造成女性尿道综合征的原因中既具有刺激因素，又具有感染因素，可以是机械性、化学性或过敏性等因素的作用，甚至还与尿道或周围的某些影响休戚相关，所以是一种错综复杂的综合因素在作怪。
1.泌尿系统感染：
患者尿道口组织的病理改变均为慢性炎症反应，多数患者尿培养可能阳性，46%为大肠埃希菌，18%为衣原体，厌氧菌培养可增加阳性发现，32%患者病因不确切。
2.尿道外口解剖异常：
如尿道处女膜融合，处女膜伞，小阴唇融合等，有报道，尿道外口至阴道口距离与尿道综合征关系密切，间距越近患病率越高，间距在3mm以下者患病率达72.15%。
3.尿道梗阻：
如膀胱颈梗阻，尿道远端周围组织纤维化或括约肌痉挛导致远端尿道缩窄。
4.神经功能异常：
损伤，感染，X线照射等引起尿道内纤维组织增生，使神经发生异常反射。
5.心理因素：
如紧张焦虑，多疑及内向等心理状态是尿道综合征的易感因素。
6.其他：
如免疫因素，雌激素水平下降，镁离子缺乏，医源性因素等。平时常穿紧身尼龙内裤的女性，由于外阴部透气性和吸湿性不好，以及运动时外阴与尼龙裤产生摩擦，同样会刺激局部而引起尿道综合征。此外，情绪波动，如生气、悲伤、急躁等，也可诱发或加重尿道综合征。
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