Amygdala Insula Retraining in the Management of Perimenopause Symptoms

Perimenopause is a transitional reproductive stage marked by fluctuations in ovarian steroid hormones. It is often associated with sleep disruption, fatigue, mood changes, anxiety, cognitive changes, and diminished quality of life. Emerging evidence suggests that, in addition to hormonal changes, alterations in central threat processing, interoception, and autonomic nervous system regulation may contribute to symptom amplification and persistence during this period.

Amygdala and Insula Retraining (AIR) is a structured, neuroplasticity-based behavioral intervention designed to modulate the autonomic nervous system. The program integrates cognitive reframing, somatic retraining, mindfulness practices, breathwork, behavioral pattern interruption, and safety-signal conditioning with the aim of calming hyper-reactive limbic pathways. Through repeated practice, AIR seeks to restore autonomic balance and reduce symptom burden.

This study is a 24-week, parallel-group, randomized, wait-list-controlled trial conducted remotely. A minimum of 160 perimenopausal participants aged 38 to 60 years will be randomized in a 1:1 ratio to either an active intervention arm or a wait-list control arm. Participants in the active intervention arm will receive immediate access to the 12-week AIR program in addition to treatment as usual. Participants in the wait-list control arm will continue treatment as usual for 12 weeks and will receive access to the recorded AIR intervention following completion of the primary endpoint assessment. Both groups will be followed through week 24.

The primary assessment is the the Menopause Rating Scale (MRS) total score from baseline (T0) to post-intervention at week 12 (T1). Secondary outcomes, assessed at baseline, week 12, and week 24, include insomnia severity, fatigue, anxiety, depression, patient global impression of change, and sexual function (optional). Concomitant therapies, including hormone replacement therapy and relevant medications, will be recorded at all assessment time points.

An exploratory wearable sub-study will be conducted in a randomly selected subset of approximately 50 participants distributed across both study arms. Wearable devices will be used to collect objective physiological measures, including heart rate variability, resting heart rate, sleep duration and efficiency, and activity metrics. These data will be analyzed descriptively to explore potential physiological correlates of symptom change.

• Greene Climacteric Scale [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• Hot Flash Related Daily Interference Scale (HFRDIS) [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• Insomnia Severity Index (ISI) [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• PROMIS Fatigue Short Form 8a [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• Patient Health Questionnaire-9 (PHQ-9) [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• Generalized Anxiety Disorder-7 (GAD-7) [Срок оценки: Baseline (Week 0) to post-intervention (Week 12)]
• Patient Global Impression of Change (PGIC) [Срок оценки: Assessed at Weeks 12 and 24]
• Female Sexual Function Index (FSFI) [Срок оценки: Baseline (Week 0) to post-intervention (Week 12) (optional)]