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

Area of Science:

• Pulmonary Medicine
• Genetics
• Epidemiology

Background:

• Observational studies link early menopause to reduced lung function and increased risk of spirometric restriction.
• The causal relationship between age at menopause and lung function remains unclear.
• Mendelian randomization (MR) offers a method to assess causality, mitigating confounding factors.

Purpose of the Study:

• To investigate the causal effect of age at natural menopause on lung function using MR.
• To compare MR findings with traditional observational analyses.
• To evaluate the impact on forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, spirometric restriction, and airflow obstruction.

Main Methods:

• Utilized UK Biobank data from 94,742 post-menopausal women.
• Performed MR analyses using inverse variance-weighted and pleiotropy-robust methods.
• Assessed lung function parameters including FEV1, FVC, FEV1/FVC, spirometric restriction, and airflow obstruction.

Main Results:

• MR analyses indicated a higher FEV1/FVC ratio and a 15% reduced risk of airflow obstruction in women with early menopause (<45 years) compared to normal menopause (45-55 years).
• Results remained consistent across different MR methods, despite some evidence of pleiotropy.
• No strong association was found between early menopause and FVC or spirometric restriction in MR analyses, contrasting with observational findings.

Conclusions:

• Mendelian randomization suggests that early menopause confers a protective effect against airflow obstruction.
• Inconsistencies with observational data highlight the need for further research into underlying mechanisms and the role of sex hormones.
• Future studies should explore the divergence between MR and observational findings and elucidate the biological pathways involved.