Before puberty, asthma prevalence is highest in boys but there is a sharp decrease during puberty. Two thirds of adult asthma patients are female, who typically have a more severe phenotype and a lower quality of life compared to men. In addition to genetic and environmental factors these data suggest a pivotal role of sex hormones, namely testosterone (T), in the pathogenesis of asthma.
While epidemiologic and observational studies have also suggested a sexual dimorphism in immune responses, the exact mechanisms and the direct effects of testosterone and estradiol (E2) independent of other sex-related factors (such as sex chromosomes) remain unclear. These direct effects of sex hormones will be studied longitudinally, independent of genetics, in transgender individuals starting with gender-affirming hormonal therapy (GAHT). We hypothesize an immunomodulatory effect of testosterone, which leads to suppression of lower
respiratory tract symptoms through a shift in circulating immune cells which contribute to airway inflammation. We will examine the changes in respiratory tract symptoms and lung function in transgender individuals during GAHT in the ENIGI-lung cohort study at UZ Gent. Flowcytometry will be used to assess the impact of sex hormones on circulating immune cells and single cell analysis will be
performed to unravel the role of sex hormones in asthma at the molecular level.