Long term hormone therapy for perimenopausal and postmenopausal women

 

Abstract

Background

Hormone therapy (HT) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of the original Cochrane review first published in 2005.

Objectives

To assess the effect of long-term HT on mortality, cardiovascular outcomes, cancer, gallbladder disease, cognition, fractures and quality of life.

Search methods

We searched the following databases to November 2007: Trials Register of the Cochrane Menstrual Disorders and Subfertility Group, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Biological Abstracts. Also relevant non-indexed journals and conference abstracts.

Selection criteria

Randomised double-blind trials of HT versus placebo, taken for at least one year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via oral, transdermal, subcutaneous or transnasal routes.

Data collection and analysis

Two authors independently assessed trial quality and extracted data.

Main results

Nineteen trials involving 41,904 women were included. In relatively healthy women, combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event (after one year's use), stroke (after three years), breast cancer and gallbladder disease. Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease (after one to two years, three years and seven years' use respectively), but did not significantly increase the risk of breast cancer. The only statistically significant benefits of HT were a decreased incidence of fractures and (for combined HT) colon cancer, with long-term use. Among women aged over 65 who were relatively healthy (i.e. generally fit, without overt disease) and taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism.

One trial analysed subgroups of 2839 relatively healthy 50 to 59 year old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thrombo-embolism in women taking combined continuous HT: their absolute risk remained low, at less than 1/500. However, this study was not powered to detect differences between groups of younger women.

Authors' conclusions

HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

 

Plain language summary

Long term hormone therapy for perimenopausal and postmenopausal women

Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of chronic diseases such as cardiovascular disease, osteoporosis and dementia in older women. The present review set out to assess the long term clinical effects of using HT. Nineteen randomised double-blind trials (involving 41,904 women aged 26 to 91 years) compared HT (all oestrogens, with or without progestogens, administered by oral, transdermal, subcutaneous or intranasal routes) with placebo when taken for at least one year. In healthy women (11 studies), combined continuous HT significantly increased the risk of obstruction of a vein by a blood clot (venous thrombo-embolism), fatal or nonfatal heart attack (after one year's use), stroke (after three years), breast cancer, gallbladder disease and (in women over 65 years) dementia. Long-term oestrogen alone significantly increased the risk of venous thromboembolism, stroke and gallbladder disease. Among women with cardiovascular disease (six studies) long-term use of combined HT significantly increased the risk of venous thromboembolism, particularly in the first two years of use, and gallbladder disease. HT offered the benefit of a significant reduction in the risk of fracture (no greater in women at high risk of fractures) or colorectal cancer but only after four or five years' treatment with HT, while the highest risk of cardiovascular events with combined HT occurred in the first year of use.

 

摘要

背景

長期賀爾蒙療法對更年期及停經後婦女的成效

賀爾蒙治療被廣泛用於處理停經後的症狀，同時也被用於治療及預防心血管疾病、骨質疏鬆症及老年婦女失智症。然而支持這些適應症的證據多是根據觀察性研究而來的。

目標

評估長期賀爾蒙治療對死亡率、心臟疾病、靜脈血栓栓塞、中風、短暫性腦缺血發作、乳癌、大腸直腸癌、卵巢癌、子宮內膜癌、膽囊疾病、認知功能、失智症、骨折及生活品質的影響。

搜尋策略

我們搜尋了下列資料庫(至2004年11月)：Cochrane Menstrual Disorders and Subfertility Group Trials Register、Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE, Biological Abstracts，亦搜尋相關非索引性的期刊及學術研討會論文摘要。

選擇標準

更年期或停經後婦女服用至少一年賀爾蒙治療(雌激素併用或不併用黃體素)與安慰組之隨機雙盲試驗。

資料收集與分析

本研究包含15個隨機臨床試驗，每個研究均由兩位審查作者獨立閱讀並摘錄其數據資料評估其品質。他們用危險比(Risk ratio, RR)來計算類別變項的結果，用加權平均數(weighted mean differences, WMD)來計算連續變項的結果。因為大多數臨床試驗的異質性過大，因此無法針對試驗結果進行統合分析。

主要結論

所有統計學上有意義的結果均來自兩個大型研究。在相對較健康的婦女中連續使用賀爾蒙(雌激素 + 黃體素)的合併治療會增加靜脈血栓性栓塞症或冠心病的危險(在一年的使用後)、中風的危險(在三年的使用後)、乳癌的危險(在五年的使用後)以及膽道疾病。長期單方雌激素的賀爾蒙治療也會明顯地增加中風及膽道疾病的危險性。整體而言，長期賀爾蒙療法在統計學上有意義的優勢只在於減少骨折及大腸癌的發生率。而在相對較健康且年紀超過65歲的婦女：連續使用賀爾蒙(雌激素 + 黃體素)的合併治療，統計學上有意義地增加失智症的發生率。對於有心臟血管疾病的婦女而言：長期連續使用賀爾蒙(雌激素 + 黃體素)的合併治療明顯地會增加靜脈血栓性栓塞的危險。尚未有特別針對較年輕的婦女所作的研究；然而，有一篇研究之分群分析(對象分別為2839位相對較健康的婦女，年齡50 – 59歲，連續服用賀爾蒙(雌激素 黃體素)的合併治療以及1637位只服用單方雌激素之賀爾蒙療法)與具有相近樣本數的安慰組作比較，其結果顯示：唯一會明顯增加危險性的報告是連續服用合併治療的婦女增加靜脈血栓性栓塞危險性，不過其絕對危險率很低。

作者結論

賀爾蒙療法並不建議常規用來作為慢性病的治療。雖然短期使用賀爾蒙療法對於健康年輕的婦女似乎相對上較安全，但我們仍需要更多的證據來證實賀爾蒙療法用於停經症狀控制之安全性。

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

長期賀爾蒙療法用於停經期前後及停經後婦女。 賀爾蒙療法廣泛用於控制停經症狀，也用來治療及預防慢性疾病，像是心血管疾病、骨質疏鬆症及老年婦女之失智症。本回顧性文獻評估長期賀爾蒙療法的臨床效果。15篇隨機雙盲臨床試驗(包含35,089位婦女，年齡從41到91歲)，比較至少一年的賀爾蒙療法(雌激素併用或不併用黃體素，給藥方式不論口服、經皮吸收、皮下或鼻腔內的投與路徑)及安慰組的安全性。在健康的婦女(8個研究)發現：合併連續性賀爾蒙治療會顯著增加靜脈血栓性栓塞症、致死或非致死性的心臟病發作(在一年的使用後)，中風(在三年的使用後)，乳癌(在五年的使用後)，膽囊疾病以及(超過65歲的婦女)失智症的危險性；長期雌激素單獨使用也會顯著增加中風及膽囊疾病的危險性。而對於具有心臟病的婦女來說(6個研究)長期連續服用賀爾蒙(雌激素 + 黃體素)的合併治療會顯著增加靜脈血栓性栓塞症及膽囊疾病的危險性。賀爾蒙治療提供的好處在於：明顯地降低骨折的危險性(但骨折高危險群的婦女除外)或大腸直腸癌(但是只有在使用賀爾蒙治療超過4或5年後)。在使用合併(雌激素 黃體素)賀爾蒙治療的第一年發生心臟血管疾病的危險性最高。