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Meta-Analysis
. 2009 Jan 21;2009(1):CD003799.
doi: 10.1002/14651858.CD003799.pub2.

Hormone replacement therapy to maintain cognitive function in women with dementia

Eva Hogervorst  1 , Kristine Yaffe, Marcus Richards, Felicia A H Huppert
Affiliations
Meta-Analysis

Hormone replacement therapy to maintain cognitive function in women with dementia

Eva Hogervorst et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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 strategy: 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.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Global cognitive functioning, Outcome 1 MMSE after 1,5 ‐2 months CEE (0.625 + 1.25 mg combined) or placebo.
1.2
1.2. Analysis
Comparison 1 Global cognitive functioning, Outcome 2 MMSE after 2 months with 0.625 mg CEE or placebo.
1.3
1.3. Analysis
Comparison 1 Global cognitive functioning, Outcome 3 MMSE after 1‐2 months with 1.25 mg CEE or placebo.
1.4
1.4. Analysis
Comparison 1 Global cognitive functioning, Outcome 4 MMSE after 2 months ERT or placebo.
1.5
1.5. Analysis
Comparison 1 Global cognitive functioning, Outcome 5 MMSE after 3‐6 months CEE (0.625 + 1.25 mg) or placebo.
1.6
1.6. Analysis
Comparison 1 Global cognitive functioning, Outcome 6 MMSE after 12 months with (0.625 mg + 1.25 mg) CEE or placebo.
1.7
1.7. Analysis
Comparison 1 Global cognitive functioning, Outcome 7 ADAS‐Cog after 1‐2 months with (0.625 mg + 1.25 mg) CEE or placebo.
1.8
1.8. Analysis
Comparison 1 Global cognitive functioning, Outcome 8 ADAS‐Cog after 4‐6 months with (0.625 mg + 1.25 mg) CEE or placebo.
1.9
1.9. Analysis
Comparison 1 Global cognitive functioning, Outcome 9 ADAS‐Cog after 12 months with (0.625 mg + 1.25 mg) CEE or placebo.
1.10
1.10. Analysis
Comparison 1 Global cognitive functioning, Outcome 10 ADAS‐Cog after 12 months with 0.625 mg CEE or placebo.
1.11
1.11. Analysis
Comparison 1 Global cognitive functioning, Outcome 11 ADAS‐Cog after 12 months with 1.25 mg CEE or placebo.
1.12
1.12. Analysis
Comparison 1 Global cognitive functioning, Outcome 12 Blessed (BIMC) after 2‐9 months ERT or placebo.
1.13
1.13. Analysis
Comparison 1 Global cognitive functioning, Outcome 13 HDS‐R after 16 weeks (estrogen) or vitamin B1 as placebo.
2.1
2.1. Analysis
Comparison 2 Memory tests, Outcome 1 Paragraph recall (immediate + delayed) after 2 months with E2 transdermal or placebo.
2.2
2.2. Analysis
Comparison 2 Memory tests, Outcome 2 Paragraph recall (immediate) after 1 month with 1.25 mg CEE or placebo.
2.3
2.3. Analysis
Comparison 2 Memory tests, Outcome 3 Paragraph recall (delayed) after 1 month with 1.25 mg CEE or placebo.
2.4
2.4. Analysis
Comparison 2 Memory tests, Outcome 4 Paragraph recall immediate after 4 months with 1.25 mg CEE or placebo.
2.5
2.5. Analysis
Comparison 2 Memory tests, Outcome 5 Paragraph recall (delayed) after 4 months with 1.25 mg CEE or placebo.
2.6
2.6. Analysis
Comparison 2 Memory tests, Outcome 6 Busche Selective Reminding (delayed recall) after 2 months with E2 transdermal or place.
2.7
2.7. Analysis
Comparison 2 Memory tests, Outcome 7 Buschke Selective Reminding (Ir, IR+DR) after 2 months with E2 transdermal or placebo.
2.8
2.8. Analysis
Comparison 2 Memory tests, Outcome 8 CERAD word list after 9 months with 0.625 mg CEE + MPA or placebo.
2.9
2.9. Analysis
Comparison 2 Memory tests, Outcome 9 Paired Associate word learning after 9 months with 0.625 mg CEE + MPA or placebo.
2.10
2.10. Analysis
Comparison 2 Memory tests, Outcome 10 Verbal Fluency tests (semantic memory).
2.11
2.11. Analysis
Comparison 2 Memory tests, Outcome 11 Visual Retention Test (WMS) after 2 months of E2 transdermal or placebo.
2.12
2.12. Analysis
Comparison 2 Memory tests, Outcome 12 Visual Retention Test (WMS) after 1.25 mg CEE or placebo.
2.13
2.13. Analysis
Comparison 2 Memory tests, Outcome 13 Visual span foward after 4 months of 1.25 mg CEE or placebo.
2.14
2.14. Analysis
Comparison 2 Memory tests, Outcome 14 Face recognition after 12 months of 0.625 + 1.25 mg CEE or placebo.
2.15
2.15. Analysis
Comparison 2 Memory tests, Outcome 15 Digit span forward (STM and concentration).
2.16
2.16. Analysis
Comparison 2 Memory tests, Outcome 16 Other memory tests.
3.1
3.1. Analysis
Comparison 3 Language tests, Outcome 1 Token test after 1‐2 months of HRT or placebo.
3.2
3.2. Analysis
Comparison 3 Language tests, Outcome 2 Token test after 4 months with 1.25 mg CEE or placebo.
3.3
3.3. Analysis
Comparison 3 Language tests, Outcome 3 Boston Naming Test after 4 months with 1.25 mg CEE or placebo.
4.1
4.1. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 1 TMT‐A after 1 month with 1.25 mg CEE or placebo.
4.2
4.2. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 2 TMT‐A after > 2 months HRT or placebo.
4.3
4.3. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 3 TMT‐B after 1 month with CEE or placebo.
4.4
4.4. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 4 TMT‐B after > 2 months.
4.5
4.5. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 5 Stroop after 2 months with E2 transdermal or placebo.
4.6
4.6. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 6 DSST after 12 months with (0.625 mg + 1.25 mg) CEE or placebo.
4.7
4.7. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 7 Letter Cancellation test after 12 months with (0.625 mg + 1.25 mg) CEE or placebo.
4.8
4.8. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 8 Finger tapping after 12 months with (0.625 mg + 1.25 mg) CEE or placebo.
4.9
4.9. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 9 Digit Span backwards after 1 month of 1.25 mg CEE or placebo.
4.10
4.10. Analysis
Comparison 4 Speed of information processing and concentration tests, Outcome 10 Digit Span backwards after > 4 months of CEE.
5.1
5.1. Analysis
Comparison 5 Clinical impressions of change scales, Outcome 1 CGIC (score of 4=no change from baseline, higher=worse).
5.2
5.2. Analysis
Comparison 5 Clinical impressions of change scales, Outcome 2 CDR (higher=worse).
5.3
5.3. Analysis
Comparison 5 Clinical impressions of change scales, Outcome 3 CIBIC.
6.1
6.1. Analysis
Comparison 6 Depression scales, Outcome 1 HDRS.
See this image and copyright information in PMC

Update of

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Hogervorst 2002
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