Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation

 

Abstract

Background

Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or systemic disease. Anovulation may be inferred from a number of observations but, in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those who are at the extremes of reproductive life and in women known to have polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB but the regime, dose and type of progestogen used varies widely, with little consensus about the optimum treatment approach.

Objectives

To determine the effectiveness and acceptability of progestogens alone and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation.

Search methods

We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 4 May 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (1982 to May 2007), Biological Abstracts (1969 to May 2007), Current Contents (1980 to 2007) and reference lists of articles.

Selection criteria

All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation.

Data collection and analysis

Study quality assessment and data extraction were carried out independently by two review authors. Both authors were experts in the content matter.

Main results

No randomised trials were identified which compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in women with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in women with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia.

Authors' conclusions

There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.

 

Plain language summary

Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation

There is not enough evidence to show the effect of progestogens alone or in combination with oestogens for irregular uterine bleeding. Dysfunctional uterine bleeding (DUB) is bleeding outside a usual menstrual period that is not caused by a recognised disease. It could be heavy and regular, or irregular. The menstrual cycles associated with this bleeding can either be ovulatory (normal) or anovulatory (abnormal) hormonal cycles. DUB occurs most commonly soon after a person starts to menstruate or just before menopause starts. The hormone progestogen can be used alone, or with oestrogen, to try and control DUB where cycles are anovulatory. The review of trials found there was not enough evidence to show the effect of either progestogen alone or in combination with oestrogens for DUB.

 

摘要

背景

單一使用黃體素與合併使用雌激素及黃體素對於無排卵性的子宮異常出血的比較

子宮異常出血(Dysfunctional uterine bleeding, DUB)意指在排除掉懷孕,其他骨盆腔或全身性疾病原因之後的大量,延長或經常的子宮出血。無排卵可用許多方式來證實，但在一般臨床上，若病人有大量,延長或經常的經期，則懷疑是無排卵性月經，尤其是年齡在生育年齡兩端的女性和多囊性卵巢的患者。月經量多或時間不規則對於大多數女性來說都是無法容忍的。月經週期時間的改變多與下視丘腦下垂體卵巢(Hypothalamopituitaryovarian axis, HPO)的異常有關。在無排卵性的異常出血下，雌激素的無週期性分泌(不規則)，導致子宮內膜無法受到黃體素縮退性出血，以致於月經週期的異常。內膜長期暴露在雌激素的刺激下，在剝落時會造成大量的出血。這就是在月經後半段使用黃體素來達成正常的縮退性出血的理論. 持續地黃體素使用主要是為了達到子宮內膜的萎縮，進而避免雌激素造成的內膜增生。單一使用黃體素或合併使用雌激素及黃體素經常使用在無排卵性的子宮異常出血，但是目前對於使用何種劑量，方式和黃體素的種類才能達到最好的效果並沒有共識。

目標

比較單一使用黃體素與合併使用雌激素及黃體素對於無排卵性的子宮異常出血的何者效果及接受度較高 。

搜尋策略

本篇搜尋了登記在 enstrual Disorders and Subfertility Group內的試驗,(至2007年5月4), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (198 o May 2007), Biological Abstracts (1969 to May 2007), Current Contents (198 o 2007) and reference lists of articles

選擇標準

所有比較單一使用黃體素(所有投藥方式)與合併使用雌激素及黃體素對於無排卵性的子宮異常出血的隨機對照試驗(randomised controlled trials, RCT)。

資料收集與分析

研究品質評估及數據分析由兩位審核者獨立進行。這兩位審核者皆為此專題的專家。

主要結論

並沒有RCT比較合併使用雌激素及黃體素與單一使用黃體素或安慰劑對於無排卵性的子宮異常出血的效果。唯有ㄧ小型，非隨機試驗比較了兩種黃體素方式用於以確診為無排卵性的大量及不規則出血。另有ㄧ隨機測驗比較了兩種黃體素對於有不同月經症狀的女性的子宮內膜組織變化的影響,其中有一半的病患有腺性增生。

作者結論

目前缺乏比較合併使用雌激素及黃體素與單一使用黃體素對於無排卵性的子宮異常出血的效果。近ㄧ步的研究來決定此兩種方式在治療這常見的婦科疾病的角色是需要的。

翻譯人

本摘要由高雄醫學大學附設醫院張慧名翻譯。

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

總結

單一使用黃體素與合併使用雌激素及黃體素對於無排卵性的子宮異常出血的比較。 目前沒有足夠的證據顯示單一使用黃體素或合併使用雌激素及黃體素對於子宮異常出血的效果。DUB是指在正常月經週期外，排除其他疾病後的不正常出血。它可能是大量但規則或不規則。與這種出血有關的可能是有排卵(正常)或無排卵(異常)的月經週期。DUB最常見於初經剛來或接近更年期的女性。黃體素可以單一或合併雌激素使用，來控制無排卵性的DUB。目前沒有足夠的證據顯示單一使用黃體素或合併使用雌激素及黃體素對於子宮異常出血的效果。