テストステロン補充療法は抗炎症作用を介して抗がん剤ドキソルビシンに伴う性機能障害を改善させる

抄録

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.