Erectile Dysfunction in Systemic Sclerosis: Effects of Longterm Inhibition of Phosphodiesterase Type-5 on Erectile Function and Plasma Endothelin-1 Levels

Objective. To investigate the effects of prolonged inhibition of phosphodiesterase type-5, using once-daily long-acting phosphodiesterase type-5 inhibitor (tadalafil) on erectile function and biomarkers of endothelial function in male patients with systemic sclerosis (SSc) and erectile dysfunction (ED). Methods. In an open-label study, 14 nonconsecutive male patients with SSc with different degrees of ED were enrolled into the study irrespective of their clinical response to tadalafil, and received once-daily tadalafil 10 mg for 12 weeks. Primary endpoints were variations from baseline of penile arterial inflow [peak systolic velocity (PSV, cm/s); measured with dynamic color duplex ultrasound] and the erectile function domain score (measured with the International Index of Erectile Function questionnaire). Secondary endpoints were variations from baseline of morning erections (determined by modified question 13 of the Structured Interview on Erectile Dysfunction@ questionnaire) and plasma concentrations of endothelin-1 (ET1). Results. The PSV and the erectile function domain score were significantly improved by once-daily tadalafil (from 21.3 ± 6.4 to 30.0 ± 7.0 cm/s and from 13.0 ± 6.8 to 17.0 ± 9.0 vs baseline, respectively; p < 0.05). Question 13 scores decreased dramatically after treatment compared with baseline (from 2.2 ± 0.2 to 0.8 ± 0.5 arbitrary units; p < 0.001), and plasma ET1 levels decreased (from 24 ± 15 to 9.8 ± 7.4 pg/ml; p < 0.05). Conclusion. In men with SSc-related ED, once-daily tadalafil improved both erectile function and vascular measures of cavernous arteries. Increases in morning erections and decreases in plasma ET1 levels were found, which may play a potential role in preventing progression of penile fibrosis and erectile dysfunction.