Mechanisms Driving Gender Differences in Asthma

Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis.

Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to those in boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mϕ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated. Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes in asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.