Sexual function/dysfunction/andrology: medical and non-surgical therapy (i)

SEXUAL FUNCTION/DYSFUNCTION/ANDROLOGY:
MEDICAL AND NON-SURGICAL THERAPY (I)
The association between erectile dysfunction and cardiovascular disease has been well established. It has been suggested that patients with newly diagnosed ED should undergo evaluation for other risk factors for CAD. On the other hand, the question was raised if sildenafil, an effective drug for erectile as well as endothelial dysfunction, may influence the cutaneous microcirculation in CAD patients. Jai-Wun Park et al (abstract 731) investigated this relationship in 20 CAD patients in a
prospective, randomized, double-blind, cross-over study. The effect of the medication was assessed using intravital microscopy and measuring erythrocyte velocity in nail- fold capillaries. The difference in the amplitudes of the reactive hyperemia before and one hour after the administration of Viagra vs. placebo allowed authors to make the following conclusions. Sildenafil significantly improved the endothelial dysfunction of precapillary arterioles in patients with CAD, thus, confirming the hypothesis that PDE-5 inhibitors work beyond improvement of erectile dysfunction, and specifically, improve endothelial dysfunction of the human vasculature in general. This was a very elegantly A group from Duke University, Scales et al (abstract 732) analyzed data from a
large pharmacy benefits management company concerning safety of combination drug therapy. In 1999, combination of Viagra and nitrates was the most common combination in potential Class I type of interaction. It accounted for over one half of all inappropriate co-prescriptions, and urologists were responsible for roughly one quarter of the overlapping sildenafil prescriptions. However, the overall rate of overlapping prescriptions with potential Class I interactions was low (0.05%). The study was based on data from 1999, and certainly did not reflect on today’s reality of having three different PDE-5 inhibitors on the market, as well as possibly much higher level of awareness by providers with respect to potential drug-drug interactions and contraindications for co-prescribing. Some of the suggestions made were to broaden the study to include other medications from this class. A different type of analysis might have been more beneficial to prove the point of safety. Overall the study revisited an important issue of co-prescribing medications and its safety in the era of poly-pharmacy. As we continue to look for answers to help resolve or at least alleviate erectile dysfunction following radical prostatectomy, the data is starting to come in on the long term follow up on the use of PDE-5 inhibitors to treat it. Raina et al (abstract 735)
reported their 5-year data on the efficacy of sildenafil citrate after radical prostatectomy. The overall conclusion was that at 5 years approximately 50% of initial responders continued to do well on Viagra. The other half either switched to or added other erectile aids, or discontinued therapy altogether due to various reasons. There were only 68 men who met the criteria. This the first report of a 5-year efficacy and compliance for this medication after radical prostatectomy. Another paper from the same group (abstract 737) considered a different
therapeutic modality to facilitate early return of sexual activity following radical prostatectomy with bilateral nerve sparing. Patients were started on early MUSE treatment at 125mcg 3 times/week for the first 6 weeks. At 6 weeks the dose was titrated to 250mcg 3 times/week for 4 moths. Results were assessed using the SHIM questionnaire. Out of those who were able to tolerate the treatment, 74% resumed sexual activity at 6 months, and of these, approximately one half had natural erections sufficient for penetration. In the control group, only one third resumed sexual activity, and of these, less that a third were able to obtain natural erections sufficient for penetration. While the study brings up an important issue of early intervention following radical prostatectomy, it also underscores the importance and the need to use validated instruments in the evaluation of sexual function. Yet another study presented dealt with the issue of erectile function following radical prostatectomy. Montorsi et al from Italy (abstract 736) reported their short-term
data on erectile function and its correlation with other pre-op and post-op parameters following bilateral nerve-sparing radical prostatectomy. Patients were stratified into 4 groups: #1 no treatment, #2 on demand intracavernosal PGE-1, #3 on demand PDE-5 inhibitor, and #4 rehabilitative treatment with PDE-5 inhibitor. Multivariate analysis of these data was performed and showed significant correlation between postoperative erectile function and degree of postoperative sexual desire, mood, and urinary continence. Interestingly enough there was no difference between patients in the group that used PDE-5 inhibitor on demand vs. those who took it as rehabilitative treatment. In this study the patients were self-selected and not randomized which is one of this abstract’s criticisms. Despite this, it was a well done study with a take home message that almost 50% of patients who had bilateral nerve sparing chose to have no treatment at all. This observation by itself along with the study’s conclusions about “non-surgical” factors in post-operative ED, speaks for the multifactorial hypothesis in the recovery of erectile function after radical prostatectomy. The results of work from members of multi-institutional group were presented in a study designed to address the utility of topical alprostadil in female sexual arousal disorder in pre-menopausal women (abstract 738). Prior trials demonstrated beneficial
effects of the medication in dealing with the problem in post-menopausal women. Current work was a double blind placebo controlled with crossover design. A total of 51 patients met the enrollment criteria and were randomized into 2 groups. Only half of them reported on the use of at least 6 doses during each treatment period and were considered for the valid efficacy population. There was statistically significant increased frequency in number of intercourses, satisfactory arousal and orgasm in the treatment group. The most common adverse effect reported was burning at the site of the application (43% in the treatment group and 36% in the placebo group). However, this was deemed to be mild and transient. Overall, this was a well-designed study, where vehicle for the drug was a small amount of liquid which appeared to be a fairly In abstract 740, the results of phase III clinical trials on dapoxetine for premature
ejaculation were presented. These were 2 randomized, double blind, placebo controlled, multicenter trials of identical design. The total number of patients was 2614. They were randomized to three groups: placebo, dapoxetine 30mg, and dapoxetine 60mg, and instructed to take the drug 1-3 hours prior to expected sexual activity. The efficacy of the medication was assessed using intravaginal ejaculatory latency time, which was measured by a stopwatch held by the female partner. Overall satisfaction with intercourse as well as subjects’ perceived control over ejaculation, were used as secondary end points for the study. Preliminary results were very promising. There was statistically significant difference in intravaginal ejaculatory latency time by dapoxetine compared to placebo. The response also appeared to be dose dependent: increase from 0.90 to 1.75 min for placebo, increase from 0.92 to 2.78 min and from 0.91 to 3.32 min for 30mg and 60mg of dapoxetine respectively. Proportion of subjects who perceived their control over ejaculation as fair, good, or very good changed from 3.5% to 26.4%, from 2.5% to 51.8%, and from 3.3% to 58.4% in the placebo, dapoxetine 30mg and dapoxetine 60mg groups respectively. Overall satisfaction with intercourse changed as following: from 51.8% to 55.2%, from 52.4% to 70.9%, and from 56.7% to 79.2% in three respective categories. Some side effects from the medication were noticed. The most common ones were nausea and headache with dose-dependent occurrence. Diarrhea and dizziness only occurred in the group that took 60 mg of dapoxetine. Discontinuation rate was fairly low, but once again dose-dependent: 0.9%, 4%, and 10% for the three respective Abstract 739 considered the pharmacodynamics of dapoxetine when used with
PDE-5 inhibitors. The two medications from the class were tadalafil and sildenafil. Dose of dapoxetine tested was 60 mg. It was a randomized, open label, 3-period crossover study of healthy individuals. Each treatment period was separated by a 6-14 day wash-out period. The combinations tested were dapoxetine alone, dapoxetine + Viagra 100mg, and dapoxetine + Cialis 20mg. Vital signs, ECG’s, and blood levels of drugs and their metabolites were assessed at various points during the study. As a result, there was no clinically significant effect on pharmacokinetics of dapoxetine from the two PDE-5 inhibitors tested. There was also no significant effect of dapoxetine on plasma levels of sidenafil and tadalafil. It was an important study to establish safety of co-prescribing dapoxetine with PDE-5 inhibitors as there is sometimes well demonstrated coexistence of premature ejaculation and erectile dysfunction. In the last study from this session, a group from Germany (abstract 741)
presented its results in an attempt to compare treatment of premature ejaculation by a PDE-5 inhibitor vs. that by a selective serotonin reuptake inhibitor. 34 men who met the enrollment criteria were randomized to 6 weeks of vardenafil 10mg or sertraline 50mg. Crossover design was used and the medications were switched after a 1 week wash-out period. The results of this small scale study showed some statistical significance in favor of vardenafil. However, the majority of patients with PE had secondary PE with

Source: http://www.smsna.net/pdf/MEDICAL%20AND%20NON-SURGICAL%20THERAPY%20(I).pdf