Sex-specific differences in the clinical and psychiatric phenotype of Alcohol Use Disorder

Background and aims: Alcohol use disorder (AUD) is a prevalent mental disease associated with multiple clinical manifestations, involving several organs and systems. Despite evidence supporting a sex-related disparity in AUD patients, the vast majority of data has predominantly focused on men, leaving unappreciated several features of the condition affecting women. Methods: We conducted a retrospective analysis of 907 patients with AUD from a single Alcohol-related Disease Unit over an 19-year period (2004-2022). Data encompassed demographics, smoking habits, clinical manifestations associated with chronic alcohol abuse, including psychiatric diseases and alcohol withdrawal syndrome, as well as echocardiography findings. Results: Of the 907 patients, 238 (26.2%) were women. Men exhibited a higher prevalence of atrial fibrillation, ischemic cardiomyopathy, and alcoholic cardiomyopathy, whereas women had significantly higher rates of psychiatric disorders and alcohol-related dementia. The most notable differences in psychiatric conditions between the sexes were observed in depressive disorders, feeding and eating disorders, and personality disorders. Echocardiographic evaluation was performed in a subgroup of 291 patient, prevalently men. No sex-related differences were observed in the presentation of alcohol withdrawal syndrome. Survival analysis revealed a negative impact of minor alcohol withdrawal syndrome on mortality, particularly in men. Survival analysis also highlighted a sex-related dimorphism in the prognostic factors associated with mortality. Discussion and Future directions: A clear gender-specific dimorphism is observed in AUD patients. Notably psychiatric comorbidities, particularly depression, are more strongly associated with AUD in women than in men, suggesting that depression may contribute to AUD development, with alcohol exacerbating these conditions. In contrast, alcoholic cardiomyopathy is more prevalent in men, although women appear more susceptible to its cardiotoxic effects at lower lifetime alcohol exposure; the observed men predominance may partly reflect underdiagnosis in women, mirroring the broader underestimation of cardiovascular risk in women. Additionally, delirium tremens tends to be more common in men, and the minor alcohol withdrawal syndrome has a greater impact on mortality in men. These differences raise interesting considerations regarding both the hormonal role in the pathogenesis of withdrawal syndrome and the appropriate care settings for patients with AUD. Collectively, these findings emphasize that mental health assessment is essential in the clinical evaluation of all AUD patients, while routine cardiac screening should not be neglected in women. Thus, comprehensive multidisciplinary management strategies are sorely needed, particularly for women, to improve overall outcomes.