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Sex Differences and the Role of Sex Hormones in Pulmonary Hypertension. Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and the eventual development of right heart failure. Multiple mechanisms are responsible, including vasoconstriction, metabolic flux, and inflammation. Since the early descriptions of pulmonary hypertension, female sex has been associated with increased prevalence of the disease, with research showing both detrimental and beneficial effects of estrogen and its metabolites. This article aims to describe how the female paradox arises from sex differences in pulmonary hypertension and how this has an impact on pathophysiology and future treatment.