Risk of asthma onset after natural and surgical menopause: Results from the French E3N cohort

Background: The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity. Methods: Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41-68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment. Results: During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 [95%CI 1.01-1.75]) but no association was observed for natural menopause (aHR = 1.05 [0.84-1.32]). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 [1.00-3.66] and aHR = 2.08 [1.07-4.06] respectively). Conclusion: Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause.