No abstract

Objective-To investigate possible differential effects of the coadministration of conjugated equine estrogen (CEE) and a placebo (CEE + PL), CEE and medroxyprogesterone acetate (CEE + MPA), or CEE and micronized P (CEE + MP) on aspects of cognitive functioning in naturally postmenopausal women.Design-Double-blind, randomized, controlled trial.Setting-Gynecologic screening occurred at a university hospital, and neuropsychological testing took place in a university laboratory.Patient(s)-Twenty-four naturally menopausal women with an intact uterus who had never used hormone therapy were recruited by means of newspaper advertisements. All completed the study.Intervention(s)-A battery of mood and neuropsychological tests was administered. Women were randomly assigned to receive CEE + PL (n = 7), CEE + MPA (n = 9), or CEE + MP (n = 8).The tests were readministered 12 weeks later.Main Outcome Measure(s)-Standardized tests of mood, verbal memory, working memory, spatial abilities, and visual-spatial sequencing, and assays of serum sex hormone levels. Result(s)-Mood improved after treatment in all groups.No changes in scores occurred over time in any cognitive test in the group that received CEE + PL. Only the CEE + MP group had a significant decrease in their delayed verbal memory scores from baseline to after treatment. The CEE + MP-treated women performed significantly better on a test of working memory than women in the other two groups. Conclusion(s)-Coadministration CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptAlthough there is substantial evidence that estrogen (E)-alone therapy administered to postmenopausal women at the time of menopause may protect aspects of memory function, there is reason to believe that the coadministration of P or synthetic progestins may attenuate the beneficial effect of E on cognition or even cause harm (1). In the Women's Health Initiative Memory Study (WHIMS), the largest randomized controlled trial of its kind, women whose average age was 72 years at the time of the initiation of treatment with either continuous conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA), a synthetic 17α-hydroxyprogesterone derivative, or placebo found an increased risk of probable, all-cause dementia in the combined hormone group (CEE + MPA) compared with placebo (2). Because there was no heightened incidence of dementia in 72-year-old hysterectomized women treated with CEE alone (3), one interpretation of the WHIMS findings is that, in older women, the addition of MPA to E-alone therapy caused the excess risk of all-cause dementia. Because only a single test of global cognitive function was used in the WHIMS, it was not possible to examine specific effects of CEE or MPA on aspects of memory function in their sample. An earlier prospective observational study of women over the age of 65 years had also found that whereas treatment with unopposed CEE was associated with modest beneficial effects on a test of global cognitive function over time, treatment wit...

Thyroid hormones (THs) play a critical role in differentiation, growth, and metabolism of animal and human organ systems, including the brain. Although associations between normal levels of THs and cognitive functions in healthy elderly individuals have been reported, the findings are inconsistent, possibly due to differences in study designs. Because thyroid disease occurs more frequently in women, the goal of the present study was to examine the relationship between levels of THs and performance on neuropsychological tests in 122 healthy, euthyroid women whose mean age was 51 years. Higher levels of free T3 were positively associated with longer completion times (slower performance) on Trail Making Test -Part A (p=0.006) and Part B (p=0.032) and on the Tower of London test (p=0.002). Higher levels of thyroglobulin antibodies (TgAb) were positively correlated with more errors on the Trail Making Test Part B (p=0.000), on the Word Fluency test (p=0.023), and on the Design Fluency test (p=0.045). No significant correlations between TH levels and scores on mood, verbal memory, or working memory measures were observed. The findings point to a possible link between THs and cognitive processes that are mediated primarily by frontal cortex, areas associated with executive function tasks, and suggest that elevations in levels of free T3 and TgAB within the normal range may negatively influence executive functions.

There was no relationship between neuropsychological performance, age of initiation of HT, or duration of HT use.

While cognitive complaints are common during the menopausal transition, measurable cognitive decline occurs infrequently, often due to underlying psychiatric or neurological disease. To clarify the nature, etiology and evidence for cognitive and memory complaints during midlife, at the time of the menopausal transition, we have critically reviewed the evidence for impairments in memory and cognition associated with common comorbid psychiatric conditions, focusing on mood and anxiety disorders, attention-deficit disorder, prolonged stress and decreased quantity or quality of sleep. Both the evidence for a primary effect of menopause on cognitive function and contrarily the effect of cognition on the menopausal transition are examined. Impairment in specific aspects of executive function is explored. Evaluation and treatment strategies for the symptomatic menopausal woman distressed by changes in her day-to-day cognitive function with or without psychiatric comorbidity are presented.