UMR 1152, Pathophysiology and Epidemiology of Respiratory Diseases, INSERM, Paris, France.
UMR 1152, University Paris Diderot, Paris, France.
Eur Respir J. 2019 Oct 17;54(4). doi: 10.1183/13993003.02421-2018. Print 2019 Oct.
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 (FEV), FVC, FEV/FVC, spirometric restriction (FVC<lower limit of normal (LLN)) and airflow obstruction (FEV/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 FEV/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.
在观察性研究中，早绝经与用力肺活量（FVC）降低和肺功能障碍风险升高有关，但与气流阻塞无关。然而，这种关联是否具有因果关系尚不清楚。因此，我们使用孟德尔随机化（MR）方法，该方法不受经典混杂因素的影响，评估自然绝经年龄对肺功能的影响。我们纳入了英国生物库中 94742 名自然绝经后女性，并对绝经年龄对 1 秒用力呼气量（FEV）、FVC、FEV/FVC、肺功能障碍（FVC<正常下限（LLN））和气流阻塞（FEV/FVC<LLN）的影响进行了 MR 分析。我们使用了逆方差加权法，以及调整多效性的方法，并将 MR 与观察性分析进行了比较。MR 分析表明，与正常（45-55 岁）绝经相比，早绝经（<45 岁）女性的 FEV/FVC 更高，气流阻塞风险降低 15%。尽管存在多效性的一些证据，但使用对多效性稳健的 MR 方法时，结果是一致的。在从不吸烟者和曾经吸烟者中也发现了类似的结果，而在曾经使用过绝经激素治疗和超重的女性中，这种保护作用似乎不那么强烈。没有强有力的证据表明与 FVC 或肺功能障碍限制有关。在同一数据集的观察性分析中，早绝经与 FVC 明显降低和肺功能障碍限制风险增加 13%有关。我们的 MR 结果表明，早绝经对气流阻塞有保护作用。需要进一步的研究来更好地理解与观察性发现的不一致，并研究潜在机制和女性性激素的作用。
