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Original research
Early menopause and hormone therapy as determinants for lung health outcomes: a secondary analysis using the PLCO trial
  1. Xiaochun Gai1,
  2. Yue Feng1,
  3. Tessa M Flores1,
  4. Huining Kang1,2,
  5. Hui Yu3,
  6. Kimberly K Leslie1,2,
  7. Yiliang Zhu1,
  8. Jennifer A Doherty4,
  9. Yan Guo3,
  10. Steven A Belinsky2,5,
  11. Linda S Cook6,
  12. Shuguang Leng1,2,5
  1. 1Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
  2. 2Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA
  3. 3Department of Public Health Sciences, University of Miami, Miami, Florida, USA
  4. 4Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, USA
  5. 5Lung Cancer Program, Lovelace Biomedical Research Institute, Albuquerque, New Mexico, USA
  6. 6Department of Epidemiology, Colorado School of Public Health, University of Colorado-Anschutz, Aurora, Colorado, USA
  1. Correspondence to Dr Shuguang Leng, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA; sleng{at}salud.unm.edu

Abstract

Rationale Early natural menopause (early-M; <45 years of age) increases the risk of lung morbidities and mortalities in smokers. However, it is largely unknown whether early-M due to surgery demonstrates similar effects and whether menopausal hormone therapy (MHT) is protective against lung diseases.

Objectives To assess the associations of early-M and MHT with lung morbidities and mortalities using the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) trial.

Methods We estimated the risk among 69 706 postmenopausal women in the PLCO trial, stratified by menopausal types and smoking status.

Results Early-M was associated with an increased risk of most lung disease and mortality outcomes in ever smokers with the highest risk seen for respiratory mortality (HR 1.98, 95% CI 1.34 to 2.92) in those with bilateral oophorectomy (BO). Early-M was positively associated with chronic bronchitis, and all-cause, non-cancer and respiratory mortality in never smokers with natural menopause or BO, with the highest risk seen for BO— respiratory mortality (HR 1.91, 95% CI 1.16 to 3.12). Ever MHT was associated with reduced all-cause, non-cancer and cardiovascular mortality across menopause types regardless of smoking status and was additionally associated with reduced risk of non-ovarian cancer, lung cancer (LC) and respiratory mortality in ever smokers. Among smokers, ever MHT use was associated with a reduction in HR for all-cause, non-cancer and cardiovascular mortality in a duration-dependent manner.

Conclusions Smokers with early-M should be targeted for smoking cessation and LC screening regardless of menopause types. MHT users had a lower likelihood of dying from LC and respiratory diseases in ever smokers.

  • Smoking
  • COPD epidemiology
  • Emphysema
  • Lung Cancer
  • Tobacco and the lung

Data availability statement

Data may be obtained from a third party and are not publicly available. Access to the PLCO datasets requires submitting a data-only project using the National Cancer Institute Cancer Data Access system. Data will be delivered once the project is approved and data transfer agreements are completed.

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Data availability statement

Data may be obtained from a third party and are not publicly available. Access to the PLCO datasets requires submitting a data-only project using the National Cancer Institute Cancer Data Access system. Data will be delivered once the project is approved and data transfer agreements are completed.

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Footnotes

  • XG and YF are joint first authors.

  • Contributors SL conceptualised this project, requested the PLCO data from The Cancer Data Access System (PLCO-981) and supervised the data analyses. XG, YF and HK conducted data analyses and summarised the results in tables and figures. HY, YG and SL defined early natural menopause and non-early menopause using the All of Us research program data and piloted the replication analyses, which were exclusively utilised in the peer review process. XG, YF and SL interpreted the results and drafted the manuscript. TF, KKL, YZ, JAD, SAB, LSC and SL critically edited the manuscript. SL is responsible for the overall content as a guarantor.

  • Funding This study was supported by National Cancer Institute grant P30 CA118100, National Institutes of Environmental Health Sciences R01 ES035421, National Heart Lung and Blood Institute R21 HL173388 and American Cancer Society Institutional Research Grant IRG-21-146-25-IRG-01.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.