Genetic burden similar, but HD’s social impact hits women harder
Behavioral issues, unemployment higher for women, study finds
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Women with Huntington’s disease are more likely to experience irritability and to be unemployed or working part-time than men with the neurodegenerative condition, according to a small, single-center study in Austria.
Men and women with Huntington’s showed similar genetic burden, age at disease onset, and motor symptom severity, suggesting that sex-related differences in Huntington’s may primarily influence behavioral symptoms and social functioning, the researchers said.
“Recognizing and addressing these differences may support more individualized clinical care and targeted social support strategies,” the researchers wrote, while cautioning that the study’s relatively small size and single-center design may limit how widely the findings can be generalized.
The study, “Bridging the gap: sex-specific differences in Huntington’s disease,” was published in the Orphanet Journal of Rare Diseases.
A rare neurodegenerative disorder, Huntington’s is caused by an abnormal expansion of a DNA sequence, known as a CAG repeat, in the HTT gene. This leads to the production of a longer, abnormal version of the huntingtin protein, which is thought to be toxic to nerve cells. Huntington’s symptoms include motor issues, cognitive decline, and behavioral problems such as irritability, agitation, anxiety, and depression. These have a great impact on daily life, working capacity, and employment.
Tailoring interventions
Although the length of the CAG repeat expansion, which determines Huntington’s risk, and age at symptom onset appear largely similar between female and male patients, research suggests that sex may influence how the disease presents and progresses.
“Exploring sex-related differences in disease manifestation may improve understanding and guide more tailored therapeutic and supportive interventions,” the researchers wrote.
The team retrospectively analyzed data from 102 adults with genetically confirmed Huntington’s who were participating in the Enroll-HD study (NCT01574053), the world’s largest study following people with the rare disease.
All participants, 58 women and 44 men, were enrolled at the Medical University of Innsbruck through March 2025. The mean age was 54.31 among men and 52.88 for women.
Clinicians assessed motor symptoms and functional capacity during regular study visits, and used structured interviews and questionnaires to gather information on behavioral symptoms, daily functioning, supportive therapies, and employment. The researchers used the data to assess potential sex-related differences.
They found no significant differences between men and women in CAG repeat length, age at disease onset, or motor symptom severity.
Differences did emerge in nonmotor symptoms. Those analyzed “included depression, irritability, cognitive impairment, psychosis, perseverative/obsessive behavior, apathy, and aggressiveness,” the team wrote.
Data showed that women were significantly more likely than men to experience irritability (56.9% vs. 36.4%). Rates of other behavioral symptoms were similar between the two groups.
Use of supportive therapies such as physiotherapy, occupational therapy, speech therapy, and psychotherapy did not differ significantly between men and women.
The most pronounced differences were seen in employment status. Nearly half of men (45.5%) were employed full-time, compared with fewer than one in 10 women (8.6%). Women were significantly more likely to be unemployed (69% vs. 45.5%) or working part-time (20.7% vs. 4.5%).
These employment differences remained statistically significant even after adjusting for CAG repeat length and CAP score, a measure of exposure to the expansion mutation that accounts for CAG repeat number and a person’s age. The findings suggest that reduced workforce participation among women cannot be explained solely by genetic burden.
“As employment is closely linked to functional capacity and social participation, reduced workforce engagement among women may reflect both clinical burden (e.g., irritability affecting interpersonal functioning) and socioeconomic mechanisms, including gender-based differences in caregiving roles or access to workplace accommodations,” the researchers wrote.
Overall, the findings underscore that “sex is a relevant factor in the lived experience and functional consequences of [Huntington’s disease],” and should be considered when planning both clinical care and social support strategies for these patients, the team concluded.
The study’s small sample size may limit the ability to detect subtle group differences, and the results may not be generalized to patients in other countries, the researchers said. Larger studies, involving patients in different regions, could confirm the findings.
