Sex-related differences in Huntington's disease: a scoping review

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder and emerging evidence indicates sex-specific differences in disease manifestation and progression.

To summarize current evidence on sex-related differences in HD across genetic, clinical, biomarker, and treatment domains and identify gaps in knowledge.

A literature search was performed in PubMed and Google Scholar (up to 31.01.2026). Eligible studies examined sex- or gender-related differences in individuals with genetically confirmed HD or those at risk. Meta-analyses, reviews, animal studies, theses, abstracts only, and non-English papers were excluded. After screening and full-text review, secondary citation tracking identified further studies. Sex was defined as the biological classification of participants (male/female) as originally reported, whereas gender was defined as socially constructed roles or identities, where explicitly assessed. Terminology in this review reflects the terminology used in the original publications.

Fourty-four studies met inclusion criteria. Genetic studies showed similar cytosine-adenine-guanine (CAG) repeat lengths across sexes when parent-of-origin was not considered, while paternal transmission was consistently linked to repeat expansion and earlier disease onset. Clinically, women more frequently exhibited depression, irritability, and greater functional impairment, whereas men more often showed apathy and substance misuse. Medication patterns differed, with women being more likely to receive antidepressants and anxiolytics, and men antipsychotics. Biomarker studies indicated potential sex-related differences in body composition, uric acid, neuroimaging, and hormonal profiles, though available evidence remained heterogeneous and exploratory.

Sex-related differences in HD are evident in genetic transmission, psychiatric symptoms, functional decline, and medication use. Biomarker findings suggest additional sex-specific biological signatures.