Lower lung function associates with cessation of menstruation: UK Biobank data

Amaral, André F.S.; Strachan, David P.; Real, Francisco Gómez; Burney, Peter; Jarvis, Déborah

doi:10.1183/13993003.00412-2016

Cited by 27 publications

(31 citation statements)

References 31 publications

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“…A recent systematic review supports an association of menopause with lower forced expiratory volume in 1 s (FEV1) and lower forced vital capacity (FVC) [4]. A large study in the UK Biobank (UKB) showed that women with an earlier age at menopause had lower FEV1 and FVC, and a higher risk of spirometric restriction, while no association was found with airflow obstruction [5]. These observational studies may suffer from residual confounding even when the analyses are adjusted for known confounders, including anthropometric, lifestyle, socio-economic and reproductive characteristics.…”

Section: Introductionmentioning

confidence: 99%

Age at menopause and lung function: a Mendelian randomisation study

et al. 2019

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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.

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Section: Introductionmentioning

confidence: 99%

Age at menopause and lung function: a Mendelian randomisation study

et al. 2019

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“…There has been increasing interest in understanding gender-related risk factors for lung function impairment, particularly in relation to hormonal influences and sexual development. Substantial evidence shows that lung function is influenced by sex hormones in women [ 14 ] for whom low lung function has been associated with irregular menstruation, menopausal transition, and both natural and surgical menopause, with report of improvement in lung function in postmenopausal women receiving hormone replacement therapy [ 12 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Age at menarche and lung function: a Mendelian randomization study

et al. 2017

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A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-017-0272-9) contains supplementary material, which is available to authorized users.

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“…Amaral et al previously reported decreased lung function in postmenopausal women in UK Biobank 16. We repeat these analyses for completeness alongside analyses of other female reproductive health indicators.…”

Section: Methodsmentioning

confidence: 92%

“…A recent systematic review, which included studies from UK Biobank,16 reported that postmenopausal status was associated with reduced FEV 1 and FVC but not FEV 1 /FVC 18. Current HRT use has been associated with both higher14 and lower15 lung function.…”

Section: Discussionmentioning

confidence: 99%

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Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study

2019

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ObjectivesSex differences in respiratory physiology and predilection for developing chronic obstructive pulmonary disease (COPD) have been documented, suggesting that female sex hormones may influence pathogenesis. We investigated whether aspects of female reproductive health might play a role in risk of COPD among women.DesignPopulation-based prospective cohort study.SettingUK Biobank recruited across 22 centres in the UK between 2006 to 2010.Primary and secondary outcomes measuresWe examined a range of female reproductive health indicators in relation to risk of COPD-related hospitalisation/death (n=271 271) using Cox proportional hazards regression; and lung function (n=273 441) using linear regression.ResultsParity >3 was associated with greater risk of COPD-related hospitalisation/death (adjusted HR 1.45; 95% CI: 1.16 to 1.82) and lower forced expiratory volume at 1 second/forced vital capacity ratio (FEV1/FVC) (adjusted mean difference −0.06; 95% CI: -0.07 to 0.04). Any oral contraception use was associated with lower risk of COPD-related hospitalisation/death (adjusted HR 0.85; 95% CI: 0.74 to 0.97) and greater FEV1/FVC (adjusted mean difference 0.01; 95% CI: 0.003 to 0.03). Late menarche (age >15) and early menopause (age <47) were also associated with greater risk of COPD-related hospitalisation/death (but not lung function), while endometriosis was associated with greater FEV1/FVC (not COPD-related hospitalisation/death). Early menarche (age <12 years) was associated with lower FEV1/FVC (but not COPD hospitalisation/death). Associations with polycystic ovary syndrome (PCOS) or ovarian cysts, any hormone replacement therapy (HRT) use, hysterectomy-alone and both hysterectomy and bilateral oophorectomy were in opposing directions for COPD-related hospitalisation/death (greater risk) and FEV1/FVC (positive association).ConclusionsMultiple female reproductive health indicators across the life course are associated with COPD-related hospitalisation/death and lung function. Further studies are necessary to understand the opposing associations of PCOS/ovarian cysts, HRT and hysterectomy with COPD and objective measures of airway obstruction.

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Lower lung function associates with cessation of menstruation: UK Biobank data

Cited by 27 publications

References 31 publications

Age at menopause and lung function: a Mendelian randomisation study

Age at menopause and lung function: a Mendelian randomisation study

Age at menarche and lung function: a Mendelian randomization study

Female reproductive history in relation to chronic obstructive pulmonary disease and lung function in UK biobank: a prospective population-based cohort study

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