Does hormone replacement therapy (HRT) improve cognitive function or either delay or prevent dementia in postmenopausal women?

BACKGROUND: One of the more contentious clinical issues in the use of postmenopausal hormone replacement is the association between HRT, cognitive function, and dementia. The authors of this study examined published literature that assesses the relationship between estrogens and cognition by pooling the results of individual trials.

POPULATION STUDIED: The effects of HRT were examined in postmenopausal women. The individual studies varied significantly in the types of women they included. The women ranged in age from 29 to 80 years and had both surgical and natural menopause. The degree of menopausal symptoms they experienced also differed greatly.

STUDY DESIGN AND VALIDITY: English language research articles were identified using MEDLINE, HealthSTAR, PsychINFO, and The Cochrane Library databases. Twenty-nine studies that met inclusion criteria were rated for scientific rigor by 2 independent researchers. For the outcome of dementia, only retrospective cohort and case-control studies were available. Randomized controlled trials (RCTs) and cohort studies focusing on HRT and cognitive decline were included. Three of the RCTs used a crossover design. Ultimately, only 9 RCTs and 8 cohort studies were reviewed in the final analysis. The greatest limitations of this meta-analysis stem from the relatively poor and variable study design of the original articles. As a result, the conclusions of this meta-analysis, although based on the best available evidence, should be viewed with suspicion. Of the 17 included trials, the quality of 2 of the RCTs was rated as 2 out of 5 points. Two of the cohort studies were rated poor, and 1 was rated good. Although the duration of estrogen use in the RCTs was very short (21 days to 6 months), the retrospective trials ranged from 1.5 to 15 years. Only 7 of the 40 different cognitive tests were used in more than 2 studies. There were insufficient data to make conclusions regarding differences in outcomes between estrogen type, method of administration, dose, or use with or without progestins.

OUTCOMES MEASURED: Each study measured different outcomes. Most focused on aspects of memory, attention, concept formation and reasoning, motor speed, mental status, and verbal functions and language. Patient-oriented outcomes were not assessed, such as the ability to perform activities of daily living or the ability to live independently. The development of clinically diagnosed Alzheimer disease was the main outcome of the dementia trials. Only 1 study assessed the risk of vascular dementia.

RESULTS: Overall, women with preexisting menopausal symptoms appeared to receive more cognitive benefit than those without symptoms. Estrogen exposure was associated with slightly improved verbal memory, vigilance, reasoning, and motor speed, but not with other cognitive functions. The retrospective data suggests HRT use reduces the risk of dementia by approximately one third (summary odds ratio [OR]= 0.66; 95% confidence interval [CI], 0.53-0.82). HRT did not reduce the risk of vascular dementia (OR=0.50; 95% CI, 0.20-1.2).