CLINICAL DATA ON SILDENAFIL BUILD
Title: CLINICAL DATA ON SILDENAFIL BUILD , By: Bankhead, Charles, Urology Times, 00939722, Jan97, Vol. 25, Issue 1
Section: WORLD MEETING ON IMPOTENCE
Drug showing effectiveness in psychogenic and even organic dysfunction
Clinical data continue to build a case for the effectiveness of the new oral agent sildenafil ( viagra ) in treating erectile dysfunction.
Researchers are homing in on the most effective dosage and are also discovering that the drug is helpful, not only for primarily psychogenic erectile dysfunction, but also for dysfunction with a definite organic origin.
A trio of studies showed significant improvement in the frequency and quality of erections in men treated with the drug. Collectively, the studies showed a high rate of efficacy, even in men with longstanding impotence. However, some of the improvement, though statistically significant, appeared to be modest. A fourth study showed significant improvement in erectile dysfunction among diabetic patients. Sildenafil was well tolerated in all four studies.
The largest of the studies showed that the drug’s effects were dose dependent, with the highest dose used in the studygiving the best results.
The 351 men in the study had experienced erectile dysfunction for an average of 4.5 years, ranging between 3 months and 40 years.
All the patients had impotence of psychogenic or mixed origin. To qualify for enrollment in the study, each patient had to have at least one spontaneous erection within the 4 weeks before enrollment or a positive response to intracavernosal injection, according to Wallace W. Dinsmore, MD, a urologist at Royal Victoria Hospital in Belfast, Northern Ireland. He reported the findings on behalf of investigators in a, multicenter. European trial.
The men were randomized to one of four treatment arms: placebo, or 10 mg, 25 mg, or 50 mg daily of sildenafil. Patients randomized to active therapy exhibited dose-dependent improvement in erectile dysfunction.
The placebo cohort had a fairly large improvement of almost 40%, but that was significantly less than the improvement seen with all three sildenafil groups after 1 month. Improvement with active therapy ranged from 64% with 10 mg, to 79% with 25 mg, to 88% with 50 mg (P < .0001).
Similarly, significantly more men taking sildenafil than placebo wanted to keep taking it (78%, 85%, and 91% for the three doses, P<.0001)–a significant difference despite another high placebo response (51%).
The men kept daily erection diaries and completed a 15-item self-assessment sexual questionnaire before and after the study. Sexual partners also completed questionnaires.
“A dose-response relationship was clear for frequency, hardness, and duration of erection,” said Dr. Dinsmore.
“Although there was no effect on attempts of sexual intercourse, the number of satisfactory attempts per fortnight was significantly greater with sildenafil.”
The number of successful attempts at intercourse per 2 weeks averaged 2.1 with placebo, 2.5 with 10 mg sildenafil, 3.0 with 25 mg, and 4.0 with 50 mg.
Compared with patients receiving placebo, men who took sildenafil reported increased enjoyment of intercourse and satisfaction with sex life. Sexual partners exhibited dose-dependent responses that significantly favored sildenafil.
All doses of sildenafil were well tolerated, with only 13 patients withdrawing from therapy because of adverse events.
Headache, flushing, dyspepsia, and muscle ache were the most common.
Most Take Higher Dose
Similar results emerged from a 233-patient Norwegian dose-escalation study. The men had at least 3 months of erectile dysfunction of unknown cause. Each man had experienced at least one grade 3 or 4 erection or a positive response to intracavernosal injection in the 4 weeks before enrollment.
After a 2-week placebo run-in phase, patients began taking 10 mg of sildenafil daily. The dose could be increased to 100 mg, depending on response, said Einar Christiansen, MD, of the Andrology Center in Oslo.
At the end of 16 weeks, most patients (119) were receiving 100 mg sildenafil daily; 60 were taking 50 mg, and only 3 remained on 10 mg. On self-assessment questionnaires, about 200 of the men reported overall improvement in erectile activity and increased frequency and firmness of erections.
Only 12% of the men discontinued therapy because of adverse events. The most common complaints were the same as those seen in the multicenter study.
A 17-patient crossover study provided additional evidence of sildenafil’s efficacy in men with primarily psychogenic erectile dysfunction. The study, led by Mitradev Boolell, MD, of Pfizer Central Research in Sandwich, England, included men who had suffered erectile dysfunction for 6 months to 19 years.
The patients were treated with a single 50-mg dose of sildenafil. Ten minutes after dosing, each man watched an hour-long sexually oriented video. Erectile activity was assessed by use of a plethysmograhic device attached at the base of the penis (RigiScan). Each man repeated the study with a placebo.
With sildenafil, 14 of 17 men achieved erections of at least 60% rigidity (adequate for intercourse), and duration of erections averaged 5.9 minutes. The median time to first erection was 19 minutes. During the placebo phase, 9 of 17 men achieved at least 60% rigidity, and the erections averaged 1.1 minutes.
Men with Diabetes Benefit
Dr. Boolell and colleagues at Pfizer and at hospitals in Bristol and Swansea, England, evaluated sildenafil in 21 diabetic men who had erectile dysfunction for an average of 3 years. In the crossover trial, each man received a single 25-mg or 50-mg dose of sildenafil or placebo, followed by visual stimulation. Erectile activity was assessed with plethysmography.
Sildenafil exhibited a dose-dependent effect on erection duration, which averaged 2.4 minutes with 25-mg doses and 7.2 minutes with 50-mg doses. Erections with placebo averaged 1.5 minutes.
The men continued daily sildenafil or placebo for 10 days. They maintained erection diaries and completed self-assessment questionnaires. Over 10 days, the number of erections suitable for intercourse averaged 0.7 with placebo, 1.7 with 25 mg of sildenafil, and 1.9 with 50 mg. The duration and number of erections were significantly increased by sildenafil, compared with placebo.
PHOTO (COLOR): SAN FRANCISCO 1996
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By Charles Bankhead, Contributing Editor
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Source: Urology Times, Jan97, Vol. 25 Issue 1, p11, 2p
