Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids

A Lethaby, B Vollenhoven, M Sowter
Cochrane Database of Systematic Reviews 2001, (2): 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made to identify published trials from citation lists of review articles and direct contact with drug companies for unpublished trials.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.

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