Testosterone for peri and postmenopausal women

 

Abstract

Background

The question of whether adding testosterone therapy to conventional postmenopausal hormone therapy (HT) is effective or safe is unresolved. Therefore, we aimed to determine the efficacy and safety of testosterone therapy for postmenopausal women using HT.

Objectives

To determine the benefits and risks of testosterone therapy for postmenopausal women taking HT.

Search methods

We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 21 July, November 2008), The Cochrane Library (2008, Issue 3), MEDLINE (1966 to July 2008), EMBASE (1980 to July 2008), Biological Abstracts (1969 to 2008), PsycINFO (1972 to July 2008), CINAHL (1982 to July 2008), and reference lists of articles. We also contacted pharmaceutical companies and researchers in the field.

Selection criteria

Studies included randomised comparisons of testosterone plus HT versus HT alone in peri or postmenopausal women.

Data collection and analysis

Two review authors independently assessed the quality of the trials and extracted data. For dichotomous outcomes, a Peto odds ratio (OR) and its 95% confidence interval (CI) were calculated. For continuous outcomes, non-skewed data from valid scales were synthesized using a weighted mean difference or standardized mean difference. If statistical heterogeneity was found, a random-effects model was used and reasons for the heterogeneity were explored and discussed.

Main results

Thirty-five trials with a total of 4768 participants were included in the review. The median study duration was six months (range 1.5 to 24 months). Most of the trials were of adequate quality with regard to randomisation and concealment of allocation sequence. The major methodological limitations were attrition bias and lack of a washout period in the crossover studies. The pooled estimate suggested that the addition of testosterone to HT regimens improved sexual function scores and number of satisfying sexual episodes for postmenopausal women. Significant adverse effects were decreased high-density lipoprotein (HDL) cholesterol levels and an increased incidence of hair growth and acne. The discontinuation rate was not significantly greater with the addition of testosterone therapy (OR 0.99, 95% CI 0.83 to 1.19).

Authors' conclusions

There is good evidence that adding testosterone to HT has a beneficial effect on sexual function in post-menopausal women. However, the combined therapy is associated with a higher incidence of hair growth and acne and a reduction in HDL cholesterol. These adverse events may differ by the different doses and route of testosterone administration. There is insufficient evidence to determine the effect of testosterone in long term use.

 

Plain language summary

Testosterone for perimenopausal and postmenopausal women

There is good evidence that adding testosterone to hormone therapy (HT) has a beneficial effect on sexual function in postmenopausal women. However, the combined therapy is associated with a higher incidence of hair growth and acne and a reduction in high-density lipoprotein (HDL) cholesterol. These adverse events may vary with different doses and routes of administration of testosterone. Adding testosterone to HT did not increase the number of women who stopped HT therapy.

 

摘要

背景

睪固酮應用於近停經期及已停經的婦女

近停經期及已停經婦女使用荷爾蒙療法(hormone therapy, HT)加上睪固酮的效果仍具有爭議性且尚未被有系統地的研究。

目標

為了評定近停經期及已停經婦女使用荷爾蒙(hormone therapy, HT)加上睪固酮治療的益處及風險。

搜尋策略

本篇搜尋Cochrane Menstrual Disorders and Subfertility Group Trials Register (1st November 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to 1st November 2003), EMBASE (1980 to 1st November 2003), Biological Abstracts (1969 to 2002), PsycINFO (1972 to 1st November 2003), CINAHL (1982 to 1st November 2003)資料庫的論文以及論文的參考文獻. 同時接觸了此研究領域的製藥廠及研究者。

選擇標準

近停經期及已停經婦女比較荷爾蒙加睪固酮治療與單獨使用荷爾蒙療法的隨機對照試驗。

資料收集與分析

兩位審核者獨立評估研究品質及分析數據。如有需要，將聯絡該研究的通訊作者以獲得額外資訊。二分變項的治療結果將計算其Peto odds ratios 以及 95% confidence intervals。連續變項則由可信刻度獲得的數據以weighted mean difference 或 standardized mean difference合成不偏斜的治療結果。如果發現統計的異質性(heterogeneity)，則使用隨機效應模式(randomeffects model)分析並探討異質性的原因。

主要結論

本篇研究收錄23個試驗，共1957位受試者。研究期間中位數為6個月(全距為1.5到24個月)。多數研究在隨機取樣及隱瞞配置順序上的品質是適當的。最大的研究限制是attrition bias及交叉研究中缺乏washout period。所有試驗的混合估計值顯示，在荷爾蒙療法中加入睪固酮可增加停經後婦女的性功能評分值。顯著的副作用則是降低高密度膽固醇(HDL;highdensity lipoprotein cholesterol).睪固酮治療並不會比單獨使用荷爾蒙療法有較高的停藥率(Peto odds ratio 1.01, 95% confidence interval 0.76 t .33)。並沒有足夠證據顯示對於近更年期的女性有治療效果或其他結果。

作者結論

只有少數的研究可以被納入metaanalysis中分析，而限制了這個metaanalysis提供治療效果及安全性結論的統計檢定力。但是，的確有證據顯示在停經後婦女的荷爾蒙療法中加入睪固酮有助於性功能。在荷爾蒙療法中加入睪固酮與HDL cholesterol的降低有關。這個metaanalysis包含了不同睪固酮處方的研究，因此睪固酮在任何個別荷爾蒙療法中對性功能影響的評估是有困難的。

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

睪固酮療法應用在近停經期及已停經婦女的角色仍不明確。在荷爾蒙治療中加入睪固酮對於近停經期及已停經婦女的健康價值是有爭議的。此系統性文獻回顧檢視了此療法的優點及風險。但因為只有少量的研究符合此metaanalysis的納入條件，而限制所有檢視的結果。目前能提供的證據是，睪固酮加上雌激素(不論有無黃體素)治療可有效的提升停經後婦女的性功能但與HDL的下降有關。睪固酮對其他健康結果及對近更年期婦女的影響則仍不清楚。