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Age at menopause and lung function: a Mendelian Randomization study
Jumat, 23 Ags 2019 08:15:45

Diana A. van der PlaatMiguel PereiraGiancarlo PesceJames F. PottsAndré F. S. AmaralShyamali C. DharmageJudith M. Garcia-AymerichJohn R. ThompsonFrancisco Gómez-RealDeborah L. JarvisCosetta MinelliBénédicte Leynaert on behalf of the ALEC project

European Respiratory Journal 2019; DOI: 10.1183/13993003.02421-2018

Abstract

In observational studies, early menopause is associated with lower FVC and a higher risk of spirometric restriction, but not airflow obstruction. It is however unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.

We included 94 742 naturally post-menopausal women from UK Biobank and performed MR analyses on the effect of age at menopause on FEV1, FVC, FEV1/FVC, spirometric restriction (FVC<LLN) and airflow obstruction (FEV1/FVC<LLN). We used the inverse variance-weighted (IVW) method, as well as methods that adjust for pleiotropy, and compared MR with observational analyses.

The MR analyses showed higher FEV1/FVC and a 15% lower risk of airflow obstruction for women with early (<45 years) compared to normal (45–55) menopause. Despite some evidence of pleiotropy, the results were consistent when using MR methods robust to pleiotropy. Similar results were found among never- and ever-smokers, while the protective effect seemed less strong in women ever using menopause hormone treatment and in overweight women. There was no strong evidence of association with FVC or spirometric restriction. In observational analyses of the same dataset, early menopause was associated with a pronounced reduction in FVC and a 13% higher spirometric restriction risk.

Our MR results suggest that early menopause has a protective effect on airflow obstruction. Further studies are warranted to better understand the inconsistency with observational findings, and to investigate the underlying mechanisms and role of female sex hormones.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. van der Plaat has nothing to disclose.

Conflict of interest: Dr. Pereira has nothing to disclose.

Conflict of interest: Dr. Pesce has nothing to disclose.

Conflict of interest: Mr. Potts has nothing to disclose.

Conflict of interest: Dr. Amaral has nothing to disclose.

Conflict of interest: Dr. Dharmage has nothing to disclose.

Conflict of interest: Dr. Garcia-Aymerich has nothing to disclose.

Conflict of interest: Dr. Thompson has nothing to disclose.

Conflict of interest: Prof. Jarvis reports grants from European Union, during the conduct of the study.

Conflict of interest: Dr. Minelli has nothing to disclose.

Conflict of interest: Dr. LEYNAERT has nothing to disclose.

Conflict of interest: Dr. Gómez Real has nothing to disclose.