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Eur Respir J. 2019 Oct 17;54(4). pii: 1802421. doi: 10.1183/13993003.02421-2018. Print 2019 Oct.

Age at menopause and lung function: a Mendelian randomisation study.

Author information

1
UMR 1152, Pathophysiology and Epidemiology of Respiratory Diseases, INSERM, Paris, France.
2
UMR 1152, University Paris Diderot, Paris, France.
3
National Heart and Lung Institute (NHLI), Imperial College, London, UK.
4
Allergy and Lung Health Unit, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
5
ISGlobal, Barcelona, Spain.
6
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
7
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
8
Dept of Health Sciences, University of Leicester, Leicester, UK.
9
Dept of Clinical Science, University of Bergen, Bergen, Norway.
10
Dept of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
11
Contributed equally and are considered to be joint last author.

Abstract

In observational studies, early menopause is associated with lower forced vital capacity (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 the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, spirometric restriction (FVC<lower limit of normal (LLN)) and airflow obstruction (FEV1/FVC<LLN). We used the inverse variance-weighted 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 years) 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 who had ever used menopause hormone treatment and in overweight women. There was no strong evidence of an 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 risk of spirometric restriction.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.

Conflict of interest statement

Conflict of interest: D.A. van der Plaat has nothing to disclose. Conflict of interest: M. Pereira has nothing to disclose. Conflict of interest: G. Pesce has nothing to disclose. Conflict of interest: J.F. Potts has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: S.C. Dharmage has nothing to disclose. Conflict of interest: J.M. Garcia-Aymerich has nothing to disclose. Conflict of interest: J.R. Thompson has nothing to disclose. Conflict of interest: F. Gómez Real has nothing to disclose. Conflict of interest: D.L. Jarvis reports grants from European Union, during the conduct of the study. Conflict of interest: C. Minelli has nothing to disclose. Conflict of interest: B. Leynaert has nothing to disclose.

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