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

- **DOI:** [10.1007/s10875-020-00902-7](https://doi.org/10.1007/s10875-020-00902-7)
- **Rating:** Limited (2.8 out of 5)
- **Verdict:** A useful rare-disease cohort maps postmenopausal HAE trajectories, but uncontrolled retrospective attribution prevents menopause-specific causal conclusions.
- **Framework version:** v5.9
- **Pipeline version:** v0.4
- **Evaluation date:** 2026-09-18
- **Evaluation page:** https://www.nabu.science/paper/10.1007%2Fs10875-020-00902-7

## Key claims

1. Postmenopause was associated with an improvement in HAE symptoms in 38.5% of the patients (n=25). There was no change in 46.1% patients (n=30), and 15.4% patients (n=10) worsened.
   - Support: Supported
   - Type: Primary finding
   - Basis: the sample distribution is internally consistent, though retrospective recall and severity classification limit certainty
   - Location: Results §Postmenopausal Period and Severity of HAE; Tables 3 and 4
2. Improvement was correlated with estrogen sensitivity of angioedema before menopause (p=0.06 for improvement vs no effect or worsening).
   - Support: Tentative
   - Type: Secondary
   - Basis: the uncontrolled retrospective comparison reports a non-significant trend without adjusted effect estimates
   - Location: Abstract; Results §Postmenopausal Period and Severity of HAE; Table 3
3. Only three of the 13 patients receiving MHT in our study had to stop treatment because of worsening of attacks.
   - Support: Tentative
   - Type: Secondary
   - Basis: the uncontrolled subgroup is small and its denominator conflicts across the Abstract, Results, and Table 2
   - Location: Discussion, MHT paragraph
4. HAE was associated with C1-INH deficiency in 88% (n = 57) of the patients.
   - Support: Tentative
   - Type: Secondary
   - Basis: the Results identify these 57 women specifically as type I C1-INH-HAE
   - Location: Abstract; Results, opening paragraph

## Strengths

- **Larger multicentre rare-disease cohort** The study includes 65 women from thirteen French reference centres, increasing the descriptive evidence available for an uncommon clinical population.
  - Dimension: contribution
  - Location: Abstract; Methods, opening paragraph
- **Standardized pre-post severity classification** The same previously described severity classification is applied to the premenopausal and postmenopausal periods, making the reported trajectory categories explicit.
  - Dimension: methodological rigour
  - Location: Methods, HAE disease severity score description; Table 4
- **Direct engagement with closest study** The Discussion compares its distributions with PREHAEAT and identifies differences in sample size, subtype coverage, and endpoint specification.
  - Dimension: positioning
  - Location: Discussion, paragraph 1

## Limitations

- **Conflicting MHT subgroup denominators** The Abstract reports ten treated women, the Results report thirteen, and Table 2 presents totals that do not consistently identify the denominator. This changes the apparent rate of MHT-associated worsening.
  - Dimension: reporting
  - Location: Abstract; Results §Menopause Characteristics; Table 2
- **Menopause effects remain confounded** A long retrospective pre/post comparison cannot distinguish menopause from aging, recall, comorbidity, or changing prophylactic treatment, yet the Discussion says menopause “resulted in” improvement and “caused” worsening.
  - Dimension: methodological rigour
  - Location: Results §Postmenopausal Period and Severity of HAE; Discussion, paragraph 1 and limitations
- **Adjusted analysis is not transparent** Logistic regression and multivariate analysis are described, but Table 3 provides no adjusted effect estimates or confidence intervals, limiting assessment of the estrogen-sensitivity result.
  - Dimension: methodological rigour
  - Location: Statistical Analysis; Table 3

## Reliability checks

Concerns (4 of 4 checks).

- **Internal coherence:** Concern. The main 65-patient menopause-course counts reconcile, but treatment-subgroup denominators and some Table 2 totals are internally inconsistent. The MHT discrepancy changes whether the reported worsening rate is 3/10, 3/11, or 3/13.
- **Research conduct:** Clean. Ethics approvals, funding, and conflicts of interest are explicitly declared. No supplied-text contradiction concerning approval, disclosure, registration, or availability was identified.
- **Reference integrity:** Clean. 45 of 45 checkable references verified
  - 48 references in manuscript
  - 3 have no canonical index record — counted, but not index-checkable
  - 2 references confirmed by manual review
  - References not verified automatically are resolved manually within 24 hours.

## Post-publication record

- **Status:** Clean
- **Summary:** No retraction or expression of concern found in Crossref (includes Retraction Watch).
- **Last checked:** 2026-10-17