Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women

Purpose Most types of hereditary angioedema (HAE) are worsened by endogenous or exogenous estrogens. Conversely, androgens can improve HAE with abnormal C1-Inhibitor (C1-INH) by increasing C1-INH concentrations. Menopause is associated with an extinction of ovarian estrogenic and androgenic secretion. There is currently insufficient information on postmenopausal women with HAE. The objective of this study was to describe the activity of HAE in postmenopausal women. Methods This was a French retrospective, multicenter study in postmenopausal women with HAE with or without C1-INH deficiency/dysfunction. The patients were classified before and after menopause with a previously validated HAE disease severity score. Results We included 65 women from 13 centers in France. The mean age was 62.7± 9.2 years, and the mean time between menopause and inclusion was 12.5± 9.1 years. HAE was associated with C1-INH deficiencyin 88% ( n = 57) of the patients, a mutation of factor 12 in 8% ( n = 5), a mutation in plasminogen gene in one, and unknown HAE for two. The HAE course was not different after menopause in 46.1% ( n = 30), improved in 38.5% ( n = 25), and worsened in 15.4% ( n = 10). Improvement was correlated with estrogen sensitivity of angioedema before menopause ( p = 0.06 for improvement vs no effect or worsening). In addition, we observed that only ten women received treatment (transdermal or oral estradiol+ progestogen) for their menopause symptoms. Among them, only 3 experienced worsening of symptoms (2 on transdermal and 1 on oral estradiol). Conclusion Following menopause, most women with HAE remain stable but some worsen. Improvement was mainly observed in patients with previous estrogen sensitivity. More research is required in menopausal women with HAE to better understand how to manage climacteric symptoms.