(465) Effect of Anticancer Agents on Erectile Function in Juvenile Rats

Abstract Introduction Several cancer chemotherapeutic agents are administered to patients with cancer worldwide. Our previous report on the analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database revealed that five anticancer agents (melphalan; L-PAM, methotrexate; MTX, vincristine; VCR, docetaxel; DTX, and doxorubicin; DOX) were proven risk factors for erectile dysfunction (ED). Furthermore, administering these anticancer agents to sexually mature rats reduced their erectile function. Objective To investigate the effect of anticancer agents on erectile function in juvenile rats. Methods Four-week-old male Wistar ST rats were divided into Control, L-PAM, MTX, VCR, DTX, and DOX treatment groups. L-PAM (3 mg/kg, intravenous, i.v.) and MTX (20 mg/kg, intraperitoneal, i.p.) were injected on day 1. VCR (0.1 mg/kg, i.v.), DTX (5 mg/kg, i.v.), DOX (3 mg/kg, i.v.), and saline (Control, i.v.) were injected on days 1, 8, 15, and 22, respectively. Erectile function was measured following one-, two-, and four-week treatment periods. In the Control, VCR, DTX, and DOX groups, erectile function was also evaluated after four weeks of treatment and a subsequent 4, 8, and 12-week rest period without any treatments. Furthermore, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve. Results After a one-week observation period, the ICP/MAP ratio in the L-PAM group (0.39±0.08) decreased significantly compared to that in the Control group (0.60±0.03) (P<0.01); however, no change was observed in the MTX group (0.59±0.06). The ICP/MAP ratio in the L-PAM group at week 4 (0.66±0.05) increased significantly compared to that at week 1. However, after the four-week observation period, the ICP/MAP ratio in the VCR (0.46±0.04), DTX (0.28±0.01), and DOX (0.38±0.03) groups was significantly decreased compared to that in the Control group (0.66±0.05) (P<0.05). The ICP/MAP ratio in the VCR (0.55±0.05) group after a 12-week rest was decreased compared to that in the Control group (0.68±0.03) (P=0.06). Furthermore, these ratios in the DTX (0.26±0.02) and DOX (0.36±0.02) groups significantly decreased compared to that in the Control group (P<0.01). Conclusions In conclusion, ICP measurements revealed that the four anticancer drugs (L-PAM, VCR, DTX, and DOX) significantly reduced erectile function in juvenile rats. Furthermore, in the VCR, DTX, and DOX groups, the erectile function of rats remained compromised 12 weeks post-drug administration. Notably, VCR and DOX are general-purpose anticancer agents for treating leukemia in children, underscoring the requirement for long-term monitoring of the erectile function in cancer survivors. Thus, monitoring the dose and the possibility of recovery after administering anticancer agents is vital, especially considering the risk of developing ED as a side effect. Disclosure No