Early menopause and hormone therapy as determinants for lung health outcomes: a secondary analysis using the PLCO trial

Thorax. 2024 Sep 18;79(10):961-969. doi: 10.1136/thorax-2023-220956.

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.

Keywords: COPD epidemiology; Emphysema; Lung Cancer; Smoking; Tobacco and the lung.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Estrogen Replacement Therapy
  • Female
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Lung Diseases*
  • Menopause / physiology
  • Menopause, Premature
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Smoking / adverse effects
  • Smoking / epidemiology