Intervention Review

Hormone replacement therapy to maintain cognitive function in women with dementia

  1. Eva Hogervorst1,*,
  2. Kristine Yaffe2,
  3. Marcus Richards3,
  4. Felicia AH Huppert4

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 8 APR 2008

DOI: 10.1002/14651858.CD003799.pub2

How to Cite

Hogervorst E, Yaffe K, Richards M, Huppert FAH. Hormone replacement therapy to maintain cognitive function in women with dementia. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD003799. DOI: 10.1002/14651858.CD003799.pub2.

Author Information

  1. 1

    Loughborough University, Department of Human Sciences, Loughborough, Leicestershire, UK

  2. 2

    University of California, San Francisco, Psychiatry, Neurology and Epidemiology, San Francisco, California, USA

  3. 3

    University College London Department of Epidemiology & Public Health, London, UK

  4. 4

    University of Cambridge, Department of Psychiatry, Cambridge, UK

*Eva Hogervorst, Department of Human Sciences, Loughborough University, Loughborough, Leicestershire, LE11 3TU, UK. .

Publication History

  1. Publication Status: Edited (conclusions changed)
  2. Published Online: 21 JAN 2009




  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要


As estrogens have been shown to have several potentially beneficial effects on the central nervous system, it is biologically plausible that maintaining high levels of estrogens in postmenopausal women by means of estrogen replacement therapy (ERT) could be protective against cognitive decline in women with Alzheimer's disease (AD) or other dementia syndromes.


To investigate the effects of ERT (estrogens only) or HRT (estrogens combined with a progestagen) compared with placebo in randomized controlled trials (RCTs) on cognitive function of postmenopausal women with dementia.

Search methods

The Cochrane Dementia and Cognitive Improvement Group Specialized Register, which contains records from many medical databases, The Cochrane Library, EMBASE, MEDLINE, CINAHL, PsycINFO and LILACS were searched on 7 November 2007 using the terms ORT, PORT, ERT, HRT, estrogen*, oestrogen* and progesterone*.

Selection criteria

All double-blind randomized controlled trials (RCTs) into the effect of ERT or HRT for cognitive function with a treatment period of at least two weeks in postmenopausal women with AD or other types of dementia.

Data collection and analysis

Abstracts of the references retrieved by the searches were read by two reviewers (EH and KY) independently in order to discard those that were clearly not eligible for inclusion. The two reviewers studied the full text of the remaining references and independently selected studies for inclusion. Any disparity in the ensuing lists was resolved by discussion with all reviewers in order to arrive at the final list of included studies. The selection criteria ensured that the blinding and randomization of the included studies was adequate. The two reviewers also assessed the quality of other aspects of the included trials. One reviewer (EH) extracted the data from the studies, but was aided and checked by JB from Cochrane.

Main results

A total of seven trials including 351 women with AD were analysed. Because different drugs were used at different studies it was not possible to combine more than two studies in any analysis.

On a clinical global rating, clinicians scored patients taking CEE as significantly worse compared with the placebo group on the Clinical Dementia Rating scale after 12 months (overall WMD = 0.35, 95% CI = 0.01 to 0.69, z = 1.99, P < 0.05).

Patients taking CEE had a worse performance on the delayed recall of the Paragraph Test (overall WMD = -0.45, 95% CI = -0.79 to -0.11, z = 2.60, P < 0.01) after one month than those taking placebo. They had a worse performance on Finger Tapping after 12 months (WMD = -3.90, 95% CI = -7.85 to 0.05, z = 1.93, P < 0.05).

Limited positive effects were found for the lower dosage of CEE (0.625 mg/day) which showed a significant improvement in MMSE score only when assessed at two months, and disappeared after correction for multiple testing. No significant effects for MMSE were found at longer end points (3, 6 and 12 months of treatment). With a dosage of 1.25 mg/d CEE, short-term significant effects were found for Trial-Making test B at one month and Digit Span backward at four months. After two months of transdermal diestradiol (E2) treatment, a highly significant effect was observed for the word recall test (WMD = 6.50, 95% CI = 4.04 to 8.96, z = 5.19, P < 0.0001). No other significant effects were found for other outcomes measured.

Authors' conclusions

Currently, HRT or ERT for cognitive improvement or maintenance is not indicated for women with AD.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要

There is no evidence of a positive effect that estrogen replacement therapy can maintain cognitive function for a longer period of time (> five months) in women with Alzheimer's disease

After the menopause, in women levels of estrogens decline. Estrogen replacement therapy (ERT) or replacement therapy with both estrogens and progestagens (hormone replacement therapy or HRT) might theoretically help to maintain cognitive function in postmenopausal women with dementia. We therefore investigated the results of randomized controlled trials of the effects of ERT and HRT on cognitive function in postmenopausal women with AD.

Overall, however, there was no evidence for positive effects of ERT or HRT which was sustained after two months of treatment. This is similar to results of studies of ERT and HRT in women without dementia, which additionally found that HRT increases the rate of dementia in women over 65 years.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要







以下の用語を用いて多数の保健医療データベースからの記録を含むCochrane Dementia and Cognitive Improvement Group Specialized Register、コクラン・ライブラリ、EMBASE、MEDLINE、CINAHL、PsycINFOおよびLILACSを2007年11月7日に検索した:ORT、PORT、ERT、HRT, estrogen*(エストロゲン)、oestrogen*(エストロゲン)およびprogesterone*(プロゲステロン)。






AD女性351例を対象とした計7件の試験を解析した。研究ごとに異なる薬剤が使用されていたため、いずれの解析でも3件以上の研究を統合することはできなかった。臨床的総合評価を行うと、臨床医による12ヵ月後のClinical Dementia Ratingによるスコアは、プラセボ群に比して、結合型ウマエストロゲン(CEE)投与患者で有意に不良であった(全体での重み付き平均差(WMD)=0.35、95%CI=0.01~0.69、z=1.99、P<0.05)。CEE投与患者は1ヵ月後のParagraph Testで遅延再生の成績がプラセボ群の患者よりも悪かった(全体でのWMD=-0.45、95%CI=-0.79~-0.11、z=2.60、P<0.01)。CEE投与患者は12ヵ月後のFinger Tappingの成績も悪かった(WMD=-3.90、95%CI=-7.85~0.05、z=1.93、P<0.05)。低用量のCEE(0.625mg/日)に対しては限定的ながら効果が認められ、2ヵ月時点で評価した際にのみMMSEスコアに有意な改善が認められたが、多重検定による補正すると消失した。より長期のエンドポイント(3ヵ月間、6ヵ月間、12ヵ月間の治療)でMMSEに対する有意な効果は認められなかった。用量1.25mg/日のCEEでは、1ヵ月時点でのTrial-Making test B、4ヵ月の時点でのDigit Span backwardに対して短期的に有意な効果が認められた。2ヵ月にわたるジエストラジオール(E2)の経皮的投与後に、単語再生検査できわめて有意な効果が認められた(WMD=6.50、95%CI=4.04~8.96、z=5.19、P<0.0001)。その他測定したアウトカムについては、有意な効果は認められなかった。




監  訳: 大神 英一,2009.5.13

実施組織: 厚生労働省委託事業によりMindsが実施した。

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  1. Top of page
  2. Abstract
  3. Plain language summary
  4. アブストラクト
  5. 摘要





收錄所有隨機對照組試驗,這些試驗主要是比較安慰劑與ERT (只有estrogens) 或是HRT (estrogens 合併progestagen)對於患有失智症的停經後婦女的認知功能的影響。


在2007年11月7日使用Cochrane Dementia and Cognitive Improvement Group Specialized Register(包含有許多醫藥資料庫)、The Cochrane Library、EMBASE、MEDLINE、CINAHL、 PsycINFO和LILACS以「ORT, PORT, ERT, HRT, estrogen*, oestrogen* 和 progesterone* 」為關鍵字進行檢索。






總共有7組試驗納入351位患有阿茲海默氏症的女性被分析。因為不同的試驗使用不同的藥物,所以沒辦法合併超過2組以上的試驗。一個整體性評估試驗中發現,使用CEE治療病患12個月比起安慰劑有較差的Clinical Dementia Rating scale分數(所有WMD = 0.35, 95%信心區間 = 0.01到0.69, z = 1.99, P < 0.05)。病患使用CEE一個月後比起安慰劑在 delayed recall of the Paragraph Test 中有較差的表現 (所有WMD = −0.45, 95%信心區間 = −0.79到 −0.11, z = 2.60, P < 0.01)。經過12個月,有較差的finger tapping 測試(WMD = −3.90, 95%信心區間 = −7.85到0.05, z = 1.93, P < 0.05)。使用兩個月低劑量的CEE(0.625 mg/日)對於MMSE分數的改善有些許的療效,但若控制其他的變數則療效便不明顯了。較長的試驗(治療時間3,6和12個月)發現對於MMSE沒有明顯效果。使用每日1.25mg劑量的CEE,可以發現在一個月後的TrialMaking test B和在四個月後的Digit Span backward有短期的療效。經過兩個月的transdermal diestradiol (E2)治療,在word recall test 上有明顯的療效(WMD = 6.50, 95% CI信心區間 = 4.04 到 8.96, z = 5.19, P < 0.0001)。在其他測試結果上沒有發現顯著的療效。




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