Relative Effects of Tamoxifen, Raloxifene,
and Conjugated Equine Estrogens on Cognition
Mark A. Espeland, Ph.D.,1Sally A. Shumaker, Ph.D.,1Marian Limacher, M.D.,2Stephen R. Rapp, Ph.D.,1
Therese B. Bevers, M.D.,3David H. Barad, M.D., M.S.,4Laura H. Coker, Ph.D.,1Sarah A. Gaussoin, M.S.,1
Marcia L. Stefanick, Ph.D.,5Dorothy S. Lane, M.D., M.P.H.,6Pauline M. Maki, Ph.D.,7
and Susan M. Resnick, Ph.D.,8for the WHIMS and CoSTAR Study Groups
Objective: To compare the relative effects of conjugated equine estrogens (CEE), raloxifene, and tamoxifen
therapies on cognition among women aged ?65 years.
Methods: Annual Modified Mini-Mental State (3MS) examinations were used to assess global cognitive function
in the two randomized placebo-controlled clinical trials of CEE therapies of the Women’s Health Initiative
Memory Study (WHIMS) and the Cognition in the Study of Tamoxifen and Raloxifene (CoSTAR). Analyses were
limited to women who had 3MS testing at baseline and the first 3 years of follow-up and, because of potential
ethnic-related differences between studies, to Caucasian women (WHIMS n¼6211, CoSTAR n¼250). Covariate
adjustment was used to compare the postrandomization mean 3MS scores among the three active therapies with
placebo therapy while controlling for differences between groups with respect to dementia risk factors.
Results: At baseline, the average (SD) 3MS scores by group were 95.24 (4.28) for placebo, 95.19 (4.33) for CEE,
94.60 (4.76) for raloxifene, and 95.02 (4.03) for tamoxifen. Compared with placebo, each active therapy was
associated with a small mean relative deficit in 3MS scores of ?0.5 units, which was fairly consistent between
women with and without prior hysterectomy. Relative deficits were slightly greater for tamoxifen (p¼0.001)
and less marked for raloxifene (p¼0.06) and CEE (p¼0.02) therapies. Relative deficits appeared to be greater
among women with lower baseline 3MS scores: p¼0.009 (tamoxifen), p¼0.08 (raloxifene), and p¼0.03 (CEE).
Conclusions: Although unmeasured differences between trials may have confounded analyses, these findings
raise the possibility that both tamoxifen and raloxifene adversely affect cognitive function in older women;
however, the magnitude of the effect is small, and the long-term consequences are unknown.
risk reductions and recommended that raloxifene be adopted
as a first-line therapy for cancer prevention based on better
tolerability.1Within the full trial, no material differences in
self-reported forgetfulness or mental health were found be-
tween the two drugs.2Its ancillary study on cognition, Cog-
nition in the study of Tamoxifen and Raloxifene (CoSTAR),
he Study of Tamoxifen and Raloxifene (STAR) re-
ported that these two agents yielded similarbreast cancer
found that women assigned to the two agents had similar
cognitive profiles over time.3Because a placebo arm was not
included in the STAR trial, these results do not address how
raloxifene and tamoxifen may affect cognition compared with
Two placebo-controlled studies have reported that the
60mg=day dose of raloxifene used in STAR has little effect
on cognitive test scores or incident cognitive impairment in
women with osteoporosis.4–6No placebo-controlled clinical
trials evaluating tamoxifen’s impact on cognition have been
1Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
2University of Florida, Gainesville, Florida.
3MD Anderson Cancer Center, University of Texas, Houston, Texas.
4Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine Bronx, New York.
5Center for Disease Prevention Research, Stanford University, Palo Alto, California.
6Department of Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, New York.
7Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.
8Laboratory of Personality and Cognition=03, Gerontology Research Center, NIA, NIH, Baltimore, Maryland.
JOURNAL OF WOMEN’S HEALTH
Volume 19, Number 3, 2010
ª Mary Ann Liebert, Inc.
published; however clinical and preclinical studies describe
both potentially adverse7–11and beneficial12–15effects on cog-
nition and brain function.
This article describes exploratory analyses that pool cog-
nitive data from CoSTAR with those of the Women’s Health
Initiative Memory Study (WHIMS), which consisted of two
large placebo-controlled clinical trials of postmenopausal
hormone therapy. CoSTAR and WHIMS shared many design
features, including age range, measurement protocols, and
time frame.16,17Both programs included annual assessments
of global cognitive function with the Modified Mini-Mental
State (3MS) examination.18We focus on the subset of women
in these trials whose cognitive assessments began at baseline.
By aligning women according to measured dementia risk
factors, we develop cross-trial estimates of the relative effects
of tamoxifen and raloxifene on global cognition compared
with placebo and hormone therapy.
Materials and Methods
CoSTAR volunteers were recruited from the STAR breast
cancer prevention trial,1,2in which women were randomly
assigned to 20mg=day oral tamoxifen or 60mg=day oral
raloxifene. Women eligible for STAR had a 5-year predicted
breast cancer risk of ?1.66%,19were at least 35 years of age,
were postmenopausal, and had not taken postmenopausal
hormone therapy, tamoxifen, raloxifene, oral contraceptives,
or androgens for at least 3 months. Additional exclusion cri-
teria were based on competing risks (e.g., history of stroke,
pulmonary embolism, deep vein thrombosis, uncontrolled
diabetes, or hypertension).1CoSTAR began enrolling women
18 months after STAR enrollment had started, beginning in
October 2001, and collected annual batteries of cognitive
outcomes, including 3MS examinations.3STAR enrollment
ceased in November 2004. Women aged ?65 years were
eligible to join CoSTAR any time during their first 4 years
of CoSTAR follow-up; most did not have baseline cognitive
assessments. Enrollment in CoSTAR continued until the
unmasking of STAR in June 2006. Analyses described in this
report are limited to the 274 (18.3%) of 1498 CoSTAR women
who were enrolled in CoSTAR at STAR baseline and who had
at least one follow-up 3MS.
WHIMS tested the relative effect of 0.625mg=day conju-
gated equine estrogens (CEE) alone and in combination with
2.5mg=day of the progestin medroxyprogesterone acetate
(CEEþMPA) on the incidence of probable dementia and,
secondarily, global cognitive function and other cognitive
procedures have been reported previously.16,17Volunteers
aged 65–80 years were recruited from the Women’s Health
Initiative (WHI) hormone trials beginning in June 1996.
to active therapy (CEE-alone if prior hysterectomy, CEEþ
MPA if no hysterectomy) or matching placebo. A 3-month
washout from any current hormone therapy was required
before baseline evaluation. Exclusion criteria were based on
competing risks(medicalconditions withapredicted survival
of <3 years), safety (e.g., prior breast cancer at any time or
breast cancer suspected at baseline screening, other invasive
cancer within the past 10 years except nonmelanoma skin
cancer, low hematocrit or platelet count), adherence and re-
tention factors (e.g., dementia, unwillingness or inability to
complete study requirements, alcoholism, adherence during a
pill run-in), and probable dementia. Analyses in this article
are limited to the 7168 (95.8% of 7479) women enrolled in
WHIMS for which a baseline 3MS test (i.e., within 6 months
of randomization) was recorded and who had at least one
follow-up 3MS test.
The National Institutes of Health and Institutional Review
Boards for all participating institutions approved protocols
and consent forms. Informed written consent was obtained
from all participants.
The 3MS test consists of 15 items, the sum of which ranges
between 0 and 100. Higher scores reflect better cognitive
functioning.18Test items measure temporal and spatial ori-
entation, immediate and delayed recall, executive function,
naming, verbal fluency, abstract reasoning, praxis, writing,
and visuoconstructional abilities. The 3MS test has good re-
liability, sensitivity, and specificity for detecting cognitive
impairment and dementia.203MS tests were administered by
trained and certified technicians who were masked to treat-
ment assignment and other outcomes. Technicians for both
trials were centrally trained by staff and investigators at the
Wake Forest University Coordinating Center according to
Baseline demographic and clinical factors were collected
with self-report and standardized assessments. Factors in-
cluded in our analyses were those collected in a similar
manner in both studies: age, education, ethnicity, body mass
index (BMI), hypertension, diabetes, and prior hysterectomy.
Weight was measured to the nearest 0.1kg, and height was
recorded to the nearest 0.1cm. BMI was calculated as weight
in kilograms divided by the square of height in meters.
Follow-up and retention
After discovery of an unfavorable risk=benefit ratio of its
noncognitive end points for CEEþMPA therapy, the WHI trial
of this regimen was discontinued in July 2002.21The WHI trial
of CEE-alone therapy was discontinued in February 2004
because of an increased risk of stroke and embolic events and
the lack of any favorable effect on cardiovascular disease
(CVD) for CEE-alone therapy.22These decisions discontinued
the WHIMS trials. Mean follow-up for women included in our
analyses was 4.6 (range 1–8) years, and at annual follow-up
of expected women provided 3MS data. The STAR study was
(year 1), 87.1% (year 2), and 77.8% (year 3) of expected for
women included in this report. Because only 15 CoSTAR
women who were enrolled at baseline had an on-trial year 4
examination, these data were excluded from analyses.
separate eligibility criteria, recruitment processes, and study
objectives produce cohorts that may differ according to many
measured and unmeasured attributes. Covariate adjustment
with respect to risk factors for cognitive impairment is nec-
essary to reduce biases. We used tests of interactions to assess
372ESPELAND ET AL.
the comparability of risk factor relationships with baseline
3MS between trial cohorts. Factors for which relationships
were similar between trials were used as covariates in all
comparisons. Factors for which relationships did not appear
to be similar were used to stratify analyses. 3MS scores were
left-skewed; to address this, inference was based on trans-
formed data calculated as the logarithm of 102 minus the
score.23Generalized linear models were used to contrast
longitudinal postrandomization transformed 3MS scores,
with adjustment for baseline 3MS and dementia risk factors.24
Means and confidence intervals (CIs) were reported for scores
back-transformed to original units. Participants were ana-
lyzed according to their assigned therapy. Because WHIMS
found little difference in how CEE and CEEþMPA affect 3MS
scores25and because this comparison is not a feature of this
article, data from the two WHIMS hormone therapy trials
were pooled. As the adverse effect of hormone therapy on
3MS scores in the WHIMS trial was greatest among women
than a perfect score) to estimate the effects of tamoxifen and
raloxifene in women with some evidence of pretrial cognitive
deficits. The p values from pairwise comparisons of treatment
groups that we report are not adjusted for multiple compar-
isons in our exploratory analyses.
Characteristics of WHIMS and CoSTAR women at the time
of enrollment into their parent WHI and STAR trials were
balanced with respect to treatment assignment within each
trial (Table 1). However, differences between trial cohorts
with respect to many of the characteristics are evident.
Compared with WHIMS women, CoSTAR women tended to
Table 1. Characteristics of WHIMS and CoSTAR Women at Enrollment into WHI and STAR Trials:
Grouped According to Treatment Assignment
WHIMS n (%)CoSTAR n (%)
<High school graduate
High school graduate
3MS mean (SD)
aChi-square test or analysis of variance.
WHIMS, Women’s Health Initiative Memory Study; CoSTAR, Cognition in the Study of Tamoxifen and Raloxifene; CEE, conjugated
TAMOXIFEN, RALOXIFENE, AND COGNITION 373
be younger and were less likely to have a college education,
less likely to be from an ethnic minority, less likely to have
diabetes, and more likely to have had a hysterectomy. The
distributions of obesity and the prevalences of hyperten-
sion were similar between the two trials. The baseline mean
3MS (SD) scores of the four treatment groups also appear in
Table 1. These did not differ significantly between trials, and
their cumulative distributions were nearly identical (Fig. 1).
At baseline, age-adjusted associations of 3MS scores with
education, BMI, hypertension, and diabetes status appeared
to be fairly similar in the two study cohorts (nonsignificant
tests of interactions) (Table 2). Relationships that 3MS scores
had with hysterectomy status differed between trials
(p¼0.046), so that results of analyses stratified by hysterec-
tomy status are presented. Because of small cell sizes, there
was little power to detect between-trial differences in rela-
tionships that 3MS scores had with ethnicity, for which the
trial’s distributions differed markedly. Because of this, we
focused this report on analyses limited to Caucasian partici-
pants (87% of WHIMS women; 91% of CoSTAR women),
whose baseline mean 3MS scores are shown in Table 1.
We also conducted analyses using the full cohort with cov-
ariate adjustment for the most prevalent ethnic groups; these
yielded comparable results and are not reported.
Most women in this CoSTAR cohort had only 2 or fewer
years of follow-up (Table 3). Follow-up rates did not vary by
treatment assignment. Among these WHIMS women, follow-
up of ?2 years was more common among women who were
older or lesseducated or haddiabetes (all p<0.05). Because of
the earlier termination of the CEEþMPA trial, follow-up was
shorter for women without prior hysterectomy. In this
CoSTAR cohort, none of these relationships approached sta-
tistical significance. Table 3 provides fitted mean 3MS scores
(from the log-transformed data), with adjustment for base-
line 3MS, age, education, BMI, hypertension, and diabetes
status. These estimates were from Caucasian participants and
stratified by hysterectomy status. The log-transformation, by
reducing the skew, yielded means that were greater than raw
averages. Adjusted 3MS means were slightly lower among
women assigned to active therapies compared with the
WHIMS placebo at most time points. When averaged across
follow-up, these did not reach statistical significance for
women without prior hysterectomy (overall, p¼0.18): 97.56
(95% CI 97.49-97.63, placebo), 97.48 (97.40-97.55, (hormone
therapy), 97.32 (96.78-97.80, raloxifene), and 97.16 (96.56-
97.69, tamoxifen). For women with prior hysterectomy, dif-
ferences among arms were ordered similarly and reached
statistical significance (p¼0.007). Pairwise (unadjusted for
multiple comparisons) p values contrasting active thera-
pies with placebo were p¼0.10 (hormone therapy), p¼0.09
(raloxifene), and p¼0.003 (tamoxifen). The adjusted means
were 97.29 (97.19-97.38, placebo), 97.17 (97.06-97.27 hormone
therapy), 96.89 (96.41-97.34, raloxifene), and 96.55 (96.02-
97.04, tamoxifen). Figure 2 portrays these differences as mean
deficits from the perfect score of 100.
Because patterns appeared similar, an analysis was con-
ducted that included women both with and without a uterus
(with hysterectomy status as a covariate). Treatment groups
means were 97.46 (97.40-97.52, placebo), 97.36 (97.30-97.42,
hormone therapy), 97.14 (96.79-97.47, raloxifene), and 96.88
(96.49-97.24, tamoxifen). With the larger sample size, overall
differences were statistically more marked (p¼0.001). Dif-
ferences from placebo were most striking for tamoxifen
(p¼0.001) and less so for hormone therapy (p¼0.02) and
Mean adjusted 3MS scores over follow-up were also esti-
mated for the subset of Caucasian women with baseline 3MS
score <95, 1746 (28.1%) of the WHIMS participants and 86
(31.4%) of the CoSTAR participants. Because of the limited
Cumulative distribution of baseline 3MS scores from the WHIMS and CoSTAR cohorts.
374ESPELAND ET AL.
which was included as an additional covariate. The adjusted
mean postrandomization 3MS scores for women were 95.51
(95.33-95.68, placebo), 95.25 (95.07-95.43, hormone therapy),
94.46 (93.41-95.38, raloxifene), and 94.15 (93.04-95.12, tamox-
ifen). Overall differences among groups were significant
(p¼0.003), with the most marked differences between pla-
cebo and each of the active therapies. Figure 3 portrays the
mean differences between each therapy and placebo for
the women with baseline 3MS scores <95 and, for com-
parison, for all women. For each therapy, the relative decre-
ments appeared to be larger for women with lower baseline
3MS scores: 0.26 (SE¼0.004) vs. 0.09 (0.001) for CEE therapy,
1.05 (0.41) vs. 0.32 (0.14) for raloxifene, and 1.36 (0.44) vs. 0.58
(0.16) for tamoxifen. For the separate tests of interaction be-
tween baseline 3MS and the relative effects of each drug vs.
and p¼0.009 (tamoxifen).
Our findings add support to the hypothesis that tamoxifen,
one of the most widely used selective estrogen receptor
modulators (SERMs), may have a small negative effect on a
globalmeasureofcognitive functioninolder postmenopausal
Table 2. Age-adjusted Relationships Between Baseline Dementia Risk Factors and 3MS Scores
in WHIMS and CoSTAR
trials p valuea
Baseline characteristicMean 3MS (SE)p value Mean 3MS (SE)p value
<High school graduate
High school graduate
<0.001 95.01 (0.39)
<0.001 94.92 (0.28)
aAnalyses of covariance.
Hypertension, BMI, and Baseline 3MS (Whites Only): Stratified by Hysterectomy Status and Based on Log
Transformation of (102 - 3MS Score): Included in Each Cell Is Number of Women Who Had 3MS Testing
Fitted Mean 3MS Scores, by Treatment Assignment, with Adjustment for Age, Education, Diabetes,
WHIMS participants fitted mean (95% CI)CoSTAR participants fitted mean (95% CI)
CEE therapy PlaceboRaloxifene Tamoxifen
No prior hysterectomy
97.26 (97.16-97.36) n¼1870
97.57 (97.47-97.66) n¼1801
97.60 (97.50-97.69) n¼1776
97.34 (97.24-97.44) n¼1934
97.62 (97.52-97.71) n¼1852
97.74 (97.64-97.83) n¼1833
96.90 (96.21-97.51) n¼51
97.80 (97.11-98.39) n¼35
97.07 (95.97-97.97) n¼18
96.93 (96.19-97.58) n¼45
96.75 (95.80-97.55) n¼30
98.27 (97.35-99.01) n¼16
96.89 (96.74-97.03) n¼1129
97.22 (97.08-97.35) n¼1053
97.41 (97.27-97.54) n¼1041
97.04 (96.91-97.18) n¼1155
97.40 (97.27-97.53) n¼1093
97.43 (97.30-97.56) n¼1080
96.80 (96.21-97.34) n¼75
96.73 (95.99-97.38) n¼46
96.83 (95.86-97.64) n¼25
96.53 (95.88-97.11) n¼71
96.46 (95.68-97.14) n¼47
96.20 (95.01-97.18) n¼21
TAMOXIFEN, RALOXIFENE, AND COGNITION
women across 1–3 years. Raloxifene was also estimated to
have a negative effect on cognition, which did not reach sta-
tistical significance. The primary conclusion from the full
CoSTAR trial was that any effects that raloxifene and
tamoxifen had on cognition over time were similar. The
magnitude of the mean differences, a 3MS point or less, may
be undetectable and has little clinical significance for an in-
dividual woman. If, as seen in the WHIMS study,27these
translate to an increased risk for cognitive impairment, they
may have important public health consequences.
limited to white participants and included age, baseline 3MS score, education, BMI, hypertension, and diabetes as covariates.
Means are provided for women stratified by hysterectomy status and for all participants (with additional adjustment for
hysterectomy status in the pooled analysis). Listed are p values from pairwise comparisons of each active therapy vs. the
placebo from general linear models, which have not been adjusted for multiple testing.
Mean deficits from 100 adjusted postrandomization 3MS scores across years 1–3 of follow-up. Estimates were
therapy. Estimates are provided for all women and for the subset of women whose baseline 3MS score was <95.
Estimated mean relative decrements in postrandomization 3MS scores of active therapies compared with placebo
376 ESPELAND ET AL.
Analogous to findings for CEE-based therapies, the esti-
mated relative treatment effects on cognition for tamoxifen
and raloxifene were larger among women whose baseline
cognitive function was lower. For those with 3MS scores <95,
error, and formal tests of interactions were significant or of
borderline significance. It would be of interest to examine
however, the relatively few CoSTAR women available in this
range limit our ability to do this.
Our findings must be viewed with some caution. The
covariate adjustment we used for cross-trial comparisons is
not likely to provide as balanced comparisons as would be
achieved within a randomized trial.28We cannot rule out that
there may be some unmeasured factors that confound our
comparisons. Nevertheless, this comparison is aided by the
many commonalities between the trials, including similar
aims, measures, training, and quality control procedures.
Futhermore, the within-trial randomization reduces some
of the biases compared with observational studies. CoSTAR
was designed to promote comparisons with data collected by
a substudy of WHIMS, the Women’s Health Initiative Study
of Cognitive Aging.29The analyses we describe, which were
limited to women in both programs who had baseline as-
sessments of cognition, were not described in study protocols
and, thus, must be considered exploratory.
Clinical studies of raloxifene
Prior clinical studies examining the effect of raloxifene on
cognition have been conducted in women with elevated risk
for osteoporosis and have produced mixed results. The mul-
tiple outcomes of raloxifene evaluation (MORE) trial investi-
gated the cognitive effects of 60 and 120mg doses relative to
placebo in 5386 women.4,5After 3 years, the study found no
effect of either dose on risk of Alzheimer’s disease and a de-
creased risk of cognitive impairment with the 120-mg dose.5
Overall, there was no cognitive benefit of either dose on
standardized tests of global cognitive function, memory, or
other cognitive abilities, but analyses ofa subgroup ofwomen
aged ?70 years found some cognitive benefits of both ralox-
ifene doses to memory and psychomotor speed.4Nickelsen
et al.4conducted a 1-year randomized clinical trial in which
60mg=day raloxifene was compared with placebo in 96
women (mean age 69 years) and found no significant differ-
ences in a battery of 11 cognitive tests. In the Eurolox 1 ran-
with significantly worse reported memory=concentration
over 6 months compared with 17b-estradiol plus progestin
therapy.30In a 3-month case-control study of the 60mg dose
in 49 women, raloxifene was associated with impaired at-
tentional task performance but no difference in memory.31
Clinical studies of tamoxifen
Clinical trials of the effects of tamoxifen on cognitive
function typically have been performed in combination with
other chemotherapeutic agents and, thus, do not allow as-
sessment of the effects of tamoxifen alone on cognitive func-
tion. Several small studies have suggested negative effects of
tamoxifen on cognitive function, particularly memory. In a
retrospective assessment by mail of 1163 women, Paganini-
Hill and Clark10found those who currently or in the past
received tamoxifen for breast cancer treatment reported
seeing their doctors more often for memory concerns than
never users. In another study, the cognitive function of 94
women receiving anastrozole, tamoxifen-alone, or both drugs
for treatment of breast cancer was compared to that of 35
postmenopausal women without cancer who were chosen to
have similar demographic backgrounds.32Relative to con-
trols, the patients receiving active therapy had poorer per-
formance on tests of immediate verbal memory and
processing speed. Although no patients in this trial received
other chemotherapeutic agents, 67% of the women had re-
could not be excluded. Differences among active treatment
groups were not explored. Other studies of small samples
of breast cancer patients treated with chemotherapy and
tamoxifen have confirmed the generally negative impact of
tamoxifen on cognitive function beyond that attributable to
adjuvant chemotherapy alone.33
The WHIMS program found that CEE-based hormone
therapy increased the risks of dementia and produced a small
average decrement in cognitive function.25,27More recently, it
has been reported that the adverse effects on cognition and
increased risk for dementia of CEE-based therapy may be
primarily conveyed through increased brain atrophy, in-
cluding decreased hipppocampal volume,34,35and one report
suggests that tamoxifen use also may be associated with
smaller hippocampal volume.11However, raloxifene and
tamoxifen may influence cognition through several path-
ways, which may be distinct from CEE-based therapy.36For
example, raloxifene may alter brain activation patterns dif-
ferently from estrogen therapy. Although in separate human
studies, estrogen therapy and raloxifene treatments are asso-
ciated with decreased left parahippocampal and increased
right parietal lobe activation during visual recognition tasks;
raloxifene, but not estrogen, was associated with increased
activation in the right superior frontal gyrus and right pre-
Our findings are limited by the relatively short follow-up
period (primarily ?2 years) and by the noted difficulties in
comparisons between trials that do not contain a common
arm. There likely are differences in selection factors in women
who enrolled in WHI vs. those who enter a breast cancer
prevention trial. Differences in eligibility criteria, recruitment
WHIMS and CoSTAR study periods overlapped, they were
not identical, so that secular trends also may influence dif-
ferences. Because eligibility was limited to women aged ?65
years, our findings may not apply to younger women. The
women in CoSTAR and WHIMS tend to be relatively healthy,
on a test of global cognitive function and may not generalize
to individual cognitive domains.
CEE, raloxifene, and tamoxifen all may induce small but
detectable adverse effects on global cognition across 2–3 years
TAMOXIFEN, RALOXIFENE, AND COGNITION 377
of therapy in women aged ?65 years. These effects may be
most pronounced among women with lower pretreatment
levels of cognitive function.
This work was supported by the following sources. The
Women’s Health Initiative was funded by the National Heart,
Lung, and Blood Institute of the National Institutes of Health,
U.S. Department of Health and Human Services. WHIMS
was funded by Wyeth Pharmaceuticals, Inc., St. Davids, PA,
Wake Forest University Health Sciences, and by the National
Heart, Lung, and Blood Institute (N01-WH-4-4221). STAR
was supported by Public Health Service grants U10-CA-
37377, U10-CA-69974, U10CA-12027, and U10CA-69651 from
the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services, AstraZeneca
Pharmaceuticals, and Eli Lilly and Co. CoSTAR was funded
by the National Institute on Aging (NO1-AG- 2106). S.M.R. is
supported by the Intramural Research Program, National
Institute on Aging, and National Institutes of Health.
The authors have no conflicts of interest to report.
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Address correspondence to:
Mark A. Espeland, Ph.D.
Department of Biostatistical Sciences
Wake Forest University School of Medicine
Medical Center Boulevard
Winston-Salem, NC 27157
TAMOXIFEN, RALOXIFENE, AND COGNITION379
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