In men with severe ED after nerve sparing radical retropubic prostatectomy,
vardenafil significantly improved key indices of erectile function.
-----
Urology. 2003 Sep;62(3):519-23; discussion 523-4.
Efficacy and tolerability of vardenafil for treatment
of erectile dysfunction in patient subgroups.
Porst H, Young JM, Schmidt AC, Buvat J; International Vardenafil
Study Group.
Urological Practice, Hamburg, Germany.
OBJECTIVES: To assess whether vardenafil would improve erectile
function irrespective of etiology, baseline severity, or patient
age. The consistency of the response over time was also evaluated.
METHODS: A multicenter, randomized, double-blind, placebo-controlled
at-home study of vardenafil treatment (5, 10, and 20 mg) was performed.
This secondary analysis compared the mean International Index
of Erectile Function (IIEF) erectile function domain scores of
various subgroups at 12 weeks of treatment. These populations
included organic, psychogenic, or mixed etiologies; mild, moderate,
or severe baseline severity; and four age groups (younger than
45, 45 to 55, 56 to 65, and older than 65 years). In addition,
all IIEF domains were compared at sequential 4-week periods, before
and during treatment. RESULTS: In the 580 men of the intent-to-treat
population, the mean erectile function domain scores were statistically
greater than placebo, irrespective of etiology, baseline severity,
or age. This was seen at all dosages. Compared with placebo, vardenafil
statistically improved the IIEF domain scores of erectile function,
orgasmic function, intercourse satisfaction, and overall satisfaction
after 4 weeks of treatment, and these improvements were maintained
for 12 weeks. The rates of the most common adverse events (headache,
flushing, and dyspepsia) were either constant or declined over
time; they were generally mild to moderate and transient in nature.
CONCLUSIONS: Vardenafil improved erectile function regardless
of the general etiology, baseline severity of erectile dysfunction,
or patient age. Improvements in erectile function and other key
IIEF domains were consistently seen throughout the study.
-----
Urology. 2003 Sep;62(3):400-3.
Minimal time to successful intercourse after sildenafil
citrate: results of a randomized, double-blind, placebo-controlled
trial.
Padma-Nathan H, Stecher VJ, Sweeney M, Orazem J, Tseng
LJ, Deriesthal H.
Department of Urology, University of Southern California Keck
School of Medicine, Los Angeles, California, USA.
OBJECTIVES: To determine the minimal time to successful intercourse
after taking sildenafil citrate for erectile dysfunction (ED).
METHODS: Male patients with ED (mean age 60 years; mean ED duration
7.0 years) who were successfully treated with sildenafil (100
mg) for 2 months or longer were randomized to sildenafil (n =
115) or placebo (n = 113) for 4 weeks of double-blind treatment.
Using a stopwatch, patients recorded the time needed to obtain
an erection hard enough for sexual intercourse after taking the
study drug at least 2 hours after eating. RESULTS: Within 14 and
20 minutes of sildenafil dosing, 35% and 51% of sildenafil-treated
patients, respectively, versus 22% and 30% of placebo-treated
patients, respectively, had an erection that led to successful
intercourse (P <0.05 for both). The median time to erection
leading to successful intercourse after sildenafil dosing was
36 minutes compared with 141 minutes for placebo. CONCLUSIONS:
In this study, slightly more than one half of a population of
prior sildenafil responders achieved an erection that led to successful
sexual intercourse within 20 minutes of sildenafil administration,
suggesting that the onset of action of sildenafil can be less
than 30 minutes in men with ED.
-----
Presse Med. 2003 Sep 27;32(31):1469-73.
[Management of sexual dysfunction in patients
with coronary heart disease]
[Article in French]
Philippe F.
Departement de pathologie cardiaque, Institut mutualiste, Montsouris,
Paris. francois.philippe@imm.fr
THE CONTEXT: Patients with coronary heart disease are generally
males aged more than 55 and in whom the question of sexual activity
must be evoked, not only with regard to the risks involved with
the sexual act itself but also regarding the management of an
eventual erectile dysfunction. POSITIVE DATA: A negative and maximal
for the age stress test is of predictive value and can eliminate
the hypothesis of recurrent coronary ischaemia during sexual intercourse.
Drug-induced effects on the libido and erectile function are known
but only led to suspension of treatment in one out 438 patients
treated for one year. THERAPEUTIC MANAGEMENT: In the case of documented
erectile dysfunction, the combination of sildenafil nitrate derivatives
or NO suppliers is formally contra-indicated because of the risk
of hypotension. Post-marketing registers and specific studies
in patients with coronary heart disease demonstrate the good haemodynamic
and coronary tolerance to sildenafil in this category of patient,
so long as the contra-indications are respected. The Princeton
Consensus Panel has proposed a therapeutic strategy adapted to
each patient and according to their level of risk and its treatment.
-----
Int J Clin Pract. 2003 Sep;57(7):597-600.
Clinical trials of sildenafil citrate (Viagra)
demonstrate no increase in risk of myocardial infarction and cardiovascular
death compared with placebo.
Mittleman MA, Glasser DB, Orazem J.
Institute for Prevention of Cardiovascular Disease, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
02215, USA.
We pooled data regarding myocardial infarction (MI) and cardiovascular
death from more than 120 clinical trials of sildenafil citrate
(Viagra) conducted from 1993 to 2001. During placebo-controlled
trials, the rate of MI or cardiovascular death was 0.91 (95% CI:
0.52-1.48) per 100 person-years (PY) of follow-up among sildenafil-treated
patients compared with 0.84 (95% CI: 0.39-1.60) per 100 PY of
follow-up among placebo-treated patients. The relative risk of
MI or cardiovascular death was 1.08 (95% CI: 0.45-2.77) for sildenafil
compared with placebo (p = 0.88). During open-label studies, the
rate of MI or cardiovascular death was 0.56 (95% CI: 0.44-0.72)
per 100 PY of follow-up. This analysis showed that the rates of
MI and cardiovascular death were low and comparable between men
treated with sildenafil and those treated with placebo. The use
of sildenafil was not associated with an increase in the risk
of MI or cardiovascular death.
-----
Tidsskr Nor Laegeforen. 2003 Sep 11;123(17):2449-50.
[Expandable penile implants in patients with erectile
dysfunction]
[Article in Norwegian]
Schultz A, Hedlund H, Talseth T.
Urologisk seksjon, Kirurgisk avdeling, Rikhospitalet, Oslo. alexander.schultz@rikshospitalet.no
Modern medical treatment can restore normal sexual function
in the majority of men with erectile dysfunction, but some men
will not obtain an erection sufficient for sexual intercourse.
In some of these men, with a strong desire to have an active sexual
life including intercourse, it is possible to restore the function
by the use of a penile implant. We describe the indications, the
surgical procedure and the results with an expandable penile implant.
-----
BJU Int. 2003 Sep;92(4):441-6.
Trazodone for erectile dysfunction: a systematic
review and meta-analysis.
Fink HA, MacDonald R, Rutks IR, Wilt TJ.
Geriatric Research Education and Clinical Center, Section of General
Internal Medicine, VA Medical Center, Minneapolis, USA. howard.fink@med.va.gov
OBJECTIVE: To determine the efficacy and safety of trazodone
in the treatment of erectile dysfunction (ED) in a meta-analysis.
METHODS: The data sources used were Medline and the Cochrane Library
databases (January 1966 to May 2002), bibliographies of retrieved
articles and review articles, and conference proceedings and abstracts.
Trials were eligible for inclusion in the review if they included
men with ED, compared trazodone with a control, were randomized,
of > or = 7 days' duration and assessed clinically relevant
outcomes. Two reviewers independently evaluated study quality
and extracted data in a standardized fashion. RESULTS: Six trials
(comprising 396 men) met the inclusion criteria; they consisted
of heterogeneous populations, were small, brief and in some cases
methodologically weak. Three of the six trials showed an apparently
clinically meaningful benefit of trazodone for ED compared with
placebo, the differences being statistically significant in two.
In pooled results, trazodone monotherapy appeared more likely
than placebo to lead to a 'positive treatment response', although
this difference was not statistically significant (37% vs 20%;
relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3).
Subgroup analyses suggested that men with psychogenic ED might
be more likely to benefit from trazodone than those with mixed
or physiological ED. The efficacy of trazodone also appeared greater
at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone
were not significantly more likely than those receiving placebo
to withdraw for any reason or for an adverse event, or to have
specific adverse events, but wide CIs could not exclude a greater
risk of these adverse outcomes with trazodone. Specific adverse
events with trazodone included dry mouth (19%), sedation (16%),
dizziness (16%) and fatigue (15%). CONCLUSION: Trazodone may be
helpful in men with ED, possibly more so at higher doses, and
in men with psychogenic ED. Future high-quality trials should
compare trazodone with placebo and other therapies in men with
depression and psychogenic ED.
-----
BJU Int. 2003 Sep;92(5):516-20.
The ageing male and erectile dysfunction.
Montorsi F, Briganti A, Salonia A, Deho' F, Zanni G, Cestari
A, Guazzoni G, Rigatti P, Stief C.
Department of Urology, University Vita-Salute San Raffaele, Milan,
Italy. montorsi.francesco@hsr.it
Erectile dysfunction is common in the ageing man and reliable
therapies are needed. The pathophysiology of erectile dysfunction
in this group mainly includes chronic ischaemia, which triggers
the deterioration of cavernosal smooth muscle and the development
of corporeal fibrosis. Assessing the ageing man with erectile
dysfunction who seeks medical treatment should comprise a thorough
medical and sexual history, a systemic and focused physical examination
and selected blood tests. Oral drug therapy represents a safe
and effective option for most ageing men.
-----
Ned Tijdschr Geneeskd. 2003 Aug 30;147(35):1687-90.
[Favorable effect of sildenafil on erectile dysfunction
in patients after radiotherapy for prostate cancer; randomised,
double-blind, placebo-controlled crossover study]
[Article in Dutch]
Incrocci L, Hop WC, Slob AK.
Erasmus Medisch Centrum, Daniel den Hoed Kliniek, Rotterdam, Netherlands.
l.incrocci@erasmusmc.nl
OBJECTIVE: To determine the efficacy of sildenafil in patients
with erectile dysfunction after external beam radiotherapy for
prostate cancer. DESIGN: Randomised, double-blind, placebo-controlled,
crossover study. METHOD: A total of 406 patients with erectile
dysfunction reported in their medical records who had completed
external beam radiotherapy at least 6 months prior to the study,
were approached by letter. Sixty patients were included in a study
which lasted 12 weeks. They received 50 mg of sildenafil citrate
or placebo for two weeks; during week 2 the dose could be increased
to 100 mg in the case of unsatisfactory erectile response. At
week 6 patients crossed over to the alternative treatment. Data
were collected using the validated 'International index of erectile
function' (IIEF) questionnaire, and side-effects were recorded.
Patients were given the possibility of continuing to a 6-week
open-label phase. RESULTS: The mean age of those participating
was 68 years. All patients completed the double-blind phase. For
the majority f questions in the IIEF questionnaire, there was
a significant increase in mean scores from baseline with sildenafil,
but of the patients with sildenafil, versus 18% with placebo.
Ninety percent of the patients required a dose adjustment to 100
mg sildenafil, and 100% of the patients in the placebo group increased
the dose. Side-effects were mild or moderate. Patients who proceeded
to the open-label phase reported the same results as in the double-blind
phase. CONCLUSION: Sildenafil improved erectile function in about
half of the patients with erectile dysfunction after external
beam radiotherapy for prostate cancer, and it was well tolerated.
-----
Clin Geriatr Med. 2003 Aug;19(3):539-51.
Erectile dysfunction: etiology and treatment in
young and old patients.
Tariq SH, Haleem U, Omran ML, Kaiser FE, Perry HM 3rd,
Morley JE.
Division of Geriatric Medicine, Saint Louis University School
of Medicine, Room M-238, GREEC VA Medical Center, St. Louis, MO
63104, USA. Tariqsh@slu.edu
This study shows that endocrine and vascular etiologies of
erectile dysfunction are more common in the older age group, whereas
depression and marital discord are more common in the younger
age group. There is considerable overlap between various factors
pointing to the multifactorial nature of erectile dysfunction.
Review of the treatment option chosen reveals that the invasive
modalities were least common as compared with the popular vacuum
tumescence device (although cumbersome) and testosterone replacement.
Persons with low testosterone have an improved efficacy of sildenafil
when hypogonadism is treated. Sildenafil with its ease of administration
and high efficacy seems to be the logical first choice for most
of the patients. If contraindications exist or treatment failures
occur, other treatment options should be offered to patients.
-----
Int J Impot Res. 2003 Aug;15(4):287-9.
Effects of moxonidine and metoprolol in penile
circulation in hypertensive men with erectile dysfunction: results
of a pilot study.
Piha J, Kaaja R.
Mehilainen Co, Erectile Dysfunction Clinic, Turku, Finland. juhana.piha@pp.fimnet.fi
Centrally acting (moxonidine) and peripherally acting (metoprolol)
sympatholytic agents might have different actions upon penile
circulation in hypertensive men with erectile dysfunction. A total
of 11 nonsmoking, hypertensive but otherwise healthy men with
erectile dysfunction were studied after 8 weeks on moxonidine
monotherapy (0.4 mg per day, increased to 0.6 mg if needed) and
then after 8 weeks of metoprolol monotherapy (100 mg per day,
increased to 200 mg if needed) in a crossover design. At the end
of each treatment phase, the subjects were asked about their subjective
erectile capacity (nocturnal and coital erections), and resting
and stimulated (after intracavernosal injection of a mixture of
alprostadil and phentolamine) penile deep artery diameters and
systolic peak velocities were measured by color Doppler ultrasonography.
There were no significant differences in blood pressure after
either therapy. The change from earlier antihypertensive therapy,
moxonidine produced significant subjective amelioration of sexual
dysfunction in 9/11 of the men (< or = 0.001), whereas 9/11
returned to impaired dysfunction after crossover to metoprolol
treatment. Resting and stimulated deep penile diameters and peak
systolic velocities were higher after moxonidine treatment compared
with metoprolol (diameters: < or = 0.004, < or = 0.0001;
velocities: < or = 0.008, < or = 0.038). The centrally acting
sympatholytic agent moxonidine seems to improve erectile function
both subjectively and objectively and has a better effect on penile
circulation compared with the peripherally acting sympatholytic
agent metoprolol.
-----
Int J Clin Pract. 2003 Jul-Aug;57(6):484-7.
Comparison of finasteride and alpha-blockers as
independent risk factors for erectile dysfunction.
Sadeghi-Nejad H, Sherman N, Lue J.
Division of Urology, Department of Surgery, UMD-New Jersey Medical
School, Newark, New Jersey 07103-2714, USA.
There are insufficient data on the effects of alpha-blockers
and finasteride on erectile function in men who have other risk
factors for erectile dysfunction (ED). This study was conducted
to compare the relative effects of these medications on ED in
men who may be on other medications or have other risk factors
for ED. Patients attending urology and primary care clinics were
asked to complete an IRB-approved questionnaire that combined
the validated Sexual Health Inventory for Men (SHIM) and a detailed
medical history. A total of 123 patients completed the questionnaire.
The age range was 28-88 years (mean: 68 years). Eighty-one per
cent of patients had SHIM scores <21, indicating some degree
of ED. The average SHIM scores in a population of patients with
similar age and risk factors who had been on finasteride or alpha-blockers
indicated the presence of ED but did not reveal a significant
difference between the two groups. The scores were no different
from an age-matched group of patients who were not on either medication,
demonstrating the relatively greater importance of various other
risk factors for ED. There was an inverse linear relationship
between the number of ED risk factors and SHIM scores. There does
not appear to be a significant difference between alpha-blockers
and finasteride as independent risk factors for ED. Age and other
risk factors (heart disease, diabetes, hypertension, smoking,
and hypercholesterolaemia) tend to have a much stronger influence
on the severity of ED as assessed by SHIM scores.
-----
Rev Med Brux. 2003 Jun;24(3):169-75.
[Erectile dysfunction and phosphodiesterase type
5 inhibitors]
[Article in French]
Roumeguere T, Sternon J, Schulman CC.
Service d'Urologie, Hopital Erasme, U.L.B.
Erectile dysfunction affects 150 millions of men and its prevalence
increases with age. The improvement of life expectancy will increase
the worldwide prevalence to 300 million in 2025. Oral treatments
are nowadays the first line therapy for the vast majority of people
as they have a good reliability and tolerance and restore more
spontaneity. The authors relate the widespread interest in phosphodiesterase
type 5 inhibitors with the advent of sildenafil for the treatment
of erectile dysfunction and present characteristics of 2 new phosphodiesterase
type 5 inhibitors in Belgium, tadalafil and vardenafil.
-----
J Urol. 2003 Aug;170(2 Pt 1):503-6.
Clinical efficacy of sildenafil citrate and predictors
of long-term response.
Gonzalgo ML, Brotzman M, Trock BJ, Geringer AM, Burnett
AL, Jarow JP.
The James Buchanan Brady Urological Institute, Johns Hopkins Medical
Institutons, Baltimore, Maryland 21287, USA.
PURPOSE: We assessed the long-term clinical efficacy of sildenafil
citrate (SC) and predictors of satisfactory outcome. MATERIALS
AND METHODS: All patients were evaluated with a self-administered
questionnaire or by telephone interview before, and 3 months and
2.5 years following the initiation of SC therapy. Current SC use,
other therapies and overall level of sexual satisfaction were
assessed. Sexual function was measured using an abbreviated version
of the International Index of Erectile Function questionnaire.
RESULTS: Of the 197 men 97 (49%) were using SC at 2.5 years. Patients
with a history of diabetes mellitus or prostate surgery were least
likely to be satisfied with SC therapy. Men with vasculogenic
etiologies for erectile dysfunction were more likely to be on
SC and had better sexual function scores at 2.5 years than men
with a history of prostate surgery. The 3-month International
Index of Erectile Function questionnaire score was an excellent
predictor of sexual satisfaction in men who continued to use SC
at 2.5 years. Of the 100 men who discontinued treatment with SC
56% chose not to pursue any other treatment. CONCLUSIONS: SC remains
a highly effective and durable oral agent for erectile dysfunction.
Improved sexual function and sexual satisfaction were well maintained
2.5 years following the initiation of SC therapy, especially in
patients with vasculogenic or psychogenic etiologies of erectile
dysfunction. Patients who discontinued SC reported significantly
decreased sexual function than their counterparts but under used
alternative therapies to improve erectile dysfunction.
-----
J Urol. 2003 Aug;170(2 Pt 2):S31-4; discussion S34.
Neuroprotection and nerve grafts in the treatment
of neurogenic erectile dysfunction.
Burnett AL.
Department of Urology, The James Buchanan Brady Urological Institute,
The Johns Hopkins Hospital, Baltimore, Maryland 21287-2411, USA.
PURPOSE: The rationale for protecting the nerve supply of the
penis derives mainly from the fact that neurological injury or
disease states involving this organ commonly result in erectile
dysfunction. Novel directions in the management of neurogenic
erectile dysfunction that pertain specifically to sustaining penile
neuronal function are described. MATERIALS AND METHODS: The review
constitutes a summary of neuroprotective strategies for penile
erection that are under investigation at the basic science level
or have been brought to clinical practice. The basic exercise
consisted primarily of a literature search using the National
Library of Medicine PubMed Services, with references made to such
keywords as nerve grafts, nerve growth factors, neuroprotection
and nerve regeneration. RESULTS: Primary advances in this field
have centered on repairing structural defects and restoring the
functional integrity of the cavernous nerves of the penis. In
the former autologous nerve conduits, such as sural nerve grafts,
have been explored and used prominently in the context of radical
prostatectomy. In the latter diverse neurotrophic treatments have
been investigated, with progress mostly limited to animal models
of cavernous nerve injury. Basic concepts and ongoing developments
in the neurobiology of axonal regeneration were identified as
being applicable to this area of neurourology. CONCLUSIONS: Because
neurogenic origins represent a leading categorical cause of erectile
dysfunction, the importance of developing and applying treatment
approaches to alleviate neuropathic effects on the erectile tissue
of the penis is certain. Medical and surgical innovations for
preserving and reconstituting the functional nerve supply of the
penis offer great promise in the management of erectile dysfunction.
-----
J Urol. 2003 Aug;170(2 Pt 2):S20-3; discussion S23.
Viability and safety of combination drug therapies
for erectile dysfunction.
Steers WD.
Department of Urology, University of Virginia Health System, P.O.
Box 800422, Charlottesville, VA, USA. wds6t@Virginia.edu
PURPOSE: In some patients with erectile dysfunction (ED) oral,
topical or intracavernous drug therapy fails. However, several
classes of drugs demonstrate efficacy for ED, creating the potential
for pharmacological combinations preferable to implantation of
a penile prosthesis. MATERIALS AND METHODS: Preliminary reports
suggest that combining oral, topical or intracavernous drugs may
salvage patients in whom monotherapy fails. RESULTS: Agents that
lead to activation or increases in cyclic nucleotides (cyclic
adenosine monophosphate and guanosine monophosphate) with or without
nitric oxide donors or nitrates, or alpha-adrenergic antagonists
have been used to treat ED. The phosphodiesterase-5 inhibitor
sildenafil has been combined with alprostadil (prostaglandin E1)
and administered by either the intraurethral or intracavernous
route. Successful intercourse following this combination varies
from 47% to 100% when monotherapy with each has failed. The introduction
of apomorphine has led to its unapproved use in combination with
sildenafil in Europe. Combination strategies may allow lower drug
doses and reduced adverse effects. CONCLUSIONS: The encouraging
preliminary observations combined with the potential for adverse
events provide a scientific rationale for prospective, randomized
clinical trials with adequate numbers of subjects.
-----
Orv Hetil. 2003 Jun 1;144(22):1061-6.
[Conservative treatment of erectile dysfunction]
[Article in Hungarian]
Papp G, Erdei E.
Orszagos Gyogyintezeti Kozpont, Andrologiai es Urologiai Osztaly,
Budapest. pappgy@hiete.hu
The development of diagnostical and therapeutical methods of
erectile dysfunction opened new possibilities for patients. In
our time, andrologists are capable of treating most patients.
The ones who cannot be helped are unable to lead sexual life due
to physical reasons. The application of hormone examinations,
color Doppler and Rigiscan exams help at establishing diagnoses.
In the therapy, modern peroral pharmacotherapy is dominant, mainly
phosphodiesterase inhibitors and central peroral pharmacon are
applied. The means of getting the vasoactive drugs into the body
have been extended (subcutan, transdermal, and drugs absorbable
through mucosa). Psychotherapy is indispensable at some patients.
The surgical solution (mainly prosthesis implantation) can be
regarded critically, yet their presence among therapies is necessary.
According to authors' opinion, the qualitative development of
vasoactive drugs (efficacy extension and side-effect reduction)
that can be simply and conveniently applied in the future.
-----
J Clin Psychiatry. 2003 Jun;64(6):721-5.
High-dose sildenafil citrate for selective serotonin
reuptake inhibitor-associated ejaculatory delay: open clinical
trial.
Seidman SN, Pesce VC, Roose SP.
Department of Psychiatry, College of Physicians and Surgeons of
Columbia University, and the New York State Psychiatric Institute,
New York, NY 10032, USA. Sns5@columbia.edu
BACKGROUND: Selective serotonin reuptake inhibitor (SSRI)-induced
ejaculatory delay is a common problem that has no treatment with
established efficacy. Sildenafil citrate is effective for erectile
dysfunction and appears to be safe at doses up to 200 mg. METHOD:
We enrolled men who were in remission from depression according
to DSM-IV criteria and who reported that they had developed new-onset
ejaculatory delay in the setting of SSRI treatment. Enrolled patients
were instructed to use 25 mg of sildenafil 1 hour prior to sexual
activity on at least 2 occasions. If this was not effective for
the ejaculatory delay, they were instructed to increase the dose
progressively up to a maximum of 200 mg. We compared baseline
sexual functioning to 2 phases of open treatment: low-dose phase
(sildenafil 25-100 mg) and high-dose phase (sildenafil 150-200
mg). The primary outcome measure was a modified, self-report Clinical
Global Impressions (CGI) scale that was specific for erectile
(CGI-EF) and ejaculatory (CGI-EJF) aspects of sexual function.
RESULTS: Twenty-one men (mean age = 56 years) with major depressive
disorder (MDD) in remission and SSRI-associated ejaculatory delay
enrolled in the study and received sildenafil. At baseline, 14
of 21(67%) had comorbid erectile dysfunction. At the low-dose
phase follow-up assessment, 12 of 14 achieved full erectile dysfunction
remission, and 4 of 21 achieved ejaculatory delay remission. Sixteen
patients with persistent ejaculatory delay were eligible for the
high-dose phase: 5 withdrew from the study, 4 increased to a maximum
dose of 150 mg, and 6 increased to a maximum dose of 200 mg. The
1 patient who had clinically significant erectile dysfunction
and ejaculatory delay reported improvement of both conditions
after the high-dose phase. Of the 10 patients who had ejaculatory
delay without significant erectile dysfunction and who chose to
take high-dose sildenafil, 9 reported a significant clinical improvement
in ejaculatory delay (CGI-EJF improvement score of 1 or 2) and
7 achieved full remission (CGI-EJF severity score of 1 or 2 and
CGI-EJF improvement score of 1 or 2). CONCLUSION: In this open
clinical trial with men who had SSRI-induced ejaculatory delay,
high-dose sildenafil appeared to be effective in reducing ejaculatory
latency.
-----
Phys Ther. 2003 Jun;83(6):536-43.
Treatment of erectile dysfunction by perineal
exercise, electromyographic biofeedback, and
electrical stimulation.
Van Kampen M, De Weerdt W, Claes H, Feys H, De Maeyer M,
Van Poppel H.
Department of Physiotherapy, University Hospital, Katholieke Universiteit
Leuven, Herestraat 49, 3000 Leuven, Belgium. marijke.vankampen@uz.kuleuven.ac.be
BACKGROUND AND PURPOSE: Only a few investigators have described
the involvement of the perineal muscles in the process of human
erection. The aim of this research was to evaluate a re-education
program for men with erection problems of different etiologies.
SUBJECTS AND METHODS: Fifty-one patients with erectile dysfunction
were treated with pelvic-floor exercises, biofeedback, and electrical
stimulation. RESULTS: The results of the interventions can be
summarized as follows: 24 patients (47%) regained a normal erection,
12 patients (24%) improved, and 6 patients (12%) did not make
any progress. Nine patients (18%) did not complete the therapy.
On the basis of several variables, a prediction equation was generated
to determine the factors that would predict the effect of the
interventions. The outcome was most favorable in men with venous-occlusive
dysfunction. DISCUSSION AND CONCLUSION: Comparison of the results
of the physical therapy protocol reported here with those obtained
for other interventions reported in the literature shows that
a pelvic-floor muscle program may be a noninvasive alternative
for the treatment of patients with erectile dysfunction caused
by venous occlusion.
-----
J Urol. 2003 Jun;169(6):1999-2007.
Erectile dysfunction in the elderly: epidemiology,
etiology and approaches to treatment.
Seftel AD.
Case Western Reserve University, Department of Urology, University
Hospital of Cleveland, Cleveland VA Medical Center, Cleveland,
Ohio, USA.
PURPOSE: Erectile dysfunction is experienced at least some
of the time by most men who have reached 45 years of age, and
it is projected to affect 322 million men worldwide by 2025. The
prevalence of erectile dysfunction is high in men of all ages
and increases greatly in the elderly. MATERIALS AND METHODS: This
paper reviews the epidemiology of erectile dysfunction with an
emphasis on the experience of older men, normal age related changes
in the structure and function of the penis that may contribute
to increased risk with age, how the accumulation of risk factors
with age may contribute to the high prevalence of the disease
in older men, and established and emerging therapies. The normal
aging process and age related risk factor accumulation contribute
to the increased prevalence of erectile dysfunction in the elderly.
RESULTS: Remarkable progress has been made in the treatment of
erectile dysfunction. At present inhibition of phosphodiesterase
5 with oral agents such as sildenafil would appear to be the initial
treatment of choice. These drugs have been shown to be safe and
effective, and sildenafil has demonstrated efficacy in patients
with many of the comorbidities observed in older men with erectile
dysfunction. New treatments, in particular transfection with genes
for key mediators of erectile function that are known to be down-regulated
in elderly men, also hold promise. CONCLUSIONS: Further research
into the neural, vascular and molecular mechanisms involved in
penile erection will lead to the development of even safer, more
effective and more convenient therapies for men with erectile
dysfunction.
-----
Arch Ital Urol Androl. 2003 Mar;75(1):18-20.
The start of pharmacological activity after sublingual
administration of sildenafil citrate in 30 patients affected by
erectile dysfunction.
De Siati M, Saugo M, Franzolin N.
Divisione di Urologia, Ospedale De Lellis, Via Camillo de Lellis,
36017 Schio, VI, Italy.
INTRODUCTION AND OBJECTIVES: Sildnenafil citrate is a powerful
phosphodiesterase type 5 isoenzyme; it is the first oral treatment
to have had a significant success in treatment of erectile dysfunction
(ED). After oral dosing on an empty stomach the pharmacological
activity starts within 30 to 120 minutes (average 60 minutes)
whereas the effect of this medication after a meal could be notably
delayed. We evaluated the start of pharmacological activity in
30 patients affected by non-psychogenic ED after sublingual administration
of Sildenafil citrate. METHODS: Patients participating in our
study were all affected by ED whose etiology was assessed as vasculogenetic
or diabetic. The study lasted 6 months. For the first 3 months
patients were asked to take Sildenafil (50-100 mg) for oral administration,
under normal everyday conditions, 30 minutes before planned sexual
relations. During the second 3 months the patients were asked
to take Sildenafil for sublingual administration (crushing the
pill in the mouth and dissolving the drug under the tongue) 15
minutes before planned sexual relations. The patients did not
know the purpose of the study. RESULTS: An appreciable reduction
in the start of pharmacological activity was reported during the
time of sublingual administration. In fact, while throughout the
first 3 months the average pharmacological onset was 62.8 minutes
(DS +/- 16.8), during the second 3 months it was 29.3 minutes
(DS +/- 8.1), the mean difference in the start of pharmacological
activity was 35.3 (DS +/- 12.4). The results of T-student test
for paired observation were T (29) = 15.629; p-value 0.00001.
During the two modalities of administration no differences were
noted in the efficacy or in the frequency of adverse events. All
the patients declared they preferred the sublingual way because
of faster onset. CONCLUSIONS: Even though ours is a limited study,
our clinical data points out that the sublingual administration
of Sildenafil is useful because of the rapid onset unrelated to
meals. All the patients were reported to appreciate this method
of administration, particularly in the case of unplanned sexual
relations.
-----
Clin Endocrinol (Oxf). 2003 May;58(5):632-8.
Androgens improve cavernous vasodilation and response
to sildenafil in patients with erectile dysfunction.
Aversa A, Isidori AM, Spera G, Lenzi A, Fabbri A.
AFaR-CRCCS, Ospedale Fatebenefratelli Isola Tiberina, Rome, Italy.
antonio.aversa1@fastwebnet.it
OBJECTIVES: We have recently shown that, in men with erectile
dysfunction (ED), free testosterone (FT) directly correlates with
penile arterial inflow. This led us to further investigate the
effect(s) of androgen administration on cavernous arteries in
patients failing sildenafil treatment. DESIGN: Prospective randomized
placebo-controlled pilot study. PATIENTS: Twenty patients with
arteriogenic ED as evaluated by dynamic colour duplex ultrasound
(D-CDU) studies, normal sexual desire but testosterone (T) and
FT in the lower quartile of normal range (low-normal), not responding
to sildenafil treatment (100 mg) on six consecutive attempts.
MEASUREMENTS: All patients had D-CDU, hormonal [LH, prostate-specific
antigen (PSA), total and free testosterone, sex hormone-binding
protein (SHBG), oestradiol], biochemical [haematocrit, low-density
lipoprotein (LDL) and HDL cholesterol, triglycerides], and sexual
evaluations [International Index of Erectile Function (IIEF)]
before and after 1 month of therapy with transdermal testosterone
(5 mg/day, n = 10) or placebo along with sildenafil treatment
on demand. Measurement of flow parameters by D-CDU on cavernous
arteries was the primary endpoint of the study. Improvement of
erectile function was assessed using the IIEF questionnaire and
the Global Assessment Question (GAQ). RESULTS: One month treatment
with transdermal testosterone led to a significant increase in
T and FT levels (23.7 +/- 3.3 SD vs. 12.8 +/- 2.1 nmol/l and 473
+/- 40.2 vs. 260 +/- 18.1 pmol/l, P < 0.01, respectively).
In addition testosterone administration induced a significant
increase in arterial inflow to cavernous arteries measured by
D-CDU (32 +/- 3.6 vs. 25.2 +/- 4 cm/s, P < 0.05), with no adverse
effects. Also, a significant improvement in erectile function
domain score at IIEF was found in the androgen but not in the
placebo-treated patients (21.8 +/- 2.1 vs. 14.4 +/- 1.4, P <
0.05) which was associated with significant changes in the GAQ
score (80%vs. 10%, P < 0.01). CONCLUSIONS: In patients with
arteriogenic ED and low-normal androgen levels, short-term testosterone
administration increases T and FT levels and improves the erectile
response to sildenafil likely by increasing arterial inflow to
the penis during sexual stimulation.
-----
Drugs Today (Barc). 2003 Jan;39(1):51-9.
Effective treatment of erectile dysfunction with
vardenafil.
Martin-Morales A, Rosen RC.
Unidad de Andrologia, Complejo Hospitalario Carlos Haya, Malaga,
Spain.
Inhibitors of phosphodiesterase type 5 are playing a large
role in the revolution in the treatment of sexual dysfunction
that has taken place in recent years. The revolution was launched
in 1998 with the introduction of a phosphodiesterase type 5 inhibitor,
sildenafil, which opened up new avenues of investigation and greater
recognition of the prevalence and various characteristics of these
conditions. As more treatments with this and other mechanisms
of action reach advanced stages of development and international
markets, clinicians and patients alike are gaining confidence
in the idea that sexual dysfunction can be successfully treated,
and this, in turn inspires further research. While the efficacy
of sildenafil has been striking, the drug is not effective and
agreeable for all patients. Researchers have naturally sought
to exploit this drug's mechanism of action in the hope that other
agents can be found that are more selective, potent and tolerable.
The etiology of sexual dysfunction is variable, as are its manifestations
and the requirements patients have for therapy, and it is therefore
likely that numerous treatments will be used to enhance sexual
satisfaction in this population. Vardenafil, a new phosphodiesterase
type 5 inhibitor, is an agent which has shown promise at each
stage of development. The drug is currently in the third phase
of clinical testing for the treatment of erectile dysfunction.
(c) Prous Science 2003. All rights reserved.
-----
Eur Urol. 2003 Apr;43(4):412-20.
Effects of visual sexual stimuli and apomorphine
SL on cerebral activity in men with erectile dysfunction.
Hagemann JH, Berding G, Bergh S, Sleep DJ, Knapp WH, Jonas
U, Stief CG.
Department of Urology and Pediatric Urology, University School
of Medicine, Carl-Neuberg-Strasse 1, D-30625, Hannover, Germany.
PURPOSE: The present study investigates whether cerebral activation
during visually evoked sexual arousal is different in patients
with erectile dysfunction (ED) compared to the known pattern observed
in healthy men, and additionally how cerebral activity during
visual sexual stimulation is modified by treatment with apomorphine
SL and whether the observed cerebral activity correlates with
penile rigidity. PATIENTS AND METHODS: Cerebral activity was measured
before and after treatment in 12 patients with erectile dysfunction
randomised to receive either apomorphine SL or placebo using [15O]H(2)O-PET.
Two PET scans were performed prior to administration of the study
medication, the first after a neutral audiovisual stimulus and
the second following a sexually stimulating audiovisual presentation.
After receiving the study medication, patients were subjected
to two additional scans each preceded by a sexually stimulating
stimulus. Penile rigidity was assessed with the RigiScan device.
Evaluation for significant regional cerebral activation was performed
using statistical parametric mapping (SPM99). RESULTS: Cerebral
activity increased significantly after the sexually stimulating
video sequence compared to the neutral one in the inferior frontal
cortex (Brodmann areas [BA] 47, 10, 11) and the rostral anterior
cingulate (BA 32), and cerebral activity was observed to decrease
in both inferior temporal cortices (BA 20). 4 out of 6 patients
showed significant penile rigidity after apomorphine SL and in
none of those receiving placebo. Apomorphine SL was observed to
increase cerebral activity in the right superior prefrontal area
(BA 6) that was not seen with placebo, while neither apomorphine
SL nor placebo produced decreased cerebral activity. Penile rigidity
correlated with increased cerebral activity in the anterior cingulum
and right prefrontal cortex, and with decreased activity in the
temporal cortex. CONCLUSIONS: In patients with erectile dysfunction,
the pattern of increased and decreased cerebral activity in response
to visual sexual stimuli in this study is similar to that reported
in the literature in healthy men. Apomorphine SL appears to induce
additional cerebral activity in the right prefrontal cortex, an
area previously shown to be associated with sexual arousal in
male volunteers during orgasm. This increased cerebral activity
was associated with penile rigidity, further supporting the conclusion
that apomorphine SL improves erectile function in men with ED
by enhancing the natural central erectile signals that normally
occur during sexual stimulation.
-----
Eur Urol. 2003 Apr;43(4):405-11.
Brain activation patterns during video sexual
stimulation following the administration of apomorphine: results
of a placebo-controlled study.
Montorsi F, Perani D, Anchisi D, Salonia A, Scifo P, Rigiroli
P, Deho F, De Vito ML, Heaton J, Rigatti P, Fazio F.
Department of Urology, University Vita e Salute-San Raffaele,
Via Olgettina 60, 20132, Milan, Italy. montorsi.francesco@hsr.it
OBJECTIVES: To evaluate the in vivo effect of apomorphine sublingual
versus placebo on cortical and subcortical brain activation during
video sexual stimulation. METHODS: Ten patients with psychogenic
erectile dysfunction and six potent controls underwent functional
magnetic resonance of the brain during video sexual stimulation
after the administration of either apomorphine sublingual 4mg
or placebo following a randomized, double blind design. Functional
magnetic resonance sessions were performed with a 7-day interval.
RESULTS: In potent controls, viewing erotic versus neutral films
induced bilateral activations in a network of occipito-parietal
and temporal inferior regions, in dorsolateral and premotor frontal
cortex, in anterior temporal limbic areas and the thalamus, which
were comparable to the patient activations during erotic stimulation
in the placebo condition. However, a striking difference was found
in patients, who demonstrated a significant and extended activation
in the cingulate gyrus, frontal mesial and frontal basal cortex,
bilaterally, in comparison with potent controls. These activated
neural systems were modulated by apomorphine administration which
produced a picture that was similar to the one seen in potent
controls. In patients with spychogenic erectile dysfunction apomorphine
sublingual caused an increase in the extension of the activated
networks, plus additional activation foci in subcortical and deep
structures, namely in the nucleus accumbens, hypothalamus and
mesencephalon: this activation was greater than that seen with
placebo. Interestingly, a down-regulation in the frontal basal
and temporal limbic cortex was present as shown by a decrease
of functional magnetic resonance imaging signal reflecting a deactivation
of these regions. CONCLUSIONS: Apomorphine significantly enhances
the activation of cortical and subcortical brain function during
video sexual stimulation. Patients with psychogenic erectile dysfunction
may have an underlying functional abnormality of the brain acting
as a previously unrecognised aetiological factor.
-----
Can J Urol. 2003 Feb;10 Suppl 1:17-22.
Tadalafil: a new agent for erectile dysfunction.
Brock GB.
Department of Surgery, Division of Urology, St. Joseph's Health
Centre, 268 Grosvenor Street, London, Ontario N6A 4V2, Canada.
Oral phosphodiesterase 5 (PDE5) inhibitors for the treatment
of erectile dysfunction are preferred by most men, and are recommended
in guidelines as first-line therapy, because of convenience, high
efficacy, and low rates of side effects. Tadalafil (Cialis) is
a new agent that has been studied in different patient populations.
It has a different molecular structure than other PDE5 inhibitors,
and a different pharmacologic profile that provides a longer period
of effectiveness than other agents. This article will review clinical
trials on tadalafil, to provide a comprehensive overview of its
efficacy and safety.
-----
Can J Urol. 2003 Feb;10 Suppl 1:12-6.
Pharmacology of phosphodiesterase 5 inhibitors.
Carrier S.
McGill University Health Centre, CUSM-Royal Victoria Hospital,
687 West Pines Avenue, Montreal, Quebec H3A 1A1, Canada.
The phosphodiesterase enzymes, of at least 11 types, are ubiquitous
throughout the body, and perform a variety of functions. Phosphodiesterase
type 5 (PDE5) is the predominant enzyme in the corpus cavernosum,
and plays a crucial role in penile erection. Inhibitors of PDE5
are the most effective oral agents in the treatment of erectile
dysfunction. Sildenafil, tadalafil, and vardenafil are all potent
inhibitors of PDE5 and show the same mechanism of action, although
they have some pharmacological differences that may translate
into varying clinical effects.
-----
BJU Int. 2003 Mar;91(5):446-54.
Pharmacological management of erectile dysfunction.
Montorsi F, Salonia A, Deho' F, Cestari A, Guazzoni G,
Rigatti P, Stief C.
Departments of Urology, University Vita-Salute San Raffaele, Milan,
Italy. montorsi.francesco@hsr.it
Erectile dysfunction (ED) is a common medical condition that
affects the sexual life of millions of men worldwide. Many drugs
are now available for treating ED; oral pharmacotherapy represents
the first-line option for most patients with ED. Sildenafil, an
inhibitor of the enzyme phosphodiesterase type 5, is currently
the most widely prescribed oral agent and has a very satisfactory
efficacy-safety profile in all patient categories. Apomorphine
SL is a dopamine D1- and D2-receptor agonist which has recently
been approved for marketing in Europe. It is best selected for
treating patients with mild to moderate ED. Vardenafil and tadalafil
are new phosphodiesterase type 5 inhibitors which are expected
to be approved this year. Both of them have significant positive
efficacy-safety profiles. Patients who do not respond to oral
pharmacotherapy or who cannot use it are good candidates for intracavernosal
and intraurethral therapy. Alprostadil is the most widely used
drug, both for injection therapy and for the intraurethral route.
The efficacy of second-line treatment is high but the attrition
rate remains significant.
-----
Urol Int. 2003;70(2):141-6.
Contemporary aspects of penile prosthesis implantation.
Montague DK, Angermeier KW.
Section of Prosthetic Surgery and Genitourethral Reconstruction,
Urological Institute, Cleveland Clinic Foundation, Ohio 44195,
USA. montagd@ccf.org
PURPOSE: Erectile dysfunction today has a number of effective
treatment options. This review was undertaken to examine the contemporary
role of penile prosthesis implantation in the treatment of this
disorder. MATERIALS AND METHODS: A MEDLINE search was performed
on the topic of penile prostheses and implants. Current literature
was reviewed with regard to types of penile implants, issues related
to prosthesis implantation, results, and patient/partner satisfaction.
RESULTS: Mechanical failure rates for early penile prostheses,
especially the inflatable type, were unacceptably high. Advances
in both prosthesis design and implantation techniques have resulted
in increased device survival with 5-year actuarial survival rates
free of mechanical failure ranging from 86.2 to 93.6%. Recent
reviews of implant recipients show 83 and 85% satisfaction and
for partners 70 and 76% satisfaction. CONCLUSIONS: When systemic
therapy for erectile dysfunction fails, men have a variety of
other options to choose from. Penile prosthesis implantation is
an option that is feasible for nearly every man with this disorder.
Current device survival rates and patient and partner satisfaction
rates are high. Copyright 2003 S. Karger AG, Basel
-----
JAMA. 2003 Jan 1;289(1):56-64.
Treatment of antidepressant-associated sexual
dysfunction with sildenafil: a randomized controlled trial.
Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, Lauriello
J, Paine S.
Department of Psychiatry, Health Sciences Center,University of
New Mexico School of Medicine, 2400 Tucker NE, Albuquerque, NM
87131-5288, USA. geon@unm.edu
CONTEXT: Sexual dysfunction is a common adverse effect of antidepressants
that frequently results in treatment noncompliance. OBJECTIVE:
To assess the efficacy of sildenafil citrate in men with sexual
dysfunction associated with the use of selective and nonselective
serotonin reuptake inhibitor (SRI) antidepressants. DESIGN, SETTING,
AND PATIENTS: Prospective, parallel-group, randomized, double-blind,
placebo-controlled trial conducted between November 1, 2000, and
January 1, 2001, at 3 US university medical centers among 90 male
outpatients (mean [SD] age, 45 [8] years) with major depression
in remission and sexual dysfunction associated with SRI antidepressant
treatment. INTERVENTION: Patients were randomly assigned to take
sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting
at 50 mg and adjustable to 100 mg before sexual activity for 6
weeks. MAIN OUTCOME MEASURES: The primary outcome measure was
score on the Clinical Global Impression-Sexual Function (CGI-SF);
secondary measures were scores on the International Index of Erectile
Function, Arizona Sexual Experience Scale, Massachusetts General
Hospital-Sexual Functioning Questionnaire, and Hamilton Rating
Scale for Depression (HAM-D). RESULTS: Among the 90 randomized
patients, 93% (83/89) of patients treated per protocol took at
least 1 dose of study drug and 85% (76/89) completed week 6 end-point
assessments with last observation carried forward analyses. At
a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared
with 4.4% (2/45) of placebo patients were much or very much improved
(P<.001). Erectile function, arousal, ejaculation, orgasm,
and overall satisfaction domain measures improved significantly
in sildenafil compared with placebo patients. Mean depression
scores remained consistent with remission (HAM-D score < or
=10) in both groups for the study duration. CONCLUSION: In our
study, sildenafil effectively improved erectile function and other
aspects of sexual function in men with sexual dysfunction associated
with the use of SRI antidepressants. These improvements may allow
patients to maintain adherence with effective antidepressant treatment.
-----
Urol Int. 2003;70(2):132-40.
Penile revascularization surgery in erectile dysfunction.
Hauri D.
Urologische Universitatsklinik, Zurich, Switzerland. HAURI@uro.usz.ch
Anastomoses between the dorsal artery of penis and the deep
penile artery are necessary for revascularization of penile arteries.
Radiologic and anatomic proof is provided. Arterio-arterial anastomosis
represents a risk factor for thrombosis. For its exclusion the
necessary operative course of action is showed. By building an
additional arteriovenous shunt close to the arterio-arterial anastomosis
the risk of thrombosis is markedly decreased. Our technique produces
good results in patients with diagnosed erectile dysfunction of
vascular origin with a spontaneous erection when the occasion
arises. Copyright 2003 S. Karger AG, Basel
-----
Zhonghua Nan Ke Xue. 2002 Dec;8(6):438-41.
[Current opinion in vasculogenic erectile dysfunction]
[Article in Chinese]
Li HJ, Huang YF.
Laboratory of Reproduction & Genetics, Nanjing General Hospital
of Nanjing Command, PLA, Nanjing, Jiangsu 210002, China. hongjun63@btamail.net.cn
Diagnosis of vasculogenic erectile dysfunction (ED), which
can not based on single method, is the key for the successive
surgical treatment. Revascularization is a safe, effective method
to treat arteriogenic ED. The key for successive treatment is
to select the most suitable patients and to avoid any risk factors
for the surgical candidates, especially for those revascularization
as the only therapeutic method. The high failure rate in surgery
of ED is due to venous leakage which has led to these techniques
being abandoned by almost all urologist. Newly appeared methods
with little or no damage are welcome by the patients with vasculogenic
ED, and the better results can be achieved by the combination
of general treatment.
-----
Urologiia. 2002 Nov-Dec;(6):34-7.
[Yohimbine in the treatment of erectile dysfunction]
[Article in Russian]
Pushkar' DIu, Segal AS, Bagaev AG, Nosovitskii PB.
Iochimbin hydrochloride was given to 153 men with erectile
dysfunction. The results are available for 140 of them. The ability
of iochimbin in a single dose of 5-10 mg to enhance arterial blood
inflow to cavernous bodies of the penis was confirmed by dynamic
angiopenoscintigraphy and Doppler ultrasonography. Iochimbin hydrochloride
in a mean daily dose of 15-20 mg proved effective in erectile
dysfunction--38 to 84% responders depending on the type of erectile
dysfunction. Occasional side effects can be relieved by reducing
the drug dose.
-----
J Am Osteopath Assoc. 2002 Dec;102(12 Suppl 4):S12-8.
Therapeutic strategies for managing erectile dysfunction:
a step-care approach.
Carson CC 3rd.
Division of Urology, School of Medicine, University of North Carolina
at Chapel Hill, 427 Burnet-Womack Bldg, Campus Box 7235, Chapel
Hill, NC 27599-7235, USA. Culley_Carson@med.unc.edu
During the past two decades, advances in the understanding
of erectile dysfunction have provided primary care physicians,
urologists, and other healthcare providers with additional treatment
options. The introduction of sildenafil citrate, the first oral
phosphodiesterase type 5 (PDE5) isoenzyme inhibitor, has helped
to restore erectile function and improve overall health and quality
of life. The step-care approach to the treatment of erectile dysfunction
can be divided into first-, second-, and third-line modes of therapy.
Most patients with erectile dysfunction will choose oral agents
because of their simplicity and ease of administration. This article
reviews all treatment strategies for erectile dysfunction, with
a focus on PDE5 inhibitors, including novel agents that may optimize
patient outcomes.
-----
Actas Urol Esp. 2002 Oct;26(9):667-90.
[Erectile dysfunction]
[Article in Spanish]
Rodriquez Vela L, Gonzalvo Ibarra A, Pascual Regueiro D, Rioja
Sanz LA.
Unidad de Andrologia, Servicio de Urologia, Hospital Universitario
Miguel Servet, Zaragoza.
In Spain, based on the IIEF, 19% of males between 25 and 70
years old present some degree of erectile dysfunction (ED). Therefore,
around 2,000,000 Spanish men present this condition and could
require medical attention for it. Here, we present an up-date
of the most important aspects of erectile dysfunction (pathophysiology,
diagnosis and treatment). We review, in detail, the oral treatments
and future drugs that are presently in the premarketing experimental
phase. Diagnostic and therapeutic management of the patient with
erectile dysfunction should be individualized, taking into account
the goals of each patient. It is highly recommendable to carry
out a basic assessment (comprehensive clinical history, physical
examination, recommended lab testing). If previously undiagnosed
diseases are discovered (diabetes, arteriosclerosis, etc.) these
should be treated and modifiable risk factors should be corrected.
There are numerous therapeutic options for the treatment of erectile
dysfunction. Replacement therapy with testosterone should only
be used in males with ED and low levels of this hormone, under
medical supervision. At present, first line treatment consists
of the administration of oral drugs (sildenafil, apomorphine).
There are two new PDE 5 inhibitors (tadalafil and vardenafil)
that will be released on the market 2003, which will provide better
selectivity. Moreover, several drugs for oral administration are
in the initial phases of research that will facilitate erection
via a direct penile action. When oral drugs are contraindicated,
are not effective or when they are unpopular with the patient,
the second line of treatment is intracavernous injection. Prostaglandin
E1 is the initial drug of choice in patients using intracavernous
autoinjection for the first time and has a high efficacy. Implantation
of a penis prosthesis and penile revascularisation are appropriate
for highly selected patients. Psychotherapy can be an option for
men with ED of psychogenic origin, either as a monotherapy or
combined with sildenafil or apomorphine.
-----
Urology. 2002 Dec;60(6):1077-82.
Topical alprostadil cream for the treatment of
erectile dysfunction: a combined analysis of the
phase II program.
Steidle C, Padma-Nathan H, Salem S, Tayse N, Thwing D,
Fendl J, Yeager J, Harning R.
Northeast Indiana Research, Fort Wayne, Indiana, USA.
OBJECTIVES: To present a meta-analysis of the efficacy and
safety data of two recently completed Phase II studies examining
a novel alprostadil topical cream for the treatment of erectile
dysfunction (ED). METHODS: Patients (n = 303) with ED of at least
3 months' duration were randomized to receive placebo or 50, 100,
200, or 300 microg alprostadil in two nearly identical 11-dose,
multicenter, at-home studies of a novel topical cream containing
alprostadil and a proprietary skin permeation enhancer. The primary
efficacy endpoint was the change in erectile function domain score
from baseline to the final visit. Secondary endpoints included
changes in scores for questions 3 and 4 of the International Index
of Erectile Function and standard diary analyses. Safety was assessed
by analysis of adverse events, changes in laboratory test results,
and physical examination findings. RESULTS: The mean baseline
parameters for the erectile function score, ED history, and secondary
diagnoses suggested no significant differences among the treatment
groups. The changes from baseline to the final visit erectile
function scores were 0.98 +/- 0.84, 3.4 +/- 1.3, 3.4 +/- 0.88
(P <0.05), 5.3 +/- 0.92 (P <0.001), and 9.4 +/- 1.43 (P
<0.001) for the ascending dose groups. Most secondary efficacy
endpoints were significant for the 200 and 300-microg dose groups.
Dose-related trends in efficacy were observed. Adverse events
were localized to the application site, were of mild or moderate
intensity, and were of short duration. CONCLUSIONS: These results
suggest topical alprostadil cream, when combined with a novel
dermal permeation-enhancer, to be a potentially useful agent for
the treatment of ED.
-----
Aging Male. 2002 Sep;5(3):177-80.
Intracavernous injection as an option for aging
men with erectile dysfunction.
Wespes E.
Department of Urology, CHU de Charleroi, Boulevard Zoe Drion Drion,
1 6000 Charleroi, Belgium.
Sexuality remains a vital aspect of life in spite of aging.
Advances in impotence research and increased knowledge of the
pathophysiology of erection have completely changed the treatment
of erectile dysfunction. Before oral therapy, intracavernous injection
was considered as the first-line therapy for impotent patients.
However, the new simple oral treatment raises the question as
to whether intracavernous injection therapy is still a useful
tool for treatment of aging men with erectile dysfunction. The
efficacy and safety of oral therapy and intracavernous injection
are reviewed.
-----
Rev Med Brux. 2002 Oct;23(5):451-5.
[Partial androgenic deficit in the aging male]
[Article in French]
Mockel J, Schulman C, Sternon J.
Service d'Endocrinologie, Hopital Erasme.
It is possible to observe in the aging male an hypotestosteronemia
below 3 ng/ml. The indications of an androgenic treatment are
discussed with their benefits, risks, contra-indications and choices
of molecules. Testosterone-gel seems to be now the first choice
for this type of patient. In case of normal testosteronemia and
erectile dysfunction, the benefits/risks ratio of sildenafil is
very favorable, except when contra-indicated.
-----
Ter Arkh. 2002;74(10):75-7.
[A new approach to raising the efficiency of drug
therapy for erectile dysfunction]
[Article in Russian]
Dmitriev DG, Gamidov SI, Mazo EB, Ovchinnikov RI.
AIM: To try combined treatment of erectile dysfunction with
viagra and alprostadil in case of failure of their monotherapy;
to compare effectiveness of viagra in dynamics of treatment, in
various doses and dose adjustment. MATERIAL AND METHODS: 82 patients
with ED of different genesis received a course of intracavernous
injections of alprostadil followed by a course of viagra; 25 patients
received combined treatment with alprostadil and viagra. Each
course lasted for 3 months. Viagra efficiency was also assessed
in long-term use (12 months) and different initial doses (50 or
100 mg). RESULTS: Monotherapy with alprostadil or viagra was effective
in 73.2 and 75.6% patients, respectively. Their combination was
more beneficial--88.0%. When used for a long time, viagra lost
efficiency in psychogenic ED by 17.7%, in organic ED--by 16.9%.
In an initial viagra dose 50 mg efficiency reached 70.3%, 100
mg--80.0%. CONCLUSION: Combined treatment of ED is a method of
choice in monotherapy failure and in severe ED. Lowering of viagra
efficiency in long-term administration may be explained by disappearance
of placebo effect.
-----
Expert Opin Pharmacother. 2002 Nov;3(11):1613-29.
Current oral treatments for erectile dysfunction.
Kalsi JS, Cellek S, Muneer A, Kell PD, Ralph DJ, Minhas
S.
The Institute of Urology and Nephrology, University College London,
48 Riding House Street, London, W1P 7NN, UK. j.kalsi@ucl.ac.uk
Erectile dysfunction (ED) is defined as the inability to achieve
and maintain a penile erection adequate for satisfactory sexual
intercourse. It is a significant male health problem of global
dimensions affecting approximately 150 million men worldwide.
A broad range of options are currently available for the management
of ED. They include oral agents (phosphodiesterase 5 inhibitors,
dopamine agonists and alpha-receptor blocking drugs), intracavernosal
injection (papaverine, phentolamine, prostaglandin E1, vasoactive
intestinal peptide), transurethral vasoactive agents (prostaglandin
E1), vacuum erection devices, vascular surgery and penile prostheses.
Here we review the physiology of penile erection and the currently
available oral preparations. In addition, novel therapeutic strategies
to improve erectile function are discussed.
-----
Curr Urol Rep. 2002 Dec;3(6):471-6.
Topical agents and erectile dysfunction: is there
a place?
Yap RL, McVary KT.
Department of Urology, Northwestern University Medical School,
Tarry 11-725, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Despite the proven efficacy of oral therapy for erectile dysfunction
(ED), some patients are unable to take these medications because
of drug interactions (ie, sildenafil and nitroglycerin) or a lack
of response. Topical agents represent another minimally invasive
option for the treatment of ED. This review discusses the impediments
to effective topical therapy and examines the developmental status
of several candidate drugs. Although still in the investigative
stage, topical medications can be another tool in the urologist's
armamentarium against ED.
-----
Urology. 2002 Sep;60(2 Suppl 2):67-90.
A 4-year update on the safety of sildenafil citrate
(Viagra).
Padma-nathan H, Eardley I, Kloner RA, Laties AM, Montorsi
F.
The Male Clinic, Keck School of Medicine at the University of
Southern California School of Medicine, Beverly Hills, California,
USA. hpn@insyght.com
Clinical studies have demonstrated that sildenafil citrate
(Viagra) is an effective and well-tolerated oral treatment for
erectile dysfunction. Despite its established safety profile,
concern about its cardiovascular safety persists among some physicians
and the general public. This concern has stemmed primarily from
sporadic reports of adverse events published in the literature
and sensationalized by the media. However, the only absolute contraindication
for sildenafil is concurrent use of nitrates. Because sildenafil
has been on the market for 4 years and under clinical investigation
for even longer, we can now evaluate its long-term safety in men
who have been taking the drug for several years. We review this
issue from 3 perspectives. First, we reassess the overall safety
profile of sildenafil by reviewing the initial controlled clinical
trials and open-label studies. We present new data from patients
who have been exposed to sildenafil for up to 4.5 years. We also
evaluate the results from independent postmarketing studies. Second,
we review the cardiovascular-specific results from the clinical
trials, long-term extension, and postmarketing studies. Lastly,
we review the specific effects on the visual system based on findings
from studies conducted during drug development and post marketing.
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