Abstract 6465: Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Our previous study using the Lovelace Smokers cohort identified early natural menopause (i.e., age at menopause<45 yr), which is a biomarker of ovarian aging, as a risk factor for lung disease and mortality among female smokers. However, most of the associations reported in female smokers with natural menopause were not observed in those with surgical menopause, (a mixed group of subjects with bilateral oophorectomy or hysterectomy without bilateral oophorectomy). Females with bilateral oophorectomy lose ovarian estrogen and progesterone production, while females with hysterectomy, +/- unilateral oophorectomy, maintain some of this hormone production. We hypothesize that associations between early menopause, lung health and mortality will vary based on type of menopause. Among 69,071 females from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, early menopause rates were 8.7%, 44.1%, and 72.8% in never smokers versus 12.1%, 51.6%, and 78.0% in ever smokers with natural, bilateral oophorectomy, or hysterectomy without bilateral oophorectomy, respectively. We analyzed the associations of early menopause and hormone therapy with lung health (physician diagnosed emphysema and chronic bronchitis and lung cancer incidence) and mortality (all-cause and cause-specific) outcomes by smoking status and menopause types. The most consistent associations were observed for all-cause mortality: 1) Except in never smokers who received hysterectomy only, early menopause was associated with higher all-cause mortality regardless of smoking status 2) hormone therapy was associated with lower all-cause mortality in all groups and the longer the use, the more beneficial the outcome; 3) the magnitude of this association was strongest in those who underwent bilateral oophorectomy. Furthermore, in ethnic disparity analysis, all-cause mortality was affected by early menopause to a lesser degree in non-Hispanic black ever smokers and there was increased benefit from hormone therapy in non-Hispanic black never smokers. Overall, we identified further evidence supporting early menopause as a risk factor for lung health and mortality and hormone therapy as being beneficial regardless of smoking status or menopause type. Our results support the “shorter lifetime estrogen exposure in early menopause” hypothesis and the clinical importance of hormone therapy beyond withdrawal symptom coping. Supported by National Cancer Institute (NCI) grant P30 CA118100. The authors thank the NCI for access to NCI's data collected by the PLCO Cancer Screening Trial (the Cancer Data Access System Project Number PLCO-981). Citation Format: Tessa Flores, Xiaochun Gai, Yiliang Zhu, Kimberly Leslie, Shuguang Leng. Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6465.