Researchers examined evidence from more than 24,000 women to investigate a poorly understood question in midlife mental health: how does anxiety reporting differ before, during, and after menopause?
Study: Anxiety symptoms across menopausal stages: a systematic review and meta-analysis. Image Credit: Faizal Ramli / Shutterstock
In a recent systematic review and meta-analysis published in the journal Scientific Reports, researchers synthesized decades of observational evidence to assess associations between menopausal stage and the reporting of anxiety symptoms.
The review evaluated data from 21 peer-reviewed studies involving 24,523 women from multiple countries; 15 of these studies contributed to the meta-analysis, which compared the odds of reporting anxiety symptoms across premenopausal, perimenopausal, and postmenopausal stages.
Study findings revealed that perimenopausal and postmenopausal women had significantly higher odds of anxiety symptoms compared to their premenopausal counterparts, with the highest odds observed during perimenopause. These findings support greater clinical awareness of anxiety symptoms during the menopause transition, but do not establish that menopause causes anxiety or that symptoms increase within individual women over time.
Background
Menopause is clinically defined as the permanent cessation of menstrual periods and is determined retrospectively after 12 consecutive months of amenorrhea (absence of menstruation) without any other pathological or physiological cause.
Menopause typically occurs between the ages of 45 and 55 and is preceded by ‘perimenopause’, a protracted window characterized by irregular ovulatory cycles and erratic hormonal shifts.
While psychiatric literature has long recorded that the menopause transition (MT) is accompanied by increased risk of depressive symptoms, the exact temporal trajectory of psychiatric distress (e.g., anxiety) remains understudied.
Previous systematic evaluations have aimed to elucidate the co-occurrence of menopausal stages and psychiatric distress, but a 2012 narrative review, which reported generally low anxiety across menopausal stages, lacked standardized staging criteria and could not pool quantitative risk estimates, limiting firm conclusions.
Public health information and clinical recommendations differ in how they address anxiety during menopause. For example, while the World Health Organization (WHO) recognizes anxiety as a possible menopause-related symptom, the United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines do not explicitly identify anxiety as a menopausal symptom, though they address other psychological symptoms.
A clearer understanding of the association between menopausal stage and anxiety symptoms could inform clinical guidance and may help improve women’s mental health in the coming years.
About the review
The present review aimed to address this knowledge gap and inform future mental healthcare policies by providing the first comprehensive meta-analysis of anxiety across defined menopausal stages.
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identified the sample of publications through a custom keyword search across MEDLINE, PsycINFO, Embase, and Web of Science from database inception through August 16, 2024.
Titles, abstracts, and full texts were screened for cross-sectional and longitudinal observational studies involving women aged 18 or older, with anxiety assessed using standardized questionnaires, interviews, or broader scales containing multiple anxiety items, such as the Hospital Anxiety and Depression Scale (HADS), the State-Trait Anxiety Inventory (STAI), and the Generalized Anxiety Disorder 7-item (GAD-7) scale.
The review included studies that used the Stages of Reproductive Aging Workshop +10 (STRAW+10) criteria or equivalent definitions of menopausal stage, while excluding studies involving surgical menopause or co-occurring physical or psychiatric conditions.
The methodological quality of included publications was appraised using the Critical Appraisal Skills Program (CASP) checklists for cohort and cross-sectional studies. Following quality assessment, one study rated as low quality was excluded from the meta-analysis. The researchers pooled eligible datasets using a random-effects meta-analysis with inverse-variance weighting. Only baseline observations from longitudinal cohorts entered the pooled analyses alongside cross-sectional studies.
Review findings
The analyses revealed that, compared to premenopausal women, women in perimenopause had 59% higher odds of reporting anxiety symptoms.
Postmenopausal women also had 63% higher odds of anxiety than premenopausal women.
A direct comparison of perimenopause and postmenopause revealed that postmenopausal women had 21% lower odds of reporting anxiety symptoms relative to perimenopausal individuals. This pattern suggests that anxiety reporting may be greatest during perimenopause, but results varied substantially between studies.
The authors drew on wider research to propose that fluctuations in estrogen may influence the metabolism of central neurotransmitters (e.g., serotonin, dopamine, and gamma-aminobutyric acid [GABA]) and alter hypothalamic-pituitary-adrenal (HPA) axis responses to stress, potentially affecting cortisol levels.
These proposed biological pathways may interact with vasomotor symptoms (e.g., hot flashes) and sleep fragmentation alongside cognitive appraisals and social stressors to shape anxiety symptoms.
While the mechanistic underpinnings of these observations were not directly tested, the authors also cautioned that anxiety measures differed across studies, with possible overlap between physical anxiety and menopausal symptoms. The least-adjusted estimates used for pooling may leave residual confounding from prior anxiety, sleep problems, vasomotor symptoms, and psychosocial stressors. The pooled analyses excluded extreme effect estimates, and no separate formal risk-of-bias or certainty-of-evidence assessment was conducted.
Conclusions
The present review found that perimenopause and postmenopause were associated with higher odds of reporting anxiety symptoms, but could not establish the biological mechanisms underlying these associations. Clinicians should consider asking about anxiety symptoms alongside vasomotor complaints, with appropriate referral and evidence-based psychosocial interventions where clinically indicated.
Future large-scale prospective longitudinal cohorts that track detailed reproductive substages, use consistent anxiety measures, and account for important confounders are necessary to clarify symptom trajectories and possible underlying mechanisms and to inform timely psychiatric support for midlife women.
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