Local oestrogen for vaginal atrophy in postmenopausal women

 

Abstract

Background

Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring).

Objectives

The objective of this review was to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy.

Search methods

We searched the Cochrane Menstrual Disorders and Subfertility Group Register of trials (searched January 2006), The Cochrane Library (2006,Issue 2), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), Current Contents (1993 to January 2006, Biological Abstracts (1969 to 2006), Social Sciences Index (1980 to January 2006), PsycINFO (1972 to February 2006), CINAHL (1982 to January 2006) and reference list of articles. We also contacted manufacturers and researchers in the field.

Selection criteria

The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis.

Data collection and analysis

Thirty-seven trials were identified: of these 18 were excluded. Included trials were assessed for quality and two reviewer authors extracted data independently. The ratios for dichotomous outcomes and means for continuous outcomes were calculated. The outcomes analysed were categorised under the headings of: efficacy, safety and acceptability.

Main results

Nineteen trials with 4162 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy ,with various outcome measures. When comparing the efficacy of different oestrogenic preparations (in the form of creams, pessaries, tablets and the oestradiol-releasing vaginal ring) in relieving the symptoms of vaginal atrophy, results indicated significant findings favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel.

Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and seven looked at adverse effects. One trial showed significant adverse effects of the cream (conjugated equine oestrogen) when compared to tablets (oestradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by a progestagen challenge test with the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to the cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (oestradiol).

Eleven studies compared acceptability to the participants by comparing: comfort of product use, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the oestradiol-releasing vaginal ring.

Authors' conclusions

Creams, pessaries, tablets and the oestradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following use of the cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the oestradiol-releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

 

Plain language summary

Using creams, pessaries or a vaginal ring to apply oestrogen vaginally relieves the symptoms of vaginal atrophy, although some creams may cause adverse effects.

Vaginal atrophy is a common condition in women after menopause. It causes vaginal dryness and itching and can make intercourse painful. The female hormone oestrogen is a treatment option for vaginal atrophy, but can cause adverse effects such as bleeding and breast tenderness. Women can take oestrogen through tablets or injections. Alternatively, they can apply the hormone locally using creams, pessaries (tablets placed in the vagina) or a hormone-releasing ring placed in the vagina. The review found that all methods of delivering oestrogen relieved the symptoms. However, some creams may cause adverse effects and women preferred vaginal rings.

 

摘要

背景

局部雌激素治療停經後婦女之陰道萎縮症

陰道萎縮症是停經後婦女常見的抱怨之一，其症狀包括陰道乾澀、癢、性交不適感及疼痛感。處理這些症狀時不一定需要口服荷爾蒙補充治療的全身性療法。 另一種替代性的選擇為經由陰道局部給藥(製劑的型式包括乳霜、子宮托、錠劑、雌激素陰道釋放環)。

目標

這篇文獻回顧的目標在比較各種雌激素製劑治療婦女陰道萎縮症之效果、安全性及接受度。

搜尋策略

我們搜尋了Cochrane Menstrual Disorders and Subfertility Group Register of trials(2006年1月)、Cochrane Library(2006年, Issue 2)、MEDLINE(1966年到2006年1月)、EMBASE(1980年到2006年1月)、Current Contents(1993年到2006年1月)、Biological Abstracts(1969年到2006年)、 Social Sciences Index(1980年到2006年1月)、PsycINFO(1972年到2006年2月)、CINAHL(1982年到2006年1月)以及論文的參考文獻。另外，我們也跟廠商及該領域的專家連絡。

選擇標準

納入標準為比較經陰道給藥的各種雌激素製劑治療停經後婦女之陰道萎縮症或陰道炎所造成症狀的隨機試驗。

資料收集與分析

根據納入標準共找到37篇研究，但排除其中的18篇。納入的研究都評估其品質，並由兩位審查作者獨立摘錄其數據資料。使用比率來計算類別變項，而用平均值來計算連續變項的結果。分析出來的結果再依據不同的標題(效力、安全性及接受度)來分類。

主要結論

這篇回顧中收錄了19篇試驗，包括4162位婦女。雖然並非所有的試驗都用相同的結果項目來做測量評估，但整體的品質不錯。所有的試驗用各種測量結果來評估其有效性。當比較不同雌激素製劑(包括乳霜、子宮托、錠劑、雌激素陰道釋放環)的有效性時，其結果指出：含賀爾蒙製劑(乳霜、雌激素陰道釋放環、錠劑)其緩解陰道萎縮症之症狀的效果均明顯較安慰組及非賀爾蒙凝膠佳。 4個研究是針對安全性作比較：4個研究是觀察過度增生的情形，4個研究是觀察子宮內膜過度刺激的情形，7個研究則是觀察不良反應。一篇研究指出相較於含oestradiol成分的錠劑，含conjugated equine oestrogen 的乳霜製劑有較明顯的不良反應，包括子宮出血、乳房痛、會陰疼痛(一篇隨機對照試驗OR = 0.18，95% I = 0.07到0.50)。 有2篇利用黃體素激發試驗(progesterone challenge test)評估子宮內膜的研究，顯示含conjugated equine oestrogen乳霜比雌激素陰道釋放環，有較明顯的內膜過度刺激情形(OR0.29，95% I = 0.11到0.78)。雖然不具統計學上的差異，但是雌激素陰道釋放環組相較於含conjugated equine oestrogen乳霜組，有2% 單純性過度增生的發生率；含conjugated equine oestrogen乳霜組相較於含oestradiol錠劑組有4% 的過度增生發生率(一篇是單純性，另一篇則是複雜性過度增生)。11個研究比較受試者使用的接受度，評估的項目包括產品使用的舒適性、使用的難易度、整體產品的評估、給藥方式及滿意度，其結果顯示受試者明顯地偏愛使用雌激素陰道釋放環。

作者結論

乳霜、子宮托、錠劑、雌激素陰道釋放環等緩解停經後婦女陰道萎縮症症狀的效果相當。 一篇研究發現使用含conjugated equine oestrogen乳霜比使用錠劑，有更顯著的副作用造成子宮出血、乳房痛、會陰疼痛。 另1個試驗發現使用含conjugated equine oestrogen乳霜比使用雌激素陰道釋放環有較明顯的子宮內膜過度刺激的情形。作為一個治療選項，婦女似乎因為較容易使用且產品的舒適性及整體滿意度較佳而偏愛使用雌激素陰道釋放環。

翻譯人

本摘要由高雄醫學大學附設醫院許郁笙翻譯。

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

總結

雖然有些乳霜可能會造成副作用，臨床上仍會使用乳霜、子宮托、或陰道環等經陰道投與雌激素來緩解婦女陰道萎縮症之症狀。陰道萎縮症是停經後婦女常見的狀況，它造成陰道乾澀、搔癢、性交疼痛感。女性賀爾蒙雌激素是治療陰道萎縮症的選擇之一，但也會造成一些副作用，像是出血及乳房觸痛。婦女可以經口服錠劑或注射方式補充雌激素，或以乳霜、子宮托、將錠劑置於陰道內或在陰道放置雌激素釋放環等局部投與賀爾蒙方式作為替代方案。本回顧發現所有投與方式補充雌激素均能緩解症狀，但是某些乳霜可能造成副作用，而且婦女較喜歡使用陰道環。