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

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.