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Evidence summaries

Hormone Replacement Therapy for Cognitive Function in Postmenopausal Women

Estrogen or combined estrogen and progestagen therapy does not protect against a decline in overall cognitive functioning in postmenopausal women. Level of evidence: "A"

A Cochrane review [Abstract] 1 included 24 studies, but only 16 with a total of 10 114 women had analysable data. Meta-analyses showed no effects of either estrogens only (ERT) or estrogens combined with a progestagen (HRT) on prevention of cognitive impairment after five (OR 1.34, 95% CI 0.95 to 1.9; 1 study, n=2942) and four (OR 1.05, 95% CI 0.72 to 1.54; 1 study, n=4532) years of treatment (trend favouring control in both instances). Analyses assessing the effects of treatment over time found that both ERT and HRT did not maintain or improve cognitive function and may even adversely affect this outcome (WMD = -0.45, 95% CI -0.99 to 0.09, 1 study; WMD = -0.16, 95% CI -0.58 to 0.26, 1 study, respectively at maximum follow up). Negative effects were found for ERT after one year and HRT after three and four years of therapy. Results from smaller trials assessing effects on individual cognitive domains mostly reported no evidence of benefit. There is insufficient evidence to determine whether subgroups of women using specific types of hormone therapy could benefit from treatment.

Postintervention follow-up 2 was conducted with annual cognitive assessments of 2 randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1 376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2 880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.

    References

    • Lethaby A, Hogervorst E, Richards M, Yesufu A, Yaffe K. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database Syst Rev 2008 Jan 23;(1):CD003122. [PubMed]
    • Espeland MA, Rapp SR, Manson JE et al. Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups. J Gerontol A Biol Sci Med Sci 2017;72(6):838-845.[PubMed]

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