Hormone replacement therapy and asthma onset in menopausal women: National cohort study

There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma. We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women. We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs. During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset. We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.