Psychoneuroendocrinology (2008) 33, 989—998

a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m

j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / p s y n e u e n

Sustained attention is favored by progesterone during

early luteal phase and visuo-spatial memory by
estrogens during ovulatory phase in young women
S. Solı́s-Ortiz a,*, M. Corsi-Cabrera b

a
Instituto de Investigaciones Médicas, Universidad de Guanajuato, León, Guanajuato, Mexico
b
Facultad de Psicologı́a, Posgrado, Universidad Nacional Autónoma de Mexico, Mexico

Received 25 June 2007; received in revised form 8 March 2008; accepted 29 April 2008

KEYWORDS Summary Studies examining the influence of the menstrual cycle on cognitive function have
Attention; been highly contradictory. The maintenance of attention is key to successful information
Memory; processing, however how it co-vary with other cognitive functions and mood in function of
Menstrual cycle; phases of the menstrual cycle is not well know. Therefore, neuropsychological performance of
Progesterone; nine healthy women with regular menstrual cycles was assessed during ovulation (OVU), early
Estrogens; luteal (EL), late luteal (LL) and menstrual (MEN) phases. Neuropsychological test scores of
Cognition sustained attention, executive functions, manual coordination, visuo-spatial memory, verbal
fluency, spatial ability, anxiety and depression were obtained and submitted to a principal
components analysis (PCA).
Five eigenvectors that accounted the 68.31% of the total variance were identified. Perfor-
mance of the sustained attention was grouped in an independent eigenvector (component 1), and
the scores on verbal fluency and visuo-spatial memory were grouped together in an eigenvector
(component 5), which explained 17.69% and 12.03% of the total variance, respectively. The
component 1 ( p < 0.034) and the component 5 ( p < 0.003) showed significant variations during
the menstrual cycle. Sustained attention showed an increase in the EL phase, when the
progesterone is high. Visuo-spatial memory was increased, while that verbal fluency was
decreased during the OVU phase, when the estrogens levels are high. These results indicate
that sustained attention is favored by early luteal phase progesterone and do not covaried with
any other neuropsychological variables studied. The influence of the estrogens on visuo-spatial
memory was corroborated, and covaried inversely with verbal fluency.
# 2008 Published by Elsevier Ltd.

1. Introduction

* Corresponding author at: Hacienda del Palote 426, Balcones del

Fluctuation of the ovarian hormones might influence some
Campestre, León 37138, Guanajuato, Mexico. Tel.: +52 477 7143812; aspects of the cognitive functions in women (Richardson,
fax: +52 477 7168354. 1992; McEwen et al., 2002). Cognition refers to the human
E-mail address: silviasolis17@prodigy.net.mx (S. Solı́s-Ortiz). information processing, and includes functions such as

0306-4530/$ — see front matter # 2008 Published by Elsevier Ltd.

doi:10.1016/j.psyneuen.2008.04.003
990
attention, memory, learning, language processing, problem
solving, abstract reasoning, planning, inference, and visual
processes (Kolb and Whishaw, 1990). Changes in scores on
neuropsychological tasks have been used to assess possible
influence of ovarian hormone secretion during different
menstrual cycle phases. This approach has demonstrated
that some impairment in cognitive performance is a char-
acteristic feature of the premenstrual period. Performance
on motor coordination and verbal fluency show improvement
during the periovulatory or early luteal (EL) phases, when
estrogen and progesterone levels are high, but performance
on spatial skills tasks is worse. During menstruation, when
estrogen and progesterone levels are low, performance on
spatial skills tasks improve and verbal and manual skills
decline (Broverman et al., 1981; Hampson, 1990; Phillips
and Silverman, 1997; Hausmann et al., 2000). Cyclic varia-
tions in the verbal memory and spatial memory (Phillips and
Sherwin, 1992; Postma et al., 1999) have also been reported,
with better performance during periods in which estrogen is
high. Performance on frontal lobe tasks is better in the early
luteal phase, when the progesterone level is high (Solı́s-Ortiz
et al., 2004a), and high levels of estradiol and progesterone
in the midluteal phase increase the attentional blink (Hol-
lander et al., 2005). However, with the exception of abilities
associated with gender differences (Hampson and Kimura,
1992), contradictory results have been reported for the
other domains of cognitive function tested. Some of these
problems may be related to methodological inconsistencies
which are common in the majority of these studies (Sommer,
1992; Epting and Overman, 1998; Sherwin, 2003). The incon-
sistencies have been attributed in part to an inadequate
capacity on the part of the research designs used, lack of
control for anxiety and depressive symptoms that can nega-
tively impact scores on neuropsychological tests, and the
tests employed to assess cognition that inappropriately have
been used may be insensitive to the possible influence of the
menstrual cycle upon cognitive performance (Richardson,
1992; Sherwin, 2003).
Several studies made in human and animal models have
suggested that ovarian steroids have diverse effects on brain
function, in particular the hippocampus and prefrontal cor-
tex (McEwen and Woolley, 1994; McEwen et al., 1997; Berman
et al., 1997), brain regions involve in memory processes.
Cognitive data from human using neuropsychological tests
that measure prefrontal functions, have showed that young
women performed better on frontal lobe task in the early
luteal phase of menstrual cycle (Solı́s-Ortiz et al., 2004a).
The performance on Trailmaking Test, Trail B was better
during the follicular phase than during the luteal phase of
the menstrual cycle (Kennan et al., 1992). Estrogen therapy
administrated to perimenopausal or postmenopausal women
selectively reduced errors of perseveration in the California
Verbal Learning Test, a test that examines executive func-
tions, mediated by the frontal cortex (Kennan et al., 2001;
Joffe et al., 2006).
Behavioral data from rodents using tasks that involve
hippocampal and prefrontal cortex functions have showed
that estrogens and progestins enhance spatial learning of
intact rats during proestrus or estrus and in ovariectomized
rats administered estrogens, progesterone, or estrogens
and progesterone in the object placement task (Frye et al.,
2007). Rats in proestrus performed better than diestrus or
S. Solı́s-Ortiz, M. Corsi-Cabrera
estrus in the object recognition task associated with
increases in serum of estrogens and progestins (Walf
et al., 2006). It was also found that estrogens levels in
the hippocampus and 5a-pregnan-3a-ol-20-one in the hip-
pocampus and cortex were positively correlated with the
performance in the object recognition task (Walf et al.,
2006). Moreover, estrogen administration to ovariecto-
mized female rats and young or aged mice also enhanced
performance in a water escape working memory task
(O‘Neal et al., 1996) and in T-maze task (Heikkinen
et al., 2004), tasks that are also mediated by the pre-
frontal cortex.
Progestins have also important effects and on EEG activity
in humans (Friess et al., 1997), as well as in rats (Corsi-
Cabrera et al., 2000; Fernandez-Guasti et al., 2003) and may
influence motivation, reward, conditioning and stress in rats
(Frye, 2007). One study found that ovariectomized rats
treated with progesterone, dihydroprogesterone and 5a-
pregnan-3a-ol-20-one performed better in the Y-maze, inhi-
bitory avoidance and object recognition tasks (Frye and
Lacey, 2000).
Most studies have made a comparison between test
scores and phases of the menstrual cycle as a method to
evaluate the neuropsychological function and its possible
relation to sex hormones during the different phases of the
menstrual cycle in women. In some cases, this method has
provided of relevant information but in other cases the
findings reported are discrepant. An analysis of the struc-
ture and the interrelationships of neuropsychological vari-
ables may help to better understand the effect of the
menstrual cycle on cognitive performance. PCA allows
for grouping variables that co-vary together separating
them from others that are orthogonally independent and
they are not correlated; it is therefore a useful statistical
method to reduce variables and to investigate relation-
ships between the new variables (Flury and Reidwyl, 1988).
Those variables that get gathered in the same eigenvector
are reflecting some common influence, while they are
independent from those gathered in a different eigenvec-
tor. PCA, therefore, can be used to investigate how neu-
ropsychological variables are grouped depending of the
menstrual cycle phases.
The aim of the present investigation was to explore, by
means of PCA, which neuropsychological test scores vary
together or separately in a function of the phases of the
menstrual cycle. It was hypothesized that the neuropsy-
chological test scores extracted by PCA as gathered in the
same eigenvector would reflect a common influence and
those which are independent gather in several eigenvec-
tors and this could better explain the neuropsychological
changes in young women during the different menstrual
cycle phases. With this purpose, scores on neuropsycholo-
gical tests measuring sustained attention, executive func-
tions, manual coordination, visuo-spatial memory, verbal
fluency and spatial ability obtained from four phases of the
menstrual cycle were submitted to PCA. Because variations
on mood are also characteristic of the menstrual cycle
(Bäckström et al., 1983; Solı́s-Ortiz and Corsi-Cabrera,
2002), and can influence cognitive performance, scores
of anxiety and depression were also obtained in four
phases of the menstrual cycle and were included in the
PCA.
Sustained attention and visuo-spatial memory favored by ovarian hormones
2. Methods
2.1. Subjects
This study was approved by the Ethics Committee of the
University of Guanajuato, and all of the women gave their
written informed consent. Nine healthy volunteers aged
between 19 and 34 years old (mean 25.7  4.3 years) with
regular menstrual cycle (28  2 days) were assessed in a
counterbalanced repeated measure design. None of them
were under any type of medication nor were taking or had
taken oral contraceptives or other hormonal treatment. All
women underwent a medical and psychological interview and
completed a modified version of the Menstrual and Pre-
menstrual Symptoms Questionnaire (Chesney and Tasto,
1975). No abnormalities were present in the group.
Each woman was tested for a total of four sessions during
performance tests across the menstrual cycle at the same
time of the day (between 0900 h and 1100 h). Four different
phases of the menstrual cycle were determined according to
results obtained in previous studies (Solı́s-Ortiz et al., 1994,
2004a), where we observed that EEG activity showed sig-
nificant changes in the ovulatory phase (OVU), days 13—14 of
the cycle; in the early luteal phase (EL) days 20—21, in the
late luteal phase (LL) days 24—25 and in the menstrual phase
(MEN) days 1—2 of bleeding. We also used the method of daily
oral basal body temperature monitoring to confirm the ovu-
latory period. Temperature rises very slightly after ovulation,
and is known to be a function of elevated progesterone levels
(Little et al., 1974). It also provides a physiological index of
ovulation (Bonnar, 1984). Women recorded their body tem-
perature during two cycles. Temperatures during the first
cycle, previous to the test sessions, were taken in order to
obtain a pattern along the menstrual cycle and were useful to
determine the ovulatory period in the second cycle.
Recorded temperatures during the two cycles together with
verbal reports on the date of menstrual bleeding were used to
decide the precise dates of test sessions which started at the
subjects’ own convenience. Thus, initial starting sessions of
the four phases of the menstrual cycle were randomly dis-
tributed among subjects. One trained female investigator
tested each participant during the four phases of the cycle.
In the present study, to avoid a possible learning effect,
the different tests were presented in a random order in each
session. This supports the assumption that subjects come to
each first session with an equal allocation of resources and
eliminates potentially confounding time-based effects, fac-
tors as learning, strategy change, boredom and/or fatigue
(Lovett et al., 1999, p. 158). It has been found that despite
the practice and training and resulting performance on WCST,
women showed a better performance during the progester-
one phase (Solı́s-Ortiz et al., 2004a).
2.2. Neuropsychological tests
Six standard neuropsychological tests were used to evaluate
the cognitive performance. Each test was administered four
times during one menstrual cycle distributed at random.
Hidden Figures (spatial ability), Purdue Pegboard (manual
coordination), Word Fluency (verbal fluency) and Localiza-
tion (visuo-spatial memory) tests were selected because they
have been shown to measure sexually dimorphic cognitive
991
abilities (Hampson and Kimura, 1992). Additionally, we
employed the Continuous Performance Test that measures
sustained attention, because we considered that in any
evaluation of cognitive abilities it is necessary to establish
the ability of women to focus and sustain attention. A test
that demands prefrontal function was also used in order to
establish menstrual cycle influence on executive functions.
The neuropsychological tests according to the abilities they
represent are described below.
2.2.1. Spatial ability
The spatial ability was evaluated with a modified version
from Hidden Figures Test (Ekstrom et al., 1976). Although the
spatial ability shows a sex difference in favor of men (Hamp-
son and Kimura, 1992), it was included because Broverman
et al. (1981) reported that women performed better in the
early luteal phase. The participants were required to find
eight simple geometric figures embedded within a more
complex design. The final score was the number of correct
figures found within 12 min.
2.2.2. Manual coordination
In the present study a modified version from Purdue Pegboard
Test was used (Tiffin, 1968), to evaluate manual coordina-
tion. This test was chosen because it traditionally favors
women (Hampson and Kimura, 1992). Participants performed
the single-peg condition that consisted in inserting the peg
unimanually into consecutive holes in a board according to
determinate design. The score was the total number of
correctly placed parts and the total of performing time in
seconds.
2.2.3. Verbal fluency
The Word Fluency Test (Benton et al., 1983) was used to
evaluate the spontaneous generation of words according to
an initial given letter. We chose this test because it has been
positively correlated with FSH and LH hormones (Gordon
et al., 1986). The word production test consisted in asking
subjects to write as many words as they could in 1 min that
begin with the alphabet letters F, L, and M, excluding proper
nouns, numbers, and the same word with a different suffix.
The score was the sum of three 1 min trials with different
letters.
2.2.4. Visuo-spatial memory
A modified version from the Localization Test (Gordon et al.,
1986) was used to evaluate visuo-spatial memory. This test
was chosen because localization is an ability that favors
women (Postma et al., 1999; De Goede et al., 2006) and
has been used in studies of menstrual cycle (Gordon et al.,
1986). The localization test consisted in a black ‘‘x’’ which
appears within a rectangle in a white sheet, and must be
placed exactly in a white rectangle. A total de 24 ‘‘x’’ trials
was presented to participants distributed in random order, in
each sheet. The score was the linear error in mm for 24 trials.
2.2.5. Sustained attention
A computerized version of the Continuous Performance Test
(CPT) (Lorenzo et al., 1995) was used to examine the ability
to sustain and focus attention. We chose this test because it
has been shown to be sensible to hormonal changes during
the menopause (Solı́s-Ortiz et al., 2004b). Sustained atten-
992
tion test consists of one hundred and fifty visual stimuli
displayed, one at a time, for 50 ms on a video screen. The
inter-trial interval ranged randomly from 5 to 7 s. Stimuli
consisted of four white squares (3.7 cm  3.3 cm), each one
missing one of the corners and presented in a random
sequence. Preceding the task, one of the four patterns
was selected and the subject was asked to press the ‘‘enter’’
button on the keyboard as soon as possible each time the
selected pattern appeared. Reaction time, omissions, errors
and correct responses were computed.
2.2.6. Executive functions
The Wisconsin Card Sorting Test (WCST) (Grant and Berg,
1948; Heaton, 1981) was used to evaluate executive func-
tions of the frontal lobe and it has been demonstrated that
this test is sensitive to hormonal changes in women (Ber-
man et al., 1997; Solı́s-Ortiz et al., 2004a). The WCST is an
abstract reasoning and problem solving task involving the
use of working memory to form a cognitive set and apply a
conceptual strategy but also necessitating maintenance
and then shifting of the set when appropriate. The per-
formance of the WCST produces physiological activation in
a network of regions including the dorsolateral prefrontal
cortex, the inferior parietal lobule, and the posterior
portion of the inferior temporal cortex (Berman et al.,
1995). The stimuli were shown on a screen facing the
subjects. The WCST requires subjects to discover the prin-
ciple under which a deck of cards must be sorted. The
standard material consists of cards bearing geometric fig-
ures that vary in color (red, green, blue, or yellow), form
(triangle, star, cross, or circle) and number (1, 2, 3 or 4
items). Four reference cards are aligned in front of the
subject throughout the test. Another deck of cards serves
as response cards. The subject is instructed to place each
response card in front of 1 of the 4 reference cards,
wherever she thinks it should go. After each response,
she is told whether the response was ‘‘right’’ or ‘‘wrong’’
but not where the card should have gone. The goal for the
subject is to get as many ‘‘right’’ responses as possible.
Initially, cards must be sorted according to color. When
performance is successful, the sorting rule is changed,
from color to form or number; the subject must reconize
the change and discover the new correct rule. We analyzed
the number of correct responses (trials) taking into account
the ability to reach successful or unsuccessful outcomes,
perseverative errors, non-perseverative errors, and the
number of sequences made.
2.3. Mood questionnaires
During each test session, the participants also completed an
anxiety questionnaire (Spielberg et al., 1970) and a depres-
sion questionnaire (Beck and Sleer, 1993) in a standardized
version for the Mexican population (Spielberg et al., 1980;
Jurado et al., 1998).
2.4. Statistical analysis
A principal component analysis (PCA) was used to investigate
the structure and the relationships between the variables
and to determine which score tests and score mood covaried
together and which were independent, followed by varimax
S. Solı́s-Ortiz, M. Corsi-Cabrera
rotation with the new variables using the scores from each
test and mood questionnaires as variables (Flury and Reid-
wyl, 1988). To test the significance between the four phases
of the menstrual cycle the new variables were submitted to
one-way ANOVA for repeated measurements followed by
Tukey’s Student tests for posthoc comparisons (Tukey,
1995). Differences were considered significant when
p < 0.05.
3. Results
The participants in the present study showed regular men-
strual bleeding. The basal body temperature started to rise
from day 15 to reach maximum values in days 27 or 28 of the
luteal phase, and then the temperature decreased in the
menstrual phase. The increase in the temperature presented
the typical curve associated with an elevated progesterone
level in the luteal phase (Ferin et al., 1973; Marshall, 2001).
This suggests the presence of ovulatory cycles. Consequently
the basal body temperature pattern could be used to corro-
borate the dates of the test sessions.
Results from the principal component analysis are shown
in Table 1. This analysis found that the first five components
explained 68.31% of the total variance. The varimax rotation
of these five components showed that the first component
was formed by the sustained attention (Continuous Perfor-
mance Test) and explained 17.69% of the total variance; the
second component was formed by spatial ability (Hidden
Figures Test) and accounted for 13.39% of the variance;
the third component: anxiety and depression scores
explained 12.63% of the variance; the fourth component
by the executive functions (Wisconsin Card Sorting Test)
explained 12.57% of the variance; and the fifth component
was formed by verbal fluency (Word Fluency Test) and the
visuo-spatial memory (Localization Test) explaining 12.03% of
the variance.
One-way ANOVAs made with the component scores of the
new variables showed significant differences only for two
components (1 and 5) during the menstrual cycle, which
included the tests that measure sustained attention
( p < 0.034), verbal fluency and visuo-spatial memory
( p < 0.003), respectively. The rest of the components did
not show significant differences among the four phases of the
menstrual cycle.
Fig. 1 shows the results of the sustained attention test
clustered in the component 1 across the four phases of the
menstrual cycle. The reaction time was slow during the
ovulatory phase and in the late luteal phase, and significantly
higher in the early luteal phase. The number of correct
responses was low in the ovulatory phase and high in the
early luteal phase. The number of errors and omissions were
higher in the ovulatory phase and lower in the early luteal
phase, late luteal phase and menstrual phase.
Fig. 2 shows the results for the visuo-spatial memory (A)
and the verbal fluency (B) tests clustered in component 5
across the four phases of the menstrual cycle. The distance
(mm) in the visuo-spatial memory test was shorter (better)
in the ovulatory phase and longer (worse) in the late luteal
phase and in the menstrual phase. The number of gener-
ated words from the verbal fluency test was significantly
lower in the ovulatory phase, and was higher in the late
luteal phase.
Sustained attention and visuo-spatial memory favored by ovarian hormones 993

Table 1 Results of principal component analysis on neuropsychological performance and mood during the menstrual cycle

Eigenvectors
1 2 3 4 5
Neuropsychological tests
Executive functions
Correct responses 0.173 0.063 0.002 S0.796 0.127
Perseverative errors 0.088 0.286 0.208 0.834 0.086
No perseverative errors 0.150 0.077 0.097 0.751 0.007
Unique responses 0.009 0.472 0.322 0.013 0.369
Manual coordination
Time (s) 0.281 0.495 0.003 0.064 0.119
Errors 0.117 0.370 0.070 0.048 0.468
Verbal fluency
Words 0.011 0.247 0.061 0.058 S0.819
Sustained attention
Correct 0.800 0.030 0.169 0.025 0.095
Errors 0.894 0.192 0.005 0.030 0.066
Reaction time 0.545 0.257 0.118 0.189 0.217
Omissions 0.947 0.014 0.002 0.105 0.035
Visuo-spatial memory
Distance (mm) 0.101 0.089 0.200 0.086 0.733
Spatial ability
Correct 0.145 S0.865 0.081 0.020 0.148
Errors 0.130 0.877 0.116 0.002 0.133
Mood questionnaires
Anxiety 0.367 0.046 0.522 0.467 0.191
Depression 0.154 0.066 0.931 0.030 0.156

Percentage of the explained variance 17.69 13.39 12.63 12.57 12.03

F values F = 3.37 F = 1.76 F = 1.67 F = 1.43 F = 6.13
p significant levels p < 0.034 p = 0.180 p = 0.200 p = 0.259 p < 0.003
Rotated values, bold values correspond to relevant eigenvectors >0.50.

4. Discussion covaried and separated from other neuropsychological vari-

An increase of the body basal temperature in the luteal phase
and regular menstrual bleeding were observed as expected in
all women participating in the present study. The rise of the
body temperature reaching a maximum in the luteal phase, is
associated with an elevated progesterone level delivered by
the corpus luteum and is considered an ovulation index
(Bonnar, 1984). The increase of the body basal temperature
and the observed regularity of the menstrual bleeding, indir-
ectly suggest that the women showed ovulatory cycles. This
pattern allows us to suppose that the estrogen and proges-
terone levels presented typical fluctuations across the men-
strual cycle (Ferin et al., 1973; Marshall, 2001). Thus, a
variation in the performance tests by the women during
the menstrual cycle could be established. Although the size
of the sample was small, each woman was tested four times
during the cycles.
As hypothesized the principal component analysis identi-
fied five components (eigenvectors) that covaried across the
menstrual cycle. All components were related to specific
cognitive domain and mood in young women. The neuropsy-
chological test scores gathered in component independent
ables studied, suggest an independent influence of the men-
strual cycle on these cognitive processes and mood. The test
scores gathered in a component indicating that the perfor-
mance of these tests covaried together in a dependent
manner, reflecting some common influence of the menstrual
cycle on these cognitive domains.
The ability to sustain alertness to process high priority
signals is a fundamental aspect of an attention function
system (Denckla, 1996), and is the key to successful informa-
tion processing. The present study found that the scores on
sustained attention covaried independently from other test
scores studied. During the EL phase, when the progesterone
surge, women showed an increased reaction time and an
increase in the number of correct responses and a decrease of
the number of errors and omissions compared with other
phases of the menstrual cycle. Women showed a reduced
sustained attention during the ovulatory phase (estrogen
transient peak), indicated by an increase in the number of
errors and omissions and slow reaction time.
Progesterone metabolites bind to the GABAA receptor
complex potentiating GABAergic inhibitory mechanisms
(Majewska, 1992; Ruprecht, 1997). Sustained attention test
994 S. Solı́s-Ortiz, M. Corsi-Cabrera

Figure 1 Shows mean and standard error in the sustained attention test (component 1) during the ovulatory phase (OVU), in the early
luteal phase (EL), in the late luteal phase (LL), and the menstrual phase (MEN). The reaction time is shown in (A), the number of correct
responses in (B), the number of errors in (C), and number of omissions in (D). Asterisks indicate significant differences between the
phases (*p < 0.05).

demands target detection, orientation, recognition of the lobes (Posner and Raichle, 1994; Riccio et al., 2001; Bearden
object’s identity, maintaining alertness, working memory et al., 2004). The inhibitory role of progesterone during the
and selective response over time, all of them executive EL phase, particularly at the frontal cortex, where proges-
attention functions attributed to right frontal and parietal terone receptors have been found (Blaustein and Wade,

Figure 2 Shows mean and standard error in the visuo-spatial memory test and verbal fluency test (component 5) during the ovulatory
phase (OVU), in the early luteal phase (EL), in the late luteal phase (LL), and the menstrual phase (MEN). The distance in mm is shown in
(A) and the number of words generated in (B). Asterisks indicate significant differences between the phases (*p < 0.05).
Sustained attention and visuo-spatial memory favored by ovarian hormones
1978; Blaustein, 2003), might favor a test where working
memory, concentration and focusing awareness are neces-
sary to perceive relevant external stimuli while inhibiting
intrusion from distracting stimuli. Influence of progesterone
in the nervous system and on cognition have been reviewed in
several studies (Mani and O’Malley, 2002; Schumacher et al.,
2004; Stein, 2005), which suggest that progesterone plays an
important role in facilitating cognition. Progesterone during
the midluteal phase in women was positively correlated with
better performance on perceptual tasks (Broverman et al.,
1981), the visual memory task (Phillips and Sherwin, 1992),
with an improvement in the performance of a task demanding
prefrontal functions (Solı́s-Ortiz et al., 2004a) and implicit
memory (Maki et al., 2002), and with an increase in the
attentional blink in the right hemisphere (Hollander et al.,
2005).
In animal models using tasks that involve hippocampal and
prefrontal cortex functions, it has been found that ovariec-
tomized rats treated with progesterone, dihydroprogester-
one and 5a-pregnan-3a-ol-20-one performed better in the Y-
maze and in the object recognition tasks (Frye and Lacey,
2000), and rats in proestrus performed better than in dies-
trous or estrous in the object recognition task, concomitant
with an increase in serum estradiol and progestins levels
(Walf et al., 2006).
The present study also found that the scores on visuo-
spatial memory and verbal fluency tests were grouped in the
component 5, but in inverse directions, and covaried across
the menstrual cycle. The component scores of these two
cognitive processes that favor women (Postma et al., 1999;
Hampson and Kimura, 1992), also showed significant changes
during the four phases of the menstrual cycle tested. Women
exhibited an increase in visuo-spatial memory tests indicated
by more precise positioning of the ‘‘X’’, and a decrease in the
verbal fluency test, indicated by a low number of words
generated during the OVU phase, accompanying an estrogen
surge. In the LL phase, when estrogens and progesterone are
at low levels, women showed a decrease in the spatial
memory test, and an increase in the verbal fluency test,
indicated by a larger number of generated words. The women
did not show significant changes on Hidden Figures Test
(spatial ability), in contrast with Broverman et al. (1981)
probably because this ability favors men (Hampson and
Kimura, 1992).
In animal models it has been described that estrogens play
a role in regulating the structure and function on many
neuronal systems in the adult rat brain (McEwen et al.,
1997; McEwen, 2001; Bjömström and Sjöberg, 2005). Estro-
gens increase the number of the spines on the dendrites of
hippocampus (Woolley and McEwen, 1992; Woolley, 1998;
Yankova et al., 2001), and they might improve cognitive
behavior related with this cerebral structure (McEwen and
Alves, 1999). Estradiol binds with a high affinity to both
estrogen receptor (ER) isoforms, ERa and ERb, which are
expressed in many regions of rat brain, including the hippo-
campus and cerebral cortex (Shughrue et al., 1997), brain
regions considered important for learning and memory pro-
cesses. Intracellular progestin receptors have been also
localized in the frontal cortex (Blaustein and Wade, 1978;
Blaustein, 2003) and in the CA1 region of the hippocampus
(Hagihara et al., 1992), a structure critically important to
spatial memory (Squire and Zola-Morgan, 1991; Lavenex and
995
Amaral, 2000; Shrager et al., 2007). Studies in humans using
functional magnetic resonance imaging (fMRI), found that
the perirhinal cortex and anterior parahippocampal cortex
were active during spatial and object memory encoding
(Buffalo et al., 2006).
The visuo-spatial memory test employed in the present
study in women, demanding retention of the precise metric
positions of the ‘‘X’’, named positional encoding, spatial
localization, and built in cognitive maps of the space, are
functions attributed to the hippocampus (O’Keefe and Nadel,
1978). The activational role of the estrogen in the hippo-
campus, where receptors to estrogen have been found (Reg-
ister et al., 1998; Blurton-Jones et al., 1999; Gundlah et al.,
2000), might aid in the performance of the spatial memory
tasks, requires positional encoding, which favor women (Eals
and Silverman, 1994; James and Kimura, 1997; Postma et al.,
1999), while that other spatial skills, as mental rotation, are
better in the menstrual phase (Hampson and Kimura, 1988;
Hampson, 1990; Silverman and Phillips, 1993; Hausmann
et al., 2000).
The verbal fluency found also in component 5, showed a
significant increase in the number of the words generated
during the late luteal phase, when the estrogen and proges-
terone are at low levels. This finding suggests that low levels
of the ovarian hormones which might facilitate verbal skills
require complex verbal processing such as word generation
with a specific letter of the alphabet. Some studies suggest
that simple verbal output tasks, such as speed and accuracy
of articulatory performance, may be facilitated during
phases of the menstrual cycle characterized by higher serum
concentration of estrogen (Hampson, 1990; Hampson and
Kimura, 1992; Maki et al., 2002).
The spatial ability grouped in the component 2, anxiety
and depressive symptoms grouped in component 3, and the
executive function grouped in component 4 covaried inde-
pendently from other cognitive functions measured.
Although the component scores did not reach significant
levels when they were compared with the four phases of
the cycle, these components accounted for 38.59% of the
total of the variance (13.39%, 12.63%, and 12.57%, respec-
tively). The women did not show significant changes on
performance of these neuropsychological variables, prob-
ably due to an absence of the premenstrual syndrome.
However, several studies have reported that spatial ability
is better in the menstrual phase, when estrogen and pro-
gesterone are at low levels (Hampson and Kimura, 1988;
Silverman and Phillips, 1993; Hausmann et al., 2000),
depressive symptoms are high in the late luteal phase (Rubi-
now and Schmidt, 1987; Endicott, 1993; Halbreich, 2003),
and the executive functions are improved in the early luteal
phase, when the progesterone is at high levels (Solı́s-Ortiz
et al., 2004a).
The variations on cognition found in the present study are
not due to changes in anxiety or depression because the mood
scores were separated in different components, and perhaps
because the women tested did not show a premenstrual
syndrome. Still in young women without premenstrual syn-
drome there are variations in cognition.
In conclusion, the findings indicate that sustained atten-
tion is favored by the early luteal phase progesterone and do
not covaried any other neuropsychological variables studied.
The influence of the estrogens on visuo-spatial memory
996
during the ovulatory phase was corroborated and covaried
inversely with verbal fluency. The PCA was useful to deter-
mine the structure and relationships between the neuropsy-
chological variables and the components accounted close to
70% of the total variance across the menstrual cycle.
Role of funding source
Funding for this study was provided by CONCyTEG Grant 06-
16-k117-142 and CONACYT Grant 060645 and Grant 52365 and
University of Guanajuato. The CONCyTEG, CONACYT and
University of Guanajuato had no further role in study design;
in the collection, analysis and interpretation of data; in the
writing of the report; and in the decision to submit the paper
for publication.
Acknowledgements
Consuelo Murphy corrected the English version of the manu-
script. We thank volunteer women for their participation in
this study.
Conflict of interest
The authors declare that they have not conflicts of interest.
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