输精管阻断术的远期安全性

2015-01-27 06:30刘小章岳焕勋
中国计划生育学杂志 2015年9期
关键词:输精管队列病死率

刘小章 岳焕勋

1.成都中医药大学,四川省人口和计划生育科研所(610041);2.四川大学华西第二医院

根据联合国人口署最新发布的全球避孕模式,近20%的已婚或同居育龄避孕妇女实施了绝育术,其中18.9%采用输卵管阻断,2.4%采用输精管阻断[1]。尽管输精管阻断术在安全性、有效性及费用方面比女性同类手术更优越,使用的第三年其成本效益为所有避孕方法之首[2-4],但应用却远低于女性手术。全球男、女绝育手术比例约为1∶8,发达地区为1∶1.6(5.3:8.4),发展中地区则高达1∶10.8(1.9∶20.6)[1]。缺乏男性的参与导致妇女承担了过多的生殖和避孕负担[5-6]。对手术的误解及安全性的担忧在一定程度上影响了输精管阻断术的可接受性。本文旨在阐述当前对该手术远期安全性的理解。

1 总发病率及病死率

对输精管阻断术后男子远期发病率和病死率已有广泛研究[7]。一项对10 000多名行输精管阻断男子与同等数量对照的回顾性队列研究显示,98种疾病,包括各类癌症、自身免疫性疾病、心脏疾病等的发病率,受术者与对照男子相似,病死率低于对照男子,肿瘤病死率仅为对照的50%[8]。另一大样本回顾性队列研究同样显示癌症总病死率无增高,但观察到术后>20年者肺癌死亡风险增加[9]。然而,如结肠或直肠癌、肾癌死亡风险降低,肺癌死亡风险增加可能仅为一种巧合[10]。国内进行的回顾性队列研究也显示输精管阻断男子总病死率降低,但死亡原因不确定[11]。这些观察结果与其他研究报告[10,12-17]的发病率无增加相一致。唯一证实的相关风险是术后近期(2年内)受术者罹患泌尿生殖道感染或炎症的风险是非受术者的1.5~2.5倍[16-18]。另外,少数男子术后发生单侧或双侧慢性阴囊或睾丸疼痛或不适,可持续数月至数年[3]。欧洲泌尿学会(EAU)将这种慢性疼痛视为一种特殊类型的阴囊疼痛综合征,定义为持续或间歇发作局限于阴囊内器官的疼痛,常伴有负面的认知、行为、性或情绪改变,及提示下尿路和性功能障碍的症状,未证实存在感染或其他明显局部病变[19]。慢性阴囊疼痛的发生风险为1%~2%[19-21],应在术前告知[3,19-22]。

2 抗精子抗体

几乎所有被研究的哺乳动物和50%~70%的男子在输精管阻断术后发生循环抗精子抗体(ASAb),可持续多年。约4%男子可检测到精浆ASAb,精浆ASAb更常见于输精管复通术后和循环ASAb阳性者[16,20]。未做输精管阻断手术男子中约2%~8%也见有ASAb,常见于精道梗阻、手术、感染或先天性异常。循环免疫复合物(CIC)在术后亦见增加,但在术后三个月逐渐消失。对精子的抗体反应是否会影响人体免疫系统并增加自身免疫疾病或动脉硬化风险的担忧引发了长达10年的研究。不过,迄今为止不论是在发达国家还是发展中国家进行的大样本队列及病例对照研究均未发现ASAb的产生会增加人远期免疫相关疾病的风险,包括哮喘、糖尿病、强直性脊柱炎、甲亢、多发性硬化症、重症肌无力、炎性肠病、类风湿性关节炎、睾丸及肾脏改变,也未证实输精管阻断与人动脉硬化有任何关系[8,11,13,16,18,23-25],伴有冠心病(CHD)风险因素的男子(如高龄、吸烟、胆固醇升高、高血压、家族史)也不例外。鉴于现有证据表明输精管阻断不是CHD的危险因素,美国泌尿学会(AUA)认为术前咨询无需涉及该内容[20]。

输精管阻断术后循环ASAb的临床意义仍不明确,其重要性可能是降低输精管复通术后成功妊娠的几率[10,26-27]。不过,仅有抗体的存在尚不足以诊断精子自身免疫[28]。ASAb是男性生育力低下的罕见原因[29],即使是最严格的研究也未能证实ASAb与生育损伤之间存在因果关系。ASAb检测方法、有意义的水平以及对ASAb阳性的处置亦未获得广泛共识[16,30]。约3%~6%的受术者术后因各种原因要求输精管复通[31]。随着显微外科重建技术的发展,输精管吻合和输精管附睾吻合的复通率和妊娠率已分别达到70~99.5%/36~92%和30~90%/20~50%[32]。鉴于术后总体妊娠率相对较高,ASAb存在与否与术后生育力恢复关系并不密切,术前检测ASAb的价值未被肯定[33-34]。AUA也不认为血清ASAb存在是输精管复通术的障碍[20]。

3 前列腺癌

1990年美国两项以医院为基础的病例对照研究分别报告输精管阻断术后男子发生前列腺癌的风险显著升高(RR5.3,95%CI=2.7,10.0)[35]和非显著性中度增高(RR2.2,95%CI=1.0,4.6)[36]。1993年 Giovannucci等[37-38]的大样本回顾性和即时性队列研究(HPFS)报告,输精管阻断术与前列腺癌有阳性关联(RR1.66,95%CI=1.25,2.21),且相对风险随输精管阻断年限而增高(≥20年RR1.85,95%CI=1.26,2.72),认为是对因果关联的支 持。2014 年 Siddiqui 等[39]对 同 一 队 列(HPFS)24年随访数据的分析发现,受术男子发生高分级前列腺癌(RR1.22,95%CI=1.03,1.45)和致死性前列腺癌(RR1.19,95%CI=1.00,1.43)风险增高,定期接受前列腺癌抗原筛查的亚组致死性前列腺癌风险更高(RR1.56,95%CI= 1.03,2.36),关联不受性激素水平、性传播感染以及癌症治疗的影响,也与输精管阻断年限无关。不过,这些研究数据被认为存在方法学缺陷、偏倚(检测、误分类或发表偏倚)及混杂[40-48]。研究结果也未得到其他病例对照研究[49-59]和队列研究[25,60-64]的支持。尤其是来自新西兰的研究[54-55],新西兰的输精管阻断术应用率为全球最高(40~49岁男性中57%接受了该手术)并有国家肿瘤登记,其研究结果显示前列腺癌既与输精管阻断手术无关联(RR0.92,95%CI=0.75,1.14),也与输精管阻断年限无关联(≥25年 RR0.92,95%CI= 0.68,1.23),且受术男子发生高分级前列腺癌(T4期)的风险较T1期(RR0.87,95%CI=0.61,1.25)进一步降低(RR 0.53,95%CI= 0.21,1.41),但差异没有统计学意义。

也有文献对输精管阻断与前列腺癌的关联进行系统评价研究。近期发表的队列研究文献荟萃分析[65],纳入发表于1991~2014年的10篇队列研究,包括429 914名参与者和7027例前列腺癌病例,结果显示输精管阻断与前列腺癌风险无明显相关(合并 RR1.11,95%CI=0.98,1.27)。较早DerSimonian等[42]、Bernal-Delgado等[43]及 Dennis等[66]发表的荟萃分析分别报告合并RR估值1.5(95%CI =1.0,2.2)、1.23(95%CI =1.01,1.49)、1.37(95%CI=1.15,1.62),并都注意到研究间存在显著的异质性,RR估值随研究设计、研究人群不同而不同,提示高风险的选择偏倚。

对研究人群多重比较的观察性研究可能导致随机的错误结论[67]。如一篇病例对照研究报告的输精管阻断与前列腺癌的强相关[35]被同一作者基于同一监测系统补充数据的第二篇病例对照研究[49]否定。这类研究抑或可以证明关联,但非因果关系[68]。Grimes等[69]指出观察性流行病学的识别能力不能满足对弱关联的评价。一般情况下,除非队列研究中RRs超过2~3或病例对照研究中ORs超过3~4,研究发现的关联不应被视为可信。由于前列腺癌的病因尚不清楚,某些未知因素导致的混杂可能影响与输精管阻断的关联,因此对病例对照或队列研究所显示的RRs轻度升高需要谨慎解释[55]。

世界卫生组织(WHO)[70](1991)和美国国立卫生院(NIH)(1993)[41]曾就前列腺癌与输精管阻断术安全性的生物学和流行病学证据进行审查,鉴于研究发现的不一致,报告的关联微弱,无已知的生物学机制,WHO和NIH否定了输精管阻断与前列腺癌之间存在因果关系,并建议不改变有关输精管阻断术的临床及公共卫生实践。现有证据继续支持输精管阻断术是一种安全、高效的重要节育措施。当男、女绝育手术都可以接受时,前者是一个更好的选择。

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