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.
↳ Abstract; Methods, opening paragraph
Abstract not available — view at DOI
Key Claims
Primary findingSupported
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.
Fragile — the claim's weakest requirement is that the effect exists at all. Experimental. Every point below is traceable to a quoted passage, but this forecast has not yet been validated against known replication outcomes.
the sample distribution is internally consistent, though retrospective recall and severity classification limit certainty
Results §Postmenopausal Period and Severity of HAE; Tables 3 and 4
SecondaryTentative
Improvement was correlated with estrogen sensitivity of angioedema before menopause (p=0.06 for improvement vs no effect or worsening).
the uncontrolled retrospective comparison reports a non-significant trend without adjusted effect estimates
Abstract; Results §Postmenopausal Period and Severity of HAE; Table 3
SecondaryTentative
Only three of the 13 patients receiving MHT in our study had to stop treatment because of worsening of attacks.
the uncontrolled subgroup is small and its denominator conflicts across the Abstract, Results, and Table 2
Discussion, MHT paragraph
SecondaryTentative
HAE was associated with C1-INH deficiency in 88% (n = 57) of the patients.
the Results identify these 57 women specifically as type I C1-INH-HAE
Abstract; Results, opening paragraph
Derived from the full evaluation — not a separate score.
Strengths · Limitations
Strengths
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.
↳ 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.
↳ 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.
↳ 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.
↳ 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.
↳ Statistical Analysis; Table 3
Nabu Commentary
The study provides a useful descriptive update by recruiting 65 postmenopausal women across thirteen French HAE reference centres and extending the sample to nC1-INH-HAE subtypes. Its main trajectory counts are coherent, but attributing those changes to menopause is undermined by retrospective recall, aging, and substantial prophylaxis changes between comparison periods. Table 3 does not provide adjusted estimates despite the stated multivariate analysis, and the p=0.06 estrogen-sensitivity result is stronger in the Abstract than in the Results. Interpretation of MHT tolerance requires additional caution because the reported treatment denominator varies across the Abstract, Results, and Table 2.
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Author Note / Field Feedback
Nabu’s assessment, alongside the field’s view.
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Dimension breakdown
Study Quality
Limited2.8
Confidence mediumContribution
3.4
The study expands the closest cited series from 44 to 65 women and includes nC1-INH-HAE subtypes, creating a useful descriptive extension. The advance remains incremental because those added subtypes total only eight patients and the estrogen-sensitivity comparison reaches p=0.06.
Introduction; Results §Postmenopausal Period and Severity of HAE; Discussion, paragraph 1
We set out to update this information in a larger series of patients including women with both C1-INH-HAE and nC1-INH-HAE.
Methodological Rigour
2.0
The standardized severity classification and multicentre recruitment support descriptive analysis, but the long retrospective comparison cannot separate menopause from aging, recall, or changing prophylaxis. Explicit causal wording compounds the absence of an adequately reported adjustment strategy.
Methods; Statistical Analysis; Results §Postmenopausal Period and Severity of HAE; Discussion, paragraphs 1 and limitations
Menopause resulted in an improvement in HAE for at least a third of the patients included.
Reporting
3.1
The article is logically organized and the main trajectory counts are readily traceable to Tables 3 and 4. Reporting is reduced by describing p=0.06 as a correlation and by reporting conflicting MHT denominators in the Abstract and Results.
Abstract; Results §Menopause Characteristics; Tables 3–4
Improvement was correlated with estrogen sensitivity of angioedema before menopause (p = 0.06).
Positioning
3.6
The Discussion directly compares the findings with PREHAEAT and engages relevant hormonal and kinin-system literature. It also traces how retrospective scoring may overestimate stability, although uncertainty around selection into the small MHT subgroup is not comparably developed.
Discussion, paragraphs 1–3 and limitations
This may result in an overestimation of patients with no menopausal effect at the expense of patients improving at menopause.
Reliability
Concerns4 of 4 checks
Internal CoherenceConcern
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 ConductClean
Ethics approvals, funding, and conflicts of interest are explicitly declared. No supplied-text contradiction concerning approval, disclosure, registration, or availability was identified.
Flags: 2 declared / 5 total
Reference IntegrityClean
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 RecordClean
No retraction or expression of concern found in Crossref (includes Retraction Watch).
Last checked: 17 Oct 2026
Sources: Crossref (incl. Retraction Watch) ✓
Readiness
Where this paper’s evidence sits on the path from initial observation to real-world use.
Mechanistic
The evidence comes from real clinical care but remains a retrospective observation without prospective validation or a controlled treatment comparison. It therefore supports hypothesis generation rather than implementation guidance.
Methods; Discussion, limitations and MHT paragraph
However, we would need a prospective trial to further confirm this hypothesis.
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