{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:14:58Z","timestamp":1788264898327,"version":"build-2803163510"},"reference-count":67,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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\u2013pituitary\u2013adrenal axis activity (cortisol) and sympathetic nervous system function (alpha-amylase).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will recruit 80 menstruating individuals aged 21\u201345 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\u2009min, 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\u2009min 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration details<\/jats:title>\n                    <jats:p>\n                      Open Science Framework preregistration:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.17605\/OSF.IO\/F3T5U\">https:\/\/doi.org\/10.17605\/OSF.IO\/F3T5U<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-123210","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:30:25Z","timestamp":1788262225000},"page":"e123210","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Psychobiological stress and premenstrual symptoms across the menstrual cycle: protocol for an ecological momentary assessment (ISSAC) study"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3802-1339","authenticated-orcid":false,"given":"Celine","family":"Bencker","sequence":"first","affiliation":[{"name":"Department of Clinical and Health Psychology, Faculty of Psychology, University of Vienna, Vienna, Austria"},{"name":"University Research Platform \u2018Stress of Life (SOLE) \u2013 Processes and Mechanisms Underlying Everyday Life Stress\u2019, University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5405-1933","authenticated-orcid":false,"given":"Katja Maria","family":"Schmalenberger","sequence":"additional","affiliation":[{"name":"Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University Hospital, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Comasco","sequence":"additional","affiliation":[{"name":"Department of Women's and Children\u2019s Health, Uppsala University, Uppsala, Sweden"},{"name":"Science for Life Laboratory (SciLifeLab), Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2430-5090","authenticated-orcid":false,"given":"Urs M","family":"Nater","sequence":"additional","affiliation":[{"name":"Department of Clinical and Health Psychology, Faculty of Psychology, University of Vienna, Vienna, Austria"},{"name":"University Research Platform \u2018Stress of Life (SOLE) \u2013 Processes and Mechanisms Underlying Everyday Life Stress\u2019, University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2026090104302007000_16.9.e123210.1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1258\/mi.2012.012013","article-title":"Epidemiology of premenstrual symptoms and disorders","volume":"18","author":"Dennerstein","year":"2012","journal-title":"Menopause Int"},{"key":"2026090104302007000_16.9.e123210.2","doi-asserted-by":"crossref","unstructured":"Eisenlohr-Moul TA . 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