Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study

Abstract

To evaluate the safety and efficacy of cabergoline in men with erectile dysfunction (ED) who did not respond to sildenafil. Four hundred two sildenafil nonresponders aged from 21 to 59 years were included in the study. Patients were randomly divided into group 1, those who received 0.5-1 mg cabergoline weekly for 6 months and group 2, who received placebo for the same period. They underwent preliminary assessment, including medical and sexual history, self-administered International Index of Erectile Function (IIEF) and intravaginal ejaculatory latency time (IVELT) evaluation. Standard biochemistry and hematological laboratory tests, and measurement of serum testosterone and prolactin levels were also carried out. When indicated, other tests were used to establish the diagnosis of vasculogenic and neurogenic ED, including penile color duplex Doppler ultrasonography, pudendal nerve conduction test and impaired sensory-evoked potentials studies. The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of the study, using responses to IIEF, IVELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. The trial was completed by 370 (92%) men. Positive clinical results were seen in 31.2% of patients in the cabergoline group compared with 7.1% of patients in the placebo group (P ¼ 0.04). The mean weekly intercourse episodes increased from pretreatment values of 1.4 and 1.2 to 2.2 and 1.4, for cabergoline and placebo, respectively (P ¼ 0.04). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 15 and 10 at 6-month treatment in groups 1 and 2, respectively (P ¼ 0.04). The IVELT after cabergoline and placebo gradually increased from 98 and 101 s to approximately 242 and 116 s, respectively (P ¼ 0.001). More drug-related adverse effects occurred in cabergoline group and 12 (5.9%) had to discontinue treatment (P ¼ 0.001). Cabergoline is moderately effective salvage therapy for sildenafil nonresponse. Further studies with different dosages and treatment regimens are necessary to draw final conclusions on the efficacy of this drug in ED.

Effect of prescription medications on erectile dysfunction

“…It is estimated that up to 30%–40% of patients do not respond sufficiently to PDE-5 inhibitor therapy 96. A randomised clinical trial found that 31.2% of sildenafil non-responders responded to cabergoline, while only 7.1% of patients responded within the placebo group 97. There is evidence that diabetes affects the central dopaminergic pathways, resulting in increased rates of ED and Parkinson’s disease 98.…”

Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil

“…8,9 Sildenafil's efficacy is also lower in patients with some risk factors and diseases such as diabetes mellitus, 10,11 hypertension, 12 multiple sclerosis 13 and combat-related posttraumatic stress disorder. 14 Centrally acting drugs, such as dopamine agonists 15 and melanocortin analog, 16 have been used as less invasive modalities (vs intracavernous injection, vacuum constrictive device and penile prosthesis) with various success rates to salvage sildenafil nonresponders. However, the growing numbers of men with ED, and the significant number of patients for whom this treatment is ineffective or contraindicated, make sildenafil nonresponders a great challenge for urologists.…”

“…The instruction sheet emphasized its use on an empty stomach, the proper timing of sildenafil administration (30 min-2 h before sexual attempt) and the absolute need for appropriate sexual stimulation. Erectile function was categorized as follows using the 5-item version of the International Index of Erectile Function (IIEF-5) total scores: no ED (22)(23)(24)(25), mild ED (17-21), mild to moderate ED (12)(13)(14)(15)(16), moderate ED (8-11) and severe ED (5-7). 30,31 Participants were further categorized into five age groups according to their age: 18-30, 31-40, 41-50, 51-60 and 61-70.…”

Sildenafil in the treatment of erectile dysfunction: an overview of the clinical evidence

“…However, combination therapy was associated with a 33% incidence of adverse effects, including a 20% incidence of dizziness side effects (McMahon et al 1999). Finally, preliminary data suggest a possible role for combination treatment with cabergoline (Safarinejad 2006) or statins (Herrmann et al 2006; Osborne 2006) in non-responders to sildenafil alone.…”