A predominance in females is associated with the estrogen hormone, a hallmark of HAE with normal C1-INH.5, 7Estrogen has a regulatory role in the synthesis of FXII protein, as well as of several genes and proteins of the coagulation cascade and of the kallikrein-kinin system, increasing synthesis of bradykinin, kallikrein, vascular permeability and consequently causing edema.9This association is important in worsening the attacks in women, ranging from childhood, puberty, menses, pregnancy and menopause.1 The gene discussed is KLK4; the disease is hereditary angioedema.