Female Reproductive Factors and Incidence of Nontuberculous Mycobacterial Pulmonary Disease Among Postmenopausal Women in Korea

Abstract

Background There are conflicting results regarding endogenous estrogen exposure and risk of incident nontuberculous mycobacterial pulmonary disease (NTM-PD). In addition, evidence on impact of hormone replacement therapy (HRT) on risk of NTM-PD is lacking. This study aimed to evaluate the impacts of endogenous estrogen exposure and HRT on risk of NTM-PD in postmenopausal women. Methods This population-based cohort study comprised 1 400 095 postmenopausal women without previous NTM-PD who participated in the 2009 national health screening exam in South Korea. The cohort was followed until the date of incident NTM-PD, death, or December 2018. We evaluated whether lifetime endogenous estrogen exposure and HRT were associated with incident NTM-PD. Endogenous estrogen exposure was evaluated using age at menarche and menopause and reproductive period (duration between age at menarche and age at menopause). Results During a median of 8.4 (interquartile range, 8.2-8.7) years of follow-up, 0.1% of participants (1818/1 400 095) developed NTM-PD, with an incidence rate of 0.15/1000 person-years. Multivariable Cox regression analyses showed no significant relationship between endogenous estrogen exposure (age at menarche, age at menopause, and reproductive period) and risk of NTM-PD. In contrast, duration of HRT showed a significant dose-response relationship with incident NTM-PD even after adjustment for demographics and reproductive factors (adjusted hazard ratio [95% CI]: 1.30 [1.12-1.51] in HRT for <2 years; 1.28 [1.03-1.59] in 2-5 years; and 1.65 [1.33-2.05] in >= 5 years). Conclusions While there was no significant association with endogenous estrogen exposure, HRT was monotonically associated with increased risk of NTM-PD in postmenopausal women. There was a significant dose-dependent relationship between the duration of hormone replacement therapy and the risk of nontuberculous mycobacterial pulmonary disease in postmenopausal women.