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

Journal of Clinical Immunology volume 41, pages 163–170 (2021)Cite this article

Abstract

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.

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Abbreviations

C1-INH:

C1-Inhibitor

HAE:

Hereditary angioedema

C1-INH-HAE:

Hereditary angioedema with C1-Inhibitor deficiency/dysfunction

nC1-INH-HAE:

Hereditary angioedema with normal C1-Inhibitor

pdC1-INH:

Plasma-derived concentrate C1-Inhibitor

COC:

Estroprogestin combined (oral) contraception

POP:

Progestin-only pills

AGP:

Antigonadotropic

MHT:

Menopause hormone treatment

TTS-E2:

Transdermal estradiol

BMI:

Body mass index

TA:

Tranexamic acid

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Acknowledgements

Centre de Référence sur les angiœdèmes à kinines [CRéAk] includes S. Amarger, MD (CHU Estaing, Clermont Ferrand, France), C. Blanchard-Delaunay, MD (CH Niort, France), B. Coppere, MD (Hospices Civils de Lyon, CHU Edouard Herriot, Lyon, France), A. DuThanh, MD (CHU Montpellier, France), B. Floccard, MD (Hospices Civils de Lyon, CHU Edouard Herriot, Lyon, France), S. Gayet, MD (Hospital La Timone, APHM, Marseille, France), P. Y. Jeandel, MD (CHU Nice, France), L. Martin, MD PhD (CHU Angers, France), F. Pelletier, MD (CRHU Besançon, France), F. N. Raison Peyron, MD (Hospital St Eloi, Montpellier, France). Thanks to Felicity Neilson for editing the manuscript in English.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. AP-HP, HUPC, Unité de Gynécologie Endocrinienne, Centre de Référence sur les angiœdèmes à kinines (CRéAk), Hôpital Port Royal, Université de Paris, Paris, France

    Aurore Billebeau, Geneviève Plu-Bureau & Anne Gompel

  2. AP-HP, Médecine Interne, DHUi2B, Centre de Référence associé sur les angiœdèmes à kinines (CRéAk), Hôpital Saint-Antoine, Sorbonne Université, Paris, France

    Olivier Fain & Delphine Gobert

  3. Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Centre de Référence sur les angiœdèmes à kinines (CRéAk), France Service de Médecine Interne, Université de Lille, F-59000, Lille, France

    David Launay

  4. Unité Inserm 1036, Service de Médecine Interne, Centre de Référence sur les angiœdèmes à kinines (CRéAk), CHU de Grenoble Alpes, Université Grenoble Alpes, Grenoble, France

    Isabelle Boccon-Gibod & Laurence Bouillet

  5. Université de Paris, 123 bd de Port Royal, 75014, Paris, France

    Anne Gompel

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  1. Aurore Billebeau
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French National Reference Center for Hereditary Angioedema (CREAK)

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Correspondence to Anne Gompel.

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Conflict of Interest

AB: no conflict of interest, OF: Consultant arrangements for Shire/Takeda and Behring, travel and accommodation to a Congress from GSK, honorarium for a talk from Sanofi, DL: consultant arrangements, research grant and travel and accommodation from Actelion, GSK, Octapharma, Pfizer, and Shire/Takeda. LB: Consultant arrangements, research grant and travel and accommodation from Shire/Takeda, CSL Behring, Pharming, GSK, Novartis, Sanofi. I B-G: Consultant arrangements, research grant, travel and accommodation from Shire/Takeda, CSL Behring, Pharming, Biocryst, Novartis DG: Consultant arrangements for Shire/Takeda honorarium for talks for Shire/Takeda, travel and accommodation from Shire/Takeda et Pharming. G.P-B: no conflict of interest. AG: member of an advisory board for Mithra (Estetrol).

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Billebeau, A., Fain, O., Launay, D. et al. Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women. J Clin Immunol 41, 163–170 (2021). https://doi.org/10.1007/s10875-020-00902-7

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Keywords

  • Hereditary angioedema
  • menopause
  • female
  • estrogen
  • androgen
  • aging