Theophylline as a cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor (cAMP-PDEI) elevates cAMP levels. We aimed to evaluate the therapeutic effect and toxicity of theophylline on the sperm parameters, oxidative stress (OS), and inflammation in asthenoteratozoospermic men. Sixty asthenoteratozoospermic patients were divided into groups of placebo and theophylline (200mg/day). After 3 months of oral treatment, sperm parameters, viability, and DNA fragmentation were analyzed by the CASA system, eosin nigrosin staining, sperm DNA fragmentation kit, respectively. The seminal plasma level of reactive oxygen species (ROS) of neat semen samples, malondialdehyde (MDA), total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-a), and interleukin-10 (IL-10) was assessed. Data were analyzed statistically using the independent samples t-test and the paired t-test and the means were considered significantly different at p<0.05. Sperm motility, viability, and the number of sperms with normal morphology and the seminal plasma level of TAC and IL-10 and also sperm DNA fragmentation increased significantly in the theophylline group compared to the placebo. The MDA, TNF-a, and ROS levels decreased significantly in the theophylline group compared to the placebo. Theophylline improved sperm parameters, reduced OS and inflammation, but also created genotoxicity and increased sperm DNA fragmentation. Therefore, to benefit from the desired effects of theophylline and inhibit the toxicity of it in the treatment of men with asthenoteratozoospermia, it is suggested to be used simultaneously with another antioxidant to protect sperm DNA from fragmentation.
