Why Men Fare Worse: Understanding Gender Disparities in Systemic Sclerosis-Associated Pulmonary Hypertension

Abstract Objective: This study investigates gender disparities in clinical outcomes among patients with systemic sclerosis (SSc)- associated pulmonary arterial hypertension (PAH), focusing on cardiovascular events, right ventricular function, and survival. Introduction: PAH is a severe and life-threatening complication of SSc, with male patients often experiencing worse outcomes despite its higher prevalence in women. Comparative data on gender differences in this population remain limited. Methods: We conducted a retrospective, single-center study including 61 patients with SSc-associated PAH (52 women, 9 men), confirmed by right heart catheterization. Clinical, serological, pulmonary, and echocardiographic data were analyzed. Differences between sexes in cardiovascular events, right ventricular dilation, and survival were evaluated using appropriate statistical methods. Results: Male patients had a significantly higher incidence of cardiovascular events (median: 2.00 vs 1.00 in women; P = .031) and a greater prevalence of right ventricular dilation (100.00% vs 44.23%; P = .002). Kaplan-Meier analysis demonstrated reduced cardiovascular event-free survival (P = .001) and overall survival (P = .014) in men. Although mortality was higher in men (88.89%) than in women (57.69%), the difference was not statistically significant (P = .134). Conclusion: Men with SSc-associated PAH experience worse clinical outcomes, including more frequent cardiovascular events and reduced survival. The absence of estrogen’s protective effects and the adverse influence of testosterone on cardiac remodeling may contribute to these disparities. These findings highlight the importance of early gender-specific risk stratification and the need for tailored therapeutic strategies to improve outcomes in this high-risk group.