Elsevier

Psychoneuroendocrinology

Volume 60, October 2015, Pages 96-104
Psychoneuroendocrinology

Insomnia in women approaching menopause: Beyond perception

https://doi.org/10.1016/j.psyneuen.2015.06.005Get rights and content

Highlights

  • Insomnia that develops in the approach to menopause is poorly characterized.

  • Perimenopausal women with insomnia have a measurable sleep deficit.

  • Hot flashes, frequent in insomniacs, contribute to their poorer sleep quality.

  • Insomnia in perimenopausal women should be treated to avoid negative consequences.

Abstract

The menopausal transition is marked by increased prevalence in disturbed sleep and insomnia, present in 40–60% of women, but evidence for a physiological basis for their sleep complaints is lacking. We aimed to quantify sleep disturbance and the underlying contribution of objective hot flashes in 72 women (age range: 43–57 years) who had (38 women), compared to those who had not (34 women), developed clinical insomnia in association with the menopausal transition. Sleep quality was assessed with two weeks of sleep diaries and one laboratory polysomnographic (PSG) recording. In multiple regression models controlling for menopausal transition stage, menstrual cycle phase, depression symptoms, and presence of objective hot flashes, a diagnosis of insomnia predicted PSG-measured total sleep time (p < 0.01), sleep efficiency (p = 0.01) and wakefulness after sleep onset (WASO) (p = 0.01). Women with insomnia had, on average, 43.5 min less PSG-measured sleep time (p < 0.001). There was little evidence of cortical EEG hyperarousal in insomniacs apart from elevated beta EEG power during REM sleep. Estradiol and follicle stimulating hormone levels were unrelated to beta EEG power but were associated with the frequency of hot flashes. Insomniacs were more likely to have physiological hot flashes, and the presence of hot flashes predicted the number of PSG-awakenings per hour of sleep (p = 0.03). From diaries, women with insomnia reported more WASO (p = 0.002), more night-to-night variability in WASO (p < 0.002) and more hot flashes (p = 0.012) compared with controls. Women who develop insomnia in the approach to menopause have a measurable sleep deficit, with almost 50% of the sample having less than 6 h of sleep. Compromised sleep that develops in the context of the menopausal transition should be addressed, taking into account unique aspects of menopause like hot flashes, to avoid the known negative health consequences associated with insufficient sleep and insomnia in midlife women.

Introduction

Sleep difficulties, particularly night-time awakenings, are a major complaint in the approach to menopause, being present in 40–60% of women (Joffe et al., 2010, Polo-Kantola, 2011) and are one of the top health issues in peri- and postmenopausal women (van Dijk et al., 2015). Together with hot flashes/night sweats, feeling tired and weight gain, sleep problems are the most common symptoms women discuss with their healthcare providers (Williams et al., 2007). In 26% of perimenopausal women (a prevalence that is higher than in premenopausal or postmenopausal women), sleep disturbances cause significant distress and impact women's daytime functioning qualifying them for a diagnosis of insomnia disorder (Ohayon, 2006).

Untreated insomnia is associated with several adverse physical (e.g. hypertension, stroke, diabetes) and psychological (e.g. depression) consequences (Buysse, 2013, Irwin, 2015), yet it is under-appreciated and under-treated, possibly due to its subjective diagnostic nature and multifactorial etiology making it difficult to recognize and treat. The economic burden of insomnia is substantial, with decreased productivity and increased healthcare utilization (Buysse, 2013). The impact of insomnia is particularly relevant in midlife women; in the United States, an estimated 2 million women reach menopause every year (The North American Menopause Society, 2010) and by 2030 more than 1.2 billion women will be 50 years or older.

There is overwhelming evidence of an increase in perceived sleep difficulties as women approach menopause from several large longitudinal studies like the Study of Women's Health Across the Nation (SWAN) (Kravitz and Joffe, 2011), the Australian Longitudinal Study on Women's Health (Berecki-Gisolf et al., 2009), and the Seattle Midlife Women's Health study (Woods and Mitchell, 2010). However, polysomnographic (PSG) evidence of poorer sleep during this stage is sparse (Shaver et al., 1988, Young et al., 2003, Kalleinen et al., 2008), with a large epidemiological study showing even better PSG sleep in peri- and postmenopausal women, despite less sleep satisfaction, compared with premenopausal women (Young et al., 2003). Similarly, while there is substantial evidence associating self-reported hot flashes and self-reported sleep disturbances in peri- and post-menopausal women, there are conflicting data about a link between menopausal hot flashes and PSG-defined measures of sleep quality (Joffe et al., 2010). The discordance between subjective perceptions and “objective” PSG and hot flash findings has led to a lack of clarity in the medical field about the nature of sleep problems in midlife women and how to treat them most effectively.

Conflicting results, both when considering subjective versus objective measurement of sleep as well as across PSG studies, could be due to several factors, including the possibility that subjective and objective sleep assessments tap into different constructs, different analytical approaches, and poor characterization of sub-groups of women with and without clinically-significant sleep disturbances. The presence of insomnia disorder, which reflects a more severe form of interference of poor sleep on a woman's quality of life and daytime functioning, has not been previously considered.

Here, the major aim was to determine whether there is physiological evidence of disturbed sleep, based on PSG and spectral EEG analysis, in women who developed DSM-IV insomnia in the context of the menopausal transition (with no past history of insomnia disorder) compared with age-matched women in the menopausal transition without insomnia. We also investigated the contribution of physiological night-time hot flashes to physiological sleep disturbance. We hypothesized that women with insomnia would have more hot flashes and that a diagnosis of insomnia would be associated with more indications of difficulty maintaining sleep (e.g., more awakenings and more wakefulness within the sleep period, more high frequency EEG power) controlling for effects of menopausal stage, menstrual cycle phase, presence of hot flashes, and depression symptoms.

Section snippets

Participants and procedure

The study was reviewed and approved by SRI International's Institutional Review Board. Participants were recruited from the San Francisco Bay Area community area through flyers, announcements, advertisements, or word of mouth. 72 participants gave written informed consent and received compensation for participation. Sample characteristics and screening procedures are fully described in Sassoon et al. (2014). Briefly, all women had to be in the menopausal transition (menstrual cycle lengths that

Results

Groups did not differ in age, BMI, FSH, or estradiol levels (Table 1). Compared with controls, women with insomnia reported more severe psychological, somatic, and vasomotor symptoms, and had higher scores on the BDI-II (p < 0.05).

Discussion

Sleep difficulties are common and cause clinical distress in a significant proportion of women approaching menopause. We show that women with no past-history of sleep difficulties, who developed DSM-IV insomnia disorder in the approach to menopause, have a severe sleep deficit, with shorter sleep duration, more WASO, and poorer sleep efficiency compared to women in the menopausal transition without insomnia. Nocturnal physiological hot flashes are more common in insomniacs and contribute to

Conclusions

Difficulty sleeping in women who developed insomnia in the context of the menopausal transition is not limited to their perception, being supported by a measurable PSG-defined sleep deficit. Hot flashes, measured in more than half of the insomniacs, contribute to a poorer PSG sleep. Insomnia in midlife women should be routinely assessed and appropriately treated early on to reduce the risk for psychological and medical adverse consequences and to maintain a better quality of life.

Role of funding source

This study was performed at SRI International (Menlo Park, CA, USA) and was supported by National Institutes of Health (NIH), Grant HL103688 to Dr Fiona C Baker. NIH had no role in study design, data analysis and writing of the manuscript.

Conflict of interest

None of the authors has any conflict of interest to report.

Acknowledgements

This study was performed at SRI International (Menlo Park, CA, USA) and was supported by National Institutes of Health, Grant HL103688 to Dr Fiona C Baker. Hormone analysis was conducted by The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core, which is supported by the Eunice Kennedy Shriver NICHD/NIH (NCTRI) Grant P50-HD28934.

We thank our research assistants Justin Greco, David Sugarbaker, David Dresser, Stephanie Claudatos, Sarah Inkelis, and Lena

References (54)

  • A. Beck et al.

    Beck Depression Inventory-II (BDI-II)

    (1996)
  • J. Berecki-Gisolf et al.

    Symptoms reported by women in midlife: menopausal transition or aging?

    Menopause

    (2009)
  • D.J. Buysse

    Insomnia

    JAMA

    (2013)
  • I. Campbell et al.

    Evaluation of the association of menopausal status with delta and beta EEG activity during sleep

    Sleep

    (2011)
  • J.-C. Chen et al.

    Sleep duration and risk of ischemic stroke in postmenopausal women

    Stroke

    (2008)
  • de Zambotti M. et al.

    Interaction between reproductive hormones and physiological sleep in women

    J. Clin. Endocrinol. Metab.

    (2015)
  • M. de Zambotti et al.

    Menstrual cycle-related variation in physiological sleep in women in the early menopausal transition

    J. Clin. Endocrinol. Metab.

    (2015, June)
  • M. de Zambotti et al.

    Magnitude of the impact of hot flashes on sleep in perimenopausal women

    Fertil. Steril.

    (2014)
  • L. Dennerstein et al.

    New findings from non-linear longitudinal modelling of menopausal hormone changes

    Hum. Reprod. Update

    (2007)
  • K. Ensrud et al.

    Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes

    Sleep

    (2015)
  • K.E. Ensrud et al.

    Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy menopausal women with hot flashes: a randomized controlled trial

    Menopause

    (2012)
  • Y. Erlik et al.

    Association of waking episodes with menopausal hot flushes

    JAMA

    (1981)
  • J. Fernandez-Mendoza et al.

    Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study

    Sleep

    (2010)
  • J. Fernandez-Mendoza et al.

    Insomnia with objective short sleep duration and incident hypertension: the Penn State Cohort

    Hypertension

    (2012)
  • M.B. First et al.

    Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) Version 2.0

    (1998)
  • R. Freedman

    Laboratory and ambulatory monitoring of menopausal hot flashes

    Psychophysiology

    (1989)
  • R. Freedman et al.

    Sleep disturbance in menopause

    Menopause

    (2007)
  • Cited by (73)

    • Sleep During Menopause

      2023, Sleep Medicine Clinics
    • Sleep and sleep health

      2023, Encyclopedia of Mental Health, Third Edition: Volume 1-3
    • Assessing and treating insomnia with specific comorbidities

      2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
    • Special considerations for the nonpharmacological treatment of insomnia

      2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
    • The role of ovarian hormones in the pathophysiology of perimenopausal sleep disturbances: A systematic review

      2022, Sleep Medicine Reviews
      Citation Excerpt :

      Further, sleep significantly improved through treatment with selective estrogenic activity regulators, including tibolone, raloxifene or bazedoxifene [39–41]. Several studies (including three with estrogen therapy) showed a lack of association between estrogen and sleep disturbances in perimenopausal women, e.g. waking during the night or early morning awakenings [42–49]. Objective studies of the effects of estrogen treatment on sleep showed mixed effects, with some finding reduced wakefulness [50,51], reduced sleep latency and increased REM sleep [50,52] and others finding no effect [53], despite finding positive improvements in sleep based on subjective reports [28].

    View all citing articles on Scopus
    View full text