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

J Heart Lung Transplant. 2022 Apr;41(4):445-457. doi: 10.1016/j.healun.2021.11.004. Epub 2021 Nov 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Familial Primary Pulmonary Hypertension
  • Female
  • Gonadal Steroid Hormones
  • Heart Ventricles / diagnostic imaging
  • Humans
  • Male
  • Pulmonary Arterial Hypertension*
  • Ventricular Dysfunction, Right*
  • Ventricular Function, Right


  • Gonadal Steroid Hormones