Pulmonary arterial hypertension: basis of sex differences in incidence and treatment response

Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of PAH with an approximate female to male ratio of 4:1, depending on the underlying disease pathology. Overall, the therapeutic strategy for PAH remains suboptimal with poor survival rates observed in both genders. Endogenous sex hormones, in particular 17β oestradiol and its metabolites, have been implicated in the development of the disease; however, the influence of sex hormones on the underlying pathobiology remains controversial. Further understanding of the influence of sex hormones on the normal and diseased pulmonary circulation will be critical to our understanding the pathology of PAH and future therapeutic strategies. In this review, we will discuss the influence of sex hormones on the development of PAH and address recent controversies. Linked Articles This article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-3