Abstract Rationale Sex steroid hormones partly explain age- and sex-specific differences in asthma and may contribute to the pathogenesis and severity of asthma. Dehydroepiandrosterone sulfate (DHEA-S), an endogenous hormone secreted by the adrenal cortex in response to adrenocorticotropic hormone (ACTH), has anti-inflammatory and immune-modulating properties but its role in asthma is unclear. We aimed to examine the relation between serum DHEA-S and asthma and asthma exacerbations in U.S. adults. Methods Cross-sectional study of serum DHEA-S levels and asthma in 4,212 adults (2,334 females and 1,878 males) aged 18-79 years who participated in the 2021-2023 U.S. National Health and Nutrition Examination Survey (NHANES). Eosinophilic and non-eosinophilic asthma were defined by an absolute blood eosinophil count (AEC) ≥300 and 300 cells/uL, respectively. An asthma exacerbation was defined as an asthma attack or an emergency room or urgent care visit due to asthma in the previous year. Logistic regression was used for the multivariable analysis of DHEA-S and asthma or asthma exacerbations, which was conducted separately in females and males. All models were adjusted for age, race/ethnicity (non-Hispanic White, non-Hispanic Black, Mexican American or other Hispanic, and other), education, family monthly poverty level index, body mass index, and smoking status (never, former, or current), and other sex hormones. Results Serum DHEA-S levels were higher in males than in females and decreased with age in both genders. In a multivariable analysis, serum DHEA-S levels in the fourth quartile were associated with decreased odds of asthma in females (odds ratio OR for quartile Q 4 vs. Q1=0.55, 95% confidence interval CI=0.30-0.98) and in males (OR for Q4 to Q1=0.42 95% CI = 0.20-0.87, see Figure). Similar findings were obtained for non-eosinophilic asthma but not for eosinophilic asthma. There was a non-significant trend for an association between elevated DHEA-S levels and reduced odds of asthma exacerbations in females with asthma (OR for Q4 to Q1=0.45 (95% CI = 0.20, 1.01, p = 0.05) but no association in males with asthma. Conclusions In a representative sample of U.S. adults, an elevated serum DHEA-S level was significantly associated with reduced odds of asthma in both female and male participants, and with reduced odds of asthma exacerbations in female with asthma. Our findings suggest that DHEA-S may contribute to asthma pathogenesis in adults. This abstract is funded by: NIH grants: HL079966, HL117191, HL159333
Han et al. (Fri,) studied this question.