Neuroscience & Medicine, 2013, 4, 217-222
Published Online December 2013 (http://www.scirp.org/journal/nm)
http://dx.doi.org/10.4236/nm.2013.44034
Open Access NM
217
Prospective Memory Assessment, before and after the Use
of Concentrated Extract of Soy, in Postmenopausal
Women Complaining of Memory Impairment
Lucia Helena Laprano Vieira, Teresa Raquel Embiruçu de Araújo, Mauro Abi Haidar, Ivaldo Silva
Gynecological Endocrinology, Department of Gynecology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
Email: lucia.andalo@terra.com.br, ivaldo.toco@epm.br
Received August 3rd, 2013; revised September 1st, 2013; accepted October 1st, 2013
Copyright © 2013 Lucia Helena Laprano Vieira et al. This is an open access article distributed under the Creative Commons Attribu-
tion License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
ABSTRACT
Obje ctive: To evaluate the performance of a sample of postmenopausal women complaining of decline of prospective
memory, undergoing therapy with concentrated extract of soy (CES) for six months, through specific neuropsycho-
logical assessment, developed for this purpose. Materials and Methods: A randomized and double-blind study was
with 90 women, 12-month amenorrhea, 40 years to 65 years and body mass index (BMI) above 30 kg/m2, whose com-
plaints were reduction of cognitive efficiency. The participants were randomly divided into two treatment groups:
Group I—received one capsule of 150 mg extract of soy, with 60 mg isoflavones orally/day; Group II—received one
capsule placebo, for six months. All participants underwent a detailed interview, the MMSE, depression scale, and as
they were being included in the study, self-perception scales and neuropsychological tests before and after six months
of treatment. For analysis purposes, we applied the ANOVA and t-student tests. Results: Our results suggest a possible
positive effect regarding the improvement in verbal fluency and executive function tasks of planning and mental flexi-
bility, in women undergoing therapy with concentrated extract of soy in postmenopause. There was no correlation be-
tween prospective memory and cognitive performance, and there were only intensity scores of the depressive symptoms.
Conclusion: Isoflavones act favorably on the cognitive function, amongst all functions, only on verbal memory and
executive function tasks of planning and mental flexibility. The others showed no signs of improvement. We concluded
that concentrated extract acts only on some cognitive functions.
Keywords: Menopausal Transition; Postmenopausal; Isoflavones; Prospective Memory; Neuropsychology
1. Introduction
Menopause is defined as the permanent cessation of
menstruation, and normally occurs around the age of 40
[1]. Estrogen deficiency of this phase is associated with
vasomotor symptoms, trophic changes, bone loss, car-
diovascular disease [2,3], psychological disorder and
decline in terms of cognitive effectiveness [4-6].
Regarding the reduction of the effectiveness of cogni-
tive functioning after menopause, about 60% of women
in the menopausal transition have worsened memory,
showing difficulty in remembering words and numbers,
and evoking previous situations and intentions that must
be performed in the future, thus having complaints of
difficulty in concentrating very frequently [7].
The memory is, however, a complex working system
and difficulties in remembering intentions that should be
turned into actions in the future, within a short period of
time or longer, are referred to as prospective memory
failure (PM). Difficulties in recalling previous events and
situations are called retrospective memory failures (RM)
[8].
The prospective memory is widely used in daily ac-
tivities such as work, study or social life and is fully in-
tegrated in the social relations of daily life, and prospec-
tive memory-related failures, as in the case of forgetting
an appointment may have extremely negative social
consequences [9,10].
For several decades, the use of hormone therapy was
considered as the ideal treatment for climacteric symp-
toms; however, the controversy over its hormonal effects
Prospective Memory Assessment, before and after the Use of Concentrated Extract of Soy,
in Postmenopausal Women Complaining of Memory Impairment
218
has caused a significant increase in the search for natural
forms of treatment. There is evidence demonstrating that
the use of soy-derived isoflavones might be a good al-
ternative for the treatment of various symptoms associ-
ated with menopause transition, as well as for patients
with contraindications to conventional TH [11-13].
Although several studies have demonstrated the influ-
ence of isoflavones on cognitive performance, the results
are still contradictory. A review by MacReady et al.
(2009) [14], about the effects of concentrated extract of
soybean (ECS) on cognition in postmenopausal women,
showed discrepancies in the results of different studies,
with justifications pointing to variations in sample size,
composition of phytoestrogens, time management, and
study design, suggesting the need for further studies to
understand the influence of the long-term effects of soy
isoflavones on cognitive functioning, because of the high
prevalence of complaints related to memory difficulties,
reported in the postmenopausal period.
The aim of our study was to evaluate the performance
of a sample of postmenopausal women complaining of
decay in prospective memory, undergoing therapy with
concentrated extract of soy and possible correlations with
scales of self-perception and mood indicators.
2. Materials and Methods
The study group consisted of 90 postmenopausal women
assisted in the Menopausal and Postmenopausal Transi-
tion sector, regarding the discipline of Gynecological
Endocrinology, Department of Gynecology, Federal
University of São Paulo, Paulista School of Medicine
(UNIFESP-EPM), from May 2009 to May 2013. This
project has been approved by the Ethics Committee of
the Federal University of São Paulo/São Paulo hospital,
as part of the research project “Effects of isoflavones on
sexual response in postmenopausal women”. The diag-
nosis of menopause was based on clinical data, that is,
amenorrhea for at least 12 months, confirmed by the in-
crease of gonadotropin, follicle stimulating hormone
(FSH > 40 mIU/mL) and low amounts of estrogen (E2 <
20 ng/dl). The patients who met this criteria, complaining
of decline in cognitive efficiency, that hadn’t undergone
previous hormone treatments, and hadn’t made use of
herbal or diet rich in soy foods, for three months, were
selected to participate in the study.
Patients suffering from cognitive impairment, accord-
ing to the MMSE Mini-Mental State Examination criteria,
having scored 36 or more on the Beck Depression In-
ventory, aged less than 40 years of age and more than 65
years of age, body mass index (BMI) greater than 30
kg/m2 or contraindication to estrogen therapy haven’t
been included.
Patients were randomly divided into two groups (the
choice of treatment was determined by computer pro-
gram randomized number generator, and just after the
end of the study, the researcher knew which group the
patient belonged to: Group I—received 150 mg of con-
centrated extract of soy in the form of a capsule with 60
mg of total isoflavones orally/day, herbal product, com-
mercialized by the Herbarium Isoflavine laboratory;
group II—received a capsule containing inactive sub-
stance (placebo). All made use of the medication con-
tinuously for six months. The capsules have a white color,
thus making it impossible for the researcher and patient
to distinguish which one was the substance. All studied
patients underwent the routine laboratory exams (Pap
smear (maturation index, and hormonal evaluation), tran-
svaginal ultrasonography, mammography), whose results
will not be discussed in this paper. In addition, we col-
lected information on the age, weight and height, age,
race and time since menopause (Table 1).
All participants underwent a detailed interview, the
MMSE, the depression scale, and as they were being
included in the study, they were subjected to the self-
Table 1. Socio-demographic and clinical variables, related
to samples of women have been included in the study .
Group I Group II (p)
Isoflavones
n = 43
Age (average in years)* 53.5 ± 4.07 55.1 ± 3.810.062
IMC (kg/m2)* 24.7 ± 2.65 25.4 ± 2.710.221
Date of last menstrual period
(age)* 4.2 ± 2.47 4.4 ± 2.650.819
Previo 61% (25) 69.8% (30)0.492
Maritual status** (frequency %) 0.227
Married/Stable relationship (n) 65.9%(27) 81.4% (35)
Divorced/separated (n) 24.4% (10) 11.6% (5)
Single/widow (n) 9.8% (4) 7% (3)
Schooling (frequency) 0.774
From 0 to 3 years of age (n) 0 0
From 4 to 8 years of age (n) 14.6% (6) 20.9% (9)
From 9 to 11 years of age (n)39% (16) 37.2% (16)
Above 12 years of age (n) 46.3% (19) 41.9% (18)
Profession (frequency) 0.696
Economically active (n) 58.5% (24) 53.5% (23)
Retired (n) 19.5% (8) 16.3% (7)
Hosewife/student (n) 22% (9) 30.2% (13)
*Fisher’s exact test
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Prospective Memory Assessment, before and after the Use of Concentrated Extract of Soy,
in Postmenopausal Women Complaining of Memory Impairment
219
perception scales and neuropsychological tests in the
beginning of and after the six months of treatment.
2.1. Evaluation of Prospective Memory
The main objective of this study was to evaluate the pro-
spective memory; however, we have used neuropsy-
chological tests to assess various cognitive domains such
as intellectual efficiency, attention, memory, language
and executive function, to understand other areas of cog-
nitive whose deficits could have a say in the performance
tests of prospective memory.
The prospective memory was assessed with two scales
of self-perception: Subjective Perception Memory Test
(MAC-Q) [15], used to assess memory complaints re-
lated to five everyday situations and Prospective and
Retrospective Memory Questionnaire (PRMQ) [8], ela-
borated to assess failure of prospective memory (PM)
and retrospective memory (RM) in patients with cogni-
tive impairment, clinical and healthy populations.
2.2. Neuropsychological Evaluation
Neuropsychological assessment tests that were used fol-
lowed the protocol widely used for cognitive research:
attention, language, executive functions and memory.
The test battery included measures of language and ex-
ecutive function (Semantic Verbal Fluency Test—SVF);
attention (A and B Trails, codes), memory (the memory
list words TMLP), executive functions (Stroop Color
Test and Forward and Backward Digits)
2.3. Sample Size and Statistical Analysis
Initially we calculated the sample size with the aid of the
computer program. The required number to estimate an
association between adherence to treatment and clinical
improvement in postmenopausal women complaining of
memory impairment was 45 women. For the treatment of
multivariate correlations, a 50% increase in sample size,
with a total number of about 90 women has been pro-
posed. For analysis purposes, we applied the ANOVA
and t-Student tests. In all comparisons, it was considered
as significant probabilities associated with tests less than
0.05, i.e., with a maximum of 5% chance of rejecting the
hypothesis of equality when it is true.
3. Results
In total, 90 postmenopausal patients, Who met the initial
criteria, were included in the study and randomly divided
into two groups: Group 1—received 150 mg of concen-
trated extract of soy in the form of a capsule, with 60 mg
of total isoflavones, orally/day group II—received a cap-
sule containing inactive substance (placebo) for six
months.
During the study, four patients from the placebo group
gave up (one for the sake of weight gain, one by private
issues and two for lack of adherence). In the group
treated through isoflavones, one patient gave up due to
weight gain and lack of adherence. At the end, 84 com-
pleted the study as outlined in the sample study scheme
(Figure 1).
In the assessment of sociodemographic and clinical
characteristics of patients participating in the study, at the
beginning of the treatment, there was no statistically sig-
nificant difference between the two groups, which dem-
onstrated that they were similar in the pre-treatment (Ta-
ble 1). The performance results scored in the scales of
perception, depression and assessment of cognitive point
of view, isoflavone and placebo groups, are widely
shown in Table 2.
Regarding performance in the self-perception scales,
we found no statistically significant difference (p < 0.05)
between the groups; however, at the data analysis in or-
der to investigate the reliability of the changes, between
pre and post treatment, and the clinical significance of
these changes, the isoflavone group had a reliable change
Randomized
(
N=90
)
Loss to
follow-up
(N=2)
Apparent
weight gain
(N=1)
No adherence
(N =1)
Loss to
follow-up
(N=4)
Apparent
weight gain
(N=1)
Family
problems
(N=1)
No adherence
(N=2)
Analized
(N= 43)
Excluded (N= 734)
Phones not found = 206
No sexual complaint = 69
More than 10 years of
menopausal or over 65
years of age = 48
Premenopausal or
menopausal transition =
154
Undergoing treatment or
less than three months
without treatment = 57
Gynecological cancer,
previous surgery with
unknown diagnosis or
contraindication to TH =
31
BMI > 30 = 52
Endometrial thickening or
breast abnormality = 17
Would not wish to
participate by TH = 5
Lack of availability or
did
not show up = 95
Analized
(N= 41)
Placed in
Group B:
placebo
(N= 45)
Placed in
Group A:
isoflavones
(N= 45)
Women interested in
taking part in the
study (N = 824)
Figure 1. Study sample sc he me.
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Prospective Memory Assessment, before and after the Use of Concentrated Extract of Soy,
in Postmenopausal Women Complaining of Memory Impairment
220
Table 2. Summary of the overall results of the study of the
placebo groups and isoflavones at the first visit (pretreat-
ment) and after 6 months of treatment.
placebo Isoflavonevalue p*
BDI 6.2 (11.28) 7.8 (10.10)0.486
MAC-Q 2.3 (15.46) 7.3 (17.94)0.172
OVERALL TOTAL PRMQ 2.9 (15.94) 7.3 (18.74)0.250
TRAIL A (seconds) 6.7 (15.82) 2.8 (21.07)0.340
TRAIL B (seconds) 10.0 (27.28) 8.4 (50.91)0.852
STROOP I 1.4 (6.95) 3.6 (7.00)0.146
STROOP II 2.2 (5.85) 1.5 (7.78)0.663
STROOP III 4.8 (10.82) 4.1 (9.20)0.891
LIST OF WORDS (Total) 6.7 (11.69) 5.9 (11.88)0.764
CODES 2.4 (6.66) 2.5 (5.48)0.973
OD Digits 0.9 (11.43) 5.6 (13.00)0.078
OI Digits 2.0 (14.76) 0.6 (15.04)0.657
TOTAL OF Digits 1.4 (8.37) 3.3 (8.98)0.319
VERBAL FLUENCY 0.3 (2.48) 1.3 (1.72)0.027*
*comparison between groups
in the scale of self-reported failures of prospective mem-
ory (p = 0.027) (Figure 2).
In the group of isoflavones there was no statistically
significant difference (p < 0.05) between prospective
memory and performance on neuropsychological tests of
controls: Track A (p = 0.340), Track B (p = 0.852), word
list (p = 0.764), Codes subtest (p = 0.973), Stroop I (p =
0.146), Stroop II (p = 0.663), Stroop III (p = 0.891), To-
tal Digits Forward and Backward (p = 0.319). In the ver-
bal fluency test that assesses processing of language and
executive function, the isoflavone group had better per-
formance when compared to the control group. (p =
0.027).
The correlation of the scales of self-perception (MAC-
Q, MP and MR) with neuropsychological tests was sta-
tistically weak, however there was a positive correlation
between the scale that assesses the severity of Beck de-
pressive symptoms with the scale of self-perception
PRMQ in Total (p = 0.001), mp (p = 0.002), and MR (p
0.001).
4. Discussion
This study aimed at analyzing the effects of the concen-
trated extract of soy in the perception of prospective
memory, after menopause. We know that cognitive de-
cline is very common in the transition and postmeno-
Figure 2. Reliability of the pre- and post-intervention
changes on the self-reported prospective memory failures
scale.
pause. Several theories attempting to explain the retarda-
tion appeared through that stage, and the more likely is
the one regarding the reduction of the levels of estrogens,
by changing some neurotransmitters and synaptic density
in key areas of the central nervous system (CNS) [16].
Investigations on the effects of HT on cognitive func-
tioning revealed positive effects, particularly in verbal
memory, verbal fluency, concentration, attention and
speed of information processing [17,18].
Our results partially confirm these data and suggest a
possible positive effect of isoflavones regarding greater
verbal fluency and executive function tasks of planning
and mental flexibility, in women undergoing therapy
with concentrated extract of soy in postmenopausal.
Our sample showed some important characteristics,
such as an average age of 55 years, which can be indi-
cated as a negative factor, since it excludes the possibil-
ity of research into the effect of age and frequency of
memory failures; however, results reported by Hachul et
al. (2009) [19] reported that patients in the early post-
menopausal period claimed to have more memory fail-
ures compared to women in pre-menopause and during
the late postmenopause. Possibly, these subjective mem-
ory difficulties reflect a greater perception of cognitive
performance that was strongly reflected in the average
age of our sample.
Another important demographic characteristic was the
average schooling, mostly 9 to 11 years and above 12
years, as well as the highest percentage regarding profes-
sions: economically active patients. According to De
Lorenzi et al. (2006) [20] as they approach menopause,
women bring questions about the physical changes that
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Prospective Memory Assessment, before and after the Use of Concentrated Extract of Soy,
in Postmenopausal Women Complaining of Memory Impairment
221
will occur and how to handle them. The higher education
not only facilitates access to information about meno-
pause, but also reduces anxiety, which is so common in
this phase. The very self-care itself is affected by school-
ing and is related to the increased demand for medical
care at this stage [21].
As for the intensity of depressive symptoms, we ob-
served a reduction in two groups: control and isoflavones,
suggesting the existence of a placebo response often re-
ported in clinical trials for the treatment of neuro-vege-
tative symptoms associated with menopause [22].
With respect to subjective perception of prospective
memory, our data indicate that the group receiving iso-
flavones had better performance, so this improvement
was not significant when compared to the placebo group.
When we investigate the reliability of the changes be-
tween pre- and post-treatment and clinical significance,
we found that the isoflavone group showed clinical im-
provement (perception) after six months of treatment.
In our study, the group of isoflavones performed bet-
ter on the verbal fluency test when compared to the con-
trol group. Verbal fluency tasks have been widely used to
assess processing of language and executive function,
and our results are consistent with studies by Howes et al.
(2004), Kreijkamp-Kaspers et al. (2004) e Ho et al. (2007)
[23-25].
Unexpectedly, our data suggest that the placebo group
showed significant improvement in tests of selective and
divided attention when compared to isoflavones. These
results need further studies, and a hypothesis to be raised
is that possibly these measures were not sensitive enough
to detect improvement in the performance of the function
evaluated [14,17,23,24].
The evaluation of immediate memory, storage capacity
and recovery, and the memory test of word list (TLMP)
showed no differences between the number of words
recalled and raised in the two groups. It is noteworthy,
that schooling, according to Beeri et al. (2006) [26], may
have been a factor positively associated with the outcome
of the cognitive performance presented by two groups.
Similarly to the previous result, no differences were
found in relation to performance in the operational mem-
ory, when compared to the placebo group and the group
of isoflavones.
There are limitations in our study concerning the se-
lection of instruments for evaluating the performance of
prospective memory. According to Mizuno (2001) [9],
the methods used to study prospective memory currently
involve questionnaires, naturalistic ecological evidence
and laboratory studies. Although we’ve used a question-
naire of quick application and easy understanding, its
validity is questioned by the ratio between the direct re-
sponse and the actual daily routine.
Despite of the updating of self-perception question-
naires and neuropsychological tests, we need more long-
term studies, so that they are able to achieve more con-
clusive evidence of the action of phytoestrogens on cog-
nitive function at the postmenopause.
5. Acknowledgements
This work has been supported by CNPq, National Coun-
cil for Scientific and Technological Development.
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