Platelet cyclic guanosine monophosphate as a biomarker of phosphodiesterase type 5 inhibitor efficacy in the treatment of erectile dysfunction: a randomized placebo-controlled study.
BACKGROUND
Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF).


OBJECTIVE
To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED.


METHODS
The study enrolled 46 patients with psychogenic, organic, and mixed ED (20-71 yr of age; IIEF score<26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.


METHODS
All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment.


METHODS
Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment.


CONCLUSIONS
Platelet cGMP production was significantly (p<0.05) elevated in patients taking 5mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p<0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p=0.0037) but not with IIEF-EF and SEP.


CONCLUSIONS
Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.
Mirone
Vincenzo
V
Interdepartmental Research Center for Sexual Medicine, University of Naples Federico II, Naples, Italy.
d'Emmanuele di Villa Bianca
Roberta
R
Mitidieri
Emma
E
Imbimbo
Ciro
C
Fusco
Ferdinando
F
Verze
Paolo
P
Vitale
Dino F
DF
Sorrentino
Raffaella
R
Cirino
Giuseppe
G
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D010919:Placebos; D015203:Reproducibility of Results; D013450:Sulfones / Q000008:administration & dosage; D014227:Triazines / Q000008:administration & dosage; D000069058:Vardenafil Dihydrochloride; D055815:Young Adult
D015415:Biomarkers; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D010919:Placebos; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP