4 - SLEEP AND HEALTH
Sleep, Sex Differences, and Women's Health
Women from adolescence
to post-menopause are underrepresented in studies of sleep and
its disorders. Although sleep complaints are twice as prevalent
in women, 75% of sleep research has been conducted in men. More
sleep studies in the past five years have included women, but
small sample sizes prohibit meaningful sex comparisons. Thus,
sex differences in sleep and sleep disorder characteristics,
in responses to sleep deprivation, and in sleep-related physiology
remain unappreciated. Furthermore, findings from studies based
primarily in men are often considered to be representative of
'normal' even when it is recognized that there are important
sleep-related physiological differences in women, including
timing of nocturnal growth hormone secretion and differential
time course of delta activity across the night.
in the central nervous system has been well documented but the
functional implications of sex differences in the neurotransmitter
and peptide systems that modulate sleep and wake are unknown.
There is a need to study sex differences in sleep and homeostatic
regulation across species to more fully understand the role
that sleep plays in normal development, maturation, adaptation,
aging, and disease propensity. Sex hormones influence sleep
and circadian rhythms, and sleep affects neuroendocrine functioning,
in particular the episodic secretion of gonadatropin hormones.
There are potentially different effects of endogenous sex hormone
cycling on neuronal groups involved in regulating behavioral
states and circadian rhythms. Of importance is understanding
how sex-related differences in sleep and its regulation influence
the risk for and mechanisms of sleep disorders and other diseases.
Evidence from animal
studies supports the presence of sex-related differences throughout
the lifespan in susceptibility to disease in general and to
sleep disorders in particular. As classic examples of sexual
dimorphism, both the long-term neurobehavioral consequences
of sleep-associated intermittent hypoxia as occurs in Sleep-Disordered
Breathing (SDB) and the consequences induced by early life maternal
separation stress exposures are reduced in female animals when
compared to male littermates. The mechanistic roles of sex-related
hormones and their receptors and signaling pathways in mediating
the emerging sex-dependent differences in susceptibility to
specific neural insults are only now beginning to be explored,
and the new insights achieved should have major implications
for the development of novel therapeutic interventions.
in neuroendocrine hormones, body temperature, mood, and emotional
state during puberty, the menstrual cycle, pregnancy, and menopause
have profound effects on sleep quality, daytime functioning,
and well-being in adolescent girls and adult women. It generally
has been assumed that sleep prior to puberty is similar in girls
and boys, and that sex differences first emerge during this
developmental transition. The validity of this assumption, however,
and the extent of sex differences in sleep and sleep disorders
in children and adolescents are not known. There have been no
cross-sectional or longitudinal studies of subjective and objective
measures of sleep coupled with measures of neuroendocrine functioning
during and after puberty. Despite the propensity for mood disorders
to emerge during adolescence and the greater prevalence in girls
compared to boys, little is known about how changes in sleep,
sex hormones, and sleep deprivation affect mood and emotional
problems in this age group.
Although female sex
is a risk factor for Insomnia, and Insomnia is a risk factor
for depression, little is known about how changes in sex hormones
during the menstrual cycle impact sleep physiology and mood
in adolescent girls and women. In fact, most of what is known
about sex hormones and sleep is derived from studies of exogenous
hormones in adult rodents and humans. Little is known about
endogenous sex hormones, changes in sleep physiology, and the
development of dysphoric mood and dysmenorrhea during the menstrual
cycle. There have been only a few sleep laboratory studies in
small samples of adult women during all phases of the menstrual
cycle. Findings show wide individual variation with no consistent
relationships between menstrual phase and changes in sleep physiology.
There are considerable
methodological challenges in studying sleep across phases of
the menstrual cycle. Without normative data based on ovulating
and non-ovulating women, however, neither the researcher nor
the clinician have reference points to aid in the interpretation
of menstrual cycle effects on sleep or its disorders. Although
not all women of childbearing age experience premenstrual symptoms
and secondary Insomnia, Insomnia and related symptoms may occur
associated with onset of menses. Insomnia related to menses
may be related to a fall in endogenous progesterone or a differential
sensitivity to endogenous hormone fluctuations, but these hypotheses
require further testing. Potential health consequences or disease
risk that are engendered by this repetitive 'incident' insomnia
that can occur every month for 40 years of a woman's life are
not known. However, menstrual cycle symptoms and premenstrual
dysphoria correlate with. Women with significant dysmenorrhea
may be at higher risk for developing insomnia and depression.
and physical discomfort are common during pregnancy and both
can affect sleep. Although nearly all pregnant women will experience
disturbed sleep by the third trimester, there have been only
two longitudinal sleep studies of subjective and objective sleep
measures during pregnancy. There have been no reports of intervention
studies to improve sleep quality during pregnancy. Some have
assumed that disturbed sleep is a 'natural' consequence of pregnancy,
labor, delivery, and post-partum that resolves over time since
few women seek assistance to improve sleep. Research has not
shown a relationship between sleep quality and quantity and
any perinatal adverse outcome, length of labor, or type of delivery.
More studies are needed, however, to clarify the extent to which
sleep-related problems during pregnancy may have adverse fetal,
perinatal, or infant-related consequences.
Very little is known
about the effects of late stage pregnancy sleep disturbances
on labor and delivery, emotional distress, or post-partum depression.
However, nighttime labor and a history of sleep disruption in
late stage pregnancy are related to a higher incidence of post-partum
'blues.' Certain sleep disorders such as Restless Legs Syndrome
(RLS), Periodic Limb Movement Disorder (PLMS), SDB, or Insomnia
may emerge during pregnancy and the extent to which these disorders
resolve or place women at higher risk for sleep disorders later
in life is not clear. Pregnancy induces changes in the upper
airway and in functional residual capacity that predispose women
to snoring, SDB, and reduced oxygen stores. Pregnant women who
snore may be at risk for pre-eclampsia and/or SDB. The number
of pregnant women with SDB may be substantial, but the prevalence
has not been defined in either uncomplicated or complicated
pregnancy. Women with pre-eclampsia and excessive weight gain
during pregnancy are at greater risk for the development of
SDB and pregnancy-induced hypertension, which have been associated
with adverse perinatal outcomes, but few polysomnographic studies
have been done in these women.
Many women during
the menopausal transition (perimenopause, menopause, post-menopause)
complain of sleep disturbances that are attributed to vasomotor
symptoms (e.g., hot flushes and night sweats) rather than to
menopausal status. Estimates of self-reported menopausal-related
Insomnia range from 33 to 51%, but the actual prevalence of
sleep disturbances in midlife women, particularly as a function
of race, ethnicity, and body size is not well defined. Although
there have been only a few sleep studies with both subjective
and objective measures, a majority of midlife women with self-reported
poor sleep quality report high psychological distress without
objective evidence of poor sleep efficiency. Whether these women
are physiologically hyperaroused (e.g., increased hypothalamic-pituitary-adrenal
axis or sympathetic activity) without significant impact on
standard indices of laboratory sleep remains to be clarified.
Data on changes in
sleep physiology in women during the menopausal transition are
sparse and no longitudinal sleep studies have been conducted.
Compared to placebo, short-term hormone replacement therapy
(HRT) has shown beneficial effects on improving subjective and
objective sleep quality in women with menopausal symptoms, but
not all studies show the same effects. Menopause may be a significant
risk factor for SDB. It has been suggested that menopause-induced
sex hormone deficiency might explain the increased prevalence
of SDB in post-menopausal women and that women on HRT might
be at lower risk. Given concerns about disease risk such as
related to thromboembolic events, cardiovascular disease, and
breast cancer) associated with hormone replacement therapy for
the treatment of menopausal symptoms, fewer women in the future
may receive HRT and hence more women may experience menopause-related
insomnia or HRT withdrawal symptoms that could exacerbate insomnia.
Alternative and established therapies for insomnia need to be
systematically evaluated in women during and after menopause.
In addition to perimenopausal
and menopausal effects on sleep in women, surveys show that
more than 80% of working women report fatigue and exhaustion,
and half of them obtain inadequate sleep. Women shift workers
with altered sleep and circadian rhythms are at increased risk
for menstrual irregularities, infertility, miscarriage, and
low birth weight infants. Women remain the main caregivers for
children and elderly family members. These responsibilities
may add a significant stress burden and increased vulnerability
for sleep disturbances with negative impact on health and quality
of life. In addition, significant life events such as spontaneous
abortions, stillbirth, or death of a child or spouse have been
associated with development of posttraumatic symptoms, including
sleep disturbances. Women who consume alcohol as a method of
coping with work, family, and social demands are at increased
risk for alcohol-induced sleep disturbances.
In The Last 5 Years
Sleep and the
Menstrual Cycle/Premenstrual Syndrome:
- Sleep architecture
is unaffected by menstrual cycle phase. But body temperature
is elevated and circadian rhythm amplitude is reduced during
sleep, however, in the high progesterone phase (luteal) of the
menstrual cycle, but the underlying mechanism is not known.
Compared to men, women have a blunted drop in body temperature
and an earlier nadir of the circadian body temperature rhythm.
- Women on oral contraceptives
have reduced slow wave sleep and REM latency. Body temperature
throughout the menstrual cycle is similar to that of normal
cycling women in the luteal phase.
- Dysmenorrhea is
associated with significantly disturbed sleep quality prior
to menses. Compared to control women, women with dysmenorrhea
had altered sex hormones, body temperature, and sleep throughout
the menstrual cycle.
Sleep in Pregnancy
- Longitudinal studies
indicate that age combined with anemia is related to first trimester
fatigue and that reduced sleep time is related to fatigue during
the third trimester. Both reduced sleep time and anemia are
related to fatigue post-partum. Significant changes in sleep
are evident in the first trimester of pregnancy with increased
total sleep time coupled with more awakenings, but post-partum
sleep efficiency is lower than pre-pregnancy. Slow wave sleep
percentage is reduced throughout pregnancy compared to pre-pregnancy
and post-partum. REM sleep was s reduced during pregnancy in
one study, but was reduced in another longitudinal study, most
notably during the third trimester.
- Restless Legs Syndrome
(RLS) occurs in about 20% of pregnant women and may be associated
with reduced levels of folate.
- Thirty percent
of pregnant women begin snoring for the first time during the
- Pre-eclamptic women
show evidence of SDB associated with increased blood pressure.
Pregnant women who snore have a twofold greater incidence of
hypertension, pre-eclampsia, and fetal growth restriction compared
- Self-reported sleep
quality derived from sleep diaries shows considerable sleep
disturbances in the early post-partum period. Sleep efficiency
improves during the first year post-partum, but it is unclear
whether sleep quantity and quality return to pre-pregnancy levels.
- There is a relationship
between sleep and mood during pregnancy and through the first
three to four months post-partum. Increased disturbances in
self-reported sleep and decreased reported total sleep time
are associated with depressed mood post-partum.
Sleep and Menopausal
- Longitudinal studies
of midlife women showed increased self-reported insomnia, night
sweats, and hot flushes across the menopausal transition from
late peri-menopause to post-menopause. Self-reported sleep disturbance
in middle-aged women also has been associated with worse mood,
higher blood pressure, higher waist/hip ratios, and chronic
dissatisfaction with sleep.
- The prevalence
of self-reported insomnia is 17% in a community-based cohort
of racially mixed peri-menopausal menstruating women. Reduced
estradiol, increased hot flashes, and psychosocial factors are
all associated with poor sleep quality after controlling for
current sleep medication use.
- Sleep quality as
measured by polysomnography (PSG) does not appear to be different
in peri- or post-menopausal women compared to premenopausal
women. Also, there do not appear to be any differences in PSG
sleep quality in women who use HRT versus those who do not.
These observations imply that sleep disturbances in midlife
women are not a 'normal' part of the menopausal transition.
- Hormone replacement
therapy (estrogen preparations) is effective in reducing menopausal
symptoms and self-reported sleep disturbances (insomnia and
daytime sleepiness), and in increasing REM sleep and the amount
of slow wave sleep in the first third of the night. In one randomized
trial comparing two different forms of progesterone in combination
with estrogen therapy, PSG sleep efficiency improved with reduced
wake after sleep onset in the group receiving micronized progesterone.
- The prevalence
of SDB in postmenopausal women on HRT is significantly lower
than in postmenopausal women not on HRT, indicating that menopause
may be a significant risk factor for SDB in women and HRT may
reduce that risk. The hypothesis that healthy postmenopausal
women not on HRT have more SDB compared to women on HRT has
also been confirmed in a large population-based study.
- Establish how sex-related
differences in sleep and its regulation influence the mechanisms
and risks of developing disease and sleep disorders. We need
to study sex differences in sleep and homeostatic regulation
across species to more fully understand the role that sleep
plays in normal development, maturation, adaptation, aging,
and disease propensity. Animal models of sleep disorders need
to be developed and incorporate careful delineation of sex-related
differences in susceptibility to development of these disorders
and their consequences. The specific cellular and molecular
mechanisms underlying sex differences in sleep disorders throughout
the lifespan should be pursued.
- Conduct longitudinal
studies of sleep during pregnancy and through the post-partum
period that include both subjective and objective sleep indicators
and include baseline measurements. We need to describe more
fully the extent of sleep disorders developing during pregnancy
and post-partum so that novel and existing therapies can be
instituted to reduce health risks to the mother and the fetus.
The relationship between extent of disturbed sleep during the
late stages of pregnancy and delivery and the development of
post-partum depression warrants study as a basis for designing
novel interventions. Effects of sleep disturbance post-partum
on maternal-infant interactions also require further study.
- Determine the extent
to which the prevalence of insomnia and sleep disorders increases
during the menopausal transition, identify factors that predict
which premenopausal women are at high risk for developing insomnia,
and evaluate alternative and traditional therapies for improving
sleep in menopausal women.
- Obtain normative
sleep data from girls before, during, and after puberty, as
well as from women of child-bearing age, to assess changes associated
with different phases of the menstrual cycle, changes in endogenous
sex hormones, and in response to exogenous hormones.
- Determine the extent
to which adolescent girls and young women with significant dysmenorrhea
are at risk for insomnia and depression.
- Study how sleep
disturbance in pregnancy affects fetal development and health
as well as the maturation of fetal physiology related to sleep,
and the extent to which fetal effects may be associated with
long-term pediatric consequences.