Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels. Effects of estrogen on memory function in surgically menopausal women. A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life. Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life. Estrogen improves psychological function in asymptomatic postmenopausal women. Effects of hormone replacement therapy on cognitive performance in elderly women. Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients. The effect of hormone replacement on physical performance in community-dwelling elderly women. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females. Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women. The effect of short-term estrogen replacement therapy on cognition: a randomized, double-blind, cross-over trial in postmenopausal women. Sex steroids modify working memory. Estrogen replacement therapy and postural stability in the elderly. Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.
The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).
                To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.
                Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.
                In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.
                Probable dementia and MCI.
                In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).
                Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended. Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.
                To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.
                The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.
                Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).
                Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment.
                The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72).
                Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits. The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations. The effects of estrogen (E) on memory were assessed in 19 women who required a hysterectomy and bilateral oophorectomy for benign disease. Blood samples were drawn and memory tests were administered before surgery and again after 2 mo of postoperative treatment consisting of either monthly E or placebo (PL) injections. Scores on the immediate and delayed recall of paired-associates stayed at the same level in E-treated women, whereas they decreased significantly pre- to post-operatively in the PL-treated subjects. In the immediate recall of paragraphs, the scores of those given E improved postoperatively compared to baseline; scores remained unchanged in the PL group. No hormonal effects were apparent on the immediate or delayed recall of visual material, delayed recall of paragraphs, or digit span scores. These findings suggest that variations in specific aspects of memory function may occur in surgically menopausal women coincident with changes in plasma estrone and estradiol levels. The results of several observational studies suggest that the use of estrogen replacement is associated with better mood, cognitive function and quality of life. Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting, enhances cholinergic activity in the brain, decreases brain and plasma levels of beta-amyloid, increases serotonin postsynaptic responsivity and the turnover of noradrenaline, and inhibits monoamine oxidase activity. However, the findings from the Women's Health Initiative controlled trial showed that hormone replacement (estrogen plus progestin) not only failed to improve mood, cognition and quality of life but also increased the risk of dementia. At present, there is limited information about the effect of unopposed estradiol replacement therapy (ERT) on the mental health outcomes of women at increased risk of cognitive decline (aged 70 years and over). We designed the present randomized, double-blind, placebo-controlled trial to clarify this issue. One hundred and fifteen women were randomized to treatment with estradiol (n=58; 2mg per day) or placebo for a total period of 20 weeks. The outcomes of interest in this study included changes in the Beck Depression Inventory (BDI) scores between baseline and week 20, as well as changes in quality of life scores (as measured by the SF-36) and cognitive function (CAMCOG, Block Design, Memory for Faces, California Verbal Learning Test (CVLT) and verbal fluency (VF)). Nineteen women treated with estradiol and 10 of those treated with placebo discontinued the use of the medication during trial, most frequently due to adverse reactions (OR=4.11, 95% CI=1.29-15.37). Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures (p>0.05). A separate analysis restricted to women who completed the 20-week-trial produced similar negative results. The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function, mood and quality of life. Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women. Several small trials and many observational studies suggest that estrogen treatment in postmenopausal women improves cognition, but 2 large randomized trials have shown harm. The effect of an ultra-low- dose of unopposed transdermal estradiol on cognition and health-related quality of life is unknown.
                To investigate the effect of unopposed ultra-low-dose transdermal estradiol on cognitive function and quality of life in postmenopausal women.
                Randomized, placebo-controlled, double-blind trial with 2-year follow-up. The main outcome of the trial was change in bone density. Changes in cognitive function and quality of life were preplanned secondary outcomes of the trial.
                Nine clinical centers in the United States.
                Postmenopausal women (N = 417), aged 60 to 80 years, with a normal bone density for age and an intact uterus.
                A weekly transdermal patch that delivers estradiol, 0.014 mg/d (n = 208), or placebo (n = 209).
                Seven standardized cognitive tests (a total of 10 scores) administered at baseline and years 1 and 2 to test global cognitive function, verbal and visuospatial memory, language, executive function, and semantic memory. The 36-Item Short-Form General Health Survey was administered to assess health-related quality of life in physical and mental domains. The sample size provided 80% power to detect a standardized effect of 0.29 SD, a small-to-moderate difference.
                Baseline characteristics were similar in the 2 treatment groups. At 2 years of follow-up, we found no statistically significant differences between treatment groups in change on any of the cognitive test scores or on the 36-Item Short-Form General Health Survey (P > .12 for all). There was no consistent evidence that the effect of treatment on change in cognitive or 36-Item Short-Form General Health Survey scores depended on the level of baseline endogenous estradiol.
                Postmenopausal treatment with ultra-low-dose unopposed transdermal estradiol for 2 years had no effect on change in cognitive function or in health-related quality of life over 2 years of treatment. Estrogen treatment of postmenopausal women has been suggested to improve mood and psychological function. However, this remains controversial because previous studies involved heterogeneous groups, were not double blind, and included women who were also experiencing somatic symptoms that were relieved by estrogen. A randomized double-blind study was carried out comparing the effects of placebo and conjugated equine estrogens (0.625 and 1.25 mg) on psychological function over 3 months in 36 asymptomatic women, aged 45-60. The tests included the Minnesota Multiphasic Personality Inventory-168, the Profile of Adaptation to Life, and the Beck Depression Inventory. Memory was assessed directly by the Wechsler Adult Intelligence Scales, measuring both digit span and digit symbol. All women were well-adjusted psychologically. The income management scale of the Profile of Adaptation to Life improved (P less than .05) with estrogen, as did the Beck Depression Inventory (P less than .05), but these results were not dose-related. Memory assessed prospectively by the Wechsler Adult Intelligence Scales was not affected significantly. These results suggest that estrogen use may improve the overall quality of life in postmenopausal women. To determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older.
                A 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests.
                At baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy.
                Although conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression. The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant. Our aim was to determine the effect of hormone replacement on physical performance measures, functional ability, physical activity, falls, and cognitive function in elderly women.
                Following a 3-month, open-label, run-in phase, we randomized 373 community-dwelling women aged 65 years and older to receive conjugated equine estrogen 0.625 mg/day plus or minus medroxyprogesterone 2.5 mg/day vs placebo for 3 years in a double-blind fashion. We assessed time to rise from a chair, timed walking, balance, Instrumental Activities of Daily Living, Physical Activity Scale of the Elderly, Folstein Mini-Mental State Examination, and falls.
                Over 3 years, except for balance scores, performance measures declined significantly (all P<.05). There were no significant mean differences between women on hormone replacement versus placebo for rising time (0.1, -0.5 to 0.7 seconds [mean, 95% confidence interval]), walking normal (0.0, -0.4 to 0.4 seconds), and walking fast (0.2, -0.1 to 0.6 seconds). There were no significant mean differences between the two groups for the Instrumental Activities of Daily Living (0.1, -0.1 to 0.3 points), Physical Activity Scale of the Elderly (-3, -15 to 8 points), Folstein Mini-Mental State Examination (-0.1, -0.3 to 0.3 points), or the proportion of participants reporting falls (-1, -11 to 9%).
                In elderly women, hormone replacement had no statistically significant effect on cognition or balance, nor did it prevent the age-related decline in physical measures of mobility, ability to rise from a chair, self-reported activities of daily living, physical activity scores, or falls. Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory.
                The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women.
                This study was a randomized, double-blind, placebo-controlled clinical trial.
                Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI).
                Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied.
                Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE + MPA) or placebo.
                Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured.
                CEE + MPA had a negative impact on verbal memory (P <or= 0.01) and a trend to a positive impact on figural memory (P = 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms.
                The effect of CEE + MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research. Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition. It is suggested that replacement of estrogen would reinstate, at least in part, cognitive abilities. Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement and are mostly in the perimenopausal age-band.
                The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement (EHR) previously.
                EHR (Progynova TS, transdermal estradiol; n=19) or placebo (n=18) was given for a period of 3 weeks to elderly healthy female subjects. Memory, frontal lobe functions (inhibition and planning) and visuospatial abilities (mental rotation) were tested before and after treatment. Estrogen plasma levels were measured to confirm the result of EHR. Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo-pituitary-adrenal (HPA) axis to mild mental stress.
                Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman (0.21+/-0.5 nmol/l). Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR. However, there was no effect of EHR on frontal lobe functions. The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage. EHR was found to increase the HPA response to task-induced stress, as indicated by an increase in cortisol plasma levels.
                The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women. Furthermore, the present study has demonstrated a differential effect of EHR on memory, visuospatial abilities and frontal lobe function. The question of whether estrogen replacement therapy (ERT) is beneficial to cognitive functioning in postmenopausal women has become controversial in the past several years. Early studies suggested that ERT improved cognitive functioning and decreased the risk of Alzheimer's disease, but recent studies have failed to find any benefit. However, studies have varied in terms of the age of participants, the estrogen preparation used, whether progesterone is administered concurrently, and the study design. The present study used a randomized, placebo-controlled design and a transdermal estrogen preparation composed of 17-beta estradiol. A neuropsychological battery was administered at baseline and after completion of the 10-week trial, and test scores were grouped into four composite scores using psychometric techniques. Baseline to follow-up change was analyzed using multiple regression techniques. Results indicate that while little overall beneficial effect of estrogen was found, years since menopause was significantly related to change in executive functioning in the estrogen but not the placebo group, such that more recently postmenopausal women demonstrated greater positive change than older women. Body mass index, a gross estimate of circulating estrogen, was significantly positively related to change in attentional and psychomotor processes regardless of treatment group, and to a weaker extent, verbal memory, but only in the estrogen-treated group. These results suggest that reproductive events and levels of endogenous estrogen are related to the clinical response to ERT, but larger studies with longer follow-up periods are needed to determine the strength of these effects. To evaluate the effect of estrogen replacement therapy on cognitive functioning.
                The study consisted of two 3-month treatment periods, one with estrogen and one with the placebo, in random order, separated by a 1-month wash-out period. The study group comprised 70 healthy postmenopausal women, aged 47-65 years, with previous hysterectomy. Sixty-two women completed the study. Cognitive speed and accuracy, attention, and memory were evaluated. Serum estradiol (E2) and FSH levels were controlled at the end of the estrogen, placebo, and wash-out periods.
                Most of the cognitive tests correlated with age: older women were slower and made more errors than younger women. Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance. In two out of ten visual detection tasks, recognition thresholds were longer with estrogen than with the placebo (P < .001 and P = .004). On the most demanding test of working memory, the reaction times (P = .045) and error rates (P = .043) differed between treatments, yet this finding proved to be an effect of learning rather than treatment. There was no correlation between cognitive performance and serum E2 levels.
                Cognitive performance decreased with age. Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance. In the last ten years, numerous mechanisms by which sex steroids modify cortical function have been described. For example, estrogen replacement improves verbal memory in women, and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function. Little is known about sex steroid effects on other aspects of memory, such as frontal lobe-mediated working memory. We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women. Before hormone supplementation, working memory, tested with the Subject Ordered Pointing Test (SOP), was worse in older subjects than younger subjects, and there was no evidence of gender differences at either age. Testosterone supplementation improved working memory in older men, but a similar enhancement of working memory was not found in older women supplemented with estrogen. In men, testosterone and estrogen effects were reciprocal - with better working memory related to a higher testosterone to estrogen ratio. These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life. Postural instability and falls in the elderly patient constitute a major health care problem. The etiology is often multifactorial, involving abnormal sensory input (visual, vestibular, and somatosensory), poor central processing, and suboptimal musculoskeletal biomechanics. Estrogen replacement therapy has been shown to prevent Alzheimer's disease and to improve cognitive performance in women with dementia. It was, therefore, postulated that estrogen replacement may improve central processing speed, which would result in improved postural stability. In this prospective, randomized, double-blinded study, 87 elderly female subjects (age > 69) were examined by repeated dynamic platform posturography, to measure the effect of estrogen therapy versus placebo upon postural stability. Results indicate that those receiving estrogen had no significant improvement in postural stability at 2 and 8 months of treatment relative to those receiving placebo. Trail Making B test was used as the psychometric test of central processing speed. There was no significant effect of estrogen on this measure over the 8 months of observations. It is concluded that 8 months of estrogen replacement therapy has no significant effect on central processing speed or postural stability in a healthy older female population. Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women.
                To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks.
                Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998.
                Community volunteers tested in a hospital setting.
                Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years).
                Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments.
                Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory.
                Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks.
                Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.