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11145 Journal of Physiology (2001), 530.1, pp.

161–166 161

The influence of menstrual cycle phase on skeletal muscle


contractile characteristics in humans
X. A. K. Janse de Jonge, C. R. L. Boot*, J. M. Thom, P. A. Ruell
and M. W. Thompson
School of Exercise and Sport Science, Faculty of Health Sciences, The University of
Sydney, East Street, Lidcombe, Australia and *Department of Physiology, University of
Nijmegen, The Netherlands
(Received 22 May 2000; accepted after revision 22 September 2000)
1. The influence of the different phases of the menstrual cycle on skeletal muscle contractile
characteristics was studied in 19 regularly menstruating women. Muscle function was
measured when (i) oestrogen and progesterone concentrations were low (menstruation),
(ii) oestrogen was elevated and progesterone was low (late follicular phase), and (iii) oestrogen
and progesterone were both elevated (luteal phase).
2. Maximal isometric quadriceps strength, fatiguability and electrically stimulated contractile
properties were measured. Isokinetic knee flexion and extension strength and fatiguability
were also assessed as well as handgrip strength. Menstrual cycle phases were confirmed through
measurement of oestrogen, progesterone, follicle stimulating hormone and luteinising
hormone.
3. No significant changes were found in any of the muscle function parameters throughout the
menstrual cycle (n = 15). The muscle function measurements showed no significant correlations
with any of the female reproductive hormone concentrations.
4. These results suggest that the fluctuations in female reproductive hormone concentrations
throughout the menstrual cycle do not affect muscle contractile characteristics.

During their reproductive years the hormone levels in not clear. Greeves et al. (1999), however, reported the
women fluctuate due to the menstrual cycle. The four highest quadriceps strength during the mid-luteal phase
hormonal markers of the menstrual cycle (oestrogen, and found a positive relationship between strength and
progesterone, follicle stimulating hormone (FSH) and progesterone concentration. Several other studies have
luteinising hormone (LH)) change continuously throughout found no changes in skeletal muscle strength over the
the cycle. These fluctuations in female steroid hormones menstrual cycle (DiBrezzo et al. 1991; Quadango et al.
affect the autonomic nervous system and metabolic 1991; Lebrun et al. 1995; Gür, 1997).
functions (Florini, 1987). Therefore certain physiological
parameters and athletic performance could change along The main problem in the measurement of maximum
with the menstrual cycle phases (Becker et al. 1982). voluntary strength is ensuring that the contraction truly
However, the influence of the menstrual cycle phase on reflects the maximum force-generating capacity of the
exercise performance, particularly muscle strength, is muscle. Even well-motivated subjects may not always
unclear. reach full neural activation of their muscles (Rutherford
et al. 1986). The extent of neural activation can be
Sarwar et al. (1996) tested skeletal muscle strength, evaluated by applying a superimposed electrical stimulus
relaxation rate and fatiguability of the quadriceps during to the muscle during the performance of a maximal
the menstrual cycle. They found no changes in these voluntary contraction (MVC). When comparing strength
parameters for women taking oral contraceptives. For over a period of time, such as in menstrual cycle research,
women not taking oral contraceptives, however, the it is especially important to ensure maximal neural
quadriceps were stronger, more fatiguable and had a activation during each test.
longer relaxation time at mid-cycle (day 12–18). Phillips
et al. (1996) reported a higher adductor pollicis strength A further problem encountered in research on the
during the follicular phase than during the luteal phase, influence of the menstrual cycle on physical performance
with a rapid decrease in strength around ovulation. They is the timing of the testing. It is difficult to predict the
suggested that oestrogen has a strengthening action on exact phases of the menstrual cycle and the concurrent
skeletal muscle, although the underlying mechanism is reproductive hormone concentrations. Counting days
162 X. A. K. Janse de Jonge and others J. Physiol. 530.1

from the onset of bleeding and basal body temperature Hormone analysis
(BBT) charting can be used to estimate the different Before each muscle function testing session, blood samples were
phases of the menstrual cycle. These methods, however, taken from an antecubital vein. The serum collection was
only provide predictions, and serum hormone level standardized by taking a fasting blood sample at 08.00 h after the
measurements of at least oestrogen and progesterone are subjects had rested for 20 min. The serum concentrations of
necessary to confirm the menstrual cycle phase. oestrogen, progesterone, FSH and LH were later measured using
ELISA kits (DSL, TX, USA and Bioclone, Australia). A serum
Most of the studies on muscle strength during the progesterone concentration greater than 16 nmol l_1 was required for
menstrual cycle have either not measured hormone levels confirmation of an ovulatory cycle (Landgren et al. 1980).
or relied upon the assumption that voluntary strength Isometric strength, fatigue and contractile properties
measurements were maximal. These problems have been Prior to the strength testing all subjects performed a 10 min warm-
addressed in this investigation of the influence of the up on a cycle ergometer at 50 W with a cadence of 60 r.p.m. To
menstrual cycle phase on skeletal muscle strength, measure isometric quadriceps strength and contractile properties the
fatigue and contractile properties. subjects were seated in a steel-framed adjustable, straight-backed
chair. The pelvis and trunk were tightly secured by adjustable
webbing straps and the knee joint angle was set at 60 deg from full
METHODS leg extension. The ankle was secured to a fixed force transducer from
Subjects which the analog signal was amplified, digitized and collected using
the data acquisition program ASYST. A high voltage stimulator
Nineteen healthy women with regular menstrual cycles volunteered (DS7, Digitimer Ltd, UK) programmed by a digital timer (D4030,
to take part in this study. All subjects provided written informed Digitimer Ltd) was used to deliver percutaneous electrical pulses to
consent and all procedures were approved by The University of the quadriceps via two electrodes placed proximally and distally on
Sydney Human Ethics Committee and conformed to the Declaration the anterolateral thigh. Prior to the maximal voluntary strength
of Helsinki. Subjects were medically screened and were healthy and measurement a series of electrical stimuli was applied during which
not taking any medication. They had not been taking oral the current was increased in 50 mA steps. When the involuntary
contraceptives or hormone supplements for at least the preceding force created by the electrical stimuli reached a plateau, the current
6 months. Subjects with an irregular menstrual cycle history were of the third stimulus in the plateau was defined as the supra-
excluded from this study. Seven subjects volunteered to continue the maximal response. Two types of electrical stimuli were used: (i) a
testing for a consecutive cycle. twitch at 400 V and (ii) an 80 ms tetanus at 50 Hz (5 impulses) with
Protocol 50 µs pulsed square waves at 400 V. The supra-maximal stimuli
responses were analysed for time to peak tension (TPT), peak tension
The muscle strength, fatiguability and contractile properties of the (PT), half-relaxation time (1/2RT), normalized peak rate of force
subjects were measured during different phases of the menstrual development (normPRFD) and normalized peak rate of relaxation
cycle. This study aimed to include the three distinctly different (normPRR). To monitor full neural activation during the strength
combinations of oestrogen and progesterone concentrations that measurements, a supra-maximal twitch was superimposed on each
occur during the menstrual cycle: firstly menstruation (day 1–3), MVC. The central activation ratio (CAR) was used to quantify the
during which both oestrogen and progesterone concentrations are extent of neural activation (Kent-Braun & Le Blanc, 1996). CAR =
relatively low; secondly the late follicular phase, when oestrogen is MVC/total force, in which total force = voluntary force +
elevated and progesterone remains low; and finally the luteal phase, superimposed force. CAR = 1.0 indicates full voluntary activation of
during which both oestrogen and progesterone are elevated. BBT the muscle (Kent-Braun & Le Blanc, 1996). Contractions during
patterns were used to estimate the different phases of the menstrual which CAR was smaller than 1.0 were excluded from analysis.
cycle (Vollman, 1977). The timing of the testing during the late During each test session the subjects performed five MVCs of the
follicular phase is difficult because the oestrogen peak only lasts quadriceps of their dominant leg. Each MVC was preceded by a 2 min
approximately 3 days (Landgren et al. 1980). To increase the rest period. The subjects were well motivated and received verbal
likelihood of testing during the late follicular oestrogen peak, two encouragement during the performance of the MVC. The peak force
tests were conducted during this phase. The muscle function test recorded in each session was taken as the MVC. The electrically
coinciding with the highest oestrogen concentration and a low stimulated fatigue test consisted of 300 ms stimuli every second for
progesterone concentration was analysed as the late follicular phase 2 min at 20 Hz at a current that elicited at least 50% of the MVC
test. During each test session isometric strength and fatiguability of force (modified from Burke et al. 1973).
the quadriceps were assessed first. After a 5 min rest period
isokinetic knee flexion and extension strength and fatiguability were Isokinetic strength and fatigue
measured. This was followed by the handgrip strength assessment. An isokinetic dynamometer (Biodex Multi-Joint System II, Biodex
Basal body temperature Medical Systems Inc., USA) was used to record torques about the
knee joint at constant angular velocities during MVCs of the knee
During the familiarization period the subjects were informed on how flexors and extensors. The subjects performed five knee flexions and
to measure their own BBT. Mercurial ovulation thermometers with five knee extensions at a velocity of 60 deg s_1 and repeated this
scale steps of 0.05°C were used and BBT was measured orally for protocol at a velocity of 240 deg s_1 with a 2 min rest interval
5 min, before rising in the morning. The subjects continued to between each set of five contractions. The final isokinetic test was a
measure and record their BBT throughout the study. The pattern of voluntary fatigue test, which consisted of 60 knee flexions and
the BBT was used to estimate the duration of the different phases of extensions at a velocity of 240 deg s_1.
the cycle (Vollman, 1977) and determine the testing schedule. The
subjects also completed a daily questionnaire about symptoms such as Handgrip strength
breast tenderness and fluid retention. Changes in these symptoms in Dominant handgrip strength was measured using a force transducer
the 2 weeks preceding the menstrual flow indicate an ovulatory cycle set within an adjustable frame. The subjects stood with their arms
(Lebrun et al. 1995).
J. Physiol. 530.1 Muscle function during the menstrual cycle 163

Table 1. Serum hormone concentrations of oestrogen, progesterone, follicle stimulating


hormone (FSH) and luteinising hormone (LH) throughout the menstrual cycle
Hormone concentration Menstruation Late follicular Luteal
_1
Oestrogen (pmol l ) 170.1 ± 116.8 533.5 ± 289.6* 369.7 ± 126.9*†
Progesterone (nmol l_1) 6.53 ± 12.12 2.45 ± 1.30 40.63 ± 19.17*†
FSH (i.u. l_1) 5.18 ± 2.31 7.56 ± 3.85* 3.29 ± 3.38†
LH (i.u. l_1) 6.01 ± 3.87 24.87 ± 21.12* 4.76 ± 2.96†
Data are shown as means ± S.D., n = 15. *Significantly different from Menstruation (P < 0.05).
†Significantly different from Late follicular (P < 0.05).

Table 2. Muscle strength and fatigue parameters throughout the menstrual cycle
Muscle function Menstruation Late follicular Luteal
Isometric quadriceps (N) 571 ± 114 551 ± 114 570 ± 109
Isokinetic ext 60 deg s_1 (Nm) 153.6 ± 33.0 148.9 ± 27.7 152.8 ± 27.8
Isokinetic flex 60 deg s_1 (Nm) 76.6 ± 13.7 71.1 ± 13.3 73.0 ± 12.0
Isokinetic ext 240 deg s_1 (Nm) 92.0 ± 17.9 88.8 ± 18.9 90.9 ± 20.6
Isokinetic flex 240 deg s_1 (Nm) 54.4 ± 9.0 51.9 ± 8.2 52.3 ± 8.0
Fatigue index – ext 0.470 ± 0.12 0.479 ± 0.09 0.471 ± 0.15
Fatigue index – flex 0.553 ± 0.19 0.476 ± 0.13 0.517 ± 0.17
Handgrip (N) 348 ± 43 341 ± 39 340 ± 44
Data are shown as means ± S.D., n = 15. Ext, knee extension; flex, knee flexion. There were no
significant differences between menstrual cycle phases for any of the variables.

beside their body and the elbow extended. As with the quadriceps, pattern of a regular ovulatory menstrual cycle. As can be
MVCs were performed with a 2 min rest interval between each seen in Table 1, there was a very large variation in serum
contraction. The MVC was the highest score recorded over five hormone levels throughout the menstrual cycle, but also
consecutive trials.
within each menstrual cycle phase.
RESULTS Strength, fatiguability and contractile properties
Hormone analysis Repeated measures ANOVA showed no significant
The blood sample analysis for progesterone showed that changes over the phases of the menstrual cycle for
four of the 19 subjects did not exceed the 16 nmol l_1 limit isometric quadriceps strength with superimposed
that confirms ovulation had occurred (Landgren et al. electrical stimulation (see Table 2). All subjects reached a
1980). These four subjects were therefore excluded from CAR equal to or greater than 1.0 during the quadriceps
the results. The mean ± S.D for age, height and weight contractions with superimposed electrical stimulation. No
for the remaining 15 subjects was 29.9 ± 8.0 years, significant changes in the extent of neural activation
167 ± 7 cm and 61.4 ± 8.4 kg, respectively. The results were found throughout the menstrual cycle. The twitch and
for the serum hormone concentrations of oestrogen, tetanus characteristics (TPT, PT, 1/2RT, normPRFD,
progesterone, FSH and LH are shown in Table 1. normPRR) and the electrically stimulated fatigue test
also did not show any change over the menstrual cycle
As expected, repeated measures ANOVA showed (see Table 3). No significant changes over the menstrual
significant changes for the hormone concentrations cycle were found for isokinetic strength and fatiguability
throughout the menstrual cycle. Tests of within-subject of the knee flexors and extensors. The repeated measures
contrasts showed that the oestrogen level during ANOVA for handgrip strength also showed no significant
menstruation was lower than that during both the late changes throughout the menstrual cycle (see Table 2).
follicular and the luteal phase (both P < 0.01). The
oestrogen concentration during the late follicular phase Figure 1 shows the maximal isometric quadriceps strength
was also higher than during the luteal phase (P < 0.05). with superimposed electrical stimulation throughout the
For progesterone, the concentration during the luteal menstrual cycle and the corresponding oestrogen
phase was significantly higher than during the rest of the concentrations. No correlations were found between any
menstrual cycle (P < 0.01 for both menstruation and of the strength and fatigue parameters and the serum
follicular phase). The FSH and LH concentrations were concentrations of oestrogen, progesterone, LH and FSH
significantly higher during the late follicular phase than (see Table 4).
during menstruation (P < 0.05 for FSH and P < 0.01 for Repeatability
LH) and the luteal phase (P < 0.01 for FSH and LH). All The test–retest repeatability of the strength parameters
these findings agree well with the hormone concentration was demonstrated with an intra-class correlation
164 X. A. K. Janse de Jonge and others J. Physiol. 530.1

Table 3. Electrically evoked contractile characteristics of the quadriceps throughout the


menstrual cycle
Contractile characteristics Menstruation Late follicular Luteal
Fatigue index quadriceps 0.877 ± 0.21 0.819 ± 0.15 0.870 ± 0.24
Twitch PT (N) 77.93 ± 26.65 79.86 ± 24.11 78.21 ± 27.20
Twitch TPT (ms) 85.55 ± 6.86 87.02 ± 11.74 85.04 ± 7.05
Twitch 1/2RT (ms) 74.64 ± 13.96 76.60 ± 18.9 73.64 ± 16.50
Twitch normPRFD (% ms_1) 2.41 ± 0.19 2.36 ± 0.25 2.38 ± 0.20
Twitch normPRR (% ms_1) _1.15 ± 0.24 _1.15 ± 0.26 _1.14 ± 0.32
Tetanus PT (N) 281.63 ± 54.67 269.33 ± 55.35 274.89 ± 56.37
Tetanus TPT (ms) 154.51 ± 12.76 155.12 ± 14.00 153.88 ± 9.60
Tetanus 1/2RT (ms) 63.86 ± 7.12 65.00 ± 10.87 64.12 ± 12.37
Tetanus normPRFD (% ms_1) 1.74 ± 0.23 1.76 ± 0.14 1.80 ± 0.17
Tetanus normPRR (% ms_1) _1.24 ± 0.15 _1.21 ± 0.14 _1.25 ± 0.17
Data are shown as means ± S.D., n = 15 for twitch and tetanus characteristics and n = 12 for Fatigue
index. PT, peak tension; TPT, time to peak tension; 1/2RT, half-relaxation time; normPRFD,
normalized peak rate of force development; normPRR, normalized peak rate of relaxation. There were
no significant differences between menstrual cycle phases for any of the variables.

coefficient (ICC) ranging from 0.88 to 0.96. Only handgrip strength at mid-cycle, which was defined as day 12 to day
strength showed a lower ICC of 0.73. 18. For most women ovulation would occur during these
6 days, so the female reproductive hormone concentrations
DISCUSSION would be expected to fluctuate significantly. Sarwar et al.
(1996) did not measure hormone concentrations, but
Muscle function was measured during three phases of assumed that oestrogen levels would be high during mid-
the menstrual cycle with significantly different cycle and suggested that oestrogen increases muscle
concentrations of circulating female reproductive strength. To explain why strength did not increase during
hormones. The results showed no change over the the luteal phase they suggested that progesterone might
menstrual cycle for any of the strength parameters, inhibit the proposed strength-enhancing effect of
including maximal isometric quadriceps strength with oestrogen.
superimposed electrical stimulation, isokinetic knee
flexion and extension strength at 60 and 240 deg s_1 Phillips et al. (1996) also suggested that oestrogen has a
and handgrip strength. The quadriceps contractile strengthening effect on skeletal muscle. They reported an
properties, the electrically stimulated quadriceps increase in maximal voluntary adductor pollicis strength
fatigue and the isokinetic knee flexor and extensor during the follicular phase and a drop in strength at
fatigue also did not change throughout the menstrual ovulation. Hormone concentrations in a sub-group of
cycle. subjects (n = 9) were assessed but did not show a
correlation between strength and oestrogen concentration.
The present findings for the isometric quadriceps Phillips et al. (1996) explain this lack of correlation by
strength do not agree with the results reported by Sarwar suggesting that the strengthening effect of oestrogen
et al. (1996). These authors also used superimposed could have a delayed onset.
electrical stimulation and found the highest quadriceps

Figure 1. Maximal isometric quadriceps strength


with superimposed stimulation and serum oestrogen
concentration throughout the three phases of the
menstrual cycle
The columns represent the means of the quadriceps
strength (+S.D.) and show no significant differences
between menstrual cycle phases. The dotted line
represents the means of the oestrogen concentration
(_S.D.). *Significantly different from Menstruation
(P < 0.01). **Significantly different from Menstruation
(P < 0.01) and significantly different from Late
follicular phase (P < 0.05).
J. Physiol. 530.1 Muscle function during the menstrual cycle 165

Table 4. Correlation coefficients between the muscle strength and fatigue parameters and the
serum hormone concentrations of oestrogen, progesterone, FSH and LH
Muscle function Oestrogen Progesterone FSH LH
Isometric quadriceps 0.025 0.005 _0.074 0.039
(0.872) (0.975) (0.631) (0.798)
Fatigue index _0.288 0.096 0.153 _0.146
quadriceps (0.088) (0.579) (0.374) (0.396)
Isokinetic ext 0.120 0.004 0.032 0.045
60 deg s_1 (0.438) (0.980) (0.836) (0.770)
Isokinetic flex 0.004 0.070 0.159 0.022
60 deg s_1 (0.979) (0.654) (0.307) (0.890)
Isokinetic ext 0.122 0.016 0.069 0.119
240 deg s_1 (0.429) (0.916) (0.654) (0.442)
Isokinetic flex 0.046 _0.069 0.130 0.048
240 deg s_1 (0.765) (0.658) (0.400) (0.758)
Fatigue index – ext 0.089 0.073 _0.273 0.142
(0.577) (0.648) (0.080) (0.371)
Fatigue index – flex _0.289 0.119 _0.170 _0.114
(0.063) (0.452) (0.283) (0.473)
Handgrip _0.015 _0.089 _0.046 _0.214
(0.922) (0.559) (0.766) 0.158
Data are shown as Pearson correlation coefficients with P values below. n = 45 (15 subjects over 3
phases), except for the Fatigue index quadriceps (n = 36) and the Fatigue index – extension and flexion
(n = 42). Ext, knee extension; flex, knee flexion. There were no significant correlations between the
strength and fatigue parameters and the serum hormone concentrations.

Contrary to the work by Phillips et al. (1996) and Sarwar In the present study a large variation in hormone
et al. (1996), Greeves et al. (1997) showed in patients concentrations was found throughout the menstrual
undergoing in vitro fertilization that supra-physiological cycle, but also within each menstrual cycle phase.
levels of oestrogen did not cause any changes in strength Especially during the late follicular phase the variation in
of the first dorsal interosseus muscle. The present study hormone levels was very large, with a range from 157 to
found no changes in strength over the menstrual cycle 1038 pmol l_1 for oestrogen concentration. This large
and did not show a correlation between oestrogen variation in hormone levels within each phase is partly
concentration and strength. Based on these findings the due to the secretory pulses of these hormones (ultradian
suggested effect of oestrogen on strength (Phillips et al. rhythm). Serum collection for the hormone analysis was
1996; Sarwar et al. 1996) is questionable. standardized, but it should be noted that rapid
fluctuations in the reproductive and pituitary hormones
The isokinetic findings from this study agree well with could occur at any time during the day throughout the
studies by Gür (1997) and Lebrun et al. (1995), who also menstrual cycle.
did not find any changes over the menstrual cycle for
maximal isokinetic knee flexion and extension strength. Besides the sudden daily fluctuations, the large variation
Both these studies suggested that menstrual cycle phase in hormone concentrations reported was also likely to be
does not affect isokinetic strength, which is confirmed by caused by timing problems within each menstrual cycle
the present results. phase. The days of testing for each subject were estimated
based on the BBT pattern of their previous cycle.
This study showed that fatiguability and electrically However, the length of the menstrual cycle can vary
stimulated contractile properties of the quadriceps did from cycle to cycle. The BBT charting does give an
not change over the menstrual cycle. This supports the indication of whether or not ovulation took place, but is
findings of White & Weekes (1998) who found no changes not accurate enough to predict the exact menstrual cycle
in fatiguability and maximal electrically evoked phase. To increase the chance of testing during the
contractile character of the triceps surae during the oestrogen peak, two tests were conducted during the late
menstrual cycle. Sarwar et al. (1996) reported an increase follicular phase. The variation in hormone concentrations
in fatiguability and a slowing of the half-time of within each menstrual cycle phase was decreased by
relaxation at mid-cycle (day 12–18), but did not measure analysing only the test with the highest oestrogen
hormone concentrations. Greeves et al. (1997), however, concentration as the late follicular phase. This way a more
showed no changes with extreme oestrogen fluctuations, accurate representation of the three phases of a regular
which supports the present findings and confirms the menstrual cycle was given. Thus the chances of showing a
suggestion that oestrogen concentration does not affect relationship between hormone concentrations and muscle
skeletal muscle fatiguability and contractile properties.
166 X. A. K. Janse de Jonge and others J. Physiol. 530.1

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following oral contraceptives. Psychoneuroendocrinology 7, 75–90. X. A. K. Janse de Jonge: School of Exercise and Sport Science,
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