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RELATIONSHIP BETWEEN MENSTRUAL CYCLE PHASES
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5/08 K lProj/Acc8Pres/CIRC/Date0ue indd

 

 

RELATIONSHIP BETWEEN MENSTRUAL CYCLE PHASES AND COGNITIVE
FUNCTION IN FEMALES WHO USE AND DO NOT USE ORAL
CONTRACEPTIVES
BY

MEREDITH G. COCKERELL

A THESIS
Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of
MASTER OF SCIENCE

Department of Kinesiology

2008

ABSTRACT
RELATIONSHIP BETWEEN MENSTRUAL CYCLE PHASES AND COGNITIVE
FUNCTION IN FEMALES WHO USE AND DO NOT USE ORAL
CONTRACEPTIVES
By

Meredith G. Cockerell
Purpose: The purpose of this study was to evaluate the cognitive function of
females who use oral contraceptives and do not use oral contraceptives during
the three phases of the menstrual cycle. Cognitive function was measured using
the Immediate Post-Concussion Assessment and Cognitive Testing (lmPACT)
neuropsychological test battery.
Methods: A total of 32 participants (19 females not taking oral contraceptive, 13
females taking oral contraceptives) volunteered for this study. Immediate Post-
Concussion Assessment and Cognitive Testing (lmPACT) was administered
during each phase of the menstrual cycle, follicular, luteal and menses.
Results: There were no differences in lmPACT scores during the different phases
of the menstrual cycle for females who do and no not take oral contraceptives.
Conclusion: Results suggest that there is no cognitive impairment throughout the

different phases of the menstrual cycle. This is true for females who take and

who do not take oral contraceptives.

ACKNOWLEDGEMENTS

I would to acknowledge the efforts of my thesis committee Dr. Tracey
Covassin, Dr. Sally Nogle, and Dr. Michelle Brewer for their help and guidance
with this thesis.

To Dr. Tracey 00vassin I would not have been able to finish this thesis
without you. Thank you for your long hours, and hard work on this project.

To Dr. Michelle Brewer, thank you for serving on my committee and for
your help throughout this project. Thank you all your help this fall, Everett High
School is extremely grateful.

To Dr. Sally Nogle, thank you for your help and guidance on this project.
Thank you for serving on my committee and for sharing all your wonderful
knowledge about Athletic Training.

To my family, thank you for your guidance throughout my years of
education and the ever lasting encouragement you have given me. Without you,
none of this would have-been possible.

To all of my participants, thank you for volunteering to be part of this

study.

iii

TABLE OF CONTENTS

LIST OF TABLES ............................................................................
CHAPTER 1
INTRODUCTION... .. . .. .....................................................................

Overview of the Problem ..........................................................
Significance of the Problem ......................................................
Statement of the Problem .........................................................
Hypothesis ............................................................................
Definition of terms ..................................................................

CHAPTER 2 ‘
LITERATURE REVIEW .....................................................................

Anatomy of the Menstrual Cycle ................................................
Menstrual Cycle and Cognitive Function ......................................
Menstrual Cycle and Mood Disorders ..........................................
Hormone Replacement ............................................................
Oral Contraceptives ............................................................ .. . . .
Review of Method Literature .....................................................
Immediate Post-Concussion Assessment

and Cognitive Testing (lmPACT) .......................................
Summary ..............................................................................

CHAPTER 3
METHODS .....................................................................................

Research Design ....................................................................
Participants ...........................................................................
Immediate Post-Concussion Assessment

and Cognitive Testing (lmPACT) .......................................
Reliability and Validity of lmPACT ..............................................
First Response Ovulation Test ...................................................
Data Collection Procedures ......................................................
Testing Session .....................................................................
Data Management ..................................................................
Data Analyses ........................................................................
Threats to lntemal Validity ........................................................
Threats to External Validity .......................................................

CHAPTER 4
RESULTS ......................................................................................

Demographic lnfonnation .........................................................
Baseline Data ........................................................................
Evaluation of Hypothesis .........................................................

CHAPTER 5
DISCUSSION .................................................................................

iv

8
8
9
12
14
15
17

17
18

19
19
19

20
23
25
25
26
27
28
28
29

31
31
31
33

39

Discussion of lmPACT Composite Scores .................................... 39

Clinical Interpretation of Results ................................................ 41

Limitations ............................................................................ 42

Future Research Considerations ................................................ 43

Conclusion... ... ...................................................................... 43
APPENDICES

A. Human Subject Consent Form .............................................. 44

B. Health Questionnaire .......................................................... 47
REFERENCES ............................................................................... 49

LIST OF TABLES
Table
4-1 Descriptive Baseline lmPACT Composite and Symptom
Scores for the Total Sample ................................ 32

4-2 Descriptive Statistics for No Oral Contraceptives and
Oral Contraceptives Groups on lmPACT

Composite Scores and Total Symptoms ................. 34
4-3 Box's Test of Equality of Covariance Matrices(a) ........................ 35
4-4 Levene's Test of Equality of Error Variances(a) ......................... 36

4-5 MANCOVA within Subjects Effect for
Time and Group X Time ....................................................... 37

4-6 MANCOVA between Oral Contraceptive
and No Oral Contraceptive .................................................... 38

vi

CHAPTER 1
INTRODUCTION
Overview of Problem
The menstrual cycle is a natural monthly event in young women,
influenced by physiological and pathological changes that occur during a
female’s life (Redman, Scroop, & Norman, 2003). The female menstrual cycle
has been studied using a variety of different research methods. One main focus
of research has concentrated on symptoms women experience during the
different phases of the menstrual cycle (Friedman, Hurt, Amoff & Clarkin, 1980;
Brooks, Ruble, & Clark, 1977; Keenan, Lindsmer, & Jong, 1995; Olasov &
Jackson, 1987; Abplanalp, Donnelly, & Rose, 1979). Another area that has
been researched concentrates on the cognitive function of females during
phases of the menstrual cycle (Shaywitz et al., 1999; Sommer, 1972; Sherwin,
2003; Dietrich et al., 2001; Owens, Matthews, & Everson, 2002; Morgan &
Rapkin, 2002). However, most menstrual cycle and cognitive function research
concentrates on irregular menstrual cycles of females, or females who have
problems such as pain or negative moods during their menstrual cycle (Keenan
et al., 1995). Very few researchers have investigated, cognitive function of
normally cycling females during the menstrual cycle.
The primary function of the menstrual cycle is to allow females to
reproduce. Themenstrual cycle occurs in all healthy females and has specific
hormonal changes throughout the cycle. The main female sex hormones that

regulate the menstrual cycle are progesterone and estradiol. Progesterone and

estradiol are responsible for the start and cessation of bleeding (Gruhn & Kazer,
1989). These hormones may play a role in cognitive function; as a result they
need to be more clOsely examined to determine if cognitive function changes
during the menstrual cycle.

The menstrual cycle has historically been associated with discomfort and
pain. Several studies tested menstrual pain through the use of questionnaires
such as the Social-Sexual Activities Log (SSAL), Profile of Mood States (POMS),
Menstrual Distress Questionnaire (MDQ), Zung Self-Rating Anxiety Scale, and
Daily monitoring forms (Abplanalp et al., 1979; Keenan et al., 1995; Olasov &
Jackson, 1987; Collins, Eneroth, & Landgren, 1985; Brooks, Ruble, & Clark,
1977). Some of the symptoms studied were tension/anxiety, depression, anger,
fatigue, and confusion (Abplanalp et al., 1979). However, none of these studies
examined if cognitive function changes during the menstrual cycle.

Cognitive function is the ability to use reasoning, judgment, memory, and
perception effectively and in a timely manner (Saladin, 2001 ). Cognitive function
has previously been assessed through Ieaming tests such as the California
Verbal Learning Test (CVLT), stroop test, Digit Span-Backward, Symbol Digit-
Correct and the Wechsler Memory Scale (Keenan et al., 1995). Recently,
cognitive function has been examined through computerized neurocognitive test
batteries or functional magnetic resonance imaging (fMRI) (Maki & Resnick,
2001). To date there have been no studies that have investigated the use of a
computerized neurocognitive test battery during the phases of the menstrual

cycle.

There are many discrepancies in the literature on menstrual cycle and
cognitive function. Some researchers suggest that cognitive function is affected
by different phases of the menstrual cycle (Shaywitz et al., 1999; Maki &
Resnick, 2001; Dietrich et al., 2001; Schoning et al., 2007) whereas other
research studies reported no difference in cognitive function during the different
phases of the menstrual cycle (Sommer, 1972; Owens et al., 2002; Morgan &
Rapkin, 2002; Owens, Matthews, & Everson, 2002). Shaywitz et al. (1999) found
that postmenopausal females who were administered estrogen performed better
on working memory tasks than postmenopausal females not taking estrogen
supplements. The researchers suggest that pre-menopausal estrogen levels are
depleted during the menses phase of the menstrual cycle. In another study by
Morgan and Rapkin (2002), hormone replacement therapy was found to
influence the brain function and cognition status across phases of the menstrual
cycle. In contrast, Sommer (1972) concluded that there are no declines in
intellectual performance across phases of the menstrual cycle. Due to these
discrepancies in the literature more research is needed to determine if cognitive
function differs during the different menstrual cycle phases.

Oral contraceptives are the most used form of reversible contraception in
the United States and throughout most of the wortd (Abraham, Luscombe, & $00,
2003). Oral contraceptives are small tablets taken orally for either 21, 24, or 28
days or longer each month. Oral contraceptives release synthetic hormones that
prevent the release of eggs from the ovaries (Ernst, Baumgartner, Bauer, &

Janssen, 2002). Due to the high rate of oral contraceptive usage among females

the positive and negative side effects of oral contraceptives have been widely
studied. However, most of the literature has concentrated on physical or mental
pain and not on Cognitive function.

Significance of the Problem

The menstrual cycle occurs in all females and is individualized to every
woman. The three different menstrual cycles include menses, follicular, and
luteal phase. Research has shown that many females have problems during at
least one phase of the menstrual cycle (Keenan et al., 1995). Problems such as
pain, arousal, negative moods and the inability to focus during daily activities all
commonly occur during the menstrual cycle (Abplanalp et al., 1979). Some
researchers have tried to determine if problems during the menstrual cycle such
as negative moods are due to the negative connotations of the menstrual cycle
or an outside source (Olasov & Jackson, 1987). For example, Olasov and
Jackson (1987) found that expectancies regarding the mood-menstrual
relationship could be altered by means of a brief lecture on the menstrual cycle.
Results found changes in the mood-menstrual relationship could still be detected
as long as 40 days post-lecture.

Female sex hormones such as progesterone and estradiol have been
evaluated during different phases of the menstrual cycle. Estradiol is a steroid
hormone produced primarily by the ovaries and adrenal gland. Estradiol is the
most active form of estrogen in the human body and is responsible for a normal
monthly cycle. Estradiol is also known to play a role in quite a number of

important physiological processes such as bone mineral density and

osteoporosis prevention. Progesterone is the other important female hormone.
Like estradiol, progesterone is responsible for a normal monthly cycle.
Progesterone is a precursor for most other hormones including
Dehydroepiandrosterone (DHEA), estradiol, testosterone and cortisol. However,
more research is needed on progesterone to determine all functions this
hormone plays in the human body. It is important to study hormone fluctuations
according to the different menstrual phases, because the difference in hormone
levels may affect cognitive function and in turn may have an affect on the
females’ daily life.

Oral contraceptives work by controlling the release of hormones. There
are two main types of birth control pills: the combination pills and the progestin-
only pill. Combination oral contraceptives consist of synthetic versions of
estrogen and progestin and are taken daily to block the usual hormone
messages that direct ovulation. As a result, egg development is blocked
preventing conception. Other effects of combination oral contraceptives help
prevent sperm from reaching the egg and reduce the chance of the egg
implanting in the uterus (O’Connell, Davis, & Kems, 2007). Unlike combination
oral contraceptives, progestin-only pills contain no estrogen and have a lower
dose of progestin than combined birth control pills. Progestin-only oral
contraceptives work in three different ways: (1) they make the cervical mucus at
the entranceto the uterus too thick for the sperm to get through to the egg; (2)
they prevent ovulation in about half of the users; and (3) they affect other

hormones, the fallopian tubes, and the lining of the uterus (O’Connell et al.,

2007). Since oral contraceptives pharrnacologically control the hormones
estrogen and progesterone, it is important to study the effects of oral
contraceptives on cognitive function. Very little research has been conducted in
the past two decades on cognitive function and menstrual cycle. Furthermore,
there have only been a few studies that have evaluated the use of oral
contraceptives on cognitive function during different phases of the menstrual
cycle (Brooks et al., 1977; Wright & Badia, 1999).
Statement of the Problem

The purpose of this study was to evaluate the cognitive function of
females who use oral contraceptives and do not use oral contraceptives during
the three phases of the menstrual cycle. Cognitive function was measured using
the Immediate Post-Concussion Assessment and Cognitive Testing (lmPACT)
neuropsychological test battery.
Hypothesis

There will be no difference in cognitive function during the three different
phases of the menstrual cycle for females who do not take oral contraceptives
and females who take oral contraceptives.
Definition of terms

Estradiol: The most active naturally occurring estrogen (Gruhn and Kazer,
1989)

Follicular Phase: Phase in the menstrual cycle were levels of estradiol are
high, the first day of the menstrual cycle usually lasting 14 days until ovulation

(Walpurger, Pietrowsky, Kirschbaum, & Wolf, 2004)

Luteal Phase: Phase in the menstrual cycle were estradiol and
progesterone are high, the time from when the egg is released until the first day
of menstruation (Walpurger et al., 2004)

Menses phase: Phase in the menstrual cycle where levels of estradiol and
progesterone are low, usually occurring in the second to forth day of bleeding
(Walpurger et al., 2004)

Menstrual Cycle: The number of days between the beginning menstrual
bleeding to the day preceding the onset of the next bleeding (Abplanalp et al.,
1979)

Neu_rocogn_itive Fu_nction: The ability to use reasoning, judgment, memory,
and perception effectively and in a timely manner (Saladin, 2001)

Progesterone: A sex hormone that regulates the menstrual cycle (Gruhn
and Kazer, 1989)

Verbal Memory: recall of word lists (Kolb & Wishaw, 2003)

Visual Memory: recall of geometric shapes and faces (Kolb & Wishaw,
2003)

Reaction Ti_me: The time between the onset of a stimulus and the

beginning of a movement response (Haywood & Getchell, 2005)

CHAPTER 2
LITERATURE REVIEW

This seCtion will outline background information pertaining to anatomy of
the menstrual cycle, menstrual cycle and cognitive function, menstrual cycle and
mood disorders, hormone replacement, oral contraceptive use, and the
importance of lmPACT.

Anatomy of the Menstrual Cycle.

The menstrual cycle is made up of many changes that take place inside
the body. These changes help prepare a female’s body for pregnancy each
month. The progression of the cycle from one to the next is caused by the rise
and fall of hormones throughout a specific interval, usually about 28 days, or one
month. Although the typical menstrual cycle lasts 28 days, it can range anywhere
from 21 to 38 days, and it can vary from female to female. The follicular phase is
the time from the first day of the menstrual cycle until ovulation, when a mature
egg is released from the ovary. It’s called the follicular phase because growth or
maturation of the egg is taking place inside the follicle, a small sac where the egg
matures. Ovulation occurs around day 14 of the cycle, in response to a surge of
luteinizing hormone (LH) when the egg is released from the ovary. The luteal
phase is the time from when the egg is released (ovulation) until the first day of
menstruation. It is named after the corpus Iuteum, and is a structure that grows in
the ovary where a mature egg was released at ovulation. (Gruhn & Kazer, 1989).
The declining levels of progesterone at the end of the normal menstrual cycle

causes a process that allows the inner layer of the uterus, the endometrium, to

becomes necrotic and then discarded, leading to menstruation (Gruhn 8 Kazer,

1 989).
Menstrual Cycle and Cognitive Function.

There have been several studies that have investigated cognitive function
and the menstrual cycle. Some studies have found that the menstrual cycle
causes changes in cognitive function across all the different phases of the
menstrual cycle (Maki & Resnick, 2001; Dietrich et al., 2001). For example, Maki
and Resnick (2001) conducted a review of studies pertaining to the activational
effects of estrogen on cerebral activity during rest and during performance of
cognitive tasks in pre and postmenopausal women. The researchers found that
specific neuroimaglng outcomes fluctuate across the menstrual cycle in young
women. Dietrich et al., (2001) used fMRI and blood oxygenation level-dependent
(BOLD) contrast to study hemodynamic menstrual cycle dependant changes for
a verbal, spatial, and motor task. Six females with a normal menstrual cycle
participated in the study. The participants were scanned twice, once during
menses and once on the 11/12th day of the menstrual cycle. Results found that
blood estrogen level strongly influenced cerebral hemodynamics and that these
changes dramatically alter the size but not the pattern of cortical activation during

performance of cognitive task.

Schoning et al., (2007) conducted a study that investigated gender
differences in mental rotation performance and brain activation patterns

measured through fMRI. In addition, variations in gender differences to

menstrual cycle phases were also evaluated. Twelve women and 12 men were
scanned once in the fMRI while performing a mental rotation task. Results
revealed men and women exhibited significant differences of brain activation
patterns. The researchers also found differences across menstrual cycle in
females. Several regions such as the left middle temporal gyrus, left lentifonn
nucleus and thalamus, left and right cingulated gyrus, corpus callosum, right
middle temporal gyrus, superior occipital and angular gyrus, and right middle and
superior frontal gyrus, exhibit enhanced activation patterns when female
hormones are at their peak (midluteal). The researchers concluded that estrogen
might enhance vasoreactivity and therefore lead to an increased activation of the

(Schoning et al., 2007).

Keenan et al. (1995) conducted a study to determine if memory
impairment on the California Verbal Learning test (CVLT) was generalizable to
memory for narrative or nonverbal material. Thirty-six women were analyzed that
had PMS. Keenan et al. (1995) suggests that women with prospectively
documented premenstrual syndrome have a subtle, yet consistent, relative
memory impairment. These findings were consistent regardless of phase the
participants were in during their menstrual cycle. However, Collins et al. (1985)
conducted a study to examine whether there is a difference in
psychoneuroendocrine reactivity to psychologic stress as a function of the normal
menstrual cycle. Fifteen normally cycling females were participated in this study.
The participants were induced with a stressful activity such as cognitive-conflict

task, mental arithmetic test or a computer game. Hormone levels were taken

10

during different menstrual cycle phases. The researchers concluded that
although some women do report an impairment of their mental capacity before or
during menstruation, when objective measures of performance were employed
the majority of studies have failed to demonstrate significant phase-related

changes.

When the Watson-Glaser Critical Thinking Appraisal test was used to
determine intellectual performance, it failed to show an association between
menstrual cycle phase and test performance (Sommer, 1972). Sommer (1972)
conducted a study with college aged females using the Watson-Glaser Critical
Thinking Appraisal test to determine if intellectual performance was altered during
different menstrual cycle phases. Sommer (1972) found no difference in
intellectual performance, however, the author suggest that there may be changes
in other subdivisions of intellectual function. Owens et al. (2002) conducted
another study that did not find any differences in cognitive function across the
phases of the menstrual cycle. This study utilized the Welchsler Adult Intelligence
Scale-Revised Information Subset, California Verbal Learning Test, Digit Span
Test, and Verbal Fluency Test to assess cognitive function. Results revealed no
differencesin test score across the phases of the menstrual cycle. In a study
done by Morgan and Rapkin (2002), cognitive function was evaluated throughout
the menstrual cycle in women who suffer from premenstrual dysphoric disorder
and controls. Participants included 37 women who met prospectively documented
criteria of premenstrual dysphoric disorder and 32 control women who did not

have the disorder. Cognitive function was examined using the Digit Span test,

11

Extended Digit Symbol test, California Computerized Assessment Package, and
Simple reaction time test. The researchers found that females who suffer from
premenstrual dysphoric disorder exhibit no difference when compared to a control

group in the late luteal phase of the menstrual cycle (Morgan & Rapkin, 2002).

Owen, Matthews, and Everson (2002) conducted a study to evaluate the
effects of a pharrnacologically induced, temporary suppression of ovarian
hormones on healthy women’s cognitive function. The researchers used tests
such as the Wechsler Adult Intelligence Scale, California Verbal Learning Test,
Digit Span test and Verbal Fluency Test. Sixteen healthy women were tested
three times, once during normal follicular phase, a second time after four monthly
injections of gonadotropin-releasing hormone (GnRH) agonist, and a third time
after either 3 more GnRH agonist injections or after resuming follicular cycles.
Experimental participants were compared to a control group that were tested
three times during the normal follicular phases. Results showed no evidence
that a decline in ovarian hormones was associated with change in short-term

verbal memory, concentration, attention, or mood.

Menstrual Cycle and Mood Disorders

The menstrual cycle has commonly been associated with negative moods
and symptoms. Abplanalp et al. (1979) conducted a study to better understand
the psychological function of women during the menstrual cycle. Mood was
assessed with the POMS and SSAL questionnaires and revealed that there was

no relationship between cycle phase and mood or enjoyment of activities

12

(Abplanalp et al.,-1979). Abplanalp et al. also suggested that daily events had a
greater impact on moods and enjoyment of daily life than the menstrual cycle.
The results of their study might have been affected by the participants knowing
that they were being tested for menstrual cycle symptoms, which is a common
problem in most menstrual cycle studies (Abplanalp et al.).

Olasov and Jackson ( 1987) found that expectancies regarding the mood-
menstrualrelationship could be altered by means of a brief lecture on the topic.
Olasov and Jackson took four groups of college aged females and had them
listen to a lecture that either associated the menstrual cycle as a negative
experience, a positive experience, not related to the menstrual cycle, or no
lecture at all. Results indicated that females who received the lecture associated
the menstrual cycle with negative experiences had more negative feelings toward
their own menstrual cycle.

Brooks et al. (1977) conducted a study to explore the range of
expectations and attitudes associated with menstruation. The self-reported study
included 191 college-aged females who reported experiencing more severe
symptoms in premenstrual phase than intramenstrual phase. The researchers
suggest these findings may reflect stereotypical expectations. However some
researchers have stated that self-reporting is not a reliable source of information.
According to Friedman et al. (1980) self-reporting symptoms and attitudes cause
too much discrepancy, therefore, alternative methods should be used to test

symptoms such as anxiety and cognitive function.

13

Hormone Replacement

Post-menopausal women have been widely studied due to the loss of
estrogen they experience during menopause. The effects of estrogen may have
positive effects on the brain and cognitive function. Shaywitz et al. (1999)
performed a study to determine the effects of estrogen on brain activation
patterns in post-menopausal women as they performed verbal and nonverbal
working memory task. The study was conducted in a hospital setting using forty-
six post-menopausal women. Results indicated that estrogen produces
significant alterations in brain activation patterns as seen by an fMRI as post-
menopausal women performed a working memory task. Sherwin (2003)
conducted a review a literature investigating estrogen and its role in cognitive
function. It was found that estrogen replacement therapy (ERT) aids in
protecting verbal memory in post-menopausal women. Dietrich et al. (2001)
examined if hemodynamic menstrual cycle dependant changes for verbal, spatial
and motor task. An fMRl using blood oxygenation level-dependent contrast was
used to examine cognitive function. Results revealed normal cycling females
blood estrogen level have a significant difference between the sizes of activation
in an fMleor cognitive task when estrogen is at peak levels (Dietrich et al.,
2001)

In contrast to previous research, one study found that during high levels of
the sex hormones (estrogen and progesterone) spatial test score decreased
(Hausmann, Slabbekoom, Van Goozen, Cohen-Kettenis, & Gunturkun, 2000).

Hausmann et al. (2000) administered a mental rotation test during the menses

14

and midluteal phase and found that all women had higher test scores in the
menses phase, specifically when estrogen levels are at its lowest point during the
menstrual cycle. Hausmann et al. concluded that spatial performance is
sensitive to hormonal fluctuations across the menstrual cycle and that different
aspects of spatial performance are related to different hormones. Similarly, in
another study that suppressed estrogen in normally functioning females it was
found that a decline in ovarian hormones was associated with change in short-
tenn verbal memory concentration and attention (Owens et al., 2002).
Oral Contraceptives

Oral contraceptives have been a widely studied topic for there use in
protecting women against pregnancy. There are two primary types of oral
contraceptives, combination and progestin-only pills. Combination oral
contraceptives consist of synthetic versions of estrogen and progestin taken
daily, which block the usual hormone interaction that direct ovulation. Estrogen
and progestin, the active ingredients in the pill, are similar to the hormones that a
female’s body naturally makes. Females taking oral contraceptives results in egg
development being blocked, preventing conception (Damey, 1997). Unlike
combination oral contraceptives, progestin-only pills contain no estrogen and
have a lower dose of progestin than combined birth control pills. Progestin-only
oral contraceptives work in 3 different ways: (1) they make the cervical mucus at
the entrance to the uterus too thick for the sperm to get through to the egg; (2)
they prevent ovulation in about half of the users; and (3) they affect other

hormones, the fallopian tubes, and the lining of the uterus (Graham, Ramos,

15

Bancroft, Maglaya, & Farley, 1995). There have been several studies that have
examined the possible side effects of oral contraceptives which include nausea,
breast pain, and headache (O’Connel, Davis, & Kems, 2006; Ernst,
Baumgartner, Bauer, & Janssen, 2002). However oral contraceptives have not
been widely investigated for their affect on cognitive function during different
menstrual cycle phases.

Brooks et al. (1977) conducted a study to explore the range of
expectations and attitudes associated with menstruation. The researchers found
that women who were taking oral contraceptives had the same attitudes and
accepted the same cycle-related symptoms as women who were not taking oral
contraceptives. Abraham et al., (2003) conducted a study to examine the
cyclicity and group differences in daily menstrual cycle mood and physical
experiences of three groups of healthy women using monophasic, triphasic OC
or non-hormonal contraception. It was found that there were no differences
between oral contraceptive users and non-oral contraceptive users in mood and
physical experiences (Abraham et al.). In contrast, Wright and Badia (1999)
conducted a study to examine the influence of menstrual cycle phase and oral
contraceptives on nighttime alertness and performance on the circadian rhythms
and body temperature. Oral contraceptive users had higher alertness and
performance in the follicular phase when compared to non-oral contraceptive

users.

16

Review of Method Literature

Phases of the menstrual cycle have been determined by either self-
reporting when the first day of bleeding occurred, ovulation tests, or by taking
blood samples. Ablanalp et al. (1979) found that taking blood samples was much
more accurate in determining the stage of menstrual cycle. Hausmann et al.
(2000) also determined that by taking blood samples the researcher is then
certain that the female is in the correct menstrual cycle phase. However, taking
blood samples is extremely costly and invasive to the participant. Therefore,
many studies have used seIf-reporting to determine which menstrual cycle phase
the participants are in (Abplanalp et al., 1979; Brooks et al., 1977). Furthermore
self-reporting is commonly used when there is a large sample size due to the
cost involved in blood samples.

The ovulation test is a good method to determine phase of the menstrual
cycle, because it considered non-invasive and not as costly as blood samples.
An ovulation test can confirm that ovulation has occurred and the participant has
moved from the follicular phase to the luteal phase by identifying a surge in
urinary luteinising hormone (LH). Once the LH surge has been shown to occur, it
can be assumed with a confidence level of 95% that ovulation will take place
within the next 14 to 26 hours (Janse de Jonge, 2003).

Immediate Post-Concussion Assessment and Cognitive Testing (lmPACT)
Neuropsychological testing has evolved from the traditional paper and
pencil test to the computerized test. Immediate Post-Concussion Assessment

and Cognitive Testing (lmPACT) is a computer-based program used to assess

17

neurocognitive function. The neurocognitive test, lmPACT has been most widely
used for establishing neurocognitive deficits after sustaining a concussion. The
lmPACT test consists of a demographic section, self-report concussion
symptoms, and six individual test modules that measure aspects of cognitive
function including attention, memory, reaction time, and processing speed
(lverson, Lovell, 8 Collins, 2003). Detailed information and psychometric
properties of lmPACT are covered under the methods section.
Summary

Overall it has been shown that there are many discrepancies in the
literature regarding the menstrual cycle and cognitive function. Furthermore, oral
contraceptives have not been widely investigated for their effect on cognitive
function during different menstrual cycle phases. The main female sex
hormones that regulate the menstrual cycle are progesterone and estradiol.
These hormones may play a role in cognitive function; as a result they need to be
more closely examined to determine if cognitive function changes during the
menstrual cycle. Therefore, the purpose of this study was to evaluate the
cognitive function of females who use oral contraceptives and do not use oral

contraceptives during the three phases of the menstrual cycle.

18

CHAPTER 3
METHODS

This chapter describes the design, procedures, and methodology used in
this research. Included in this chapter are the following: Research Design,
Participants, Immediate Post-Concussion Assessment and Cognitive Testing
(lmPACT), First Response Ovulation Test, Data Collection Procedures,
Management, and Analysis, and Threats to lntemal and External Validity.
Research Design

This study was a quasi-experimental two group counterbalance research
design. This study is considered a two group counterbalance design because
there will be two groups; oral contraceptives and no oral contraceptives. The
participants acted as their own control for this study. The independent variable is
phase of the menstrual cycle. It has three levels: menses phase, follicular phase,
and luteal phase. The dependent variable is the lmPACT neurocognitive test
battery. lmPACT consists of verbal memory composite score, visual memory
composite score, reaction time composite score, and processing speed
composite score.
Participants

Thirty-two adult females were asked to volunteer for this study.
Specifically, 19 females who were not taking oral contraceptives and 13 females
who were taking ortho tri-cyclen lo (norgestimate/ethinyl estradiol). Ortho tri-
cyclen lo (norgestimate/ethinyl estradiol) is comprised of a combination of

progestational compound norgestimate and the estrogenic compound ethinyl

19

estradiol. Participants were between the ages of 18 to 28 years. Prior to taking-
part in the study participants signed an informed consent. Females had no
history of menstrual cycle problems, or history of pregnancy. All participants had
no history of concussions within the past six months. Participants taking oral
contraceptives were all taking the same dosage birth control pill, ortho tri-cyclen
lo (norgestimate/ethinyl estradiol). The participants took a different pill every
week. First the white pill was comprised of 0.18mg of progestational compound
and 0.025mg of the estrogenic compound. The light blue pill was comprised of
0.215mg of the progenstational compound and 0.025 mg of the estrogenic
compound. The dark blue pill was comprised of 0.250 mg of the progenstational
compound and 0.025 mg of the estrogenic compound. The dark green pill has
no active ingredients.
Immediate Post-Concussion Assessment and Cognitive Testing (lmPACT)

lmPACT version 5.0 (lmPACT Applications Inc.) is a computer-based
program that was used to assess neurocognitive function (Lovell et al., 2006).
The software program is run from either a desktop PC or laptop using Windows
NT operating system or higher(Lovell, Collins, Podell, Powell & Maroon, 2000).
The program uses a keyboard and external mouse to allow participants to select
responses and navigate through the six test modules.

The lmPACT protocol consists of three categories. The first category
included a demographic information section. The user was asked to navigate

through a series of instructional screens where they are asked to enter

20

descriptive information about themselves, such as years in school, presence of
Ieaming disabilities, and neurological disorders.

The second category censists of 22 symptoms that participant’s rate using
a seven point Likert scale. These symptoms include headache, nausea, vomiting,
balance problems, dizziness, fatigue, trouble falling asleep, sleeping more than
usual, sleeping less than usual, drowsiness, sensitivity to light, sensitivity to
noise, irritability, sadness, nervousness, feeling more emotional, numbness or
tingling, feeling slowed down, feeling mentally foggy, difficulty concentrating,
difficulty remembering, and visual problems. Participants self-rated their
symptoms by clicking on a number between zero (not experiencing) and six
(severe) using an external mouse.

The third category consists of six neurocognitive test modules. It is
important to note that lmPACT has multiple built-in word/design groups. This is
important to limit practice effects. A different word/design group was
administered to the participant for each lmPACT test. Module one of the
neurocognitive test battery focuses on word discrimination. This section is used
to evaluate verbal memory and attentional processes. Subjects are presented
with 12 words two times each for 750 milliseconds. Individuals are then tested to
recall words from a 24 word list. There are 12 target words and 12 non-target
words. Using the mouse, subjects are prompted to select “yes” or “no” depending
on whether or not the word was presented in the original list. After a 20 minute
delay, subjects are asked again to recall this list of words. A total score of

percent correct is given at the end of the battery.

21

Module two evaluates attention and visual recognition through design
memory. Similar to module one, 12 target designs are presented twice for 750
milliseconds. Following the presentation subjects are asked to recall these
designs, choosing from the 12 target and 12 non-target designs presented.
Subjects are prompted to click “yes” or “no” depending on whether or not the
design was originally presented. After a 20 minute delay, subjects are asked
again to recall this list of designs. A total score of percent correct is given at the
end of the battery.

Module three is designed to measure visual working memory, visual
processing speed, and visual memory. This section incorporates a distracter
which is a reaction time test that asks the subject to click the left mouse button if
a blue square appears, and the right mouse button if a red circle appears. For the
memory test, a random assortment of X’s and Os are displayed for one and one-
half seconds. Of this random assortment, three X’s and O’s are illuminated in
yellow. The subject is instructed to remember the placement of these illuminated
objects. Immediately following the presentation of the three illuminated X’s and
O’s, the subject is asked to complete the distractor task. After the completion of
the distractor task, the memory screen reappears and the subject is asked to
click on the X’s and O’s that were originally highlighted. Four trials are completed
for this section. Scores for this section include percent correct for identification of
the X’s and 0’s and reaction time scores for the distractor task.

Module four is a symbol-matching task that evaluates processing speed,

Ieaming, and memory. A grid with nine common symbols and accompanying

22

numbers is presented to the subject. The subject is presented with a symbol
below the grid, and is asked to click the number of the corresponding design.
After 27 trials, the symbols are removed from the grid. The symbols are
presented below the grid, and the subject is asked to recall the correct
symbol/number pairing by clicking the appropriate button. Reaction time scores
and memory scores are both calculated.

Module five measures choice reaction time and impulse control. Subjects
are presented with the words red, green, and blue each written in their respective
color. Subjects are instructed to click the mouse when the word correctly
matches with the color ink. For this section, a reaction time score and task error
score are provided.

The sixth and final module examines working memory and visual motor
response speed. This module is comprised of both a distractor task and memory
component. Participants are presented with and asked to remember three letters.
Once the letters are removed from the screen, the participant is presented with
the distractor task. A 5x5 grid appears on the screen consisting of 25 numbered
boxes. The participant is asked to count backwards, clicking on the
corresponding numbered box. with the mouse. Following the completion of the
distractor task, the participant must input the three letters in the exact order they

were previously presented. There are five trials for this test module.
Reliability and Validity of lmPACT

Test-retest reliability for lmPACT was assessed over eight days across

four administrations, yielding correlation coefficients ranging from 0.66 to 0.85 for

23

the verbal memory index, 0.75 — 0.88 for the processing speed index, and 0.62 to
0.66 for the reaction time index(Lovell, Collins, Fu, Burke & Podell, 2001). Using
reliable change indices, repeated administrations over a 2-week period revealed
no practice effects (lverson, Lovell, Collins & Norwig, 2002). In another study,
one week test-retest reliability coefficients were as follows: 0.70 for verbal
memory, 0.67 for visual memory, 0.79 for reaction time, and 0.86 for processing
speed, with significant teSt-retest differences for only the processing speed
composite scores on with-in subject comparisons (lverson, Lovell & Collins,
2005). Concurrent validation of lmPACT revealed correlations with the Symbol-
Digit Modalities test (SDMT) which ranged from 0.37 and 0.46 for visual and
verbal memory indices, t00.60 and 0.70 for reaction time and processing speed
indices (lverson, Lovell & Collins, 2005). Since the SDMT is believed to measure
scanning and tracking aspects of attention, as well as processing speed (Spreen
& Strauss, 1998), these coefficients represent good convergent and divergent
validity. Correlations between lmPACT visual and verbal memory composites
with the Brief Visual Spatial Memory Test-Revised total score (r=.50) and the
delayed recall score (r=.85) have been established (lverson, Franzen, Lovell &
Collins, 2004); the processing speed composite was shown to correlate with the
Trailmaking Tests A (r= -.49).and B (r= -.60), and the SDMT (r=.68). Schatz and
colleagues documented a combined sensitivity of 81.9% for lmPACT indices and
total symptom score, and a specificity of 89.4%; positive likelihood ratio was
approximately 8:1 and negative likelihood ration was 2:1 (Schatz, Pardini, Lovell,

Collins & Podell, 2006).

24

First Response Ovulation Test

In order to confirm that ovulation has occurred in naturally cycling females,
and, the participant has m0ved from the follicular phase to the luteal phase, an
ovulation test was taken. The ovulation test identified a surge in urinary
luteinising hormone (LH). Once the LH surge occurred, it can be assumed with a
confidence level of 95% that ovulation took place within the next 14 to 26 hours
(Janse de Jonge, 2003). ' This is important because ovulation marks the end of
the follicular phase and the start of the luteal phase.

Data Collection Procedures

Michigan State University’s Institutional Review Board approved this study
prior to data collection. Participants were chosen solely on a volunteer basis.
The participants were recruited by word of mouth and through fliers. The fliers,
were posted in IM Circle and IM West in the women’s locker room. Once
participants were recruited,they were selected by a convenience sampling
method. '

Participants were asked to sign an informed consent form prior to testing
and data collection (see Appendix A). The consent included: the purpose of
research, the duration of data collection, the testing procedure, the potential risk
and/or benefits of the testing, confidentiality, contact information for myself, my
advisor, as well as Michigan State University’s UCRIHS office, and a place for
the participant to sign and date. The Participant was also given a health history
questionnaire to determine if they met the requirements for this study (see

Appendix B)

25

Testing for this research was done over the course of each participant’s
menstrual cycle. All tests were done at approximately the same time of day. The
participant was asked to report the start of her last menstrual cycle. Based on
the first date of the last menstrual cycle, the follicular, luteal, and menses was
then approximated. Ovulation was confirmed by the First Response Ovulation
test to ensure the change from the follicular phase to the luteal phase. In 15 out
of the 19 participants ovulation was confirmed, the other three participants’ luteal
phase was approximated. Each participant’s menstrual cycle was calculated and
a testing schedule was determined.

Participants taking oral contraceptives did not take the ovulation test.
Participants were taking orth-tricyclin lo (norgestimate/ethinyl estradiol) resulting
in a 28 day menstrual cycle. Participants took lmPACT during day 1 to 4 for
follicular phase, day 15 to 19 for luteal phase and day 22 to 26 for menses
phase.

Testing Session

This study was performed in the computer lab in IM Sports Circle, on the
Michigan State University campus during pre-arranged times convenient for the
participants and researchers. There was a total of three testing sessions. For
naturally cycling females (no oral contraceptive) the first testing session was
determined by the start of their first day of bleeding of their last menses cycle.
Their current menstrual cycle phase was determined by counting the days from
the last menstrual cycle which determined if they are in the follicular phase which

occurs 15 to 22 days before onset of new menstrual cycle, luteal phase which

26

occurs 3 to 9 days before the onset of a new menstrual cycle, or menses the
second to fourth day of bleeding. The participant then took the lmPACT
neurocognitive test battery. After the participants completed the lmPACT test
battery the remaining two testing sessions were determined and scheduled.

Participants taking oral contraceptives were all on a 28 day menstrual
cycle, and taking ortho tri-cyclen Io (norgestimate/ethinyl estradiol). All phase
cycles were approximated because the participants had a set menstrual cycle.
Participants took lmPACT during day 1 to 4 of the start of a new oral
contraception pill pack for follicular phase, day 15 to 19 for luteal phase and day
22 to 26 for menses phase.
Data Management

Data was recorded through the lmPACT software. The data were then
transferred into a Microsoft Excel spreadsheet and imported into an SPSS data
file for statistical analysis. All data files were kept on a password protected
personal computer in a locked office. A backup of the data was kept on a USB
travel drive that was kept in a locked desk in a locked office. All consent forms
and results of the ovulation test were also kept in a locked office and only
authorized researchers had access to the consent forms and data files.
Participant privacy was assured by issuing a participant number to each person
to ensure that their names are not linked to their data after the testing procedure

is complete.

27

Data Analyses
The lmPACT yields composite scores for verbal memory, visual memory,

visual processing speed, and reaction time. A higher score by the participant on
verbal and visual memory, and processing speed indicates better performance.
Verbal and visual memory scores are presented as a percentage of 100 and
processing speed as a number composite score. A lower score on reaction time
indicates a better performance. The lmPACT also yields individual scores for
concussion symptoms. A 2 group (oral contraceptive, no oral contraceptive) X 3
time (menses, follicular, luteal) multivariable analysis of variance (MANCOVA)
controlling for history of concussion was performed on the lmPACT composite
scores. The statistical significance level was set at p<0.05. All analyses were
conducted using SPSS version 15.1 (SPSS Inc, Chicago, IL).
Threats to Internal Validity

There are many threats to lntemal validity in this study; however, maximum
efforts will be taken to minimize the effects of these threats. Reverse causation
was a threat because a decreased lmPACT score could have several possible
explanations. This was controlled for by have the participants take lmPACT
during every phase of the menstrual cycle.

There are numerous time threats that occurred in this study. History was a
threat in this study because the participants took lmPACT on three different days
within the menstrual cycle. History was controlled for by having each participant
take lmPACT during each phase, therefore, acting as their own control.

Maturation was also a threat to this study because the participants had

28

approximately a week and half in between testing sessions. This was controlled
for by having the participant take the test as soon as possible during the
menstrual cycle phase. Instrumentation is a threat because lmPACT could
malfunction at any point therefore tainting the data. The computers used for
lmPACT were piloted to make sure the program is working before each testing
session. Reactivity to testing is controlled by lmPACT itself, the computer test
has been tested to minimize Ieaming affects.

Researcher expectancy could have had a negative effect because the
researcher might expect a change in lmPACT scores through the different
menstrual cycle phases. This was controlled for by the researcher not being in
the room when the participant was taking the test. On-stage effects could pose a
threat if the researcher was watching the participant take the lmPACT test, or
other participants are taking the test at the same time. This was controlled for by
having the researcher not in the room when the test is being taken and by having
each participant take the test in a separate room. Group threats could pose a
problem because there will not be random assignment of groups. This was
minimized because the participants served as their own control.

Threats to External Validity

Threats to external validity were identified and efforts were made to
minimize the effects of these threats. Due to the repetitive testing procedures
there may be reactive/interactive effects of testing. This was controlled by the
nature of the lmPACT test. There should not be an interaction of selection bias

and treatment in the current study. In an effort to minimize the threat of a

29

reaction to experimental setting, the test was done in a computer lab where it is
very quiet and free of any distractions. Multiple treatment interference is not a

threat because there were no actual treatment.

30

CHAPTER 4
RESULTS

The results section is separated into demographic information, baseline
data, and evaluation of the research questions. Overall the there were no
significant differences with lmPACT during the three menstrual phases between
participants in the oral contraceptive and no oral contraceptive groups.
Demographic Information

A total of 32 collegiate females from a Mid-Westem Division l-A university
participated in the current study. All demographic information was collected by
lmPACT and a short questionnaire. Nineteen participants (age= 21.05 1 2.25
years, height: 65.65 1 2.681 inches, weight= 149.40 + 24.96 lbs.) comprised the
no oral contraceptive group and 13 participants (age= 21.34 1 2.10 years,
height= 65.461 2.22 inches, weight= 138.77 1 23.08 lbs.) were on the ortho tri-
cyclen lo (norgestimate/ethinyl estradiol) birth control pill.
Baseline Data 1

A MANCOVA controlling for concussion history was used to examine
differences in baseline lmPACT composite scores between the oral contraceptive
and no oral contraceptive groups. Baseline lmPACT composite scores and
normative data are presented in Table 4-1. In general, the baseline lmPACT
composite scores for this sample were average compared to established

normative data for this population.

31

Table 4-1 Descriptive Baseline lmPACT Composite and Symptom Scores for the

 

 

Total Sample (N=32)
lmPACT Mean SD lmPACT Norms
Module University Women1'
Verbal Memory
No 00 .88 .07 0.92
00 .91 .06
Visual Memory
No OC .78 .09 0.79
00 .81 .1 1
Motor Speed
No OC 38.67 9.85 38.25
00 41.85 7.91
Reaction
No 0C .55 .05 0.55
OC .51 .05

 

TMedian values of women’s lmPACT scores

Oral Contraceptive (0C)

32

A comparison of oral contraceptive and no oral contraceptive participants
indicated no significant differences on baseline lmPACT composite scores
between groups (Wilk’s A: 0.696, F [5, 25] = 2.18, p= 0.088, n2: 0.504). Similarly,
a comparison of all participants and normative data revealed no significant
differences on baseline lmPACT composite scores. The data suggests that
participants were similar in regard to baseline lmPACT composite scores
regardless of these potential confounding factors. Hence, any differences
between lmPACT composite scores would likely be due to menstrual cycle
phases and/or oral contraceptives.

Evaluation of Hypothesis

Hypothesis: There will be no difference in cognitive function during the
three different phases of the menstrual cycle for females who do not take oral
contraceptives and females who take oral contraceptives.

A 2 group (oral contraceptive, no oral contraceptive) x 3 time (menses,
follicular, luteal) repeated measures MANCOVA controlling for concussion history
was used to assess within and between group differences on lmPACT composite
scores and total symptoms during the three phases of the menstrual cycle.
Descriptive statistics of each lmPACT composite score and symptom totals can

be found in Table 4-2.

33

Table 4-2 Descriptive Statistics for No Oral Contraceptives and Oral
Contraceptives Groups on lmPACT Composite Scores and Total Symptoms.

 

 

 

Menses Follicular Luteal
M SD M SD M SD

Verbal Memory

No OC* 0.88 0.08 0.89 0.08 0.92 0.06

OC 0.91 0.07 0.92 0.07 0.90 0.05
Visual Memory

N0 OC 0.78 0.09 0.76 0.12 0.73 0.13

OC 0.80 0.12 0.73 0.10 0.77 0.13
Processing Speed

No OC 38.67 9.85 41.29 8.15 40.84 8.73

OC 41.86 7.91 41.54 7.41 42.81 4.90
Reaction Time

No OC 0.55 0.05 0.54 0.05 0.53 0.04

OC 0.51 0.05 0.51 0.05 0.52 0.06
Total Symptoms

No OC 4.42 5.49 6.42 9.20 3.95 7.02

00 9.85 13.38 7.54 11.19 7.08 12.22

 

*Oral Contraceptive (0C)

34

Box's M test of equality of covariance matrices (see Table 4.3) and
Levene’s test of equality of error variances (see Table 4.4) were both upheld.
Therefore, both the oral contraceptive and no oral contraceptive groups had an
equal distribution. The MANCOVA resultslindicated no significant differences for
within subject effects for time (erk’s A: 0.68, Fis. 18] = .91, p= 0.54, n2: 0.32),
and the interaction between group and time (Wilk’s ll: 0. 56, F [5. 131 = 1.09,
p= 0.42, n2: 0.35) (see Table 4.5). The MANCOVA results also indicated a no
significant differences between the oral contraceptive and no oral contraceptive

groups (Wilk’s A: 0.80, F[5, 18] = 1.25, p= 0.32, n2: 0.20) (see Table 4.6).

Table 4.3 Box's Test of Equality of Covariance Matrices(a)

 

Box’s M 144.86
F 0.98

Df1 78

Df2 2112.12

Significance 0.54

 

35

Table 4.4 Levene's Test of Equality of Error Variances(a)

 

Verbal Memory
Menses
Follicular
Luteal

Visual Memory
Menses
Follicular
Luteal

Processing Speed
Menses
Follicular
Luteal

Reaction Time
Menses
Follicular

Luteal

 

F df2 Sig.
0.32 30 0.58
0.17 30 0.68
0.10 30 0.76
0.21 30 0.65
1.25 30 0.27
0.02 30 0.90
0.10 30 0.76
0.03 30 0.87
1.50 30 0.23
0.66 30 0.42
0.03 30 0.87
2.07 30 0.16

 

36

Table 4.5. MANCOVA within Subjects Effect for Time and Group X Time

 

 

 

 

Effect Value F Hypothesis Error Sig
Time+ Pillai’s Trace .315 .919 (1110.00 (20.00 .535
Wilks’ Lambda .685 .919 10.00 20.00 .535
Hotelling’s .460 .919 10.00 20.00 .535
Trace .460 .919 10.00 20.00 .535
Roy’s Largest
Root
Group++ X Pillai’s Trace .354 1.094 10.00 20.00 .412
Time Wilks’ Lambda .646 1 .094 10.00 20.00 .412
Hotelling’s .547 1 .094 10.00 20.00 .412
Trace .547 1.094 10.00 20.00 .412
Roy’s Largest
Root
*p50.05

+Time: All Participants
++Group: Menstrual Cycle Phases

37

Table 4.6. MANCOVA between Oral Contraceptive and No Oral Contraceptive

 

 

 

Groups
Effect Value F Hypothesis Error Sig

Group Pillai’s Trace .200 1 .249 (51.00 (215.00 .317
Wilks’ Lambda .800 1.249 5.00 25.00 .317
Hotelling’s .250 1.249 5.00 25.00 .317
Trace .250 1.249 5.00 25.00 .317
Roy’s Largest
Root

*p50.05

38

CHAPTER 5
DISSCUSSION

Previous research has demonstrated numerous discrepancies on the
effects menstrual cycle has on cognitive function (Maki & Resnick, 2001, Dietrich
et al., 2000, Keenan et al., 1995). The current study adds to the present body of
literature that states that the menstrual cycle phases have no impact on cognitive
function.
Discussion of lmPACT Composite Scores

The findings of this study found no differences on cognitive function during
the three phases of the menstrual cycle. These results were similar to other
studies that found no significance differences on cognitive function and menstrual
cycle phases (Collins et al., 1985, Sommer, 1972, & Owens et al., 2002). For
example, Owen et al. (2002) found no significant differences in verbal Ieaming
when ovarian hormone levels were changed. The authors suggest no changes
were found because the participants that were tested were healthy, intelligent
young females, similar to the participants in this study. Although Owen et al.
(2002) chemically altered ovarian hormone levels the results can be applied to
this study because horrnone levels naturally change throughout the different
menstrual cycle changes.

Comparable to the present study and others, Collins et al. (1985) found no
difference in cognitive function when using neuropsychological tests such as
cognitive-conflict, mental arithmetic and a computer game, all similar to the

lmPACT test used in this study. Collins et al. (1985) attributed no significant

39

change in test results to the sample selection. All participants were well
educated college aged females that had no history of menstrual cycle problems.
Similarly this study also found no differences in cognitive function across the
phases of the menstrual cycle.

Contrary to the findings of this study there have been a few studies that
have found changes in brain function during the different phases of the menstrual
cycle (Maki & Resnik, 2001, Dietrich et al., 2000, & Schoning et al., 2007). For
example, Schoning et al. (2007) used mental rotation of 3-D objects which tested
participants’ visuo-spatial memory. This study used functional MRI (MRI), and
found an increase in cortical activation across the phases of the menstrual cycle.
The luteal phase of the menstrual cycle demonstrated the greatest increase in
cortical activation. However, this study did not use mental rotation testing
techniques or an fMRI. Hence, the different findings between Schoning et al.
(2007) and this study could be attributed to different methodologies used.
Schoning et al. (2007) used fMRI which measures brain activation while this
study examined a behavioral cognitive task measure by lmPACT.

There have been very few studies that have evaluated cognitive function
during phases of the menstrual cycle on females taking oral contraceptives.
According to our findings there were no significant differences between the oral
contraceptive and the no oral contraceptive groups. In contrast with this study,
Wright and Badia (1999) found that oral contraceptive users had higher alertness
and performance in skills such as switching task, two column addition, digit

recall, reaction time task, dual task, continuous recognition, memory recall and

40

dual task when compared to females who did not take oral contraceptives during
sleep deprivation. Wright and Badia ( 1999) contributed the higher scores to the
participants on oral contraceptives having significantly higher body temperature
than participants not taking oral contraceptives. Wright and Badia (1999)
suggest that temperature level strongly relates to nocturnal waking
neurobehavioral function. The contrary in findings could be attributed to the
small sample size and sample selection. The participants in this study were
healthy and fully rested, whereas in Wright and Badia’s (1999) study the
participants were sleep deprived.
Clinical Interpretation of Results

It appears that when testing verbal and visual memory, reaction time and
processing Speed across the menstrual cycle phases there are no difference in
cognitive function. A possible reason may be because lmPACT is not sensitive
enough to detect any changes through the three different phases. The lmPACT
neurocognitive test was originally developed to evaluate the neurocognitive
impairments that can occur after a concussion. The participants in this study did
not have any injury therefore; the lmPACT test might not have been sensitive
enough to pick up on any minor changes in cognitive function that possibly could
occur during the different phases of the menstrual cycle.

It could be possible that when testing normal females that the hormonal
fluctuations are not great enough to detect. Another possible explanation may be
due to verbal and visual memory, reaction time and processing speed are not

affected by the hormonal changes in females. Estrogen and progesterone are

41

the two main hormones involved in the menstrual cycle. This study
demonstrates that females have the same thought process regardless of
progesterone or estrogen levels. It can be stated that although some women do
report an impairment of their mental capacity before or during menstruation,
when objective measures of performance were employed this study failed to
demonstrate significant menstrual cycle phase-related changes.

Limitations

There were several limitations in this study. One limitation to the current
study was the sample population and size. Only females from one Division l-A
Institution participated in this study. Recruiting females from various institutions
and from multiple regions of the country would aid in providing a more diverse
sample. In addition the current study had a small sample size which may have
contributed to the findings.

Another limitation was the use of only one type of oral contraceptive, ortho
tri-cyclen lo. Although it was necessary to control oral contraceptives for this
study, ortho tri-cyclen lo (norgestimate/ethinyl estradiol) is not the only oral
contraceptive on the market. Other forms of oral contraceptives might effect the
results due to different doses and combinations used. Other forms of birth
control were also not used in this study. Evaluating other forms of birth control
such as the. patch or intra-uterus devices might affect the results of this study.

Other limitations that occurred in this study were the estimation of
menstrual cycle phases. Blood samples were not taken to confirm blood

hormone levels throughout the menstrual cycle phases. Although an ovulation

42

test was done to confirm ovulation and resulting in changes from the follicular
phase to the luteal phase not all participants displayed a positive test.
Performing blood samples would ensure that all participants were in the correct
menstrual phase.

Future Research Considerations

Future research considerations should include differentiations in sample
population to include NCAA athletes and other physically active populations.
There have been many documented studies that illustrate differences in females
who exercise and females who do not exercise.

Future research needs to test concussed females during the different
phases of the menstrual cycle. The lmPACT test is more commonly used for
post-concussion testing. Incorporating menstrual cycle phases in concussion
testing would be beneficial. Involving females who have abnormal menstrual
cycles would also be beneficial to researchers.

Conclusion

The menstrual cycle is a complex process that all females experience.
Most females have attributed pain, mood disorders, and decreased mental
function to the menstrual cycle at least once. However, this study along with
many othershas shown that there is no evidence to support that the menstrual
cycle is responsible for any differences in cognitive function. The information
presented in this study provides more insight into the cognitive function of
females menstrual cycle. Overall this study failed to demonstrate any significant

changes in cognitive function across the different phases of the menstrual cycle.

43

APPENDIX A

Human Subjects Consent Form

Relationship between Menstrual Cycle Phases and Cognitive Function in Females
who Use and Do Not Use Oral Contraceptives

Informed Consent

 

For questions regarding this study, For questions regarding your rights
Please contact: as a research participant, please contact:
Tracey Covassin Ph.D, ATC Peter Vasilenko, Ph.D.
Department of Kinesiology Director of MSU’s Human Research Protection
Programs
Michigan State University Michigan State University
Phone: (517) 353-2010 202 Olds Hall
E-mail: covassin@msu.edu or East Lansing, MI 48824

irb@msu.edu

Phone: (517) 355-2180
Fax: (517) 432-4503

1. Purpose of Research:
You are being asked to participate in a research study to determine if phases of the menstrual
cycle affect your cognitive function. You have been selected as a possible participant in this
study because you are a female either taking oral contraceptive or are naturally cycling. From
this study, the researchers hope to learn if neurocognitive function changes during the
different phases of the menstrual cycle. Your participation in this study will take about 90

minutes to complete (3 sessions for 30 minutes each). You must be 18 years or older to
participate in this research study.

2. WHAT YOU WILL DO:

The study will use the Immediate Post-Concussion Assessment and Cognitive Testing
(lmPACT) computer program as an assessment tool. In this study, lmPACT will be used
to test your short and long term memory, concentration level, processing speed, and
reaction time during the different phases of the menstrual cycle. Screening is neither
intelligence, nor achievement testing. Non-oral contraceptive users will be required to
take a urine test to confirm ovulation. No invasive procedures are performed.

3. POTENTIAL BENEFITS:

You will directly benefit from participation in this study. You will receive test scores
from all phases of the menstrual cycle. You will benefit from determining if the phase of
the menstrual cycle affects neurocognitive dysfunction.

4. POTENTIAL RISKS:

You are aware that your participation in the above stated study involves little or no
discomfort or harm to you. Please be assured that you may choose to not answer certain
questions and still continue to participate in this study. All answers are strictly
confidential and will not be released to anyone.

45

5. PRIVACY AND CONFIDENTIALITY:

The researcher and one graduate student will have access to your data and will be able to link data
to you. This data will be destroyed in seven years. Participation in this study is completely
voluntary. You have the right to say no. You may change your mind at any time and withdraw.
Confidentiality will be protected by; (a) results will be presented in aggregate form in any
presentations and publications; and (b) all data will be stored in a computer that has a
password necessary to see confidential data. Your privacy will be protected to the
maximum extent allowable by law. You may also discontinue participation at any time
without penalty. Your participation in this research project will not involve any additional
costs to you or your health care insurer. The results of this study may be published or

presented at professional meetings, but the identities of all research participants will remain
anonymous.

6. COSTS AND COMPENSATION FOR BEING IN THE STUDY:

Procedures being performed for research purposes only will be provided free of charge by Dr.
Covassin and her research assistant. You will not receive money or any other form of
compensation for participating in this study.

7. CONTACT INFORMATION FOR QUESTIONS AND CONCERNS

If you have any questions about this study, such as scientific issues, how to do any part of it, or to
report an injury, please contact the researcher Dr. Tracey Covassin at 517-353-2010 or e-mail her
at covassin@msu.edu (105 IM Sport Circle, Department of Kinesiology, East Lansing, MI
48824).

If you have any questions about your role and rights as a research participant, or would like to
register a complaint about this study, you may contact, anonymously if you wish, the Director of
MSU’s Human Research Protection Programs, Dr. Peter Vasilenko, at 517-355-2180, FAX 517-
432-4503, or e-mail irb@msu.edu. or regular mail at: 202 Olds Hall, MSU, East Lansing, MI
48824.

8. DOCUMENTATION OF INFORMED CONSENT.

Your signature below indicates your voluntary agreement to participate in this study.

 

 

 

I, have read and agree to participate in this study as
(Please Print Your Name) described above.
/ /
(Please Sign Your Name) (Date)

46

APPENDIX B

Health History Questionnaire

47

Relationship between Menstrual Cycle Phases and Cognitive Function in
Females who Use and Do Not Use Oral Contraceptives

MICHIGAN STATE UNIVERSITY
HEALTH HISTORY QUESTIONAIRE
Name

Age

 

E-mail Address

 

Phone Number

 

How much exercise do you do a week?

 

Do you have any Ieaming disabilities?

 

Have you had any concussions within the last 6 months?

 

Do you take oral contraceptives?

 

If so, when did you start taking the oral contraceptive and what kind are

you taking?

 

Do you have any documented menstrual cycle problems?

 

When was the start of your last menstrual cycle?

 

48

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