Psychobiological stress and premenstrual symptoms across the menstrual cycle: protocol for an ecological momentary assessment (ISSAC) study

INTRODUCTION: Premenstrual symptoms occur on a continuum from mild experiences to clinically significant, menstrual cycle-related mood disorders, including premenstrual dysphoric disorder (PMDD). Stress has been implicated as a key pathophysiological factor, yet the temporal coupling and dynamics between psychobiological stress patterns and premenstrual symptom expression across the menstrual cycle remain poorly characterised. The Interactions between premenstrual Symptoms and Stress Across the menstrual Cycle (ISSAC) study investigates how daily and momentary stress relates to premenstrual symptoms across two consecutive cycles, integrating ecological momentary assessments (EMA) with salivary biomarkers of hypothalamic-pituitary-adrenal axis activity (cortisol) and sympathetic nervous system function (alpha-amylase). METHODS AND ANALYSIS: We will recruit 80 menstruating individuals aged 21-45 years with regular cycles, spanning the full spectrum of premenstrual symptom severity (from none/mild to PMDD). Following a follicular-phase baseline visit, participants will complete an EMA protocol across two menstrual cycles (ovulation to ovulation): five daily assessments during cycle 1 (awakening, +30 min, 14:00, 19:00, bedtime) and a bedtime-only prompt during cycle 2. Assessments will include momentary and daily subjective stress, momentary affective premenstrual symptoms and a daily diary including all symptoms of PMDD as defined by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Saliva will be collected on awakening, +30 min and at 19:00 to assess the cortisol/alpha-amylase awakening response, overall output and diurnal slopes. Ovulation will be confirmed by chromatographic ovulation tests. Primary analyses will use linear mixed-effects models to test daily, concurrent and time-lagged associations between stress and symptoms, cycle-phase specific effects and group differences. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the University of Vienna (reference: 00883). All participants will provide written informed consent. Findings will be disseminated via peer-reviewed publications, conference presentations and targeted stakeholder outreach (patient associations and clinicians). Analysis code and data will be openly shared to enhance transparency and reproducibility. REGISTRATION DETAILS: Open Science Framework preregistration: https://doi.org/10.17605/OSF.IO/F3T5U.