Q 62What are the optimum methods of management for sexual dysfunction in adults with Type 1 diabetes?

Author / Title / Reference / YrPrice, D. E., Gingell, J. C., Gepi-Attee, S., Wareham, K., Yates, Boolell, M. (1998). Sildenafil: Study of a novel oral treatment for erectile dysfunction in diabetic men. Diabetic Medicine, 15, 821–825.
N=N= 21 participants
UK
Sites=2
Research DesignRandomised controlled trial
AimTo assess the efficacy and safety of 25mg or 50 mg of sildenafil taken as a single dose, followed by once daily dosing for 10 days in diabetic men with ED.
PopulationPenile plethysmography was used to measure rigidity at the base of the penis and at the tip of the penis below the glans. After 15min of continuous recording, a single dose of sildenafil or placebo (25mg or 50mg) was administered. Using video’s and magazines, visual sexual stimulation commenced 30min after dosing and continued for 90min. The duration (min) of penile rigidity greater than 60% was monitored.
Daily diary records of erectile activity (grading scale 1–4) and a global efficacy question (did the quality of their erections improve during the 10 days you took the treatment?) were used to evaluate once-daily dosing with 25mg or 50mg of Sildenafil or placebo for 10 days.
InterventionSildenafil 25mg or 50mg
ComparisonPlacebo
OutcomePenile plethysmography (RigiScan, Dacomed Corporation, Minneapolis, Minnesota, USA).
Daily diary records of erectile activity (grading scale 1–4)
Global efficacy question (did the quality of their erections improve during the 10 days you took the treatment?)
Characteristics(Type 1: N=7; Type 2: N=14), Mean age=51yrs/Age range: 42yrs–65yrs, Mean duration of diabetes=11yrs (3–32yrs)
ResultsPenile rigidity
After a single dose of sildenafil, the adjusted geometric mean (95% CI) duration (min) of penile rigidity greater than 60% at the base of the penis during visual stimulation was significantly increased with 50mg of sildenafil compared with placebo (25mg sildenafil: 5.0 (1.9–12.4); 50mg sildenafil: 10.1 (4.2–23.1, p=0.0053 versus placebo) and placebo: 2.8 (0.7–8.4).
At the tip of the penis the adjusted geometric mean duration of rigidity was 1.2 (0.2–3.8) for 25mg of sildenafil, 2.2 (0.7–6.0) for 50mg of sildenafil (p=0.0126 vs placebo) and 0.4 (−0.2–2.1) for placebo.
Daily diary records of erectile activity
Both 25mg and 50mg doses of sildenafil significantly increased the total number of erections hard enough for sexual intercourse (i.e. grade 3 or 4) compared with placebo. The mean numbers of erections sufficiently rigid for sexual intercourse per week were 1.3 (0.9–1.8, p=0.0025) for patients taking 25mg of sildenafil and 1.6 (1.1–2.1, p=0.0002) for patients taking 50mg of sildenafil compared with 0.6 (0.4–0.9) for placebo treated patients.
Global efficacy question
At the end of 10 days of treatment, a significant percentage of patients reported improvement in their erections with daily administration of sildenafil. Of the 20 patients who completed treatment with both placebo and 25mg of sildenafil, 10 patients (50%) reported that their erections were improved on 25mg of sildenafil compared with two patients (10%) on placebo (p=0.048).
After treatment with placebo and 50mg of sildenafil, 11 of 21 patients (52%) recorded improvement in the quality of their erections on 50mg of sildenafil compared with two patients (10%) on placebo (p=0.028).
There were no serious adverse events judged to be related to treatment.
Hierarchy of Evidence GradingIb
CommentsSmall sample size
No power analyses
The study documents randomisation of subjects but randomisation methodology is not specified.
The study documents double-blinding but blinding methodology is not specified.
Washout period is 3–10 days at each cross-over stage. Not clear why this variation in washout period, nor is it clear what effect this variation in washout period might have on the study outcome
Reference / Citation253
Author / Title / Reference / YrRendell, M. S., Rajfer, J., Wicker, P. A., Smith, M. D. (1999). Sildenafil for treatment of erectile dysfunction in men with diabetes: A randomized controlled trial. JAMA, 281,5, 465–426.
N=Total N=268 participants, Sildenafil =136, Placebo =132
United States
Sites=19
Research DesignRCT multi-centre, randomised, double-blind, placebo controlled, flexible dose-escalation study.
AimTo assess the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction in men with diabetes.
PopulationPatients were randomised to receive sildenafil or placebo as needed, but no more than once daily, for 12 weeks. Patients took the study drug or placebo 1 hour before anticipated sexual activity. The starting dose off sildenafil was 50mg, with the option to adjust the dose to 100mg or 25mg based on the efficacy and tolerability, to be taken as needed.
InterventionPatients were included if they had:
Medically documented ED (as defined by the National Institutes of Health Consensus Panel) which was documented in the prior medical record to be at least 6 months duration
A clinical diagnosis (as defined by the National Diabetes Group) of at least 5 years duration of Type I and at least 2 years duration for Type II.
ComparisonSildenafil (orally at 100mg/day (for 93% of intervention group)
OutcomeA control of placebo
Characteristics(IIEF) Self-administered International Index of Erectile Function.
Global Efficacy Questionnaire (Did the treatment improve your erections?)
Event log in which patients recorded the number of attempts at sexual intercourse and the number of attempts that were successful.
Results(IIEF) Self-administered International Index of Erectile Function.
By ITT analysis, at 12 weeks, the least squares mean score to the IIEF questions assessing the ability to achieve (Q3) and maintain (Q4) erections demonstrated significant improvements among patients receiving sildenafil compared with those receiving placebo (p less than 0.001). For question 3, the mean score was 3.2 for patients in the sildenafil group compared with 2.0 for those in the placebo group, which represent increases from baseline of 78% and 25% respectively. For question 4, the sildenafil group had a 93% increase compared with a 14% increase for the placebo group.
Of the remaining 13 questions of the IEFF, mean scores for 11 questions assessing other aspects of male sexual function showed significant improvements for the sildenafil group compared with the placebo group (p less than 0.001).
The mean scores for IEFF questions 11 and 12, which assessed frequency of sexual desire and the level of sexual desire, indicated no statistically significant differences between the two groups (p=.71 and p=.17).
Global Efficacy Questionnaire
56% of patients taking sildenafil reported improved erections compared with 10% taking placebo (p less than 0.001).
Event log
The proportion of attempts at sexual intercourse that were successful during the last 4 weeks of treatment was significantly greater for all patients. The proportion of men reporting this was 48% in the sildenafil group compared with 12% in the placebo group (p less than 0.001). The proportion of men with at least 1 successful attempt at intercourse was 61% for the sildenafil group vs 22% for the placebo group (p less than 0.001).
Treatment with sildenafil significantly improved erectile function across all 3 efficacy variables regardless of patient age (p less than 0.002 vs placebo), the duration of ED (p less than 0.001 vs placebo) and the duration of diabetes (p less than 0.001).
Each of the 3 efficacy variables demonstrated a significant improvement with sildenafil treatment in patients with type 2 diabetes (p less than 0.001 vs placebo). 2 of 3 variables were significantly improved with sildenafil treatment in patients with type I diabetes (P less than 0.03 vs placebo).

Adverse events related to treatment were reported for 22 (16%) of 136 patients taking sildenafil and 1 (1%) of 132 patients receiving placebo. The most common adverse events were headache (11% sildenafil, 2% placebo), dyspepsia (9% sildenafil, 0% placebo), and respiratory tract disorder (6% sildenafil, 2% placebo), predominantly sinus congestion or drainage.
The incidence of cardiovascular adverse events was comparable for both groups (3% sildenafil, 5% placebo).
Hierarchy of Evidence GradingIb
CommentsNo Confidence intervals available
Reference / Citation

From: Appendix D, Evidence tables

Cover of Type 1 Diabetes in Adults
Type 1 Diabetes in Adults: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 15.1.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2004, Royal College of Physicians of London.

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