Sleep and Women’s Health

Article information

Sleep Med Res. 2013;4(1):1-22
Publication date (electronic) : 2013 June 30
doi : https://doi.org/10.17241/smr.2013.4.1.1
1Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA
2University of Texas Medical Branch, School of Medicine, Galveston, TX, USA
Correspondence: Sara Nowakowski, PhD, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0587, USA, Tel +1-409-772-3996, Fax +1-409-747-5129, E-mail sanowako@utmb.edu
Received 2014 August 10; Revised 2014 October 07; Accepted 2014 October 10.

Abstract

Sex differences in sleep begin at a very early age and women report poorer sleep quality and have higher risk for insomnia than do men. Sleep may be affected by variation in reproductive hormones, stress, depression, aging, life/role transitions, and other factors. The menstrual cycle is associated with changes in circadian rhythms and sleep architecture. Menstruating women (even without significant menstrual-related complaints) often report poorer sleep quality and greater sleep disturbance during the premenstrual week compared to other times of her menstrual cycle. In addition to these sleep disturbances, women with severe premenstrual syndrome often report more disturbing dreams, sleepiness, fatigue, decreased alertness and concentration during the premenstrual phase. Sleep disturbances are also commonly reported during pregnancy and increase in frequency and duration as the pregnancy progresses. The precipitous decline in hormones and unpredictable sleep patterns of the newborn contribute to and/or exacerbate poor sleep and daytime sleepiness during the early postpartum period. Insomnia is also among the most common health complaints that are reported by perimenopausal women. Women are particularly vulnerable to developing insomnia disorder during these times of reproductive hormonal change. In this review, we present a discussion on the most relevant and recent publications on sleep across the woman’s lifespan, including changes in sleep related to menstruation, pregnancy, postpartum, and the menopausal transition. Treatment for sleep disturbances and insomnia disorder and special considerations for treating women will also be discussed.

INTRODUCTION

Research has shown that women report more sleep difficulties1,2 and are at greater risk for a diagnosis of insomnia compared to men.3,4 In the National Sleep Foundation’s 2007 poll, 30% of pregnant women and 42% of postpartum women reported rarely getting a good night’s sleep, compared with 15% among all women. Additionally, 25% of perimenopausal women and 30% of postmenopausal women reported getting a good night’s sleep only a few nights per month or less.5,6 In general, there is a higher prevalence of insomnia, restless leg syndrome, and dissatisfaction with sleep in women. In contrast, objective measures of sleep, measured by actigraphy and polysomnography (PSG), have demonstrated shorter sleep onset latency, increased sleep efficiency and total sleep time in women compared to men.79 Yet, a meta-analysis of sex differences of sleep behaviors in older adults (aged 58+) revealed no sex differences in total sleep time.10 Although sleep disturbances and insomnia disorder are widespread in the general population, each tends to occur more frequently in women, particularly during times of hormonal fluctuation. In addition to sex differences found in complaint of sleep disturbances and prevalence of sleep disorders, sex differences may also exist when treating men versus women. For example, in 2013 the U.S. Food and Drug Administration (FDA) required the manufacturers of Ambien to lower the recommended dose of zolpidem for women from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for extended-release products due to the risk of next-morning impairment and motor vehicle accidents. Women appear to be more susceptible to this risk because they eliminate zolpidem from their bodies more slowly than men. Zolpidem is the first drug in the U.S. to have different recommended doses for women versus men, but it seems likely pharmacokinetic sex differences would lead to differences in rates of absorption, metabolism, and excretion of other medications as well. Other biopsychosocial factors, such as discomfort during pregnancy, breastfeeding and infant/child care during the postpartum period, and potential ongoing nocturnal vasomotor symptoms (hot flashes and night sweats) during peri- and postmenopause, may complicate insomnia treatment and require special treatment considerations for sleep disturbances in women.

THE MENSTRUAL CYCLE AND MENSTRUAL CYCLE DISORDERS

The menstrual cycle of healthy women is characterized by cyclic changes in production of estradiol, progesterone, lutenizing hormone, follicle stimulating hormone, prolactin, and growth hormone. Reproductive hormones not only regulate reproductive function during the menstrual cycle, but also influence sleep and circadian rhythms. Negative menstrual symptoms are most commonly experienced by women during the last few days of the cycle, as progesterone and estrogen levels decline.11 Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) are characterized by emotional, behavioral, and physical symptoms that occur in the premenstrual phase of the menstrual cycle, with resolution at the onset of menses or shortly thereafter. Many women of reproductive age experience some premenstrual symptoms, but 3–8% of women have clinically relevant premenstrual symptoms that they perceive as distressing and that affect daily function and meet diagnostic criteria.6,12,13 Women with PMS/PMDD typically report sleep-related complaints such as insomnia, frequent awakenings, non-restorative sleep, unpleasant dreams or nightmares, and poor sleep quality associated with their symptoms; and daytime disturbances such as sleepiness, fatigue, decreased alertness, and an inability to concentrate during the during the premenstrual week and during the first few days of menstruation.1419 Women who experience severe premenstrual syndrome report significant declines in sleep quality in association with their symptoms during the late luteal phase compared with early follicular phase of their cycle.20,21 These corresponding changes, however, were not found in PSG sleep.2224 Recently, actigraphic sleep was examined in participants from the Study of Women’s Health Across the Nations (SWAN) and investigators found that among later reproductive-age women, sleep efficiency declines across the menstrual cycle with the most pronounced decline in the last week of the menstrual cycle.25 Another recent study demonstrated that a steeper rate of rise in progesterone levels from follicular phase through midluteal phase was associated with greater PSG wake after sleep onset and sleep fragmentation in the late luteal phase.26 Sleep studies across the menstrual cycle have been limited by small sample sizes, heterogeneous cycle lengths, lack of ovulation timing controls, and oral contraceptive use. Due to these methodological issues and the limited nature of these studies, much remains unknown about premenstrual sleep.

Most women with PMDD seeking psychiatric help for this disorder present with symptoms of premenstrual depression, anxiety, and/or irritability. A number of treatment strategies currently exist that target these symptoms and appear beneficial in treating them.27 The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline have been approved by the U.S. FDA for the treatment of PMDD. Fluoxetine,2831 sertraline,32 and clomipramine33,34 appear to be highly effective for treatment of depression, however little data is available on the safety and efficacy of using SSRIs to treat sleep disturbance and insomnia in PMS and PMDD. Nonpharmacological interventions for insomnia, such as Cognitive Behavioral Therapy for Insomnia (CBTI), have not been empirically examined for premenstural insomnia. CBTI is a brief, structured, skill-focused psychotherapy aimed at changing maladaptive cognitions (i.e., thoughts and beliefs) and behaviors contributing to insomnia. The weight of evidence supporting CBTI, summarized in several meta-analyses,3537 led to its recognition as a first-line treatment for insomnia by the NIH Consensus Statement.38 Improvements following CBTI are equivalent to those achieved during acute treatment with hypnotic medications39,40 and its effects are more durable after treatment discontinuation.39 Although efficacy has been demonstrated for adults with insomnia, it remains unclear if it is efficacious for women with PMS/PMDD and if special treatment considerations should be made (e.g., targeting other PMS symptoms such as menstrual pain41 or using CBTI skills intermittently during late luteal phase of a women’s menstrual cycle, as it is done to treat mood symptoms,4244 when symptoms are likely to be the most problematic) (Table 1).

Menses and sleep

PREGNANCY

Pregnancy brings about significant fluctuations in hormones that affect the sleep-wake cycle and cause physiologic changes that lead to sleep disturbance. In addition to the hormonal changes, pregnancy itself causes a multitude of anatomic and physiologic changes; which are essential to maintain the pregnancy, but can also contribute to sleep problems. Common physical symptoms, such as anxiety, urinary frequency, backache, fetal movement, general abdominal discomfort, breast tenderness, leg cramps, heart burn, and reflux cause sleep disturbance during pregnancy. Complaints of sleep disturbance during pregnancy generally start at the onset of pregnancy and increase in frequency and duration as the pregnancy progresses due to pregnancy-related anatomic, physiologic, and hormonal changes.45,46 During the first trimester women tend to sleep longer and experience greater daytime sleepiness. Cross sectional and longitudinal studies that use subjective (self-report) and objective (PSG) measures of sleep have consistently documented increased wake after sleep onset and decreased sleep quality during the first trimester relative to pre-pregnancy.47,48 During the second trimester, daytime sleepiness improves. During the third trimester there is an increase in sleep disruptions with typically 3–5 awakenings per night, more daily naps,49 diminished daytime alertness, more disturbed dreams,50 and approximately 21% report disturbed sleep at levels consistent with a diagnosis of insomnia disorder.47,51 Decreased sleep efficiency, increased wake after sleep onset, increased total sleep time (decreased by third trimester), increased stage 1 and 2 sleep, and decreased rapid eye movement (REM) sleep (during late pregnancy) have been noted by PSG recordings.5255 Poor and insufficient sleep during pregnancy are also associated with increased circulating levels of inflammatory markers involved in poor health5660 and adverse pregnancy outcomes, including intrauterine growth restriction and preterm delivery.6167 During the third trimester of pregnancy, insufficient and poor sleep may place women at increased risk for prolonged labor and cesarean deliveries6870 and for having an infant small for gestational age (Table 2).71

Pregnancy and sleep

For most women, sleep disruptions are caused by factors related to pregnancy, such as frequent need for urination during pregnancy.51 Some women, however, have difficulties initiating sleep and/or returning to sleep, which may be unrelated to peri-natal factors. When sleep disturbances are substantial (occur for 3+ nights per week for a period of 3+ months) and are associated with clinically significant distress or impairment of performance or other aspects of functioning, a diagnosis of insomnia disorder diagnosis is warranted. The prevalence of sleep disturbance among perinatal women is as high as 58%,7274 and a probable diagnosis of perinatal insomnia is estimated at 10%.75 Daytime coping strategies such as napping, spending more time in bed, or increasing caffeine intake can perpetuate sleep difficulties. The presence of insomnia has a significant impact on quality of life and daytime functioning and its management is imperative.

Pharmacologic treatments, including sedative-hypnotics, benzodiazepines, and ramelteon for insomnia during pregnancy are typically avoided because of the potential for adverse effects such as low birth weight, preterm deliveries, and cesarean sections in pregnancy.7678 Over-the-counter antihistimines and herbal and nutritional substances may be associated with fewer risks, but there have been fewer studies of their safety in pregnant women and their use is not recommended.79

Concerns regarding use of sleep medication during pregnancy and lactation make non-pharmacological treatment options for insomnia particularly attractive. Nonpharmalogical treatments such as CBTI should be the initial therapy. Current randomized clinical trials are under way to examine the efficacy and special considerations of CBTI during pregnancy. Additionally, studies of other nonpharmacological treatments options such as yoga,80,81 acupuncture,82,83 yoga combined with mindfulness,84 and exercise85 have been shown to be safe and effective treatments.

POSTPARTUM

Sleep disturbance during the postpartum period and its effects on maternal role functioning and mother-infant interactions are not well understood (Table 3). Both self-report and actigraphy studies have demonstrated that nearly 30% of mothers have disturbed sleep after the birth of their baby. The precipitous drop in hormone levels after the birth and unpredictable infant sleep patterns can affect a new mother’s sleep. Longitudinal studies have documented that the first six months postpartum are associated with a significant increase in wake after sleep onset and a decrease in sleep efficiency compared to the last trimester of pregnancy.46,55,74,86,87 Fatigue and lack of energy remain high from pregnancy into postpartum period through the first year after delivery. Sleep begins to normalize around 3–6 months postpartum, around the time when infants begin distinguishing between day and night and sleep for longer periods of time during the night. Other factors such as the mother’s age, type of delivery, type of infant feeding, infant temperament, return-to-work issues, prior birth experience, number of other children at home, and availability of nighttime support from the partner or other family member can have an impact on quality and quantity of sleep in new mothers. Many women compensate for their sleep disruptions by spending more time napping during the early postpartum period.88

Postpartum and sleep

Negative effects of poor and insufficient sleep have been observed during the postpartum period. Mothers with poorer sleep (lower self-reported sleep quality and a higher number of night waking resulting from infant awakenings) perceived their infants as having lower mood and as being more distressed and tearful.89 Moreover, insufficient sleep and more time tending to the infant at night predicted poorer maternal-infant attachment. Several studies have documented the relationship between sleep disturbance and subsequent reports of depressive symptoms at a later time among perinatal women (later in pregnancy9092 or in the early postpartum).91,9396 The association between poor sleep and subsequent depressive symptoms also holds when sleep disturbance is experienced during the early postpartum period and postpartum depression develops at a later postpartum time.9799

Interventions to improve maternal sleep and fatigue are limited, perhaps because of the universal nature of the experience and the belief that disturbed sleep is an unavoidable part of motherhood. In general, pharmacological interventions are seldom used in postpartum women who are breastfeeding. Even for women who are not breastfeeding, many choose not to take sedatives or other pharmacological options due to the need to have a more flexible sleep schedule for infant care. Therefore, behavioral interventions are the primary treatment options. Two pilot studies provide preliminary evidence for the efficacy of CBTI for postpartum insomnia and both studies demonstrated that the benefits of CBTI extended beyond improvement in sleep to other domains. One study provided five CBTI sessions, between the second and seventh postpartum weeks, to women who stopped smoking during pregnancy and found a significant decrease in time awake in the middle of the night and a significant increase in nocturnal (as well as per 24-hour) sleep time. Importantly, compared to women who did not receive the sleep intervention, those who did undergo CBTI had lower average daily cigarettes smoked and higher percent cigarette-free days.100 The second study provided CBTI to women with postpartum depression who also had disturbed sleep and reported pre to post treatment improvement in insomnia severity, sleep quality, sleep efficiency (% time asleep relative to time in bed), mood, and daytime fatigue.101 Studies of other nonpharmacological treatments such as reflexology,102 massage,103 and exercise104 have shown these options to be safe alternative treatments for postpartum women.

MENOPAUSE

Menopause is a natural process that occurs in women’s lives as part of normal aging. Menopause is defined as the cessation of menstruation due to degeneration of ovaries and follicles accompanied by changing ovarian hormone levels (estrogen and progesterone). The World Health Organization105 characterizes menopause as the permanent cessation of menstrual periods that occurs naturally or is induced by surgery, chemotherapy, or radiation. More recently menopause has been categorized in stages such as menopausal transition (defined by standardized criteria106 as variable cycle length seven days different from the normal cycle or > 2 skipped cycles and an interval of amenorrhea of 2–12 months) or postmenopausal (defined as > 12 months since last menstrual period). Menopause occurs between 50 and 52 years of age for Western women, but the range can vary based on race and ethnicity as well as lifestyle factors.107 The worldwide population of 470 million postmenopausal women is expected to increase, as 1.5 million women enter menopause each year, reaching a total of 1.2 billion by the year 2030.105 Most women now live long enough to become menopausal and can expect to live at least another 30 years beyond their final menstrual period (Table 4).

Menopause and sleep

Many women go through the menopausal transition with few or no symptoms, while a small percentage of women suffer from symptoms severe enough to interfere with their ability to function effectively at home, work, or school. Common complaints include hot flashes, night sweats, insomnia, mood changes, fatigue, and excessive daytime sleepiness. In the 2005 NIH State-of-the-Science Conference panel report on menopause-related symptoms, sleep disturbance was identified as a core symptom of menopause.108 The prevalence of insomnia, defined as disturbed sleep associated with distress or impairment, is estimated at 38–60% in peri- and postmenopausal women.109,110 Troubled sleep was reported by 54–58% of women between 40 and 60 years of age in the Ohio Midlife Women’s study.111 The Wisconsin Sleep Cohort found that perimenopausal women and postmenopausal women were twice as likely to be dissatisfied with their sleep as premenopausal women.112 SWAN has shown that difficulty sleeping is reported by 38% of women between 40 and 55 years of age, with higher levels among late perimenopausal (45.4%) and surgical post-menopausal (47.6%) women.110

We are unable to find an estimate of prevalence on nocturnal hot flashes/night sweats; however, it is generally believed that hot flashes occur in 60% to 80% of women during the menopausal transition113 and persist for 4 to 5 years on average.114,115 When hot flashes occur during the night, they frequently awaken women from sleep; although not every nocturnal flash is associated with an awakening. Women with nocturnal flashes may also experience awakenings that are unrelated to a vasomotor event. Indeed, insomnia can occur during menopause independent of nocturnal flashes. Although self-reported nocturnal flashes correlate with poor subjective sleep quality, such association is less clear when objective sleep measures are used.112,116,117 There is only limited and contradictory evidence supporting an association between nocturnal flashes and sleep disturbance when both variables were measured objectively.112,116122

The most common pharmacological treatments for menopausal insomnia include hormone replacement therapy (HRT), hypnotics and sedatives, and antidepressants. HRT is the primary treatment for menopausal symptoms, particularly vasomotor symptoms. The efficacy of HRT for sleep and mood disturbances remains unclear, with some studies finding positive results123128 and others finding no benefit.129131 Hypnotics and sedatives such as zalepon (Sonata), zolpidem (Ambien),132 and eszopiclone (Lunesta)127,133 have been shown to be effective in short-term use for acute, initial insomnia treatment in menopausal women. However, tolerance, withdrawal, dependence, and rebound depression at discontinuation may occur when drugs are used for longer than two weeks.134 Another psycho-pharmacological option is ramelteon, a selective melatonin receptor agonist, which has shown some efficacy.135 Antidepressant use has been effective in treating sleep disturbance in those with comorbid depression.136139 Using antidepressants to treat sleep disruption in those without major depression, however, is not recommended.140 Herbal and dietary supplements such as black cohosh,141 omega-3,142 valerian,143 and isoflavens144,145 have gained popularity for the treatment of menopausal symptoms; however few studies have examined their direct effect on insomnia symptoms.

Hormonal fluctuation and vasomotor symptoms such as night sweats may be the initial cause of insomnia symptoms, but physiological arousals, behavioral conditioning, and misguided coping attempts appear to prolong insomnia.146 CBTI targets these behaviors and has been shown to be efficacious for the treatment of chronic insomnia in randomized trials of adults40 and in older adults.147 It may be beneficial for insomnia syndrome in menopausal women, however, to date, no randomized clinical trials have been conducted to examine efficacy of CBTI in menopausal women or special treatment considerations in this population. Preliminary data148 do demonstrate promising results for using CBTI for sleep disruptions affected by menopause. Other nonpharmacological options such as acupuncture,149,150 mindfulness,151 reflexology,152 exercise,153 and yoga154 have also shown some promise, however more evidence is needed to confirm their therapeutic benefits.

CONCLUSION

Sleep disturbances and disorders are common across a woman’s lifespan. Important biological events, often mediated by hormones and physiological changes, such as menstruation, pregnancy, and menopause commonly impact and often cause dissatisfaction with sleep. Given the fact that the negative impacts of poor sleep extend beyond tiredness and fatigue but also impair daytime functioning and mood, identification and treatment of these disorders is vital to a woman’s quality of life. Women looking to treat their sleep problems have many options from pharmacological help from drugs such as sedatives and hypnotics to HRT for those with menopause-related insomnia. Behavioral treatments such as CBTI offer longer-lasting improvements in sleep without the side-effects that are often accompanied by medications.

Despite advancing research in sleep and women’s health, there are several areas that deserve more focused research. Recently, there has been an increased interest on the menstrual cycle’s impact on the sleep cycle. While it is known that the hormones are linked to sleep and that the variability across the menstrual cycle causes changes in sleep quality, there are few studies that have explored treatment options in women with PMS and PMDD and significant sleep concerns. Additionally, though CBTI has been shown to be efficacious in treating chronic insomnia within various populations, including adult men and women and older adults, and among comorbid conditions like chronic pain and major depression, there is still a paucity of literature examining the efficacy of CBTI among women suffering from insomnia during times of reproductive change and special treatment considerations that may need to be taken into account. Future studies should include full-scale randomized trials of CBTI for women experiencing during the perinatal and perimenopausal periods. Treatment of sleep disturbances in women may have direct effects on quality of life as well as effects on mental and physical health.

Acknowledgements

We would like to thank Sooyeon Suh, PhD for her support and funding from National Institute of Nursing Research (grant #NR014008).

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

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Table 1.

Menses and sleep

Study author Study of Population Group design and sample size Study length/Assessment points Attrition rates Follow up Outcome measure Results
Intervention studies

Freeman et al. (2004) Continuous vs. intermittent sertraline treatment Women with severe premenstrual syndrome (PMS) Randomized, double-blind; Continuous (n = 56)
Intermittent (luteal phase) (n = 56)
Placebo (n = 55)
3 months 29% No Daily Symptom Rating Form (DSRF), & Patient Global Ratings of Functioning Intermittent dosing does not differ from continuous. Both sertraline groups improved significantly.
Halbreich et al. (2002) Luteal Phase sertraline treatment for premenstrual dysphoric disorder (PMDD) Women with PMDD Randomized, double-blind; Luteal phase 50–100 mg (n = 142)
Placebo (n = 139)
3 cycles 21% No Clinical Global Impression Severity & Improvement (CGI), Daily Record of Severity of Problems (DRSP) Intermittent luteal-phase sertraline is effective and well tolerated.
Kornstein et al. (2006) Sertraline for PMS Women with PMS Randomized, single blind; Sertraline 25 mg (n = 98)
Sertraline 50 mg (n = 97)
Placebo (n = 101)
4 menstrual cycles 27% No Daily Symptom Report, CGI, Quality of life questionnaire, Social Adjustment Scale (SAS) Intermittent luteal-phase low dose sertraline produced significant symptom improvement. Continuous and symptom-onset dosing also effective, particularly at lower dose.
Menkes et al. (1992) Fluoxetine for PMS Women with PMS Double-blind, crossover, n = 37; Fluoxetine 20 mg
Placebo
3 cycles followed by crossover 24% No Premenstrual Assessment Form Fluoxetine an effective treatment for severe PMS.
Steiner et al. (1995) Fluoxetine for PMDD Women with late luteal phase dysphoric disorder (LLPDD) Randomized, double-blind; Fluoxetine 20 mg (n = 102)
60 mg (n = 106)
Placebo (n = 105)
8 cycles 56% No Visual Analogue Scales (VAS) for tension, irritability, & dysphoria Fluoxetine useful in treatment of PMDD. Lower dosing clinically effective and reduced side effects.
Stone et al. (1991) Fluoxetine Women with LLPDD Randomized; Fluoxetine 20 mg (n = 10)
Placebo (n = 10)
4 menstrual cycles (2 all placebo, 2 randomized) 0% No Self-report of symptoms 9 of 10 fluoxetine subjects responded to treatment. Symptoms ↓ in all 10 LLPDD diagnostic categories in fluoxetine group.
Sundblad et al. (1993) Clomipramine for PMS Non-depressed women with premenstrual irritability & LLPDD Clomipramine (n = 15)
Placebo (n = 14)
3 cycles 24% No VAS for irritability, depressed mood Low doses of clomipramine effective for PMS. Lag between onset of medication and effect shorter for PMS than for anxiety/depression.
Sundblad et al. (1992) Clomipramine for PMDD Nondepressed women with premenstrual irritability & LLPDD Randomized; Clomipramine (n = 20)
Placebo (n = 20)
3 cycles 27% No VAS for premenstrual irritability Low doses of clomipramine effective in reducing premenstrual irritability and dysphoria.
Wood et al. (1992) Fluoxetine for PMS Women with severe & persistent PMS Randomized, double-blind, crossover; n = 8
Fluoxetine
Placebo
6 months 0% No Calendar of Premenstrual Experiences, Beck Depression Inventory (BDI), Profile of Mood States Fluoxetine associated with ↓ in PMS symptoms including ↓ in behavioral, physical, and anxiety/depression scores.
Yonkers et al. (1997) Sertraline for PMDD Women with PMDD Randomized, double-blind; Sertraline (n = 121)
Placebo (n = 122)
3 cycles 18% No DRSP, Hamilton Rating Scale for Depression (HRSD), CGI, & SAS Sertraline ↓ PMDD symptoms, improved functional impairment.

Observational studies

Araujo et al. (2011) Sleep patterns & menstrual pain Menstruating women aged 25–48 Ancillary; n = 24 1 night N/A No Polysomnography (PSG), Women’s Questionnaire, Pre/Post sleep questionnaires Menstrual pain, use of pain medication did not alter sleep patterns.
Baker et al. (2012) Sleep quality in women with severe PMS Premenopausal women Severe PMS (n = 18)
Minimal symptoms (n = 18)
1 night in midfollicular phase, 1 night in late-luteal phase N/A No PSG, Perceived Stress Scale, Profile of Mood States, Sleep Diary, anxiety & depression scales Poorer subjective sleep quality reported when symptomatic in the late-luteal phase. No corresponding changes in objective sleep quality.
Baker et al. (2007) Sleep quality, composition in severe PMS Women aged 18–40 PMS/PMDD (n = 9)
Asymptomatic control (n = 12)
1 night in midfollicular phase, 1 night in late-luteal phase 28% No PSG, BDI-II, Profile of Mood States, Sleep diary Women with severe PMS reported significantly poorer sleep quality during the late luteal phase.
Baker & Driver (2004) Sleep across menstrual cycle Healthy ovulating women (mean age 21) n = 40 1 menstrual cycle 35% No Sleep Diary ↓ Sleep quality over the 3 premenstrual days and 4 days during menstruation
Cohen et al. (2002) Prevalence & predictors of PMDD Older premenopausal women (36–44) n = 513 1 menstrual cycle N/A No Moos Premenstrual Inventory, DRSP PMDD associated with ↓ education, history of depression, current cigarette smoking. Women not working outside the home less likely to meet criteria for PMDD.
Hachul et al. (2010) Sleep across menstrual cycle Women with sleep complaints n = 931 1 night N/A No PSG, Sleep Questionnaire, Gynecological Questionnaire Irregular menstrual cycle associated with sleep difficulties.
Lamarche et al. (2007) Sleep & significant emotional premenstrual symptoms Women aged 20–37 Significant emotional premenstrual symptoms (n = 10)
Minimal symptoms (n = 9)
1 night in follicular phase & 2 nights in late-luteal phase N/A No PSG, Stanford Sleepiness Scale, Subjective Alertness Scale Women with significant symptoms sleepier and less alert during the late-luteal phase.
Parry et al. (1999) Sleep deprivation & PMDD Premenstrual women with PMDD Randomized, cross-over trial;
PMDD (n = 23)
Normal comparison (n = 18)
3 months N/A No PSG, HRSD, BDI, Atypical & Mania Rating Scores ↑ REM latencies, ↓ REM in luteal phase. PMDD subjects had no sleep architecture changes like those in depression. Sleep deprivation may correct circadian rhythm disturbances in PMDD.
Sharkey et al. (2014) Sleep Disturbance across the menstrual cycle Healthy premenopausal women (18–45) n = 27 1 menstrual cycle 1% No PSG, progesterone, estradiol, estrone, wake after sleep onset (WASO) The steeper rate of rise in progesterone from follicular through mid-luteal phase associated with ↑ WASO.
Woosley & Lichstein (2014) Dysmenorrhea, the menstrual cycle, & sleep Women aged 18–24 n = 89 5 weeks N/A No ISI, International Classification of Sleep Disorders, 2nd Edition, Sleep diary, Brief Pain Inventory Insomnia severity associated with dysmenorrhea severity. ↑ Sleep onset latency, ↓ sleep efficiency in severe dysmenorrhea.
Zheng et al. (2014) Sleep across menstrual cycle Late-reproductive-age, menstruating women n = 163 1 menstrual cycle N/A No Actigraphy Sleep efficiency ↓ gradually across menstrual cycle, more pronounced in premenstrual period.

Table 2.

Pregnancy and sleep

Study author Study of Population Study design and initial sample size Study length/Assessment Points Attrition rates Follow up Outcome measure Results
Intervention studies

Beddoe et al. (2010) Mindful yoga Pregnant women n = 15 7 weeks N/A No Actigraphy, General Sleep Disturbance Scale (GSDS) Initiating yoga in 2nd trimester associated with ↓ awakenings, ↓ time awake, and ↓ perceived sleep disturbance. Beginning in 3rd associated with poorer sleep over time.
Chang et al. (2011) Sleep in pregnancy & maternal, fetal outcomes Pregnancy women Pilot, n = 31 1 week at each time point: 5–20 weeks, 21–28 weeks, 30–36 weeks 0% No Actigraphy, socio-demographic questionnaires, medical records Each additional hour of sleep per day in late pregnancy ↓ odds of small for gestational age, one hour hin mid pregnancy ↓ the odds of preeclampsia. Each hour ↑in sleep per day in early pregnancy associated with ↓ weight gain.
da Silva et al. (2005) Acupuncture Pregnant women Quasi-randomized; Acupuncture (n = 17)
Sleep Hygiene (n = 13)
8 weeks 27% No Numerical rating scale of insomnia Acupuncture ↓ insomnia ratings.
Field et al. (2013) Tai chi/yoga Pregnant women Tai chi/yoga (n = 46)
Control (n = 46)
1 group session per week, 12 weeks 11% No Center for Epidemiologic studies Depression Scale (CES-D), State Trait Anxiety Inventory, (STAI) Tai chi/yoga ↓ depression, negative affect, and somatic/vegetative symptoms, ↓ anxiety and sleep disturbance scores.
Manber et al. (2010) Acupuncture for depression Pregnant women with Major Depression Randomized; Depression-specific acupuncture (n = 52)
Acupuncture (control, n = 49)
Massage (control, n = 49)
8 weeks 23% No Hamilton Rating Scale for Depression Depression-specific acupuncture ↓ symptom severity, showed greater response rate.

Observational studies

Baratte-Beebe & Lee (1999) Sources of awakenings Pregnant women Longitudinal, Secondary Analysis (n = 25) Preconception, 1st, 2nd, & 3rd trimesters N/A No Sleep diary ↑ In awakenings pre-conception through 3rd trimester. Need to urinate the primary source of awakening in 1st & 3rd trimesters. Parity & environment impact awakenings.
Driver & Shapiro (1992) Sleep stages across pregnancy Primiparous pregnant women Longitudinal, n = 5 Between 8 & 16 weeks, then bimonthly N/A 1 month postpartum Polysomnography (PSG) No reduction in stage 4 sleep. Slow-wave sleep ↑at 27–39. REM sleep time ↓ in last 2 months and wake after sleep onset (WASO) ↑.
Field (2007) Sleep disturbances & depression in pregnancy & newborns Pregnant women & their newborns Depressed (n = 83)
Non-depressed (n = 170)
20–24 weeks, 30–35 weeks, infants observed at birth N/A No SCID, CES-D, STAI, Sleep scale, Visual-Analogue Scale (VAS) of pain perception Depressed women: ↑sleep disturbances, depression, anxiety, & anger in 2nd & 3rd trimesters. ↑Norepinephrine & cortisol. Newborns: ↑sleep disturbances, ↓ deep sleep, ↑disorganized sleep, more active/fussy.
Hedman et al. (2002) Sleep Pregnant women n = 325 3 mo. pre-conception, 1st, 2nd, 3rd trimesters, & 3 months postpartum 62.9% No Basic Nordic Sleep Questionnaire, 5-point scale by Partinen & Gislason Total sleep time (TST) ↑in 1st trimester, ↓ thereafter. Sleep shortest in 3 months postpartum. ↓ Sleep in late pregnancy over age 30. Sleep in all more restless, fragmentary.
Hertz et al. (1992) Sleep Pregnant women in 3rd trimester Pregnant (n = 12)
Age-matched controls (n = 10)
1 night in pregnancy, 1 night 3–5 months postpartum 30% No PSG, Stanford Sleepiness Scale Late pregnancy: ↑WASO, ↓ sleep efficiency, ↓ REM, and ↑stage 1 sleep. Postpartum: ↓ WASO, and ↑sleep efficiency; slight ↑REM.
Kizilirmak et al. (2012) Insomnia Pregnant women Cross sectional, n = 486 N/A N/A No Women’s Health Initiative Insomnia Rating Scale, Beck Depression Inventory (BDI) 52.2% insomnia prevalence. ↑Risk of insomnia in 3rd trimester, for those aged 20 and over, and for those with depression.
Lara-Carrasco et al. (2014) Dreaming in pregnancy 3rd trimester nulliparous pregnant women Prospective, nulliparous 3rd trimester pregnant (n = 57)
Non-pregnant control (n = 59)
14 days 0% No STAI, Edinburgh Postnatal Depression Scale (EPDS), BDI-Short form(SF), Sleep Disorders Questionnaire, Sleep diary No difference in dream recall. Pregnant women ↑ bad dreams, ↓ sleep quality, ↑ awakenings, ↑ recall of bad dreams, nightmares.
Lee et al. (2004) Sleep & labor type Pregnant women in 9th month of pregnancy n = 131 48 hours N/A N/A Actigraphy, Sleep diary, GSDS, VAS for fatigue < 6 hr/a night sleep, severely disturbed sleep associated with longer labors, C-Sections. Fatigue unrelated to labor outcomes.
Lee et al. (2000) Parity & sleep patterns Pregnant women Planning to conceive within 1 year (n = 45)
Those who conceived (n = 33)
Postpartum (n = 29)
2 nights preconception, 1st, 2nd, & 3rd trimesters 12 did not conceive & were not included in the 2nd group No PSG ↑ TST by 11–12 weeks, ↓ deep sleep, ↑ awakenings. By the 3rd month postpartum sleep characteristics improved, but sleep efficiency ↓.
Little et al. (2014) Sleep changes in pregnancy Pregnant women n = 9 7 nights each trimester 0% No Actigraphy WASO and awakenings ↑as pregnancy progressed. Sleep onset latency ↓ as pregnancy progressed, but not significantly. No difference in TST.
Manber et al. (2013) Insomnia in pregnancy Pregnant, low-income Latinas Cross sectional, n = 1289 One-time questionnaire N/A No Insomnia Severity Index (ISI), EPDS Correlates of insomnia: ↑EPDS scores, completing measures in English, and income. ↑Insomnia in those with EPDS scores ≥9.
Mindell et al. (2000) Sleep disturbances in pregnancy Pregnant women Cross sectional; 8–12 weeks (n = 37)
18–22 (n = 28)
25–28 (n = 24)
35–38 (n = 38)
One-time questionnaire Each woman participated only one time No Self-reported sleep, Epworth Sleepiness Scale Common sleep disturbances: frequent awakenings, difficulty falling asleep, sleep apnea symptoms. Few differences in sleep patterns across pregnancy, however, women in late pregnancy slept and napped more.
Swanson et al. (2011) Anxiety, depression, & insomnia Perinatal women in outpatient psychiatric treatment Archival; n = 257 N/A N/A No ISI, EPDS, Penn State Worry Questionnaire (PSWQ) Women with clinically significant ISI scores had ↑ odds for reporting depression and anxiety.
Tsai et al. (2012) Sleep, depressive symptoms, & perception of fatigue 3rd trimester, nulliparous, Taiwanese, pregnant women Prospective; n = 38 7 days 12% No Actigraphy, Sleep Diary, PSQI, CES-D Most napped during the day. Antecedent night sleep duration inverse association with fatigue. More depressive symptoms predicted more severe daytime fatigue.
Wang et al. (2010) Zolpidem Pregnant women Population-based; zolpidem (n = 2,497)
No zolpidem (n = 12485)
N/A N/A N/A N/A Adverse outcomes: low-birth-weight, preterm deliveries, small-for-gestational-age infants, congenital anomalies, C-sections.

Table 3.

Postpartum and sleep

Study author Observational or Treatment Study Population Group design and sample size Study length/assessment points Attrition rates Follow up Outcome measure Results
Intervention studies

Ashrafinia et al. (2014) Pilates exercise Primigravada postpartum women Pilates (n = 40)
Control (n = 40)
8 weeks 0% No Pittsburgh Sleep Quality Index (PSQI) Pilates group showed improvement in subjective sleep quality, sleep onset latency, daytime dysfunction and PSQI score.
Ko & Lee (2014) Back massage Postpartum women Randomized; Back Massage (n = 31)
Control (n = 31)
5 days 1% No PSQI Back massage in the postnatal period significantly improved the sleep quality.
Li et al. (2011) Foot reflexology Postpartum women reporting poor sleep quality Randomized; Foot reflexology (n = 34)
Control (n = 34)
5 days 0% No PSQI Foot reflexology in postnatal period significantly improved the sleep quality.
Swanson et al. (2013) CBT for insomnia Postpartum women with insomnia & depression Pilot; n = 12 5 weeks N/A No Sleep diary Statistically significant improvements in sleep efficiency and total wake time, mood, insomnia severity, sleep quality, and fatigue.

Observational studies

Bei et al. (2010) Disrupted sleep & mood disturbance Healthy women at low risk for postpartum depression n = 44 3rd trimester & 1 week postpartum 0% No PSQI, actigraphy, depression & anxiety scales, Affect Schedule Perception of poor sleep and conscious awareness of its impact during wake might be more related to immediate postpartum mood disturbances than actual sleep quality and quantity.
Dorheim et al. (2014) Insomnia in pregnancy & postpartum depression Perinatal women Longitudinal, population-based; n = 2088 Weeks 17 & 32 & 8 weeks postpartum 55% No Bergen Insomnia Scale, Edinburgh Postnatal Depression Scale (EPDS) After delivery women slept ↓ at night, had ↑ awakenings, but improved insomnia scores. Insomnia in pregnancy may be marker for postpartum depression in women with previous depression.
Dorheim et al. (2009) Postpartum sleep & depression Postpartum women Population-based, cross-sectional; n = 2830 One-time assessment at 7 weeks N/A No PSQI, EPDS Depression, previous sleep problems, being primiparous, not exclusively breastfeeding, or having a younger or male infant associated with poor postpartum sleep quality.
Montgomery-Downs et al. (2010) Sleep during 4 months postpartum Postpartum women Longitudinal; 2–13 weeks (n = 50)
9–16 weeks (n = 24)
7–12 weeks N/A No Actigraphy Though postpartum mothers’ total sleep time (TST) was ↑ in initial postpartum months, sleep was fragmented and inefficient.
Okun et al. (2011) Sleep quality & hormones postpartum Pregnant women with history of major depressive disorder/postpartum major depression (PPMD) (not depressed in current pregnancy) n = 56 First 17 weeks postpartum 0% No PSQI, Hamilton Rating Scale for Depression (HRSD), estradiol, prolactin, cortisol, IL-6 Poor sleep quality in 17 weeks post-delivery ↑ risk for recurrent PPMD in women with history of depression. Changes in the hormonal milieu not associated with recurrence.
Park et al. (2013) Sleep variables & postpartum depression Healthy primiparous women n = 25 3rd trimester (1 week), 2, 6, 10, & 14 weeks postpartum 0% No Actigraphy, Sleep diary, EPDS Sleep fragmentation, efficiency, and wake after sleep onset (WASO) correlated with EPDS scores postpartum.
Swain et al. (1997) Sleep patterns, mood states, cognitive functioning Primiparous mothers Primiparous (n = 53)
Non-postpartum controls (n = 30)
First 3 weeks postpartum 30% No Sleep diary, Visual Analogue Scale (VAS) for mood, Cognitive & psychomotor tests Postpartum women reported ↑ awakenings, ↑ WASO, and ↑ naps, but overall sleep time was similar to control.
Tikotzky et al. (2010) Maternal sleep & depression & infant affectivity Women 6 months postpartum n = 69 1 week N/A No HRSD, Sleep diary, Infant Behavior Questionnaire-Revised (IBQ-R) Maternal depression severity a predictor of IBQ-R Distress & Falling Reactivity scales. Poor maternal sleep a predictor of the IBQ-R Sadness scale.
Tsai & Thomas (2012) Sleep disturbances & depressive symptoms Healthy primiparous postpartum women n = 22 1 week 15% No Actigraphy, General Sleep Disturbance Scale, EPDS Variable sleep duration from night to night and awakening too early correlated with ↑ depressive symptoms.
Wilkie & Shapiro (1992) Sleep disruption & postnatal blues Perinatal women n = 63 10 days 21% No Sleep Diary, Stein Questionnaire, VAS for mood states Nighttime labor, history of sleep disruption in late pregnancy may be associated with postnatal blues.
Wolfson et al. (2003) Sleep patterns & depressive Symptoms First-time mothers n = 56 3rd trimester, Postpartum: 2–4 & 12–16 weeks, & 12–15 months 32% No Sleep diary, Center for Epidemiologic Studies Depression Scale Differences in rise time, time awake due to disruptions, & naps at 2–4 weeks. Depressive symptoms ↑ at 2–4 weeks. Women with depressive symptoms at 2–4 weeks had ↑ TST, later rise times, more naps in late pregnancy.

Table 4.

Menopause and sleep

Study author Study of Population Group design and initial sample size Study length/Assessment points Attrition rates Follow up Outcome measure Results
Intervention studies

Afonso et al. (2012) Yoga Postmenopausal women Randomized; Yoga (n = 15)
Passive stretching (n = 14)
Control (n = 15)
16 weeks 0% No Insomnia Severity Index (ISI) ↓ Insomnia scores for both groups
Agosta et al. (2011) Magnolia bark + isoflavones, & lactobacilli Menopausal women Randomized; Isoflavones, lactobacillus, calcium & vitamin D3 (n = 300)
Magnolia bark + estromineral serena (n = 334)
0, 4, 8, 12 weeks N/A No Self-report of menopausal symptoms ↓ Menopausal symptoms for both groups. Magnolia bark + Estromineral serena more active on insomnia & mood.
Archer et al. (2009) Desvenlafaxine Postmenopausal women with vasomotor symptoms Randomized; desvenlafaxine 100 mg (n = 153) 150 mg (n = 152)
Placebo (n = 153)
12 weeks + 1 week taper period 13% 1 week after taper period Hot flash (HF) diary ↓ HF, HF severity, and nighttime awakenings.
Asltoghiri et al. (2012) Reflexology Postmenopausal women Randomized; Reflexology (n = 53)
Non-specific foot massage (n = 47)
21 days 10% No Pittsburgh Sleep Quality Index (PSQI) ↓ Sleep disorder symptoms.
Borud et al. (2009) Acupuncture Postmenopausal women with vasomotor symptoms Randomized; Acupuncture (n = 134)
Control (n = 133)
12 weeks 7% No HF diary ↓ HF frequency
↑ Hours of sleep
Carmody et al. (2011) Mindfulness-Based Stress Reduction (MBSR) Late perimenopausal & early postmenopausal women with vasomotor symptoms Randomized; MBSR (n = 57)
Control (n = 53)
8 weeks 9.3% Follow-ups at weeks 12, 16, 20 HF diary, Depression/Anxiety/Quality of life measures ↓ HF bother. Significant difference in perceived sleep quality but within subject differences not significant
Cohen et al. (2014) Omega-3 Supplements Peri- & postmenopausal women with vasomotor symptoms Randomized; Oral omega-3 (n = 177)
Placebo (n = 178)
12 weeks 1% No ISI and PSQI No significant differences in vasomotor or sleep variables
Dobkin et al. (2009) Ramelteon (Rozeram) Peri- & postmenopausal women with sleep latency insomnia Open label pilot; Ramelteon 8 mg (n = 20) 6 weeks 30% No Sleep diary Ramelteon effective in improving subjective reports of sleep onset latency (SOL), total sleep time (TST), and sleep quality.
Dorsey et al. (2004) Zolpidem (Ambien) Peri- & postmenopausal women with insomnia Randomized; Zolpidem 10 mg (n = 68)
Placebo (n = 73)
4 weeks 11% No Subjective sleep reports Zolpidem ↑ TST, ↓ wake after sleep onset, and inumber of awakenings.
Hachul et al. (2011) Isoflavones (soy) Postmenopausal women with sleep disturbance Randomized; Oral isoflavones (80 mg; n = 19)
Placebo (n = 19)
16 weeks 2% No Polysomnography (PSG) Isoflavones ↑ sleep efficiency, ↓ intensity and number of HF, and ↓ subjective insomnia.
Hachul et al. (2008) Estrogen and/or progesterone replacement therapy Postmenopausal women Randomized; Conjugated equine estrogens 0.625 mg (n = 14)
Placebo (n = 19)
All received medroxyprogesterone acetate 5 mg in addition to previous tx after 12 weeks
24 weeks 0% No Standardized questionnaire of sleep quality; PSG, Epworth Sleepiness Scale Estrogen + progesterone more effective than estrogen alone in ↓ PLM, HF, and bruxism. ↓ Breathing irregularities, arousals, anxiety and memory impairment in both groups following progesterone treatment. Hormone therapy did not significantly affect sleep quality.
Huang et al. (2006) Acupuncture Postmenopausal women with HF Pilot; Randomized; Active acupuncture (n = 12)
Placebo acupuncture (n = 17)
7 weeks; 2 20-min treatments a week first 2 weeks, 1 a week thereafter 24% 1-month follow up HF diary & PSQI Nocturnal HF severity reduced, but not significantly, however correlations between improvements in PSQI and reductions in nocturnal HF severity and frequency significant.
Joffe et al. (2010) Eszopiclone Peri- & postmenopausal women with HF & depression and/or anxiety symptoms Randomized, double blind, crossover; eszopiclone 3 mg
Placebo; n = 59
11 weeks 22% No ISI, Sleep diary, depression/anxiety/quality of life measures Eszopiclone improved all sleep parameters, depressive symptoms, anxiety symptoms, quality of life, and nighttime (but not daytime) HF.
Joffe et al. (2007) Duloxetine Postmenopausal women with major depressive disorder Pilot; Oral duloxetine (60–120 mg; n = 20) 8 weeks 25% No Montgomery-Asberg Depression Rating Scale (MADRS), PSQI Significant improvements in depression, vasomotor, anxiety, and pain.
Mansikkamaki et al. (2012) Sleep quality & aerobic activity Sedentary menopausal women Randomized; Aerobic training 4x/week (n = 88)
Control (n = 88)
6 months 13% No Daily subjective sleep reports Sleep quality improved significantly. Hot flushes related to sleep ↓ .
Nowakowski et al. (2012) Cognitive behavioral therapy (CBT) for Insomnia Perimenopausal women Archival; Group CBT for insomnia (n = 44)
Control (n = 63)
7 sessions, 1 a week for 5 weeks, then biweekly for 4 weeks N/A N/A ISI, Beck Depression Inventory (BDI), Dysfunctional Beliefs & Attitudes about Sleep Scale Significant ↓ in ISI and BDI. Women who perceive their sleep as disrupted by menopausal symptoms may benefit from CBT for insomnia.
Pickett et al. (1989) Progesterone & estrogen replacement therapy Postmenopausal women Combined oral estrogen & progesterone 7 days 0% No PSG No differences before and after administration of hormones.
Scharf et al. (1997) Estrogen replacement therapy Postmenopausal women with hot flushes n = 7; Placebo baseline then estrogen 0.625 mg 5 weeks 0% No Stanford Sleepiness Scale, Subjective sleep assessment, HF log ↓ In number of hot flushes and number of hot flushes associated with awakenings. Sleep efficiency ↑.
Schiff et al. (1979) Estrogen replacement therapy Hypogonadal women Double-blind, crossover, n = 16;
Estrogen 0.625 mg
Placebo
128 days, 10 total nights in sleep lab N/A No PSG, Clyde Mood Scale, Gottschalk-Gleser Test ↓ Number of vasomotor flushes, mean sleep latency. ↑ REM. Positive correlation between psychological intactness and SOL.
Schüssler et al. (2008) Progesterone replacement therapy Postmenopausal women Randomized, double-blind, crossover, n = 10;
Oral micronized progesterone 300 mg
Placebo
2 treatment intervals of 21 days separated by 2 weeks washout 0% No PSG, St. Mary’s Hospital Sleep Questionnaire, HF diary, cognitive performance tests Progesterone ↓ intermittent time awake. ↑ REM sleep in first third of night, no effect on cognitive performance.
Sivertsen et al. (2006) CBT vs. Zopiclone Older adults Randomized, double-blind; CBT (n = 18)
Zopiclone 7.5 mg (n = 16)
Placebo (n = 12)
6 weeks 21% 6 months PSG, Sleep Diary CBT was superior to zopiclone in short- and long-term management of insomnia. CBT ↑ sleep efficiency and slow-wave sleep, and ↓ awakenings.
Soares et al. (2006) Eszopiclone (Lunesta) Peri- or early postmenopausal women with insomnia Randomized; Eszopiclone 3 mg (n = 201)
Placebo (n = 209)
4 weeks 12.4% No ISI 58% of those treated with eszopiclone ↓ ISI score to “non-significant clinical insomnia.”
Soares et al. (2006) Escitalopram (Lexapro) vs. estrogen & progesterone Peri- & postmenopausal women with depressive disorders & menopause related symptoms Randomized; Escitalopram 10–20 mg (n = 20)
Ethinyl estradiol 5 microg + norethindrone acetate 1 mg (n = 20)
8 weeks 20% No MADRS, Greene Climacteric Scale, Clinical Global Impression (CGI), sleep & quality of life scales Escitalopram more efficacious for treatment of depression. Improved sleep, HF, and quality of life.
Taavoni et al. (2013) Valerian/Lemon balm Postmenopausal women Triple blind; Valerian officinalis 160 mg + lemon balm 80 mg (n = 50)
Placebo (n = 50)
Not reported Not reported 1 month follow up PSQI ↓ Levels of sleep disorders.
Vermes et al. (2005) Remifemin Women aged 40–65 not on estrogen therapy n = 2016 0, 4, 8, & 12 weeks 7.5% No Kupperman Menopause Index Remifemin ↓ menopausal symptoms. Most favorable changes in HF, sweating, insomnia, and anxiety.
Voshaar et al. (2004) Zolpidem & rebound insomnia Aged 18–65 with insomnia diagnosis Randomized; zolpidem 10 mg (n = 74)
temazepam 20 mg (n = 85)
6 weeks 29% No Sleep diary, sleep questionnaire, State Trait Anxiety Inventory, CGI, Physician-rated tremor, sweating, agitation Both improved total sleep time (TST) and SOL no differences in rebound insomnia, efficacy, or safety.
Zanardi et al. (2007) SSRIs with or without hormone therapy (HT) Postmenopausal women with depression Prospective; SSRIs + HT (n = 47)
SSRIs, no HT (n = 123)
7 weeks 8% No Hamilton Rating Scale for Depression, CGI, Serum levels of gonadotropins & sex hormones HT appeared to improve the antidepressant response to SSRIs.

Observational studies

Bliwise et al. (1992) Factors related to sleep quality Elderly women “Good sleepers” (n = 22)
“Poor sleepers” (n = 16)
N/A N/A No PSG Using estrogen did not differentiate good from poor sleepers.
Col et al. (2009) Duration of vasomotor symptoms Healthy women Longitudinal; n = 438 13 years 33% N/A Somatic & vasomotor symptom checklist, Health behavior assessments Mean duration of bothersome symptoms was estimated at 5.2 years. The only factor associated with duration of HF was exercise (↑ exercise associated with ↓ symptom duration).
Ensrud et al. (2009) Relationship between frequency and severity of HF and insomnia Postmenopausal women with HF n = 217; (Actigraphy subcohort: n = 112) One time questionnaire (+1 week for subcohort) N/A N/A HF diary, ISI, Actigraphy ISI score associated with ↑ frequency moderate/severe HF. ↑ Frequency of moderate/severe HF independently associated with ↑ nighttime wakefulness and ↑ number of long wake episodes, but not sleep efficiency, TST, or SOL.
Erlik et al. (1981) Relationship between HF and waking episodes Postmenopausal women with HF Postmenopausal, severe HF (n = 9)
Asymptomatic premenopausal (n = 5)
3 nights 0% No PSG, finger temperature, skin resistance Significant correlation between HF and waking episodes. Estrogen ↓ HF and waking symptoms.
Freedman et al. (2006) To determine regions of brain activation associated with HF Postmenopausal women Symptomatic postmenopausal (n = 12)
Asymptomatic eumenorrheic (n = 8)
Up to 12 10-min functional magnetic resonance imaging (fMRI) scans N/A No fMRI Activation of insular cortex associated with the “rush of heat” of HF. Thermo-regulation represented in a distributed cortico-subcortical network rather than a single localized structure.
Freedman & Roehrs (2004) Determine if HF produce disordered sleep Menopausal women with HF Symptomatic postmenopausal (n = 12)
Asymptomatic Postmenopausal (n = 8)
Premenopausal (n = 11)
3 nights N/A No PSG, Sternal skin conductance, Sleep Latency Test, Post sleep questionnaire, Fatigue Assessment Inventory, Divided attention task, Psychomotor Vigilance Task No significant group differences on sleep stage measure. No evidence that HF produce sleep disturbance in symptomatic postmenopausal women.
Glazer et al. (2002) Predictors, moderators, and outcome variables associated with the transition to midlife Midlife women aged 40–60 n = 160 0, 9, and 18 months 20% No Hobfall Conservation of Resources tool, coping scale, menopause symptom/attitude scales, health behavior profile, anxiety/depression measures Anxiety predictors: loss of resources, coping effectiveness, education. Depression predictors: loss of resources, education. Health promoting activities predicted by attitude toward menopause, coping effectiveness. Stress a better predictor of negative outcomes than menopause.
Gold et al. (2000) Factors related to menopausal and other symptoms Women aged 40–55 Cross sectional survey, n = 16065 N/A N/A N/A Self-report of symptoms Peri- or postmenopausal women reported the most symptoms. Lifestyle, menstrual status, race/ethnicity, socioeconomic status, & BMI affect symptoms.
Kravitz et al. (2003) Sleep difficulty Women aged 40–55 Cross sectional, n = 12603 N/A N/A N/A Symptom questionnaire Menopausal status associated with difficulty sleeping, ethnicity, vasomotor & psychological symptoms, self-perceived health, health behaviors, arthritis, education.
Kravitz et al. (2008) Sleep disturbance Women aged 42–52 Longitudinal, n = 3302 7 annual assessments 27.2% No Self-report of sleep Progression through menopausal transition associated with self-reported sleep disturbances.
Savard et al. (2004) Sleep & nocturnal HF Breast cancer survivors n = 24 3 nights at each of 4 time points N/A N/A PSG, Skin conductance, Self-report of HF 10-min periods around HF had more wake time and more stage changes to lighter sleep. Nights with HF had ↑ wake time, ↓ Stage 2 sleep, and ↑ REM latency.
Terauchi et al. (2010) Insomnia in menopause Peri- & postmenopausal Japanese women Archival; n = 1451 N/A N/A N/A Health-related Quality of Life Insomnia more correlated with depressed mood than vasomotor symptoms. Hormone therapy & nightly hypnotics improved insomnia, ‘as needed’ hypnotics did not.
Woodward & Freedman (1994) Thermo-regulatory effects of HF on sleep Postmenopasual women with HF Postmenopausal with HF (n = 12)
Postmenopausal without HF (n = 7)
24 hours N/A No PSG, Ambulatory recordings of HF HF associated with ↑ Stage 4 sleep and ↓ first REM period. HF 2 hours prior to sleep onset correlated with slow-wave sleep.
Young et al. (2003) Sleep quality across menopause Pre-, peri-, & postmenopausal women Population-based; n = 589 N/A N/A No PSG, Self-report of sleep Menopause not associated with sleep quality. Peri- & postmenospausal women more dissatisfied with sleep, but menopause not a strong predictor of sleep disorder.