Maturitas 71 (2012) 248–256

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Maturitas
jo ur n al hom ep age :
w w w .e l s e v i e r . c o m / l o c a t e / m a t u r i t a s
Review

Sex hormones, appetite and eating behaviour in women

∗
Angelica Lindén Hirschberg
Department of Women’s and Children’s Health, Karolinska Institutet and Karolinska University Hospital, SE-171 76 Stockholm, Sweden

A R T I C L E I N F O A B S T R A C T

Article history: Sex hormones play essential roles in the regulation of appetite, eating behaviour and energy
Received 12 December 2011
metabolism and have been implicated in several major clinical disorders in women. Estrogen inhibits
Accepted 23 December 2011
food intake, whereas progesterone and testosterone may stimulate appetite. This review describes
recent findings concerning interactions between sex hormones and neuroendocrinological
mechanisms in the control of appetite and eating in women. Furthermore, we are gaining insights into the
Keywords:
roles played by sex hormones in the development of eating disorders and obesity. For instance,
Appetite
Eating disorders androgens may promote bulimia by stimulating appetite and reducing impulse control, a proposal
Obesity supported by the observation that antian- drogenic treatment attenuates bulimic behaviour.
Sex steroids Androgens are also involved in the pathophysiology of abdominal obesity in women. On the other
Weight hand, hormone replacement therapy with estrogen coun- teracts the weight gain and accumulation of
Women’s health abdominal fat associated with the menopausal transition. In conclusion, sex hormones and/or agents
that exhibit similar activities may provide novel strategies for the treatment of eating disorders and
android obesity, two of the most serious health problems for women today.
© 2012 Elsevier Ireland Ltd. All rights reserved.

Contents

1. Introduction............................................................................................................................................................................................................................ 249
2. Hormonal control of appetite and food intake.................................................................................................................................................................... 249
2.1. Central regulation of feeding.................................................................................................................................................................................... 249
2.2. Signals produced in response to a meal.................................................................................................................................................................. 249
2.3. Adiposity signals........................................................................................................................................................................................................ 249
2.4. Sex hormones............................................................................................................................................................................................................. 249
3. Regulation of normal eating in women by sex hormones.................................................................................................................................................. 250
3.1. During the various phases of the menstrual cycle..................................................................................................................................................250
3.2. Menopause.................................................................................................................................................................................................................. 250
3.3. Pregnancy and lactation............................................................................................................................................................................................ 251
4. The involvement of sex hormones in eating disorders and obesity.................................................................................................................................252
4.1. Anorexia nervosa....................................................................................................................................................................................................... 252
4.2. Bulimia nervosa.......................................................................................................................................................................................................... 252
4.3. Obesity......................................................................................................................................................................................................................... 252
5. Effects of treatment with sex hormones on appetite and body weight............................................................................................................................253
5.1. Oral contraceptives.................................................................................................................................................................................................... 253
5.2. Hormone replacement therapy................................................................................................................................................................................ 254
6. Conclusions............................................................................................................................................................................................................................. 255
Contributors........................................................................................................................................................................................................................................255
Competing interests.............................................................................................................................................................................................................. 255
Provenance and peer review................................................................................................................................................................................................ 255
Acknowledgement................................................................................................................................................................................................................. 255
References...........................................................................................................................................................................................................................................255

∗ Tel.: +46 8 517 733 26; fax: +46 8 517 742 52.

E-mail address: angelica.linden-hirschberg@karolinska.se

0378-5122/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.maturitas.2011.12.016
1. Introduction
other factors produced in the hypothalamus also regulate appetite,
including the anorectic peptide corticotrophin-releasing hormone
The sex hormones estrogen, progesterone and androgens are
and the orexigenic hormones melanin concentrating hormone and
involved in the complex regulation of appetite, eating and energy
orexins [2,3].
metabolism. In most species, including man, food intake and
There is also some evidence that food intake by humans is
reproductive functions are closely linked. Thus, during the dif-
under the control of cortical and subcortical areas of the brain
ferent hormonal phases of the menstrual cycle daily food intake
associated with reward and cognition (Fig. 1) [4]. The mesolimbic
varies and, moreover, remarkable physiological adaptations of
dopamine system, including the ventral tegmental area of the
appetite and body composition occur during pregnancy and lac-
midbrain and the nucleus accumbens in the striatum, is
tation. In addition, regulation of eating behaviour and metabolic
considered to be the primary neural reward system. In response
functions by sex hormones is of considerable general importance
to environmental and psychological stimuli this network may
for women’s health, as indicated by the disturbances in this regula-
enhance food intake inde- pendent of caloric need, the so-called
tion associated with a number of clinical disorders. In this context
hedonic feeding system.
eating disorders and obesity, which are becoming more and more
widespread and are coupled to severe morbidity and mortality, are
2.2. Signals produced in response to a meal
of particular concern. Recent research designed to elucidate mech-
anisms and provide strategies for the prevention and treatment of
The peripheral feeding system regulates short-term food intake
these major health problems has revealed new insights into the
in response to a meal by releasing a cascade of peptides from the
regulation of appetite and eating behaviour by sex hormones.
gastrointestinal tract, where they interact with dietary
The present overview of the role of sex hormones in the control
components and act peripherally to modulate digestion and
of appetite and regulation of normal, as well as pathological eating
absorption of nutri- ents (Fig. 2). By activating vagal afferent nerve
behaviour in women focuses on recent findings in the following
fibers, these peptides also signal via the nucleus of the solitary
areas:
tract in the brain stem that the stomach is full. In addition, gastric
distention evokes a feeling of satiety, also through activation of
1. Interactions between sex hormones and neuroendocrinological the vagal nerve, causing us to stop eating and reduce the size of
factors our meals [1–4]. The gastrointesti- nal peptides proposed to
2. Regulation of eating behaviour by sex hormones during the dif- produce satiation include cholecystokinin (CCK), glucagon-like
ferent phases of the menstrual cycle, menopause, pregnancy peptide-1 and peptide YY [2–4]. On the other hand, the appetite-
and lactation stimulating hormone ghrelin is secreted from the gastric mucosa
3. The potential role of sex hormones in eating disorders and obe- during fasting and reaches the brain via the bloodstream to signal
sity hunger (Figs. 1 and 2) [5].
4. The effects of treatment with estrogens (i.e., oral contraception
and menopausal hormone therapy) on appetite and body 2.3. Adiposity signals
weight
Circulating adiposity signals produced in amounts directly pro-
2. Hormonal control of appetite and food intake portional to body fat depots are also involved in the feedback
regulation of energy homeostasis [1–3]. For instance, leptin and
In response to hunger or the desire for some specific item of insulin have been implicated in long-term control of food intake
food, we normally eat until satiated. In this connection, various and energy expenditure (Fig. 2). Produced by adipocytes, leptin
factors such as the size of meals and rate and frequency of food inhibits food intake and stimulates the metabolic rate in experi-
intake may vary greatly in response to various environmental, mental animals by acting directly on specific leptin receptors in the
psychological, social and cultural influences. hypothalamus [6], thereby inhibiting orexigenic NPY/AgRP
neurons and stimulating anorexigenic POMC/CART neurons in the
ARC, as well as activating satiety neurons in the VMH (Fig. 1) [3].
2.1. Central regulation of feeding
However, the reported effects of administration of leptin to obese
humans have been modest and variable [7]. These observations
The hypothalamus plays a major role in the regulation of
have led to the concept of leptin resistance in obese individuals
appetite and food intake, both on a meal-to-meal and longer-term
[8].
basis. As part of the central feeding system, this organ coordinates
Insulin released from the pancreas elevates leptin production
a number of hormonal and neural inputs and also responds to
and, at the same time, like leptin, acts directly on the hypothala-
blood levels of nutrients, in turn generating behavioural and
mus and other areas of the brain to exert anorexigenic effects [9].
autonomic outputs designed to meet caloric needs and maintain
However, systemic administration of insulin elicits hypoglycaemia,
energy bal- ance [1,2]. In this regard a key role is played by the
which in itself enhances food intake [2].
hypothalamic arcuate nucleus (ARC), which extends projections to
the paraven- tricular nucleus (PVN) and the lateral
2.4. Sex hormones
hypothalamic area (LHA), as well as to other nuclei involved in
appetite regulation, such as the dorsomedial hypothalamus and
The sex hormones estrogen, progesterone and androgens are
ventromedial hypothalamic nucleus (VMH) (Fig. 1).
important modulators of food intake and energy balance in mam-
Two major populations of ARC neurons influence food intake
mals (Fig. 2) [10], where, as in most species, food intake and
and, thereby, energy homeostasis: those that extend projections
reproductive function are closely linked. Sex hormones both inter-
to the LHA and express neuropeptide Y (NPY) and Agouti-related
act with gastrointestinal peptides and neurotransmitters to
peptide (AgRP) stimulate food intake and decrease energy expen-
achieve central control of appetite and energy expenditure, while
diture and are therefore referred to as orexigenic effectors (Fig. 1).
also exerting direct peripheral action on adipocytes [10].
Other ARC neurons extend projections to the PVN and express pro-
Ovariectomy of rats increases food intake and, concomitantly,
opiomelanocortin (POMC) and cocaine-amphetamine-regulated
body weight [11] and these effects can be reversed by restoring
transcript (CART), which inhibit food intake and increase energy
physiological levels of estradiol [11]. There is evidence that the
expenditure, i.e., anorexigenic effectors [2,3]. In addition, several
effects of estradiol on food intake are mediated via estrogen recep-
tors in the hypothalamus (e.g., the ARC and the PVN) and in the
nucleus of the solitary tract in the brain stem [11]. However, it
Fig. 1. Central neuroendocrinological control of appetite and food intake. The hypothalamus plays a key role in the central regulation of feeding, coordinating various
neuroendocrinological inputs and signals from absorbed nutrients to meet caloric needs and maintain energy balance. In the arcuate nucleus of this organ, activation of
POMC/CART neurons inhibits, whereas activation of NPY/AGRP neurons stimulates food intake. Circulating signals such as sex hormones, leptin, insulin and ghrelin
activate theses neurons through specific receptors. Cortico-limbic systems, including the ventral tegmental area of the midbrain and the nucleus accumbens in the
striatum, are involved in the hedonic response to food and modulate hypothalamic centers. The nucleus of the solitary tract receives afferent signals from the
gastrointestinal tract via the vagus nerve and then transfers this information to the hypothalamus. AgRP, agouti-related peptide; CART, cocaine-amphetamine-regulated
transcript; NPY, neuropeptide Y; POMC, pro-opiomelanocortin.

remains unclear whether estrogen receptor (ER) α or β is involved

that specific central neural mechanisms promote either feeding or
[11–13]. Moreover, these effects of estradiol appear to involve
sexual behaviour at the appropriate times [22].
several different mechanisms. For instance, estradiol potentiates
Similarly in the case of women, food intake during the different
the effect of the satiating CCK peptide released from the small
phases of the menstrual cycle varies (Fig. 3). Thus, a meta-analysis
intestine in response to food intake [14,15], while attenuating the
revealed that mean food intake is lowest during the periovulatory
appetite-stimulating potency of the gastric hormone ghrelin [16].
phase of the menstrual cycle, when estradiol levels are high [23].
Furthermore, estradiol stimulates anorexigenic POMC/CART activ-
In contrast, a peak in food intake occurs during the premenstrual
ity and inhibits orexigenic NPY/AgRP neurons in the ARC [17,18].
period, when progesterone levels are high [23–28].
In contrast to estrogen, progesterone itself does not
These cyclic variations have been documented in several stud-
significantly influence feeding behaviour in ovariectomized rats,
ies, particularly in women exhibiting the premenstrual syndrome
except when administered in non-physiological, pharmacological
[23–28]. Moreover, binge-eating may be more pronounced during
doses [11]. However, in the presence of estrogen, progesterone
the premenstrual period [29], a process which may involve low
does stimulate appetite and promote weight gain [19].
lev- els of serotonin in the brain [25]. In addition, alterations in
Testosterone stimulates appetite and eating in a manner thought
energy expenditure during the course of the menstrual cycle are
to be mediated centrally [10], selectively increasing the number
related to variations in eating. For instance, during the
of meals, but not the size of each individual meal in rats [20].
postovaluatory phase elevated energy expenditure is associated
Recently, neonatal exposure of female mice to testosterone was
with the higher levels of progesterone [30].
found to enhance food intake and attenuate the expression of
Although the relevant reports have been somewhat contradic-
anorexigenic POMC/CART neurons in the ARC of these same
tory, intake of specific macronutrients may also vary during the
animals as adults [21].
menstrual cycle [24]. Some investigators have observed enhanced
intake of fat [27,31], carbohydrate [26] or both [25] during the
3. Regulation of normal eating in women by sex hormones pre- menstrual period; whereas others have not seen any change
in food preferences during the course of the menstrual cycle [24].
3.1. During the various phases of the menstrual cycle
3.2. Menopause
In the female of numerous species, eating behaviour is closely
linked to the functioning of the hypothalamic–pituitary–gonadal
During the menopausal transition, cyclic secretion of estradiol
(HPG) axis. For example, both female rodents and primates eat less
and progesterone disappears and production of the female sex
during the estrus phase prior to and following ovulation, when
hor- mones declines rapidly. However, circulating levels of
they are more sexually receptive and active [10]. It has been
androgens
proposed
Fig. 2. Afferent mechanisms in the control of appetite and energy homeostasis. The peripheral feeding system involves signals produced in response to a meal, including
gastrointestinal peptides and gastric distention, which reduce short-term food intake. Information from these signals is transmitted through vagal afferent fibers to the
nucleus of the solitary tract in the brain stem, where the first relay and integration of afferent inputs takes place. This information is subsequently transmitted to the
hypothalamus to activate anorexigenic systems that cause termination of eating. Long-term mechanisms regulate food intake to maintain energy homeostasis. Circulating
adiposity signals, the secretion of which is proportional to the amount of adipose tissue present, send negative feedback to the brain which evokes anorexigenic
mechanisms in the hypothalamus that reduce food intake and energy storage. Through central mechanisms, as well as peripheral effects on adipose tissue, sex hormones
also play an important role in the coordination of appetite and energy metabolism with reproductive state. CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; PYY,
peptide YY.

decline as a consequence of age-related reductions in secretion by
both the adrenal gland and ovaries. Weight gain is common during
these years and longitudinal studies have demonstrated an
increase in total and abdominal fat and a decrease in lean body
mass [32,33]. These changes have been observed as early as 3–4
years prior to the onset of menopause and to remain relatively
stable for at least 1–2 years after menopause [33].
At present, little is known about the relationship between
eat- ing and physical activity, on the one hand, and estrogen
depletion and subsequent cessation of ovarian function in
women, on the other. However, menopause is associated with
reductions in energy expenditure and oxidation of fat that can
predispose to weight gain [33,34]. The attenuated resting
metabolic rate is probably a consequence of the loss in lean
body mass, while the alterations in fat distribution appear to
reflect modified metabolism in adi- pose tissue. Estradiol
stimulates the activity of lipoprotein lipase (LPL) in femoral
adipocytes and lipolysis in abdominal adipocytes [35], thereby
promoting accumulation of gluteo-femoral fat. On the other
hand, estrogen deficiency is associated with enhanced
accumulation of abdominal fat [35].
3.3. Pregnancy and lactation
The major physiological changes in appetite and body composi-
tion that occur during pregnancy and lactation represent
functional adaptations. Both female animals (especially when they
give birth to large litters) and women eat more during pregnancy
to ensure normal growth and development of the fetus. In the rat
food intake is doubled, whereas in humans the increase is 10–15%
[19]. At about the twelfth week of pregnancy women begin to eat
progressively
more until somewhere around midgestation, when physical activ-
ity and, subsequently, food intake both decline [36].
Although the mechanisms underlying this enhancement of
appetite during pregnancy remain to be elucidated, it is likely that
sex hormones, and in particular progesterone are involved [37].
Progesterone may exert this effect via specific receptors on neu-
rons in the VMH and ARC [37]. Furthermore, the levels of adiposity
signals and of factors produced in response to a meal are altered
as a consequence of positive energy balance. For example, the level
of satiating CCK peptide is elevated [38], whereas basal levels of
the hunger hormone ghrelin are lower [39]. In addition, circulating
concentrations of leptin rise during a normal human pregnancy, an
effect which may be secondary to augmented leptin resistance
[40]. As expected, maternal fat deposition during gestation reflects
maternal food consumption. Under the influence of estrogen and
progesterone, fat is deposited primarily in gluteofemoral regions
to provide an energy reserve for lactation [41]. During lactation,
energy requirements are even higher than during pregnancy, with
breastfeeding demanding approximately 500 extra kcal per day
[42]. This elevated need is met by eating 20–25% more, along with
mobilization of femoral fat through enhanced lipolysis and
reduced LPL activity in response to prolactin, insulin and growth
hormone [19]. At the same time, the woman tends to be less
physically active
[42].
The mechanisms underlying stimulation of food intake during
lactation have not yet been clarified, but prolactin has been pro-
posed to play a major role in this connection [19]. In the lactating
rat, hyperphagia is a response to the suckling stimulus and the
metabolic demands associated with milk production per se [19].
These animals may also be less sensitive to satiating factors such
as CCK [43].

Fig. 3. Food intake during the different phases of the menstrual cycle. Food intake
is reduced during the periovulatory phase of the menstrual cycle, when estradiol
levels are high, and elevated during the premenstrual period, when progesterone
levels are high.
4. The involvement of sex hormones in eating
disorders and obesity
4.1. Anorexia nervosa
The fact that eating disorders are much more common in
women than in men suggests that sex hormone signaling may be
involved in their etiologies. Moreover, both anorexia nervosa (AN)
and bulimia nervosa (BN) are associated with endocrinological
abnormalities that disrupt the menstrual cycle and give rise to
metabolic disor- ders. These alterations may be the cause and/or
an effect of the abnormal eating behaviour. We are gaining some
insight into the roles played by sex hormones in connection with
disturbed eating behaviour.
AN, which is characterized by underweight (a body mass index,
BMI < 17.5), intense fear of becoming fat, distorted body image
and amenorrhea [44], has a strong genetic component, but its
detailed etiology remains unknown. This syndrome debuts most
commonly during early adolescence, simultaneously with dramatic
changes in growth and body composition in response to rising
levels of sex hormones. The associated amenorrhea is thought to
reflect hypothalamic inhibition of the HPG axis as a secondary
consequence of starvation, i.e., not to be primarily an endocrine
disorder. Energy deficiency disrupts the pulsatile secretion GnRH
and reduces secretion of FSH and LH, thereby lowering estrogen
levels [45]. Overzealous exercise, which is common among indi-
viduals with AN, also contributes to inhibition of the reproductive
system.
The potential role of gonadal hormones in the pathogenesis of
AN is not yet known. Recently, an association between paternal
polymorphisms in the gene encoding ERα receptors and restric-
tive AN was reported [46], indicating the involvement of estrogen.
In addition, this disease is associated with alterations in the lev-
els of appetite-regulating hormones and neuropeptides, including
corticotrophin-releasing hormone, NPY, serotonin metabolites and
leptin, in the cerebrospinal fluid [47]. However, recovery tends to
eliminate these abnormalities, suggesting that they may be a con-
sequence of starvation rather than a primary cause of the disease
[47].
4.2. Bulimia nervosa
Bulimia nervosa is characterized by frequent episodes of binge
eating, followed by attempts to compensate by vomiting, abuse of
laxatives, excessive exercise and/or other purging behaviours [44].
Although it’s etiology has yet to be elucidated in detail, a genetic
predisposition, biological disturbances (including dysregulation of
the serotonin system) and socio-psychological factors all appear to
be involved [47].
Even though body weight remains normal, the menstrual cycle
of bulimic women is often disturbed, probably as a consequence
of several different processes. As in the case of AN, low circulating
levels of estradiol and gonadotropins, indicative of hypothalamic
inhibition of the HPG axis, are observed in bulimic women [48]. In
addition, BN may be connected with the polycystic ovary
syndrome (PCOS) [49,50], which has a prevalence of 5–10% in the
general pop- ulation and is thus the most common endocrinological
disorder in women of fertile age. This syndrome is associated with
disturbance of the menstrual cycle, hyperandrogenism and
polycystic ovaries (as detected by ultrasound) [51] and is also
related to insulin resis- tance and abdominal obesity. There is
evidence that PCOS has a strong genetic component, although
environmental factors appear to be important as well.
Women with hyperandrogenism and PCOS exhibit dysregula-
tion of appetite, together with a craving for carbohydrates and fat,
as also observed in bulimics [52–54]. Similarly, elevated
incidences of polycystic ovaries, acne and hirsutism, along with
abnormally high serum levels of androgens have been observed in
bulimic women [49,50]. Female mice in which the gene encoding
estrogen receptor β has been knocked out (βERKO mice) display
atten- uated fertility due to ovarian dysfunction and dysregulation
of androgen receptors [55]. Interestingly, an association between
polymorphisms in the ERβ gene and bulimia has been demon-
strated in humans as well [56], an observation which may have
important consequences for the development and treatment of
both menstrual disorders and abnormal eating behaviour in
bulimic women.
Testosterone stimulates appetite [10] and high circulating lev-
els of this androgen in women have been associated with impaired
impulse control, irritability and depression [57], i.e., common
features of women with bulimia [57]. Accordingly, it has been
proposed that elevated levels of androgens may promote bulimic
behaviour by influencing craving for food and/or impulse con-
trol. Hypothetically, bulimia may, in some cases, have a hormonal,
rather than a psychiatric etiology, a suggestion supported by
the observation that antiandrogenic treatment reduces bulimic
behaviour [58,59]. This may turn out to be a novel and valu-
able approach to treating women with BN, particularly those with
hyperandrogenic symptoms.
4.3. Obesity
Obesity (body mass index (BMI) > 30 kg/m 2) is a growing health
problem that has reached epidemic proportions worldwide. The
Fig. 4. Weight gain initiates a vicious circle of endocrine/metabolic abnormalities. An increase in body weight results in insulin resistance and compensatory hyperinsulinemia.
The excess insulin stimulates, in turn, ovarian biosynthesis of testosterone and inhibits SHBG production in the liver, resulting in a higher level of testosterone. This
elevated level of testosterone may then promote accumulation of abdominal fat and insulin resistance in women. SHBG, sex hormone-binding globulin.

etiology involves both environmental and genetic factors, with the

5. Effects of treatment with sex hormones on appetite and
latter exerting an impact of 40–70% [60]. Only in rare cases, such
body weight
as congenital leptin deficiency, does a disturbance in appetite and
weight regulation appear to play a primary role [61]. In other
5.1. Oral contraceptives
obese individuals the hedonic response to food, particularly
enjoyment of high-fat foods, seems to be greater than in lean
Oral contraceptives (OCs) containing both estrogen and pro-
individuals [62]. Obesity is also associated with several
gestin are used by countless women for birth control, as well as for
endocrinological abnormal- ities, most of which are secondary, but
medical treatment of dysmenorrhea, heavy bleeding, endometrio-
some of which may actually be involved in its etiology and
sis and menstrual disorders. Such treatment is generally tolerated
development.
well, with few side-effects and only a small risk for thromboem-
Interactions between glucocorticoids and sex hormones partic-
bolic events. Nonetheless, many women, especially adolescents,
ipate in the pathophysiology of abdominal obesity [63], which is
stop taking OCs because of weight gain, mood swings and sexual
associated with stressful life events leading to over-stimulation
dissatisfaction [66]. An American survey found that more than
of the hypothalamic–pituitary–adrenal axis (HPA) [64]. Such
50% of women believe that OCs cause weight gain and 20% said
hyperactivity elevates levels of cortisol, increases lipolysis and
that this was the reason they had stopped taking them [67].
stimulates the conversion of free fatty acids to glucose and stor-
Although some women do experience alterations in appetite and
age of fat in abdominal depots. Central fat depots predispose an
weight when using such combination OCs, several investigations
individual to insulin resistance and secondary hyperinsulinemia,
have all concluded that these do not significantly affect body
which, in turn, stimulates ovarian biosynthesis of testosterone
weight or com- position [68,69]. At the same time, individual
and inhibits hepatic production of sex-hormone binding globu-
women may respond differently and, moreover, different types of
lin (SHBG), thereby enhancing levels of free testosterone (e.g.,
OCs may differ in this respect.
in women with PCOS). High levels of testosterone may then
Combination OCs usually contain the synthetic estrogen
induce accumulation of abdominal fat and insulin resistance
ethinylestradiol or, more recently, the natural estradiol, whereas
(Figs. 4 and 5) [65].
the type of progestin present varies. The major progestins
It has been proposed that testosterone might cause hepatic
employed are derivatives of either 19-nortestosterone or 17- α-
insulin resistance by facilitating catecholamine-stimulated lipol-
hydroxyprogesterone. The former exhibits varying degrees of
ysis in visceral fat tissue, thus exposing the liver to a surge of free
androgenic activity, whereas the latter, which are related struc-
fatty acids [65]. In addition, testosterone may promote insulin
turally to progesterone, lack androgenic effects and may also
resis- tance by decreasing the density of capillaries in peripheral
demonstrate antiandrogenic activity. Combinations of androgenic
muscles. Such a vicious circle could aggravate metabolic
progestins with ethinylestradiol appear to be associated with a
complications and thus enhance the long-term risk of developing
lower risk for vascular thromboembolism and are therefore the
type 2 diabetes and cardiovascular disease (Fig. 4).
recommended choice in a number of countries [70]. On the other
Whereas testosterone may influence fat distribution in women
hand, side-effects such as acne, mood swings, and weight gain may
adversely, it is noteworthy that the situation appears to be exactly
be more common with androgenic OCs [71].
the opposite in men. Larger depots of abdominal fat in men are
Progestins are known to stimulate food intake (Fig. 5) [72].
associated with lower testosterone levels because gonadotropin
For example, cancer-related cachexia and anorexia and other
secretion is reduced [63], while upon weight loss testosterone lev-
forms of malnutrition can be effectively treated with high doses
els and insulin sensitivity return to normal. Furthermore, long-
of megestrol acetate. Such treatment enhances serum levels of
term treatment of obese men with testosterone causes them to
insulin and insulin-like growth factor (IGF)-I markedly [72]. More-
burn fat and enhances lean body mass [63]. This apparent sex
over, an androgenic OC can interfere with regulation of appetite,
difference has not yet been clarified.
 Fig. 5. Effects of sex hormones on appetite, food intake and body weight in women.

suppressing secretion of the satiating peptide CCK and increas-

Many women are concerned about gaining weight during
ing body fat [73,74], which may be one mechanism underlying the
menopause and believe that HRT may increase their appetite and,
weight gain experienced by certain women.
thereby, weight. However, studies have shown that energy intake
In contrast, treatment of women with bulimia nervosa with an
is not affected by HRT [77,78] and, furthermore, numerous
antiandrogenic OC containing ethinylestradiol and drospirenone
random- ized trials have failed to reveal any evidence that HRT,
not only reduces androgen levels, but also attenuates binge eating
either with estrogen alone or in combination with progestin,
and appetite in connection with meals [59]. Furthermore, users of
elevates body weight or BMI [76,79]. In contrast, most such
this particular OC exhibit a small reduction in body weight [75].
investigations con- clude that HRT actually lowers weight gain and
However, despite extensive clinical experience with OC treatment,
body fat [76,80,81]. In addition, HRT prevents the shift in fat
little is presently known concerning the effects of different types of
deposition from the normal female condition to the more
OCs on appetite and body weight and much more research in this
unhealthy central fat depots associ- ated with the menopausal
area is clearly motivated.
transition (Fig. 5) [76,82,83].
The mechanism(s) in this case probably involves metabolic
effects of HRT on adipose tissue. Thus, treatment of post-
5.2. Hormone replacement therapy
menopausal women with estrogen enhances LPL activity in the
femoral region and at the same time lipolysis in the abdominal
For decades now, hormone replacement therapy (HRT) has
region, which might promote fat accumulation in the former region
been employed to relieve menopausal symptoms such as flush-
and fat loss from the abdomen [84]. In addition, as demonstrated
ing, sweating and sleep disturbances, as well as for to prevent
by the large Women’s Health Initiative Study [83], lean body mass
osteoporosis and related bone fractures. However, more recent
may be preserved by combined HRT. Interestingly, the route of
ran- domized, as well as, epidemiological investigations have
estrogen administration may be an important factor in this
revealed that HRT of postmenopausal women with estrogen and
context, since one crossover study found less fat gain with
progestin increases the risk for breast cancer, as well as for
transdermal than with oral administration [85]. Oral
cardiovascular disease and thrombosis. Consequently, the benefits
administration of estrogen stimulates the secretion of growth
versus risks of such treatment have been discussed extensively
hormone, reduces circulating levels of IGF-I and raises circulating
and new guide- lines proposed. Importantly, a women’s age or the
levels of triglycerides; whereas none of these changes appears to
period that has elapsed since her menopause appears to influence
occur following transdermal administration [76].
the benefit–risk ratio in this connection. Recently, the Endocrine In recent years, there has been increasing interest in treating
Society Scientific Statement concluded that HRT provides highly postmenopausal women with androgens because of the benefi-
effective allevia- tion of climacteric symptoms and that the risk– cial effects, including improved sexual functioning, energy and
benefit ratio is favourable if treatment is initiated shortly after overall quality of life [86]. Testosterone treatment also enhances
onset of menopause and limited to approximately five years [76]. bone mineral density, lean body mass and muscle strength [86].
However, there remain concerns about potential adverse effects
of androgens on body weight, as well as carbohydrate and lipid
metabolism similar to those observed in individuals with excess
endogenous androgens, e.g., women with PCOS. For instance,
short- term oral treatment of postmenopausal women with
testosterone induces insulin resistance, produces an adverse lipid
pofile and alters the expression of lipolytic signaling proteins,
which may pro- mote the accumulation of fat [87,88]. Transdermal
preparation of testosterone is now available for treatment in
women, and this kind of administration may be associated with
less risk of adverse metabolic effects [86]. Furthermore, the safety
of long-term testos- terone administration with respect to the
endometrium and breast has not yet been elucidated.
6. Conclusions
The present review highlights the complex involvement of
sex hormones in the regulation of appetite and eating behaviour
in women. In both experimental animals and humans, estrogen
reduces food intake; whereas testosterone, as well as proges-
terone in combination with estrogen, may enhance food intake. Sex
hormones modulate appetite and energy expenditure during the
menstrual cycle, pregnancy, lactation and menopause. Moreover,
alterations in sex hormones may play a role in disturbed eating
behaviour. For example, elevated levels of androgens in women
have been associated with impaired impulse control and bulimic
behaviour. In addition, antiandrogenic oral contraceptives appear
to reduce meal-related appetite and bulimic behaviour. Accord-
ingly, at least hypothetically, bulimia may in some cases be a
hormonal rather than primarily a psychiatric illness.
The development of obesity, and particularly the visceral type
thereof, may also be influenced by sex hormones. Thus,
interactions between glucocorticoids and elevated levels of
androgens play a role in the pathophysiology of abdominal obesity
and insulin resis- tance in women. In contrast, abdominal obesity
in men is associated with lower testosterone levels. Furthermore,
treatment with estro- gen and progestin counteracts weight gain
and the accumulation of abdominal fat associated with the
menopausal transition. In con- clusion, sex hormones and/or
agents that exhibit similar activities may provide novel strategies
for the treatment of eating disorders and android obesity, two of
the most serious health problems for women today.
Contributors
All authors contributed equally.
Competing interests
None declared.
Provenance and peer review
Commissioned and externally peer reviewed.
Acknowledgement
Financial support by the Swedish Research Council (20324),
Karolinska Institutet and the Stockholm County Council.
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