Eur J Appl Physiol (2009) 106:105–112
DOI 10.1007/s00421-009-0995-8
ORIGINAL ARTICLE
The role of the menstrual cycle phase in pain perception
before and after an isometric fatiguing contraction
Marie K. Hoeger Bement Æ Rebecca L. Rasiarmos Æ
John M. DiCapo Æ Audrey Lewis Æ Manda L. Keller Æ
April L. Harkins Æ Sandra K. Hunter
Accepted: 14 January 2009 / Published online: 3 February 2009
Ó Springer-Verlag 2009
Abstract The purpose of this study was to compare
exercise-induced analgesia in young women after a
fatiguing isometric contraction during different phases of
the menstrual cycle. Twenty female subjects performed a
submaximal (25% maximal voluntary contraction) iso-
metric contraction until task failure during both the mid-
follicular and mid-luteal phases of their menstrual cycle.
Pain perception (i.e., pain threshold and pain ratings) was
measured before and after the isometric fatiguing con-
traction. Other measures included mean arterial pressure,
heart rate, and anxiety levels. Time to task failure of the
fatiguing contraction was similar for the two phases of the
menstrual cycle. Following the performance of the iso-
metric contraction: (1) pain thresholds increased and pain
ratings decreased; (2) anxiety levels increased; and (3)
mean arterial pressure and heart rate increased. These
changes were not dependent on the phase of the menstrual
cycle. Thus, the menstrual cycle phase does not influence
the magnitude of exercise-induced analgesia.
Keywords Exercise-induced analgesia

Elbow flexor muscles
Muscle fatigue
Women

Cortisol
M. K. Hoeger Bement (&)
R. L. Rasiarmos

J. M. DiCapo
A. Lewis
M. L. Keller
S. K. Hunter
Department of Physical Therapy, Marquette University,
P.O. Box 1881, Milwaukee, WI 53201, USA
e-mail: mariehoeger.bement@marquette.edu
A. L. Harkins
Department of Clinical Laboratory Science,
Marquette University, Milwaukee, WI, USA
Introduction
Pain perception decreases following the performance of
isometric contractions (Hoeger Bement et al. 2008; Koltyn
et al. 2001; Kosek and Ekholm 1995; Kosek and Lund-
berg 2003; Staud et al. 2005). This decrease in pain
perception is known as exercise-induced analgesia and is
often quantified by a reduction in pain ratings and/or
increase in time to detection of a noxious stimulus (pain
threshold) after exercise (Hoeger Bement et al. 2008;
Hoffman et al. 2004; Koltyn et al. 2001; Kosek and
Lundberg 2003). The magnitude of exercise-induced
analgesia following an isometric contraction is dependent
on the intensity and duration. For example, the greatest
decrease in pain occurs after a low-intensity and long-
duration isometric contraction [25% maximal voluntary
contraction (MVC) held to task failure] compared with
high- and low-intensity contractions of shorter duration
(Hoeger Bement et al. 2008).
There are sex differences in pain perception because
women report higher pain ratings before and after the
performance of isometric contractions compared with men
(Hoeger Bement et al. 2008) and greater exercise-induced
analgesia (Koltyn et al. 2001). The cause for the sex dif-
ference in exercise-induced analgesia is not well
understood. One possibility is that pain perception may be
influenced by the menstrual cycle in women, particularly at
rest (baseline levels). A meta-analysis examining baseline
pain perception across the menstrual cycle concluded that
pain threshold and tolerance are higher during the follicular
phase, when gonadal hormone levels are relatively low,
than during the luteal phase (Riley et al. 1999). However, a
more recent review concluded that this view is not con-
sistently supported by the literature (Sherman and
LeResche 2006). Thus, the magnitude of exercise-induced
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106
analgesia in women may be influenced by the phase of the
menstrual cycle but this has not been previously examined.
The purpose of our study was to compare exercise-
induced analgesia during the mid-follicular and mid-luteal
phases of the menstrual cycle in young women. Exercise-
induced analgesia was quantified as the change in pain
perception (pain threshold and pain ratings) during a 2 min
pressure pain test in response to an isometric fatiguing
contraction with the elbow flexor muscles. The timing of
our protocol was established to control for the changes in
acute hormonal fluctuations in relation to the menstrual
cycle.
During the mid-luteal phase there is greater secretion of
progesterone and estradiol than during the mid-follicular
phase (Sherman and LeResche 2006). Typically, menstrual
cycle phase does not influence motor performance includ-
ing strength and muscle fatigability (Janse de Jonge 2003).
We hypothesized that the changes in pain perception fol-
lowing an isometric fatiguing contraction would also be
unaffected by the menstrual cycle. We expected therefore,
that the magnitude of exercise-induced analgesia after the
fatiguing contraction would not differ between different
phases of the menstrual cycle. Because anxiety can influ-
ence pain perception (Willer et al. 1981), we also examined
the relation between exercise-induced analgesia, arousal
(stress) and anxiety that may have been induced by the
exercise and testing.
Methods
Subjects
Twenty young women (20.9 ± 1.0 years, 65.2 ± 3.4
inches, 63.1 ± 8.1 kg) who had regular menstrual cycles,
in which menstruation occurred in recurring intervals every
22–36 days (Fregly and Luttge 1982), participated in this
study. The premenstrual record of impact and severity of
menstruation was completed by the subjects for two cycles
to further verify that they experienced regular menstrual
cycles (Reid and Yen 1983). Subjects were not on hormone
contraceptives and were screened for known cardiopul-
monary and orthopedic problems, menstrual cycle
disorders, and use of hormonal contraceptives. Subjects
provided informed consent, and the protocol was approved
by the Institutional Review Board at Marquette University.
Experimental design
Subjects participated in three sessions: one familiarization
session and two experimental sessions which involved
measurement of pain perception before and after an iso-
metric fatiguing contraction of the elbow flexor muscles.
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Eur J Appl Physiol (2009) 106:105–112
During the familiarization session, subjects were familiar-
ized to the pressure pain device and instructed on correct
use of the ovulation kit (used to identify timing of ovula-
tion and thus menstrual cycle phase) and the premenstrual
record of impact and severity of menstruation. Each subject
performed three MVCs to determine maximum strength
and the intensity for the submaximal isometric fatiguing
contraction in the subsequent sessions. MVCs were per-
formed during the familiarization session only, and not
prior to the submaximal isometric contractions during the
last two sessions, because pain perception may change
following the performance of MVCs (Hoeger Bement et al.
2008; Koltyn et al. 2001). Reliability of the performance of
MVCs across days is high with less than 5% change in
force (Hunter et al. 2000) and strength does not change
across the menstrual cycle (Janse de Jonge 2003).
The MVC task involved a gradual increase in force from
zero to maximum over *2 s, with the maximal force held
for 2–3 s. During performance of the MVC, the force
exerted by the elbow flexor muscles was displayed on a
monitor and each subject was verbally encouraged to
achieve maximal force. One-minute rest was given
between each MVC. The subject setup and force recording
is detailed below in the sustained submaximal isometric
contractions section.
The two experimental sessions were scheduled during
the subject’s mid-follicular phase (5–7 days post menses)
and mid-luteal phase (6–8 days post ovulation, per the
ovulation kit; Fillingim et al. 1997; Pfleeger et al. 1997).
All twenty subjects completed both of the experimental
sessions. The sessions were counter balanced so that half of
the subjects completed the mid-follicular session as their
first experimental session. The two experimental sessions
included measurements of pressure pain perception (i.e.,
pain ratings and pain threshold), salivary cortisol, blood
pressure, heart rate, and anxiety levels before and after the
performance of a sustained submaximal (25% MVC) iso-
metric contraction held to task failure.
Sustained submaximal isometric contractions
During the two experimental sessions, subjects performed a
sustained isometric fatiguing contraction at 25% of their
MVC until task failure. The target force was calculated
based on MVCs performed during the familiarization ses-
sion. Task failure was determined as the decline in force by
10% of the target value for 3 out of 5 consecutive seconds.
The fatiguing contraction was initiated 25 min after the
initial baseline pain test. This duration was necessary
because our previous data indicated that *30 min was
necessary between pain measurements to minimize the
influence of the initial pain measurement on subsequent
measurements (Hoeger Bement et al. 2008). To perform
Eur J Appl Physiol (2009) 106:105–112
the submaximal isometric contractions and the MVCs in
the familiarization session, subjects were seated in an
adjustable chair with the left arm slightly abducted and the
elbow resting on a padded support. The forearm was
positioned horizontally with the elbow joint flexed to 90°.
The hand and forearm were placed in a modified wrist–
hand–thumb orthosis held in place with Velcro straps
(Orthomerica, Newport Beach, CA, USA), and the forearm
was placed midway between pronation and supination. The
force at the wrist was directed upward when the elbow
flexor muscles were activated voluntarily. Force was
measured using a JR3 force transducer (JR-3 Inc., Wood-
land, CA, USA) mounted on an adjustable support and
attached to the subject’s hand-arm orthosis. The forces
detected by the transducer were recorded online using a
Power 1401 A–D converter and Spike2 software (Cam-
bridge Electronics Design, Cambridge, UK). The force
signal was digitized at 500 samples/s. Subjects received
force feedback on a 19-inch monitor and were verbally
encouraged to sustain the force for as long as possible.
Ovulation kit
Timing of the menstrual cycle phase was determined for
each subject with an ovulation kit. A midstream ovulation
test (Clearblue Easy, Unipath Diagnotics) was used by each
subject to detect the day of the luteinizing hormone surge,
which occurs immediately prior to ovulation. The Clear-
blue Easy ovulation kit is 99% accurate in laboratory tests
(Ghazeeri et al. 2000). Each subject was given seven
midstream tests with instructions to start testing just before
the midpoint of their usual menstrual cycle. The length of
the menstrual cycle among subjects varied between sub-
jects (23–35 days). The mid-luteal session was scheduled
6–8 days past ovulation, per the ovulation kit. During the
mid-luteal phase of the menstrual cycle, estrogen and
progesterone are relatively high compared with the mid-
follicular phase (Sherman and LeResche 2006).
Pain perception
A pressure pain device was used to assess pain perception.
A 200 g mass was applied to a second class lever at a
distance from the axis to ensure a 10 N force (equivalent to
a 1 kg mass) on the finger. The force at the finger was
applied through a Lucite edge (8 9 1.5 mm) (Romus Inc.,
Milwaukee, WI, USA) and was placed on the right index
finger midway between the distal and proximal interpha-
langeal joints for 2 min. Subjects pressed a timing device
when they first felt pain (i.e., pain threshold) and pain
ratings were reported every 20 s using a 0–10 scale. The
scale had the following terminology: 0 = no pain,
5 = moderate pain, and 10 = worst pain (McCaffery and
107
Pasero 1999). This procedure results in a painful sensation
but does not cause tissue damage. We previously estab-
lished the reliability of this device (Hoeger Bement et al.
2008).
Anxiety
State anxiety was assessed by the Spielberg State Anxiety
Inventory, which has been demonstrated to be a reliable
assessment tool (Barnes et al. 2002; Spielberg 1983).
Anxiety was evaluated to examine the association between
anxiety and pain perception during different phases of the
menstrual cycle before and after sustained submaximal
isometric contractions.
Salivary cortisol
Free cortisol levels were collected through salivary sam-
ples, which parallel that of total serum cortisol and is
recommended for the assessment of dynamic hypotha-
lamic–pituitary–adrenal (HPA) axis activity (Gozansky
et al. 2005). All experiments were conducted in the after-
noon when the cortisol levels are nearing their diurnal
trough (Schmidt-Reinwald et al. 1999). Subjects’ saliva
was collected with a salivette that was placed in the mouth
for approximately 1 min at the following time points: (1)
upon entering the laboratory; (2) 20 min after the first pain
measurement but prior to performing isometric contrac-
tions; (3) immediately after the second pain measurement;
and (4) 20 min after the second pain measurement. Saliva
collection was taken 20 min after the isometric contraction
and pain test because free cortisol takes 10–20 min to
peak in the saliva after release from the adrenal glands
(Kirschbaum and Hellhammer 1994). After collection,
salivary samples were stored at -20°C until later analysis.
Salivary cortisol levels were quantified using an enzymatic
immunosolvent assay (Salimetrics LLC, State College, PA,
USA). Previous studies have established the reliability of
this technique (Pruessner et al. 1997). Our intra- and inter-
assay coefficients of variation were less than 6%.
Mean arterial pressure
Mean arterial pressure (MAP) and heart rate were mea-
sured at rest and during the sustained submaximal
isometric contraction using an automated beat-by-beat
blood pressure monitor (Finapres 2300, Ohmeda, Madison,
WI, USA). MAP and heart rate were not measured during
exposure to the pressure pain device because subjects
reported that it was too distracting. The small blood pres-
sure finger cuff was placed around the middle finger of
the non-exercising hand. MAP and heart rate were ana-
lyzed by comparing *15-s averages at 50% intervals of
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the duration of the isometric contraction (i.e., 0%, 50%,
and 100%). For each interval, the blood pressure signal was
analyzed for the mean peaks [systolic blood pressure
(SBP)], mean troughs [diastolic blood pressure (DBP)],
and the number of pulses per second (multiplied by 60
to determine heart rate). MAP was calculated for each
epoch with the following equation: MAP = DBP ? 1/3
(SBP - DBP) (Cywinski 1980).
Data and statistical analysis
Data are reported as means ± SD within the text and as
means ± SE in the figures. Multivariate repeated measures
ANOVA was used to analyze the following variables: pain
threshold and pain ratings [trial (pre and post)], cortisol
levels [trial 9 time (baseline, 20-min post pain #1,
immediately post pain #2, and 20-min post pain #2)], state
anxiety levels [trial 9 time (baseline, post pain #1, post
pain #2)], and MAP and heart rate [trial 9 time (baseline,
start of contraction, 50% of time to task failure, immedi-
ately prior to task failure)]. Menstrual cycle phase (luteal
and follicular) was a within-subject factor. Estimates of
effect size were calculated using partial eta-squared (g2p).
Time to task failure and post hoc analysis within subjects
was analyzed using paired t-tests. Pearson correlations
were calculated to determine associations between depen-
dent variables. Significance was indicated as P \ 0.05.
Results
Maximal voluntary contractions
The three MVC trials that were performed during the
familiarization session were similar in value (180.4 ±
32.8 N, 183.7 ± 31.2 N, 177.1 ± 49.2 N, respectively,
P = 0.60).
Time to task failure
Time to task failure of the sustained 25% MVC was similar
when performed during the follicular and luteal phases of
the menstrual cycle (524 ± 213 s vs. 521 ± 181 s, res-
pectively, P = 0.88).
Pain perception
Baseline (pre-contraction) pain perception was not influ-
enced by the phase of the menstrual cycle because pain
threshold (Fig. 1) and pain ratings (Fig. 2) were similar
between the mid-follicular and mid-luteal phases at base-
line. Furthermore, there was no main effect for the menstrual
cycle across the entire session for either pain threshold
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Eur J Appl Physiol (2009) 106:105–112
Luteal
Follicular
*
50
40
Threshold (s)
30
20
10
0
pre post
Trial
Fig. 1 Pain thresholds before (pre) and after (post) a submaximal
(25% MVC) isometric contraction held until task failure. Pain
thresholds significantly increased following the isometric contraction,
which was similar between the mid-follicular and mid-luteal phases.
*P \ 0.05
(P = 0.82, g2p = 0.001) or pain ratings (P = 0.95, g2p =
0.0001).
Pain perception however, changed after the submaximal
fatiguing contraction. Following the isometric contraction,
pain threshold increased (P = 0.0001, g2p = 0.32) for both
the mid-follicular (30.1 ± 19.4 to 38.0 ± 21.1 s) and mid-
luteal (29.5 ± 14.0 to 41.1 ± 22.1 s) phases (Fig. 1).
Likewise, pain ratings decreased (P = 0.0001, g2p = 0.32;
Fig. 2). There was no interaction between the menstrual
cycle phase and trial for pain threshold (P = 0.42,
g2p = 0.02, Fig. 1) or pain ratings (P = 0.46, g2p = 0.02,
Fig. 2) indicating that the magnitude of exercise-induced
analgesia was similar across the menstrual cycle.
Anxiety
State anxiety levels were assessed at baseline, immediately
after the first pain test, and following the isometric con-
traction. Anxiety levels did not change following the first
pain test (30.5 ± 7.3 to 30.2 ± 7.4) but increased follow-
ing the fatiguing contraction (30.2 ± 7.4 to 32.2 ± 7.1)
(time effect, P = 0.006, g2p = 0.13). Anxiety levels did not
differ with menstrual cycle phase (effect of menstrual cycle
phase, P = 0.98, g2p = 0.001), nor was there an interaction
between the menstrual cycle phase and time (P = 0.50,
g2p = 0.02).
The exercise-induced change in anxiety levels was
associated with the change in pain ratings (P = 0.04,
r = 0.32) and pain threshold (P = 0.04, r = -0.33).
Subjects who had greater increases in exercise-induced
Eur J Appl Physiol (2009) 106:105–112 109

Fig. 2 Pain ratings before (pre) Follicular Luteal

10
and after (post) a submaximal
(25% MVC) isometric 8 Pre
contraction held until task Post
*

Pain Ratings
failure. Pain ratings significantly 6 *
decreased following the
isometric contraction for the 4
mid-follicular and mid-luteal
phases. *P \ 0.05 2

0 20 40 60 80 100 120 0 20 40 60 80 100 120

Time (s) Time (s)

anxiety were more likely to have decreases in pain ratings difference (P [ 0.05). Cortisol levels did not differ across
and increases in pain threshold following exercise. The low the menstrual cycle (effect of menstrual cycle phase,
correlations however indicate that the strength of the P = 0.43, g2p = 0.02; Fig. 3).
relationship is low. Anxiety levels were not associated with
baseline pain threshold or pain ratings (P [ 0.05). Mean arterial pressure and heart rate

Cortisol Both MAP and heart rate increased during the fatiguing
contraction (P = 0.0001 and 0.0001, g2p = 0.94 and 0.85;
One subject’s data from the follicular phase was excluded Fig. 4). MAP and heart rate were similar across the men-
because it was greater than three standard deviations from strual cycle because there was no main effect of the
the mean. There was no change in cortisol levels with time menstrual cycle phase for either MAP or heart rate
(P = 0.07, g2p = 0.18; Fig. 3). To control for the potential (P = 0.65 and 0.29, g2p = 0.006 and 0.03). There was also
increase in cortisol due to anxiety at the start of the no interaction between the menstrual cycle phase and over
experiment, we compared the fourth time point (20 min time for MAP (P = 0.75, g2p = 0.01) or heart rate
following the second pain test) with the first two time (P = 0.97, g2p = 0.007) indicating the rise in these car-
points averaged (baseline and post pain #1) and also with diovascular measures were similar during the fatiguing
the second time point alone (post pain #1) but found no contractions for the different phases of the menstrual cycle
(Fig. 4).

Cortisol Associations between cardiovascular measures

0.20
Follicular and pain perception
Luteal
0.18
Concentration (ug/dl)

The exercise-induced changes in pain ratings and pain

threshold were not correlated with any of the exercise-
0.16
induced changes in the cardiovascular measurements.
There were, however, a number of associations between
0.14 the cardiovascular measurements during the isometric
fatiguing contraction and pain perception before and after
0.12 the isometric contraction. MAP at the start of the con-
traction was related to the average pre-contraction pain
0.10 ratings (P = 0.05; r = -0.33), average post-contraction
pain ratings (P = 0.01; r = -0.42), pre-contraction pain
e

in

ed

in
elin

0m

0m
mm

threshold (P = 0.02; r = 0.40), and post-contraction pain

bas

1- 2

2- 2
2- i

threshold (P = 0.002; r = 0.50). Similarly, MAP at the

n#

n#

n#

end of the isometric contraction (immediately prior to task

pai

pai

pai

failure) was related to the average pre-contraction pain

Fig. 3 Cortisol levels were not significantly different following ratings (P = 0.004; r = -0.47), average post-contraction
exercise, which was similar between the mid-follicular and mid-luteal pain ratings (P = 0.001; r = -0.52), pre-contraction pain
phases. baseline = baseline; pain #1-20 min = 20 min after the first
pain test; pain #2-immed = immediately after the second pain test; threshold (P = 0.0001; r = 0.63), and post-contraction
pain #2-20 min = 20 min after the second pain test pain threshold (P = 0.0001; r = 0.60). Specifically,

123
110
140
130 Follicular
MAP (mmHg)
120 Luteal
110
100
90
80
70
rest start 50 100
Time to Failure (%)
Fig. 4 Mean arterial pressure and heart rate significantly increased
during the submaximal isometric contraction held until task failure,
which was similar between the mid-follicular and mid-luteal phases.
individuals with higher MAP during the isometric con-
traction were more likely to report lower pain ratings and
higher pain thresholds before and after the isometric
contraction.
Similar to the MAP values, heart rate at the start of the
contraction was related to the average pre-contraction pain
ratings (P = 0.0001; r = -0.57), average post-contraction
pain ratings (P = 0.0001; r = -0.69), pre-contraction pain
threshold (P = 0.007; r = 0.45), and post-contraction pain
threshold (P = 0.0001; r = 0.63). Heart rate at the end of
the isometric contraction was related to the average pre-
contraction pain ratings (P = 0.001; r = -0.54), average
post-contraction pain ratings (P = 0.0001; r = -0.56),
pre-contraction pain threshold (P = 0.002; r = 0.49), and
post-contraction pain threshold (P = 0.001; r = 0.52).
Thus, individuals with elevated heart rate during the iso-
metric contraction were more likely to report lower pain
ratings and higher pain thresholds before and after the
isometric contraction.
Discussion
The purpose of this study was to compare exercise-induced
analgesia following isometric contractions during the mid-
follicular and mid-luteal phases of the menstrual cycle.
Similar to our previous research, pain threshold increased
and pain ratings decreased following the performance of the
fatiguing isometric contraction (i.e., exercise-induced
analgesia) (Hoeger Bement et al. 2008). The new findings of
this study are that the phase of the menstrual cycle in young
women did not affect the exercise-induced changes in pain
perception, anxiety, cortisol levels, or cardiovascular
response during the fatiguing contraction. Furthermore,
time to task failure of the submaximal fatiguing contraction
was not influenced by the phase of menstrual cycle in
women. Thus, exercise-induced analgesia does not appear
to be influenced by menstrual cycle phase.
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Eur J Appl Physiol (2009) 106:105–112
120
110
Heart Rate (bpm)
100
90
80
70
60
rest start 50 100
Time to Failure (%)
rest = baseline; start = start of the isometric contraction; 50 = mid-
way point of the isometric contraction; 100 = end of the isometric
contraction
Time to task failure did not differ between the mid-
follicular and mid-luteal phases of the menstrual cycle in
the women. This confirms previous work that shows no
correlation between days of the menstrual cycle and time to
task failure in young women (Hunter et al. 2004a, b). Other
studies have also shown that strength and muscle fatiga-
bility does not vary systematically during the menstrual
cycle (DiBrezzo et al. 1991; Gur 1997; Janse de Jonge et al.
2001). A small number of studies have suggested that
muscle fatigue varies across the menstrual cycle phase
however, these findings are not supported by the majority
of studies [reviewed by Janse de Jonge (Janse de Jonge
2003)]. The most comprehensive and well controlled
studies showed hormonal fluctuations during the menstrual
cycle do not influence muscle strength and fatigability
(Janse de Jonge et al. 2001). Our data adds to this literature
showing that time to task failure of a low-force sustained
contraction is not influenced by the phase of the menstrual
cycle. Because time to task failure did not differ across
sessions we were able to assess the influence of the men-
strual cycle phase on pain perception at the same
magnitude of fatigue and performance.
We found that pain perception, including the magnitude
of exercise-induced analgesia, did not differ across the
menstrual cycle. Hormone levels, such as estrogen and
progesterone, are relatively higher during the luteal phase
than the follicular phase and have been suggested to
influence pain (Fillingim et al. 1997). Our data supports a
recent review however, in that there was no clear detect-
able and systematic change in pain perception during
different phases of the menstrual cycle (Berkley 1997;
Sherman and LeResche 2006).
Some studies however, have shown changes in pain
perception across the menstrual cycle at rest (Riley et al.
1999). The lack of consensus regarding the influence of the
menstrual cycle on pain perception may be due to differ-
ences in methodology, such as controlling for the menstrual
cycle phase, type of pain measurement (i.e., pain threshold
Eur J Appl Physiol (2009) 106:105–112
vs. pain ratings) and the type of noxious stimulus used
(mechanical, thermal, or electrical) (Berkley 1997; Fillin-
gim et al. 1997; Pfleeger et al. 1997; Riley et al. 1999;
Sherman and LeResche 2006). We used a within-subject
design with a large number of subjects (n = 20) and con-
trolled for the variability in the menstrual cycle phase by
using ovulation kits, as recommended by others (Riley
et al. 1999; Sherman and LeResche 2006). Our results
showed that pain perception and the magnitude of exercise-
induced analgesia were similar during different phases of
the menstrual cycle. Thus, when controlling for the vari-
ability in menstrual cycle length among women, the
amount of analgesia produced by performance of isometric
contractions is not dependent on the phase of the menstrual
cycle.
We recorded other physiological variables to determine
possible mechanisms and identify confounders that may
influence performance and pain perception during the
menstrual cycle. We assessed state anxiety levels to
examine if the physical stress of exercise produced stress-
induced analgesia (Willer et al. 1981). There was an
exercise-induced increase in anxiety levels that was similar
during the two phases of the menstrual cycle. Individuals
with greater increases in state anxiety levels following the
isometric contraction were more likely to experience
decreases in pain ratings and increases in pain threshold.
Previous research on exercise-induced anxiety levels has
been mixed showing no change (Koltyn and Arbogast
1998; Koltyn et al. 1996), decreases (Koltyn et al. 2001),
and increases (Hoeger Bement et al. 2008) in anxiety
reported. Despite the varied response of anxiety after
exercise, all of the previous studies reported a decrease in
pain indicating that changes in anxiety levels alone do not
explain exercise-induced analgesia. Our data however,
demonstrated that changes in anxiety levels may be
involved in the perception of pain following exercise.
Another potential mechanism for exercise-induced
analgesia is activation of the HPA axis, which we quanti-
fied using salivary cortisol levels. We found no significant
change in cortisol levels following the performance of
isometric contractions. Research specific to the perfor-
mance of isometric contractions has demonstrated
increases or no change in cortisol levels, which as far as we
know has only been studied in men (Few et al. 1975; Kjaer
et al. 1991). It is possible that the timing of cortisol sam-
pling missed the peak increase in cortisol after exercise.
Peak cortisol levels occur 10–20 min after exposure to the
stressor with some variance between subjects (Kirschbaum
and Hellhammer 1994). We chose 20 min based on other
studies but more recent pilot work in our laboratory indi-
cates 10 min post exercise may be the best indicator of
peak cortisol levels for some women. Nevertheless,
because we observed a decrease in pain and no change in
111
cortisol levels measured 20 min after exercise, increased
activation of the HPA axis does not appear to regulate
exercise-induced analgesia.
There was a cardiovascular response during the perfor-
mance of the isometric contraction with increases in heart
rate and MAP demonstrated, with similar increases
occurring during the mid-follicular and mid-luteal phases.
The cardiovascular measurements during the isometric
contraction were related to pain behaviors before and after
the isometric contraction. Individuals with elevated MAP
and heart rate were more likely to report lower pain ratings
and higher pain thresholds than individuals with lower
MAP and heart rate; although the exercise-induced changes
in the cardiovascular measurements and pain perception
were not related. This inverse relationship between blood
pressure and pain sensitivity has been well established
(Bruehl et al. 1992; Ghione 1996; Pfleeger et al. 1997). In
relation to exercise, previous research shows that increases
in blood pressure by way of exercise also results in
decreases in pain (Koltyn et al. 2001; Kosek and Lundberg
2003). Our data demonstrate similar findings with exercise-
induced increases in cardiovascular measurements and
decreases in pain; although the magnitude of changes in
cardiovascular measurements and pain perception were not
related.
Conclusions
We found that the decrease in pain following a low-
intensity, long-duration isometric fatiguing contraction was
not dependent on the phase of the menstrual cycle in
women. Furthermore, the menstrual cycle phase did not
influence the time to task failure of the submaximal
fatiguing contraction, state anxiety, cortisol levels, or the
cardiovascular response during a fatiguing contraction.
Thus, when assessing exercise-induced analgesia, the
menstrual cycle does not appear to be a confounder in
young healthy women with regular menstrual cycles.
Acknowledgments This study was supported by awards from the
American Pain Society and Arthritis Foundation to MKHB. Ethical
Standards: This protocol was approved by the Institutional Review
Board at Marquette University.
Conflict of interest statement The authors have no financial dis-
closures or conflicts of interest.
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