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CLIMACTERIC 2012;15:419–429
REVIEW Received 12-06-2012
© 2012 International Menopause Society Revised 23-06 -2012
DOI: 10.3109/13697137.2012.707385 Accepted 25-06 -2012
Correspondence: Professor S. R. Davis, Women ’ s Health Research Program, Department of Epidemiology and Preventive Medicine, Monash University,
Melbourne 3004, Austr alia
Understanding weight gain at menopause
S. R. Davis , C. Castelo-Branco
*
, P. Chedraui
†
, M. A. Lumsden
‡
, R. E. Nappi
*
*
, D. Shah
† †
and P. Villaseca
‡ ‡
as the Writing Group of the International Menopause Society for World Menopause Day 2012
Women ’ s Health Research Program, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne,
Australia;
*
Unit of Endocrinological Gynaecology, Department of Gynaecology, ICGON, Hospital Clínic de Barcelona, Universitat
de Barcelona, IDIBAPS, Barcelona, Spain;
†
Institute of Biomedicine, Facultad de Ciencias M é dicas, Universidad Cat ó lica de
Santiago de Guayaquil, Guayaquil, Ecuador;
‡
Head of Reproductive & Maternal Medicine, School of Medicine, University of
Glasgow, Scotland, UK;
*
*
Research Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, IRCCS S.
Matteo Foundation, University of Pavia, Italy;
† †
Department of Obstetrics and Gynecology, Breach Candy Hospital and Research
Center, Jaslok Hospital and Research Center, Sir Hurkisondas Hospital and Research Center, Mumbai, India;
‡ ‡
Department of
Endocrinology, Faculty of Medicine, Pontifi cia Universidad Cat ó lica de Chile, Santiago, Chile
Key words: MENOPAUSE , OBESITY , WEIGHT GAIN , ESTROGEN
ABSTRACT
Objective The aim of this review was to summarize the literature regarding the impact of the menopause
transition on body weight and body composition.
Methods We conducted a search of the literature using Medline (Ovid, 1946 – present) and PubMed
(1966 – 2012) for English-language studies that included the following search terms: ‘ menopause ’ , ‘ midlife ’ ,
‘ hormone therapy ’ or ‘ estrogen ’ combined with ‘ obesity ’ , ‘ body weight ’ or ‘ body composition ’ .
Results Whereas weight gain per se cannot be attributed to the menopause transition, the change in the
hormonal milieu at menopause is associated with an increase in total body fat and an increase in abdominal
fat. Weight excess at midlife is not only associated with a heightened risk of cardiovascular and metabolic
disease, but also impacts adversely on health-related quality of life and sexual function. Animal and human
studies indicate that this tendency towards central abdominal fat accumulation is ameliorated by estrogen
therapy. Studies mostly indicate a reduction in overall fat mass with estrogen and estrogen – progestin therapy,
improved insulin sensitivity and a lower rate of development of type 2 diabetes.
Conclusion The hormonal changes across the perimenopause substantially contribute to increased abdomi-
nal obesity which leads to additional physical and psychological morbidity. There is strong evidence that
estrogen therapy may partly prevent this menopause-related change in body composition and the associated
metabolic sequelae. However, further studies are required to identify the women most likely to gain metabolic
benefi t from menopausal hormone therapy in order to develop evidence-based clinical recommendations.
INTRODUCTION
For women aged 55 – 65 years, weight gain is one of their
major health concerns
1 . This is understandable as obesity is
one of the most common nutrition-related disorders globally,
and its prevalence is increasing. World-wide, the prevalence
of obesity has more than doubled since 1980. In 2008, 1.5
billion adults, 20 years and older, were overweight (body
mass index (BMI) 25 – 29.9 kg/m
2 ), including both developed
and developing countries. Of these, over 200 million men and
nearly 300 million women were obese (BMI ⬎
⫺ 30 kg/m
2 )
2 .
Moreover, the rates of obesity have increased notably in
developing countries adopting a Western lifestyle (decreased
physical activity and overconsumption of cheap, energy-dense
food). The sharp increase in overweight and obesity rates
observed in the last 20 years is dependent on, or controlled
by, several factors and is only in part attributable to changes
in lifestyle.
The deleterious effects of obesity are diverse, ranging from
an increased risk of premature death to several non-fatal dis-
eases with an adverse impact on quality of life. Obesity is a
major risk factor for diabetes mellitus and the cardiovascular
diseases, coronary heart disease, infarction, stroke, and hyper-
tension
2 . However, the relationship between obesity and meta-
bolic disease is complex. There is increasing recognition of a
metabolically healthy but obese phenotype, observed in about
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Understanding weight gain at menopause Davis et al.
420
9% of obese men and 16% of obese women
3 . The lower rate
of cardiometabolic abnormalities in metabolically healthy
obese individuals is not explained by diet composition or level
of physical activity, highlighting the importance of a genetic
contribution to the predisposition to the co-morbidities of
obesity
4 . Obesity is also a major risk factor for urinary incon-
tinence, dementia, some cancers (endometrial, breast and
colon) and musculoskeletal disorders, especially osteoarthritis,
a highly disabling degenerative disease of the joints
2 .
Obesity has substantial psychosocial consequences. Depres-
sion and depressive symptoms are common among obese
patients. As increasingly evidenced in the literature, obesity
substantially affects health-related quality of life (HRQOL)
5 – 7 .
It affects physical competence, appearance, self-esteem and
social functioning. There are no clear differences between
gender and ethnicity in these outcomes.
In general, obesity is characteristically more prevalent in
females than in males. Several explanations have been pro-
posed to explain this sex difference in obesity; however, none
have been conclusive. Fluctuations in sex hormones at differ-
ent stages of reproductive life, such as menarche, pregnancy,
and menopause transition, may play a role in the adipose tis-
sue expansion.
The menopause transition begins with the onset of men-
strual irregularities and ends with the last menstrual period.
Numerous studies have demonstrated that the menopausal
transition is associated with unfavorable changes in body
composition, abdominal fat deposition and general health
outcomes; for this reason, it is mandatory to investigate the
changes in these risk factors during the menopausal transition.
This review summarizes and discusses the contribution of the
menopause transition to obesity in women.
METHODS
The literature was searched using Medline (Ovid, 1946 – present)
and PubMed (1966 – 2012) for English-language studies that
included the following search terms: ‘ menopause ’ , ‘ midlife ’ ,
‘ hormone therapy ’ or ‘ estrogen ’ combined with ‘ obesity ’ ,
‘ body weight ’ or ‘ body composition ’ .
IS WEIGHT GAIN AT MIDLIFE A CONSEQUENCE
OF MENOPAUSE OR AGING?
The studies that have focussed on the question of whether
midlife weight gain is simply a function of age or due to the
hormonal changes that occur in relation to menopause have
concluded that the steady weight gain of about 0.5 kg annu-
ally is due to age rather than the menopause itself
8 – 10 . These
include both cross-sectional comparisons of weight in women
of similar chronological age but varying menopausal status
(premenopause, perimenopause and postmenopause) and lon-
gitudinal studies that have examined the rate of weight change
and the impact of menopausal status and hormonal change.
In addition, consideration of both ethnicity and physical
activity is important since these have a profound effect on
both obesity and fat distribution
11 – 13 .
The Study of Women ’ s Health Across the Nation (SWAN)
included fi ve ethnic groups in the US: Caucasians, African-
Americans, Hispanic, Chinese and Japanese
14 . In a telephone
survey of 16 000 study participants, no difference in self-
reported BMI was found between premenopausal and post-
menopausal women, adjusting for age and other covariants
15 .
This result was confi rmed in a small cross-sectional study of
energy expenditure, body composition and menopausal status
conducted as part of the SWAN, which also considered impact
of ethnicity. This sub-study reported that the median weight
of the Chinese pre- and early postmenopausal women was not
statistically different from that of the late perimenopausal and
postmenopausal women
16 . The median weight of the white
women in the study was signifi cantly greater than that of the
Chinese, and it also did not differ by menopausal status.
The mean weight gain over 3 years in the SWAN cohort as a
whole was 2.1 kg, but was unrelated to menopausal status
8 .
In summary, weight gain does not appear to be affected by
the hormonal changes of the menopause.
EFFECTS OF LOSS OF OVARIAN HORMONE
PRODUCTION ON WEIGHT AND
BODY COMPOSITION
Findings from animal models
Studies in animal models indicate that changes in the hor-
monal milieu at menopause contribute to changes in body
composition and fat distribution. Studies in mice have dem-
onstrated that the loss of ovarian function promotes a diet-
independent increase in adipose tissue mass and associated
metabolic pathologies
9 . Several studies have shown that
oophorectomy results in obesity in mice
17,18 . Oophorecto-
mized mice exhibit decreased energy expenditure, without
concomitant change in energy intake, resulting in adipocyte
hypertrophy, adipose tissue infl ammation and the develop-
ment of fatty liver
17 . However, when supplemented with
17 β -estradiol, oophorectomized mice are protected from
developing hepatic steatosis and insulin resistance
18 . In this
model, estradiol supplementation also protected against
adipocyte hypertrophy and adipose tissue oxidative stress and
infl ammation
18 . That central fat accumulation is a conse-
quence of estrogen defi ciency is also supported by studies of
aromatase gene knock-out (ArKO) mice, which cannot
synthesize endogenous estrogens. Female ArKO mice exhibit
obesity by as early as 3 months of age, which is characterized
by marked increases in the gonadal and infra-renal fat pads
19 .
This increased adiposity is not simply due to hyperphagia or
reduced resting energy expenditure but, as in oophorecto-
mized mice, is associated with reduced energy expenditure
due to reduced physical activity
20 . Studies of female mice with
total body deletion of the estrogen receptor- α (ER α ) (ER α -
knock-out mice), have reported similar fi ndings
21 . Estradiol
replacement in female ArKO mice primarily results in reduced
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Understanding weight gain at menopause Davis et al.
Climacteric 421
adipocyte volume with little change in factors that control
de novo adipocyte fatty acid synthesis, suggesting that changes
in the uptake of lipids from the circulation are the main mech-
anisms by which estradiol regulates fat accumulation
19 .
In addition to estrogen defi ciency being associated with
reduced energy expenditure, there is also evidence from ani-
mal models that estrogen is important for feeding behaviors
and meal size
21 . Estrogen may have direct actions through
ER α or act indirectly to decrease orexigenic peptides and
decrease food intake, as reviewed in detail by Brown and
Clegg
21 .
Taken together, the available data from animal models
indicate that estrogen depletion favors central abdominal fat
accumulation, and studies in animals indicate that this is
ameliorated by estrogen therapy.
Findings from human studies
The prevalence of abdominal obesity is almost double that of
general obesity, with rates in the US in 2008 of 65.5% in
women aged 40 – 59 years and 73.8% in women aged 60 years
or more
22 . It has been suggested that BMI but not menopausal
status determines central adiposity in postmenopausal women.
However, there is substantial evidence that the perimenopause
is associated with a more rapid increase in fat mass and redis-
tribution of fat to the abdomen, resulting in a transition from
a gynoid to an android pattern of fat distribution and an
increase in total body fat
11 . Studies using a range of radiologi-
cal modalities have shown that postmenopausal women have
greater amounts of intra-abdominal fat compared to pre-
menopausal women
23,24 . Waist circumference represents both
subcutaneous and visceral adipose tissue depot size and cor-
relates closely with cardiovascular disease risk. In women, it
is also closely associated with dyslipidemia
25 . The waist-to-
hip ratio is another indicator of accumulation of visceral fat
which can also be quantitated by CT scanning
26 .
Abdominal fat can be considered an endocrine organ due
to its capacity to secrete adipokines and other substances that
are closely associated with metabolic diseases such as insulin
resistance, type 2 diabetes and the metabolic syndrome
27 .
Aging and the menopause transition are each associated with
changes in adipose tissue metabolism, which may contribute
to the accumulation of body fat after menopause
28 .
Deleterious changes in infl ammatory markers and adipo-
kines correlate strongly with increased visceral adiposity at
menopause
29 . The transport protein, serum sex hormone
binding globulin (SHBG), is a strong independent marker of
insulin resistance
30 – 32 and type 2 diabetes risk
33 and has been
increasingly implicated in the pathogenesis of type 2 diabetes
and cardiovascular disease
33 – 35 . SHBG levels in postmeno-
pausal women are negatively correlated with visceral fat
26,36
and an adverse adipokine profi le
37 . Importantly, the relation-
ship between SHBG and insulin resistance in postmenopausal
women is independent of both endogenous estrogens and
androgens
38 . Thus, a high waist circumference, indicating
accumulation of excessive central abdominal fat, and a low
SHBG level are independent predictors of metabolic disease
risk in postmenopausal women.
A signifi cant change in waist circumference in relation to
fi nal menstrual period has been observed
39 and signifi cant
increases in central abdominal fat have been reported from
longitudinal studies of Caucasian and Asian women
40,41 .
Signifi cant increases in total fat mass, percentage fat mass,
truncal fat mass and visceral fat have been seen in non-obese
premenopausal women followed over several years
40 . The
women who became perimenopausal or postmenopausal by
the third follow-up year showed a signifi cant increase in
visceral fat ( p ⬍ 0.01) compared with baseline. Weight circum-
ference and fat mass (measured by bio-electrical impedance)
have also been observed to increase in relation to the fi nal
menstrual period
42 . These changes occurred similarly in both
African-American and Caucasian women.
Within Asia, different ethnic groups exhibit different levels
of insulin resistance, and ethnicity modifi es the relationship
between insulin resistance and type 2 diabetes that is related
to an increase in central adiposity
43,44 and possibly decreased
activity
43 . Women of Indian origin have a signifi cantly ele-
vated risk of type 2 diabetes but the impact of menopause
itself on this risk is unclear. Studies of the menopause transi-
tion and changes in body composition in Chinese women
suggest that the menopause has an independent effect on
the increase in fat mass as well as an increase in central
adiposity
41 .
Consistent with weight gain primarily being infl uenced by
age, not menopause, the published literature does not support
an adverse effect of spontaneous premature ovarian failure
(POF) on body weight and, in general, women with POF tend
to be leaner
45 . However, data pertaining to fat distribution in
women with spontaneous POF are lacking. Central obesity is
common in women with premature ovarian failure due to
Turner syndrome. The distinct anthropometrical composition
of women with Turner syndrome is associated with higher
BMI and waist-to-hip ratio, as well as increased fat mass,
central adiposity and liver adiposity when compared with age-
matched normal controls
46 . Even so, Turner syndrome patients
show a different metabolic pattern than that seen in natural
menopause: they frequently have abnormal glucose tolerance
and high triglycerides, but with decreased insulin secretion
instead of the expected hyperinsulinemia. It is speculated that
these women may have impaired pancreas β -cell function,
hypothetically due to the involvement of still unknown
X-chromosome genes
47 .
OTHER FACTORS INFLUENCING WEIGHT
GAIN IN MIDLIFE
Obesity is substantially infl uenced by genetic, demographic, social
and behavioral factors. Globally, obesity in women is inversely
associated with poorer education and urbanization
48,49 . Other
factors that have been found to signifi cantly predict obesity
in women include a low level of activity, parity, family his-
tory of obesity and marriage at earlier age
48 . Although
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Understanding weight gain at menopause Davis et al.
422
traditionally obesity has been related to food intake and activ-
ity, there is increasing evidence that disruption of circadian
rhythms and timing of food intake, as seen with shift work,
and sleep deprivation may contribute to weight gain
50 .
Although it seems intuitive that factors such as skipping
breakfast, daily eating frequency, snacking, irregular meals,
eating away from home, consumption of fast food, take-away
food intake, consumption of large food portions and eating
until full might predict obesity, the literature in this area
remains inconclusive due to methodological discrepancies
between studies
51,52 .
Obesity is associated with psychological distress and low
self-esteem and there is evidence for obesity predicting devel-
opment of depression. However, intrapersonal and contex-
tual factors may confound the relationship between obesity
and depression due to the variable perception of body image
issues by women according to culture. Furthermore, a spec-
trum of depression can be increased food intake and
decreased physical activity
53 and women who experience
depression tend to gain more weight across adulthood
54 .
Most population-based studies report an association between
obesity and depression
55 and a bidirectional relationship has
been found in women between depression and type 2 diabe-
tes
56 . The perimenopause is associated with a higher vulner-
ability to depression, with the risk increasing from early to
late perimenopause and decreasing during postmenopause
57 .
Weight gain and increased BMI have been related to anxiety
and depression and low life satisfaction during the meno-
pause transition
58,59 .
Diverse psychotropic drugs are also associated with
weight gain, with negative metabolic consequences. Second-
generation antidepressants are the mainstay of management
of major depression. These include selective serotonin
reuptake inhibitors (SSRIs), serotonin and norepinephrine
reuptake inhibitors (SNRIs), and other drugs with related
mechanisms of action that selectively target neurotransmit-
ters. Some SSRIs and SNRIs are more associated with weight
gain than others. Other commonly used psychotropics
associated with weight gain include clozapine, imipramine,
and amitriptyline
60 . These drugs have been found to up-
regulate sterol regulatory element-binding proteins, which are
involved in cellular cholesterol and fatty acid biosynthesis
71 .
In contrast, the antidepressants which in general are not
associated with weight gain, ziprasidone and buproprion,
have little effect on these proteins
60 .
Many studies have provided evidence that weight gain is
common during chemotherapy. There is consistency in the
observation of a signifi cant change in body composition with
an increase in total body fat and in abdominal and visceral
adiposity, while lean mass stays unchanged or slightly
decreases
61 . These changes are not attributable to a change in
resting energy expenditure
61 . Decreased voluntary energy
expenditure, not increased food intake, appears to contribute
to the observed weight gain
61 . Women who experience ovar-
ian failure during treatment have signifi cantly more weight
gain than those who remain premenopausal
62 , with greater
gains observed in truncal fat
63 .
DOES OBESITY OR WEIGHT GAIN ALTER
THE MENOPAUSE TRANSITION?
When analyzing weight increase during the menopausal tran-
sition, there are two important considerations: fi rst, the effect
of body weight over the course of the transition, including its
effect on age at natural menopause (ANM), and, second, its
effect on menopausal symptoms.
Excessive body weight and age at
natural menopause
It is well established that obesity may be associated with
altered menstrual cycle length and hormone patterns in
premenopausal women, with longer cycles due to increase in
length of the follicular phase. The rate of premenopausal BMI
increase and premenopausal episodic weight loss of more than
5 kg have been independently associated with a later ANM
64 .
A later ANM has also been associated with being a non-
smoker, higher adult weight, higher BMI, greater alcohol
consumption, regular strenuous exercise and not being
vegetarian
65 . In contrast, premenopausal smoking and type
2 diabetes predict an earlier ANM.
Longitudinal studies indicate that the greater the BMI, the
later the ANM
66 . In the Penn Ovarian Aging Study, there was
a positive association between BMI and the odds of transi-
tioning from pre- to perimenopause but not from peri- to
postmenopause
67 .
The ANM is determined by genetic factors. There are
several possible pathways and genomic regions which have
been associated with ANM. Nevertheless, fi ndings to date are
not conclusive. That obesity is in part genetically determined
is known. Enzymes involved in steroid production such as
aromatase and type 1 17 β -hydroxysteroid dehydrogenase
(HSD) can exert infl uence over estradiol levels during the
menopausal transition, particularly in obese women. The
decline in estradiol is more rapid in non-obese women
68 . For
obese women, selected variations in the aromatase gene and
type 1 17 β -HSD gene result in different estradiol trajectories
around the fi nal menstrual period and, hence, different
postmenopausal estradiol levels
68 . Thus, genetic factors may
link both ANM and BMI.
In conclusion, there is a potential circular relationship
between adiposity and the menopause. It seems that there is
a substantial effect of obesity and adiposity on the magnitude
of the hormonal changes experienced during the transition.
Nevertheless, there are other factors aside from BMI infl uencing
the ANM which may be more relevant such as genetic
predisposition, intrauterine development and subclinical
ovarian pathology.
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Understanding weight gain at menopause Davis et al.
Climacteric 423
Effect of increased weight during the menopausal
transition over menopausal symptoms
The prevalence and severity of menopausal symptoms depend
on several factors. These include not only the hormonal
changes imposed by the transition, but also psychosocial fac-
tors. During the menopausal transition, as weight increases
so do menopausal symptoms. Obesity is an independent risk
factor for more severe menopausal symptoms
69 – 71 .
Obesity and menopausal bone loss
Obese women appear to lose bone at a lower rate than non-
obese women across the menopause transition
72 . However,
the relationship between osteoporosis, fracture risk and
excessive BMI is complex. Low BMI has been associated
with osteoporosis and women with long-standing obesity
have been observed to be less at risk for osteoporosis and
fracture
73 . These views have recently been challenged by the
results provided by the Global Longitudinal study of
Osteoporosis in Women
74 . This study included 60 393
women ⬎
⫺ 55 years from ten countries and assessed patient
characteristics, fracture history, fracture risk factors, and
anti-osteoporosis medications. Using fracture as the endpoint,
the risk of incident ankle and upper leg fractures was
signifi cantly higher in obese women, while the risk of wrist
fracture was signifi cantly lower. Obese women with fracture
were more likely to have experienced early menopause and
to report two or more falls in the past year. In this population,
self-reported co-morbid conditions were highly prevalent,
including asthma, emphysema, and type 1 diabetes, and
more common in obese women with incident fracture. These
data clearly suggest that obesity is not protective against
fracture in postmenopausal women
74 .
Impact of weight gain on psychosexual well-being
at menopause
Apart from being at increased risk for a variety of chronic
diseases, overweight women may suffer from psychosocial
consequences, with a signifi cant impact on self-esteem and
general well-being
75 .
A review of eight studies examining HRQOL among women
aged over 55 years old concluded that obese postmenopausal
women have lower HRQOL in physical functioning, energy,
and vitality compared with normal-weight women
76 . Given
the evidence that mood disorders are one of the most impor-
tant co-morbid conditions of sexual dysfunction in postmeno-
pausal women, it is plausible that weight gain and obesity at
menopause may be risk factors for poor sexual functioning.
However, little is known of the specifi c impact of weight gain
on sexual function at menopause as a consequence of the
‘ domino ’ effect of other menopausal symptoms, especially
psychological symptoms. Indeed, loss of fi tness and weight
gain were not the sole factors infl uencing the intensity of
sexual complaints in a clinical sample of menopausal women
77 .
In peri- and postmenopausal women with urinary inconti-
nence, increased BMI early in menopause represents a risk not
only for urinary incontinence, but also for sexual dysfunction.
Arousal, orgasm, lubrication and satisfaction are inversely
correlated with BMI
78 .
Amongst obese postmenopausal women, the percentage of
women with sexual problems is greatest in those with
abdominal obesity
79 . Sexual well-being is adversely affected
by insulin-resistance and the metabolic syndrome
80 , and
sexual dysfunction is more prevalent in postmenopausal
women with metabolic syndrome in comparison with healthy
controls
81 . The third Princeton Consensus Conference reported
that women with the metabolic syndrome/obesity have more
sexual dysfunction than those without, and treatment of the
metabolic syndrome/obesity improves sexual function
82 .
Although cardiometabolic risk factors, diabetes, and coronary
heart disease are associated with more sexual dysfunction in
women, there are no data showing that sexual dysfunction is
a predictor of future cardiovascular events in women, as is
evident in men
82 .
That notwithstanding, there is a need for more research
into the association between female sexual health and vascular
risk factors.
Weight loss and menopausal symptom
improvement
Reductions in weight, BMI and abdominal circumference have
been associated with a reduction in vasomotor symptoms in
overweight and obese women
83 . The combination of dietary
modifi cation and exercise also has positive effects on HRQOL
and psychological health, which may be greater than that
from exercise or diet alone
84 . Improvements in weight, aerobic
fi tness and psychosocial factors may mediate some of the
effects of these interventions on HRQOL
84 . Weight loss in
overweight and obese women improves psychological well-
being, HRQOL, self-esteem and health practices
85,86 . In
addition, dietary weight loss and exercise exert a positive
effect over insulin resistance in postmenopausal women,
which together with a decrease in menopausal symptoms may
potentially decrease cardiovascular risk.
DOES MENOPAUSAL HORMONE THERAPY
AFFECT WEIGHT AND BODY COMPOSITION?
A Cochrane Review published in 2000 reported no evidence
of an adverse effect of estrogen-only or estrogen – progestin
therapy on body weight or BMI
87 . There has been no subse-
quent research that would challenge this conclusion.
The effects of estrogen therapy in postmenopausal women
on body composition vary, with most randomized, controlled
trials showing a reduction in central adiposity
88 – 91 and a few
not
92 . In a subsample of women participating in the Women ’ s
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Understanding weight gain at menopause Davis et al.
424
Health Initiative estrogen plus progestin (EPT) study, who had
body composition measurements at baseline and year 3, the
EPT intervention at 3 years signifi cantly helped to maintain
lean body mass and prevented a shift toward android fat dis-
tribution
90 . However, the size of the effect was small.
Although, overall, the effects of exogenous estrogen appear
to be favorable in terms of body composition, the route of
estrogen delivery may have subtle, but differing effects
93,94 .
Oral estrogen has been associated with a small but signifi cant
increase in fat mass and a decrease in lean mass, whereas lean
body mass and fat mass do not change signifi cantly with
transdermal estradiol
93,94 . Neither route appears to alter vis-
ceral fat mass
93 . The differing effect of oral versus transdermal
estrogen therapy may relate to the differing effects of oral
versus transdermal estrogen on growth factors and substrate
oxidation. Oral estrogen, but not transdermal estrogen, is
associated with a signifi cant decline in circulating insulin-like
growth factor 1 (IGF-1)
95 – 98 . This appears to be due to oral
estrogen impairing hepatic IGF-I production, which then
causes increased secretion of growth hormone through reduced
feedback inhibition
99 . Divergent effects on fat mass have also
been seen for oral raloxifene and transdermal estradiol. In
growth hormone-replaced hypopituitary women, treatment
with transdermal estradiol was associated with a reduction in
fat mass. This effect was attenuated when the women were
treated with raloxifene
100 .
Despite the divergent effects of oral and transdermal estro-
gen noted above, improved insulin sensitivity has been
observed with oral EPT
92 , and both oral estrogen-alone and
EPT may reduce the incidence of type 2 diabetes
101 .
In summary, menopausal hormone therapy is not associated
with increased weight or increased visceral adiposity. Studies
mostly indicate a reduction in overall fat mass with estrogen
and estrogen – progestin therapy, improved insulin sensitivity
and a lower rate of development of type 2 diabetes.
STRATEGIES TO PREVENT/MANAGE
WEIGHT GAIN
Management strategies for weight reduction in obese
individuals include physical activity, calorie-controlled diet,
pharmacotherapy or bariatric surgery. Complementary and
alternative treatments such as acupuncture, yoga, and herbal
supplements may also aid in weight loss. These strategies may
be used alone or in combination for greater effi cacy.
Physical activity
Physical activity has an inverse relationship with weight and
waist circumference independent of aging and change in
menopausal status
11 . Hence, active midlife women have an
advantage as they approach menopause with a lower BMI,
lower fat mass, greater lean mass and less central obesity. Even
though physical activity may not entirely prevent weight gain
with age, it may protect against the development of obesity
14 .
Sixty minutes/day of moderate-intensity activity are essential
to maintain normal weight
102 . One unit increase in physical
activity score decreases 4 cm
2 of intra-abdominal fat
12 . There
is concern about loss of muscle and bone mass with weight
loss in older women. Resistance exercise has been shown to
preserve lean mass during weight loss
103 .
Calorie-controlled diet
Calorie restriction alone can elicit reduction in body weight,
total body and visceral fat, similarly to exercise. The addition
of exercise, with a weight loss of more than 5%, can reduce
risk factors for cardiovascular disease, such as dyslipidemia,
hypertension, and diabetes mellitus
104 .
Conventional diets are defi ned as those providing calories
below energy requirements but above 800 kcal/day
105 . Options
include balanced low-calorie diets, low-fat low-calorie diets,
moderate-fat low-calorie diets, low-carbohydrate diets, and
the Mediterranean diet. An important determinant of weight
loss is adherence to the diet, irrespective of the particular
macronutrient composition. A diet based upon patient prefer-
ences may improve long-term adherence.
Ideally, any calorie-restricted diet should result in the lowest
possible loss of protein, keeping the calories from fat to below
30% of total calorie intake. If a low-carbohydrate diet is chosen,
healthy choices for fat (mono- and polyunsaturated) and protein
(fi sh, nuts, legumes, and poultry) should be encouraged. If a
low-fat diet is chosen, increases in healthy carbohydrates (fi sh,
vegetables, whole grains) should be selected. It has been sug-
gested that low carbohydrates may be more effective for weight
loss than low-fat diets. However, weight losses at 6 months and
at 2 years have been found to be similar for diets with differing
carbohydrate and fat macronutrient contents
106 .
Pharmacotherapy
Anti-obesity medications are pharmacological agents that
reduce or control weight. These drugs act by suppressing
appetite and increasing satiety, increasing the metabolism of
the body and interfering with the body ’ s ability to absorb
specifi c nutrients in food
107 .
Orlistat, sibutramine and rimonabant have been studied in
trials of 1 year and longer. Attrition rates averaged 30 – 40%,
limiting the validity of studies. All three anti-obesity agents
signifi cantly achieved 5 – 10% weight loss and had differing
effects on cardiovascular risk and adverse effect profi les.
At present, only one anti-obesity medication, orlistat (gas-
trointestinal lipase inhibitor) is currently approved for long-
term use. Sibutramine and rimonabant have been withdrawn
due to side-effects, including myocardial infarction, stroke
and serious psychiatric disorders, respectively
108 . Herbal
products have been used as supplements to aid weight loss
but have not been found to be signifi cantly effective
109 . Weight
loss with pharmacological intervention is not sustained when
therapy is discontinued.
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Understanding weight gain at menopause Davis et al.
Climacteric 425
Metformin, a drug approved for treatment of diabetes mel-
litus
110 , has been known to produce weight loss of 1 – 2 kg
over a 12-month period. Although metformin does not pro-
duce enough weight loss (5%) to qualify as a ‘ weight-loss
drug ’ , it is a useful choice for overweight individuals who
have diabetes or are at high risk for diabetes
111 .
Bariatric surgery
Bariatric surgery is a clinical and cost-effective intervention
for moderate to severely obese people compared to other
non-surgical interventions. The different surgical procedures
include gastric bypass, vertical banded gastroplasty, adjust-
able gastric banding, and laparoscopic sleeve gastrectomy.
In a systematic review of the effect of surgical versus non-
surgical options, a statistically signifi cant difference was seen
in fi ve out of six randomized, controlled trials. In two cohort
studies that reported the outcome at the end of 2 years,
signifi cant weight loss, varying between 16 and 28.6%, was
demonstrated as compared to the non-surgical group in
which there was weight gain. On comparison of different
surgical procedures, gastric bypass was found to be more
effective than vertical banded gastroplasty. No statistically
signifi cant difference was found in the amount of weight
loss and quality of life between open versus laparoscopic
surgery
112 .
Traditional health practices and medicines
Several studies of yoga among the middle-aged and elderly
have shown improved metabolic parameters
113 . Long-term
Hatha yoga practice is linearly associated with a decrease in
BMI
114 . An intensive yoga intervention helped to decrease
waist circumference and improve quality of life in overweight
and obese breast cancer survivors
115 . Yoga improves adi-
ponectin levels, serum lipids, and metabolic syndrome risk
factors in obese postmenopausal women. Consequently,
regular yoga practice may be effective in preventing cardio-
vascular disease caused by obesity
116 .
The effectiveness and safety of traditional Chinese
medicine, including Chinese herbal medicine (CHM) and
acupuncture, provide an alternative established therapy.
Acupuncture is believed to induce weight loss via its
regulatory effects on nerve and endocrine functions. Laser
acupuncture has been found to exert a therapeutic effect on
BMI and weight
117 .
A review of 96 randomized, controlled trials comprising
49 trials of CHM, 44 trials of acupuncture and three trials
of combined therapy has found that CHM and acupuncture
were more effective than placebo or lifestyle modifi cation
in reducing body weight. CHM and acupuncture were
found to have a similar effi cacy as anti-obesity drugs but
with fewer reported adverse effects. However, these conclu-
sions were limited by small sample size and low quality of
methodologies
118 .
In summary, various modalities are available for weight
loss in obesity. Lifestyle changes such as healthy diet, physical
activity and yoga are recommended for long-term results.
Bariatric surgery is accepted as an obesity surgery, with excel-
lent results related to weight loss and reduction in morbidity
due to metabolic syndrome. The use of acupuncture and
CHM merits further investigation. No effective and safe drug
is yet available for weight loss.
CONCLUSIONS
Obesity is a public health problem, with overweight individu-
als representing approximately 20% of the adult world popu-
lation
119 . Consistent fi ndings are that age, not menopause, is
the main determinant of weight gain at midlife, but that the
hormonal changes across the perimenopause substantially
contribute to increased central abdominal fat and abdominal
obesity. Abdominal obesity is not only associated with
increased cardiovascular and metabolic disease risk, and can-
cer, but also sexual dysfunction and poorer health-related
quality of life.
Weight control has an essential role in postmenopause
health and should be considered early in the perimenopause
to safeguard the quality of life of women. Weight loss
through diet and increased physical activity has been shown
to alleviate menopausal symptoms. Contrary to widespread
belief, menopausal hormone therapy is not associated with
weight gain and may ameliorate perimenopausal accumula-
tion of abdominal fat. Hormone therapy has also been asso-
ciated with lower rates of type 2 diabetes. In addition to
reducing food intake and increasing activity, interventions
including acupuncture and Chinese herbal medicine may be
benefi cial for weight loss. However, like dietary and activity
modifi cation, these approaches also require individual com-
mitment. As central weight gain with menopause is associ-
ated with the development of insulin resistance, there is
increasing interest in the use of metformin to ameliorate this
metabolic change and thus prevent or delay progression to
type 2 diabetes.
In summary, weight gain with age is a global sociodemo-
graphic issue that is not a consequence of the menopause. In
contrast, increased central abdominal fat appears to be a
direct consequence of the menopause. It may be prevented by
estrogen therapy and possibly by the use of metformin.
KEY POINTS
• Weight gain is a major health concern for women at
midlife.
• Weight gain per se does not appear to be affected by the
hormonal changes of the menopause.
• The fall in estrogen at menopause favors central abdomi-
nal fat accumulation.
• Other factors that may contribute to obesity in women
include a low level of activity, parity, lower level of
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Understanding weight gain at menopause Davis et al.
426
education, a family history of obesity, use of psychotropic
drugs and chemotherapy.
• In addition to the adverse physical consequences of obesity,
weight excess is a major risk factor for psychological dis-
tress, low self-esteem, depression and sexual dysfunction.
• Obesity is an independent risk factor for more severe
menopausal symptoms.
• Estrogen-only or estrogen – progestin therapy does not
adversely affect body weight and may ameliorate accu-
mulation of abdominal fat.
• Methods of weight loss must include increased exercise
and calorifi c control although this can be enhanced by
surgery, drug therapy and non-medical means.
• Metformin is a useful drug for selected overweight indi-
viduals who have diabetes or are at high risk for diabetes.
• Successful maintenance of weight loss involves lifestyle
change.
Confl ict of interest During the past 2 years, Professor S.
R. Davis has had a fi nancial relationship (member of advisory
boards and/or consultant or investigator) with Bayer-Schering
Pharma, Warner Chilcott, Biosante and Trimel Pharmaceuti-
cals; Professor R. E. Nappi has had a fi nancial relationship
(lecturer, member of advisory boards and/or consultant) with
Bayer-Schering Pharma, Eli Lilly, Merck Sharpe & Dohme,
Novo Nordisk, Pfi zer Inc; Professor P. Villaseca has had a
fi nancial relationship (member of advisory board) with Glaxo-
SmithKlein; Professor C. Castelo-Branco has had a fi nancial
relationship (lecturer and/or consultant or investigator) with
Pierre Fabre Labs, Merck Spain, Amgen and Isdin; Dr D. Shah
has had a fi nancial relationship (member of advisory board)
with Elder Pharmaceuticals, India. Professor M. A. Lumsden
is currently an advisor to Abbott Pharmaceuticals.
Source of funding Nil.
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