Sex-Related Differences in Histopathology and Hormonal Associations in Ascending Aortic Aneurysms

Abstract Background and Aims Sex-related differences in ascending aorta aneurysm (AscAA) pathology and the underlying mechanisms remain incompletely understood. In this study, sex-specific patterns of aortic media degeneration (MD) in idiopathic AscAA were investigated. Methods Aortic tissue and blood samples were obtained from 32 patients undergoing elective AscAA resection (mean age 65.6 years, 25% women). Two donor aortas served as healthy controls. Tissues were evaluated using a modified consensus scoring system assessing elastin integrity, mucoid extracellular matrix accumulation (MEMA), smooth muscle cell organization, and collagen remodeling. Immunohistochemistry was used to quantify extracellular matrix and remodeling markers. Outcome parameters included aortic diameter, immunohistochemical profiling, MD scores, and sex hormone profiling. Results Absolute ascending aortic diameters did not differ between sexes. Women exhibited significantly more advanced and diffuse MD across all sampled locations, with higher total MD scores before and after adjustment for aortic size. This was attributed to increased elastin degradation, MEMA, and elevated local MMP2 expression, consistent with a degradative remodeling profile. In contrast, men displayed a more focal and inflammatory phenotype, characterized by increased MMP9, cKIT, and CD68 expression, and relatively thicker media. Circulating hormone levels were reduced in both sexes but were not directly associated with MD severity. However, female-specific decreases in DHEA and male-specific decreases in testosterone, AMH, and androstenedione were observed. Conclusions This study reveals pronounced sex-specific differences in AscAA wall degeneration. Women demonstrate a structurally more vulnerable aortic wall at comparable dilatation, fueling discussion for revision of female treatment plans.