McMahon Chris G, McMahon Chelsea N, Leow Liang Joo, Winestock Christopher G
Australian Centre for Sexual Health, Suite 2-4, Berry Road Medical Centre, 1a Berry Road, St. Leonards, NSW, Australia 2065.
BJU Int. 2006 Aug;98(2):259-72. doi: 10.1111/j.1464-410X.2006.06290.x.
This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.
本综述探讨了一氧化氮（NO）作为一种神经递质在射精的中枢和外周控制中的作用、5型磷酸二酯酶抑制剂（PDE5I）药物治疗早泄（PE）的研究方法、这些方法与当代理想PE药物试验设计共识的契合度、方法对治疗结果的影响以及PDE5I在PE治疗中的作用。NO/cGMP转导参与了射精的中枢和外周控制，但PDE5I对射精有直接中枢或外周作用的证据尚属推测。所综述的14项研究中有13项未达到理想PE药物试验设计的循证医学标准。这些研究的局限性包括研究人群定义不充分、缺乏双盲安慰剂对照研究设计，以及缺乏一致的客观生理指标或敏感、经过验证的结局评估工具作为研究终点。PDE5I、按需服用的选择性5-羟色胺再摄取抑制剂（SSRI）药物以及联合使用的PDE5I/按需服用的SSRI所报告的阴道内射精潜伏期（IELT）增加倍数范围广泛，证明了方法存在缺陷的研究所得出的数据和结论不可靠。唯一一项符合理想临床试验设计循证医学标准的研究报告称，西地那非治疗未能显著增加基线IELT，这支持了我们的结论，即没有令人信服的证据支持PDE5I在治疗具有终身PE和正常勃起功能的男性中发挥任何作用。然而，仅有有限的证据支持PDE5I单独或与每日或按需服用的SSRI联合使用在治疗合并勃起功能障碍的男性获得性PE中可能发挥的作用。需要开展进一步遵循当代理想临床试验设计共识的对照研究，以阐明PDE5I在这一获得性PE男性亚组中的作用。
Zotero 插件