Several million women experience debilitating physical and psychological symptoms during the early menopausal transition (EMT) each year. Self-reported sleep disturbance is an almost ubiquitous phenomenon in symptomatic women, and contributes to the economic and social costs of reduced productivity and increased load to the health care system from treatment seeking behavior. Previous studies have failed to find underlying mechanisms for this perceived sleep disturbance. We hypothesize that women who develop symptoms in association with reproductive hormone changes during the EMT have altered central or autonomic nervous system (ANS) regulation that can disrupt the restorative function of sleep. We also hypothesize that regulation of the ANS in these women varies over the menstrual cycle.
We aim to test these hypotheses in Specific Aims 1 and 2 using sensitive measures of electroencephalographic (EEG) and ANS activity during sleep. Symptomatic women also consistently report higher levels of stress, exposure to which will often exacerbate menopausal symptoms. Stress is also a common precipitant of sleep disturbance via its impact on the ANS.
Specific Aim 3 will test the hypothesis that symptomatic women in the EMT will show altered reactivity of the ANS during sleep following exposure to an acute stressor. These studies provide a novel approach to investigating the mechanisms underlying sleep disturbance commonly experienced in the menopausal years. The study will also provide information as to stress reactivity in symptomatic women and inform the mechanisms underlying their observed elevated risk of cardiovascular morbidity.

Public Health Relevance

Women who are symptomatic during the menopausal transition suffer from a range of debilitating symptoms that impact their physical and mental health and that lead to major societal costs in lost productivity and health care expenditure. Sleep disturbances are a ubiquitous and particularly disruptive feature of menopause. This study will assess the relationships between autonomic nervous system dsyregulation, sleep disturbance and the response to stress in women in the early menopausal transition.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Twery, Michael
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Sri International
Menlo Park
United States
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Forouzanfar, Mohamad; Baker, Fiona C; de Zambotti, Massimiliano et al. (2018) Toward a better noninvasive assessment of preejection period: A novel automatic algorithm for B-point detection and correction on thoracic impedance cardiogram. Psychophysiology 55:e13072
Baker, Fiona C; Lampio, Laura; Saaresranta, Tarja et al. (2018) Sleep and Sleep Disorders in the Menopausal Transition. Sleep Med Clin 13:443-456
Baker, Fiona C; de Zambotti, Massimiliano; Colrain, Ian M et al. (2018) Sleep problems during the menopausal transition: prevalence, impact, and management challenges. Nat Sci Sleep 10:73-95
Baker, Fiona C; Sattari, Negin; de Zambotti, Massimiliano et al. (2018) Impact of sex steroids and reproductive stage on sleep-dependent memory consolidation in women. Neurobiol Learn Mem :
de Zambotti, Massimiliano; Trinder, John; Silvani, Alessandro et al. (2018) Dynamic coupling between the central and autonomic nervous systems during sleep: A review. Neurosci Biobehav Rev 90:84-103
de Zambotti, Massimiliano; Trinder, John; Colrain, Ian M et al. (2017) Menstrual cycle-related variation in autonomic nervous system functioning in women in the early menopausal transition with and without insomnia disorder. Psychoneuroendocrinology 75:44-51
de Zambotti, Massimiliano; Sugarbaker, David; Trinder, John et al. (2016) Acute stress alters autonomic modulation during sleep in women approaching menopause. Psychoneuroendocrinology 66:1-10
de Zambotti, Massimiliano; Willoughby, Adrian R; Sassoon, Stephanie A et al. (2015) Menstrual Cycle-Related Variation in Physiological Sleep in Women in the Early Menopausal Transition. J Clin Endocrinol Metab 100:2918-26
de Zambotti, Massimiliano; Claudatos, Stephanie; Inkelis, Sarah et al. (2015) Evaluation of a consumer fitness-tracking device to assess sleep in adults. Chronobiol Int 32:1024-8
de Zambotti, Massimiliano; Colrain, Ian M; Baker, Fiona C (2015) Interaction between reproductive hormones and physiological sleep in women. J Clin Endocrinol Metab 100:1426-33

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