Page1Women and Sleep Across the Life S
SleepWorld Magazine, Women's Health

Women and Sleep Across the Life Span

Introduction

The development of the female brain is uniquely different. The hormonal changes in utero, around early development, during pregnancy, menopause, and beyond can introduce specific challenges to a woman’s sleep and may result in sleep disorders.

Current studies show that conditions in utero may impact the development of the fetus. Exposures to toxins1 chronic stress2 may facilitate mutations in genetic material for brain development. Female brains grow in the absence of sex hormone stimulation, whereas male brains develop from stimulation of testosterone which can cross the blood-brain barrier (BBB).3 Estrogen is typically protein bound and does not cross the BBB in fetal stages. If the pregnant mother has used nicotine products, has nutritional deficiencies, or has exposure to antibiotics, then the fetus may have additional risk factors influencing its development.

Early Development

The birthing process may also affect the gut microbiome of the baby. Passage through the birth canal allows for exposure to normal vaginal flora, whereas cesarean section may not permit exposure to helpful bacteria that colonize the newborn’s skin and gut. Specific strains can help with digestion and lower the risk of food intolerances and allergies.4  Breastfeeding or formula feeding may shape the population of healthy gut microbiome further. Babies usually have proportional aerobes and anaerobes until maturation to solid foods.5 The amount of light and sleep environment the newborn is exposed to may set up the conditions required as the baby grows. Most newborns enter rapid eye movement (REM) sleep as the first stage of sleep and cycle through non-REM sleep thereafter.6 The rapidly developing brain organizes itself during the 16 or more hours of sleep during each 24-hour cycle. Although sudden infant death affects male infants more often,7 choking from regurgitation of breast milk or formula remains a concern. Thus, putting babies on their backs to sleep is still the best practice.8

Female infants are reported to have longer sleep times, fewer awakenings, and less disturbed sleep.9 Around the time children are three or older, children with higher proportions of cell bodies, neurons, and dendritic connections sensitive to norepinephrine may begin to manifest symptoms of insomnia and anxiety. Bedtime may be more challenging; fears are more common.

The digestive track and sleep connection

Young children who have sensitive digestive tracts and food allergies may not provide a balance of beneficial gut flora. Short-chain fatty acids that can cross the BBB may stimulate more inflammation and can alter the balance of neuroprotective factors for proper brain development. In boys, brain-derived neurotrophic factors and the proportion of astrocytes can be influenced by genetic mutations and nutritional support. Both estrogen and testosterone levels at this stage have protective effects against brain injuries. However, if antibiotics are introduced often to combat infections, then it is more likely that anaerobes will inhabit the intestines, and the proliferation of unhealthy bacteria will further escalate and affect brain growth for both sexes. If there are more inflammatory responses from the brain, improper brain development may ensue. Downstream, symptoms of attention deficit or attention deficit hyperactivity disorder may present in adolescence. Difficulty with sleep onset and or maintenance may then be impacted.

Besides insomnia, girls’ sleep may be more disturbed than boys’ sleep.10 Sleep efficiency may decrease. If iron deficiency occurs, restless legs syndrome (RLS) symptoms may begin to appear. Both genders are equally likely to have parasomnias such as sleepwalking, night terrors, and confusional arousals. Bruxism may also happen in various stages of sleep.

Microbiome in development may also affect brain development in children manifesting symptoms of autism and Asperger’s syndrome.11 Among children with Autism/Asperger’s Syndrome12 boys are more likely to have RLS and obstructive sleep apnea than their female counterparts. The cause of the differences is yet unexplained. Attention Deficit-Hyperactivity Disorder (ADHD) presents around elementary school age; girls are more commonly inattentive, and boys are more likely to present as hyperactive.13  Early in life, “screen” exposure to blue spectrum light in the evening, especially during the pandemic, has been correlated with later bedtime and more sleep disturbances.

A Glimpse at Parasomnias

Restless sleep is a newly described syndrome that may occur around the ages of 5-18.14 These are different from restless legs syndrome and body rocking behavior. Generally, sleep quality is worse amongst these children with more frequent arousals and “impairment in daytime functioning (sleepiness or school performance) or irritability or hyperactivity.15

Sleep talking is also equally prevalent between the two genders.16 There are early reports of higher odds of insomnia (3x) and obstructive sleep apnea (5X) amongst trans-gender or gender non-conforming youths from ages 12 to 25.17 These disorders may present right before the onset of puberty.

Teen Years

The body, brain, and sexual organs undergo rapid growth and development during the teen years. Sexual characteristics appear and mature. With sex hormone stimulation in female teens, menstruation commences. Discomfort and variability from menses initially may precipitate sleep disturbance and anxiety.18 For those with a prior history of insomnia and psychiatric diagnoses, female teens are more likely to suffer from insomnia during puberty.19 During a woman’s lifetime, her risk of insomnia remains higher by 1.4 to 2 times that of her male peers. A female teen is also more likely to sleep 10 minutes less than a male teen20 until age 19 as measured by questionnaires in the U.S. Female teens also reach “peak eveningness” earlier than males and spend more time in bed21 weekdays and weeknights.

Eating disorders may co-exist with sleep problems.

Eating disorders may appear in teens during adolescence, with a prevalence of 4% in the U.S. vs. 2% in Europe and 3.5% in Asia.22 Eating disorders occur more commonly when there are other co-morbid conditions, such as depression, anxiety, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and personality disorders.23 Compared to cis-gender counterparts, the lifetime prevalence of eating disorders by self-report was 10.5% for transgender men and 8.1% for transgender women in the U.S: anorexia nervosa (4.2 and 4.1%) and bulimia nervosa (3.2 and 2.9%) respectively for transgender men and women.24 Depending on the degree of body weight change, sleep disturbance corresponds with more rapid weight loss. This disorder has also had an increased prevalence amongst male teens in recent years.

Sleep Schedules and Parasomnias

Irregular sleep-wake cycles and/or delayed sleep-wake phase disorder (DSPS) may cause difficulty initiating and maintaining sleep. Those in lower socioeconomic strata reported or experienced poorer sleep quality or more daytime sleepiness25 in questionnaires, and shorter sleep durations, longer sleep latencies, and greater sleep timing variability by actigraphy26 impacted more African American and Latino households.

Parasomnias may persist during the teen years and often worsen27 if there is concurrent sleep deprivation, new sleep environments, substance use, or obstructive sleep apnea (OSA).

Female teens who are more predisposed to genetic factors for polycystic ovary syndrome (PCOS) may have more rapid weight gain, increased facial acne or hair growth, and truncal obesity, besides irregular menstrual cycles.28 The truncal adiposity may predispose her to OSA and further sleep fragmentation, daytime cognitive impairment, sleepiness, and fatigue.29

Mood disorders are more common in female teens,30 but certainly can affect male teens depending on family history. Those with DSPS31 are likelier to exhibit mood disorders such as depression32  than those with earlier biological clocks. Weight gain is more common in teens with DSPS due to the biological need for later feeding times and sleep loss combined.

The reactivity to sleep loss or restriction is partially genetic and partially sex-related. Literature suggests that female teens accumulate sleep debt faster and dissipate it more quickly. Sleep spindles activity, especially fast spindles, often appear earlier in the life of female teens and differentiates earlier than those of males. Complex learning tasks correlate more with the appearance of these faster spindles the night after; female teens tend to have more sleep spindles and a higher density after learning and sleep recovery than males as well.33

Pregnancy

About six percent of women may snore during the first trimester, but about 20 percent snore during the last trimester. The rapid increase of hormones during the first trimester causes nasal congestion and daytime sleepiness.34 As the fetus and placenta increase in size during the subsequent trimesters, they compress against the urinary bladder and lower abdominal contents. The increase in blood volume may also cause swelling of digits, ankles and cause discomfort with prolonged standing. The return of the additional fluid to the circulatory system while reclining and the relaxation of supportive ligaments during the last trimester likely worsen urinary urge and frequency, impacting sleep quality and causing insomnia.35 Those who snore before pregnancy are more likely to develop OSA and have a higher risk of gestational hypertension and/or gestational diabetes.36 Understandably, insomnia symptoms affect 38.2 percent of pregnant women, particularly as pregnancy progresses. Total sleep time can be less than seven hours beginning in the second trimester.37

Shortness of breath during daytime and nighttime may occur with the elevating diaphragm. The ribs and intercostal muscles expand more laterally, allowing for the lungs to expand and help decrease dyspnea to some degree.38 Progesterone, on the other hand, increases respiratory drive, which can counteract some feelings of breathlessness.

If the pregnant woman sleeps supine at 35+ weeks’ gestation, she may decrease cardiac output by 16 percent.39 This will probably cause light-headedness which requires changing sleeping position from supine to lateral.

Depending on the conditioning of the woman before pregnancy, vigorous exercise may worsen symptoms of restless legs.40 Although prenatal vitamins help lessen the risk of iron and folic acid deficiency, over-exertion with muscle fatigue, particularly in multiparous (had prior pregnancy) women, often worsen RLS. Proper hydration will alleviate some symptoms, but rest, massage, icing, or heat can provide temporary relief. Family history of severe restless legs: symptoms more than three times per week to nightly will predict more marked sleep initiation or maintenance issues during pregnancy. Alcohol use that induces dehydration may increase RLS symptoms as well.

Smoking nicotine products near bedtime may induce insomnia. Irritants from nicotine in cigarettes and vaping cartridges can produce inflammation of the posterior wall of the oral airway, which may, in turn, worsen the risk of breathing abnormality in sleep, such as asthma or OSA. Mothers and partners who are smokers also have a higher risk of gestational diabetes.41

Perinatal depression and anxiety have been reported in both birth parents.42 Birth mothers with pre-existing depression43 are more likely to exhibit mood disorders after delivery and post-partum. Prompt attention by a healthcare professional and mental health provider is highly recommended. Insomnia symptoms worsen with post-partum demands, especially if the birth mother is breastfeeding or having to tend to an infant who is pre-mature44 or is ill.

Anxiety levels may correlate with insomnia after delivery. Hypervigilance is increased with the health status of the infant. Birth mothers who are shift workers often have more difficulties sleeping during daylight hours than usual. Judicious use of a sleep aid or hypnotic may be needed for those not breastfeeding or caring for the infant alone.

Birth mothers with narcolepsy present a particular challenge in worsening grogginess45 during daytime and worsening cataplexy with continual sleep loss for the initial three months post-partum. Frequent sleep bouts and difficulty waking for feedings are common. A judgment must be made whether these mothers should operate motor vehicles post-birth until they can recover more sleep or be safely placed back on alertness-promoting medication and/or cataplexy treatment regimens.

Menopause

As the levels of estrogen and progesterone fluctuate at perimenopause, some women experience hot flashes and night sweats.46 Ethnicity, age of menarche, and family history may also help predict the severity of symptoms and sleep disturbance. However, individual variances make it hard to predict the duration of symptoms until the cessation of menses for one year, which is termed menopause. Some women may continue to have symptoms for 6-7 years after menopause.47

Insomnia48 is common at menopause. Sleep efficiency, wake after sleep onset, non-rapid eye movement stage N1, N2, and sleep increase, a decrease in stage N3, and sometimes REM sleep can result from this period.49 Daytime sleepiness may worsen for those that develop OSA post-menopausally. The ligaments that support the vocal cord apparatus also loosen along with the thickening of vocal cords,50 thickness of overlaying mucus will increase airway resistance and heighten the risk of OSA after menopause.51

Hormonal replacement for those who are appropriate candidates (see Pengo M.F. et al.) can help lessen hot flashes and night sweats, along with cooler sleep environments will aid sleep continuity.52 For those whose depression symptoms are notable, serotonin or serotonin/norepinephrine reuptake inhibitors may be used to lower mood disturbances. Melatonin at three milligrams or less were reported to help reduce insomnia.53 Over-the-counter estrogen supplements and complementary medicines or supplements54 are more controversial with variable responses. Yoga55 and acupuncture56 were reported to be helpful for insomnia in some studies and not so much in others, and herbal supplements are less so. Cognitive behavioral therapy57 can be effective at any age to recondition the attitude and response to insomnia symptoms.

Aging past menopause

Melatonin secretions are lower as women age. Depending on whether cataracts58 are lowering the blue spectrum or white light input onto the melanopsin layer, the intrinsic sleep period may change and be less adaptable. Women may have a shorter biological clock relative to their male counterparts. Phase shifting to an advanced sleep schedule is more common after menopause.59 Some women may present with insomnia symptoms with difficulty maintaining sleep if they complete their sleep by 2-3 AM when their sleep onset occurs at 7-8 PM, which is consistent with advanced sleep-wake phase disorder.

As women age and suffer sleep loss, sleeping less than four hours or more than 10 hours, more cognitive decline is reported amongst pooled subjects in Britain and China. 60 Muscular atrophy called sarcopenia61 often occurs as well. Exercise capacity may diminish, and body recovery slows. The proportion of N3 sleep likely will diminish accordingly. Sleep is more fragmented, and daytime naps become more common. Nocturnal sleep time decreases, and sleep is likely to be in blocks, though total sleep time may sum to about six hours in 24-hour cycles.

Chronic pain may become more common as women age.62 Libido and sexual health may be less robust for some individuals.63 Sensory input from sight, taste, and touch and processing speed for older adults will be decreased; chronic tinnitus may further disturb sleep in the elderly, particularly during the pandemic.64 Melatonin supplements can be helpful to re-establish a more robust circadian amplitude that has decayed over time. Physical exercise and daytime light exposure will enhance circadian pressure and promote alertness during daylight hours.

Many elderly women maintain healthy eating habits, exercise regimens, maintenance of good social contacts, and daytime cues to help them preserve good sleep during their later years.

Conclusion

The conditions in utero, birth, and post-partum period may be influenced by the gut microbiome and environmental conditioning and can affect the developing brain of the fetus/infant. Sex hormones play a role in the responsiveness of the male or female brain differently. The use of antibiotics or environmental insult coupling with the vulnerable cell population, such as locus coeruleus in the female brain and the astrocytes in the male brain, may affect the downstream hyperarousal responses in women and aspects of ADD/ADHD symptoms in male teens. When adding the circadian clock differences between the two sexes, with the male sex likely to have longer than 24-hour circadian cycles, the propensity for insomnia is heightened during adolescence and early adulthood for male teens.

Hormonal differences may also induce more symptoms of sleep disruption during pregnancy from the abundance and fluctuations of influx that add nasal congestion and edema. Thus, the risk of OSA is increased. At menopause, it is precisely the opposite, the loss of hormonal stimulation then induces a higher risk of OSA from the withdrawal of hormonal support for the vocal cord apparatus and surrounding tissues that may cause collapse of the airway. Once we are aware of the challenges one faces at different stages of life, we can help the patients understand their presentations of symptoms and treatment options better, which in turn may lead to better outcomes.

Kin M. Yuen, MD, MS, FAASM
Kin M. Yuen, MD, MS, FAASM, is a board-certified physician in sleep medicine. She is an assistant professor at UCSF and an adjunct assistant professor at Stanford University. Her research interests include cardiac arrhythmia, medical devices, and health economic evaluations in sleep disorders.

 

This article originally appeared in Sleep Lab Magazine May/Jun 2023 issue.

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