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The following is a summary of “Effect of estrogen-containing birth control pills on the constituents of bradykinin expression in plasma,” published in the May 2024 issue of Allergy & Immunology by Birmingham, et al.

Hereditary angioedema with C1-inhibitor deficiency (HAE-C1INH) is a rare autosomal disorder characterized by recurrent episodes of angioedema. In some patients, estrogen-containing medications can trigger these episodes, while progesterone may reduce the frequency of attacks. The mechanism through which estrogen exacerbates angioedema in HAE-C1INH remained unclear. For a study, researchers sought to investigate the relationship between estrogen and bradykinin constituents to elucidate the specific triggers that may exacerbate angioedema in patients with HAE-C1INH.

Given that estrogen is contraindicated for patients with HAE-C1INH, females without a history of angioedema were recruited to assess whether estrogen-containing oral contraceptive pills (OCPs) alter plasma levels of bradykinin, cleaved high-molecular-weight kininogen (cHK), and activated factor XII (FXIIa). Blood samples were collected before initiating OCP administration and three months afterward. High-molecular-weight kininogen (HK) levels were measured using ELISA, and FXIIa and cHK levels were analyzed via Western blot.

The study included 12 adult females without HAE-C1INH, all under 40. The median baseline plasma HK level was 33,976 ng/mL. After three months of OCP therapy, the median HK level increased to 38,202 ng/mL. OCP use was also associated with significantly increasing FXIIa protein levels (P < .01) and cHK protein levels.

The preliminary study in females without HAE-C1INH suggested that estrogen may exacerbate angioedema by increasing the production of cHK and FXIIa. Further research was needed to confirm these findings and understand the mechanisms involved.

Reference: jaci-global.org/article/S2772-8293(24)00022-5/fulltext