Antioxidant treatment associated with sildenafil reduces monocyte activation and markers of endothelial damage in patients with diabetic erectile dysfunction: a double-blind, placebo-controlled study.
OBJECTIVE
To investigate the synergic effect of propionyl L-carnitine (PLC) plus sildenafil in reducing monocyte oxidative activity and endothelial dysfunction markers in diabetic patients with erectile dysfunction (ED).


METHODS
Thirty-two type 2 diabetic patients with ED (according to the International Index of Erectile Function-5 [IIEF-5]) were randomized to receive PLC (2 g/d) alone (n=8) or combined with sildenafil (50 mg/d twice weekly) (n=8), sildenafil alone (50 mg/d twice weekly) (n=8), or placebo (n=8) in a double-blind, fixed-dose study. Monocyte oxidative activity (stimulation index [SI]), intercellular adhesion molecule-1 [ICAM-1], P-selectin, advanced glycation end product (AGE) levels, Doppler sonography (recording peak systolic velocity [PSV]; end diastolic velocity [EDV]; systolic wave time [SWT]; resistive index [RI]), and IIEF score were evaluated before and after 12 wk of treatment; IIEF-5 was evaluated again 4 wk posttreatment.


RESULTS
SI was reduced by treatment with PLC alone or combined with sildenafil (p<0.05). In patients treated with PLC plus sildenafil, a decrease in ICAM-1, P-selectin, and EDV values was observed compared with patients treated with sildenafil alone (p<0.05, p<0.01, p<0.001, respectively). IIEF-5 improved in all patients treated with PLC plus sildenafil or sildenafil alone (p<0.03, p<0.05, respectively). Four weeks posttreatment, patients treated with PLC plus sildenafil maintained the improvement of the IIEF-5 compared with patients on sildenafil alone (p=0.05). In patients on PLC treatment (with or without sildenafil), SI was correlated with IIEF-5 (p<0.001), glycemia with STW (p<0.03), and AGEs with IIEF-5 (p<0.01).


CONCLUSIONS
PLC plus sildenafil was more effective in reducing SI and endothelial dysfunction markers in patients with type 2 diabetes and ED.
Morano
Susanna
S
Department of Clinical Sciences, "Sapienza" University, Rome, Italy. susanna.morano@uniroma1.it
Mandosi
Elisabetta
E
Fallarino
Mara
M
Gatti
Alessandra
A
Tiberti
Claudio
C
Sensi
Maurizio
M
Gandini
Loredana
L
Buchetti
Barbara
B
Lenti
Luisa
L
Jannini
Emmanuele Angelo
EA
Lenzi
Andrea
A
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers; D002331:Carnitine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*
D000975:Antioxidants; D015415:Biomarkers; D002331:Carnitine; D006442:Glycated Hemoglobin; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D017382:Reactive Oxygen Species; D000068677:Sildenafil Citrate; D013450:Sulfones; C003223:propionylcarnitine