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Menopause and sarcopenia: A potential role for sex hormones

Authors:

Abstract

Menopause is associated with a decline in estrogen levels, which could lead to an increase in visceral adiposity 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 relevant 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.
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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... Menopause, characterized by the decline in estrogen levels, exerts a significant effect on body fat mass in postmenopausal women, with studies indicating an increase in fat mass among aging women [12,13]. However, despite the growing body of research in this field, the precise relationships between the three major nutrients and body fat distribution in both preand post-menopausal adult women remain uncertain. ...
... Menopause is accompanied by significant hormonal changes, particularly a decrease in estrogen levels [12,41]. This hormonal transition leads to various physiological alterations, including decreased bone mass density, subcutaneous fat redistribution to the visceral area, insulin resistance, increased cardiovascular disease risk, and diminished quality of life [42]. ...
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Background Obesity, characterized by excessive body fat accumulation, is associated with various chronic health conditions. Body fat plays a crucial role in health outcomes, and nutrient intake is a contributing factor. Menopause further influences body fat, but the precise relationships between nutrients and fat mass distribution in pre- and post-menopausal women are unclear. Methods Data from 4751 adult women aged ≥18 years old (3855 pre-menopausal, 896 post-menopausal) with completed information were obtained from the National Health and Examination Survey (NHANES) from 2011 to 2018. Multivariate linear regression models were used to examine the associations between protein, carbohydrate, fat intake and total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), subcutaneous adipose tissue mass (SAT), visceral adipose tissue mass (VAT). Subgroup analyses, stratified by menopausal status, were also conducted. Additionally, we employed smoothing curve fitting techniques to investigate potential non-linear relationships between fat mass distribution and nutrient intake. Results Compared with pre-menopausal women, post-menopausal women had higher body fat, BMI, and metabolic indicators but lower nutrient intake (All p<0.05). In the overall analysis, we found significant correlations between nutrient intake and fat mass. Specifically, protein intake was negatively correlated with TPF (β = -0.017, 95% CI: -0.030, -0.005), APF (β = -0.028, 95% CI: -0.044, -0.012), GPF (β = -0.019, 95% CI: -0.030, -0.008), while fat intake showed positive correlations with these measures (SAT: β = 2.769, 95% CI: 0.860, 4.678). Carbohydrate intake exhibited mixed associations. Notably, body fat mass-nutrient intake correlations differed by menopausal status. Generally speaking, protein intake showed negative correlations with body fat distribution in pre-menopausal women but positive correlations in post-menopausal women. Carbohydrate intake revealed significant negative associations with abdominal and visceral fat in post-menopausal women, while fat intake was consistently positive across all fat distribution indices, especially impacting visceral fat in post-menopausal women. Conclusion Dietary intake plays a crucial role in body fat distribution, with menopausal status significantly influencing the impact of nutrients on specific fat distribution metrics. The study emphasizes the need for dietary guidelines to consider the nutritional needs and health challenges unique to women at different life stages, particularly concerning menopausal status, to effectively manage obesity.
... 28 Decreased estrogen levels, decreased bone density and muscle mass, decreased muscle strength, and increased intramuscular fat are particularly pronounced among middle-aged women during menopause. [29][30][31] A recent study in Asia found that about 12% of postmenopausal, middle-aged women were in the pre-sarcopenic stage. 32 Furthermore, hormonal changes in menopausal women are associated with a higher risk of CVD. ...
... Results were categorized into low-risk (less than 7.5% risk) and high-risk (greater than 7.5% risk) groups. 31 Measurements and surveys were conducted following a minimum of 8 hours of fasting. Blood pressure readings were obtained using a sphygmomanometer; three measurements were taken, with the mean of the second and third readings constituting the examination blood pressure. ...
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Purpose Handgrip strength is an indicator of overall muscle strength and has been associated with an increased risk of cardiovascular disease. Evidence suggests that menopause is a risk factor for cardiovascular disease in women, and muscle strength decreases progressively after menopause. Despite the prognostic importance of the decline in muscle strength and increased cardiovascular disease risk among postmenopausal women, evidence of their association is limited. This study aimed to investigate the relationship between handgrip strength and cardiovascular disease risk among postmenopausal, middle-aged Korean women. Patients and Methods Using pooled cohort equations, we calculated the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among postmenopausal women (N = 2019) aged 50–64 years without cardiovascular disease history from the 2014–2019 Korea National Health and Nutrition Examination Survey. Relative grip strength was defined as measured grip strength divided by body mass index. Logistic regression analysis of a complex sampling design was performed to evaluate the association between relative grip strength and a predicted 10-year ASCVD risk ≥7.5%. Results The average handgrip strength was 24.8 kg, and 5.2% of women were considered for sarcopenia (<18 kg). The quartile-stratified relative grip strength was negatively associated with 10-year ASCVD risk (p < 0.001). In the multiple logistic regression analysis, the adjusted odds ratio for the highest relative grip strength quartile was 0.53 (95% confidence interval [CI]: 0.36–0.78), and that of the group who breastfed for more than 12 months was 1.75 (95% CI: 1.36–2.25) for 10-year ASCVD risk. Conclusion Increased handgrip strength may be associated with lower cardiovascular disease risk among middle-aged postmenopausal women in Korea. Our findings provide critical evidence regarding the importance of increasing handgrip strength among postmenopausal, middle-aged women to reduce cardiovascular disease risk. Handgrip strength measurement might be a valuable screening tool for cardiovascular disease prevention.
... Further studies are necessary to prevent agerelated loss of muscle mass and strength. In postmenopausal women, loss of skeletal muscle mass and function is accelerated because of decreasing sex steroid hormone secretion (Messier et al., 2011). Moreover, the hypertrophic response to resistance training decreases in elderly women compared with that in elderly men (Bamman et al., 2003). ...
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This study investigated the effects of white meat, such as chicken, intake combined with resistance training on muscle mass and strength in the elderly women, and whether the underlying mechanism involves changes in the gut microbiota. Ninety‐three volunteers (age 59–79 years) were randomly allocated to sedentary control with placebo (Sed + PL) or chicken meat (Sed + HP) and resistance training with placebo (RT + PL) or chicken meat (RT + HP). Resistance training sessions were performed 3 d/week for 12 weeks using leg extensions and curls. Boiled chicken meat (110 g, containing 22.5 g protein) was ingested 3 d/week for 12 weeks. Maximal muscle strength and whole‐body lean mass increased significantly in the RT + PL group compared to the Sed + HP group, and the RT + HP group showed a significantly greater increase than the Sed + HP and RT + PL groups. Additionally, the gut microbiota composition did not change before or after the interventions in any of the four groups. Moreover, the individual comparison of gut bacteria using false discovery rate‐based statistical analysis showed no alterations before or after the interventions in the four groups. Resistance training combined with chicken meat intake may effective have increased muscle mass and strength without drastically modifying the gut microbiota composition in elderly women.
... Multiple mechanisms (such as menopause, reproductive duration) might underly the relationship between endogenous estrogen exposure and frailty. Postmenopausal estrogen decline contributes to increased bone loss (Khosla and Pacifici, 2021), muscle weakness (known as sarcopenia) (Messier et al., 2011;Buckinx and Aubertin-Leheudre, 2022), a higher risk of CVD (Zhu et al., 2019), metabolic dysregulation (Mauvais-Jarvis et al., 2013;Jeong and Park, 2022), heightened inflammation (Abildgaard et al., 2020;Khalafi et al., 2021), and cognitive functions (Hao et al., 2023), all of which contribute to frailty. ...
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STUDY QUESTION Are women’s reproductive factors associated with physical frailty and comprehensive frailty in middle-age and later life? SUMMARY ANSWER Early menarche at less than 13 years, age at menopause less than 45 years, surgical menopause, experiencing miscarriage and a shorter reproductive period of less than 35 years were associated with increased odds of frailty, while having two or three children was related to decreased likelihood of frailty. WHAT IS KNOWN ALREADY Evidence has shown that women are frailer than men in all age groups and across different populations although women have longer lifespans. Female-specific reproductive factors may be related to risk of frailty in women. STUDY DESIGN, SIZE, DURATION A population-based cross-sectional study involved 189 898 women from the UK Biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS Frailty phenotype and frailty index were used to assess physical frailty and comprehensive frailty (assessed using 38 health indicators for physical and mental wellbeing), respectively. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% CI between reproductive factors and likelihood of physical frailty and comprehensive frailty. Restricted cubic spline models were used to test the non-linear associations between them. In addition, we examined the combined effect of categorized age at menopause and menopause hormone therapy (MHT) on frailty. MAIN RESULTS AND THE ROLE OF CHANCE There was a J-shape relationship between age at menarche, reproductive period and frailty; age at menarche less than 13 years and greater than 16 years, and reproductive period less than 35 years or greater than 40 years were all associated with increased odds of frailty. There was a negative linear relationship between menopausal age (either natural or surgical) and odds of frailty. Surgical menopause was associated with 30% higher odds of physical frailty (1.34, 1.27-1.43) and 30% higher odds of comprehensive frailty (1.30, 1.25-1.35). Having two or three children was linked to the lowest likelihood of physical frailty (0.48, 0.38-0.59) and comprehensive frailty (0.72, 0.64-0.81). Experiencing a miscarriage increased the odds of frailty. MHT use was linked to increased odds of physical frailty in women with normal age at natural menopause (after 45 years), while no elevated likelihood was observed in women with early natural menopause taking MHT. LIMITATIONS, REASONS FOR CAUTION The reproductive factors were self-reported and the data might be subject to recall bias. We lacked information on the types and initiation time of MHT, could not identify infertile women who later became pregnant, and the number of infertile women may be underestimated. Individuals participating in the UK Biobank are not representative of the general UK population, limiting the generalization of our findings. WIDER IMPLICATION OF THE FINDINGS The reproductive factors experienced by women throughout their life course can potentially predict frailty in middle and old age. Identifying these reproductive factors as potential predictors of frailty can inform healthcare providers and policymakers about the importance of considering a woman’s reproductive history when assessing their risk for frailty. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Key Research and Development Program of China (2022YFC2703800), National Natural Science Foundation of China (82273702), Science Fund Program for Excellent Young Scholars of Shandong Province (Overseas) (2022HWYQ-030), Taishan Scholars Project Special Fund (No. tsqnz20221103), and the Qilu Young Scholar (Tier-1) Program (202099000066). All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A
... annual loss of muscle [13] ..Sarcopenia was found to be as common in post-menopausal women as 31%, according to one study [14] . All of the aforementioned ndings point to a signi cant frequency of sarcopenia; also, postmenopausal women who have sarcopenia are more likely to experience falls and vertebral fractures [15] . ...
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Background:Sarcopenia is a common elderly syndrome that increases the risk of falls and fractures, affects the ability to live daily and reduces quality of life.The present study try to explore the factors associated with muscle mass by using Dual-energy X-ray absorptiometry(DXA) in Chinese postmenopausal women. Methods: The clinical information of 234 postmenopausal women, ages 50 to 79, was included in this study. Every subject's height, weight, calf circumference (CC), and grip strength were recorded. The body mass index, or BMI, was computed. All subjects' DXA characteristics, such as their total mass, lean mass, fat mass, T value, and relative skeletal muscle index (RSMI), were also noted. Based on RSMI, the patients were separated into two groups: those with sarcopenia and those without. An analysis was conducted on the variations in grip strength, CC, DXA parameters, and demographic data between the two groups. The relationship between a number of variables and RSMI was investigated using bivariate correlation analysis. The link between each index and RSMI was examined using both univariate and multiple linear regression analysis, and a regression equation was produced. Results:The study revealed that the sarcopenia group had significantly reduced BMI, grip strength, CC, RSMI, T value, total mass, lean mass, and fat mass compared to the non-sarcopenia group (P<0.05). Weight, fat mass, and CC had moderate correlations with RSMI (r=0.696, r=0.507, r=0.638, respectively, P < 0.05); T value and grip strength had weak correlations with RSMI (r=0.280, r=0.265, respectively, P < 0.05); BMI, total mass, and lean mass had strong correlations with RSMI (r=0.736, r=0.726, r=0.782, respectively, P < 0.05). The results of multiple linear regression analysis indicated that BMI (r=0.120, P<0.001) and CC (r=0.078, P<0.001) were the key variables linked to the muscle mass of postmenopausal women. We have RSMI = 0.473 + 0.120×BMI + 0.078×CC as the regression equation. Conclusions: Compared to patients without sarcopenia, people with sarcopenia have lower BMIs, grip strengths, CCs, T values, total masses, lean masses, and fat masses. In postmenopausal women, there is a positive correlation between muscle mass and BMI and CC.
... Existing evidence points to gender-specific variations in muscle composition and physiology, particularly sex hormones and the prevalence of type I (slow-twitch) muscle fibers, which could respond differently to alterations in sleep patterns, impacting muscle health (Kamei et al., 2004;Kim et al., 2018;Lucassen et al., 2017). Nonetheless, it is imperative to note that the complex interplay among sleep duration, gender, age, and sarcopenia risk is influenced by an array of factors encompassing lifestyle, genetics, hormonal variances, and individual health conditions, wherein identifying individuals' sleep behavior stages facilitates tailored interventions (Chen et al., 2014;Messier et al., 2011). Moreover, encouraging better sleep practices and optimizing sleep quality and duration in specific groups might mitigate factors contributing to sarcopenia development or progression, potentially enhancing muscle health and reducing the prevalence of this condition. ...
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Background The purpose of this study was to examine the relationship between sleep duration and risk of sarcopenia in in general U.S. population. Methods Utilizing publicly available data from the National Health and Nutrition Examination Survey spanning from 2011 to 2014, we explored the association between sleep duration and prevalence of sarcopenia. To investigate their relationship, we conducted weighted multivariate logistic regression analysis, restricted cubic splines (RCS) curve, and subgroup analysis. Results The study included 8,200 individuals, among whom 99 (0.9 %) had sarcopenia. The RCS curve revealed a U-shaped association of sarcopenia with sleep duration (P for nonlinearity = 0.020), showing that the risk of sarcopenia decreases with increasing sleep duration, reaching the lowest risk around 6.67 h. After controlling for underlying cofounders, compared to individuals with sleep duration < 5 h, the odds ratios with 95 % confidence intervals of sarcopenia were 0.64 (0.27, 1.49), 0.50 (0.20, 1.26), 0.65 (0.27, 1.60), and 2.31 (0.73, 7.30) for < 5–6, 6.5–7.5, 8–9, and > 9 h group. The U-shaped association between sleep time and prevalence of sarcopenia also was observed in the subjects who aged < 40 or ≥ 40 years, were male or female, with or without hypertension, and diabetes mellitus. Conclusions In summary, both short and long sleep durations increased prevalence of sarcopenia. Further studies are needed to explore the underlying mechanisms.
... The decrease in estrogen levels in menopausal women is associated with a decline of bone mineral density (BMD), muscle mass, and strength [10]. This is especially relevant for women with an increased risk of ovarian cancer, who are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO) at a young age [11] which may therefore result in earlier diagnosis of osteoporosis and sarcopenia [12,13]. ...
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Objective The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis of sarcopenia. Methods Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute. Results The 34 participants had a median age of 58 years (IQR 53–65) and a median body mass index of 24.6 (IQR 21.7–29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994–0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996–0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993–0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5–3.0 mSv, for DXA this was 2–4 µSv. Conclusions DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass. Trial registration Netherlands Trial Register; NL8068. Critical relevance statement DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low. Key points • Screening for sarcopenia should be optimized as the population ages. • DXA outperformed CT and MRI in the measured metrics. • DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation. Graphical Abstract
... Female reproductive characteristics are closely associated with changes in estrogen levels. Studies have suggested that decreased estrogen levels may negatively impact skeletal muscle mass (Messier et al., 2011). Iannuzzi-Sucich et al. discovered a strong positive correlation between muscle mass and plasma estrogen levels in women (Iannuzzi-Sucich et al., 2002). ...
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Background: The impact of female reproductive factors, including age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy abortion (PA), on the risk of developing frailty remains uncertain. Our objective is to examine the potential causal relationship between female reproductive traits and frailty through the utilization of two-sample univariable Mendelian Randomization (UVMR) and multivariable Mendelian Randomization (MVMR) analyses. Methods: Leveraging large-scale Genome-Wide Association Study (GWAS) data from individuals of European ancestry, we performed two-sample UVMR and MVMR analyses to examine the causal relationship between female reproductive traits and frailty. The primary analysis employed inverse-variance-weighted (IVW) estimation, and sensitivity analyses were conducted to assess the robustness of the findings. Results: The UVMR analysis revealed a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty [IVW: OR = 0.74, 95%CI(0.70–0.79), p = 0.000; OR = 0.93, 95%CI(0.92–0.95), p = 0.000; OR = 0.96, 95%CI(0.95–0.98), p = 0.000]. However, there was no significant effect of ANM and PA on frailty (p > 0.05). The sensitivity analysis results were robust, supporting the findings. Furthermore, this association remained significant even after adjusting for body mass index (BMI) and educational attainment (EA) in the MVMR analysis [IVW: OR = 0.94, 95%Cl (0.91–0.97), p = 0.000; OR = 0.77, 95%Cl (0.70–0.86), p = 0.000; OR = 0.95, 95%Cl (0.94–0.97), p = 0.000]. BMI and EA serve as mediators in this process. Conclusion: Our research has established a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty, with BMI and EA acting as mediating factors in this process. However, further research is warranted to validate our findings and elucidate the underlying biological mechanisms.
Article
Objective To investigate the effects of 12-week weight-bearing dance aerobics (WBDA) on muscle morphology, strength and functional fitness in older women. Methods This controlled study recruited 37 female participants (66.31y ± 3.83) and divided them into intervention and control groups according to willingness. The intervention group received 90-min WBDA thrice a week for 12 weeks, while the control group maintained normal activities. The groups were then compared by measuring muscle thickness, fiber length and pennation angle by ultrasound, muscle strength using an isokinetic multi-joint module and functional fitness, such as 2-min step test, 30-s chair stand, chair sit-and-reach, TUG and single-legged closed-eyed standing test. The morphology, strength, and functional fitness were compared using ANCOVA or Mann-Whitney U test to study the effects of 12 weeks WBDA. Results Among all recruited participants, 33 completed all tests. After 12 weeks, the thickness of the vastus intermedius ( F = 17.85, P < 0.01) and quadriceps ( F = 15.62, P < 0.01) was significantly increased in the intervention group compared to the control group, along with a significant increase in the torque/weight of the knee flexor muscles ( F = 4.47, P = 0.04). Similarly, the intervention group revealed a significant improvement in the single-legged closed-eyed standing test ( z = − 2.16, P = 0.03) compared to the control group. Conclusion The study concluded that compared to the non-exercising control group, 12-week WBDA was shown to thicken vastus intermedius, increase muscle strength, and improve physical function in older women. In addition, this study provides a reference exercise program for older women.
Article
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Article
The composition and biochemistry of skeletal muscle are altered in obesity and type 2 diabetes mellitus (DM) as compared to nonobese individuals. In health, skeletal muscle has a clear capacity to utilize both carbohydrate and lipid fuels and to transition between these in response to hormonal, chiefly insulin, and substrate signals. This metabolic flexibility is key for the major role that skeletal muscle can have in overall fuel balance. In obesity and type 2 DM, there is a loss of this plasticity and, instead, there is metabolic inflexibility. Rates of lipid oxidation do not suppress effectively in response to insulin, but neither do rates of lipid oxidation effectively increase during the transition to fasting conditions. An important morphological characteristic of skeletal muscle in obesity and type 2 DM is an increased content of triglyceride. The accretion of fat within muscle tissues appears to strongly correlate with insulin resistance and may not be simply a passive process, paralleling fat storage in other tissues. Instead, and of particular metabolic interest, a concept is emerging that biochemical characteristics of skeletal muscle in obese individuals dispose to fat accumulation in muscle. An effort to modify skeletal muscle in individuals with obesity and type 2 DM so that the capacity for fat oxidation and metabolic flexibility is improved should be among the goals of treatment for these disorders.
Article
Sarcopenia is defined by loss of muscular mass, strength and quality that occurs in elderly. It has become an important area of research because of its frequency and its responsibility for a significant part of the mobility disability in older people. Understanding and treating sarcopenia could probably have a dramatic impact on the disability process. A definitive consensual clinical method to assess sarcopenia is still needed in everyday clinical practice and clinical research. The different characteristics that define sarcopenia are usually studied separately. The loss of muscular mass and muscle strength is mainly caused by low physical activity, aged-related changes in steroids hormones and inflammatory processes. Treatment relies on a multidimensional approach. Preventing loss of muscle mass and preserving muscle strength is relevant if it prevents decline in physical performance and mobility disability. Identifying target elderly populations for specific treatment in clinical trial is an important issue. To date strength training is the only efficient approach to treat and prevent sarcopenia. So far, no pharmacological treatment has proven definitive evidence to treat or prevent sarcopenia. On-going and future pharmacological clinical trials may radically change our therapeutic approach of mobility disability in elderly. The endpoint prevention of mobility disability should be added to the well-established outcomes of treatment of the loss of muscular mass, muscle strength or muscle quality.
Article
Objective: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional distribution of fat and lean body mass. Research Methods and Procedures: Sixteen healthy postmenopausal women (age: 55 ± 3 years) were studied in a placebo-controlled, crossover study and were randomized to 17β estradiol plus cyclic norethisterone acetate (HRT) or placebo in two 12-week periods separated by a 3-month washout. Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods. Changes were compared by a paired Student's t test. Results: The change in body weight during HRT was equal to the change during placebo (−24.6 g vs. −164 g, p = 0.42), but relative fat mass was significantly reduced (−0.5% vs. +1.24%, p < 0.01). During HRT, compared with during placebo, lean body mass increased (+347 g vs. −996 g, p < 0.01) and total fat mass decreased (−400 g vs. +836 g, p = 0.06). Total bone mineral content increased (+28.9 g vs. −4.4 g, p = 0.04) and abdominal fat decreased (−185 g vs. +253 g, p = 0.04) during HRT compared with placebo. Discussion: HRT is linked to the reversal of both menopause-related obesity and loss of lean mass, without overall change in body weight. The increase in lean body mass during HRT is likely explained by muscle anabolism, which in turn, prevents disease in the elderly.
Article
One common approach to preventing or delaying age-related disorders is to supplement falling hormone levels. Animal studies give some evidence that dehydroepiandrosterone (DHEA) lessens age-related changes in body composition and has beneficial effects on diabetes and cardiovascular disease, but rodents-unlike humans-have very low DHEA levels. Whether or not to give supplemental testosterone to elderly men also is unsettled. This randomized 2-year placebo-controlled, double-blind study enrolled 87 men aged 60 years and older having low levels of sulfated DHEA and bioavailable testosterone, and 57 elderly women with low levels of sulfated DHEA. The men received 75 mg of DHEA daily in tablet form, 5 mg of testosterone daily via transdermal patch, or an appropriate placebo for 2 years. The women received either a 50-mg DHEA tablet daily or a placebo tablet. There were no major group differences at baseline. DHEA recipients had significant increases in levels of sulfated DHEA and estradiol, and treated women had increased total testosterone levels. Both bioavailable and total testosterone increased significantly in testosterone-treated men compared with placebo recipients. DHEA did not significantly alter gonadotropin levels in men or women, but lower levels were found in testosterone-treated men. Neither treatment significantly altered fasting plasma glucose levels or insulin sensitivity. Both men and women given DHEA had significant reductions in levels of high-density lipoprotein cholesterol. In men and women combined, those given DHEA had a slight but significant rise in fat-free mass and a reduction in proportion of body fat. Fat-free mass also increased in men given testosterone. Measures of muscle strength remained unchanged. Small increases in bone mineral density were noted at some but not all sites with both active treatments. Neither treatment significantly altered quality of life as reflected by scores on the Physical Component and Mental Component scales of the Health Status Questionnaire. Neither treatment altered prostate volume, liver function, or levels of electrolytes or hemoglobin. In this study, neither DHEA nor low-dose testosterone had physiologically meaningful beneficial effects on body composition, physical performance, or quality of life in elderly men or women. The investigators strongly recommend that these treatments not be used as anti-aging measures.
Article
Background: Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17beta-estradiol. Methods and results: The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography. Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL x min(-1) x 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P:<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/-0.3 micromol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17beta-estradiol caused similar vasodilation to genistein. Responses to genistein and 17beta-estradiol were inhibited to the same degree by the NO synthase inhibitor N:(G)-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. Conclusions: Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17beta-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.