Sex Differences in Huntington's Disease: Evaluating the Enroll-HD Database

Background: Identifying sex-related differences is critical for enhancing our understanding of factors that may impact prognosis and advance treatments in Huntington's disease (HD). Objectives: To investigate if sex-related differences exist in clinical HD. Methods: Longitudinal study of the Enroll-HD database. Manifest HD patients were included in the analysis (N = 8401). Linear mixed models were used to assess motor, behavioral, and cognitive functioning over a series of four annual visits, and compared male and female HD gene carriers. Results: HD patients showed significant sex-dependent differences in motor, cognitive, and behavioral symptoms. Both sexes had worsened motor symptoms over the course of four visits, but there was a significant disparity between sexes, with females consistently presenting with more symptoms than males. For behavioral symptoms, specifically depressive symptoms, females had significantly more depressive symptoms, although self-reported symptoms in both sexes became less severe throughout time. Conclusions: Our analyses suggest that women have worse symptoms than men during the course of HD.