Does Biological Sex Determine the Natural History and Management of Infective Endocarditis?

Sex and gender are important determinants of health. Despite growing recognition of their relevance, women remain under-represented in clinical trials and cardiovascular research. Infective endocarditis (IE) is a complex cardiovascular condition in which emerging evidence reveals sex-based disparities that extend beyond demographic differences. This narrative review aims to synthesize current evidence from large population-based studies, national registries, meta-analyses, and cohort studies to elucidate the epidemiologic landscape of sex differences in IE, including variations in clinical presentation, management, and outcomes. Women with IE are generally older and have more comorbidities than men. They more frequently exhibit mitral-valve involvement and present less often with perivalvular complications. Staphylococcus aureus infections appear to be more common in women, whereas streptococcal and enterococcal infections are reported less frequently. Although findings are not entirely consistent, most studies suggest higher short-term mortality in women, with female sex identified as an independent risk factor in several analyses. In addition, there has been an increase of 26% in cases of IE related to injection drug use among women. Of particular concern are cases occurring during pregnancy, which may or may not be associated with substance use. The underlying causes of these sex-based disparities in IE remain unclear and warrant further investigation. Future research must adopt a sex- and gender-informed perspective to improve our understanding and guide more equitable clinical management.