Estrogen is metabolized by cytochrome P450 (CYP) enzymes7,8 to both proproliferative and antiproliferative metabolites.9 CYP 1B1 (CYP1B1) is a P450 enzyme expressed in the lung, which catalyses the conversion of estrogens predominantly to 4-hydroxyestrogens but also to 2-hydroxy and 16-hydroxyestrogens,10 and has been implicated in idiopathic PAH1 and heritable PAH.3,11,12 16α-hydroxyestrone (16αOHE1) is a biologically active metabolite with estrogenic activity. This evidence concerns the gene CYP1B1 and pulmonary arterial hypertension.