JOURNALOF

PSYCHIATRIC

Journal of Psychiatric Research 39 (2005) 55–76RESEARCH

www.elsevier.com/locate/jpsychires

Women’s sleep in health and disease

Andrea Dzajaa, Sara Arberb, Jenny Hislopb, Myriam Kerkhofsc, Caroline Koppd,Thomas Pollm€achera, P€aivi Polo-Kantolae, Debra J. Skenef, Patricia Stenuitc,

Irene Toblerd, Tarja Porkka-Heiskaneng,*

a Max Planck Institute of Psychiatry, Munich, Germanyb Department of Sociology, University of Surrey, Guildford, UK

c Sleep Laboratory Vesale Hospital, Free University of Brussels, Belgiumd Institute of Pharmacology and Toxicology, University of Zurich, Switzerland

e Department of Physiology, University of Turku, Finlandf School of Biomedical and Molecular Sciences, University of Surrey Guildford, UK

g Institute of Biomedicine, University of Helsinki, Finland

Received 19 January 2004; received in revised form 29 April 2004; accepted 8 May 2004

Abstract

Ahuge amount of knowledge about sleep has accumulated during the last 5 decades following the discovery of rapid eye movement

(REM) sleep. Nevertheless, there are numerous areas of considerable ignorance. One of these concerns the particularities of sleep in

women.Most basic and clinical studies have been performed inmale subjects, and only very recently research groups around the world

have addressed women’s sleep in health and disease. In this review, we summarize the present knowledge on the influence of oestrogens

on the brain and on the distinctive changes of sleep across the menstrual cycle, during pregnancy and menopause. In addition, studies

in female rodents are reviewed as well as the knowledge on female peculiarities regarding the interactions between sleep regulation and

age-related changes in circadian rhythms. We also address specific aspects of sleep loss and sleep disorders in women. Finally, very

recent studies on the sociology of sleep are summarized and future directions in the field are discussed.

� 2004 Elsevier Ltd. All rights reserved.

Keywords: Women; Sleep; Hormones; Circadian; Menstrual cycle; Pregnancy; Sex steroids

1. Introduction

In sleep surveys, women report considerably more

sleep problems than men (e.g., Akerstedt et al., 2002a,b;

Hublin et al., 1996; Lindberg et al., 1997), while poly-

somnographically measured sleep quality in elderly men

appears to be worse than in women (Buysse et al., 1991).

But does this necessarily imply differences in sleep be-tween men and women? As most studies on sleep and

sleep loss have been conducted in males, it is not yet

clear which factors contribute most to the sleep distur-

bances reported by women. Changes in sleep patterns

are often associated with hormonal factors, particularly

* Corresponding author. Tel.: +358-9-1918533; fax: +358-9-1918681.

E-mail address: porkka@cc.helsinki.fi (T. Porkka-Heiskanen).

0022-3956/$ - see front matter � 2004 Elsevier Ltd. All rights reserved.

doi:10.1016/j.jpsychires.2004.05.008

oestrogen levels, with women typically suffering from

disturbed sleep in connection with the menstrual cycle,

pregnancy and menopause. Yet explaining disturbances

in women’s sleep is more complex. What is the role of

the genome and other biological factors as opposed to

psychological, sociological and socio-economic factors?

Men and women, even when sharing a common home,

mostly live very different lives, with different responsi-bilities and rights. Taking care of an infant or elderly

relatives, for example, also disturbs sleep (Driver and

Shapiro, 1992; Santiago et al., 2001). In this context,

women’s sleep patterns, as well as health and well-being,

may be determined not only by physiology but rather by

social roles and interactions. Using a multidisciplinary

approach, this review aims to summarise what is pres-

ently known about different aspects of sleep and sleepdisturbances in women.

56 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

2. Basics about sleep and circadian rhythms

2.1. Sleep

Sleep is a behavioural state characterised by a typicalbody position, usually the eyes are closed and respon-

siveness to external stimuli is diminished. Sleep is most

accurately defined by electroencephalography (EEG)

measures which allow, together with the electromyo-

gram (EMG) and electrooculogram (EOG) define, the

classification into different sleep stages according to a set

of criteria (Rechtschaffen and Kales, 1968). In addition,

spectral analysis of the sleep EEG has led to importantinsights into the sleep regulatory processes (e.g., Daan

et al., 1984). Spectral power, particularly in the low

frequency band, the ‘‘delta’’ band (0.75–4.5 Hz), has

proven to be a reliable marker of sleep homeostasis and

is thought to reflect sleep intensity (Borb�ely, 1982a,b).Sleep is not merely a passive state characterised by the

absence of wakefulness. During sleep the cortical ac-

tivity of the brain undergoes regular, cyclic changesbetween the two main sleep states rapid eye movement

(REM) sleep (also called active sleep or paradoxical

sleep) and non-REM sleep, which in humans and other

primates comprises 4 stages (S1–S4). Stages S3 and S4

are defined as deep sleep or slow wave sleep (SWS) in

humans (Rechtschaffen and Kales, 1968). Sleep begins

with S1, proceeds to S2 and usually through S3 and S4

to REM sleep, before the cycle starts again. During non-REM sleep physiological variables such as heart rate,

respiration and cortical activity slow down, body tem-

perature decreases and energy consumption is lower.

When REM sleep begins, cortical activity resembles the

waking pattern. During this state, activity of the motor

neurones at the level of the brain stem/spinal cord is

inhibited, so that body muscles cannot move.

SWS is generally regarded as the deeper, refreshing,restorative part of sleep, though it is not clear what

substrate in the brain and/or in the body is restored

(Rechtschaffen, 1998). The role of REM sleep is even

less clear. Despite many theories including a role in

brain plasticity and learning, experimental evidence for

any of these theories is still scarce (Siegel, 2001; Tononi

and Cirelli, 2001).

2.2. Circadian rhythms

The two main components of physiological sleep

regulation are the homeostatic and the circadian com-

ponent, described in the two process model of sleep

regulation (Borb�ely, 1982a,b). The circadian component

regulates the timing of sleep: for humans sleeping is

easier during the night than during the day. The ho-meostatic component keeps track of the duration of the

previous wakefulness period: the longer we stay awake,

the longer and deeper will be the following sleep. These

components normally work together to ensure correctly

timed and sufficient sleep. However, it is important for

the diagnosis of sleep disturbances to understand the

relation of the two components and to be able to assess

them separately. Both ageing and gender may differe-nentially affect the components of sleep regulation.

Circadian rhythms are endogenously generated by

the pacemaker localised in the hypothalamic suprach-

iasmatic nuclei (SCN). Efferent signals from the SCN

drive circadian rhythms in physiology (melatonin, core

body temperature, cortisol) and behaviour (sleep/wake

cycle, alertness, performance) that have a periodicity of

approximately (circa) 24 h. The circadian SCN clockand its output rhythms are synchronised (entrained) to

the 24-h day by environmental light which is transmitted

from the retina to the SCN primarily via the retinohy-

pothalamic tract (RHT). Ocular light is the major time

cue (also called ‘‘zeitgeber’’) for synchronisation of the

human circadian clock (e.g., Lockley et al., 1997; Skene

et al., 1999), the resetting effect of light being dependent

upon intensity (Boivin et al., 1996; Zeitzer et al., 2000)and circadian time of exposure (Czeisler et al., 1989;

Honma and Honma, 1988; Khalsa et al., 2003; Minors

et al., 1991; Van Cauter et al., 1994).

The two main sleep states, non-REM sleep and REM

sleep, are at least in part regulated separately, and un-

dergo different changes during development and ageing.

2.3. Contribution of the circadian system to age-related

changes in sleep

Studies investigating the role of the circadian system

in age-related sleep changes indicate an inability to

sustain sleep at particular circadian phases (Dijk et al.,

1999; Duffy et al., 1998, 1999a,b; Duffy and Czeisler,

2002). In strictly controlled laboratory studies, older

subjects (64–74 years) exhibited an earlier wake time andan advance (by approximately 1 h) in the rhythms of

melatonin and core body temperature compared to

younger subjects (Dijk et al., 1999; Duffy et al., 1998,

1999a,b). The circadian phase occurred later relative to

the habitual wake up time in the older subjects com-

pared to the young subjects suggesting that older people

wake up earlier in the circadian cycle.

2.4. Age-related changes in sleep

A prominent change with ageing is the reduction in

stages 3 and 4 sleep (SWS) (Feinberg, 1974; Lee and

DeJoseph, 1992; Schweiger, 1972), particularly in men.

This decline coincides with the reduction in growth

hormone (GH) secretion (Van Cauter et al., 2000). As

GH is involved in the regulation of non-REM sleep, ithas been speculated that the decrease in GH could at

least partly explain the decline in SWS. It is interesting

to note that aged women have better preserved SWS

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 57

than aged men (Webb, 1982; Reynolds et al., 1985).

Moreover, the difference in SWS appears to take place

after the age of 30 years, young women and men had

equal amounts of SWS as measured by spectral power

(Ehlers and Kupfer, 1997).Reduced sleep efficiency is also a frequent finding in

the elderly, while stage 1 sleep increases. The number of

nocturnal awakenings increases, as does nocturnal sleep

latency (Carskadon et al., 1982); fragmented sleep ap-

pears to be the main reason for subjectively poor sleep.

An additional frequent finding is an increase in early

morning awakenings and difficulty falling asleep again

(e.g., Feinsilver, 2003). REM sleep appears to be pre-served better in the course of ageing, though shorter

REM latencies have been reported, and REM latencies

are longer in old women than men (Rediehs et al., 1990).

It should be kept in mind that difficulties with sleep in

the elderly are often associated with poor health (for

example, pain, breathing problems and restless legs) and

depression. Side effects of medication may also con-

tribute to poor sleep quality.

2.5. Age-related changes in circadian rhythms

Both endogenous and exogenous factors can con-

tribute to age-related changes in circadian rhythms.

Ageing of the retina, the SCN oscillator, the SCN af-

ferent and efferent neural connections or the down-

stream target nuclei or glands such as the pineal glandare possible endogenous factors (Skene and Swaab,

2003), while changes in environmental light exposure

such as reduced daytime illumination or changes in be-

haviour including early morning awakening or daytime

napping are exogenous factors.

Changes in both the amplitude (amount) and phase

(timing) of circadian rhythms have been reported with

ageing in humans. The reduction in the amplitude of themelatonin rhythm has been widely reported (Bojkowski

and Arendt, 1990; Ferrari et al., 2000; Iguichi et al.,

1982; Kennaway et al., 1999; Luboshitzky et al., 1998;

Sack et al., 1986; Skene et al., 1990a,b; Waldhauser

et al., 1988; Young et al., 1988), as well as a reduction in

the amplitude of the core body temperature rhythm

(Carrier et al., 1996; Dijk et al., 2000; Duffy et al., 1998).

Although many reports indicate that melatonin levelsdecline with age, some recent studies do not support a

reduction (Zeitzer et al., 1999; Fourtillan et al., 2001).

The constant routine conditions (dim light, semi-

recumbent, isocaloric, sleep deprived) and the strict se-

lection criteria for the elderly subjects (non-medicated,

abstinence from alcohol, caffeine, nicotine) the subjects

underwent in these studies may explain the discrepancy

(Skene and Swaab, 2003).Another commonly reported feature in the elderly is

the earlier timing (phase advance) of circadian rhythms

in melatonin (Dijk et al., 1999; Duffy et al., 1999a,b),

core body temperature (Carrier et al., 2002; Duffy et al.,

1998) and cortisol (Sherman et al., 1985). Changes in

circadian rhythms may be due to global neurodegener-

ation with ageing, which includes the SCN (Swaab et al.,

1985), producing a general disturbance of all SCN-dri-ven circadian rhythms. Changes in the timing and

amount of light exposure either as a result of changes in

behaviour, for example, early morning awakening or

age-related changes in the photic input pathway (retina-

RHT-SCN) may also explain the age-related changes in

circadian rhythmicity. Reduced photic entrainment

could also be a result of environmental factors. For

example, there is evidence to suggest that elderly peopleare exposed to reduced illumination levels in their daily

lives (Campbell et al., 1988; Mishima, 2001; Shochat

et al., 2000; Van Someren et al., 1997). Some studies

have shown an inverse relationship between light in-

tensity and sleep disturbances in the elderly (Mishima

et al., 2001; Shochat et al., 2000).

3. Sex steroids and sleep

Sex steroids, e.g., oestrogen, progesterone and tes-

tosterone, not only exert peripheral effects on female sex

organs such as the gonads, but also have powerful ac-

tions on the brain (Baulieu, 1998; Fink et al., 1998;

McEwen, 1999a,b). It is remarkable that sex steroids are

not only involved in the regulation of gonadal hormonesecretion and reproductive behaviours, but also affect

functions such as cognitive performance and sleep

(Sherwin, 2003; Thomson and Oswald, 1977a,b; Manber

and Armitage, 1999; Empson and Purdie, 1999). Apart

from the knowledge derived from the effects of hormone

replacement therapies (HRT) and oral contraceptives on

sleep, data on the influence of steroid hormones on

human sleep are limited. While the effects of oestrogenon brain function have been intensively studied in hu-

mans, the effects of progesterone, that acts in the brain

as a neurosteroid, have been studied mainly in rodents,

and they are less well understood in humans. Thus for

example, the effects of progesterone on sleep and the

sleep EEG were investigated in a double-blind placebo-

controlled crossover study in nine male subjects (Friess

et al., 1997). Progesterone led to an increase in non-REM sleep, a decrease in slow frequency range EEG

activity (0.4–4.3 Hz), and an increase in the higher fre-

quency range activity (>15 Hz) during non-REM sleep.

Furthermore, pregnenolone, a precursor of progester-

one acting as a c-amino-butyric acid (GABA A) recep-

tor agonist, enhanced SWS and reduced EEG activity

in higher frequency bands (Steiger et al., 1993). The role

of physiological oestrous-related changes in progester-one levels on sleep as well as the consequences of pro-

gesterone treatment in females needs to be further

investigated.

58 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

Oestrogen has recently been established as a multi-

purpose brain messenger (Halbreich and Kahn, 2000;

Toran-Allerand, 2000). Through manifold interactions

with the most important neurotransmitter systems at

critical brain nuclei (e.g., the basal forebrain and theraphe nuclei) oestrogen can regulate a multitude of

brain functions, including cognitive performance, mood,

movement co-ordination, pain and sleep (Toran-Aller-

and, 2000; Hutchison and Beyer, 1994; Natale et al.,

2001). It has been shown that many of these interactions

are gender related (McEwen, 1988).

3.1. Menstrual cycle and sleep

Female sex steroids have various effects on central

and peripheral systems. The fluctuating character of

female sex hormones, which is essential for the men-

strual cycle, is reflected in changes in cognitive function,

mood, appetite and sexual activity as well as in physi-

ological changes in temperature and sexual organs such

as the uterus, ovaries and mammae. These complex in-fluences of female sex hormones on different systems

may contribute to the sleep changes that have been

observed in the course of the menstrual cycle.

3.1.1. Hormonal changes across the menstrual cycle

In the central nervous system, the menstrual cycle is

regulated by the pulsatile secretion of the hypothalamic

gonadotropin-releasing hormone (GnRH), which regu-lates the secretion of the pituitary hormones – luteiniz-

ing hormone (LH) and follicle stimulating hormone

(FSH). These hormones in turn regulate the secretion of

oestrogen. The release of GnRH is regulated by neuro-

transmitters (e.g., GABA, DA and serotonin), neuro-

peptides, endogenous opioids and steroid hormones

(oestrogen, progesterone and testosterone) (Jaffe et al.,

1990; Levine et al., 1995; Silberstein and Merriam,2000).

45

30

15

Day 2 4 6 8 10 12 14

Oestrogenpg/ml

FSHmlE/ml

LH

FSH

Oe

Fig. 1. Female sex hormone concentrations across the me

The menstrual cycle lasts, on average, 28 days and

consists of the follicular (before ovulation) and the luteal

(after ovulation) phases; ovulation takes place 14 days

before menstruation begins. Precise and co-ordinated

changes in the plasma concentration of the reproductivehormones oestrogen, progesterone, LH and FSH are

required to create the conditions needed for the matu-

ration and ovulation of a single oocyte each month from

puberty to menopause, the induction of menstruation or

the implantation of the conceptus (Chabbert et al., 1998)

(Fig. 1).

Highest values of oestrogen occur shortly before

ovulation in the follicular phase, with a second increasein the luteal phase, whereas progesterone concentrations

rise in the luteal phase. At the end of the follicular

phase, the LH peak induces ovulation leading to a rise in

body temperature of about 0.5 �C.

3.1.2. Menstrual cycle effects on circadian timing

Female sex hormones, the menstrual cycle, oral

contraceptive use and HRT may all have confoundingeffects on the measurement of circadian rhythms. Tra-

ditionally women have been excluded from most circa-

dian studies, but the recent demonstration of sex

hormone receptors (ERa, ERb and progesterone re-

ceptors) in the human SCN with increased ERa ex-

pression in premenopausal women compared to young

males (Kruijver and Swaab, 2002) suggests the possi-

bility of a direct effect of sex hormones on the humancircadian system.

A gender difference in the phase of the circadian body

temperature rhythm has been reported in young people.

Compared to men, naturally cycling women have been

shown to exhibit phase-advanced circadian temperature

rhythms (Baehr et al., 1999; Baker et al., 2001; Lee,

1988), whereas others have found no gender differences

in circadian phase (Kattapong et al., 1995; Winget et al.,1977). The amplitude of the temperature rhythm may

16 18 20 22 24 26 28

45

30

15

Progesteroneng/ml

LHmlE/ml

P

nstrual cycle (Schmidt-Matthiesen, 1992, modified).

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 59

also be reduced in cycling women compared with men

(Kattapong et al., 1995; Rogacz et al., 1988).

In general, the melatonin rhythm (phase, amplitude

and total amount produced) does not appear to change

throughout the menstrual cycle in normally cyclingwomen (Berga and Yen, 1990; Brzezinski et al., 1988;

Parry et al., 1997). This lack of effect of the menstrual

cycle on melatonin rhythmicity requires confirmation in

dim light and posture-controlled experiments. In addi-

tion, studies designed to assess gender differences in the

melatonin profile are lacking. The large inter-individual

variation in melatonin production (for review, see

Arendt, 1995) may mask observation of any genderdifferences.

3.1.3. Sleep measurements across the menstrual cycle

There are few systematic studies addressing changes

in sleep during the menstrual cycle. Driver and col-

leagues (1996) obtained polysomnographic recordings at

2-day intervals throughout the menstrual cycle in nine

healthy young women. Subjective ratings of sleep qual-ity and mood did not show significant variations across

the menstrual cycle. No differences were observed in

total sleep time, sleep efficiency, sleep latency, REM

sleep latency or SWS. However, there was a consistent

variation in EEG power density in the 14.25–15.0 Hz

band corresponding to the upper frequency range of

sleep spindles, with a maximum of power density ex-

pressed in the luteal phase, parallel with the rise in bodytemperature. A reduction in the power density of the

same frequency band has been reported during preg-

nancy (Brunner et al., 1994), suggesting that this par-

ticular frequency band is sensitive to modulation by sex

steroids and/or body temperature. It is notable that

delta power (0.75–4.5 Hz) did not show changes during

the menstrual cycle, suggesting that the homeostatic

regulation of sleep is not affected by the hormone fluc-tuation during the menstrual cycle. REM sleep, ex-

pressed as a percentage of total sleep time, tended to be

higher in the early follicular phase (27.4%) compared to

the late luteal phase (22.9%), and it was inversely cor-

related with body temperature.

Changes in sleep spindles across the menstrual cycle

were also observed in another study: the lowest spindle

frequency appeared in the follicular phase about 18days before the onset of menstruation, whereas the

highest frequency was measured in the luteal phase 3

days before the onset of menstruation (Ishizuka et al.,

1994).

A significant increase in sleepiness and occurrence of

SWS during the daytime in the luteal phase was ob-

served by Shibui et al. (2000). A decrease in the ampli-

tude of core body temperature, TSH and cortisolrhythms, as well as a decrease in melatonin secretion in

the luteal phase was reported. Also, REM sleep latency

was shorter in the luteal phase compared to the follic-

ular phase, while the percentages of various sleep stages

remained unchanged (Lee et al., 1990).

In summary, in healthy women total sleep time, sleep

efficiency, sleep latency and subjective sleep quality do

not appear to be strongly modulated by the menstrualcycle (Baker et al., 2001; Driver et al., 1996; Ishizuka

et al., 1994; Lee et al., 1990; Parry et al., 1989). In the

high frequency spindle range EEG power density un-

dergoes a marked increase in the luteal phase, coinciding

with an increase in body temperature (Driver et al.,

1996). Some changes in REM sleep and REM sleep la-

tency have been reported (Driver et al., 1996; Lee et al.,

1990), but the findings have not been consistent acrossstudies (Baker et al., 2001).

3.1.4. Sleep complaints associated with the menstrual

cycle

Sleep disturbances perceived by women in associa-

tion with the menstrual cycle often occur in parallel

with several other symptoms. The exacerbation of cer-

tain medical conditions including migraine, epilepsy,asthma, rheumatoid arthritis, irritable bowel syndrome

and diabetes, at specific phases of the menstrual cycle is

well documented (Case and Reid, 1998). Also symp-

tomatic intensification of psychiatric disorders such as

schizophrenia, bipolar disorder, depression, anxiety

disorders, bulimia nervosa and substance abuse have

been reported during the pre-menstrual and menstrual

phases (Hendrick et al., 1996). As the symptoms usuallycluster in the late luteal phase, the condition is referred

to the ‘‘pre-menstrual dysphoric disorder’’ (PMDD),

which involves various mood disturbances including

depressed mood, irritability, dysphoria, affect lability,

anxiety and changes in appetite as well as physical

symptoms such as breast tenderness, headache, acne

and cramps (Andersch and Hahn, 1981; Vanselow,

1998; Gotts et al., 1995; Hurt et al., 1992; West, 1989).Women with PMDD complain about sleep distur-

bances such as hypersomnia, insomnia, awakenings

during the night, tiredness in the morning, unpleasant

dreams, a marked lack of energy and concentration

difficulties, especially in the late luteal phase of the

menstrual cycle (Eriksson et al., 1990; Smith et al.,

2003; Cohen et al., 2002).

The subjective experience of poor sleep quality hasbeen verified in several studies by polysomnographic

recordings. When women with severe pre-menstrual

depression were compared to healthy controls, an in-

crease in stage 2 sleep and a decrease of REM sleep were

measured (Parry et al., 1989). Stage 3 sleep and the

number of intermittent awakenings varied significantly

with phases of the menstrual cycle. The number of

awakenings reached its maximum in the late luteal phasewith lowest values for all the sex hormones involved and

showed a minimum in the early luteal phase shortly after

the peak of LH and FSH when progesterone rises. The

60 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

number of awakenings was associated with LH levels.

EEG alterations similar to those associated with major

depressive disorders, such as a reduced REM sleep la-

tency and an increased REM density (Benca et al., 1992;

Parry et al., 1989).Women with negative affect symptoms (verified with

the profile of moods state scale, POMS) demonstrated

during the pre-menstruum, significantly less delta sleep

during both the follicular and luteal phases, in com-

parison to healthy controls. REM sleep latency was

shown to be significantly shorter during the luteal phase

compared to the pre-ovulatory phase, while there was

no difference in sleep latency or the percentage of REMsleep (Lee et al., 1990; Parry et al., 1989).

Subjective sleep quality, sleep efficiency and REM

sleep of women suffering from primary dysmenorrhoea

decreased in the presence of dysmenorrhoic pain, while

SWS was not affected. Even in the absence of pain the

dysmenorrhoic women had different sleep patterns to

controls: in the mid-luteal, mid-follicular and menstrual

phases, the dysmenorrhoics expressed less REM sleepcompared to the controls. The negative correlation be-

tween body temperature and the amount of REM sleep

was observed in both dysmenorrhoic and control sub-

jects (Baker et al., 1999).

In conclusion, both subjective and objective sleep

quality are impaired in women suffering from dysm-

enorrhoea and/or PMS/PMDD.

3.2. Pregnancy and sleep

Pregnancy is accompanied by dramatic changes in

hormonal levels: oestrogen, progesterone and prolactinlevels increase, as well as human chorionic gonadotropin

(HCG), that is produced by the placenta. A rapid

withdrawal of most of these hormones at the time of

childbirth is accompanied by an additional increase in

circulating prolactin (Darling and Hawkins, 1981; Go-

ebelsmann, 1979; Chrousos et al., 1998).

The subjective sleep quality of most pregnant women

is disturbed starting as early as during the first trimesterof pregnancy (Hedmann et al., 2001; Santiago et al.,

2001). According to sleep surveys, the most frequent

subjective reasons for disturbed sleep during pregnancy

are restless legs and leg cramps, low back pain, foetal

movement and frequent micturation (Hertz et al., 1992).

The prevalence of restless legs syndrome increases dur-

ing pregnancy (Hedmann et al., 2002) and has been

found to be a major factor reducing sleep (McParlandand Pearce, 1988). Periodic leg movements occurred in

all 10 women who had multiple pregnancies (Nikkola

et al., 1996).

During the first trimester of pregnancy the total

amount of sleep increased significantly, decreased in the

second trimester and was shortest three months after

delivery (Hedmann et al., 2001). Sleep became more

restless and fragmented towards the end of pregnancy

accompanied by reduced sleep quality, but was nor-

malised within approximately three months after de-

livery. Although total sleep time increased in the firsttrimester, subjective sleep quality was worse. Due to

decreased depth of sleep, woman in the third trimester

were more likely to be awakened by noise in the envi-

ronment (Hedmann et al., 2002). At the same time

mechanical effects induced a more frequent urge to

urinate, resulting in more awakenings (Baratte-Beebe

and Lee, 1999).

Polysomnographic studies during pregnancy haveshown some inconsistent findings. A decrease in REM

sleep (Brunner et al., 1994; Hertz et al., 1992), but also

no change in REM sleep was observed (Driver and

Shapiro, 1992; Lee et al., 2000a,b). Increased awaken-

ings after sleep onset as well as decreased sleep efficiency

are consistent findings (Brunner et al., 1994; Driver and

Shapiro, 1992; Hertz et al., 1992; Lee et al., 2000a,b).

SWS has been found to be decreased, increased or un-changed. Spectral analysis of the EEG in non-REM

sleep revealed a progressive reduction of power density

during the course of pregnancy; the largest decrease

(30%) occurred in the 14.25–15.0 Hz band (Brunner

et al., 1994). Sleep continues to be disturbed after de-

livery. In addition to nocturnal awakenings for breast-

feeding, hormonal changes may play a role in sleep

disturbances during the postpartum period (Lee et al.,2000a,b; Swain et al., 1997; Lee et al., 1992; Schweiger,

1972; Hertz et al., 1992).

Possible influences of prolactin on sleep were inves-

tigated in a study comparing 12 breast-feeding women

with controls and with women who bottle-fed their in-

fants. Polysomnography showed a marked increase in

SWS in lactating women as compared to the other two

groups that may be attributed to increased levels ofcirculating prolactin (Blyton et al., 2002). Postpartum

women reported more time awake after retiring and

more naps than control women while overall sleep time

was equal between the groups (Swain et al., 1997). In

summary, pregnancy- and postpartum-related sleep

disturbances have a complex background that includes

hormonal, mechanical, emotional and sociological

factors.

3.3. Menopause and sleep

3.3.1. Menopausal transition

A cessation of ovarian endocrine function at meno-

pause leads to a marked decrease in endogenous oest-

rogen and progesterone secretion. This change results in

a more than threefold increase in the secretion of FSH

from the pituitary gland. An elevation of FSH over 30

IU/L confirms the menopause. Alterations in several

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 61

other hormones, including an increase in LH or a

decrease in androgens and prolactin may also occur

(Speroff, 1994). During the menopausal transition, sev-

eral biological functions, including sleep, are affected.

During the menopause, women seek medical assis-tance for the following symptoms: vasomotor instability

(hot flashes and sweating), disturbances in the menstrual

pattern, somatic symptoms (insomnia, headache, dizzi-

ness, palpitation, numbness, myalgia, vaginal and

urinary tract symptoms), as well as psychological

symptoms (anxiety, depression, decline in libido, lack of

concentration, and memory impairment) (Erkkola et al.,

1991; Holte and Mikkelsen, 1991; Oldenhave et al.,1993). Vasomotor symptoms are observed in 68–85% of

symptomatic menopausal women, whereas insomnia is

present in 51–77% (Brincat and Studd, 1988; Erkkola

et al., 1991; Anderson and Falestiny, 2000).

3.3.2. Sleep quality during the menopausal transition

According to a study conducted in France, 73% of

12,778 subjects had experienced sleeping problems dur-

ing the month preceding the survey and 29% of them

had continuous sleeping problems (Leger et al., 2000).

Women more often reported sleep disturbances than

men (Leger et al., 2000; Ohayon, 1996). Insomnia wasreported by 25% of the women and severe insomnia by

15% of the women between 50 and 64 years of age; in the

age group over 65 years the prevalence was 25% and

16%, respectively (Leger et al., 2000). However, epide-

miological data indicating which proportion of sleep

disturbances in middle-aged women is directly linked to

the menopause is lacking.

Sleep disturbances can either be caused by the men-opause or just coincide with the menopausal period. The

clinical picture of menopausal insomnia is indistin-

guishable from common insomnia, which manifests it-

self as difficulty in falling asleep, frequent awakenings or

awakening too early in the morning (Roffwarg, 1979).

Frequent awakenings may suggest that insomnia is

secondary to vasomotor events inducing awakenings

(Woodward and Freedman, 1994). Although vasomotorsymptoms correlate strongly with sleep complaints

(Polo-Kantola et al., 1999a,b), insomnia may occur in

the absence of vasomotor symptoms and can be the

exclusive climacteric symptom. Early morning awaken-

ing may indicate menopausal depression. In the morn-

ing, women may have a feeling of insufficient and

non-refreshing sleep and complain about fatigue, tired-

ness, lack of initiative and impaired memory (Brincatand Studd, 1988).

3.3.3. Circadian rhythm changes with ageing

A few studies have investigated the circadian systemin the elderly and the influence of gender. Campbell and

colleagues showed that the acrophase of body temper-

ature was phase-advanced (by an average of 1.25 h) in

older women compared to age-matched men (Campbell

et al., 1989). The older women also woke up earlier and

had a shorter sleep duration. Similar advanced temper-ature rhythms have also been observed in healthy elderly

women compared to elderly men (Moe et al., 1991). In

this study, the older women also exhibited a larger

amplitude and a higher peak of core body temperature

compared with the men.

3.3.4. Effect of hormone replacement therapy on sleep

quality

Hormone replacement therapy (HRT) is widely used

to control climacteric symptoms (Erkkola et al., 1991;

Wiklund et al., 1992, 1993). It is also an effective treat-

ment to control menopausal sleeping complaints (Polo-Kantola et al., 1998). It facilitated falling asleep and

decreased nocturnal restlessness and awakenings. Wo-

men reported less tiredness in the morning and during

the daytime. The degree of improvement in vasomotor

symptoms was an important predictor of the degree of

improvement in sleep disturbance, providing further

evidence that these two complaints are linked. However,

the subset of menopausal women who reported insom-nia in the absence of vasomotor symptoms, also mark-

edly benefit from HRT (Polo-Kantola et al., 1998). This

was also demonstrated in a recent large randomised,

placebo-controlled study evaluating the long-term ef-

fects of HRT (Women’s Health Initiative, WHI) where

participants were mainly climacterically asymptomatic

(Hays et al., 2003). Two explanations are possible:

firstly, women regarding themselves as asymptomaticmay nevertheless have hot flushes. If this is the case,

alleviation of the vasomotor symptoms again plays an

important role in improving sleep quality. Secondly,

sleep disturbances may be a direct consequence of

changing hormone levels associated with menopause.

There are contradictory findings about the effects of

HRT on objective sleep quality as measured by all night

polysomnography. The main outcome of previousstudies in healthy women is presented in Table 1.

Menopausal insomnia is not characterised by specific

abnormalities in a polysomnographic sleep recording

(Polo-Kantola et al., 1999a,b). However, intensive hot

flashes may cause arousals (Erlik et al., 1981) and have

been found to be associated with increases in stage 4

sleep, a shortened first REM sleep period and disrupted

sleep with reduced sleep efficiency (Woodward andFreedman, 1994).

Some authors have reported fewer awakenings, a

decrease in nocturnal wakefulness and an increase in

REM sleep during HRT (Antonijevic et al., 2000;

Thomson and Oswald, 1977a,b). Moreover, a shorten-

ing of sleep latency, an increase in REM sleep (Schiff

Table 1

Previous studies about HRT effect on sleep polysomnography in heathy women

Author(s) Study design Subjects Treatment Findings Comment

Thomson and

Oswald

(1977a,b)

Prospective, placebo-con-

trolled, double-blind

34 perimeno-

pausal women

Piperazine oestrone sul-

phate

Oral 8 weeks

Decrease of wakeful-

ness and awakenings

Increase of REM

sleep

Oestrogen effect on

hot flashes, mood or

anxiety similar to

placebo

Schiff et al.

(1979)

Prospective, placebo-

controlled, double-blind,

crossover

16 hypogonadal

women

Conjugated equine oestro-

gen 0.625mg/day

Oral 100 days

Shorter sleep latency

Increase of REM

sleep

Decrease of serum

FSH and vasomotor

symptoms

Erlik et al. (1981) Case-control 4 postmeno-

pausal women

Ethinyl oestradiol 50 lg· 4/day

Decrease of

awakenings

Decrease of hot

flashes

Oral 30 days No placebo group

Pickett et al.

(1989)

Prospective, randomized,

placebo-controlled,

crossover

9 postmeno-

pausal women

Conjugated equine

oestrogen 1.25m g/day+

medroxyprogesterone

acetate 20 mg/day (MPA)

No improvement in

polysomnographic

parameters

No measurements for

symptoms or serum

hormone

concentrations

Oral 7 days

Purdie et al.

(1995)

Prospective, randomized,

placebo-controlled, single-

blind

33 postmeno-

pausal women

Conjugated equine

oestrogen 0.625 mg/day+

norgestrel 0.15 mg/day

(days 17–28)

No improvement in

polysomnographic

parameters

Decrease of meno-

pausal symptoms and

improvement of psy-

chological well being

Oral 12 weeks

Scharf et al.

(1997)

Prospective, placebo-con-

trolled, single-blind

7 postmeno-

pausal women

Conjugated equine

Oestrogen 0.625 mg/day

Oral 4 weeks

Improvement of sleep

efficiency, reduction

of cyclic alternating

patterns of sleep and

awakenings

Decrease of hot

flashes

Polo-Kantola

et al. (1999a,b)

Prospective, placebo-con-

trolled, double-blind,

crossover

62 postmeno-

pausal women

Oestradiol 50 lg/24 h

patches or gel 2.5 g/day

Transdermal 7 months

Decrease of

movement arousals

Decrease of serum

FSH and vasomotor

symptoms

Antonijevic et al.

(2000)

Prospective, crossover 11 postmeno-

pausal women

Oestradiol 50 lg/24 h

patches

Increase of REM

sleep

Decrease of serum

FSH and LH levels

Transdermal 2 weeks Reduced time awake

during first two sleep

cycles

No placebo group

Montplaisir et al.

(2001)

Prospective, randomized,

two group-treatment study

21 postmeno-

pausal women

Conjugated equine

oestrogen 0.625 mg/day+

either medroxyprogester-

one acetate 5 mg/day

(MPA) or microniced

progesterone 200 mg/day

Oral 6 months

Improvement of sleep

efficiency and reduc-

tion of time spent

awake after sleep on-

set during oestrogen

+ micronized proges-

terone but not during

oestrogen + MPA

Decrease of

menopausal

symptoms and

improvement of

subjective sleep

quality during the

both treatments

No placebo group

62 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

et al., 1979), an improvement in sleep efficiency and a

reduction of the rate of cyclic alternating patterns of

sleep (Scharf et al., 1997) or a decrease in the number of

waking episodes (Erlik et al., 1981) have also been re-

ported. In the largest study, a decrease in movement

arousals was the only objective change during HRT

(Polo-Kantola et al., 1999a,b), whereas some studies

have reported no improvement at all in polysomno-graphic sleep variables (Pickett et al., 1989; Purdie et al.,

1995).

The variation in results may be due to differences in

the study population (peri-menopausal, natural or sur-

gically induced menopause, age) and methodology

(dose, form and duration of HRT) (Thomson and Os-

wald, 1977a,b; Schiff et al., 1979).

3.3.5. Treatment of menopausal insomnia

In women with climacteric vasomotor symptoms,

HRT can be considered as the primary therapy for in-

somnia. Climacteric women, whose insomnia is essen-

tially accompanied by mental symptoms, also benefit

from HRT (Polo-Kantola et al., 1998). There is some

evidence that HRT could also alleviate sleep complaints

in women with no vasomotor symptoms (Polo-Kantolaet al., 1998). No specific therapies for insomnia need to

be initiated during the menopausal transition before the

individual response to HRT has been evaluated after 3–

6 months of the treatment. However, in women over 60

years the vascular side-effects of HRT may exceed its

beneficial effects on sleep (Hays et al., 2003) and thus

starting HRT should be considered carefully. In women

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 63

with concerns or contraindications for HRT (previous

breast and endometrium cancer, tromboembolic event,

liver disease) other treatment options, including anti-

depressants (e.g., selective serotonin reuptake inhibitors,

SSRI), gabapentin, dietary isofavones and soy foods, aswell as relaxation therapies should be considered. Al-

though menopause often causes or worsens sleep dis-

turbances, it should be remembered that part of the

disturbances may just coincide with the menopausal

period rather than being of endocrinological origin.

Thus, symptoms and signs that would normally lead to a

full sleep evaluation in premenopausal women should

also be taken seriously in postmenopausal women andnot automatically be considered as a normal conse-

quence of the menopause.

4. Contribution of animal models: influence of age and the

oestrus cycle on sleep

Animal studies, mostly conducted with rodents, have

provided essential contributions to the understanding of

the neurobiological mechanisms underlying the age- and

hormone-related changes in sleep and circadian rhythms.

4.1. Age and sleep in animals

Age-related modifications in daily and circadian

sleep–wake patterns have been investigated foremost inmale rodents. Early studies reported a shorter period of

the circadian locomotor activity rhythm (Pittendrigh

and Daan, 1974) and sleep (Van Gool et al., 1987) in

ageing hamsters and rats. However, more recent studies

performed in hamsters showed that the circadian period

does not slow down systematically with age (Davis and

Viswanathan, 1998; Duffy et al., 1999a,b). In aged mice

no change or a lengthening of the circadian period wasfound (reviewed by Weinert, 2000). These inconsistent

findings could be related to species and strain variability

and to different illumination conditions. An amplitude

decrease both in the daily sleep–wakefulness rhythm as

well as in the circadian sleep rhythm was reported in

27- to 35-month old C57BL mice compared to 3- to 15-

month old mice (Welsh et al., 1986). In the rat, an age-

dependent reduction of the sleep–wake amplitude wasfound in animals maintained under a controlled light/

dark cycle, but not under constant conditions (Men-

delson and Bergmann, 1999a,b; Van Gool and Mirmi-

ran, 1983; Van Gool et al., 1987).

Changes in sleep architecture have been reported in

ageing rodents. Early studies described a decline of total

sleep time and a shortening of individual sleep episodes

in 22- to 30-month old rats compared to 4- to 8-monthold rats (Van Gool and Mirmiran, 1983; Zepelin et al.,

1972). Exposure to a higher light intensity led to a re-

versal of these age-related changes (Witting et al., 1993).

An age-dependent reduction of sleep was found also in

mice (Eleftheriou et al., 1975). Although this result was

based on 6-h sleep records performed at an unspecifiedtime of day, the results suggested that the age at which

these modifications appeared was strain-dependent. In

C57BL/6 mice the changes had already occurred at 6

months while in DBA mice they appeared only later, at

12–23 months. Sleep was more fragmented in 27- to 35-

month old C57BL mice compared to younger, 3- to 12-

month old mice (Welsh et al., 1986). In rats and mice

recorded under constant environmental conditionssubtle age-related sleep changes were indicated by the

larger sleep fragmentation in old animals, while the

overall amount of vigilance states did not vary with age

(Van Gool et al., 1987; Welsh et al., 1986; Mendelson

and Bergmann, 1999a).

Studies investigating the effects of age on the sleep

EEG in rodents are rare and the results showed some

inconsistencies. Thus, non-REM sleep EEG power inthe delta range was either reduced or unchanged in ap-

proximately 24-month old rats (Tani and Ishihara, 1988;

Van Gool and Mirmiran, 1983). Both studies are limited

by the small amount of non-REM sleep used for the

EEG analysis that consisted either in a single 10 min

period per animal or in only a few 60–90 s periods

preceding the onset of a REM sleep episode. Delta

power based on 24 h and expressed relative to total EEGpower in non-REM sleep showed no age-related changes

between 3-, 12- and 24-month old Fischer-344 rats

(Mendelson and Bergmann, 1999a,b). On the other

hand, 24-h delta EEG power computed by a software

system was drastically reduced in 20-month-old Fischer-

344 rats, while in young and old Sprague–Dawley rats it

remained similar, approximately in the range found in

the old Fischer-344 rats (Shiromani et al., 2000).The effect of age on the homeostatic regulation of

sleep in rodents was addressed recently. The sleep re-

bound following sleep deprivation was reduced in mid-

dle-aged and old rats compared to young adults

(Mendelson and Bergmann, 2000). The typical en-

hancement of delta EEG power in non-REM sleep after

sleep deprivation was still present in rats at the age of 12,

20 and 24 months, but the effect of age on this responseremains controversial (Mendelson and Bergmann,

1999a,b; Shiromani et al., 2000).

4.2. Potential neurobiological mechanisms

The neurobiological mechanisms underlying age-de-

pendent changes in sleep remain unknown. The modifi-

cation of the daily sleep–wake pattern might be related to

a deterioration of the circadian clock itself, suggested by

a reduction of the mean peak of the neuronal firing

64 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

within the SCN in aged rats (Satinoff et al., 1993).

Moreover, the reduction of the sleep–wake amplitude

may be related to a dysfunction of the hypocretin/orexin

system. Thus, a decrease in hypocretin receptor 2 mRNA

expression in the hippocampus, thalamus and brainstemwas found in 12- to 24-month old C57BL/6 mice (Terao

et al., 2002) and a decrease in both prepro-orexin mRNA

as well as in the concentrations of the orexin peptides was

found in the ageing (12–14 months) rats (Porkka-He-

iskanen et al., 2003). A recent study claimed that the

transgenetically induced over-expression of the human

mutant b-amyloid precursor protein might enhance the

age-related disturbances in the sleep–wake distributionof 20- to 26-month old mice (Huitron-Resendiz et al.,

2002). The effects of age on sleep, however, were not

assessed statistically. A deficiency in c-fos induction by

waking in the hypothalamus and cingulate cortex might

be involved in the smaller sleep rebound after sleep de-

privation in old rats (Basheer and Shiromani, 2001).

4.3. Sleep and ageing in female rats and mice

Sleep studies in ageing female rodents are scarce. In

an old population of female Long–Evans rats Li and

Satinoff (1995) distinguished between individuals whichstill displayed a circadian rhythm of body temperature

and a sleep pattern that was similar to the one obtained

in young rats, and individuals which had no temperature

rhythm or an unstable rhythm and a concomitant

damping in their daily sleep–wake amplitude. The in-

fluence of the oestrus cycle on these patterns was not

specifically addressed.

Female C57BL/6 mouse

Female rat

Days

Days20 8 20 88

1

5

10

15

20 8 20 881

5

10

15

(a)

(b)

Fig. 2. Individual running wheel activity plots in a 12 h light–12 h dark

in a female mouse of the strain C57BL/6 (a) and a female Sprague

Dawley rat (b). Records are double-plotted, i.e. the horizontal axis

represents 48 h and each 24-h interval is represented twice. The black

and white bars at the top indicate the timing of the LD cycle.

4.4. Sleep and the oestrus cycle in rodents

A few studies focusing on young adults examined the

influence of oestrus cyclicity on sleep regulation in ro-dents. The oestrous cycle is defined by the succession of

four stages: proestrus, oestrus, metoestrus and diestrus.

Each stage can be determined according to the following

criteria based on histology of vaginal smears (Michael,

1976): proestrus, nucleated epithelial cells predominant;

oestrus, only cornified cells; metoestrus, leukocytes and

cornified cells; diestrus, leukocytes predominant. In mice

as in the rat, ovulation is preceded by a sharp rise incirculating LH and FSH (Murr et al., 1973). In outbred

mice a major surge of plasma progesterone in the late

afternoon of proestrus and a second peak in metoestrus

following a pattern similar to the rat were found (Mi-

chael, 1976). The timing of the main peak of proges-

terone was shown to depend on the mouse strain

(DeLeon et al., 1990).

Young female rats are well known to exhibit regular4- or 5-day oestrus cycles. In mice the cycle-length is

more variable, between 4 and 9 days, and cycling is less

regular. Early studies in young adult mice suggested a

complex interaction between hereditary and environ-

mental factors in the regulation of the length of the

oestrus cycle (Barkley and Bradford, 1981; Champlin,1971; De Leon and Barkley, 1987). Comparisons of

three inbred strains, C57BL/6, DBA and C3H/He, sug-

gested that the frequency of regular oestrus cycles and

their duration are differentially genetically regulated

(Nelson et al., 1992a,b).

A recent study of inbred mice reported a minor oes-

trus-dependent modulation of sleep that depended on

the genetic background (Koehl et al., 2003). In C57BL/6mice, the proestrus night was accompanied by a decrease

in REM sleep only, while in C3H/He mice a reduction of

non-REM and REM sleep was observed during diestrus.

On the other hand, BALB/c mice showed no sleep

changes across the oestrous cycle. Although infradian

rhythms of body temperature and locomotor activity

had been suggested to reflect the ovarian cycle in out-

bred mice (Weinert, 1996), such a relationship could notbe detected in C57BL/6 and C3H/He mice by Koehl

et al. (2003). Another study showed that C57BL/6 mice

recorded continuously during several oestrus cycles are

often more active in the second half of the proestrus

night compared to metoestrus and diestrus (Fig. 2), but

the increase of motor activity could not be attributed

specifically and consistently to proestrus days (Kopp

et al., 2002). In contrast to mice, female rats show amarked and consistent increase in motor activity and a

concomitant reduction in sleep during the proestrus

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 65

night (Fig. 2; Colvin et al., 1968; Kent et al., 1991;

Kleinlogel, 1983; Schwierin et al., 1998; Yokoyama

et al., 1966). This period of intense activity associated

with increased receptivity and mating behaviour is fol-

lowed by an enhancement of sleep on the oestrus day(Yokoyama et al., 1966).

Only minor changes in sleep were induced by ovari-

ectomy in the rat. Non-REM sleep was not or only

slightly increased while REM sleep was consistently

enhanced (Fang and Fishbein, 1996; Li and Satinoff,

1996). An inhibitory action of gonadal steroids on sleep,

particularly on REM sleep has been proposed (Colvin

et al., 1968; Fang and Fishbein, 1996). Sleep EEGspectral analysis revealed that the sleep rebound occur-

ring in the oestrus light period after the spontaneous

partial sleep deprivation of the proestrus night in the rat

is accompanied by an enhancement of delta activity in

non-REM sleep (Schwierin et al., 1998). Interestingly,

the study showed that homeostatic sleep response to 6 h

sleep deprivation was similar in proestrus and in oestrus.

The relation between peripheral and central con-centrations of steroids across the oestrous cycle was

investigated in young adult mice from the HsdOla

strain (Corpechot et al., 1997). The levels of proges-

terone in the brain followed a clear daily pattern, with a

peak in the first half of the night and reaching maximal

values in metoestrus and oestrus, but no correlation

was found between brain and plasma progesterone

levels. However, there was a positive correlation be-tween the concentration of pregnenolone sulphate in

the brain and the oestrous-dependent pattern of plasma

progesterone. Interestingly, exogenous progesterone

and its metabolite allopregnanolone as well as preg-

nenolone are known to affect sleep and/or the sleep

EEG in the rat (Lancel et al., 1994, 1996, 1997). These

neuroactive steroids exert their influence upon an al-

losteric modulation of the GABA-A receptors (Lam-bert et al., 1995; Lancel et al., 1999). Complex

interactions between sleep regulation, oestrous-related

patterns of steroids, and the GABAergic system can be

expected in ageing females. Further investigations

should help to clarify the mechanisms involved in the

effects of HRT in postmenopausal women.

5. Sleep disorders in women

Sleep disorders are among the most frequent prob-

lems affecting people’s health. Insomnia, for example,

affects more than 10% of the general Western popula-

tion at any given time point (e.g., Hajak, 2001). Hy-

persomnia is less frequent, but still 1–2% of the

population suffers from obstructive sleep apnoea (OSA),which, in addition to causing marked excessive daytime

sleepiness, leads to serious pulmonary and cardiovas-

cular morbidity (Young and Peppard, 2000).

Due to the aforementioned specific features of female

physiology, it is not surprising to find prominent gender

differences in the frequency of some sleep disorders. The

most important ones will be described below.

5.1. Insomnia

Insomnia is a subjective and non-specific complaint

that is related to the quantity or quality of night sleep.

Insomniacs might complain about difficulties falling

asleep, maintaining sleep or of premature morning

awakenings resulting in a subjectively reduced total

sleep time. Moreover, even the hours these people sub-jectively sleep might be perceived as superficial and

fragile and closer to dozing than to consolidated deep

sleep. Complaints of poor sleep have a myriad of causes

that encompass almost every aspect of sleep medicine

and some of them occur about twice as frequently in

women than in men (Harris, 2003).

Unfortunately, the reasons for the strong prepon-

derance of women among insomniacs have not beensystematically studied and reviewed, and in the present

context we can only examine some very obvious un-

derlying circumstances. Among these are the endocrine

peculiarities related to the menstrual cycle and to age-

ing that have been described in detail earlier in this

review article. However, it is interesting to note here

that the direct influence of hormonal changes on sleep

in women might be less pertinent for understandinginsomnia in women than expected. For example, ho-

meostatic sleep regulatory mechanisms, as indexed by

the time course of EEG slow wave activity, are not

substantially affected by the menstrual cycle (Driver,

1996). Changes in subjectively perceived and objectively

measured night sleep are only significant in women with

additional complaints summarised as the PMDD. This

suggests that hormonal changes across the menstrualcycle per se have only a minor direct and specific im-

pact on sleep in women, but in a subgroup affect sleep

and physical and psychological well-being simulta-

neously. It seems, though, that disturbed premenstrual

sleep is part of a complex of complaints rather than

reflecting a primary problem of disturbed sleep initia-

tion and maintenance.

Sleep complaints are particularly frequent in peoplesuffering from major psychiatric disorders and in par-

ticular affective disorders. Because these are about twice

as frequent in women compared to men (Harris, 2003),

psychiatric morbidity is likely to contribute significantly

to the preponderance of females among insomniacs.

Interesting sleep EEG gender differences have been re-

ported in depressed subjects (reviewed by Manber and

Armitage, 1999). Whether these differences reflect clini-cally relevant gender differences in the neurobiological

basis of the interactions between sleep and mood is an

important, but still unanswered question.

66 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

The gender differences in the EEG that have been

reported in healthy people (e.g., Carrier et al., 2001)

suggest that there may be differences in basic sleep reg-

ulating mechanisms. It is interesting to speculate that

these could lead to an increased general vulnerability ofwomen’s sleep. This should be reflected in an increased

prevalence of ‘‘pure’’ insomnia (primary and/or psy-

chophysiological insomnia) that is not related to hor-

monal changes or psychiatric morbidity. However, to

our knowledge, this has not been clearly demonstrated.

5.2. Restless legs syndrome and periodic leg movements

The restless legs syndrome (RLS) is a clinical entity

characterised by a combination of unpleasant sensations

in the legs (much less frequently also in the arms) and a

strong urge to move (Wetter and Pollm€acher, 1997).

Typically, symptoms start in the evening or upon retiring

to bed and have a major negative impact on sleep onset.

Following sleep onset the symptoms might resume dur-

ing periods of intermittent wakefulness, thereby dis-turbing sleep maintenance. During sleep itself the vast

majority of subjects affected display periodic limb

movements (PLMDs), which might or might not be ac-

companied by arousals (Pollm€acher and Schulz, 1993).

Prevalence estimates for RLS range from 5% to 10%

and, overall, no consistent gender difference has been

reported. Most researchers discriminate between an idi-

opathic form with a strong genetic background and asecondary, symptomatic RLS. Among these secondary

forms is RLS during pregnancy and, consequently, a

significant number of pregnant women experience RLS

symptoms. Recent epidemiological data suggest a prev-

alence of about 25% with an incidence peak during the

second and third trimester (Lee et al., 2001). Idiopathic

RLS has been reported to worsen during pregnancy

(Winkelmann et al., 2000). The causes of the emergenceor worsening of RLS symptoms during pregnancy are

unknown. As various lines of evidence suggest a link

between RLS and anaemia it has been hypothesised that

signs of iron deficiency during pregnancy might correlate

with the appearance of RLS symptoms. However, nei-

ther haemoglobin nor iron or ferritin predicted the oc-

currence of RLS in pregnant women, whereas folate

levels appeared to be reduced. In the same study it wasshown that RLS symptoms might persist after delivery,

but appear to cease in the majority of women (Leger

et al., 2000). This area of women’s sleep disorders is

clearly under-investigated. The epidemiological database

is small and we know almost nothing about risk factors,

cause, and specific options for treatment.

5.3. Obstructive sleep apnoea syndrome

The most common and widely studied of the sleep-

disordered breathing syndromes, affecting about 2%

of middle-aged women and about 4% of middle-aged

men (Young, 1993), is obstructive sleep apnoea syn-

drome (OSAS). Hallmarks of risk for OSAS are

overweight with snoring and excessive daytime sleep-

iness. Because clinical reports in the 1970s and 1980ssuggested that OSAS primarily affected men, women

were excluded from general epidemiological studies

until 1993 (Young et al., 1993; Kapsimalis and Kry-

ger, 2002a,b). The early studies in clinical populations

reported male:female prevalence ratios for OSAS at

10:1, while more recent studies in general population

samples report prevalence between 2:1 and 4:1

(Young et al., 1993; Kripke et al., 1997; Bixler et al.,2001; Kapsimalis and Kryger, 2002a,b). If a variant

mainly characterised by heavy snoring but few ap-

noeas is included, this ratio even goes down to 1:1.5

(Mohsenin, 2001).

One reason for the long-standing underestimation of

the prevalence of OSAS in women might be a difference

in the symptom profile. In particular, patient’s self-re-

ports (which are critical for patient’s help-seeking be-haviour and doctor’s appreciation of the complaint)

suggest that loud snoring and gasping are much more

prevalent in male OSAS patients than in females (Red-

line et al., 1994).

Obesity is typically associated with OSAS. However,

there is compelling evidence that female OSAS patients

are much more obese than males (Kapsimalis and

Kryger, 2002a,b). Interestingly, two groups of femaleOSAS patients are particularly prone to obesity: pre-

menopausal women and postmenopausal women on

HRT. Given that obesity is a strong risk factor for

OSAS, these findings suggest that female sex hormones

might be protective at least in non-obese women. This

idea is further supported by epidemiological evidence

showing that the prevalence of OSAS in premenopau-

sal and postmenopausal women on HRT is similar(<1%) (Bixler et al., 2001) and much lower than in

postmenopausal women without HRT (2.7%) (Bixler

et al., 2001). Finally, pregnancy might be protective

against OSAS even in obese women (Maasilta et al.,

2001).

Furthermore, there seem to be slight differences in the

medical consequences of OSAS between males and fe-

males. Whereas females more often display depressionand chronic obstructive lung disease, men are more

frequently diagnosed with coronary artery disease.

It is beyond the scope of the present article to dis-

cuss in detail the reasons for the prominent gender

differences in the occurrence of OSAS and in the fea-

tures of this disease. Numerous contributing factors are

likely to play a role, ranging from gender differences in

fat distribution across upper airway anatomy to en-docrine aspects. Readers are referred to a recent com-

prehensive review on this issue (Kapsimalis and

Kryger, 2002a,b).

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 67

5.4. Narcolepsy

Narcolepsy is a rare sleep disorder (prevalence

<1:2000) characterised by excessive daytime sleepiness

and cataplexy, which is manifested as a sudden short-lasting loss of muscle tone triggered by emotions (Ove-

reem et al., 2001). Further symptoms include automatic

behaviour, sleep paralysis and hypnagogic hallucina-

tions. The key pathophysiological feature of narcolepsy

is a disturbance in the transitions between wakefulness,

REM and non-REM-sleep. The causes of narcolepsy are

multifactorial, including a genetic component associated

with a human leukocyte antigen (HLA-DQB1*0602)and unknown environmental factors. Possibly through

an autoimmune mechanism these factors trigger a loss

of orexin production in the lateral hypothalamus.

Orexins, also called hypocretins, are involved in the

regulation of arousal, sleep, and appetite. Orexin defi-

ciency occurring through a number of steps that are not

yet fully understood, leads to the symptoms of narco-

lepsy (Dalal et al., 2002).Studies on the epidemiology of narcolepsy consis-

tently report a male gender predominance. The ratio of

female to male patients is around 1:1.5. The reason for

this gender difference is unknown and it has been a long-

standing assumption that the rate of diagnosed female

patients is artificially low due to a lower tendency of

women to seek medical care. It has been argued that

different social settings, in particular with respect to jobrequirements, lead to an increased (relative) disability in

males and, as a consequence, to an increased liability to

seek medical help.

However, recent epidemiological evidence points in

an interesting different direction. Tafti and colleagues

have analysed functional polymorphisms of catechol-

O-methyl transferase in narcoleptic subjects, because

this enzyme is critically involved in the metabolism ofbiogenic amines and, hence, important for vigilance

regulation. Their findings indicate a complex gender/

genotype/drug response interaction in narcolepsy: fe-

male patients with this disorder, compared to males,

have a higher probability of carrying a polymorphism

associated with low COMT activity (suggesting higher

availability of biogenic amines). These women are less

severely affected than males and respond more favour-ably to treatment that enhances DA activity (for review

see Tafti and Dauvilliers, 2003). Although these very

novel findings deserve independent replication, they

provide the first data supporting the hypothesis that

gender-related genetic peculiarities are important de-

terminants of sleep disorders in women.

5.5. REM sleep behaviour disorder

REM sleep behaviour disorder (RSBD) is a para-

somnic sleep disturbance characterised by impaired

REM sleep-related active inhibition of muscle tone

(Schenck andMahowald, 2002). This inhibition prevents

major movements during REM sleep which could occur

as a behavioural correlate of dreaming. Hence, normal

individuals might display minor face or limb movementsduring REM sleep, but they neither sit up nor leave the

bed. RSBD patients, in contrast, show major, often vi-

olent movements while vividly dreaming. This kind of

behaviour is one of the major causes of sleep-related

injury to the sleeping subjects themselves or to their bed

partners. RSBD is rare and typically occurs during the

second half of life with a peak incidence in the 50s and

60s. There is a remarkable association with Parkinson’sdisease and other neurodegenerative disorders. Surpris-

ingly, RSBD occurs almost exclusively in men. The ratio

of female to male patients is about 1:9. The reasons for

this striking gender difference are not known.

6. Effects of sleep loss in women

Chronic sleep curtailment is now a common feature

in our society both for men and particularly for women.

Average sleep duration has decreased from 9 h in 1910

to 7.5 h (Broman et al., 1996; Webb and Agnew, 1975)

and 6.22 h (Jean-Louis et al., 2000). The 24/7 focus of

modern life results in shift work for about 20% of

workers. As a consequence, sleep duration is reduced to

5 h per work day in these workers (Bliwise, 1996). Theacute and chronic effects of this sleep reduction for

women are poorly documented.

6.1. Shift work

Shift work, particularly at night, is problematic for

the worker. It represents a serious risk factor for sleep

disorders such as insomnia and daytime sleepiness(Akerstedt, 1998, 2003). The frequency of sleep com-

plaints in this population is twofold higher than in the

general population. These problems are mainly due to a

disruption of the normal sleep/wake pattern but also

involve other factors such as age, gender, stress at work,

health problems and social and family factors.

Loss of sleep is a general complaint in shift workers

of both genders (H€arm€a et al., 1998). Objective sleepmeasures indicate that 1–4 h less sleep is obtained during

daytime sleep than during a normal night (Czeisler et al.,

1980). This loss of sleep tends to accumulate with suc-

cessive night shifts. As a consequence, there is an in-

crease in daytime sleepiness and a tendency to sleep

more and to take more naps on holidays and weekends

(Webb and Agnew, 1975).

High levels of sleepiness during night and morningshifts have been documented. Moreover, involuntary

sleep episodes at work have been shown in several

studies based on questionnaire data and on continuous

68 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

EEG recordings (Kecklund and Akerstedt, 1993; Kogi

and Ohta, 1975). According to Partinen and colleagues

(1984) sleep disturbances are more frequent among

manual workers than among physicians or managers.

It is now well established that sleep disturbances aremore frequent in women and in older individuals

(Akerstedt, 2002; Avidan, 2002; Feinsilver, 2003; Ford

and Cooper-Patrick, 2001). In a representative sample of

58,115 individuals Akerstedt and colleagues found more

sleep disturbances and fatigue in women (Akerstedt,

2002). The reasons for this increased frequency is not yet

clear. It is possible that family duties and/or hormonal

factors could play a role. Several studies have analysedthe effects of night shifts and early shifts in nurses (Barak

et al., 1996; Gold et al., 1992; Kogi and Ohta, 1975;

Wootten, 2000). A recent study of health professionals

by Ohayon et al. (2002) showed that working on a ro-

tating daytime shift induces significant sleep distur-

bances, more sick leave and more work-related accidents

compared to fixed daytime and night time work.

In addition to fatigue and sleep disturbances, shiftwork, particularly at night, may also increase the risk of

some forms of cancer in women. One proposed expla-

nation is that exposure to light at night suppresses

melatonin production which has potential oncostatic

action. According to Davis and colleagues the risk of

breast cancer is higher among women who frequently do

not sleep at night with an increased risk among subjects

working in the brightest places (Davis et al., 2001). Therisk was particularly high in women who had worked 30

or more years at night (Schernhammer et al., 2001).

Moreover, a recent study indicates that working a ro-

tating night shift at least three nights per month for 15

or more years increases the risk of colorectal cancer in

women (Schernhammer et al., 2003).

6.2. Sleep deprivation studies

Total sleep deprivation and its effects on performance

have focussed on studies in men (Barak et al., 1996;

Harrison et al., 2000). The symptoms include increased

tiredness, decrease in psychomotor performance and

vigilance, mood changes, memory deficits and during a

prolonged sleep deprivation, also hallucinations

(Drummond and Brown, 2001). Functions which requireintact frontal lobe activity (e.g., motivation and creative

thinking) are particularly sensitive to the effects of sleep

deprivation (for a review see Muzur, 2002). Several hy-

potheses have been advanced to explain performance

decrements after sleep deprivation, including reduction

in the capacity to process information, overall changes in

arousal and decreased capacity to sustain attention due

to involuntary micro sleeps. During these brief sleep ep-isodes the subjects are not able to react to stimuli re-

sulting in ‘‘response lapses’’. According to this ‘‘lapse

hypothesis’’ subjects are more affected by sleep loss in

tasks involving work-paced stimuli rather than self-paced

stimuli. Furthermore, it is performance speed rather than

performance accuracy that is compromised (Koslowsky

and Babkoff, 1992). In a sleep restriction study on 8

young women impaired performance was found in asimple reaction time test (Tilley and Wilkinson, 1984).

Long term sleep restriction studies for 7 (Dinges et al.,

1997) or 14 (Van Dongen et al., 2003) consecutive days

have been performed in men and women and indicate

that even moderate sleep restriction can seriously impair

waking behavioural functions in both genders. Gender

differences were not addressed in these studies.

Sleep restriction and sleep deprivation have also beenshown to have a negative impact on carbohydrate me-

tabolism (VanHelder et al., 1993; Gonzales-Ortiz et al.,

2000), endocrine function (Spiegel et al., 1999) and on

immunity (Dinges et al., 1995; Spiegel et al., 2002) in

healthy men. However, such findings remain to be

demonstrated in women.

One important issue related to sleep deprivation

concerns the recovery process. Typically, there is anincrease in SWS during the first recovery night after

total sleep deprivation in young and elderly men and

women (e.g., Reynolds et al., 1986). Furthermore, wo-

men showed a more dramatic increase in slow wave

activity after 40 h of total sleep deprivation than age

matched men indicating a greater response to sleep de-

privation in women (Armitage et al., 2001).

In depressed patients, total, partial and selective sleepdeprivation has consistently been shown to improve

mood in men and women independent of the diagnostic

subtype of depression (Leibenluft et al., 1992; Wu and

Bunney, 1990; Wehr, 1992; Parry et al., 2000). This

short-lasting improvement of mood is followed by a

relapse after a recovery sleep episode even if it is of short

duration (Holsboer-Trachsler and Seifritz, 2000). Be-

sides these acute laboratory studies, few data exist onthe consequences of long term sleep restriction on wo-

men’s health. A recent study in 71,617 women health

professionals aged 45–65 years in the USA that was

based on questionnaires, found after a ten year follow

up, an increased risk of cardiac disease in women

sleeping both less than or more than 8 h per night (Ayas

et al., 2003). Despite their epidemiological interest, such

large population data based only on questionnaires needto be interpreted with caution. Several confounding

factors that could in turn affect sleep duration and

health status must be taken into account.

7. Sociological insights

7.1. The social context of women’s sleep

The sociology of sleep offers an exciting new dimen-

sion in sleep research. Rather than focussing exclusively

A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76 69

on the physiology of sleep, sociologists contend that

sleep takes place within a social context which influences

the patterning of sleep throughout the life course. As a

mirror of everyday life, sleep reflects the roles and re-

sponsibilities, gender divisions, health patterns andtransitions which characterise people’s lives. In the con-

text of lifestyle factors, women are more likely to expe-

rience and admit to tiredness than men (Cox et al., 1987;

Brannen and Moss, 1988; Blaxter, 1990; Popay, 1992).

Distinct from sleepiness, this tiredness may be linked to

women’s roles and responsibilities as they try to balance

the demands of motherhood, work and relationships.

While studies by Aubert and White (1959a,b), Sch-wartz (1970), Taylor (1993), Williams and Bendelow

(1998) and Williams (2002) have established the theo-

retical underpinnings and research agenda for the soci-

ology of sleep, there has until now been a lack of

empirical studies which focus specifically on an exami-

nation of the relationship between social context and

women’s sleep. Hislop and Arber’s (2003a,b,c) empirical

research on sleep in women aged 40 and over addressesthis gap.

7.2. Women’s sleep at mid-life

Hislop and Arber (2003a,b,c) suggest that sleep has

become a disposable resource for women in mid-life; a

low order priority which competes unfavourably with

the demands of motherhood, career, marriage and car-ing for ageing parents. While women accept that sleep is

essential to good health, the reality of their lives dictates

the extent to which they can access adequate sleep to

meet their needs. Women’s sleep may be affected by

expectations, responsibilities and stress associated with

their roles as partners, mothers, daughters, and em-

ployees, as well as by life crises and transitions such as

divorce, menopause, retirement, illness and widowhood.In a society in which gendered divisions of labour

ensure that women ‘continue to bear primary responsi-

bility for the completion of housework and caring work’

(Pilcher, 2000), many women find that rather than being

a place of rest and recuperation, the bedroom becomes

an ‘invisible workplace’ in which they remain on duty

throughout the night available to provide the physical

and emotional support needed to ensure the well-beingof their family. Over time, the sense of commitment to

family may mask sleep disruption to such an extent that

poor sleep patterns become the norm; an expected,

though undesired, outcome of the reality of women’s

lives. As Popay (1992) states in her study of women’s

experiences of ill health, women may accept poor sleep

and daytime fatigue as a ‘normal’ feature of everyday

life and ‘part of the price to be paid for combining paidwork and domestic labour’. For women, a good night’s

sleep may be one which follows an expected pattern of

disruption reflecting the constraints imposed by their

social roles and responsibilities. As such, a woman’s

right to sleep free from interference from others (Wil-

liams and Bendelow, 1998), is effectively challenged by

the social parameters surrounding women’s sleep.

7.3. Women’s sleep in later life

A pattern of sleep disruption may accumulate over

the life course establishing a fertile environment for poor

sleep patterns in older women. Sleep disruption, with its

consequent impact on well-being and quality of life, is

the product of the interplay of social factors as much as

it is the outcome of the biological effects of ageing.From a sociological viewpoint, later life is character-

ised by a series of transitions and changes in identity and

status as women move from work to retirement, from an

active to more sedentary lifestyle, from caring for chil-

dren and elderly parents to caring for their partner, and

from the role of spouse to widow. As lifestyles in later life

are restructured, so too are sleep patterns. The transition

from work to retirement, for example, may be charac-terised by shifts in sleep–wake patterns that were once

structured by alarm clocks and work routines. Increased

napping during the day, lack of exercise and boredom

can have adverse effects on sleep at night. Hislop and

Arber (2003a,b,c) suggest that it is the changes associated

with life course transitions during this period, acting in

combination with the physiological effects of ageing on

sleep, which may explain the increased potential for sleepdisruption in later life.

For partnered women, the quality of sleep in later life

also reflects changes in their relationship. Women’s sleep

may be affected by their partner’s increased restlessness,

with his snoring, prostate problems, and the pain and

discomfort of poor health interfering with a women’s

ability to achieve a good night’s sleep. Increased caring

responsibilities for partners as their health declines maylead to further sleep disruption.

Women’s sleep in widowhood highlights the extent to

which partners continue to influence women’s sleep

patterns even in absentia. Beyond the initial period of

grieving, women may find it difficult to regain the sleep

patterns they enjoyed during their marriage. The feelings

of loss widows experience as they contemplate a future

of empty nights without the companionship of theirpartner are a constant reminder of the shift in identity

from wife to widow. The loss of their partner’s gendered

role as protector may further erode sleep in widowhood

as women adjust to sleeping in an empty house without

the sense of security once provided by their partner.

7.4. Women’s management of sleep disruption

Hislop and Arber’s research shows that women are

proactive in seeking ways to improve their sleep. For

most women, dealing with sleep problems involves

70 A. Dzaja et al. / Journal of Psychiatric Research 39 (2005) 55–76

choosing from a range of self-help strategies, over-the-

counter remedies and alternative therapies. These

strategies, however, are also subject to social and cul-

tural constraints. While lone women faced with sleep

disruption during the night may get up, move aroundthe house, watch television or read, these options are not

always available to women with partners and/or chil-

dren. Out of commitment to their family, women often

choose to tolerate sleep disruption rather than disturb

the sleep of others in the house. While moving to an-

other room may seem like a logical solution to sleep

disruption caused by a restless or snoring partner, this is

not always a viable option. As Taylor (1993) suggested,the right to sleep privately may be linked to socio-

economic status, reflected in the availability of spare

rooms or beds. Moreover, cultural taboos associated

with the symbolic relationship between marriage and

sleeping in a double bed may prevent many women

adopting this strategy. With the double bed symbolising

the marital bond, women may be reluctant to challenge

the basis of their relationship or invite social stigma bymoving to another room, preferring to remain in an

unfavourable sleeping environment despite its adverse

effects on their sleep.

Hislop and Arber found that women continue to see

sleep disruption as an inevitable part of their roles as

mothers, wives, partners, workers, carers, and widows,

despite the efforts of the medical profession, pharma-

ceutical companies, and alternative therapists to en-courage women to regard sleep as a health issue. While

women often try to improve their diet and exercise as

part of a healthy lifestyle programme, sleep continues to

be considered an expendable luxury. It is only when

sleep disruption extends beyond ‘acceptable normality’

and seriously impacts on the enactment of roles and

responsibilities that women seek help from their doctor.

While mid-life and older women continue to accept poorsleep as a product of their social reality, the ‘true’ extent

of sleep disruption in the community may go unnoticed.

8. Summary

While many aspects of sleep and sleep disorders share

similarities across gender, there are important differ-ences which need to be recognised and acknowledged by

clinicians, general practitioners and researchers. The

quality and amount of sleep women obtain is not only

influenced by gender differences in physiology but also

by a number of sociological factors linked to the role a

woman has in society and in the family. There are cur-

rently few research studies which focus on women. Al-

most all we know about sleep and sleep debt is based onexperiments on male subjects.

While survey studies clearly point out changes in

women’s sleep quality in association with hormonal

levels during the menstrual cycle, pregnancy and men-

opause, studies specifically addressing the relationship

between hormonal levels and sleep are rare. Moreover,

although common causes of disturbed sleep such as shift

work, stress, excessive use of caffeine or alcohol, pain, anoisy environment and inappropriate temperature or

lighting in the bedroom affect both men and women, the

consequences of chronic sleep loss remain unclear. We

do not know whether women are more or less vulnerable

to the effects of sleep loss than men, and/or whether age

modulates the effects of sleep loss differently across

gender. Many women appear to accept sleep disruption

or loss as part of their natural everyday life: taking careof an infant during the first year(s) of life usually in-

volves frequent night-time awakenings, leading to

chronic sleep debt in the mother. A snoring partner, the

social habits of a teenager that stays out late, and care-

taking of parents needing night-time assistance in later

life are common circumstances in women’s lives. Nev-

ertheless, virtually no attention has been paid to the

consequences of this ‘‘natural’’ sleep loss in society. Atired mother, for example, may have less patience with

her child; a tired commuter is at greater risk in traffic

and at the work place.

Finding ways to improve sleep quality in women in-

volves addressing a range of issues. Should women use

HRT to alleviate sleep disturbances? Would hormone

treatment help alleviate sleep disturbances appearing

during specific phases of the menstrual cycle? Whatremedies and strategies do women currently use to cope

with ‘‘natural’’ and inevitable sleep loss experienced as

part of everyday life? Is it in fact possible to overcome

the disturbances which contribute to this loss of sleep?

What information should women receive and how

should this information be presented?

New methods of imaging, such as proton spectros-

copy, the fast development of molecular biology, andthe application of sociological research methods to sleep

research will open new avenues for future research on

sleep. Multidisciplinary research, which incorporates

basic research conducted both on humans and animals,

clinical research and sociological research is needed to

assess the complicated relationship between different

factors in sleep regulation. This will allow the develop-

ment of strategies which can help women fight thenegative consequences of sleep loss and lead to an

overall improvement of their health.

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