The Complex Interaction Between Polycystic Ovary Syndrome and Hereditary Angioedema: Case Reports and Review of the Literature

Abstract

Importance Hereditary angioedema (HAE) is a rare but severe disease, with high risk of death, and attacks have been associated to high estrogen levels. Polycystic ovary syndrome (PCOS) is a common hyperandrogenic condition, which is frequently treated with combined oral contraceptives. Objective The aim of this study was to describe 2 clinical cases of young women diagnosed as having PCOS who developed HAE attacks after the introduction of combined estrogen-progestin pills to treat PCOS symptoms. Evidence Acquisition Literature review of sex hormones' role in genesis of HAE attacks and possible mechanisms involved. Results In the cases reported, after initiation of combined contraceptives, patients presented with facial swelling with airway involvement (laryngeal edema) and abdominal pain. They had a familial history of angioedema and normal C1 inhibitor (C1-INH) levels, leading to the diagnosis of HAE with normal C1-INH (HAEnC1-INH) or HAE type III. After suspension of exogenous estrogen, patients remained asymptomatic from HAE. Conclusions and Relevance HAEnC1-INH is an estrogen-dependent form of HAE. It is well established that exogenous estrogen triggers attacks of all types of HAE. However, this is the first description of the association between PCOS and HAE, in which PCOS could be masking HAE symptoms. We propose that PCOS might have a protective role regarding HAE attacks, because of its particular hormonal features, that is, hyperandrogenism and relative stable levels of estradiol. The use of combined estrogen-progestin compounds in women with PCOS and HAE must be avoided, and treatment must be individualized. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to evaluate for hereditary angioedema (HAE) in patients with recurrent angioedema attacks and abdominal pain, particularly when they are under exogenous estrogen treatment; ask patients about personal or familial history of angioedema attacks before prescribing exogenous estrogen; recall that isolated progestins can be used as long-term prophylaxis to HAE patients; and explain that hyperandrogenism of polycystic ovary syndrome could mask HAE symptoms.