Journal Article

Bridging the gap: sex-specific differences in Huntington’s disease

Mahlknecht, Philipp, Djamshidian, Atbin, Krismer, Florian, Seppi, Klaus, Hemicker, Greta, Peball, Marina, Heim, Beatrice, Labrecque, Samuel, Carbone, Federico, Wimmer, Bernadette, Schwarzová, Katarína, Cerejo, Clancy

2026

Overview

Introduction Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expanded cytosine-adenine-guanine (CAG) trinucleotide repeat on chromosome 4. Exploring sex-related differences in disease manifestation may improve understanding and guide more tailored therapeutic and supportive interventions. Objective To investigate sex differences in the clinical presentation and functional outcomes in a single-center HD cohort, including employment status and use of supportive therapies. Methods We retrospectively analyzed 102 patients with HD who were regularly seen at the Department of Neurology, Medical University of Innsbruck. Exact CAG repeat length was available for 101 participants. Multinomial logistic regression was applied to assess symptom distribution, access to neurorehabilitation, and the impact on employment status. Results We included 44 men and 58 women with genetically confirmed Huntington’s Disease. Among participants with available CAG data ( n  = 101), there was no difference in CAG-Repeat length between male and female patients as well as no differences in the onset of motor or non-motor symptoms (all p-values > 0.05). We found that irritability was significantly more prevalent in female patients ( p  = 0.033). Moreover, women were significantly less likely to be employed than men ( p  < 0.001). No sex differences were observed in the utilization of non-pharmacological therapies such as physiotherapy, occupational therapy, speech therapy, or psychotherapy ( p  > 0.05). Conclusion Female patients with HD showed higher rates of irritability and lower workforce participation, suggesting clinically relevant sex-related differences. These findings highlight the importance of considering sex as a factor in both clinical management and social support strategies.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acupuncture / Adult / Age / Aggressiveness / Analysis / Apathy / Care and treatment / Chi-square test / Chromosome 4 / Cognitive ability / Cytosine / Development and progression / Employment / Female / Females / Functional capacity / Gender differences / Genetic testing / Health aspects / Human Genetics / Humans / Huntington Disease - genetics / Huntington Disease - physiopathology / Huntington's chorea / Huntington's disease / Huntingtons disease / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Neurodegenerative diseases / Neurology / Occupational therapy / Patients / Pharmacology/Toxicology / Physical therapy / Physiological aspects / Polyglutamine / Psychosis / Psychotherapy / Regression analysis / Rehabilitation / Retrospective Studies / Sex differences / Sex Factors / Sex-related differences / Social aspects / Social interactions / Trinucleotide repeat diseases / Trinucleotide Repeat Expansion - genetics / Trinucleotide repeats / Trinucleotide Repeats - genetics / Women