• Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
• Department of Public Health Sciences, University of Miami, Miami, Florida, USA.
• Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah, USA.
• Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA.
• Department of Epidemiology, Colorado School of Public Health, University of Colorado-Anschutz, Aurora, Colorado, USA.
• Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA sleng@salud.unm.edu.

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.