Department of Urology, Tulane Health Sciences Center, New Orleans, LA 70112, USA.
J Sex Med. 2011 Nov;8(11):3066-74. doi: 10.1111/j.1743-6109.2011.02425.x. Epub 2011 Aug 11.
Numerous clinical series have reported an association between 5-alpha-reductase inhibitors (5ARIs) and sexual dysfunction, but there are limited preclinical data available.
To further investigate the mechanisms of erectile dysfunction (ED) related to 5ARI therapy using a rat model.
Outcome measures include serum dihydrotestosterone (DHT), relaxant and contractile properties of cavernosal muscle, and nitric oxide synthase expression.
Twenty adult male Sprague-Dawley rats were randomized into control (N = 10) and dutasteride (0.5 mg/rat/day, in drinking water, N = 10) groups. Serum samples were obtained at baseline, from which DHT was measured after 30 days of treatment via radioimmunoassay (Beckman Coulter, Fullerton, CA, USA). Before the terminal blood draw, erectile response was measured using cavernosal nerve stimulation. The relaxant and contractile properties of cavernosal muscle strips were evaluated in tissue baths, and immunohistochemical (IHC) staining for nitric oxide synthase (NOS) and collagen deposition was performed.
Mean serum DHT was suppressed by 86.5% (range 64.2-94.8%) after 30 days of 5ARI treatment and was statistically significant (P = 0.0024). In vivo erectile response in the dutasteride treated group decreased significantly compared with control (P < 0.001). While electrical field stimulation (EFS)-induced and acetylcholine-induced relaxation was decreased, EFS-induced and phenlyephrine-induced adrenergic contraction was significantly enhanced in the dutasteride group (P < 0.01). IHC studies demonstrated increased collagen deposition in the treatment arm as well as altered expression of neuronal NOS (nNOS) and inducible NOS (iNOS).
The 5ARIs, as demonstrated in these rat cavernosal smooth muscle studies, have a detrimental effect on erectile function. Enhanced iNOS expression may protect penile smooth muscle from fibrosis. The effect of 5ARIs on human sexual function warrants further investigation.
许多临床系列报告了 5α-还原酶抑制剂（5ARIs）与性功能障碍之间的关联，但可用的临床前数据有限。
使用大鼠模型进一步研究与 5ARI 治疗相关的勃起功能障碍（ED）的机制。
观察指标包括血清二氢睾酮（DHT）、海绵体平滑肌的舒张和收缩特性以及一氧化氮合酶表达。
将 20 只成年雄性 Sprague-Dawley 大鼠随机分为对照组（N=10）和 dutasteride 组（0.5mg/大鼠/天，饮用水中，N=10）。在治疗 30 天后，通过放射免疫测定法（Beckman Coulter，Fullerton，CA，USA）从基线时获得的血清样本中测量 DHT。在终端采血前，使用海绵体神经刺激测量勃起反应。在组织浴槽中评估海绵体肌条的舒张和收缩特性，并进行一氧化氮合酶（NOS）和胶原蛋白沉积的免疫组织化学（IHC）染色。
5ARI 治疗 30 天后，平均血清 DHT 抑制率为 86.5%（范围 64.2-94.8%），具有统计学意义（P=0.0024）。与对照组相比， dutasteride 治疗组的体内勃起反应明显降低（P<0.001）。虽然电刺激（EFS）诱导的和乙酰胆碱诱导的舒张减弱，但 dutasteride 组的 EFS 诱导和苯肾上腺素诱导的肾上腺素能收缩明显增强（P<0.01）。IHC 研究表明，治疗组的胶原蛋白沉积增加，神经元型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）的表达也发生改变。
正如这些大鼠海绵体平滑肌研究所示，5ARIs 对勃起功能有不利影响。增强的 iNOS 表达可能保护阴茎平滑肌免受纤维化。5ARIs 对人类性功能的影响需要进一步研究。
