Interplay of sex hormones and long-term right ventricular adaptation in a Dutch PAH-cohort

Background: To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages. Methods: In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis, we selected patients that underwent a RHC and/or CMR maximally 1.5 years prior to an event (death or transplantation, N = 49). Results: Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAH-patients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age. Females ≤45years had best prognosis in comparison to females ≥55years and males. No differences in RV function at baseline were observed, despite higher pressure-overload in females ≤45years. Longitudinal data demonstrated a clear distinction in RV adaptation. Although females ≤45years had an event at a later time point, RV function was more impaired at end-stage disease. Conclusions: Sex hormones are differently associated with RV function in male and female PAH-patients. DHEA-S appeared to be lower in male and female PAH-patients. Females ≤45years could persevere pressure-overload for a longer time, but had a more severe RV phenotype at end-stage disease.