Sex Differences in Pulmonary Arterial Hypertension

Under normal conditions, the pulmonary circulation is a low-resistance, low-pressure system. Pulmonary hypertension (PH) is a heterogeneous condition that arises from a variety of etiologies affecting the pulmonary circulation and can be subdivided into five groups. Of these, pulmonary arterial hypertension (PAH) is the most severe, with a 5-year mortality rate near 40%. The development of PAH can be associated with various pathogenic or genetic causes, and, possibly because of this complexity, the mechanisms causing the disease are still incompletely understood. Female sex is perhaps one of the most well-established risk factors for the development of PAH, although over the past three decades, it has become increasingly clear that there are also important sex-based differences in PAH severity, response to treatment, and mortality. In this chapter, we will describe the preclinical and patient data underlying our current understanding of sex-based differences in PAH, discuss the clinical implications of these data, and point to future directions for research and patient care.