5-fluorouracil (5-FU) is a key chemotherapeutic agent in the treatment (Cardiol J 2012; 19, 5: 453-458)

High oestradiol (E2) and low dehydroepiandrosterone-sulfate (DHEA-S) levels are risk factors for pulmonary arterial hypertension (PAH) in men, but whether sex hormones are related to PAH in women is unknown.Post-menopausal women aged ≥55 years with PAH were matched by age and body mass index to women without cardiovascular disease. Plasma sex hormone levels were measured by immunoassay.Lower levels of DHEA-S (p<0.001) and higher levels of E2 (p=0.02) were associated with PAH. In PAH cases (n=112), lower DHEA-S levels were associated with worse haemodynamics (all p<0.01) and more right ventricular dilatation and dysfunction (both p=0.001). Lower DHEA-S levels were associated with shorter 6-min walking distance (6MWD) (p=0.01) and worse functional class (p=0.004). Each Ln(1 µg·dL) decrease in DHEA-S was associated with a doubling in the risk of death (hazard ratio 2.0, 95% CI 1.5-2.7; p<0.001). Higher levels of E2 were associated with shorter 6MWD (p=0.03) and worse functional class (p=0.01).High E2 and low DHEA-S levels are associated with the risk and severity of PAH in post-menopausal women. Hormonal modulation should be studied as a treatment strategy in PAH.

Female sex has been shown to be a risk factor for the development of PAH, but women have improved survival compared to men with PAH. These paradoxical observations are likely driven in part by complex sex hormone signaling and processing pathways and their interaction with the pulmonary vasculature and the right ventricle. These relationships may vary depending on an individual's underlying sex, age, and/or genetic substrate. The study of the connections between sex, sex hormones, the pulmonary circulation, and the right ventricle may improve our understanding of disease epidemiology and outcomes and lead to new treatment strategies for PAH.