BACKGROUND: AIM: METHODS: 12 male Wistar rats were assigned to each of 5 groups (group C: control; group R: radiation; group RPT: radiation, testosterone, and a PDE5I; group RP: radiation and a PDE5I; and group RT: radiation and testosterone). A 12.5 Gy/fraction dose was administered to the rectum in groups R, RPT, RP, and RT. Udenafil (20 mg/kg) was administered daily via nasogastric tubes in group RPT and group RP for 4 weeks starting 1 day after radiotherapy. Testosterone enanthate (25 mg/kg, IM) was administered immediately after radiotherapy in group RT and group RPT. 6 rats from each group were used to evaluate endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and NOX2, and cavernosal pressure was evaluated in the other 6 rats in each group. OUTCOME: RESULTS: eNOS mRNA expression increased in response to either testosterone replacement or PDE5I administration after radiotherapy. nNOS mRNA expression did not significantly increase in response to testosterone replacement, but testosterone significantly enhanced the effect of PDE5I on nNOS mRNA expression. Testosterone significantly amplified the effect of PDE5I on both eNOS and nNOS protein expression. Both testosterone and PDE5I reduced NOX2 protein expression. The intracavernosal pressure during electrical stimulation showed that testosterone alone did not significantly enhance erectile function. CLINICAL TRANSLATION: Clinicians should consider both hypoxic tissue damage and hypogonadism during and after radiation, and the combination of testosterone and PDE5I could be more beneficial for preserving erectile tissue than either individual treatment. STRENGTHS & LIMITATIONS: CONCLUSIONS:
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