Lethaby A, Vollenhoven B, Sowter M
Department of Obstetrics and Gynaecology, University of Auckland, 2nd Floor, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand.
Cochrane Database Syst Rev. 2001(2):CD000547. doi: 10.1002/14651858.CD000547.
BACKGROUND: Uterine fibroids, smooth muscle tumours of the uterus, are found in at least 25 to 35% of women over the age of 35 years. Although some of these tumours are asymptomatic, up to 50% cause symptoms severe enough to warrant therapy and surgery is the standard treatment. Fibroid growth is stimulated by oestrogen and gonadotropin releasing hormone agonists (GnRHa) which induce a state of hypoestrogenism have been investigated as a potential treatment. GnRHa treatment causes fibroids to shrink but cannot be used long term because of unacceptable symptoms and bone loss. Therefore, GnRHa may be useful pre-operatively both to reduce fibroid and uterine volume and control bleeding. OBJECTIVES: The objective of this review is to evaluate the role of pre-treatment with gonadotropin releasing hormone (GnRH) analogues prior to a major surgical procedure, either hysterectomy or myomectomy, for uterine fibroids. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, the National Research Register, the National Library of Medicine's Clinical Trials Register and Current Contents were performed. Attempts were also made to identify published trials from citation lists of review articles and direct contact with drug companies for unpublished trials. In most cases, the first author of each included trial was contacted for additional information. The search was updated in October 2000. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of GnRH analogue treatment versus placebo, no treatment, or other medical therapy prior to surgery, either myomectomy or hysterectomy, for uterine fibroids. DATA COLLECTION AND ANALYSIS: Twenty-six RCTs were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of fourteen trials where GnRH analogue treatment was compared with no pre-treatment and six trials where GnRH analogue treatment was compared with placebo. Three trials are awaiting assessment because the data were not in a suitable form for extraction or they are awaiting translation. Two trials have been excluded because the data were not in a suitable form for extraction and the authors were not able to provide additional information. One RCT compared GnRHa pre-treatment with lynestrenol pre-treatment. Results from pre-operative outcomes were combined for both types of surgery but results from intra- and post-operative outcomes were reported separately for myomectomy and hysterectomy. Subgroup analysis was performed according to type of control group, no pre-treatment or placebo, and for some outcomes there were additional subgroup analyses according to size of the uterus in gestational weeks. MAIN RESULTS: Pre- and post-operative haemoglobin (Hb) and haematocrit (HCT) were significantly improved by GnRH analogue therapy prior to surgery, and uterine volume, uterine gestational size and fibroid volume were all reduced. Pelvic symptoms were also reduced but some adverse events were more likely during GnRH analogue therapy. Hysterectomy appeared to be easier after pre-treatment with GnRH analogue therapy; there was reduced operating time and a greater proportion of hysterectomy patients were able to have a vaginal rather than an abdominal procedure. Duration of hospital stay was also reduced. Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy. Evidence of increased risk of fibroid recurrence after GnRH analogue pre-treatment in myomectomy patients was equivocal and few data were available to assess change in post-operative fertility. Lynestrenol did not offer any advantage over GnRH analogue therapy before fibroid surgery. The increased costs associated with GnRH analogue therapy were not assessed. REVIEWER'S CONCLUSIONS: The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a mid-line incision is planned, this can be avoided in many women with the use of GnRH analogues. For patients undergoing hysterectomy, a vaginal procedure is more likely following the use of these agents.
背景:子宫肌瘤是子宫的平滑肌肿瘤,在35岁以上的女性中,至少25%至35%的人患有此病。虽然其中一些肿瘤无症状,但高达50%的患者会出现严重到需要治疗的症状,手术是标准治疗方法。雌激素和促性腺激素释放激素激动剂(GnRHa)刺激肌瘤生长,诱导低雌激素状态的GnRHa已被作为一种潜在治疗方法进行研究。GnRHa治疗可使肌瘤缩小,但由于不可接受的症状和骨质流失,不能长期使用。因此,GnRHa在术前可能有助于减少肌瘤和子宫体积并控制出血。 目的:本综述的目的是评估在子宫肌瘤的子宫切除术或肌瘤切除术等大型手术前,使用促性腺激素释放激素(GnRH)类似物进行预处理的作用。 检索策略:对Cochrane月经紊乱和生育力低下小组试验注册库、MEDLINE、EMBASE、国家研究注册库、美国国立医学图书馆临床试验注册库和《现刊目次》进行了相关随机对照试验的电子检索。还试图从综述文章的引用列表中识别已发表的试验,并直接联系制药公司获取未发表的试验。在大多数情况下,会联系每个纳入试验的第一作者以获取更多信息。检索于2000年10月更新。 入选标准:入选标准为GnRH类似物治疗与安慰剂、无治疗或肌瘤切除术或子宫切除术等手术前的其他药物治疗的随机对照比较。 数据收集与分析:确定了26项符合本综述纳入标准的随机对照试验。综述作者独立提取数据,并根据14项将GnRH类似物治疗与未预处理进行比较的试验数据以及6项将GnRH类似物治疗与安慰剂进行比较的试验数据,估计二分结果的比值比和连续结果的加权平均差。3项试验正在等待评估,因为数据形式不适合提取或正在等待翻译。2项试验被排除,因为数据形式不适合提取且作者无法提供更多信息。一项随机对照试验将GnRHa预处理与炔诺酮预处理进行了比较。两种手术的术前结果合并报告,但肌瘤切除术和子宫切除术的术中和术后结果分别报告。根据对照组类型(未预处理或安慰剂)进行亚组分析,对于某些结果,还根据孕周的子宫大小进行了额外的亚组分析。 主要结果:术前使用GnRH类似物治疗可显著改善术前和术后的血红蛋白(Hb)和血细胞比容(HCT),子宫体积、子宫孕周大小和肌瘤体积均减小。盆腔症状也有所减轻,但GnRH类似物治疗期间某些不良事件更有可能发生。GnRH类似物治疗预处理后子宫切除术似乎更容易;手术时间缩短,更多子宫切除术患者能够进行阴道而非腹部手术。住院时间也缩短了。肌瘤切除术和子宫切除术的失血量和垂直切口率均降低。肌瘤切除术患者GnRH类似物预处理后肌瘤复发风险增加的证据不明确,且几乎没有数据可用于评估术后生育能力的变化。炔诺酮在肌瘤手术前未显示出优于GnRH类似物治疗的优势。未评估与GnRH类似物治疗相关的成本增加。 综述作者结论:在肌瘤手术前使用GnRH类似物3至4个月可减少子宫体积和肌瘤大小。它们有助于纠正术前存在的缺铁性贫血,并减少术中失血量。如果子宫大小需要计划进行中线切口,使用GnRH类似物可使许多女性避免这种情况。对于接受子宫切除术的患者,使用这些药物后更有可能进行阴道手术。
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