Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding.
BACKGROUND
Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many women will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection, and more recently "second generation" devices such as balloon or microwave ablation offer a day-case surgical alternative to hysterectomy for these women. They are also cheaper procedures than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than four mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery). They may also result in a greater improvement in long term outcomes such as menstrual loss and dysmenorrhoea.


OBJECTIVE
To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to endometrial destruction for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery.


METHODS
The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment. An updated search was performed in 2001-2002 to identify new trials.


METHODS
Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review.


METHODS
Twelve studies met the inclusion criteria for this review. Five studies compared goserelin (a GnRH analogue) with no treatment or placebo and one study compared decapeptyl (a GnRH analogue) with no treatment. Three studies compared goserelin with danazol. Two studies compared progestogens, danazol and triptorelin or nasal spray nafarelin (both GnRH analogues) with no treatment. Only one study comparing triptorelin with no treatment assessed outcomes after balloon ablation and no studies assessing endometrial thinning agents prior to other second generation ablation techniques were identified. One study assessed the effects of progestogens compared to no treatment. Data were extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes included the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded.


RESULTS
When compared with no treatment, GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea at 12 months with hysteroscopic resection or ablation. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues has no effect on intra-operative complication rates and patient satisfaction with this surgery is high irrespective of the use of any pre-operative endometrial thinning agent. GnRH analogues produce more consistent endometrial atrophy than danazol. For other intra-operative and post-operative outcomes, any differences are minimal and there were no benefits of GnRHa pre-treatment in the one small study where women had balloon (second generation ablation). Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Few randomised data are available to assess the effectiveness of progestogens as endometrial thinning agents. The effect of any thinning agent on longer-term results is less certain but where reported the effect of endometrial thinning agents on benefits such as post-operative amenorrhoea appears to reduce with time.


CONCLUSIONS
Endometrial thinning prior to hysteroscopic surgery in the early proliferative phase of the menstrual cycle for menorrhagia improves both the operating conditions for the surgeon and short term post-operative outcome. Gonadotrophin-releasing hormone analogues produce slightly more consistent endometrial thinning than danazol, though both agents produce satisfactory results. The effect of these agents on longer term post-operative outcomes such as amenorrhoea and the need for further surgical intervention reduces with time.
Sowter
M C
MC
Department of Obstetrics and Gynaecology, National Women's Hospital, Claude Road, Epsom, Auckland, New Zealand. martinsowter@xtra.co.nz
Lethaby
A
A
Singla
A A
AA
D003613:Danazol / Q000627:therapeutic use; D004717:Endometrium / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D015907:Hysteroscopy; D008595:Menorrhagia / Q000188:drug therapy* / Q000601:surgery; D011372:Progestins / Q000627:therapeutic use
D004965:Estrogen Antagonists; D011372:Progestins; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D003613:Danazol