 |
|
Estrogen Therapy in Postmenopausal Women
Effects on Cognitive Function and Dementia
Kristine Yaffe, MD;
George Sawaya, MD;
Ivan Lieberburg, PhD, MD;
Deborah Grady, MD, MPH
JAMA. 1998;279:688-695.
ABSTRACT
| |
Context.— Several studies have suggested that estrogen replacement therapy in postmenopausal women improves cognition, prevents development of dementia, and improves the severity of dementia, while other studies have not found a benefit of estrogen use.
Objective.— To determine whether postmenopausal estrogen therapy improves cognition, prevents development of dementia, or improves dementia severity.
Data Sources.— We performed a literature search of studies published from January 1966 through June 1997, using MEDLINE, manually searched bibliographies of articles identified, and consulted experts.
Study Selection.— Studies that evaluated biological mechanisms of estrogen's effect on the central nervous system and studies that addressed the effect of estrogen on cognitive function or on dementia.
Data Extraction.— We reviewed studies for methods, sources of bias, and outcomes and performed a meta-analysis of the 10 studies of postmenopausal estrogen use and risk of dementia using standard meta-analytic methods.
Data Synthesis.— Biochemical and neurophysiologic studies suggest several mechanisms by which estrogen may affect cognition: promotion of cholinergic and serotonergic activity in specific brain regions, maintenance of neural circuitry, favorable lipoprotein alterations, and prevention of cerebral ischemia. Five observational studies and 8 trials have addressed the effect of estrogen on cognitive function in nondemented postmenopausal women. Cognition seems to improve in perimenopausal women, possibly because menopausal symptoms improve, but there is no clear benefit in asymptomatic women. Ten observational studies have measured the effect of postmenopausal estrogen use on risk of developing dementia. Meta-analysis of these studies suggests a 29% decreased risk of developing dementia among estrogen users, but the findings of the studies are heterogeneous. Four trials of estrogen therapy in women with Alzheimer disease have been conducted and have had primarily positive results, but most have been small, of short duration, nonrandomized, and uncontrolled.
Conclusions.— There are plausible biological mechanisms by which estrogen might lead to improved cognition, reduced risk for dementia, or improvement in the severity of dementia. Studies conducted in women, however, have substantial methodologic problems and have produced conflicting results. Large placebo-controlled trials are required to address estrogen's role in prevention and treatment of Alzheimer disease and other dementias. Given the known risks of estrogen therapy, we do not recommend estrogen for the prevention or treatment of Alzheimer disease or other dementias until adequate trials have been completed.
INTRODUCTION
DEMENTIA or marked loss of intellectual function is a common and important medical problem. In 1 prospective study of ambulatory, independent persons aged 75 to 85 years, new cases of dementia occurred as frequently as myocardial infarction and more frequently than stroke.1 Approximately 10% of persons older than 65 years and almost 50% of those older than 85 years have dementia.2 Alzheimer disease (AD), the most common cause of dementia, is estimated to affect 3.75 million people in the United States and to cost $67 billion annually.3 Despite the severity and prevalence of dementia, there are few effective treatments or prevention strategies.
Some studies have suggested that postmenopausal estrogen therapy might improve cognition in nondemented perimenopausal and postmenopausal women, prevent the development of dementia, or improve the severity of dementia. We reviewed the basic biochemical and neurophysiologic evidence to support the role of estrogen in cognition and reviewed the current literature on the effects of estrogen therapy on cognitive function and dementia.
METHODS
We conducted a computerized MEDLINE search from January 1966 through June 1997, using the key words hormone replacement therapy, estrogen, estrogen replacement therapy, menopause, cognition, dementia, Alzheimer's disease, and memory, reviewed the bibliographies of identified articles, and consulted experts. We limited our review to peer-reviewed articles.
We first reviewed studies that provided evidence of possible biological mechanisms of the effect of estrogen on the central nervous system. We then located 40 articles containing primary data that addressed the effect of estrogen on cognitive function or dementia in women. After eliminating case reports and studies in premenopausal women, 27 studies were reviewed. Of these, 13 addressed the effect of estrogen use on cognitive function,4-16 10 addressed the effect of estrogen on risk for developing AD or other dementia,17-26 and 4 addressed the effect of estrogen treatment in women with AD.27-30 Our goal was to quantitatively summarize the results of these studies using formal meta-analytic techniques. However, studies of the effect of estrogen therapy on cognitive function and as treatment for AD used various designs and multiple different outcome measures, precluding quantitative summary of the data. In contrast, the predictor variable in each of the 10 studies of the effect of estrogen use on risk for dementia was previous or current postmenopausal hormone use (with or without concurrent progestin therapy) and the outcome was dementia, allowing us to perform a formal meta-analysis.
We performed separate meta-analyses of risk estimates for developing any dementia (AD and other dementia types)17-26 and for developing AD17-26 in estrogen users compared with nonusers. Studies that reported risk for AD based on criteria described by the National Institute of Neurologic and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)31 were summarized separately.17, 19-22,24-26 For each study, we used the most adjusted risk estimate and 95% confidence intervals (CIs) to calculate the summary odds ratio (OR). When 95% CIs were not reported, we calculated them from the adjusted exact P value or  2 provided in the publication17-18 or obtained them from the author.22 In studies where the control group included men, the ORs and CIs were recalculated for women subjects.19 For case-control studies with more than 1 control group, we included only the comparison with community controls.18 When authors published 2 studies with overlapping subjects, we reviewed the original study.23 The summary OR estimate and 95% CIs were calculated using a random-effects model and the general variance–based method.32-33 A test for heterogeneity was performed; P<.10 was considered statistically significant for this test.34
RESULTS
Possible Mechanisms of Estrogen's Effect on Cognition and Dementia
There are estrogen receptors in the hypothalamus, the preoptic area, anterior pituitary, CA1 region of the hippocampus, and several other brain regions.35 The role of these receptors in the function of the central nervous system is under investigation. How sex hormones may affect neuropsychologic function remains unknown, but several mechanisms have been suggested, including modulation of neurotransmitters, neurite and synapse reorganization, prevention of cerebral ischemia, and alterations in lipoproteins.
Modulation of Neurotransmitters
Cells in the basal forebrain, specifically the nucleus basalis of Meynert, send cholinergic projections to cortical, hippocampal, and amygdala regions. Degeneration of these neurons and their tracts has been shown to be one of the earliest and most pronounced neuropathologic changes in brains of patients with AD and age-related cognitive deficits.36-37 Estradiol administration to oophorectimized rats is associated with an increase in choline acetyltransferase and potassium-stimulated acetylcholine release in certain brain regions.38-40 Estradiol also prolongs survival of cholinergic neurons.41 Estrogen receptors colocalize with nerve growth factor receptors in cholinergic neurons in the rat basal forebrain.42 Estrogen-treated oophorectomized adult rats have superior performance on behavioral memory tasks compared with estrogen-deprived animals, and performance is associated with increased choline uptake and higher levels of choline acetyltransferase in the hippocampus and frontal cortex.43 Furthermore, estrogen counteracts cognitive impairments induced by scopolamine (a cholinergic muscarinic receptor blocker) in oophorectomized rats.44 These studies support the hypothesis that estrogen may, either independently or in synergy with other neurotrophic factors, improve cognitive function by promoting cholinergic activity in the brain.
Monoamine oxidase is a major enzyme in the central nervous system that metabolizes catecholamines, including serotonin, norepinephrine, and dopamine. Modulation of monoamine oxidase activity affects neurotransmitter activity in many neural pathways, including those involved in learning and memory. Abnormalities of the adrenergic, serotonergic, and dopaminergic systems have been described in AD.45 Estradiol administered to oophorectomized adult rats results in decreased monoamine oxidase activity in the amygdala and basomedial hypothalamus.46 Human studies have shown that estrogen treatment reduces serum and platelet monoamine oxidase levels47-48 and displaces tryptophan, the precursor of serotonin, from plasma albumin binding sites, possibly allowing more free tryptophan for central nervous system conversion to serotonin.49-50 In female rats, estradiol administration induces serotonin receptors in forebrain regions involved in cognition and behavior, including the frontal lobe, cingulate, and nucleus accumbens.51 The possible involvement of monoamine oxidase B inhibition with attendant increased adrenergic activity as a treatment for AD has been suggested by a recently published placebo-controlled, double-blind study in which selegiline (a monoamine oxidase B inhibitor) showed a modest beneficial effect on certain dementia-related outcome measures.52 Though the true value of such therapy is under debate,53 increased central adrenergic tone may be a mechanism whereby estrogens exert a portion of their therapeutic benefit.
Direct Effect on Neurons
Early neuron loss in the CA1 region of the hippocampus, a region associated with memory and learning, is found in patients with AD and age-related cognitive dysfunction. Decreased hippocampal pyramidal cell density, a change seen in AD and other dementias, has been correlated with verbal memory impairment.54 Estrogen regulates synaptic plasticity by stimulating axonal sprouting and dendritic spine formation in the adult rat hypothalamus and CA1 hippocampal pyramidal neurons.35, 55 Removal of circulating gonadal steroids by oophorectomy results in a profound loss of dendritic spine density in CA1 pyramidal cells in rats.56 Thus, at least in rats, estrogen plays a role in maintaining or promoting neuronal circuitry in several brain regions important in cognition.
Prevention of Cerebral Ischemia and Lipoprotein Alterations
Endogenous estrogens may protect against cerebral ischemia57 by inducing central nervous system vasodilatation, reducing central arterial smooth muscle injury response, or reducing platelet aggregation.58-60 Estrogen therapy protects rodent neurons against oxidative stress, excitotoxins, and  -amyloid–induced toxicity in cell culture.61-62 Postmenopausal estrogen therapy reduces serum low-density lipoprotein cholesterol and increases high-density lipoprotein cholesterol.58 These favorable lipoprotein changes may slow progression of cerebral atherosclerosis and prevent vascular dementia and other cognitive decline.
The apolipoprotein E isoform  4 has recently been identified as a major biological risk factor for AD and preclinical cognitive decline.63-64 Estrogen modulates the expression of the apolipoprotein E gene in rodent tissues and theoretically could reduce risk of AD in humans via apolipoprotein E alterations.65-66 Physiologic concentrations of estradiol in tissue culture promote the nonamyloidogenic metabolism of the amyloid precursor protein, which gives rise to the -amyloid peptide.67-68 Thus, estrogens may reduce the risk of AD through a variety of mechanisms.
Estrogen Therapy and Cognition in Healthy Women
Five observational studies have evaluated the association of estrogen therapy and cognitive performance (Table 1). Two of the studies reported inconclusive results,5-6 2 reported no association between estrogen and cognitive performance,4, 8 and 1 found that estrogen use improved cognitive function.7 In a cross-sectional study, Kampen and Sherwin5 administered 14 cognitive tests to 71 healthy, recently postmenopausal women and found that scores on only one of the tests (Paragraph Recall) were significantly higher in women taking estrogen compared with nonusers. There were no other differences between the estrogen users and nonusers, and there was no association of test scores with serum estrogen level. The analyses were not adjusted for education or depression. If estrogen users are better educated or less depressed than nonusers, these factors could account for the observed findings. Robinson et al6 conducted a cross-sectional study of 72 postmenopausal estrogen users and 72 nonusers matched for age and education to examine the association of estrogen use and performance on 2 recall tests. Women treated with estrogen performed significantly better on proper name recall but not on word recall compared with those not receiving estrogen.6 Kimura7 assessed performance on 10 cognitive tests and 1 mood scale in 21 postmenopausal women receiving estrogen replacement and 33 postmenopausal women not taking estrogen. Kimura concluded that the estrogen group had better overall performance on the cognitive tests, but no specific test scores or statistical analyses were reported. In the only prospective cohort study to date, Barrett-Connor and Kritz-Silverstein4 determined postmenopausal estrogen use among 800 white, upper-middle-class elderly women. Fifteen years later, cognitive function was measured using a battery of 12 cognitive function tests. Age- and education-adjusted comparisons showed no difference between users and nonusers, and no effect of dose or duration of estrogen use. Paganini-Hill and Henderson8 conducted a nested case-control study of 214 elderly upper-middle-class women to assess the association of estrogen replacement therapy and performance on a visual-spatial task, the Clock-Drawing Task. There was no statistically significant difference in percentage of normal and abnormal clock drawers in the estrogen users compared with the women not using estrogen.
|
|
|
|
Table 1.—Observational Studies of Estrogen and Cognition in Nondemented Postmenopausal Women
|
|
|
Observational studies of the association of estrogen use and cognitive performance are susceptible to confounding, especially by such strong predictors of cognitive performance as age, education, and depression.69 All of the studies described above either matched or statistically adjusted for age; only the findings of Barrett-Connor and Kritz-Silverstein4 and Robinson et al6 were matched or adjusted for education, and no study controlled for depression. Three of the studies compared estrogen users with nonusers based on the results of multiple cognitive tests.4-5,7 Such multiple comparisons between users and nonusers substantially increase the probability of obtaining at least 1 positive result by chance alone.
Seven randomized controlled trials and 1 nonrandomized controlled trial of the effect of estrogen therapy on cognitive function have been published (Table 2). 9-16 Six of these 8 trials concluded that estrogen therapy improved cognitive function.9, 11-14,16 However, substantial methodologic problems make the results of these trials difficult to evaluate. The trials are small, including only 18 to 64 subjects. Two of the older trials used neuropsychologic tests that are not validated or commonly used.9, 12 Two of the trials concluded that estrogen use improved cognitive function, despite the fact that there was improvement in only 1 or 2 of multiple cognitive tests.9, 16 Participants in 5 of the 6 studies that reported benefit from estrogen therapy included many recently menopausal women who had menopausal symptoms.11-14,16 Relief of vasomotor symptoms and insomnia might have resulted in improved cognitive performance. A recent placebo-controlled trial in asymptomatic postmenopausal women found little or no effect of estrogen therapy on cognitive test scores.15 Finally, several of these trials reported that scores on cognitive tests improved after treatment with estrogen, but did not compare these changes in the estrogen-treated group with results in the placebo-treated group.11, 15-16 In summary, all these trials have substantial methodologic problems. While there does appear to be evidence that estrogen therapy may improve cognitive performance in postmenopausal women with symptoms, there is no clear evidence of a beneficial effect in asymptomatic women.
|
|
|
|
Table 2.—Trials of Estrogen Therapy on Cognition in Nondemented Women
|
|
|
Estrogen Therapy and Risk for Dementia
The suggested beneficial effects of estrogen on cognition in normal postmenopausal women led to the hypothesis that estrogen deficiency associated with menopause may contribute to the development of dementia, including AD. In support of this theory, serum estrogens have been found to be lower in women with AD than in age-matched controls,28 and women may be at increased risk of developing AD compared with men.70 There have been 8 case-control studies (Table 3) and 2 prospective cohort studies (Table 4) conducted to evaluate the association between AD and other dementias and postmenopausal estrogen therapy. The results of these studies have ranged from suggesting a protective effect of estrogen on developing AD to suggesting an increased risk of developing AD (Figure 1). One of the case-control studies22 and the 2 prospective studies25-26 found a statistically lower risk of developing dementia in postmenopausal women who had taken estrogen compared with those who had not. Of the 7 other case-control studies, 2 showed a nonsignificant increased risk of dementia among estrogen users compared with nonusers,17-18 2 showed no difference in the risk of dementia,20-21 and 3 found a nonsignificant decreased risk of dementia among estrogen users compared with nonusers.19, 23-24 All these observational studies either matched cases and controls for age or statistically adjusted for age, but most were not adjusted for education, and none was adjusted for depression. The 1 case-control study that found an association between estrogen use and reduced risk for dementia found this association only for current estrogen users compared with nonusers (OR, 0.3; 95% CI, 0.1-0.7).22 Current use of estrogen might appear to be protective if physicians stop hormone therapy in women who develop cognitive dysfunction or dementia. In addition, retrospective studies might find an association between estrogen use and reduced risk for dementia if women with dementia do not report using estrogen in the past because they cannot remember. Two case-control studies that addressed this problem by using pharmacy records or a verified medication history reported conflicting results.21-22 Prospective studies can also avoid recall bias and the bias that may result from different prescribing practices in dementia patients. Both prospective cohort studies found a decreased risk of AD in estrogen users. In one of the prospective studies, estrogen use was recorded among 1124 elderly community-dwelling women who were evaluated for dementia 1 to 5 years later. Women who had ever used estrogen had a 50% reduction (adjusted OR, 0.5; 95% CI, 0.25-0.9) in risk of developing AD.25 The other prospective study found a similar reduction in risk of developing AD (adjusted OR, 0.46; 95% CI, 0.21-1.0) among 472 postmenopausal women enrolled in the Baltimore Longitudinal Study of Aging who were followed up for up to 16 years.26 Both prospective studies and 1 of the case-control studies examined whether increasing duration of estrogen use was associated with increasing protection of developing dementia and found conflicting results.23, 25-26
|
|
|
|
Table 3.—Case-Control Studies of the Association of Estrogen Use and Dementia*
|
|
|
|
|
|
|
Table 4.—Prospective Cohort Study of the Association of Estrogen Use and Dementia*
|
|
|
|
|
|
|
Odds ratios (circles) and 95% confidence intervals (horizontal lines) from studies of the risk of developing Alzheimer dementia (by any diagnostic criteria) in women receiving estrogens.
|
|
|
Meta-analysis of Observational Studies of Estrogen and Dementia
To provide a more precise estimate of the effect of estrogen therapy on risk of developing dementia, we performed a meta-analysis of the results of the observational studies described in Table 3 and Table 4. When the results of all studies in which the outcome was any type of dementia (AD and other dementia types),17-26 the summary OR was 0.71 (95% CI, 0.53-0.96; P for heterogeneity=.10) (Table 5). When the results of the 10 studies of AD (based on any criteria) are included in the meta-analysis,17-26 the summary OR was 0.71 (95% CI, 0.52-0.98; P for heterogeneity=.11). There was significant heterogeneity (P=.07) in the findings of the 8 studies that used the NINCDS-ADRDA criteria for diagnosis of AD.17, 19-22,24-26 Because heterogeneity might have been attributable to study design (case-control vs cohort studies), we conducted a separate analysis of the case-control studies and prospective studies. For the 8 case-control studies, the summary OR for any dementia was 0.79 (95% CI, 0.56-1.12; P for heterogeneity=.09); for any AD diagnosis, the OR was 0.8 (95% CI, 0.56-1.16; P for heterogeneity=.11); and for NINCDS-ADRDA criteria for AD diagnosis, the summary OR was 0.8 (95% CI, 0.56-1.12; P for heterogeneity=.09). The summary OR for the 2 prospective studies, both of which used NINCDS-ADRDA criteria for AD diagnosis, was 0.48 (95% CI, 0.29-0.81; P for heterogeneity=.86).
|
|
|
|
Table 5.—Results of Meta-analyses of Estrogen and Dementia Risk*
|
|
|
Trials of Estrogen in AD
Epidemiologic evidence suggesting that estrogen use may prevent development of AD and improve cognitive function has sparked interest in estrogen as a treatment for AD. There have been 4 small trials of estrogen therapy in women with AD (Table 6). In 2 uncontrolled trials that each included 7 participants, severity of dementia was measured at baseline and after 6 weeks of estrogen therapy.27-28 Each of these studies found improvement on some, but not all measures of dementia severity after treatment. Because there was no control group for comparison, this improvement may represent a practice or learning effect. In addition, these 2 trials were not blinded, which may have biased measurement of outcome. In another trial, 15 women with AD were treated with estrogen, and change in dementia severity was compared with 15 untreated controls matched for age and dementia severity at baseline.30 The treatment group improved on 1 cognitive scale and on 1 dementia rating scale compared with scores prior to treatment, while the control group did not improve, but changes in the severity of dementia in the estrogen-treated group were not compared with changes in the untreated group. In the only placebo-controlled trial, Honjo et al 29 randomly assigned 14 women with AD to receive estrogen (1.25 mg/d of conjugated oral estrogen) or placebo and found greater improvement on 1 dementia scale but not on 2 others in the estrogen-treated compared to the placebo-treated group.29 All 4 of these studies are limited by small sample size, short duration of therapy (3 to 6 weeks), and the inclusion of subjects with a wide range of dementia severity.
|
|
|
|
Table 6.—Trials of Estrogen in Alzheimer Disease*
|
|
|
COMMENT
There are plausible biological and neurophysiologic mechanisms that might account for a beneficial effect of estrogen therapy on cognition, a reduced risk for developing dementia, or improvement in the severity of dementia. Actual studies in women, however, have substantial methodologic problems and have produced conflicting results.
The largest and most methodologically sound observational study of the effect of estrogen use on cognition in nondemented women showed no benefit.4 The results of 8 small trials of estrogen therapy in nondemented women are inconclusive.9-16 Many of these trials included primarily recently menopausal women who are likely to have substantial menopausal symptoms; others showed improvement on only 1 or 2 multiple cognitive tests, and several did not compare changes in cognition in the estrogen-treated group with the placebo group. In summary, there is evidence that estrogen therapy improves cognitive performance in recently menopausal women, but no evidence of a beneficial effect in asymptomatic women.
Our meta-analysis of the observational studies of the effect of estrogen therapy on risk for developing dementia suggests a 29% decreased risk among estrogen users. If true, this risk reduction would be of major public health importance. Summary findings from meta-analysis, however, are only as reliable as the findings of the individual studies. Unfortunately, the observational studies that we summarized are susceptible to confounding and compliance bias. For example, women who choose to take estrogen have been reported to be better educated and healthier than nonusers,71-74 differences that may result in a lower risk for developing AD.75-76 In addition, compliance with assigned medication is a marker for reduced risk of various disease conditions77-80 and may also account for the reduced risk of AD in women using estrogen. In summary, the evidence from these observational studies is weak, and large, controlled, blinded trials are necessary to determine if estrogen therapy can reduce the risk of developing AD. The Women's Health Initiative Randomized Trial, which is currently enrolling participants, will include the Women's Health Initiative Memory Study. This ancillary trial will determine the effect of hormone replacement therapy on cognitive function and risk for developing AD and other dementias among approximately 8000 postmenopausal women treated for 10 years.
Should estrogen therapy be used as treatment in persons with AD? Only 58 women have been studied in trials of estrogen therapy for treatment of AD, and most of these trials were uncontrolled, unblinded, and nonrandomized. Only 1 randomized, placebo-controlled, blinded trial has been published. It was conducted in 14 women with AD who were randomly assigned to receive 1.25 mg/d of conjugated estrogen or placebo daily for 3 weeks. Estrogen-treated women improved on 1 severity scale, but not on 2 others. Based on the weakness of this evidence and the potential adverse effects of estrogen therapy (endometrial abnormalities,81 gallbladder disease,82 venous thromboembolic events,83-86 and breast cancer87-89), we do not believe that estrogen should currently be used to treat women with AD. However, given the lack of available treatment options for women with AD and the suggestive preliminary findings of benefit, we believe that a large randomized trial of estrogen therapy should be completed as soon as possible. Whether estrogen therapy might improve other forms of dementia, such as vascular dementia, should also be explored. Finally, since progestins are typically added to the estrogen regimen in women with a uterus, the role of this hormone must also be evaluated in future studies.
AUTHOR INFORMATION
Dr Lieberburg is an employee of and stockholder in Athena Neurosciences, a wholly owned subsidiary of the Elan Corporation. Elan is engaged in drug discoveries related to new treatments for Alzheimer disease. Dr Grady has received research support and honoraria from Wyeth-Ayerst.
Reprints: Kristine Yaffe, MD, UCSF/VA Medical Center (111G), 4150 Clement St, San Francisco, CA 94121 (e-mail: kyaffe{at}itsa.ucsf.edu).
From the Departments of Psychiatry (Dr Yaffe), Medicine (Drs Lieberburg and Grady), Epidemiology and Biostatistics (Drs Sawaya and Grady), and Obstetrics and Gynecology (Dr Sawaya), University of California, San Francisco, and Athena Neurosciences, South San Francisco, Calif (Dr Lieberburg).
REFERENCES
| |
1. Katzman R. Alzheimer's disease. N Engl J Med. 1986;314:964-973.
ISI
| PUBMED
2. Evans DA. Estimated prevalence of Alzheimer's disease in the United States. Milbank Q. 1990;68:267-289.
FULL TEXT
|
ISI
| PUBMED
3. Ernst RL, Hay JW. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 1994;84:1261-1264.
FREE FULL TEXT
4. Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. JAMA. 1993;269:2637-2641.
FREE FULL TEXT
5. Kampen DL, Sherwin BB. Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol. 1994;83:979-983.
ISI
| PUBMED
6. Robinson D, Friedman L, Marcus R, Tinklenberg J, Yesavage J. Estrogen replacement therapy and memory in older women. J Am Geriatr Soc. 1994;42:919-922.
ISI
| PUBMED
7. Kimura D. Estrogen replacement therapy may protect against intellectual decline in postmenopausal women. Horm Behav. 1995;29:312-321.
FULL TEXT
| PUBMED
8. Paganini-Hill A, Henderson VW. The effects of hormone replacement therapy, lipoprotein cholesterol levels, and other factors on a clock drawing task in older women. J Am Geriatr Soc. 1996;44:818-822.
ISI
| PUBMED
9. Caldwell B, Watson R. An evaluation of psychologic effects of sex hormone administration in aged women: results after six months. J Gerontol. 1952;7:228-244.
FREE FULL TEXT
10. Rauramo L, Lagerspetz K, Engblom P, Punnonen R. The effect of castration and peroral estrogen therapy on some psychological functions. Front Horm Res. 1975;3:94-104.
PUBMED
11. Hackman BW, Galbraith D. Replacement therapy and piperazine oestrone sulphate (‘Harmogen') and its effect on memory. Curr Med Res Opin. 1976;4:303-306.
PUBMED
12. Campbell S, Whitehead M. Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol. 1977;4:31-47.
ISI
| PUBMED
13. Fedor-Freybergh P. The influence of oestrogens on the wellbeing and mental performance in climacteric and postmenopausal women. Acta Obstet Gynecol Scand Suppl. 1977;64:1-91.
PUBMED
14. Sherwin BB. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology. 1988;13:345-357.
FULL TEXT
|
ISI
| PUBMED
15. Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol. 1991;78:991-995.
ISI
| PUBMED
16. Phillips SM, Sherwin BB. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology. 1992;17:485-495.
FULL TEXT
|
ISI
| PUBMED
17. Heyman A, Wilkinson WE, Stafford JA, et al. Alzheimer's disease: a study of epidemiological aspects. Ann Neurol. 1984;15:335-341.
FULL TEXT
|
ISI
| PUBMED
18. Amaducci LA, Fratiglioni L, Rocca WA, et al. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population. Neurology. 1986;36:922-931.
FREE FULL TEXT
19. Broe GA, Henderson AS, Creasey H, et al. A case-control study of Alzheimer's disease in Australia. Neurology. 1990;40:1698-1707.
FREE FULL TEXT
20. Graves AB, White E, Koepsell TD, et al. A case-control study of Alzheimer's disease. Ann Neurol. 1990;28:766-774.
FULL TEXT
|
ISI
| PUBMED
21. Brenner DE, Kukull WA, Stergachis A, et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am J Epidemiol. 1994;140:262-267.
FREE FULL TEXT
22. Henderson VW, Paganini HA, Emanuel CK, Dunn ME, Buckwalter JG. Estrogen replacement therapy in older women: comparisons between Alzheimer's disease cases and nondemented control subjects. Arch Neurol. 1994;51:896-900.
FREE FULL TEXT
23. Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of Alzheimer's disease in women. Am J Epidemiol. 1994;140:256-261.
FREE FULL TEXT
24. Mortel KF, Meyer JS. Lack of postmenopausal estrogen replacement therapy and the risk of dementia. J Neuropsychiatry Clin Neurosci. 1995;7:334-337.
FREE FULL TEXT
25. Tang MX, Jacobs D, Stern Y, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996;348:429-432.
FULL TEXT
|
ISI
| PUBMED
26. Kawas C, Resnick S, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology. 1997;48:1517-1521.
FREE FULL TEXT
27. Fillit H, Weinreb H, Cholst I, et al. Observations in a preliminary open trial of estradiol therapy for senile dementia-Alzheimer's type. Psychoneuroendocrinology. 1986;11:337-345.
FULL TEXT
|
ISI
| PUBMED
28. Honjo H, Ogino Y, Naitoh K, et al. In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer's type). J Steroid Biochem. 1989;34:521-525.
FULL TEXT
|
ISI
| PUBMED
29. Honjo H, Ogino Y, Naitoh K, et al. An effect of conjugated estrogen to cognitive impairment in women with senile dementia-Alzheimer's type: a placebo-controlled double blind study. J Jpn Menopause Soc. 1993;1:167-171.
30. Ohkura T, Isse K, Akazawa K, et al. Evaluation of estrogen treatment in female patients with dementia of the Alzheimer type. Endocr J. 1994;41:361-371.
ISI
| PUBMED
31. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34:939-944.
FREE FULL TEXT
32. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1-30.
FREE FULL TEXT
33. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin Trials. 1986;7:177-188.
FULL TEXT
|
ISI
| PUBMED
34. Oxman AD, Cook DJ, Guyatt GH, et al. Users' guides to the medical literature, VI: how to use an overview. JAMA. 1994;272:1367-1371.
FREE FULL TEXT
35. McEwen BS, Woolley CS. Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain. Exp Gerontol. 1994;29:431-436.
FULL TEXT
|
ISI
| PUBMED
36. Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408-414.
FREE FULL TEXT
37. Coyle JT, Price DL, DeLong MR. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science. 1983;219:1184-1190.
FREE FULL TEXT
38. Luine VN. Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Exp Neurol. 1985;89:484-490.
FULL TEXT
|
ISI
| PUBMED
39. O'Malley CA, Hautamaki RD, Kelley M, Meyer EM. Effects of ovariectomy and estradiol benzoate on high affinity choline uptake, ACh synthesis, and release from rat cerebral cortical synaptosomes. Brain Res. 1987;403:389-392.
FULL TEXT
|
ISI
| PUBMED
40. Gibbs RB, Hashash A, Johnson DA. Effects of estrogen on potassium-stimulated acetylcholine release in the hippocampus and overlying cortex of adult rats. Brain Res. 1997;749:143-146.
FULL TEXT
|
ISI
| PUBMED
41. Honjo H, Tamura T, Matsumoto Y, et al. Estrogen as a growth factor to central nervous cells: estrogen treatment promotes development of acetylcholinesterase-positive basal forebrain neurons transplanted in the anterior eye chamber. J Steroid Biochem Mol Biol. 1992;41:633-635.
FULL TEXT
|
ISI
| PUBMED
42. Toran-Allerand C, Miranda RC, Bentham WD, et al. Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A. 1992;89:4668-4672.
FREE FULL TEXT
43. Simpkins JW, Singh M, Bishop J. The potential role for estrogen replacement therapy in the treatment of the cognitive decline and neurodegeneration associated with Alzheimer's disease. Neurobiol Aging. 1994;15(suppl 2):S195-S197.
44. Dohanich GP, Fader AJ, Javorsky DJ. Estrogen and estrogen-progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats. Behav Neurosci. 1994;108:988-992.
FULL TEXT
|
ISI
| PUBMED
45. Palmer AM, DeKosky ST. Monoamine neurons in aging and Alzheimer's disease. J Neural Transm Gen Sect. 1993;91:135-159.
FULL TEXT
|
ISI
| PUBMED
46. Luine VN, Khylchevskaya RI, McEwen BS. Effect of gonadal steroids on activities of monoamine oxidase and choline acetylase in rat brain. Brain Res. 1975;86:293-306.
FULL TEXT
|
ISI
| PUBMED
47. Poirier MF, Loo H, Dennis T, Le FG, Scatton B. Platelet monoamine oxidase activity and plasma 3,4-dihydroxyphenylethylene glycol levels during the menstrual cycle. Neuropsychobiology. 1985;14:165-169.
ISI
| PUBMED
48. Klaiber EL, Broverman DM, Vogel W, Kobayashi Y. Estrogen therapy for severe persistent depressions in women. Arch Gen Psychiatry. 1979;36:550-554.
FREE FULL TEXT
49. Aylward M. Plasma tryptophan levels and mental depression in postmenopausal subjects: effects of oral piperazine-oestrone sulphate. IRCS Med Sci. 1973;1:30-34.
50. Thomson J, Maddock J, Aylward M, Oswald I. Relationship between nocturnal plasma oestrogen concentration and free plasma tryptophan in perimenopausal women. J Endocrinol. 1977;72:395-396.
FREE FULL TEXT
51. Summer BE, Fink G. Estrogen increases the density of 5-hydroxytryptamine(2A) receptors in cerebral cortex and nucleus accumbens in the female rat. J Steroid Biochem Mol Biol. 1995;54:15-20.
FULL TEXT
|
ISI
| PUBMED
52. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease: the Alzheimer's Disease Cooperative Study. N Engl J Med. 1997;336:1216-1222.
FREE FULL TEXT
53. Drachman DA, Leber P. Treatment of Alzheimer's disease: searching for a breakthrough, settling for less. N Engl J Med. 1997;336:1245-1247.
FREE FULL TEXT
54. Sass KJ, Spencer DD, Kim JH, et al. Verbal memory impairment correlates with hippocampal pyramidal cell density. Neurology. 1990;40:1694-1697.
FREE FULL TEXT
55. Matsumoto A. Synaptogenic action of sex steroids in developing and adult neuroendocrine brain. Psychoneuroendocrinology. 1991;16:25-40.
FULL TEXT
|
ISI
| PUBMED
56. Gould E, Woolley CS, Frankfurt M, McEwen BS. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci. 1990;10:1286-1291.
ABSTRACT
57. Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal oestrogen treatment and stroke: a prospective study. BMJ. 1988;297:519-522.
FREE FULL TEXT
58. Applebaum-Bowden D, McLean P, Steinmetz A, et al. Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopausal women. J Lipid Res. 1989;30:1895-1906.
ABSTRACT
59. Gangar KF, Vyas S, Whitehead M, et al. Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause. Lancet. 1991;338:839-842.
FULL TEXT
|
ISI
| PUBMED
60. Sullivan TJ, Karas RH, Aronovitz M, et al. Estrogen inhibits the response-to-injury in a mouse carotid artery model. J Clin Invest. 1995;96:2482-2488.
ISI
| PUBMED
61. Behl C, Widmann M, Trapp T, Holsboer F. 17-Beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995;216:473-482.
FULL TEXT
|
ISI
| PUBMED
62. Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem. 1996;66:1836-1844.
ISI
| PUBMED
63. Roses AD. Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease. Ann Neurol. 1995;38:6-14.
FULL TEXT
|
ISI
| PUBMED
64. Yaffe K, Cauley J, Sands L, Browner W. Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. Arch Neurol. 1997;54:1110-1114.
FREE FULL TEXT
65. Honjo H, Tanaka K, Kashiwagi T, et al. Senile dementia-Alzheimer's type and estrogen. Horm Metab Res. 1995;27:204-207.
ISI
| PUBMED
66. Srivastava RA, Bhasin N, Srivastava N. Apolipoprotein E gene expression in various tissues of mouse and regulation by estrogen. Biochem Mol Biol Int. 1996;38:91-101.
ISI
| PUBMED
67. Jaffe AB, Toran-Allerand C, Greengard P, Gandy SE. Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J Biol Chem. 1994;269:13065-13068.
FREE FULL TEXT
68. Green PS, Gridley KE, Simpkins JW. Estradiol protects against beta-amyloid (25-35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neurosci Lett. 1996;218:165-168.
FULL TEXT
|
ISI
| PUBMED
69. Kittner SJ, White LR, Farmer ME, et al. Methodological issues in screening for dementia: the problem of education adjustment. J Chronic Dis. 1986;39:163-170.
FULL TEXT
|
ISI
| PUBMED
70. Aronson MK, Ooi WL, Morgenstern H, et al. Women, myocardial infarction, and dementia in the very old. Neurology. 1990;40:1102-1106.
FREE FULL TEXT
71. Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med. 1991;115:455-456.
FULL TEXT
|
ISI
| PUBMED
72. Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG. Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol. 1990;163:1438-1444.
ISI
| PUBMED
73. Egeland GM, Kuller LH, Matthews KA, et al. Premenopausal determinants of menopausal estrogen use. Prev Med. 1991;20:343-349.
FULL TEXT
|
ISI
| PUBMED
74. Posthuma WF, Westendorp RG, Vandenbroucke JP. Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased? BMJ. 1994;308:1268-1269.
FREE FULL TEXT
75. Cobb JL, Wolf PA, Au R, White R, D'Agostino RB. The effect of education on the incidence of dementia and Alzheimer's disease in the Framingham Study. Neurology. 1995;45:1707-1712.
FREE FULL TEXT
76. Mortimer JA, Graves AB. Education and other socioeconomic determinants of dementia and Alzheimer's disease. Neurology. 1993;43(suppl 4):S39-S44.
77. Petitti DB. Coronary heart disease and estrogen replacement therapy: can compliance bias explain the results of observational studies? Ann Epidemiol. 1994;4:115-118.
PUBMED
78. Horwitz RI, Viscoli CM, Berkman L, et al. Treatment adherence and risk of death after a myocardial infarction. Lancet. 1990;336:542-545.
FULL TEXT
|
ISI
| PUBMED
79. Pizzo PA, Robichaud KJ, Edwards BK, et al. Oral antibiotic prophylaxis in patients with cancer: a double-blind randomized placebo-controlled trial. J Pediatr. 1983;102:125-133.
FULL TEXT
|
ISI
| PUBMED
80. The Coronary Drug Project Research Group. Influence of treatment adherence in the coronary drug project. N Engl J Med. 1981;304:612-613.
PUBMED
81. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016-1037.
FREE FULL TEXT
82. Petitti DB, Sidney S, Perlman JA. Increased risk of cholecystectomy in users of supplemental estrogen. Gastroenterology. 1988;94:91-95.
ISI
| PUBMED
83. Gutthan SP, Rodriguez LG, Castellsague J, Oliart AD. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ. 1997;314:796-800.
FREE FULL TEXT
84. Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet. 1996;348:981-983.
FULL TEXT
|
ISI
| PUBMED
85. Daly E, Vessey MP, Hawkins MM, et al. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet. 1996;348:977-980.
FULL TEXT
|
ISI
| PUBMED
86. Grodstein F, Stampfer MJ, Goldhaber SZ, et al. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet. 1996;348:983-987.
FULL TEXT
|
ISI
| PUBMED
87. Grady D, Ernster V. Does postmenopausal hormone therapy cause breast cancer? Am J Epidemiol. 1991;134:1396-1400.
FREE FULL TEXT
88. Colditz GA, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332:1589-1593.
FREE FULL TEXT
89. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet. 1997;350:1047-1059.
FULL TEXT
|
ISI
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Hormone therapy and cognitive function
Maki and Sundermann
Hum Reprod Update 2009;15:667-681.
ABSTRACT
| FULL TEXT
Reviews: Current Concepts in Alzheimer's Disease: A Multidisciplinary Review
Minati et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2009;24:95-121.
ABSTRACT
Dementia Prevention: Methodological Explanations for Inconsistent Results
Coley et al.
Epidemiol Rev 2008;30:35-66.
ABSTRACT
| FULL TEXT
A multi-center, randomized, double blind placebo-controlled trial of estrogens to prevent Alzheimer's disease and loss of memory in women: design and baseline characteristics
Sano et al.
Clin Trials 2008;5:523-533.
ABSTRACT
Prophylactic oophorectomy in premenopausal women and long-term health
Shuster et al.
Menopause Int 2008;14:111-116.
ABSTRACT
| FULL TEXT
Differential Dietary Nutrient Intake according to Hormone Replacement Therapy Use: An Underestimated Confounding Factor in Epidemiologic Studies?
Vercambre et al.
Am J Epidemiol 2007;166:1451-1460.
ABSTRACT
| FULL TEXT
Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause
Rocca et al.
Neurology 2007;69:1074-1083.
ABSTRACT
| FULL TEXT
An epidemiologic study of mild cognitive impairment in Kolkata, India
Das et al.
Neurology 2007;68:2019-2026.
ABSTRACT
| FULL TEXT
Historical Perspectives in Postmenopausal Hormone Therapy: Defining the Right Dose and Duration
Warren
Mayo Clin Proc. 2007;82:219-226.
ABSTRACT
| FULL TEXT
Behavior-Based Interventions to Enhance Cognitive Functioning and Independence in Older Adults
Shumaker et al.
JAMA 2006;296:2852-2854.
FULL TEXT
Dose and Temporal Pattern of Estrogen Exposure Determines Neuroprotective Outcome in Hippocampal Neurons: Therapeutic Implications
Chen et al.
Endocrinology 2006;147:5303-5313.
ABSTRACT
| FULL TEXT
Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women
Morrison et al.
J. Neurosci. 2006;26:10332-10348.
FULL TEXT
Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life.
Yaffe et al.
Arch Neurol 2006;63:945-950.
ABSTRACT
| FULL TEXT
Neuroprotective Effects of 17beta-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells
Wang et al.
Mol. Pharmacol. 2006;70:395-404.
ABSTRACT
| FULL TEXT
Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA.
Labrie
Endocr Relat Cancer 2006;13:335-355.
ABSTRACT
| FULL TEXT
Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men
Lu et al.
Arch Neurol 2006;63:177-185.
ABSTRACT
| FULL TEXT
Effect of Raloxifene on Prevention of Dementia and Cognitive Impairment in Older Women: The Multiple Outcomes of Raloxifene Evaluation (MORE) Randomized Trial
Yaffe et al.
Am. J. Psychiatry 2005;162:683-690.
ABSTRACT
| FULL TEXT
Effect of Estrogen-Serotonin Interactions on Mood and Cognition
Amin et al.
Behav Cogn Neurosci Rev 2005;4:43-58.
ABSTRACT
Bone Mineral Density and the Risk of Alzheimer Disease
Tan et al.
Arch Neurol 2005;62:107-111.
ABSTRACT
| FULL TEXT
The Women's Health Initiative Study of Cognitive Aging (WHISCA): a randomized clinical trial of the effects of hormone therapy on age-associated cognitive decline
Resnick et al.
Clin Trials 2004;1:440-450.
ABSTRACT
Benefits and Risks of Sex Hormone Replacement in Postmenopausal Women
Seelig et al.
J. Am. Coll. Nutr. 2004;23:482S-496S.
ABSTRACT
| FULL TEXT
Premorbid cognitive testing predicts the onset of dementia and Alzheimer's disease better than and independently of APOE genotype
Cervilla et al.
J. Neurol. Neurosurg. Psychiatry 2004;75:1100-1106.
ABSTRACT
| FULL TEXT
Effect of Soy Protein Containing Isoflavones on Cognitive Function, Bone Mineral Density, and Plasma Lipids in Postmenopausal Women: A Randomized Controlled Trial
Kreijkamp-Kaspers et al.
JAMA 2004;292:65-74.
ABSTRACT
| FULL TEXT
Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women's Health Initiative Memory Study
Shumaker et al.
JAMA 2004;291:2947-2958.
ABSTRACT
| FULL TEXT
Conjugated Equine Estrogens and Global Cognitive Function in Postmenopausal Women: Women's Health Initiative Memory Study
Espeland et al.
JAMA 2004;291:2959-2968.
ABSTRACT
| FULL TEXT
Estrogen and Dementia: Insights From the Women's Health Initiative Memory Study
Schneider
JAMA 2004;291:3005-3007.
FULL TEXT
Estrogen Decreases Zinc Transporter 3 Expression and Synaptic Vesicle Zinc Levels in Mouse Brain
Lee et al.
J. Biol. Chem. 2004;279:8602-8607.
ABSTRACT
| FULL TEXT
Cognitive Function, Fatigue, and Menopausal Symptoms in Women Receiving Adjuvant Chemotherapy for Breast Cancer
Tchen et al.
JCO 2003;21:4175-4183.
ABSTRACT
| FULL TEXT
Postmenopausal Hormone Therapy and Its Association With Cognitive Impairment
Mitchell et al.
Arch Intern Med 2003;163:2485-2490.
ABSTRACT
| FULL TEXT
The Combination of a Novel Selective Estrogen Receptor Modulator with an Estrogen Protects the Mammary Gland and Uterus in a Rodent Model: The Future of Postmenopausal Women's Health?
Labrie et al.
Endocrinology 2003;144:4700-4706.
ABSTRACT
| FULL TEXT
An Estrogen Replacement Therapy Containing Nine Synthetic Plant-Based Conjugated Estrogens Promotes Neuronal Survival
Zhao et al.
Exp. Biol. Med. 2003;228:823-835.
ABSTRACT
| FULL TEXT
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
Shumaker et al.
JAMA 2003;289:2651-2662.
ABSTRACT
| FULL TEXT
Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial
Rapp et al.
JAMA 2003;289:2663-2672.
ABSTRACT
| FULL TEXT
Hormone Therapy and the Brain: Deja Vu All Over Again?
Yaffe
JAMA 2003;289:2717-2719.
FULL TEXT
DHEA treatment of Alzheimer's disease: A randomized, double-blind, placebo-controlled study
Wolkowitz et al.
Neurology 2003;60:1071-1076.
ABSTRACT
| FULL TEXT
Estrogen and Cognitive Functioning in Women
Sherwin
Endocr. Rev. 2003;24:133-151.
ABSTRACT
| FULL TEXT
Estrogen and Cognition: The Story So Far
Asthana
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2003;58:M322-323.
FULL TEXT
Adjuvant Breast Cancer Treatment and Cognitive Function: Current Knowledge and Research Directions
Phillips and Bernhard
JNCI J Natl Cancer Inst 2003;95:190-197.
ABSTRACT
| FULL TEXT
Higher Estrogen Levels Are Not Associated With Larger Hippocampi and Better Memory Performance
den Heijer et al.
Arch Neurol 2003;60:213-220.
ABSTRACT
| FULL TEXT
Hormone Therapy and Risk of Alzheimer Disease: A Critical Time
Resnick and Henderson
JAMA 2002;288:2170-2172.
FULL TEXT
The Role of Hormone Replacement Therapy in the Prevention of Alzheimer Disease
Fillit
Arch Intern Med 2002;162:1934-1942.
ABSTRACT
| FULL TEXT
Re: The Effects of Tamoxifen and Estrogen on Brain Metabolism in Elderly Women
Benson
JNCI J Natl Cancer Inst 2002;94:1336-1336.
FULL TEXT
Cognitive Decline Among Female Estrogen Users in Nursing Homes
Ott et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2002;57:M594-598.
ABSTRACT
| FULL TEXT
Hormone Replacement Therapy for Prevention: More Evidence, More Pessimism
Petitti
JAMA 2002;288:99-101.
FULL TEXT
Neuroprotective and Neurotrophic Efficacy of Phytoestrogens in Cultured Hippocampal Neurons
Zhao et al.
Exp. Biol. Med. 2002;227:509-519.
ABSTRACT
| FULL TEXT
Achieving and Maintaining Cognitive Vitality With Aging
Fillit et al.
Mayo Clin Proc. 2002;77:681-696.
ABSTRACT
Frontiers in Neuropharmacotherapy Part I: Alzheimer's Disease and Epilepsy
Chappell and Cohen
Journal of Pharmacy Practice 2002;15:195-220.
ABSTRACT
Endogenous Estradiol in Elderly Individuals: Cognitive and Noncognitive Associations
Senanarong et al.
Arch Neurol 2002;59:385-389.
ABSTRACT
| FULL TEXT
Use of Lipid-Lowering Agents, Indication Bias, and the Risk of Dementia in Community-Dwelling Elderly People
Rockwood et al.
Arch Neurol 2002;59:223-227.
ABSTRACT
| FULL TEXT
Definition of the Molecular and Cellular Mechanisms Underlying the Tissue-selective Agonist/Antagonist Activities of Selective Estrogen Receptor Modulators
McDonnell et al.
Recent Prog Horm Res 2002;57:295-316.
ABSTRACT
| FULL TEXT
Current Concepts in Mild Cognitive Impairment
Petersen et al.
Arch Neurol 2001;58:1985-1992.
ABSTRACT
| FULL TEXT
Bone Mineral Density and Verbal Memory Impairment: Third National Health and Nutrition Examination Survey
Zhang et al.
Am J Epidemiol 2001;154:795-802.
ABSTRACT
| FULL TEXT
High-dose estradiol improves cognition for women with AD: Results of a randomized study
Asthana et al.
Neurology 2001;57:605-612.
ABSTRACT
| FULL TEXT
Hormone replacement therapy (HRT)-- risks and benefits
Barrett-Connor and Stuenkel
Int J Epidemiol 2001;30:423-426.
FULL TEXT
Cellular and Molecular Mechanisms of Estrogen Regulation of Memory Function and Neuroprotection Against Alzheimer's Disease: Recent Insights and Remaining Challenges
Brinton
Learn. Mem. 2001;8:121-133.
ABSTRACT
| FULL TEXT
The menopause and its treatment in perspective
Al-Azzawi
Postgrad. Med. J. 2001;77:292-304.
FULL TEXT
Cognitive Function in Postmenopausal Women Treated with Raloxifene
Yaffe et al.
NEJM 2001;344:1207-1213.
ABSTRACT
| FULL TEXT
Can Estrogen or Selective Estrogen-Receptor Modulators Preserve Cognitive Function in Elderly Women?
Mayeux
NEJM 2001;344:1242-1244.
FULL TEXT
Differential Mechanisms of Neuroprotection by 17 {beta}-Estradiol in Apoptotic versus Necrotic Neurodegeneration
Harms et al.
J. Neurosci. 2001;21:2600-2609.
ABSTRACT
| FULL TEXT
Reproductive Period and Risk of Dementia in Postmenopausal Women
Geerlings et al.
JAMA 2001;285:1475-1481.
ABSTRACT
| FULL TEXT
Hormone Replacement Therapy and Cognition: Systematic Review and Meta-analysis
LeBlanc et al.
JAMA 2001;285:1489-1499.
ABSTRACT
| FULL TEXT
Alzheimer's Disease in Man and Transgenic Mice : Females at Higher Risk
Turner
Am. J. Pathol. 2001;158:797-801.
FULL TEXT
Impact of Estrogen Use on Decline in Cognitive Function in a Representative Sample of Older Community-resident Women
Fillenbaum et al.
Am J Epidemiol 2001;153:137-144.
ABSTRACT
| FULL TEXT
Are Women Being Counseled about Estrogen Replacement Therapy?
Gallagher et al.
Med Care Res Rev 2000;57:72-92.
ABSTRACT
Cognitive performance in surgically menopausal women on estrogen
Verghese et al.
Neurology 2000;55:872-874.
ABSTRACT
| FULL TEXT
Effect of estrogen on cerebral glucose metabolism in postmenopausal women
Eberling et al.
Neurology 2000;55:875-877.
ABSTRACT
| FULL TEXT
Estrogen to treat Alzheimer's disease: Too little, too late?: So what's a woman to do?
Marder and Sano
Neurology 2000;54:2035-2037.
FULL TEXT
Effects of estrogen on cognition, mood, and cerebral blood flow in AD: A controlled study
Wang et al.
Neurology 2000;54:2061-2066.
ABSTRACT
| FULL TEXT
Estrogen use, APOE, and cognitive decline: Evidence of gene-environment interaction
Yaffe et al.
Neurology 2000;54:1949-1954.
ABSTRACT
| FULL TEXT
Hormone replacement therapy: discrepancies between evidence and recommendations
Hemminki
Scand J Public Health 2000;28:81-83.
ABSTRACT
Tofu and Cognitive Function: Food for Thought
Grodstein et al.
J. Am. Coll. Nutr. 2000;19:207-209.
FULL TEXT
Estrogen and Alzheimer Disease: Plausible Theory, Negative Clinical Trial
Shaywitz and Shaywitz
JAMA 2000;283:1055-1056.
FULL TEXT
Endogenous estrogen levels and Alzheimer's disease among postmenopausal women
Manly et al.
Neurology 2000;54:833-837.
ABSTRACT
| FULL TEXT
Alzheimer disease: protective factors1
Nourhashemi et al.
Am. J. Clin. Nutr. 2000;71:643s-649s.
ABSTRACT
| FULL TEXT
Use of estrogen in young girls with Turner syndrome: Effects on memory
Ross et al.
Neurology 2000;54:164-164.
ABSTRACT
| FULL TEXT
Update in Geriatrics
Hall
ANN INTERN MED 1999;131:842-849.
FULL TEXT
Estrogen use and early onset Alzheimer's disease: a population-based study
Slooter et al.
J. Neurol. Neurosurg. Psychiatry 1999;67:779-781.
ABSTRACT
| FULL TEXT
Prescribing Hormone Replacement Therapy for Menopausal Symptoms
McNagny
ANN INTERN MED 1999;131:605-616.
ABSTRACT
| FULL TEXT
Managing menopause: a critical feminist engagement
Guillemin
Scand J Public Health 1999;27:273-278.
ABSTRACT
The Endocrinology of Aging
Perry
Clin. Chem. 1999;45:1369-1376.
ABSTRACT
| FULL TEXT
Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women
Col et al.
Arch Intern Med 1999;159:1458-1466.
ABSTRACT
| FULL TEXT
Encouraging News From the SERM Frontier
Franks and Steinberg
JAMA 1999;281:2243-2244.
FULL TEXT
Estrogen Actions in the Central Nervous System
McEwen and Alves
Endocr. Rev. 1999;20:279-307.
ABSTRACT
| FULL TEXT
Alternatives to the Use of Estrogen in Postmenopausal Women
Pinkerton and Santen
Endocr. Rev. 1999;20:308-320.
ABSTRACT
| FULL TEXT
Effect of Estrogen on Brain Activation Patterns in Postmenopausal Women During Working Memory Tasks
Shaywitz et al.
JAMA 1999;281:1197-1202.
ABSTRACT
| FULL TEXT
Medical Uncertainty and Practice Variation Get Personal: What Should I Do about Hormone Replacement Therapy?
Daley
ANN INTERN MED 1999;130:602-604.
FULL TEXT
Metrifonate for Alzheimer's disease: Is the next cholinesterase inhibitor better?
Sandson and Knopman
Neurology 1999;52:673-673.
FULL TEXT
Review: oestrogen therapy after menopause may improve cognitive performance and may reduce the risk of developing dementia
Whalley
Evid. Based Ment. Health 1998;1:119-119.
FULL TEXT
Other Articles Noted
Evid. Based Nurs. 1998;1:100-104.
FULL TEXT
Age-Associated Testosterone Decline in Men: Clinical Issues for Psychiatry
Sternbach
Am. J. Psychiatry 1998;155:1310-1318.
ABSTRACT
| FULL TEXT
Fortnightly review: Hormone replacement therapy
Barrett-Connor
BMJ 1998;317:457-461.
FULL TEXT
Telomerase and the Aging Cell: Implications for Human Health
Fossel
JAMA 1998;279:1732-1735.
ABSTRACT
| FULL TEXT
Of Designer Drugs, Magic Bullets, and Gold Standards
Rifkind and Rossouw
JAMA 1998;279:1483-1485.
FULL TEXT
|
