Clinicians reported the case of a patient who experienced a near-fatal episode after receiving oral contraceptive therapy and who was later diagnosed with estrogen-triggered hereditary angioedema (HAE), according to a study published in the Journal of Clinical Research in Pediatric Endocrinology. 

A 13-year-old girl presented with dyspnea and upper body swelling. Her past medical history included polycystic ovary syndrome that was diagnosed 2 weeks previously; her symptoms for this disorder included irregular menstruation and hirsutism. 

Her physicians prescribed her ethinyl estradiol and cyproterone acetate-containing oral contraceptive pill. On day 16 of treatment, the girl began to experience periorbital swelling that started in her face and soon involved her whole upper body. The working diagnosis was an anaphylactic reaction, but drugs typically used to treat this disorder were of no effect.

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Further history-taking revealed that her mother and two cousins had recurrent angioedema attacks. This opened up the possibility that the patient might have HAE. Without further delay, her physicians prescribed her 500 IU of C1 esterase inhibitor concentrate based on this working diagnosis. Due to fears of laryngeal edema, she was placed under intensive care. 

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The patient received 2 more does of 500 IU of C1 esterase inhibitor during her hospital stay. Fortunately, her swelling receded after 12 hours and completely disappeared within 48 hours. 

Later laboratory findings demonstrated normal C1 esterase inhibitor levels, suggesting that she had HAE with normal levels of C1 inhibitors (HAEnCI). Genetic studies revealed a heterozygous mutation in the ninth exon, resulting in a p.Thr328Lys variation. Her physicians stopped her oral contraceptive pills and she has not experienced edema attacks over the past 20 months. 

The role of estrogen in triggering HAE attacks remains largely undefined. However, studies indicate that many women experience at least 1 angioedema attack during significant exposure to estrogen, such as being on the oral contraceptive pill, hormone replacement therapy, or pregnancy. 


Balkancı UB, Demirkol D, Yeşiltepe Mutlu G, et al. A potentially fatal outcome of oral contraceptive therapy: estrogen-triggered hereditary angioedema in an adolescentJ Clin Res Pediatr Endocrinol. Published online May 29, 2023. doi:10.4274/jcrpe.galenos.2021.2021.0053