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Maturitas 68 (2011) 331–336
Contents lists available at ScienceDirect
Maturitas
journal homepage: www.elsevier.com/locate/maturitas
Review
Menopause and sarcopenia: A potential role for sex hormones
Virginie Messiera, Rémi Rabasa-Lhoreta,b,c,d, Sébastien Barbat-Artigasf,g, Belinda Elishaa,c,
Antony D. Karelisc,e,f,g, Mylène Aubertin-Leheudrec,e,f,g,∗
aInstitut de Recherches Cliniques de Montréal (IRCM), 110, avenue des Pins Ouest, Montreal, Quebec, Canada H2W 1R7
bMontreal Diabetes Research Center (MDRC), Centre Hospitalier de l’Université de Montréal (CHUM), 2901, rue Rachel Est, Montreal, Quebec, Canada H1W 4A4
cDepartment of Nutrition, Université de Montréal, 2375, chemin de la Côte-Ste-Catherine, Montreal, Quebec, Canada H3T 1A8
dDepartment of Medicine, Université de Montréal, 2900, boulevard Édouard-Montpetit, Montreal, Quebec, Canada H3T 1J4
eDepartment of Kinanthropology, Université du Québec à Montréal, 141, avenue du Président-Kennedy, Montreal, Quebec, Canada H2X 1Y4
fCentre de recherche de l’Institut universitaire de gériatrie de Montréal, 4565, chemin Queen-Mary, Montreal, Quebec, Canada H3W 1W5
gGroupe de recherche en activité physique adaptée, Université du Québec à Montréal, 141, avenue du Président-Kennedy, Montreal, Quebec, Canada H2X 1Y4
article info
Article history:
Received 17 January 2011
Accepted 23 January 2011
Keywords:
Menopause
Sarcopenia
Sex hormones
Muscle mass
abstract
Menopause is associated with a decline in estrogen levels, which could lead to an increase in visceral adi-
posity as well as a decrease in bone density, muscle mass and muscle strength. This decline in muscle mass,
known as sarcopenia, is frequently observed in postmenopausal women. Potential causes of sarcopenia
include age-related changes in the hormonal status, low levels of physical activity, reduced protein intake
and increased oxidative stress. However, the role of sex hormones, specifically estrogens, on the onset
of sarcopenia is controversial. Preventing sarcopenia and preserving muscle strength are highly rele-
vant in order to prevent functional impairment and physical disability. To date, resistance training has
been shown to be effective in attenuating age-related muscle loss and strength. However, results on the
effect of hormonal supplementation to treat or prevent sarcopenia are contradictory. Further research
is needed to identify other potential mechanisms of sarcopenia as well as effective interventions for the
prevention and treatment of sarcopenia. Therefore, the purpose of this review will be to examine the
role of sex hormonal status in the development of sarcopenia. We will also overview the physical as well
as metabolic consequences of sarcopenia and the efficiency of different interventions for the prevention
and treatment of sarcopenia.
© 2011 Elsevier Ireland Ltd. All rights reserved.
Contents
1. Introduction .......................................................................................................................................... 332
2. Menopause ........................................................................................................................................... 332
3. Definition of sarcopenia.............................................................................................................................. 332
4. Changes in muscle morphology with sarcopenia ................................................................................................... 332
5. Epidemiology of sarcopenia ......................................................................................................................... 332
6. Role of menopause associated with hormonal changes ............................................................................................. 333
7. Hormone replacement therapy (HRT) and phytoestrogens for improving muscle mass ........................................................... 333
8. Consequences of sarcopenia ......................................................................................................................... 335
9. Conclusion............................................................................................................................................ 335
Competing interests ................................................................................................................................... 335
Contributors ............................................................................................................................................ 335
Provenance and peer review........................................................................................................................... 335
References ........................................................................................................................................... 335
∗Corresponding author at: Université du Québec à Montréal, Faculty of Sciences, Department of Kinanthropology, Canada. Tel.: +1 514 987 3000x5018;
fax: +1 514 987 6616.
E-mail address: aubertin-leheudre.mylene@uqam.ca (M. Aubertin-Leheudre).
0378-5122/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.maturitas.2011.01.014
332 V. Messier et al. / Maturitas 68 (2011) 331–336
1. Introduction
It is well known that menopause is characterized by impor-
tant changes in hormonal status and that these changes have an
important effect on bone mass density and body fat distribution
[1]. In addition, a good body of evidence supports the hypothesis
that the decline in estrogen levels with menopause may play a role
in muscle mass loss in postmenopausal women [2]. The term that
is widely used to describe the normal age-related loss in muscle
mass is sarcopenia. Functional impairment and physical disabil-
ity are the major consequences of sarcopenia and are associated
with increased healthcare expenditures [3]. Indeed, it is estimated
that the consequences of sarcopenia are responsible for approxi-
mately $18 billion in direct healthcare costs in the US annually [4].
Considering that the number of older adults is expected to double
over the next 25 years, sarcopenia has become an important clinical
research topic. Therefore, investigating the mechanisms underly-
ing this condition and developing efficient interventions for the
prevention and treatment of sarcopenia may be of great interest
for health care professionals. In this review, we will (1) summarize
the hormonal changes associated with menopause; (2) examine
the role of sex hormones with regards to sarcopenia; (3) discuss the
physical and metabolic consequences of sarcopenia and (4) address
the potential effect of hormone replacement therapy and phytoe-
strogens supplementation combined or not with exercise training
on muscle mass.
2. Menopause
Menopause is defined as the permanent cessation of menstrua-
tion resulting from the loss of ovarian follicular activity and marks
the end of natural female reproductive life. Menopause is pre-
ceded by a period of menstrual cycle irregularity, known as the
menopause transition or peri-menopause, which usually begins in
the mid-40s. The menopause transition is characterized by many
hormonal changes predominantly caused by a marked decline in
the ovarian follicle numbers [5]. A significant decrease in inhibin B
appears to be the first endocrine marker of the menopause transi-
tion with follicle-stimulating hormone (FSH) levels being slightly
raised [5]. Marked decreases in estrogen and inhibin A with sig-
nificant increases in FSH are only observed in the late stage of
menopause transition [5]. At the time of menopause, FSH lev-
els have been shown to increase to 50% of final post-menopausal
concentrations while estrogens levels have decreased to approx-
imately 50% of the premenopausal concentrations [5]. Since the
decrease in estrogen levels occurs in the fifth decade of life, this
means that most women will spend more than 30 years in post-
menopausal status.
A good body of evidence suggests that changes in hormonal sta-
tus, particularly the decline in estrogen, in the menopause years
may have a detrimental effect on women’s health. Accordingly,
it has been reported that the decrease in estrogen contributes to
the decrease in bone mass density, the redistribution of subcuta-
neous fat to the visceral area, the increased risk of cardiovascular
disease and the decrease in quality of life [1]. In addition, hor-
monal changes may also have a direct effect on muscle mass.
That is, an accelerated decline in muscle mass has been shown to
occur after the 5th decade, thus around the years of menopause
[6]. Moreover, a cross-sectional study reported a decline in mus-
cle mass of 0.6% per year after menopause [7]. Furthermore,
changes in characteristics of muscle tissue during menopause
have been reported. Accordingly, Jubrias et al. [8] showed that
postmenopausal women had twice the amount of non-contractile
muscle tissue, such as intramuscular fat, compared to younger
women.
3. Definition of sarcopenia
Sarcopenia refers to the loss of muscle mass associated with
normal aging [8]. However, over the past decade, sarcopenia has
often been defined as the age-related loss in muscle mass and
muscle strength, which implies that these are causally linked and
that changes in muscle mass are directly and fully responsible
for changes in muscle strength. However, this concept has been
challenged since it has been shown that age-associated changes
in muscle mass explained less than 5% of the variance in muscle
strength [9]. Thus, in this review, the term sarcopenia will be used
only to refer to the age-related loss in muscle mass.
Although there has been an increasing interest to investigate the
functional consequences and biologic mechanisms of sarcopenia,
no international definition has been proposed to identify sar-
copenic individuals. Most of the studies investigating sarcopenia
have used a muscle mass index by dividing total muscle mass
or appendicular muscle mass, measured by dual-energy X-ray
absorptiometry (DEXA) or bioelectrical impedance analysis (BIA),
by height squared [10–14]. According to these definitions, class I
sarcopenia is defined as a muscle mass index of 1–2 standard devia-
tions below the values of a younger reference population [10,12,13]
whereas class II sarcopenia represents a muscle mass index of 2
standard deviations or more below the values of the same younger
reference population [10–14].
4. Changes in muscle morphology with sarcopenia
All skeletal muscles are composed of motor units and each motor
unit contains a motor neuron and muscle fibers. Motor units can be
differentiated in two main types based on the fiber type present
in the motor unit. Slow motor units are mainly composed of type I
fibers while fast motor units predominantly consist of type II fibers
[15]. The decrease in muscle mass with aging results from loss of
both slow and fast motor units, with an accelerated loss of fast
motor units [16]. Moreover, there appears to be an atrophy of type II
fibers [16]. As motor units are lost via denervation, surviving motor
units recruit denervated fibers, changing their fiber type to that of
the motor unit [15]. Thus, there is a net conversion of type II fibers
to type I fibers, as type II fibers are recruited into slow motor units
[15]. Clinically, the loss of fast motor units and consequently of
type II fibers results in loss of muscle strength and power which
is necessary for physical movements such as rising from a chair,
climbing steps or regaining posture after a perturbation of balance
[15]. Another morphologic aspect of the aging skeletal muscle is the
infiltration of the muscle tissue by lipids whether by an increase in
the adipocyte number [17–19] or an increased deposition of lipid
in muscle fibers [20–22].
5. Epidemiology of sarcopenia
The prevalence of sarcopenia highly depends on the criteria
used to identify sarcopenic individuals. To our knowledge, only one
study investigated the prevalence of sarcopenia in a representa-
tive sample of men and women aged 18–80 years old [12]. Indeed,
Janssen al. [12] observed that the prevalence of class I and class II
sarcopenia increased from the third to sixth decade and remained
relatively constant thereafter. In addition, it was reported that the
prevalence of class I and class II sarcopenia was 50% and 7%, respec-
tively in women aged between 50 and 59 years old (Fig. 1). This is
a 15% increment in the prevalence of class I sarcopenia compared
to women aged 40 to 49 years suggesting that the prevalence of
sarcopenia increases at the time when significant changes in the
hormonal status occur.
V. Messier et al. / Maturitas 68 (2011) 331–336 333
80+70-7960-6950-5940-4930-3918-29
0
20
40
60
80
100
11%
11%
9%
7%
61%
57%
59%
50%
34%
22%
14%
28%
32%
32%
43%
63%
76%
86%
Percentage of population
Age (years)
Normal
Class I sarcopenia
Class II sarcopenia
Fig. 1. Prevalence of sarcopenia in women aged 18–80 years old.
Adapted from Janssen et al. [12].
6. Role of menopause associated with hormonal changes
It has been hypothesized that menopause transition and the
subsequent decline in estrogen may play a role in muscle mass
loss [23–26]. That is, van Geel et al. [27] reported a positive rela-
tionship between lean body mass and estrogen levels. Similarly,
Iannuzzi-Sucich et al. [28] observed that muscle mass is correlated
significantly with plasma estrone and estradiol levels in women.
However, Baumgartner et al. [29] reported that estrogen levels
were not associated with muscle mass in women aged 65 years and
older. The mechanisms by which a decrease in estrogen levels may
have a negative effect on muscle mass are not well understood but
it has been suggested that the decrease in estrogen concentrations
may be associated with an increase in pro-inflammatory cytokines,
such as tumor necrosis factor alpha (TNF-!) or interleukine-6 (IL-6),
which might be implicated in the apparition of sarcopenia [30]. Fur-
thermore, estrogen could have a direct effect on muscle mass since
it has been shown that skeletal muscle has estrogen beta-receptors
on the cell membrane, in the cytoplasm and on the nuclear mem-
brane [31]. Therefore, a direct potential mechanistic link could exist
between low estrogens levels and a decrease in protein synthesis.
Further studies are needed to investigate this hypothesis. Neverthe-
less, before reaching a conclusion on the contribution of estrogens
to the onset of sarcopenia, it would be important to measure urinary
estrogen metabolites since a relationship between breast cancer
and urinary estrogens metabolites has been shown [32].
With aging, free testosterone levels are decreased in men and
this decline parallels the decrease in muscle mass and muscle
strength [33]. Evidence to support testosterone supplementation
in men is variable as some studies have observed an increase in
muscle mass while others have not [34]. In women, bio-available
testosterone levels are also decreased, particularly in the imme-
diate years after menopause [35,36]. This observation raises the
question whether the decline in testosterone levels plays a role in
the accelerated loss in muscle mass with menopause. Further stud-
ies are needed to investigate the relationship between testosterone
and muscle mass in women as well as testosterone supplementa-
tion in sarcopenic women.
Another hormone associated with muscle mass loss is dehy-
droepiandrosterone (DHEA), a pro-hormone that can transform
into sex steroid such as androgens and estrogens. Among the
numerous important roles of DHEA in the human body, it may
contribute to the increase in muscle mass, the improvement in glu-
cose and insulin levels, the decrease in fat mass and reduce the
risk of breast cancer [37]. Circulating levels of DHEA decline with
age, especially at menopause in women [2]. This decline in DHEA
has been shown to be associated with a decrease in muscle mass
and physical performance [37]. However, Abbasi et al. [38] did not
observe a relationship between DHEA levels and body composition
in women aged 60 years and older. Furthermore, in elderly indi-
viduals, DHEA replacement showed no improvement in physical
performance and body composition [39]. Moreover, supplemen-
tation in DHEA (50–100 mg per day) for 3–9 months has shown
no beneficial effect for improving muscle mass [35]. Additional
randomized controlled trials are needed before reaching valid con-
clusions as to the clinical utility of DHEA supplementation in the
management of sarcopenia.
Other factors contribute to the development of sarcopenia are
shown in Fig. 2: (1) increased inflammatory activity as measured
by IL-6 or TNF-!which contributes to muscle catabolism; (2) accu-
mulation of free radicals with contributes to oxidative stress; (3)
changes in mitochondrial function of muscle cells; (4) increased
apoptotic activity affecting muscle function; (5) reduced physical
activity; and (6) impaired nutrition. The contribution of these fac-
tors to the development of sarcopenia in women and men has been
the subject of numerous reviews [2,15,40,41].
As mentioned above, menopause is associated with a rapid
decline in muscle mass while sarcopenia refers to the loss of muscle
mass with age. Since muscle mass is influenced by many factors that
are all related to age and menopause status, it makes it thus difficult
to establish the relative contribution of menopause as opposed to
age on the onset of sarcopenia. However, the loss in muscle mass is
gender-specific as the prevalence of sarcopenia in women increases
around the age of 50 whereas in men the prevalence increases by
the sixth decade. Thus, the role of menopause in the development
of sarcopenia can be hypothesized but further studies are needed
to specify its contribution.
7. Hormone replacement therapy (HRT) and
phytoestrogens for improving muscle mass
Estrogen supplementation or HRT is considered as a poten-
tial strategy to play a protective role on muscle mass and muscle
strength although contradictory results have been reported. For
example, Sorensen et al. [42] performed a 12-week double-blind
study where estrogen or placebo was administered and observed a
significant increase in lean body mass. Moreover, in the Women’s
Health Initiative study, subjects who were randomized to receive
HRT for 3 years lost 0.04 kg of lean body mass, which was signifi-
cantly less than the 0.44 kg lost by women on placebo, indicating
that HRT could reduce muscle mass loss [43]. However, some
studies have failed to show a positive effect of HRT on muscle
mass [44–46]. That is, in a study conducted by Hansen et al. [44],
women were given 20 mg doses of estrogen for 64 weeks and the
increase in muscle mass was not significant. In addition, the inci-
dence of sarcopenia was investigated in women who had been
on HRT for at least 2 years. It was reported that women on HRT
had a 23% incidence of sarcopenia whereas those not on HRT
had a 22% incidence suggesting that HRT does not prevent the
development of sarcopenia [45]. Nevertheless, the contradictory
results between studies could be explained by some confound-
ing factors such as the dose of estrogen used, the duration of the
study, levels of physical activity, diet and medications [31]. It is
also possible that the differences seen are due to different times
of post-menopause when HRT is being used, with the more ben-
eficial effects of HRT being in the early post-menopause period
[36].
Resistance training has been shown to be effective in atten-
uating age-related muscle loss [47]. To our knowledge, at least
two studies combined resistance training with HRT [48,49]. Sipila
et al. [48] randomized 80 postmenopausal women to four differ-
334 V. Messier et al. / Maturitas 68 (2011) 331–336
Menopause
Changes in endocrine function
Estrogen FSH DHEA GH
IGF-1 Insulin
Changes in muscle mass
Type II fibers
Motor units
Intramuscular fat
Sarcopenia
Impacts
Muscle strength
Functional impairments
Physical disability
Other factors
Physical inactivity
Impaired diet
Oxidative stress
Inflammation
Fig. 2. Menopause-related changes on muscle mass and its impact on functional status.
ent groups: (1) resistance training only (2 supervised sessions per
week for 12 months); (2) HRT only for 12 months; (3) resistance
training combined with HRT or; (4) control group. Women per-
forming resistance training combined with HRT or receiving HRT
alone significantly increased quadriceps cross-sectional area (+7.1%
and +6.3%, respectively) compared to the exercise only (+2.2%) or
the control (+0.7%) group. Furthermore, in a partially randomized
design, Teixeira et al. [49] assigned women who were already users
or non-users of HRT to exercise or non-exercise groups. The resis-
tance exercise training program consisted of 3 training sessions per
week for 12 months. Increases in lean body mass were observed in
the HRT + exercise (+1.0 kg) and HRT only (+0.3 kg) groups. The
results of these studies suggest that HRT by itself may preserve
muscle mass. Thus, the combination of HRT and resistance training
may not be more beneficial than HRT alone for the prevention of
sarcopenia in postmenopausal women. However, given the pos-
sible increased risk of cardiovascular disease and breast cancer
associated with the use of HRT [50], estrogen supplementation
V. Messier et al. / Maturitas 68 (2011) 331–336 335
should not be recommended as a primary line of treatment for
sarcopenia.
Another prospective approach to counteract sarcopenia might
be phytoestrogen supplementation. Isoflavones supplements are
found in soy products and exert a lipid-lowering effect [51], favor
vasodilatation as well as arterial compliance [52] and contribute
to the regulation of fasting glucose and insulin levels [53]. In
addition, Aubertin-Leheudre et al. [54] investigated the effect of
a 70 mg/day of soy isoflavone supplementation for 24 weeks on
muscle mass in obese-sarcopenic postmenopausal women and
observed that isoflavone supplementation was associated with a
significant increase in appendicular fat-free mass (+0.5 kg), but this
increase was not enough to reverse sarcopenia. Moreover, Moeller
et al. [55] randomized postmenopausal women to receive either
isoflavone-rich soy protein (40 g), isoflavone-poor soy protein or
when protein (control) for 24 weeks. It was reported that changes
in total lean body mass were not different between groups; how-
ever, lean body mass at the hip increased to a greater extent in the
isoflavone-rich group (+3.4%) than in the isoflavone-poor (+1%) or
control (0%) groups. Finally, Maesta et al. [56] assessed the effect
of soy protein (25 g) combined with resistance training on body
composition in postmenopausal women. This study showed that
soy protein combined with 16 weeks of resistance training 3 times
per week did not result in greater increases in muscle mass com-
pared to resistance training alone suggesting that soy protein had
no influence on muscle mass.
8. Consequences of sarcopenia
Several studies have shown an association between the loss
in muscle mass and adverse clinical outcomes such as mobil-
ity limitations and fractures. That is, Janssen et al. [12] used
the data of the Third National Health and Nutrition Examina-
tion Survey to investigate if sarcopenia was related to functional
impairment and physical disability. Functional impairment was
defined as having limitations in mobility performance such as
walking and climbing stairs while physical disability refers to
difficulty of performing activities of daily living (shopping, light
household chores). This study showed that the prevalence of func-
tional impairment and physical disability was greater in class
I and class II sarcopenia individuals than in their counterparts
without sarcopenia [12]. The results of Janssen et al. [12] are con-
sistent with those of Baumgartner et al. [57] who reported that
sarcopenia was a associated with disability, the use of a cane
or walker and a history of falling in a sample of 808 men and
women. In addition, it was shown that lower extremity perfor-
mance score, assessed using chair stands, gait speed and standing
balance, was lower in sarcopenic women compared to nonsar-
copenic women [58]. Furthermore, longitudinal studies have been
undertaken to determine if sarcopenia precedes the onset of func-
tional impairments and physical disability. Indeed, Visser et al. [59]
reported that low muscle mass resulted in a 34% increased risk
of mobility limitations 5 years later in women. The same study
also showed that women in the lowest quartile of muscle mass
had a 30 to 40% increased risk for the inability to perform activ-
ities of daily living [59]. Recently, Woo et al. [14] showed that
sarcopenic individuals presented greater limitations in climbing
stairs and in general activities of daily living after 4-years of follow-
up.
Little is known about the association between sarcopenia,
metabolic risk factors and health status. In the cross-sectional
analysis of the New Mexico Aging Process Study, obese sar-
copenic individuals did not show a higher prevalence of congestive
heart disease [11]. Interestingly, the prevalence of the metabolic
syndrome was higher in obese nonsarcopenic subjects (37.5%)
than in obese sarcopenic individuals (19.2%) [11]. Furthermore,
Aubertin-Leheudre et al. [10] reported that nonsarcopenic obese
postmenopausal women presented more cardiovascular risk fac-
tors (higher triglycerides, lower HDL-cholesterol) compared to
obese sarcopenic postmenopausal women. Similarly, Messier et al.
[13] observed that insulin resistance and fasting glucose tended to
be lower in obese sarcopenic women compared to obese nonsar-
copenic women. As mentioned earlier, because type II muscle fibers
are recognized to be glycolytic and insulin-resistant, the acceler-
ated loss of type II fibers with aging may explain how sarcopenia
would positively alter glucose metabolism [10]. Nevertheless, it
should be noted that the physical and metabolic consequences of
sarcopenia discussed here are neither specific to menopause nor
gender-specific.
9. Conclusion
The decrease in estrogens levels with menopause may play a
potential role in the decline in muscle mass after the 5th decade
of life. Sarcopenia is a complex condition involving hormonal, bio-
logical, nutritional and physical activity mechanisms. It is however
difficult to establish the relative contribution of sex hormones on
the onset of sarcopenia. Prospective observational studies with
regular measurement of sex hormones and body composition dur-
ing menopause transition, taking into account confounding factors
such as nutrition and physical activity, will have to be undertaken
in order to determine the contribution of menopause in the devel-
opment of sarcopenia. Furthermore, the measurement of urinary
estrogens metabolites could add new evidence as for the role of
estrogens in sarcopenia. It remains certain, though, that the decline
in muscle mass is associated with an increased risk of functional
impairment and physical disability. Finally, further randomized
controlled trials are needed to investigate the effects of physical
activity as well as hormone and phytoestrogen supplementation
on sarcopenia.
Competing interests
This manuscript was supported by CIHR (Canadian Institute for
Health Research) grants: 63279 MONET study (Montreal Ottawa
New Emerging Team) and 88590 SOMET study (Sherbrooke Mon-
treal Ottawa Emerging Team). Dr Rémi Rabasa-Lhoret and Dr
Antony D. Karelis are supported by the Fonds de la recherche en
santé du Québec (FRSQ). Finally, Dr Rémi Rabasa-Lhoret is the recip-
ient of the J-A De Sève Research Chair for Clinical Research. The
authors declare no conflict of interest.
Contributors
Virginie Messier: drafting; Rémi Rabasa-Lhoret: revision;
Sébastien Barbat-Artigas: revision; Belinda Elisha: revision; Antony
D. Karelis: revision; Mylène Aubertin-Leheudre: revision.
Provenance and peer review
Commissioned and externally peer reviewed.
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