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Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding

  • Review
  • Intervention

Authors


Abstract

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.

Objectives

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.

Search 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.

Selection criteria

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.

Data collection and analysis

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.

Main 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.

Authors' 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.

摘要

背景

針對月經量過多的子宮內膜去除手術的術前內膜打薄用藥

對於停經之前的婦女們而言,在許多必須要去找婦科醫生求診的理由之中,經血過多就是其中1種最常見的因素。雖然藥物療法通常都是首要的措施,但是很多婦女們最終還是需要或是會要求進行子宮切除術。子宮切除必定會有一段的住院時間,而且還需要一陣子的恢復期,所以這樣的治療方式就顯得令人退卻,對於很多婦女們來說,更會覺得沒有必要去接受這樣的侵入性治療選項。子宮鏡的子宮內膜破壞或是切除術,以及像是氣球或是微波切除術之類的更近期之「第2代」設備,對於這些婦女們而言,提供了除子宮切除之外可以當天完成的手術選擇。跟子宮切除術比較起來,它們還能夠算是價格更為低廉的程序。將子宮內膜完全清除或是去除,對於治療成功而言,是其中1項最重要的決定因素。因此,假使要採取這樣的手術,那麼當子宮內膜的厚度低於4毫米,通常要在月經剛結束時進行,將會是最有效的。然而,要在這樣的時間點上妥善地安排手術,通常會遇到許多困難。另外還有可供選擇的方法,就是使用荷爾蒙類的藥物,讓子宮內膜能夠變薄,或是在手術之前自行萎縮。到目前為止,最常受到評估的藥物為 goserelin(某種GnRH的類似物)與danazol。針對黃體酮類的藥物與其他種GnRH的類似物,雖然目前可以取得的資料並不多,但是都已經有人加以研究過。在使用這些藥物的時候,尤其是針對GnRH的類似物而言,人們認為將會因此而縮短操作時間、改善子宮內的操作環境,並且降低膨脹介質的吸收(這是在手術期間為了擴張子宮容積時所使用的流體)。在長期的結果方面,它們也可能會帶來某種較大幅度的改善,其中包括了月經時的血液流失量,以及經痛的現象。

目標

因經血量過多而接受內膜去除術,探討在術前使用釋放促性腺激素荷爾蒙(GnRH)的類似物、danazol,以及黃體酮類等藥,以用來改善子宮內部的操作環境與手術之後的治療結果。

搜尋策略

採用Menstrual Disorders以及Subfertility Group搜尋策略 (請參閱Review Group詳細資料) 以找出採用隨機對照試驗將這三種藥物相互比較,或是與其他藥物、安慰劑、或是未在手術前治療進行比較。並在2001 – 2002年更新搜尋以找出新的試驗

選擇標準

假使有某些試驗針對相關的手術內部以及手術後的治療結果,而將這些藥物之間相互進行了比較,或是將藥物與安慰劑或是不進行治療之間進行比較,那麼它們就會被收集在內。在本篇回顧之中,只有隨機型的研究會被收集在內。

資料收集與分析

共有12份研究符合了收集的標準。共有5份研究將 goserelin(某種GnRH的類似物)與不採取治療或是安慰劑之間進行了比較,還有1份研究是將 decapeptyl(某種GnRH的類似物)與不採取治療之間進行了比較。有3份研究將 goserelin與danazol之間進行了比較。有2份研究將黃體酮類、danazol與triptorelin或是鼻腔噴霧劑的 nafarelin(這2者都是GnRH的類似物),與不採取治療之間進行的比較。在氣球燒灼術之後,只有1份將triptorelin與不採取治療之間進行了比較的研究,曾經評估過這些結果,而且沒有發現到有任何研究曾經在其他種的第2代氣球燒灼技術之前,曾經對子宮內膜的打薄藥物加以評估。有1份研究曾經評估過黃體酮類與不採取治療之間進行比較之後的影響。有2位審稿者獨立地擷取出這些資料。第3位審稿者則是為了正確性而檢查了資料擷取的工作,並且會在相關資料遺失或是不清楚的時候,寫信給這些作者。操作內部的因素包含了子宮內膜的厚度、手術的時間長度、手術的難易程度、膨脹介質的吸收,以及病發症的發生率。手術後的結果則包含了發生閉經的婦女比例、手術後的月經血液流失量與經痛現象,以及是否有對於後續手術的需求。對於副作用方面的資料也會被記錄下來。

主要結論

在進行子宮鏡內膜切除術或是燒灼術後12個月內,當我們跟不採取治療來當作比較,GnRH的類似物可以帶來較為短暫的手術時間、較容易進行的手術操作,以及較高比率的手術後閉經現象。至於手術後的經痛狀況,看起來也減輕了。使用GnRH的類似物之後,對於術中發症發生比率方面並不會產生影響,而且不論使用了任何1種手術前的子宮內膜打薄藥物,病患對這樣的手術都會有相當高的滿意程度。跟danazol比較起來,GnRH的類似物會讓子宮內膜萎縮的情況更加穩定。對於其他的術中與手術後狀況而言,任何的差異都達到了最小的程度,而且只有在其中1份小型研究當中的術前GnRH前使用,會認為並沒有任何優點,至於這份小型研究中的婦女則曾經使用了氣球(第2代的燒灼術)。在這些婦女們當中,雖然只有少數幾份研究曾經詳細地提出過報告,但確實有很高的比例會因為使用了GnRH的類似物與danazol而產生副作用。若是要用黃體酮類藥物來當作子宮內膜的打薄藥物,那麼手邊僅有少數的隨機化資料可以用來評估它們的功效。以更為長期的結果方面來看,所有的打薄藥物都很難確定會產生什麼影響,但是關於子宮內膜打薄藥物有什麼優點的報告,像是手術後的閉經現象等等,看起來卻隨著時間而逐漸減少。

作者結論

對於月經血量過多而言,若是在月經週期的初期增生階段就進行子宮鏡手術,而且在手術之前就將子宮內膜打薄的話,將可以提升外科醫生在操作手術時的條件,並改善短期的手術後狀況。雖然說這2類藥物都可以提供讓人滿意的結果,但是跟 danazol比較起來,釋放促性腺激素荷爾蒙的類似物在讓子宮內膜打薄的時候,會顯得更為穩定。以更為長期的手術後結果來看,像是閉經以及對於後續之手術性醫療介入行為方面的需求,這些藥物會帶來的影響會隨著時間而逐漸減少。

翻譯人

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

NA

Plain language summary

Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding

Menorrhagia (heavy menstrual bleeding) is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Endometrial thinning before to hysteroscopic surgery improves both the operating conditions for the surgeon and short term benefits after surgery. 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.

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