Sex steroids to maintain cognitive function in women after the menopause: A meta-analyses of treatment trials

Abstract 

It is still debated whether estrogen treatment after the menopause could result in improved cognitive function in women. This debate is based on many animal and cell culture data showing that estrogens can positively affect the aging brain. Observational data also show a halved risk of dementia in women who took estrogens around the age of menopause. However, large treatment trials have shown negative effects of long-term treatment with estrogens in older women. The present meta-analyses included 36 randomised treatment trials and tested various hypotheses which have been developed to attempt to explain discrepant data. Results indicated that, contrary to expectations, age of women and duration of time elapsed when treatment was initiated since menopause (‘window of opportunity’ hypothesis) did not significantly affect treatment outcome, nor did it matter whether women were symptomatic or not. It was not clear whether bilateral oophorectomy affected the outcome, as this effect was based on only a few studies from the same group and some observational studies show negative effects on cognition in surgical menopausal women treated with hormones for more than 10 years. Duration of treatment overall significantly affected outcome. More negative effects were seen in longer studies, where positive effects were mainly seen in short term studies (<4 months). Treatment with combined estrogens and progestagens also negatively affected the outcome. Whether women with symptoms should be treated for a couple of months or using other (intermittent) modes of treatment and whether this could have long-term positive consequences remains to be investigated.

Abbreviations: AD, Alzheimer's Disease, ARIC, Atherosclerosis Risk In Communities study, BETAM, Berlin Test for Associative Memory, BNT, Boston Naming Test, BSO, Bilateral Salpingo-Oophorectomy, B–W, Bourdon–Wiersma Test, BVRT, Benton Visual Retention Test, CANTAB, Cambridge Neuropsychological Test Automated Battery, CAMDEX-CAMCOG, Cambridge Dementia Examination Cognitive Tests, CEE, Conjugated Equine Estrogen, COWAT, Controlled Oral Word Association Test, CRT, Complex Reaction Time, CVLT, Californian Verbal Learning Test, IR, Immediate Recall, DR, Delayed Recall, DSMT/DSST, Digit Symbol Modalities/Substitution Test, E2, Estradiol, E1, Estrone, E3, Estriol, ED, Extradimentional, ID, Intradimensional, fMRI, functional Magnetic Resonance Imaging, HT/HRT, Hormone(Replacement) Therapy, KEEPS, Kronos Early Estrogen Prevention Study, KVT, Konzentrations Verlaufs Test, MMSE, Mini-Mental Status Examination, 3MSE, Modified Mini-Mental Status Examination, MPA, Medroxyprogesterone Acetate, P, Progesterone, PAL, Paired Associate Learning, PASAT, Paced Auditory Serial Addition Test, PMA, Primary Mental Abilities, SRT, Simple Reaction Time, RT, Reaction Time, RCT, Randomised Controlled Trial, SHBG, Sex Hormone Binding Globulin, T, testosterone, TMT, Trial Making Test, USTM, Unitary Space Time Modulation, VRT, Visual Reaction Time, WAIS-R, Wechsler Adult Intelligent Scale-Revised, WCST, Wisconsin Card Sorting Test, WMS-R, Wechsler Memory Test-Revised, WHI/WHIMS/WHISCA, Women's Health Initiative Memory Study–Study of Cognitive Aging

Keywords: Conjugated equine estrogens, Estradiol, Treatment, Cognition, Memory, Meta-analyses