Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment

CONTEXT: Endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Circulating EPC concentration is low in conditions characterized by endothelial dysfunction but their number can be increased by treatment with phosphodiesterase-5 (PDE5) inhibitors. EPCs are also reduced in hypogonadal men and testosterone (T) treatment restores their concentration. OBJECTIVE: To evaluate the relationship between the effect of PDE5 inhibitors and T on EPCs, we analysed the acute effect of vardenafil on the number of EPCs in hypogonadotrophic hypogonadal (HH) patients, before and after T treatment. DESIGN AND SETTING: A case-control study at a university andrology centre. PATIENTS: Fifteen HH subjects and 25 aged-matched controls. MAIN OUTCOME MEASURES: The number of circulating EPCs and progenitor cells (PCs) in HH patients was evaluated after acute vardenafil administration at baseline and after 6 months of T supplementation. RESULTS: At baseline, HH men had significantly lower numbers of PCs and EPCs with respect to controls and vardenafil administration had no effect on the number of these cells. After 6 months of T treatment, all HH patients were eugonadal. With respect to baseline, PCs and EPCs were significantly higher and reached the levels observed in controls. Vardenafil administration in HH men at the end of T treatment induced a significant increase in PCs and EPCs in a manner similar to that in controls. CONCLUSIONS: This study showed that normal T levels are necessary to restore the responsiveness of EPCs to PDE5 inhibitors, suggesting that T positively modulates PDE5 in bone marrow.