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Arch Gynecol Obstet
DOI 10.1007/s00404-008-0708-2
123
REVIEW ARTICLE
Cognitive, sensory, and emotional changes associated
with the menstrual cycle: a review
Miranda A. Farage · Thomas W. Osborn ·
Allan B. MacLean
Received: 11 March 2008 / Accepted: 2 June 2008
© Springer-Verlag 2008
Abstract The hormones progesterone and estrogen and,
more precisely, their sophisticated interdependent Xuctuations
over the course of the female human lifespan, have long been
known to play a dominant role in the physiological develop-
ment and homeostasis of the human female. What is only
recently coming to light, however, is that the Xuctuation of
these two hormones also plays a crucial role in neurological
and psychological development and function which impacts
brain function, cognition, emotional status, sensory process-
ing, appetite, and more. The ability of reproductive hormones
to impact psychoneurological processes involves the interplay
of several body systems, lending credibility to the view of
premenstrual syndrome (PMS) as a disorder founded in real
biochemical disturbances. The eVects of the menstrual cycle
on cognitive, emotional, and sensory function in the female of
childbearing age are reviewed. In addition, recent evidence is
discussed which conWrms the biological basis of PMS as a
real disorder of primarily autoimmune origin.
Keywords Menstrual cycle · PMS · Mood ·
Sensory changes · Cerebral asymmetry · Premenstrual
The menstrual cycle
The menstrual cycle begins, by deWnition, with the onset of
menstrual Xow on day 1. The menstrual phase (generally
lasting between 4 and 6 days) is deWned by the shedding of
the thickened endometrium, a process known as menstrual
bleeding. The follicular or proliferative phase continues
until ovulation, typically days 7 through 14. The luteal, or
secretory phase begins at ovulation and continues until the
onset of the menstrual Xow, typically days 15 through 28
[1].
The menstrual phase and early follicular phase of the
menstrual cycle are characterized by low levels of both pro-
gesterone and estrogen. Estrogen levels rise rapidly late in
the follicular phase, peaking 1 day before ovulation. The
luteal phase sees a steady rise in progesterone levels that
peaks mid-luteal phase, in parallel with a second estrogen
peak. Late luteal phase is characterized by declines in both
estrogen and progesterone levels that reach baseline shortly
before the onset of menstruation, which begins the cycle
again [2], as shown in Fig. 1.
The cyclic hormonal changes which regulate the men-
strual cycle are an important biological inXuence on the
female body, with numerous physical ramiWcations [1].
Estrogen initiates or mediates an impressive array of bio-
logical functions (Table 1), with receptors in a multitude of
tissues and cell types. In fact, Xuctuating levels of estrogen
have been shown to have physiologically demonstrable
eVects on virtually every organ system in the body [3]. The
inXuences of progesterone on the body are less studied and
more limited, but still an important determinant [3]. Our
companion paper reviews the modulation of physiological
processes by these hormones as they Xuctuate over the
menstrual cycle [4].
The eVects of the menstrual cycle on emotional state and
cognitive function have been long recognized (if only
recently systematically studied), a fact easily conWrmed by
the observation that a signiWcant proportion of internet
humor exchanged by modern women deals with the
M. A. Farage (&) · T. W. Osborn
The Procter & Gamble Company, Winton Hill Business Center,
6110 Center Hill Road, Box 136, Cincinnati, OH 45224, USA
e-mail: farage.m@pg.com
A. B. MacLean
Department of Obstetrics and Gynaecology,
University College, London, UK
Arch Gynecol Obstet
123
emotional impact of menses, particularly during the pre-
menstrual period [5]. As medical science continues to
investigate the complex interplay of the hormones which
inXuence the menstrual cycle and their interdependent
inXuence on the mind and body, it is becoming clear that
the Xuctuating levels of these hormones aVect both physio-
logical and psychological processes (Table 2).
EVects of menstrual cycle on mood
A widespread belief that negative moods are characteristic
of the premenstrual period is replete in the popular culture.
This belief has scientiWc support. In an early landmark
study of neurotic women, psychoanalytic analysis of diaries
in which women recorded emotional status and dreams was
able to correctly identify hormonal status in 94% of patient
cycles analyzed. Patients were consistently more restless,
irritable, fatigued, fearful, and depressed during the pre-
menstrual period than other phases of the menstrual cycle,
as well as being hypersensitive to various stimuli [6].
Benedek was doubtful that her results could be extrapo-
lated to normal women, but ensuing decades of research has
Fig. 1 Hormonal Xuctuations over the menstrual cycle. This Wikipe-
dia and Wikimedia Commons image is from the user Chris 73 and is
freely available at http://commons.wikimedia.org/wiki/Image:Men-
strualCycle.png under the creative commons cc-by-sa 2.5 license
Table 1 Organs, tissues and cell types with conWrmed estrogen recep-
tors
By body system Reference no.
Cardiovascular system
Cardiovascular system overall Millikan [81]
Blood vessels Brincat [77]
Endothelial cells Sekigawa et al. [76]
Central nervous system
Central nervous system overall Millikan [81]
Cerebral cortex Hall and Phillips [2]
Digestive system
Gallbladder Millikan [81]
Liver Millikan [81]
Pancreas Millikan [81]
Endocrine system
Adrenal gland Millikan [81]
Hypothalamus Hall and Phillips [2]
Parathyroid Millikan [81]
Thymus tissue Tamer et al. [82]
Thyroid Millikan [81]
Female reproductive system
Breast carcinoma Brincat [77]
Cervix Brincat [77]
Fallopian tubes Brincat [77]
Mammary glands Millikan [81]
Ovaries Millikan [81]
Placenta Millikan [81]
Uterus Brincat [77], Millikan [81]
Vaginal epithelium Hall and Phillips [2]
Immune system
B cells Sekigawa et al. [76]
CD4+ T cells Sekigawa et al. [76]
CD8+ T cells Sekigawa et al. [76]
Macrophages Sekigawa et al. [76]
Thymocytes Sekigawa et al. [76]
Integumentary system
Corneal epithelia Suzuki et al. [83]
Cutaneous mucinous carcinoma Brincat [77]
Cutnaeous vascular tumors Brincat [77]
Fibroblasts Brincat [77]
Hair (dermal pappila of
hair follicles)
Millikan [81] [84]
Melanocytes Brincat [77]
Sebaceous glands Hall and Phillips [2]
Skin (facial much higher than
breast or thigh)
Hall and Phillips [2],
Millikan [81]
Dermis Brincat [77]
Epidermis Brincat [77]
Skeletal system
Bone Millikan [81]
Arch Gynecol Obstet
123
shown conclusively that estrogen and progesterone do have
substantial eVects on mood and mental function. One telling
statistic is that until puberty, boys require psychiatric treat-
ment at a rate twice that of girls; after puberty, that statistic
is reversed, with women suVering from anxiety and depres-
sion at a rate twice that of men [7]. Women with mood dis-
orders evidence deWnite peaks related temporally to times of
substantial hormonal Xuctuation: i.e., adolescence, perimen-
opause, and, in the reproductive years, the week before the
onset of menses [8–11]. Negative premenstrual changes in
mood, in studies that evaluated self-reports, range widely
[12, 13], but it is believed that about 95% of women have
recurrent and noticeable increase in negative emotions [14].
Highest levels of well-being and self esteem are reported
during mid-cycle and increasing negative feelings (anxiety,
hostility, and depression) occur premenstrually as both
estrogen and progesterone levels decline.
Recent research has compiled statistics that lend tragic
support to long-standing observation of an increase in nega-
tive emotion in the premenstrual period. Baca-Garcia et al.
demonstrated that, in a group of 113 Spanish women who
had attempted suicide, 36% of attempts had occurred in the
Wrst week of the menstrual cycle (i.e., during the menstrual
phase), while only 19% had occurred during the second
week, and 16% during the third. Interestingly 29% of
attempts had occurred during the fourth week, meaning that
65% of all suicide attempts occurred during the premen-
strual and menstrual period. In a follow-up study, which
compared 134 women who had attempted suicide with 108
female controls, the percentage of suicide attempts during
the menstrual phase exceeded that predicted by representa-
tion of menstrual phase women in the group by 75% [15,
16]. This work conWrmed earlier reports of increased risk of
suicides during the premenstrual and menstrual phases [17].
A recent meta-analysis which evaluated 44 studies of
suicide in fertile women found that a positive relationship
does appear to exist between the Xuctuating hormone levels
of the menstrual cycle and suicidal behavior. Suicide
attempts appear to correlate to the periods of time when
estrogen levels are lowest (late luteal and early follicular,
i.e., menstrual, phases). The authors suggest that interaction
between circulating estrogen and the serotonergic system
may contribute to the risk of suicidal behavior associated
with this period of the menstrual cycle [18].
The speciWc pathways by which the neuroendocrine
changes that occur over the menstrual cycle aVect central
nervous system (CNS) control of mood and emotion are
currently the focus of much research. The autonomic ner-
vous system may be an important intermediary mechanism
in mood cycling that parallels hormonal changes in women,
especially with regard to the premenstrual period [19].
Numerous studies have looked at indicators of auto-
nomic nervous system function, including heart rate, blood
pressure, respiration rate, cardiovagal response, and body
temperature and attempted to correlate these objective
assessments with mood and/or hormone Xuctuations, with
nonconclusive results [11, 19].
Luteal phase connection, however, with an activated
sympathetic nervous system (with its connection to height-
ened emotional state) is supported by the Wndings of Sig-
mon et al. (2000) [11]. In a study that evaluated autonomic
nervous responses speciWcally in women with anxiety dis-
orders, women with panic disorders had signiWcantly higher
response, both in frequency and degree of reactions, to anx-
iety-provoking stimuli than controls during the premen-
strual phase. Mood disorder subjects, however, did not
evidence elevated arousal across the menstrual cycle [11].
EVects of menstrual cycle on mental function
The last few decades have conWrmed scientiWcally that
gender resides in the nervous as well as the reproductive
Table 2 Menstrual cycle symptoms
Sources: adapted from Ref. [17, 85]
Concentration Negative eVect
Accidents Anxiety
Confusion Crying
DiYculty concentrating Depression
Distractible Irritability
Forgetfulness Loneliness
Insomnia Mood swings
Lowered judgment Restlessness
Lowered motor coordination Tension
Pain Control
Backache Blind spots, fuzzy vision
Cramps Chest pains
Fatigue Feeling of suVocation
General aches and pains Heart pounding
Headache Numbness, tingling
Muscle stiVness Ringing in the ears
Behavioral change Arousal
Avoid social activities AVectionate
Decreased eYciency Bursts of energy, activity
Lowered school or work
performance
Excitement
Stay at home Feelings of well-being
Take aps; stay in bed Orderliness
Autonomic reactions Water retention
Cold sweats Painful breasts
Dizziness, faintness Skin disorders
Hot Xashes Swelling
Nausea, vomiting Weight gain
Arch Gynecol Obstet
123
systems. Estrogens are critical elements in the imprinting of
gender on a developing fetus, creating a synaptic plasticity
that becomes abundantly evident during puberty and there-
after during the menstrual cycle [20]. The distinct diVer-
ences between men and women with regard to information
processing is thought to stem from diVering exposure to sex
hormones in utero, which lays down gender-speciWc wiring
that will be activated by surges in gonadal steroids at
puberty [21]. Interestingly, these early hypotheses have
been conWrmed by studies in unfortunate natural experi-
ments such as Turner Syndrome children [who have only
one sex chromosome (an X)] and in another congenital dis-
order called congenital adrenal hyperplasia, in which con-
genital disturbances in the levels of sex hormones carry
predictable eVects on mental processing [22].
Neurocognitive processes
For the last few decades, the conWrmation of estrogen
receptors spread throughout the brain—hypothalamus, pitu-
itary, hippocampus, cerebral cortex, mid-brain, and brain-
stem—has suggested a potential for numerous inXuences of
estrogen on neurocognitive processes [21]. Estrogen acts on
the central nervous system on a variety of levels (genomic
and beyond) directing and modulating neurotransmitter
production and action, inXuencing electrical excitability
and synaptic function, and changing the morphological fea-
tures of neural elements involved in function [20]. Estrogen
has been demonstrated to aVect numerous neurotransmitter
systems, including the dopaminergic [21], catecholaminer-
gic, serotonergic, cholinergic, and gamma-aminobutyric
acidergic systems [23].
Information processing in the human brain is complex
and multifactorial, involving attention, learning, memory,
pattern recognition, problem solving, language processing,
abstract intellectual processing, and psychomotor skills
[21]. From animal studies, consolidation of memory seems
to occur in the hippocampus [24]. Estrogen has been shown
to aVect cyclic changes in the hippocampus [25] as well as
enhancing short-term memory, thereby inXuencing the acu-
ity of working memory [21]. The largest concentration of
estrogen receptors (beta) in the human brain are in the
hypothalamus, amygdala, and the hippocampus [26]; and
its strongest upregulation of neurotransmitters is associated
with acetylcholine [27].
The eVects of estrogen on cognitive processing are also
seen at menopause; the estrogen withdrawal typical of this
period has pronounced inXuences on mood, behavior, and
cognition [20]. Early experiments found that estrogen
replacement in postmenopausal women increased verbal IQ
scores after 1 year of treatment. Numerous later studies
found that estrogen administration after surgical meno-
pause improved memory, abstract reasoning, and reaction
times, while those patients who were given placebo had
signiWcant deterioration of cognitive function in these areas
[21]. Other studies had less consistent results, however, and
in a recent nine-year study of more than 2,300 women
given estrogen replacement, those on hormone replacement
therapy had no signiWcant mental gains over those who
were not taking estrogen [28].
A closer look at the data, however, helps to clarify an
apparent conXict. Randomized controlled trials in which
patients were given estrogen replacement therapy (ERT)
either post natural menopause or coincident with surgical
menopause have repeatedly shown signiWcant protection of
memory associated with the estrogen replacement [21].
However, the 9-year Women’s Health Initiative Memory
Study, a randomized controlled trial which evaluated ERT
in 2,302 women after surgical or natural menopause, found
no protective eVect [29]. Careful study of the existing body
of literature revealed, that the strongest data showing mem-
ory protection from ERT was derived from surgical meno-
pause studies in which ERT was begun immediately after
surgery, whereas the Women’s Health Initiative Memory
Study provided ERT to women often long after natural
menopause had occurred. Sherwin (2007) has proposed the
existence of a critical window of opportunity that is at or
near the time of natural menopause or surgical ovariectomy
in which administration of estrogen protects mental acuity,
particularly with regard to retention of memory [30]. This
theory is supported by evidence from both basic neurosci-
ence and existing animal studies, as well as providing a
plausible explanation for the apparent conXict between the
Women’s Health Initiative study and the Wndings of the
bulk of controlled trials that predated it [30].
Cerebral assymetry
The extreme complexity of neurocognition in general
makes it very unlikely that one molecule will inXuence all
cognitive functions [21], and not all mental processes seem
to be aVected by estrogen. Particular mental functions,
however, display very strong sexual dimorphism [31].
Women tend to outdo men in verbal facility, memory, Wne
motor skills, and perception (both speed and accuracy),
while men are generally superior on tests of visual memory,
mathematical ability, and spatial ability [31].
Brain hemispheres represent a division of labor, with the
left hemisphere largely responsible for male-dominance
functions like spatial orientation and lexical decision, while
the right brain is responsible for more female-dominance
tasks like Wgural comparisons and facial discrimination
[32]. The right hemisphere has an advantage in women,
while the left hemisphere has the advantage in men [33].
The foundation for these dimorphic diVerences appears
to be a cerebral asymmetry associated with estrogen [32].
Arch Gynecol Obstet
123
Women’s brains are believed to be less lateral, due to an
increased number of mid-brain connections in the corpus
callosum [34]. These gender diVerences were long thought
to be static [33]. Interestingly, a study of the changes in
processing over the menstrual cycle has done much to
change that view.
It has been consistently observed that while male perfor-
mance on cognitive tasks does not vary signiWcantly over
time, female performance shows consistent Xuctuations.
The most dramatic diVerences have been observed with
regard to tests of mental rotation, a task shown to have a
strong male dominance. Women’s scores on mental rota-
tion tests show a strong negative correlation to estrogen
levels, with lowest scores during the mid-luteal phase and
highest scores during menstruation. Men score signiWcantly
higher than women in all points of the menstrual cycle
except menses [35–37]. Mental rotation scores in cycling
women in the luteal phase were lower than scores in
women on oral contraceptives [38]. There is a strong posi-
tive correlation with circulating testosterone levels in the
female subject [35]. Asymmetry in lexical tasks did not
change over the cycle, but asymmetry in face perception
did [34]. Hampson and Kimura found decreased perfor-
mance on perceptual/spatial tasks during the mid-luteal
phase [39].
Women scored higher in memory tasks in the mid-luteal
phase, and lower during menstruation [36]. Concentration
(assessed by the Stroop color-word test) in 50 women dem-
onstrated lower scores during the premenstrual period [40].
The same pattern was seen in performance of Wne motor-
skill tasks [36]. Semantic processing in word-matching
tests also increased during the mid-luteal (premenstrual)
phase [41]. Hampson and Kimura found increased mid-
luteal scores on tests of speed and motor coordination when
compared to early follicular performance [39]. Phillips and
Sherwin found verbal memory, attention and visual mem-
ory enhanced in the mid-luteal phase, which they speciW-
cally determined to be correlated to progesterone levels
[42], while Maki et al. determined that poorer performance
on tests of spatial ability during the mid-luteal phase, as
well as increased Wne motor dexterity and verbal Xuency to
be correlated with estrogen (E
2
) [36].
Hausman and Güntürkün concluded that functional cere-
bral asymmetries exist in women due to changes in hor-
mone levels. Although function is somewhat bilateral when
progesterone levels are highest in mid-luteal phase, strong
lateralization appears during menses [32]. This has been
interestingly demonstrated in sensory-acuity tests.
Sanders and Wenmoth (1998) evaluated auditory
responses and cerebral asymmetry; typically (apart from
hormonal Xuctuations) the right ear has an advantage on
verbal auditory acuity, while the left ear has an advantage
with music. In this study, the right-ear advantage during
verbal listening increased during mid-luteal phase com-
pared to menses, while the left-ear advantage for music
increased during menses compared to the luteal phase. Over
the course of the menstrual cycle, left-ear performance
decreased substantially on both tasks, while right-ear per-
formance increased steady but less substantially [43].
Olfactory acuity was found to have a similar pattern. The
right nostril had higher olfactory acuity during menses,
while the left nostril had more acuity around ovulation [33].
Overall eVect of hormone levels
Early published studies yielded inconsistent data in terms
of meaningful studies which were needed to deWne cycle
phases more clearly, use cognitive tests that have dimorphic
variation, correlate Wndings to hormone levels, and include
suYcient sample size for statistical power. However, more
recent well-done studies have yielded dimorphic diVer-
ences that, although small, are consistent [21]. On tasks in
which women typically score better than men, women score
higher during mid-luteal phase than within menstrual phase
(although some results correlate with progesterone levels
more than estrogen, both of which have peaks during the
mid-luteal phase) [21]. On tasks in which men typically
outperform women, women typically do best during men-
ses [21]. In other words, estrogen positively inXuences per-
formance on sexually dimorphic tasks that favor females
and negatively inXuences performance on tasks that favor
males [44].
EVects of menstrual cycle on sensory function
EVect on hearing
In numerous reports of both animal and human studies,
estrogen has been suggested to have positive eVects on the
auditory process. Women have consistently been found to
have more acute hearing than men of a similar age [45, 46].
Parlee found the auditory threshold to be lower around the
time of ovulation [47]. Swanson and Dengerink found the
pure-tone thresholds at 4 kHz were poorer during menses
(when plasma levels of estrogen are lowest) than over the
rest of the cycle [48].
EVect on smell
Asso found that olfactory acuity reaches a peak at about the
time of ovulation [49]. Direct association exists between
estrogen levels and olfactory sensitivity, with fertile women
more sensitive to the macrocyclic musk exaltolide than
premenarchal or postmenopausal women [49]. Parlee found
that the olfactory threshold was lower around ovulation
Arch Gynecol Obstet
123
[47]. Sommer similarly found increased olfactory sensitiv-
ity around the time of ovulation [50]. In a more recent
study, Navarrete-Palacios evaluated the olfactory thresh-
old in 332 ovulatory women, using diVerent log-based
concentrations of amyl acetate. Olfactory thresholds diVered
signiWcantly over the cycle, with the lowest thresholds
during the ovulatory phase and the highest during the
menstrual Xow [51].
EVect on vision
Parlee, Asso, and Sommer all demonstrated increased
visual sensitivity during the time of ovulation [47, 49, 50].
Friedman and Meares demonstrated, in 21 women with nor-
mal menstrual cycles, that visual sensitivity was enhanced
during the late follicular phase of the cycle as ovulation
approached, while at other points in the cycle visual acuity
was constant and comparable to women on oral contracep-
tives [52]. Barris et al. in a small study in Wve fertile
women found a consistent increase in visual acuity on the
day of highest basal body temperature, with no correspond-
ing increase in Wve controls [53].
EVect on touch/pain
Numerous studies have been performed in women which
attempted to evaluate potential diVerences in pain percep-
tion across the menstrual cycle, for both intrinsic and
experimentally induced pain [54] but no conclusive Wnd-
ings have been obtained. Studies involving pressure stimu-
lation, cold pressor pain, and ischemic muscle pain have
produced a pattern of diminished sensitivity in the follicular
phase as compared to the ovulatory, luteal, and premen-
strual phases, but not a consensus. Limited studies on pain
induced by electrical stimulation have produce conXicting
results [55, 56].
The majority of pain studies, however, have relied on
subjective self-reports of perceived pain, in addition to
being plagued with the same issues of patient population
selection and hormone status veriWcation that confound
menstrual-cycle research in general. A recent study of pain
across the menstrual cycle utilizing nocioceptive Xexion
reXexes as an objective and easily quantiWed measure of the
pain response compared these objective measures with sub-
jective perceptions in 14 normal fertile women. Tassorelli
et al. found that both reXex thresholds and psychophysical
pain thresholds were signiWcantly reduced in the luteal
phase as compared with the follicular phase. In addition,
pain sensitivity as revealed by the reduction in the reXex
threshold was signiWcantly correlated to the total mental
distress score reported by the patient for that day [57].
Far less work has focused on tactile sensitivity apart
from pain sensation. Henkin (1974), studying tactile spatial
acuity on the skin and using two-point thresholds as the
assessment, found acuity to be higher in the luteal phase
than in the follicular or ovulatory phases of the menstrual
cycle [58]. A study that evaluated sensitivity to electrical
stimulation at various tissue depths in the abdomen and
limbs found increased cutaneous sensitivity in the periovu-
latory period, while subcutaneous tissue and muscle were
more sensitive during the menstrual and follicular phases
[55]. Bajaj et al. studying tactile threshold sensitivity on the
abdomen and lower back, found no diVerences across the
menstrual cycle, although women were signiWcantly more
sensitive than males [59]. Gescheider et al. evaluated vibro-
tactile sensitivity throughout the menstrual cycle (at either
15 or 250 Hz) and observed signiWcant changes in threshold
sensitivity over the menstrual cycle, but only at the 250 Hz
level of stimulation. The 250 Hz threshold decreased
steadily in the premenstrual period; once menstruation had
begun, threshold levels increased steadily until approxi-
mately the time of ovulation, then began to fall again. Tac-
tile sensation on the breast, speciWcally, has also been
evaluated. Before puberty, no gender diVerences are pres-
ent; but after puberty, women’s breasts are considerably
more sensitive than men’s. Maximal sensitivity in adult
women was observed during the periovulatory period and
again during menstruation [60].
EVect on taste and appetite
The predictable hormonal Xuctuations characteristic of the
menstrual cycle have also been shown to aVect appetite and
food preferences. Numerous studies have demonstrated a
distinct increase in energy consumption in the premenstrual
period [61–63], with lowest levels of food intake occurring
during the periovulatory period [64, 65].
Hormone levels appear to regulate consumption of spe-
ciWc macronutrients as well, although the numerous studies
have yielded somewhat conXicting data. Numerous studies
have observed signiWcantly increased consumption of car-
bohydrates during the premenstrual period [61–63]; some
have demonstrated an increase in fat intake during this
period as well [63, 66] Rogers et al. found a 61% increase
in energy intake during the premenstrual period, with a
strong preference for foods with a high concentration of
both fat and sugar, foods with high hedonistic properties
[67]. Consumption of these foods, however, was found to
be independent of premenstrual changes in mood [68].
These changes in energy intake parallel well-documented
changes in basal metabolism that are also dependent on
menstrual changes in hormone levels [69]. Some studies,
however, have not found these increases [63].
A paper by Cross et al. reveals that part of the reason for
the existing inconsistencies in the current body of research
may be related to the way that the populations were deWned
Arch Gynecol Obstet
123
as well as the way that the results were analyzed [62]. Cross
et al. looked at both total energy intake as well as intake of
speciWc macronutrients in 154 women by a dietary intake
diary and found that the total intake of energy was
increased in the premenstrual period, with a speciWc
increase in intake for fat and carbohydrates, especially sim-
ple sugars. When the increase in carbohydrate and fat con-
sumption was expressed as the percentage of increase in the
total energy intake, however, no preference for these
macronutrients was found, at least among normal women.
In women with premenstrual syndrome (PMS) (deWned by
prescreening using the Steiner self-rated questionnaire),
however, a distinct preference for sugars and fat during the
premenstrual period was documented, with calorie-dense
foods like cakes and cookies, high in both fat and sugar,
preferentially consumed. A signiWcant increase in binging
behaviors was also observed [62].
The mechanism for this preference for sweets has been
elucidated. Alberti-Fidanza et al. (1998) in a study of eight
fertile women with regard to alterations in taste sensation
and food preferences over the menstrual cycle, found a sig-
niWcant increase in sensitivity to sweet tastes which paral-
leled estrogen concentrations, and an increase in sensitivity
to bitter taste which paralleled progesterone concentrations
[70]. Than et al. (1994) observed the same preovulatory
increase in sensitivity to sugar in 14 ovulatory women [71].
Men had no temporal variations in sucrose sensitivity.
EVect on premenstrual syndrome
Premenstrual syndrome is a disorder characterized by a
diverse set of symptoms, primarily mood-oriented and cuta-
neous but encompassing numerous other systems that recur
in concert with the 2 weeks before onset of menses [72].
PMS tendencies are heritable and persistent throughout
adult life [73]. PMS is oYcially diagnosed in 30–40% of
the female population, with less than 10% aVected severely
[74]. Virtually every adult female in the western world,
however, experiences some PMS symptoms at some time.
Approximately 70% of women report an increase in acne
and other cutaneous eruptions, associated with increased
greasiness of the skin and hair [72]. Pruritus vulvae and
hyperpigmentation deteriorate in the premenstrual period as
well [74]. In atopic patients, predictable exacerbations of
atopic dermatitis (AD) occur [74], including increases in
pruritis as well as erythematous papules and pustules [75].
Although the speciWc etiology of AD is not understood,
dysregulation of the autonomic nervous system is a promi-
nent feature, with a growing association of AD with stress,
anxiety, and depression [75]. SeiVert et al. demonstrated a
higher heart rate and lower vagal activity that persisted
throughout both resting and stress phases of testing,
indicating an increased vegetative excitability in AD
patients [75].
There are also indications of allergic hypersensitivity in
the premenstrual phase, in some individuals, which may be
associated with PMS. Systemic lupus erythematosus is
believed to result from an overproduction of autoantibodies
during the luteal phase [76]; autoimmune progesterone der-
matitis and estrogen dermatitis are abnormal responses to
the endogenous hormones themselves [77, 78].
An unusual case of premenstrual eruptions related to
sensitization to a copper intrauterine contraceptive device
(IUCD) that was in place for 12 years was characterized by
cutaneous eruptions appearing 3–7 days before menses and
resolving with the beginning of Xow. Patch testing con-
Wrmed copper sensitization, and symptoms resolved upon
removal of the IUCD [79].
Itsekson et al. investigated the connection of hypersensi-
tivity to female hormones, dermatologic manifestations,
and PMS. They studied a total of 30 fertile women, 10 who
had both PMS and a concomitant skin disease, 10 with
PMS but no cutaneous manifestation, and 10 healthy con-
trols [74]. Immediate and delayed hypersensitivity reac-
tions to both estradiol and progesterone were observed in
all of the women with PMS, whether or not they displayed
cutaneous symptoms, but none of the controls. Even more
compelling with regards to an immunologic etiology of
PMS, desensitization treatment resulted in substantial ame-
lioration of both emotional and cutaneous PMS symptoms
[74].
The authors speculated, on the basis of their results, that
both autoimmune estrogen dermatitis and autoimmune pro-
gesterone dermatitis may be a dermatologic expression of
PMS. In addition, the association of delayed hypersensitiv-
ity to female sex hormones in PMS with skin disease as
well as a multitude of mental and emotional processes dem-
onstrates a genuine relationship between endocrine,
immune, and neural responses [74].
Although the precise hormonal origin for PMS remains
elusive, its obligatory correlation with the period shortly
before menses suggests a predominant role for progesterone.
Itsekson’s demonstration of positive progesterone and estra-
diol sensitization in PMS patients is compelling support for
an immune component to the disorder, as is the response of
PMS symptoms to immuno-desensitization treatment. PMS,
then, may represent an abnormal immunologic response to
normal hormonal changes, with far-reaching consequences to
both physical and emotional health [74, 80].
Conclusion
The complex interplay of the central nervous system with
the autonomic nervous system, reproductive system, and
Arch Gynecol Obstet
123
immune system, an interplay that produces subtle but far-
reaching changes in mood, emotion, sensory processing,
appetite, and neurocognitive function are just beginning to
be elucidated. What is clear is that estrogen and progester-
one are central players. As the prevalence of estrogen and
progesterone receptors continues to be deWned and the roles
that these two hormones play are more completely under-
stood, the interactions of these molecules within the exqui-
sitely balanced milieu that is the female body, particularly
of child-bearing age, will also continue to be teased out. As
women today spend much of their lives beyond menopause,
the hope is that by gaining an understanding of the interplay
of estrogen and progesterone—hormones that deWne female
biochemistry for much of a woman’s life—in regulating so
many physiological and psychological processes, we will
be able to more eVectively maintain women’s health
throughout their lifespan.
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