The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study

PURPOSE:To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency. METHODS:Fifty rats were randomly divided into 5 groups (group-1: sham group-placebo, group-2: bilateral orchiectomy (ORX), group-3: bilateral ORX+tadalafil, group-4: bilateral ORX+testosterone, group-5: bilateral ORX+tadalafil+testosterone). Group-3 received tadalafil (5mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100mg/kg i.m., single dose). Group-5 was administered a combination of tadalafil and testosterone undecanoate. All groups were compared with regard to serum nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels. RESULTS:Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (p=.001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (p=.001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values. CONCLUSIONS:The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.