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Clinical Science (1999) 97, 79–84 (Printed in Great Britain)
Changes in muscle strength in women
following the menopause: a longitudinal
assessment of the efficacy of hormone
replacement therapy
Julie P. GREEVES*, Nigel T. CABLE*, Thomas REILLY* and Charles KINGSLAND†
*Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Henry Cotton Campus, 15–21 Webster
Street, Liverpool L3 2ET, U.K., and †Reproductive Medicine Unit, Liverpool Women’s Hospital, Liverpool L8 7SS, U.K.
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The effects of hormone deficiency at the menopause on muscle strength was examined in
10 healthy middle-aged women (1–3 years post-menopause) in a longitudinal trial over 39 weeks.
Performance was compared with that of age-matched females (n l 11) taking a course of
hormone replacement therapy (HRT). Muscle strength of the quadriceps was measured
isometrically at 90m of knee flexion and at angular velocities of 1.05, 2.09 and 3.13 rad/s using an
isokinetic dynamometer. Hand grip strength was assessed by means of a portable dynamometer.
Measurements were taken every 13 weeks for 39 weeks. Significant decreases in isometric
strength (k10 %) and dynamic leg strength at 1.05 rad/s (k9 %) were found in the postmenopausal women over 39 weeks. There was no change in strength in the HRT group. There
were also no changes in leg strength at higher angular velocities or in grip strength for either the
post-menopausal group or those taking HRT. While HRT preserved muscle strength, there was
no evidence of a strengthening effect on skeletal muscle within this short period of treatment.
A rapid loss of leg strength occurs post-menopausally in hormone-depleted women. HRT may
offer protection against muscle weakness, although the hormone responsible for regulating
strength is not evident using this model.
INTRODUCTION
The higher incidence of falls with age [1] has been
attributed to muscle weakness [2], although impaired
balance [3,4] and a deterioration in neuromuscular
function [4] are also important risk factors for falling. A
decline in strength is an inherent process of aging which
has been reported extensively as a result of muscle
atrophy [5–7]. A specific weakening of muscle, expressed
as force per cross-sectional area (force\CSA), has also
been demonstrated in aged human adductor pollicis (AP)
[8] and hindlimb muscles in animals [9,10]. A closer
examination of the time course of this specific muscle
weakness in humans has revealed a disparity in its onset
between males and females. A rapid decrease in force\
CSA of the AP occurs from 50 years onwards in females,
a trend that is not evident in males until 60 years of age
[11]. Since the average age at which the menopause occurs
is 50 years, these findings suggest a hormone-dependent
loss of strength.
Whereas a hormonal component in the regulation of
force production has been indicated for hand muscles, it
is not known whether leg strength is also compromised as
a result of ovarian failure in middle-aged women.
Weakening of the quadriceps, the main weight-bearing
muscle group concerned with ambulation and balance,
Key words : force production, isokinetic, isometric, oestrogen, post-menopause, progesterone.
Abbreviations : AP, adductor pollicis ; CSA, cross-sectional area ; HRT, hormone replacement therapy.
Correspondence : Dr Julie Greeves.
# 1999 The Biochemical Society and the Medical Research Society
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J. P. Greeves and others
may result in a greater number of falls post-menopause.
This would present important clinical implications for
these women, who are already prone to losing bone at a
rapid rate following the menopause [12–14]. Indeed, a
high incidence of falls leading to an increase in Colles ’
fractures has been reported previously in peri-menopausal women [1], although it would be imprudent to
attribute this rate of falling to muscle weakness without
concomitant assessment of leg strength.
The specific force of the quadriceps has been found not
to differ when measured in young and old women [15],
and, given the differences in reproductive status between
these sample groups, it may be extrapolated that there are
no hormonal influences regulating quadriceps strength.
Conversely, Rutherford and Jones [16] reported a lower
force-generating capacity of the quadriceps in osteoporotic females compared with healthy age-matched
controls, which suggests a hormonal component of
muscle weakness. Whereas computed tomography (CT)
was used in the latter study to measure muscle size,
Young et al. [15] employed ultrasound imaging. This
technique does not yield the same resolution or sensitivity as CT scans, factors that are important in the
estimation of the size of complex multi-pennated muscle
groups such as the quadriceps. Cross-sectional comparisons of absolute strength may also disguise hormonal
effects ; Bassey et al. [17] failed to detect differences in
absolute leg or grip strength in hormone replacement
therapy (HRT) and oestrogen-depleted subjects. To
overcome the problems of cross-sectional measurements
and to determine the rate of strength loss 1–3 years postmenopause, we measured the maximal strength of a
functional muscle group, the quadriceps, over 39 weeks
in recently amenorrhoeic middle-aged women. Furthermore, based on the observation that muscle weakness is
not manifest in women taking HRT [11], the role of
hormone repletion in the regulation of force production
was investigated to assess whether muscle strength is
restored or maintained by HRT following the menopause.
Preliminary data have been presented to the Physiological Society [18].
METHODS
women (age 51.97p3.11 years ; height 1.62p0.07 m ;
mass 72.33p14.57 kg) who had experienced the menopause within the previous 1–3 years from the time of
testing, as determined retrospectively from questionnaire
reports. A venous blood sample was taken to confirm
high levels of follicle-stimulating hormone and luteinizing hormone ( 20 units\l). The women who began
taking HRT had been referred to the Menopause Clinic
for advice on taking the treatment.
A questionnaire was completed by all subjects for
inclusion into\exclusion from the study. No subject had
sustained fractures within the 5 years before recruitment,
had suffered any pain or neuromuscular disease of the
legs and hands, or was taking any treatment likely to
affect performance. Physical activity levels of subjects
were monitored upon recruitment using the Leisure
Time Physical Activity Questionnaire [19]. Of the initial
27 subjects who were recruited, six dropped out (three
from each group).
This study was carried out in accordance with the
Declaration of Helsinki (1989) of the World Medical
Association, and was approved by the Human Ethics
Committee of Liverpool John Moores University and
The Royal Liverpool Hospital Trust. Written informed
consent was obtained from all participants.
Procedure
Body mass, height and blood pressure were recorded
before strength testing. Subjects rested for 5 min before
blood pressure was monitored using an automatic sphygmomanometer (Model 8111 ; DINAMAP, Critikom,
Bracknell, U.K.). Values greater than 150\100 mmHg
were recognized as hypertensive, and subjects were
requested to seek medical advice before continuing with
the study. A 5 min self-paced warm-up on a cycle
ergometer (Monark) was performed before commencing
the strength assessments.
Subjects attended a practice session 1 week before the
baseline measurements to allow familiarization with the
procedure and tests involved. Following the baseline test,
measurements were taken on three occasions separated
by 13-week intervals.
Assessment of muscle strength
Quadriceps
Subjects
A total of 21 women with a sedentary lifestyle volunteered to participate in the study. Subjects were
recruited from the Menopause Clinic at Liverpool
Women’s Hospital and through advertisements in a local
newspaper. Eleven women [age 50.05p3.84 years ; height
1.59p0.05 m ; mass 67.50p10.31 kg (meanspS.D.)] began taking HRT of various preparations at the onset of
the study. The post-menopausal group comprised 10
# 1999 The Biochemical Society and the Medical Research Society
The maximal dynamic and isometric strength of the
quadriceps was measured using the LIDO Active2
isokinetic dynamometer (Loredan, Davis, CA, U.S.A.).
The dynamic strength of the quadriceps was assessed at
three angular velocities of 1.05, 2.09 and 3.13 rad\s.
Subjects were seated in an adjustable chair, and the upper
body was stabilized with straps secured across the
shoulders, chest and hips. A resistance pad was also
positioned on the thigh, proximal to the knee joint, to
Strength loss and hormonal therapy post-menopause
Maximal muscle strength over 39 weeks in post-menopausal women with (n l 11) and without (n l 10) HRT
CV is the coefficient of variation of test–retest data measured in a homogeneous group of age-matched females. * and ** represent significant differences in strength
from baseline at P 0.01 and P 0.05 respectively. † and †† represent significant group-by-time interactions at P 0.01 and P 0.05 respectively. Results are
means (S.E.M.).
Table 1
Treatment group
Strength measure (CV %)
Baseline
Week 13
Week 26
Week 39
HRT
Non-HRT
HRT
Non-HRT
HRT
Non-HRT
HRT
Non-HRT
HRT
Non-HRT
Isometric (N) (10.1 %)
114.7 (8.5)
122.3 (6.3)
127.1 (7.6)
127.5 (5.6)
93.6 (4.8)
90.9 (5.3)
80.5 (4.5)
76.8 (5.0)
27.2 (1.4)
28.5 (2.2)
114.0 (7.2)
123.8 (6.6)
125.9 (7.7)
131.0 (8.7)
94.8 (5.8)
90.5 (7.0)
80.4 (5.0)
77.4 (4.4)
26.2 (1.4)
27.2 (2.1)
113.8 (6.7)
113.5 (7.2)*
125.8 (7.6)
122.8 (8.7)**
94.4 (5.8)
89.7 (6.5)
79.4 (4.3)
78.0 (5.6)
27.4 (1.1)
27.2 (2.2)
112.4 (7.1)
109.7 (6.5)*
128.8 (7.8)
116.5 (8.4)**
93.7 (4.9)
86.7 (6.4)
79.9 (4.5)
75.3 (6.3)
26.2 (1.6)
27.0 (2.1)
1.05 rad/s (Nm) (9.0 %)
2.09 rad/s (Nm) (7.4 %)
3.13 rad/s (Nm) (6.1 %)
Handgrip (kg) (7.6 %)
localize the quadricep and hamstring muscle groups. The
axis of rotation of the dynamometer shaft was aligned
with the axis of rotation of the knee joint, midway
between the lateral condyle of the tibia and the lateral
condyle of the femur. The cuff of the dynamometer’s
lever arm was attached to the ankle, proximal to the
malleoli. These positions were standardized for each
subject. The range of motion was preset at 0–90 m, and
torque measures were corrected for gravity. Subjects
performed four maximal reciprocal efforts through the
entire range of motion, preceded by two submaximal
warm-up trials. Each effort, undertaken with the arms
folded, was supported by verbal encouragement. A 1 min
rest period was allowed between measurements at each
angular velocity. The order of testing at each angular
velocity was standardized, beginning with dynamic leg
strength at the lower angular velocity of 1.05 rad\s as
recommended by Wilhite et al. [20].
Maximal voluntary isometric contraction of the quadriceps was assessed at 90 m flexion of the knee joint 5 min
after undertaking the dynamic strength tests. Maximal
activation of the muscle groups was determined using
percutaneous electrical stimulation [21]. Electrical impulses were delivered through surface electrodes
(7.6 cmi12.7 cm ; Chattanooga, Bicester, U.K.) at 250 V
with a pulse width of 200 µs using a computer-driven
stimulator (Model DS7 ; Digitimer Ltd., Welwyn Garden
City, U.K.). The electrodes were positioned on the
proximal and distal anteriolateral side of the thigh of the
dominant leg. Subjects were required to ‘ kick out ’ as
hard as possible on instruction while the 1 Hz electrical
impulses were delivered to the contracting muscle.
Maximal activation was confirmed when no extra force
could be generated by the superimposed twitches. A
1 min rest period was allowed between each of three
maximal efforts, the greatest of which was recorded.
P values for
group-by-time
interaction
0.007†
0.011††
0.430
0.416
0.694
Handgrip strength
Handgrip strength was measured using a hand-held
dynamometer (model 5101 Grip-D ; Takei, Tokyo,
Japan) with the subject standing in an upright position.
The handle of the dynamometer was supported between
the interphalangeal joints and the base of the AP of the
dominant hand. The dynamometer, held above the head
with an extended arm, was adducted towards the lateral
side of the body while maximal effort was exerted on to
the force transducer. The greatest of three maximal
contractions was recorded.
Data analysis
Means, S.E.M. values and percentage changes from
baseline were calculated. A two-way analysis of variance
(Statistical Package for the Social Sciences, 1993) with a
repeated-measures factor (time) was employed to calculate strength changes between groups over time and
differences in the relative force–velocity relationship.
The Huynh–Feldt correction factor was used. Post-hoc
tests (Scheffe! ) were carried out to determine differences
between variables from the analysis of variance. Significance was set at the 5 % level.
RESULTS
There were no significant differences in body mass
between the two groups for the duration of the study (P
l 0.430). Height was not significantly different between
the two groups at the start of the study (P l 0.296), and
did not change over the course of testing. Mean scores
(pS.E.M.) for the isometric and dynamic strength of the
quadriceps and handgrip strength are shown in Table 1.
Physical activity levels were assessed using the Leisure
Time Physical Activity Questionnaire [19]. Subjects,
# 1999 The Biochemical Society and the Medical Research Society
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Figure 1 Changes in maximal isometric and dynamic
strength (at 1.05 rad/s) between baseline and 39 weeks in
post-menopausal women with (empty bars) and without
(shaded bars) HRT
Results are meanspS.E.M. Differences between * and ** are significant at P
0.05.
who all met the inclusion criteria of a sedentary lifestyle,
did not report any leisure time physical activity above
that of everyday household tasks. Additionally, subjects
did not report any change in physical activity levels over
the duration of the study.
Strength performance in women postmenopause
There was a significant group-by-time interaction over
39 weeks for isometric leg strength (P 0.01) and
dynamic leg strength at 1.05 rad\s (P 0.05). There were
no significant changes in strength at the higher angular
velocities of 2.09 and 3.13 rad\s. Force in the HRT group
remained constant across all angular velocities (P 0.05).
There was no significant change in grip strength over
time for the two groups (Table 1).
Post-hoc power analysis, calculated using the methods
of Pearson and Hartley [22], confirmed that the groupby-time interaction yields 85 % power at the 5 % significance level.
Percentage change in strength in postmenopausal women and those on HRT
The percentage change in strength between baseline and
39 weeks was significantly greater in post-menopausal
women than in the HRT group for isometric strength
(k10.3 % and k1.0 % respectively) and dynamic
strength at 1.05 rad\s (k9.3 % and j1.5 % respectively)
(P 0.05). These results are plotted in Figure 1.
Standardized force–velocity relationships
Figure 2 shows a comparison of the speed-dependent
change in relative force between baseline and 39 weeks in
the post-menopausal (upper panel) and HRT (lower
panel) groups. Force is expressed as a percentage of
isometric force at each velocity. There were no significant
differences in standardized force–velocity relationships
over time or between groups (P 0.05).
# 1999 The Biochemical Society and the Medical Research Society
Figure 2 Comparison of relative peak torque at increasing
angular velocities at baseline (4) and at 39 weeks () in
post-menopausal women (upper panel) and in women taking
HRT (lower panel)
DISCUSSION
The present data suggest that muscle strength of the
quadriceps declines at a rapid rate within the first 3 years
post-menopause in women who do not take hormonal
therapy. To our knowledge, this is the first longitudinal
study to demonstrate that weakness occurs in a functional
muscle group in response to the hormone deficiency at
the menopause. This strength loss, which mirrors the
accelerated loss of bone mineral density [13,14], presents
a complex interaction between muscle weakness, bone
loss and the associated risk of fracture.
Women taking HRT have higher muscle force\CSA
ratios than age-matched females who are hormonally
depleted [11]. In the present study, the possible role of
exogenous hormones in preserving muscle strength was
examined over 39 weeks, and a maintenance of leg
strength was found to be associated with the initiation of
HRT. While we did not find an increase in strength
which would suggest that this weakening is reversible,
Skelton et al. [23] reported a strengthening effect of HRT
on the AP muscle in post-menopausal women of " 12 %
over 52 weeks. In contrast with the present findings,
these workers did not report a decrease in strength in the
non-hormone group. However, these women were older
(60.8 years) than the post-menopausal women in the
present study, and it is possible that they had already
experienced the initial post-menopausal strength loss that
we report. This would also explain the lack of change in
leg strength measured at 0 and 1.05 rad\s over 11 months
Strength loss and hormonal therapy post-menopause
in hormone-depleted women aged 60–72 years [24]. The
lack of strength gain in the HRT group in the present
study compared with the data of Skelton et al. [23] may
be also explained by the HRT preparations administered
to the subject groups. Unlike in the study of Skelton et al.
[23], it was not possible to standardize the preparations
administered to subjects in the present study, as they
were recruited from a menopause clinic. Nevertheless, it
is apparent from both studies that HRT is capable of
modulating muscle strength. By careful manipulation of
HRT preparations in future work, it may be possible to
discern the hormone responsible for these observations.
A loss of strength in women aged around 50 years was
initially observed in the late 1970s [25], although Phillips
et al. [11] were the first to confirm a sex-hormonedependent loss of specific force in menopausal women,
measured as force\CSA. There have been arguments
raised since as to the validity of measuring ‘ specific ’ force
using linear potentiometers to estimate muscle size [17],
particularly in older women who experience an infiltration of fat into muscle [26] and the replacement of
contractile material with connective tissue [27]. Estimating fat-free mass from skinfold measurements, Bassey
et al. [17] claimed that post-menopausal women are more
prone to accumulating fat in muscle compared with those
taking HRT, leading to an overestimation of CSA of the
AP in hormone-depleted women and a consequent
underestimation of specific force. However, studies that
have measured fat mass using dual photon absorptiometry have not found any differences between HRT and
non-HRT women [28]. Even if HRT were associated
with less fat deposition, it is unlikely that this would
account for the 20 % difference in specific force reported
by Phillips et al. [11].
In a recent randomized controlled trial over 54 weeks,
performance parameters, including leg power and grip
strength, were not found to change in post-menopausal
women aged 45–70 years [3]. These authors suggest that
the decline in muscle strength reported after the menopause [11] can be explained by a decline in physical
activity levels at this time [3]. Such a decline would not
explain the strength changes we found for the quadriceps.
Levels of physical activity were the same in the HRT and
post-menopausal groups, but there was no change in leg
strength in the women taking exogenous hormones.
Furthermore, strength at higher angular velocities (2.09
and 3.13 rad\s) did not change, suggesting that factors
other than activity levels are responsible for the loss in
strength post-menopause.
While there is growing evidence that reproductive
hormones are involved in the regulation of muscle
strength, it is not known whether oestrogen or progesterone is primarily responsible, since both ovarian
hormones are deficient at the menopause. In addition,
HRT, which appears to confer protection against muscle
weakness, may contain both oestrogen and a pro-
gestogen. Based on the findings that the force of the AP
is highest at the pre-ovulatory peak in oestrogen in the
menstrual cycle [29], loss of oestrogen is currently
thought to be responsible for strength changes in postmenopausal women [11]. However, these claims are
conjectural, as Greeves et al. [30] have provided unequivocal evidence that oestrogen is not the sole regulator
of these strength changes. The maximal strength of the
first dorsal interosseus muscle was measured in women
receiving in vitro fertilization treatment, who experience
changes in oestrogen comparable with those of postmenopausal women. Strength measured during a hypoestrogenic state following the down-regulation of hypothalamic pituitary receptors was not different from
strength measured at supraphysiological oestrogen levels
following a course of exogenous gonadotropins. We
suggest that low progesterone levels may be responsible
for the loss of strength during early post-menopause.
Indeed, this is supported by the fact that progesterone is
the first hormone to become deficient at the menopause
due to the failure of corpus luteum formation [31]. The
maintenance of strength we report in women taking
HRT may therefore be mediated by the progestogen dose
or by an interactive effect of progestogen and oestrogen
in the combined preparations.
It is apparent from these observations that skeletal
muscle is responsive to the deficiency in reproductive
hormones during the early post-menopausal period.
Although HRT appears to maintain the strength of the
quadriceps, thereby reducing the risk of falling and
sustaining a fracture, this treatment is contra-indicated in
hormone-sensitive females. Future work is warranted to
elucidate the exact hormonal milieu responsible for these
strength changes. This will allow appropriate treatment
to be offered to all post-menopausal women who are
currently deprived of the possible protective benefits of
progesterone.
ACKNOWLEDGMENTS
We thank Professor Alan Nevill for his assistance with
the treatment of data and advice with the statistical
analysis. The help of statistician Dr. Mike Kenward is
also gratefully acknowledged.
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Received 3 December 1998/25 February 1999; accepted 8 April 1999
# 1999 The Biochemical Society and the Medical Research Society