Department of Urology, Ankara Numune Education and Research Hospital, Ankara, Turkey.
J Sex Med. 2012 Jul;9(7):1773-81. doi: 10.1111/j.1743-6109.2012.02759.x. Epub 2012 May 8.
The association of 5-alpha reductase inhibitor (5ARI) therapy and sexual dysfunction has been reported. Some patients claim persistent erectile dysfunction despite long-term discontinuation of 5ARI treatment. The aim of this study was to assess erectile function after cessation of 5ARI therapy using a rat model.
Twenty-six adult male Sprague-Dawley rats were randomized into three groups: (i) control (N = 10); (ii) 8-week dutasteride treatment (0.5 mg/rat/day, in drinking water, N = 8); and (iii) 6-week dutasteride treatment followed by a 2-week washout period (N = 8). The experiments were performed after 8 weeks from the initiation of treatment in all groups. In vivo erectile activity and in vitro contractile and relaxant responses of cavernosal smooth muscle were investigated.
In vivo erectile activity (intracavernosal pressure [ICP]/mean arterial pressure [MAP] and total ICP) in treatment groups were significantly decreased compared with controls (ICP/MAP: P < 0.001 for 2.5 v, 5 v, and 7.5 v; total ICP: P < 0.001 for 5 v and P < 0.01 for 7.5 v). Acetylcholine-induced relaxations were diminished in treatment groups (P < 0.05). Relaxant responses to electrical field stimulation (EFS) were decreased in the 8-week treatment group (P < 0.05) but were similar to controls in the washout group. Sodium nitroprusside (SNP)-induced endothelium-independent relaxations were reduced in the 8-week dutasteride treatment group (P < 0.01), while these responses were restored in the washout group. The contractile responses to the alpha1-adrenergic agonist phenylephrine were decreased in treatment groups compared with controls (P < 0.01). Direct neurogenic contractile responses in the dutasteride groups were significantly lower than controls between 1 and 15 Hz frequencies (but not at 20 Hz) and washout partially restored the responses at 10 and 15 Hz.
Discontinuation of dutasteride improved the relaxant responses to EFS and SNP, while cholinergic and adrenergic responses remained depressed. Our findings suggest a time-dependent detriment of dutasteride on erectile function. The withdrawal/washout effect of 5ARIs on parameters of human sexual function warrants further investigation.
已有报道称 5-α 还原酶抑制剂（5ARI）治疗与性功能障碍有关。一些患者在长期停止 5ARI 治疗后仍持续存在勃起功能障碍。本研究旨在通过大鼠模型评估停止 5ARI 治疗后的勃起功能。
26 只成年雄性 Sprague-Dawley 大鼠随机分为三组：（i）对照组（N=10）；（ii）8 周度他雄胺治疗组（0.5mg/大鼠/天，溶于饮用水中，N=8）；和（iii）6 周度他雄胺治疗后 2 周洗脱期组（N=8）。所有组在治疗开始后 8 周进行实验。研究了海绵体平滑肌的体内勃起活性和体外收缩及舒张反应。
与对照组相比，治疗组的体内勃起活性（海绵体内压[ICP]/平均动脉压[MAP]和总 ICP）显著降低（ICP/MAP：2.5v、5v 和 7.5v 时 P<0.001；总 ICP：5v 时 P<0.001，7.5v 时 P<0.01）。乙酰胆碱诱导的舒张反应在治疗组减弱（P<0.05）。电刺激（EFS）诱导的舒张反应在 8 周治疗组降低（P<0.05），但在洗脱组与对照组相似。8 周度他雄胺治疗组硝普钠（SNP）诱导的非内皮依赖性舒张反应降低（P<0.01），而在洗脱组恢复。与对照组相比，治疗组对α1-肾上腺素能激动剂苯肾上腺素的收缩反应降低（P<0.01）。度他雄胺组的直接神经源性收缩反应在 1-15Hz 频率下显著低于对照组（但在 20Hz 时没有），洗脱部分恢复了 10 和 15Hz 时的反应。
停止度他雄胺治疗可改善 EFS 和 SNP 的舒张反应，而胆碱能和肾上腺素能反应仍受抑制。我们的研究结果表明，度他雄胺对勃起功能的损害具有时间依赖性。5ARI 对人类性功能参数的停药/洗脱作用值得进一步研究。
