Objectives: The anti-cancer drug doxorubicin (DOX) can induce erectile dysfunction (ED) and decrease testosterone levels. We investigated the effect of testosterone replacement therapy (TRT) on ED by DOX.
Methods: Twelve-week-old male Wistar-ST rats were untreated (Control) or administered DOX (3 mg/kg i.v. weekly for 4 weeks) in DOX and DOX+T groups. Testosterone undecanoate (25 mg/kg s.c.) was administered in the DOX+T group. Erectile and endothelial functions were measured using intracavernosal pressure (ICP) and isometric tension. Expressions of inflammation and oxidative stress markers (NADPH oxidase-1, IL-6) were assessed via quantitative PCR.
Results: ICP/MAP ratio in the DOX group (0.32 ± 0.03) was significantly decreased compared to the Control group (0.72 ± 0.05). The ratio was significantly increased in the DOX+T group (0.61 ± 0.07). Acetylcholine reactivity was significantly lower in DOX group than in Control group (35.0 ± 5.1% vs 77.6 ± 7.9%) and was higher in DOX+T group (69.8 ± 8.5%). NADPH oxidase-1 and IL-6 mRNA expressions were higher in DOX group and lower in DOX+T group.
Conclusion: TRT in rats may improve ED induced by DOX. This is likely because TRT improved vascular endothelial function by suppressing inflammatory response. TRT may be a treatment option for symptoms of androgen deficiency following anticancer drug therapy.