Associations Between Reproductive Factors and the Risk of Adult-Onset Asthma: A Prospective Cohort Study of European Ancestry

Background Multiple studies showed sex discrepancies in the prevalence, incidence, and disease control of asthma. The relationships between different reproductive factors and the risk of asthma in females remain uncertain. Design A prospective cohort study recruited 239,701 female participants from the UK Biobank. The Cox proportional hazard model and multiple adjusted restricted cubic splines were used to evaluate the association between each reproductive factor and the risk of adult-onset asthma. Key Results We observed that the association of age at menarche and age of menopause with adult-onset asthma risk presented as U-shaped, with multiple adjusted HRs for age at menarche being 1.129 (95% CI, 1.038–1.228) for ≤ 11 years old and 1.157 (95% CI, 1.058–1.265) for ≥ 15 years old referenced to 13 years old, and for age at menopause being 1.368 (1.237–1.512) for ≤ 46 years old and 1.152 (1.026–1.294) for ≥ 55 years old referenced to 50–52 years old. Early age at first live birth (≤ 20 years old), a greater number of miscarriages (≥ 2) or stillbirths (≥ 2), more children (≥ 4), and shorter reproductive years (≤ 32 years) were associated with elevated risk of asthma. In addition, history of hysterectomy or oophorectomy was associated with increased risk of adult-onset asthma, particularly in those with simultaneous hysterectomy and oophorectomy (HR, 1.239; 95% CI, 1.063–1.445). For exogenous sex hormones, hormone replacement therapy (HR, 1.482; 95% CI, 1.394–1.574) was identified to be associated with elevated risk of adult-onset asthma. Conclusions This study not only demonstrated significant associations between multiple reproductive factors and the risk of adult-onset asthma in a female’s later life, but also found that history of hysterectomy or oophorectomy, as well as hormone replacement therapy, was linked to an elevated incidence of adult-onset asthma. Our findings highlighted the significance of reproductive factors in the development of asthma in female populations.