Two prevalent risk factors, obesity and estrogen-based oral contraceptives (OCAs), contribute substantially to VTE in premenopausal women (1–3) The prothrombotic effect of estrogen-based OCAs is well established (4, 5), in part due to reductions in the anticoagulant protein S (PS) (6, 7). Here, PRB2 is linked to obesity due to melanocortin 4 receptor deficiency.