Research Advances and Future Directions in Female ADHD: The Lifelong Interplay of Hormonal Fluctuations with Mood, Cognition, and Disease

Johanna Jacoba Sandra Kooij^1,2*Maxime De Jong²Jessica C. Agnew-Blais³Silvia Amoretti^4,5Kathrine Bang Madsen^6,7Isabella Barclay⁸Sven Bölte^10,11,9Charlotte Lotta Borg Skoglund^12,13Thomas Broughton¹⁴Sara Carucci^15,16Dorenda K.E. van Dijken¹⁷Julia Ernst^18,19Blandine French^20,21Matilda A. Frick^22,23Cedric Galera^24,25Annabeth Groenman^26,27,28Helena Kopp Kallner^29,30Julia Kerner auch Koerner^31,32Sarah Kittel-Schneider^33,34Joanna Martin⁸Iris Manor³⁵Emilia Matera³⁶Alexandra Philipsen³⁷Valeria Parlatini^38,39Josep Anthoni Ramos-Quiroga^4,40,41,5Iris L. Rapoport²⁶Karl Lundin Remnélius⁹Amandine Sénéquier¹⁴Lisa B. Thorell¹³Janneke M.E. Wittekoek⁴²Dora S.M.R. Wynchank²

• ¹Amsterdam University Medical Center/VUmc, Department of Psychiatry, Amsterdam, Netherlands
• ²Expertise Center Adult ADHD, PsyQ, Psycho-medical Programs, The Hague, Netherlands
• ³School of Biological and Behavioural Sciences, Faculty of Science and Engineering, Queen Mary University of London, London, England, United Kingdom
• ⁴Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
• ⁵Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Barcelona, Spain
• ⁶Department of Clinical Research, University of Southern Denmark, Odense, Denmark
• ⁷National Centre for Register-based Research, Department of Public Health, Aarhus University, Aarhus, Denmark
• ⁸Centre for Neuropsychiatric Genetics and Genomics & Wolfson Centre for Young People’s Mental Health, Cardiff University, Cardiff, United Kingdom
• ⁹Center of Neurodevelopmental Disorders (KIND), Department of Women’s and Children’s Health, Centre for Psychiatry Research, Karolinska Institutet & Region Stockholm, Stockholm, Sweden
• ¹⁰Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
• ¹¹Curtin Autism Research Group, Curtin School of Allied Health, Curtin University, Perth, Australia
• ¹²Department of Women's and Children's Health, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
• ¹³Department of Clinical Neuroscience, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden
• ¹⁴Department of Psychology, School of Biological and Behavioural Sciences, Queen Mary University of London, London, United Kingdom
• ¹⁵University of Cagliari, Cagliari, Sardinia, Italy
• ¹⁶Child and Adolescent Unit P.O. Microcitemico ASL, Cagliari, Italy
• ¹⁷Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, Netherlands
• ¹⁸Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, Germany
• ¹⁹German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm, Mannheim, Germany
• ²⁰School of Psychology, Faculty of Science, University of Nottingham, Nottingham, England, United Kingdom
• ²¹Institute of Mental Health, University of Nottingham, Nottingham, England, United Kingdom
• ²²Department of Medical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
• ²³Department of Psychology, Faculty of Social Sciences, Stockholm University, Stockholm, Stockholm, Sweden
• ²⁴University Bordeaux, INSERM, BPH, U1219, F-33000 Bordeaux, Bordeaux, France
• ²⁵Centre Hospitalier Charles Perrens, Bordeaux, Aquitaine, France
• ²⁶Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, Netherlands
• ²⁷Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
• ²⁸Accare Child Study Center, Groningen, Netherlands
• ²⁹Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet (KI), Stockholm, Stockholm, Sweden
• ³⁰Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden
• ³¹Institute for Psychology in Education, University of Münster, Münster, Germany
• ³²IDeA - Center for Research on Individual Development and Adaptive Education of Children at Risk, Frankfurt am Main, Germany
• ³³Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
• ³⁴APC Microbiome, University College Cork, Cork, Ireland
• ³⁵ADHD Clinic, Geha Mental Health Center, Petach Tikva, Israel
• ³⁶Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy
• ³⁷Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany
• ³⁸University of Southampton, Southampton, Hampshire, United Kingdom
• ³⁹IOW Healthcare NHS Foundation Trust, Isle of Wight, United Kingdom
• ⁴⁰Department of Mental Health, Hospital Universitari Vall d’Hebron, Barcelona, Spain
• ⁴¹Department of Psychiatry and Forensic Medicine, School of Medicine, Autonomous University of Barcelona, Barcelona, Catalonia, Spain
• ⁴²HeartLife Clinics, Utrecht, Netherlands

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) in girls and women is 2 under-recognised and under-researched, despite increasing awareness of clinical 3 challenges and unmet needs. This review by the Eunethydis Special Interest Group 4 on Female ADHD, addresses current knowledge and identifies research gaps for 5 future work. Issues in women with ADHD across the lifespan such as late diagnosis, 6 pubertal development, sexual health, hormonal birth control, executive function 7 difficulties, and gynaecological disorders associated with ADHD are highlighted. 8 Methods: The review synthesises existing literature and self-reported experiences of 9 women with ADHD to explore the impact of hormonal fluctuations (puberty, menstrual 10 cycle, pregnancy, (peri)menopause) on ADHD symptoms and mood disturbances. It 11 examines the interplay of oestrogen and progesterone with dopaminergic pathways, 12 when periods of lower oestrogen may affect cognition, as well as the manifestation of 13 executive function deficits, and the intersection of ADHD with reproductive health. 14 Results: Hormonal transitions exacerbate ADHD symptoms and mood disturbances, 15 yet pharmacological research and tailored treatments are lacking. Executive function 16 deficits manifest differently in girls and women with ADHD and are influenced by 17 neuropsychological and neurobiological profiles. Diagnostic practices and 18 sociocultural factors contribute to delayed diagnoses, increasing the risk of 19 comorbidities, impaired functioning, and diminished quality of life. Undiagnosed 20 women have increased vulnerability to premenstrual dysphoric disorder, postpartum 21 depression, and cardiovascular disease during perimenopause. Discussion: 22 Longitudinal, sex-specific studies incorporating hormonal status and lived experience 23 are needed. Individualised interventions should be developed to address the unique 24 needs of girls and women with ADHD. Addressing these gaps will advance more 25 equitable diagnosis, management, and support for girls and women with ADHD, 26 improving outcomes across the female lifespan.