Mental illness in perimenopause: Longitudinal predictors and preventive treatment opportunities (360G-Wellcome-331773_Z_25_Z)

Perimenopause is increasingly recognised as a high-risk period for mental illness. Yet, despite its relevance to a global population of ~725 million middle-aged women, it remains strikingly under-investigated. This project aims to transform early prediction and intervention by identifying women at heightened risk of first-onset or recurrent anxiety, depressive, bipolar, and psychotic disorders during perimenopause. We will leverage four large-scale longitudinal cohorts—the Danish Nurse Cohort, Danish Twin Registry, Swedish Women’s Lifestyle and Health cohort, and Swedish Twin Registry—linked to national registers in Denmark and Sweden. Our three aims are to: (1) quantify risk of psychiatric disorders and functional impairment during perimenopause compared to pre- and post-menopause and the general population; (2) develop and externally validate dynamic prediction models for perimenopausal psychiatric episodes; and (3) emulate a target trial estimating the effect of hormone therapy (HT) on mental health outcomes. Key deliverables include population-level psychiatric risk estimates across menopause stages, two web- based risk calculators to support clinical decision-making, and evidence-based guidance on HT for psychiatric risk reduction. Drawing on multidisciplinary expertise and lived experience, this project addresses long-standing sex- and age-related disparities in mental health and delivers actionable tools to support early detection and personalised prevention, advancing healthy ageing in women.