Sleep Disturbances during Menopause: Mechanisms and Management Approaches

Abstract

Sleep disturbances are highly prevalent during menopausal transition and postmenopause; however, the underlying mechanisms remain incompletely understood. Epidemiological cohort studies demonstrate a sharp increase in the occurrence of insomnia symptoms in midlife coincident with declining estradiol levels, vasomotor symptoms (VMS), and increased susceptibility to depression and anxiety. These psychological factors interact bidirectionally with insomnia, amplifying its adverse impacts on health-related quality of life. Additional contributors—including lower urinary tract symptoms, musculoskeletal pain, reduced muscle mass, and sleep-disordered breathing—emphasize the multifactorial nature of menopausal insomnia. Management includes hormonal, pharmacological, and nonpharmacological strategies. Although menopausal hormone therapy remains the most effective treatment for VMS, its benefits for sleep are inconsistent and largely limited to subjective improvement. Randomized trials suggest that non-benzodiazepine hypnotics can enhance sleep initiation and maintenance; moreover, traditional herbal formulas (e.g., Kampo) may benefit selected women, although the evidence is limited. Newer dual orexin receptor antagonists, such as suvorexant, daridorexant, and lemborexant, have shown efficacy with regard to sleep onset and maintenance in adults, including women in their midlife. By integrating epidemiological findings, mechanistic insights, and comparative treatment data, this review emphasizes individualized care tailored to symptom profile, risk factors, and patient preference. Future research should bridge gaps between subjective and objective evaluations and delineate biological pathways (neuroendocrine, circadian, orexin, and inflammatory/myokine) to guide targeted therapies.

Graphical Abstract

INTRODUCTION

It is well established that women are more frequently affected by sleep disturbances than men. A classic epidemiological study of more than one million United States (U.S.) residents reported higher insomnia complaints among women across the lifespan, with the disparity most pronounced between ages 40–50, coinciding with the menopausal transition [1]. Consistent with this, the Study of Women’s Health Across the Nation (SWAN) found that difficulty initiating sleep, maintaining sleep, and early morning awakening increased significantly from the menopausal transition to postmenopause compared with the premenopausal stage [2].

Complementing these large-scale data, institutional analyses from our Systematic Health and Nutrition Education Program (SHNEP) provide clinical insight from a Japanese cohort. Among 1,451 peri- and postmenopausal participants attending our menopause clinic, more than half reported moderate-to-severe insomnia that interfered with daily activities, and greater insomnia severity correlated with poorer quality of life (QOL) across physical, mental, social, and life-satisfaction domains [3]. These single-site results are presented to illustrate clinical burden in routine care and should be interpreted alongside broader epidemiological evidence.

Multiple physiological and psychological mechanisms likely contribute to the rise in insomnia during the transition, including estrogen decline with vasomotor symptoms (VMS) and increased vulnerability to anxiety and depression [4,5,6].

ESTROGEN AND MENOPAUSAL INSOMNIA

During the transition from perimenopause to postmenopause, estradiol decreases while follicle-stimulating hormone rises; VMS (hot flashes, night sweats) are the symptoms most clearly linked to these hormonal changes. One hypothesis posits that insomnia during perimenopause results directly from estrogen withdrawal; however, the prevailing view is that sleep disturbance is primarily driven by nocturnal VMS triggered by reduced estrogen. Several studies demonstrate significant correlations between VMS severity and insomnia [7,8,9].

Our own analyses provide complementary evidence: night sweats independently contributed to both difficulty initiating sleep (DIS) and non-restorative sleep (NRS) (Tables 1 and 2) [10], and principal component analysis of 21 symptoms showed DIS clustering with night sweats and hot flushes [11]. At the same time, objective evidence has been mixed: polysomnography combined with skin-conductance monitoring has not consistently demonstrated a temporal association between VMS episodes and sleep disruption [12,13]. These discrepancies highlight challenges in aligning subjective and objective measures and suggest potential roles for perception, arousal mechanisms, and circadian factors.

Table 1. Contributing factors to DIS.

	Crude OR (95% CI)	P value	Adjusted OR (95% CI)	Wald Chi-square	P value
Age	1.015 (0.962–1.070)	0.594
Menopausal status (peri- vs. post-)	0.624 (0.328–1.187)	0.151
Hot flushes	1.258 (0.984–1.609)	0.068
Night sweats	1.524 (1.194–1.946)	< 0.001	1.488 (1.142–1.938)	8.684	0.003
HADS depression	1.174 (1.088–1.266)	< 0.001	1.061 (0.959–1.174)	1.312	0.252
HADS anxiety	1.246 (1.136–1.367)	< 0.001	1.182 (1.050–1.331)	7.638	0.006

Contribution of age, menopausal status, MHR-QOL scores for vasomotor symptoms, and HADS depression and anxiety scores to DIS experienced almost every night (n = 237).

DIS: difficulty initiating sleep, OR: odds ratio, Cl: confidence interval, HADS: hospital anxiety and depression scale, MHR-QOL: menopausal health-related quality of life questionnaire.

Adapted from the article of Terauchi et al. (Maturitas 2012; 72: 61-5) [10].

Table 2. Contributing factors to NRS.

	Crude OR (95% CI)	P value	Adjusted OR (95% CI)	Wald Chi-square	P value
Age	0.997 (0.949–1.047)	0.892
Menopausal status (peri- vs. post-)	0.827 (0.466–1.466)	0.515
Hot flushes	1.266 (1.008–1.589)	0.042	1.125 (0.848–1.491)	0.664	0.415
Night sweats	1.538 (1.222–1.938)	< 0.001	1.423 (1.077–1.881)	6.160	0.013
HADS depression	1.192 (1.108–1.283)	< 0.001	1.128 (1.023–1.244)	5.846	0.016
HADS anxiety	1.198 (1.104–1.300)	< 0.001	1.092 (0.979–1.217)	2.514	0.113

NRS: non-restorative sleep, OR: odds ratio, Cl: confidence interval, HADS: hospital anxiety and depression scale.

Adapted from the article of Terauchi et al. (Maturitas 2012; 72: 61-5) [10].

DEPRESSION, ANXIETY, AND INSOMNIA DURING MENOPAUSAL TRANSITION

Insomnia is closely—and bidirectionally—associated with depression and anxiety. Patients with mood disorders frequently report sleep disturbance, and chronic insomnia increases risk for subsequent depressive and anxiety disorders [5,6]. Importantly, depressive and anxious symptoms rise during the transition [14], and population data show correlations between VMS and depression [15]. In our cohort, over one-third of women with moderate-to-severe insomnia had severe depression [3], with anxiety independently associated with DIS and depression with NRS (Tables 1 and 2) [10]. Recent reviews further emphasize reciprocal amplification among VMS, mood symptoms, and insomnia, including bidirectional links between VMS and mood symptoms in which sleep disruption may act as an intermediary mechanism (Fig. 1) [16,17,18].

Fig. 1. Conceptual model of reciprocal amplification among VMS, insomnia/poor sleep, and mood symptoms (anxiety/depression). Declining estradiol and neuroendocrine changes contribute to VMS and mood vulnerability. VMS and insomnia, and mood symptoms and insomnia, are bidirectionally linked. VMS and mood symptoms may also reinforce one another, partly mediated by sleep disruption. Additional factors (e.g., nocturia/LUTS, pain, low muscle mass, sleep-disordered breathing, shift work, psychosocial stress) can exacerbate insomnia and/or mood symptoms. VMS: vasomotor symptoms, LUTS: lower urinary tract symptoms.

PERIMENOPAUSAL SLEEP DISTURBANCE AND OTHER RELATED FACTORS

Beyond VMS and mood symptoms, additional factors contribute to sleep problems in midlife women. Actigraphy studies show that subjective insomnia corresponds with reduced sleep efficiency and increased fatigue [19]. Lower urinary tract symptoms (LUTS)—notably nocturia and frequency—are associated with sleep disturbance in community samples and clinic cohorts [20,21]. Musculoskeletal pain is also linked to impaired sleep quality, with bidirectional influences [22,23]. Lower muscle mass correlates with more severe insomnia, potentially via altered myokines that influence sleep regulation [24]. Sleep-disordered breathing in postmenopausal women relates to fatigue and musculoskeletal pain [25,26], and occupational factors such as shift work are associated with excessive daytime sleepiness and metabolic risk [27,28]. These observations underscore the need for comprehensive, multifactorial assessment and management.

DRUG TREATMENT OF PERIMENOPAUSAL INSOMNIA

The triad of VMS, depression/anxiety, and insomnia—each influenced by declining estrogen—interacts to reduce QOL in perimenopausal women (Fig. 1). Addressing each component may yield overall benefit. Pharmacologic options therefore include: hypnotics for insomnia; menopausal hormone therapy (MHT) for VMS; antidepressants or anxiolytics for mood symptoms; and traditional herbal medicine commonly used in Japan. From a mechanistic perspective, MHT (also termed hormone replacement therapy) is reasonable when VMS contribute substantially to sleep complaints.

Historically, MHT was applied for symptom relief and prevention of cardiovascular disease and osteoporosis; its broad use declined after the Women’s Health Initiative reports, though MHT remains the most effective therapy for VMS. Subjective insomnia can improve with MHT even when objective sleep measures show minimal change [29,30,31,32]. These discrepancies suggest perceptual or affective pathways (e.g., mood improvement) may mediate perceived sleep benefit; baseline depressive symptom severity has been linked to greater sleep improvement with estrogen therapy [33].

In traditional practice, Kampo formulas such as Kamishoyosan are prescribed for women with psychological symptoms and somatic complaints. Small observational studies—including our own—suggest potential benefit for sleep initiation and depth, but limited sample sizes and retrospective designs warrant caution [34].

Modern pharmacotherapy commonly employs non-benzodiazepine hypnotics (e.g., zolpidem, eszopiclone), which have demonstrated efficacy for sleep initiation and maintenance in peri-/postmenopausal women; eszopiclone has also shown benefits for VMS and mood symptoms in some trials [33,35,36]. An randomized controlled trial directly comparing zolpidem with MHT (n = 72) reported greater improvement in subjective insomnia with zolpidem than with MHT or placebo [32]; however, this study was small, and conclusions should not be overgeneralized. Our institutional data similarly suggested improvements in sleep and cardiometabolic parameters with hypnotics [37], but methodological limitations temper inference.

Dual orexin receptor antagonists (DORAs) represent a newer class with evidence for sleep onset and maintenance benefits, and relatively low next-day residual effects. Beyond lemborexant, which has phase III data—including analyses in midlife women [38,39,40]—the class includes suvorexant and daridorexant with supportive trials in adults [41,42]. These agents should be considered alongside established options (non-benzodiazepines, melatonin agonists) in individualized treatment plans.

CONCLUSION

Menopausal insomnia reflects a complex interplay among hormonal change, VMS, mood vulnerability, and additional contributors such as LUTS, musculoskeletal pain, reduced muscle mass, and sleep-disordered breathing. Persistent gaps include discordance between subjective symptoms and objective measurements and incomplete understanding of biological pathways. Priority areas for future work include (i) elucidating neuroendocrine, circadian, orexinergic, and inflammatory/myokine mechanisms and (ii) developing individualized multimodal strategies integrating hormonal, pharmacologic, behavioral (e.g., cognitive behavioral therapy for insomnia), and complementary approaches. Advances along these lines should improve both scientific understanding and QOL for affected women.